Reflist_20130917
 Share
The version of the browser you are using is no longer supported. Please upgrade to a supported browser.Dismiss

 
View only
 
|
 
Still loading...
ABCDEFGHIJKLMNOPQRSTUVWXYZAAABACADAEAFAGAHAIAJAKALAMANAOAPAQARASATAUAVAWAXAYAZBABBBC
1
Reference Type
Authors, Primary
Title Primary
Periodical Full
Periodical Abbrev
Pub Year
Pub Date Free From
VolumeIssueStart Page
Other Pages
KeywordsAbstractNotes
Personal Notes
Authors, Secondary
Title Secondary
EditionPublisher
Place Of Publication
Authors, Tertiary
Authors, Quaternary
Authors, Quinary
Title, Tertiary
ISSN/ISBNAvailability
Author/Address
Accession Number
Language
Classification
Sub file/Database
Original Foreign Title
LinksDOICall NumberDatabase
Data Source
Identifying Phrase
Retrieved Date
Shortened Title
User 1User 2User 3User 4User 5User 6User 7User 8User 9User 10User 11User 12User 13User 14User 15
2
Journal Article
Adham,I. M.;Agoulnik,A. I.
Insulin-like 3 signalling in testicular descent
International journal of andrology
Int.J.Androl.2004Oct275257265
Animals;Cryptorchidism/genetics;Humans;Insulin-Like Growth Factor Binding Protein 3/genetics;Male;Mice;Mice, Transgenic;Signal Transduction;Testis/growth & development
Undescended testis is one of the most common congenital defects in the newborn boys and the common cause of cryptorchidism. If left untreated, this condition is strongly associated with infertility and drastically increased risk of testicular cancer in adulthood. Testis position in developing males is defined by sexual dimorphic differentiation of two gonadal ligaments, gubernaculum and cranial suspensory ligament. Recent transgenic mouse studies identified testicular hormone insulin-like 3 (INSL3), and its receptor, GREAT/LGR8, as the critical regulators of the gubernacular differentiation. Mutation analysis of the two genes in patients with undescended testis revealed functionally deleterious mutations, which may be responsible for the abnormal phenotype in some of the patients.
LR: 20110922; GR: HD36289/HD/NICHD NIH HHS/United States; GR: HD37067/HD/NICHD NIH HHS/United States; GR: R01 HD037067-04/HD/NICHD NIH HHS/United States; JID: 8000141; 0 (Insulin-Like Growth Factor Binding Protein 3); RF: 72; ppublish
England
0105-6263; 0105-6263
Institute of Human Genetics, University of Gottingen, Gottingen, Germany.
PMID: 15379965; IJA481 [pii]
eng
Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Review; IM
10.1111/j.1365-2605.2004.00481.x
49
3
Journal Article
Adonizio,A.;Kong,K. F.;Mathee,K.
Inhibition of quorum sensing-controlled virulence factor production in Pseudomonas aeruginosa by South Florida plant extracts
Antimicrobial Agents and Chemotherapy
Antimicrob.Agents Chemother.
2008Jan521198203
4-Butyrolactone/analogs & derivatives/metabolism;Anti-Bacterial Agents/pharmacology;Bacterial Proteins/genetics/metabolism;Biofilms/drug effects/growth & development;Florida;Gene Expression Regulation, Bacterial;Humans;Phytotherapy;Plant Extracts/pharmacology;Plants, Medicinal;Pseudomonas aeruginosa/drug effects/growth & development/pathogenicity;Quorum Sensing/drug effects;Signal Transduction;Virulence Factors/biosynthesis
Quorum sensing (QS) is a key regulator of virulence and biofilm formation in Pseudomonas aeruginosa and other medically relevant bacteria. Aqueous extracts of six plants, Conocarpus erectus, Chamaesyce hypericifolia, Callistemon viminalis, Bucida buceras, Tetrazygia bicolor, and Quercus virginiana, were examined in this study for their effects on P. aeruginosa virulence factors and the QS system. C. erectus, B. buceras, and C. viminalis caused a significant inhibition of LasA protease, LasB elastase, pyoverdin production, and biofilm formation. Additionally, each plant presented a distinct effect profile on the las and rhl QS genes and their respective signaling molecules, suggesting that different mechanisms are responsible for efficacy. Extracts of all plants caused the inhibition of QS genes and QS-controlled factors, with marginal effects on bacterial growth, suggesting that the quorum-quenching mechanisms are unrelated to static or cidal effects.
LR: 20130606; GR: 1-R15-AT002626-01/AT/NCCAM NIH HHS/United States; GR: 1-T32-AT01060-01/AT/NCCAM NIH HHS/United States; GR: R35 GM61347/GM/NIGMS NIH HHS/United States; JID: 0315061; 0 (Anti-Bacterial Agents); 0 (Bacterial Proteins); 0 (Plant Extracts); 0 (Virulence Factors); 1192-20-7 (homoserine lactone); 96-48-0 (4-Butyrolactone); OID: NLM: PMC2223872; 2007/10/15 [aheadofprint]; ppublish
United States
0066-4804; 0066-4804
Department of Biological Sciences, Florida International University, HLS673A, University Park, Miami, FL 33199, USA.
PMID: 17938186; AAC.00612-07 [pii]
eng
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; IM
10.1128/AAC.00612-07
105
4
Journal Article
Adonizio,A.;Leal,S. M.,Jr;Ausubel,F. M.;Mathee,K.
Attenuation of Pseudomonas aeruginosa virulence by medicinal plants in a Caenorhabditis elegans model system
Journal of medical microbiology
J.Med.Microbiol.
2008Jul57Pt 7809813
Animals;Caenorhabditis elegans/growth & development/microbiology;Disease Models, Animal;Humans;Myrtaceae/chemistry;Plant Extracts/pharmacology;Plants, Medicinal/chemistry/classification;Pseudomonas Infections/microbiology;Pseudomonas aeruginosa/drug effects/pathogenicity;Virulence
Expression of a myriad of virulence factors and innate antibiotic resistance enables the opportunistic human pathogen Pseudomonas aeruginosa to create intractable infections. Using a nematode model, we screened for novel inhibitors of this pathogen. Aqueous extracts of three plants, Conocarpus erectus, Callistemon viminalis and Bucida buceras, were examined for their effects on P. aeruginosa killing of the nematode Caenorhabditis elegans. The results were evaluated in toxin-based and infection-based assays using P. aeruginosa strains PAO1 and PA14. The tested plant extracts prevented mortality via gut infection in approximately 60 % of the worms and caused a 50-90 % reduction in death from toxin production. All extracts inhibited nematode death by P. aeruginosa without host toxicity, indicating their potential for further development as anti-infectives.
LR: 20100630; GR: 1R15 AT 002626-01/AT/NCCAM NIH HHS/United States; GR: 1T32 AT 01060-01/AT/NCCAM NIH HHS/United States; GR: R01 AI 064332/AI/NIAID NIH HHS/United States; GR: R01 AI 072508/AI/NIAID NIH HHS/United States; GR: R01 AI064332-05/AI/NIAID NIH HHS/United States; GR: R01 AI072508-03/AI/NIAID NIH HHS/United States; GR: R25 GM 61347/GM/NIGMS NIH HHS/United States; JID: 0224131; 0 (Plant Extracts); ppublish
England
0022-2615; 0022-2615
Department of Biological Sciences, College of Arts and Sciences, Florida International University, Miami, FL 33199, USA.
PMID: 18566137; 57/7/809 [pii]
eng
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; IM
10.1099/jmm.0.47802-0; 10.1099/jmm.0.47802-0
105
5
Journal Article
Adonizio,A. L.;Downum,K.;Bennett,B. C.;Mathee,K.
Anti-quorum sensing activity of medicinal plants in southern Florida
Journal of ethnopharmacology
J.Ethnopharmacol.
200624-May1053427435
Anti-Bacterial Agents/pharmacology;Bacterial Infections/drug therapy;Florida;Phytotherapy;Plant Extracts/pharmacology;Plants, Medicinal;Signal Transduction/drug effects
Bacterial intercellular communication, or quorum sensing (QS), controls the pathogenesis of many medically important organisms. Anti-QS compounds are known to exist in marine algae and have the ability to attenuate bacterial pathogenicity. We hypothesized that terrestrial plants traditionally used as medicines may also produce anti-QS compounds. To test this hypothesis, 50 medicinal plants from southern Florida were screened for anti-QS activity using two biomonitor strains, Chromobacterium violaceum and Agrobacterium tumefaciens. Of these plants, six showed QS inhibition: Conocarpus erectus L. (Combretaceae), Chamaecyce hypericifolia (L.) Millsp. (Euphorbiaceae), Callistemon viminalis (Sol. ex Gaertn.) G. Don (Myrtaceae), Bucida burceras L. (Combretaceae), Tetrazygia bicolor (Mill.) Cogn. (Melastomataceae), and Quercus virginiana Mill. (Fagaceae). This study introduces not only a new mode of action and possible validation for traditional plant use, but also a potentially new therapeutic direction for the treatment of bacterial infections.
LR: 20071203; GR: 1-T32-AT-01060-01/AT/NCCAM NIH HHS/United States; JID: 7903310; 0 (Anti-Bacterial Agents); 0 (Plant Extracts); 2005/06/27 [received]; 2005/11/22 [revised]; 2005/11/23 [accepted]; 2006/01/06 [aheadofprint]; ppublish
Ireland
0378-8741; 0378-8741
Department of Biological Sciences, Center for Ethnobiology and Natural Products, CENaP, Florida International University, 11200 SW 8th Street, University Park, Miami, 33199, USA.
PMID: 16406418; S0378-8741(05)00790-7 [pii]
eng
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; IM
10.1016/j.jep.2005.11.025
105
6
Journal Article
Agarwal-Kozlowski,K.;Lorke,D. E.;Habermann,C. R.;Am Esch,J. S.;Beck,H.
CT-guided blocks and neuroablation of the ganglion impar (Walther) in perineal pain: anatomy, technique, safety, and efficacy
The Clinical journal of pain
Clin.J.Pain2009Sep257570576
Adult;Aged;Aged, 80 and over;Female;Ganglia, Sympathetic/injuries/surgery;Humans;Male;Middle Aged;Nerve Block/methods;Neuralgia/etiology/pathology/radiography/surgery;Pain Measurement/methods;Pelvic Pain/pathology/radiography/surgery;Retrospective Studies;Tomography, X-Ray Computed/methods
OBJECTIVE: An alternate approach to the ganglion impar was chosen to minimize the risk of adverse events. Efficacy of the procedure was evaluated. METHODS: Charts and computed tomography (CT)-scans of patients who underwent block and neuroablation of the ganglion impar (Walther) between 2003 and 2007 were systematically reviewed with respect to adverse events and efficacy by rating pain intensity. A total of 76 blocks were performed, 48 of them being diagnostic blocks and 28 neuroablations. Chemical destruction was performed with ethanol, if pain recurred despite injection of local anesthetic. RESULTS: Interventional pain therapy was performed in 43 patients (age: 64.6+/-12.4 y, median 49.5 y, range: 36 to 86 y, male/female: 27/16) presenting with perineal pain of unknown origin (n=15), carcinoma of the prostate (n=8), colorectal carcinoma (n=7), postsurgery of thrombosis of perineal veins (n=3), postherpetic neuralgia (n=4), malformation of the spinal cord (n=2), vaginal protrusion (n=2), failed back surgery syndrome (n=1), and ablation of testis (n=1). CT-guided puncture was not associated with any adverse events and resulted in a reduction of numeric rating scale values from 8.2+/-1.6 to 2.2+/-1.6 (P<0.0001, 95% confidence interval 0.5) immediately at discharge and to 2.2+/-1.4 (P<0.0001, 95% confidence interval 0.4) at 4 months on follow up. DISCUSSION: CT-guided block and neuroablation of the ganglion impar (Walther) results in a significant reduction of pain scores and carries virtually no hazards.
JID: 8507389; ppublish
United States
1536-5409; 0749-8047
Center for Palliative Care and Pain Management, Doerenberg Medical Center, Am Kurgarten 7, 49186 Bad Iburg, Germany. kagarwal@doerenberg-klinik.de
PMID: 19692797; 00002508-200909000-00003 [pii]
eng
Clinical Trial; Journal Article; IM
10.1097/AJP.0b013e3181a5f5c7; 10.1097/AJP.0b013e3181a5f5c7
21
7
Journal Article
Agarwal-Kozlowski,K.;Lorke,D. E.;Habermann,C. R.;Schulte am Esch,J.;Beck,H.
Interventional management of intractable sympathetically mediated pain by computed tomography-guided catheter implantation for block and neuroablation of the thoracic sympathetic chain: technical approach and review of 322 procedures
AnaesthesiaAnaesthesia2011Aug668699708
Adult;Aged;Aged, 80 and over;Algorithms;Anesthetics, Local/administration & dosage;Catheter Ablation/adverse effects/methods;Female;Humans;Lung/radiography;Male;Middle Aged;Nerve Block/methods;Pain Measurement/methods;Pain, Intractable/radiography/surgery;Radiography, Interventional/methods;Retrospective Studies;Sympathectomy/adverse effects/methods;Thoracic Vertebrae/radiography;Tomography, X-Ray Computed/methods
We retrospectively evaluated the safety and efficacy of computed tomography-guided placement of percutaneous catheters in close proximity to the thoracic sympathetic chain by rating pain intensity and systematically reviewing charts and computed tomography scans. Interventions were performed 322 times in 293 patients of mean (SD) age 59.4 (17.0) years, and male to female ratio 105:188, with postherpetic neuralgia (n = 103, 35.1%), various neuralgias (n = 88, 30.0%), complex regional pain syndrome (n = 69, 23.6%), facial pain (n = 17, 5.8%), ischaemic limb pain (n = 7, 2.4%), phantom limb pain (n = 4, 1.4%), pain following cerebrovascular accident (n = 2, 0.7%), syringomyelia (n = 2, 0.7%) and palmar hyperhidrosis (n = 1, 0.3%). The interventions were associated with a total of 23 adverse events (7.1% of all procedures): catheter dislocation (n = 9, 2.8%); increase in pain intensity (n = 8, 2.5%); pneumothorax (n = 3, 0.9%); local infection (n = 2, 0.6%); and puncture of the spinal cord (n = 1, 0.3%). Continuous infusion of 10 ml.h(-1) ropivacaine 0.2% through the catheters decreased median (IQR [range]) pain scores from 8 (6-9 [2-10]) to 2 (1-3 [0-10]) (p < 0.0001). Chemical neuroablation was necessary in 137 patients (46.8%). We conclude that this procedure leads to a significant reduction of pain intensity in otherwise obstinate burning or stabbing pain and is associated with few hazards.
CI: (c) 2011 The Authors. Anaesthesia (c) 2011; JID: 0370524; 0 (Anesthetics, Local); 2011/05/13 [aheadofprint]; ppublish
The Association of Anaesthetists of Great Britain and Ireland
England
1365-2044; 0003-2409
Centre for Palliative Care and Pain Management (T.I.P.S!), Stade, Germany.
PMID: 21564048
eng
Evaluation Studies; Journal Article; AIM; IM
10.1111/j.1365-2044.2011.06765.x; 10.1111/j.1365-2044.2011.06765.x
21
8
Book, Section
Agioulnik,I. U.;Weigel,N. L.
Roles of androgen receptor coregulators and cell signaling in the regulation of androgen-responsive genes
2012 11-Jan Wang,Z.
Androgen-Responsive Genes in Prostate Cancer
SpringerNew York 19
9
Book, Section
Agoulnik,A. I.
The Genetics of Cryptorchidism
2006 185-198 Carrell,D. T.
The Genectics of Male Infertility
Human Press
Totowa, USA
49
10
Book, Section
Agoulnik,A. I.;Feng,S.
The Genetics of Cryptorchidism
2007 185-198 Carrell,D. T.
The Genectics of Male Infertility
Humana Press
USA 49
11
Book, Section
Agoulnik,A. I.;Poirier,C.
Transgenic models in reproduction research
2006 Klonisch,T.
Biology in Reproduction
Research Signpost
Kerala, India 49
12
Book, Section
Agoulnik,A. I.;Sargan D.R.
Genomi research and progress in understanding inherited disorders in mammals
2005
Mammalian Genomics
CAB International
Wallingford, UK
49
13
Journal Article
Agoulnik,A. I.
Relaxin and related peptides in male reproduction
Advances in Experimental Medicine and Biology
Adv.Exp.Med.Biol.
2007 612 4964
Animals;Female;Gene Expression Regulation, Developmental/physiology;Humans;Insulin/genetics/metabolism;Intercellular Signaling Peptides and Proteins/genetics/metabolism;Intracellular Signaling Peptides and Proteins/genetics/metabolism;Leydig Cells/cytology/metabolism;Male;Mice;Peptide Hormones/genetics/metabolism;Pregnancy;Prostate/cytology/embryology/metabolism;Proteins/genetics/metabolism;Receptors, G-Protein-Coupled;Relaxin/genetics/metabolism;Reproduction/physiology
The relaxin hormone is renowned for its function in pregnancy, parturition and other aspects of female reproduction. At the same time, the role of relaxin in male reproduction is still debated. Relaxin is prominently expressed in prostate and its receptors are found in several male reproductive organs; however, the data indicative of its contribution to differentiation and functioning of prostate or testis are contradictory. Prostate relaxin is a main source of this peptide in the seminal plasma. The relaxin effects on sperm motility and fertilization have been reported. The expression of other relaxin related peptides, such as INSL5 and INSL6 was described in testis; yet, currently there are no experimental data to pinpoint their biological functions. The other member of relaxin peptide family, insulin-like 3 peptide (INSL3), is a major player in male development. The INSL3 peptide is expressed in testicular fetal and adult Leydig cells and is directly responsible for the process of abdominal testicular descent (migration of the testes towards the scrotum during male development). Genetic targeting of the Insl3 gene or INSL3 GPCR receptor Lgr8/Rxfp2 causes high intra-abdominal cryptorchidism due to a differentiation failure of testicular ligaments, the gubernacula. Several mutations of these two genes rendering nonfunctional proteins have been described in human patients with testicular maldescent. Thus, in this chapter we review the data related to the expression and function of relaxin and related peptides in male reproduction.
LR: 20111117; GR: R01 HD037067-10/HD/NICHD NIH HHS/United States; JID: 0121103; 0 (INSL6 protein, human); 0 (Insl5 protein, mouse); 0 (Insl6 protein, mouse); 0 (Insulin); 0 (Intercellular Signaling Peptides and Proteins); 0 (Intracellular Signaling Peptides and Proteins); 0 (Leydig insulin-like protein); 0 (Peptide Hormones); 0 (Proteins); 0 (RXFP2 protein, human); 0 (Receptors, G-Protein-Coupled); 9002-69-1 (Relaxin); RF: 116; ppublish
United States
0065-2598; 0065-2598
Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas 77030, USA. agoulnik@bcm.edu
PMID: 18161481
eng
Journal Article; Research Support, N.I.H., Extramural; Review; IM
10.1007/978-0-387-74672-2_5
49
14
Book, Section
Agoulnik,A. I.
Relaxin and related peptides in male reproduction
2007 612 49-64
Agoulnik,A. I.
Relaxin and related peptides
SpringerNew York 49
15
Journal Article
Agoulnik,A. I.
Cryptorchidism--an estrogen spoil?
The Journal of clinical endocrinology and metabolism
J.Clin.Endocrinol.Metab.
2005Aug90849754977
Cryptorchidism/etiology/genetics;Environmental Exposure;Estrogen Receptor alpha/genetics;Estrogens;Humans;Male
LR: 20110922; GR: R01 HD037067-05/HD/NICHD NIH HHS/United States; JID: 0375362; 0 (Estrogen Receptor alpha); 0 (Estrogens); CON: J Clin Endocrinol Metab. 2005 Aug;90(8):4716-21. PMID: 15899960; RF: 19; ppublish
United States
0021-972X; 0021-972X
PMID: 16087960; 90/8/4975 [pii]
eng
Comment; Editorial; Review; AIM; IM
10.1210/jc.2005-1290
49
16
Book, Section
Agoulnik,A. I.;Huang,Z.;Ferguson,L.
Spermatogenesis in cryptorchidism
2012 825 127-147
Chan,Wai-Yee;Blomberg,Le Ann
Germline Development
SpringerNew York 495253
17
Journal Article
Agoulnik,A. I.;Huang,Z.;Ferguson,L.
Spermatogenesis in cryptorchidism
Methods in molecular biology (Clifton, N.J.)
Methods Mol.Biol.
2012 825 127147
Cryptorchidism/epidemiology/genetics;Environment;Hormones/metabolism;Humans;Male;Risk Factors;Spermatogenesis/genetics;Testicular Neoplasms/genetics;Testis/embryology/metabolism
Cryptorchidism or undescended testis is the most frequent congenital abnormality in newborn boys. The process of testicular descent to the scrotum is controlled by hormones produced in Leydig cells, insulin-like3, and androgens. Variation in genetic and environmental factors might affect testicular descent. A failure of spermatogenesis and germ cell apoptosis resulting in infertility as well as an increased risk of neoplastic transformation of germ cell are the direct consequences of cryptorchidism in adulthood.
GR: R01HD37067/HD/NICHD NIH HHS/United States; JID: 9214969; 0 (Hormones); ppublish
United States
1940-6029; 1064-3745
Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA. Alexander.Agoulnik@fiu.edu
PMID: 22144242
eng
Journal Article; Research Support, N.I.H., Extramural; IM
10.1007/978-1-61779-436-0_11; 10.1007/978-1-61779-436-0_11
52
18
Journal Article
Agoulnik,A. I.;Lu,B.;Zhu,Q.;Truong,C.;Ty,M. T.;Arango,N.;Chada,K. K.;Bishop,C. E.
A novel gene, Pog, is necessary for primordial germ cell proliferation in the mouse and underlies the germ cell deficient mutation, gcd
Human molecular genetics
Hum.Mol.Genet.
200215-Nov112430473053
Animals;Cell Differentiation/genetics;Cell Division/genetics;Cell Movement/genetics;Embryo Loss/genetics;Embryonic and Fetal Development/genetics;Fetal Weight/genetics;Gene Expression Regulation, Developmental;Germ Cells/cytology/physiology;Mice;Mutation;Proteins/genetics/metabolism;Sequence Analysis, DNA
Primordial germ cells (PGCs) are the precursor of the germ cells in adult gonads. They arise extra-gonadally and migrate through somatic tissues to the presumptive genital ridges, where they proliferate and differentiate into oogonia or spermatogonia cells. Abnormalities in this developmental process can cause embryonic depletion of germ cells leading to infertility in the adult. We report here that the mouse gcd (germ cell deficient) mutant phenotype, characterized by reduced numbers of PGCs and adult sterility, is due to reduced PGC proliferation rather than aberrant migration and is caused by the partial deletion of a single novel gene, Pog (proliferation of germ cells). Pog is critical for normal PGC proliferation, starting between 9.5 and 10.25 dpc when germ cells begin to migrate to the developing genital ridge. Deletion of Pog is also accompanied by reduced embryonic body weight and, on some genetic backgrounds, embryonic lethality. Thus, in addition to being necessary for PGC proliferation, Pog may have a wider significance in early embryonic development.
LR: 20071114; GR: P01 HD 36289/HD/NICHD NIH HHS/United States; JID: 9208958; 0 (Pog protein, mouse); 0 (Proteins); ppublish
England
0964-6906; 0964-6906
Department of Obstetrics and Gynecology, Baylor College of Medicine, 6550 Fannin Street (#880), Houston, TX 77030, USA.
PMID: 12417526
eng
Journal Article; Research Support, U.S. Gov't, P.H.S.; IM
49
19
Journal Article
Agoulnik,I. U.;Bingman,W. E.,3rd;Nakka,M.;Li,W.;Wang,Q.;Liu,X. S.;Brown,M.;Weigel,N. L.
Target gene-specific regulation of androgen receptor activity by p42/p44 mitogen-activated protein kinase
Molecular endocrinology (Baltimore, Md.)
Mol.Endocrinol.
2008Nov221124202432
Acetylation;Base Sequence;Binding Sites/genetics;Butadienes/pharmacology;Cell Line, Tumor;Enhancer Elements, Genetic;Histones/chemistry/metabolism;Humans;MAP Kinase Signaling System;Male;Mitogen-Activated Protein Kinase 1/adverse effects/genetics/metabolism;Mitogen-Activated Protein Kinase 3/antagonists & inhibitors/genetics/metabolism;Nitriles/pharmacology;Promoter Regions, Genetic;Prostatic Neoplasms/genetics/metabolism;Protein Kinase Inhibitors/pharmacology;Protein Stability;RNA, Messenger/genetics/metabolism;RNA, Neoplasm/genetics/metabolism;RNA, Small Interfering/genetics;Receptors, Androgen/genetics/metabolism
Evidence that the androgen receptor (AR) is not only important in androgen-dependent prostate cancer, but also continues to play a role in tumors that become resistant to androgen deprivation therapies, highlights the need to find alternate means to block AR activity. AR, a hormone-activated transcription factor, and its coactivators are phosphoproteins. Thus, we sought to determine whether inhibition of specific cell signaling pathways would reduce AR function. We found that short-term inhibition of p42/p44 MAPK activity either by a MAPK kinase inhibitor, U0126, or by depletion of kinase with small interfering RNA caused target gene-specific reductions in AR activity. AR enhances histone H3 acetylation of target genes that are sensitive to U0126 including prostate-specific antigen and TMPRSS2, but does not increase histone H3 acetylation of the U0126-resistant PMEPA1 gene. Thus, although AR induces transcription of many target genes, the molecular changes induced by AR at the chromatin level are target gene specific. Long-term treatment (24-48 h) with U0126 causes a G1 cell cycle arrest and reduces AR expression both through a decrease in AR mRNA and a reduction in AR protein stability. Thus, treatments that reduce p42/p44 MAPK activity in prostate cancer have the potential to reduce AR activity through a reduction in expression levels as well as by target gene-selective inhibition of AR function.
LR: 20130516; GR: CA58204/CA/NCI NIH HHS/United States; GR: DK65262/DK/NIDDK NIH HHS/United States; GR: R01 HG004069/HG/NHGRI NIH HHS/United States; GR: R01 HG004069-02/HG/NHGRI NIH HHS/United States; GR: R01 HG004069-03/HG/NHGRI NIH HHS/United States; GR: T32DK07696/DK/NIDDK NIH HHS/United States; JID: 8801431; 0 (Butadienes); 0 (Histones); 0 (Nitriles); 0 (Protein Kinase Inhibitors); 0 (RNA, Messenger); 0 (RNA, Neoplasm); 0 (RNA, Small Interfering); 0 (Receptors, Androgen); 0 (U 0126); EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1); EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3); OID: NLM: PMC2582542; 2008/09/11 [aheadofprint]; ppublish
United States
0888-8809; 0888-8809
Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.
PMID: 18787043; me.2007-0481 [pii]
eng
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; IM
10.1210/me.2007-0481; 10.1210/me.2007-0481
19
20
Journal Article
Agoulnik,I. U.;Hodgson,M. C.;Bowden,W. A.;Ittmann,M. M.
INPP4B: the new kid on the PI3K block
OncotargetOncotarget2011Apr24321328
Animals;Female;Humans;Male;Models, Biological;Neoplasms/etiology/genetics/metabolism;PTEN Phosphohydrolase/genetics/metabolism/physiology;Phosphatidylinositol 3-Kinases/genetics/metabolism/physiology;Phosphoric Monoester Hydrolases/chemistry/genetics/metabolism/physiology;Receptors, Androgen/metabolism/physiology;Signal Transduction/genetics/physiology
Dysregulation of phosphatidyl inositol signaling occurs in many cancers and other disorders. The lipid and protein phosphatase, PTEN (Phosphatase and Tensin homology protein on chromosome 10), is a known tumor suppressor whose function is frequently lost in various malignancies due to mutations in the coding region or genomic deletions. Recently, another lipid phosphatase, Inositol Polyphosphate 4-phosphatase type II (INPP4B), has emerged as a potential tumor suppressor in prostate, breast, and ovarian cancers and possibly in leukemia. We will review its structure and function, crosstalk with androgen receptor signaling, and regulation of INPP4B expression, as well as existing data about its role in cancer.
LR: 20130630; GR: 1R21CA129265-01A1/CA/NCI NIH HHS/United States; GR: 1U54CA126568/CA/NCI NIH HHS/United States; GR: BC097064/BC/NCI NIH HHS/United States; GR: CA58504/CA/NCI NIH HHS/United States; JID: 101532965; 0 (Receptors, Androgen); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 3.1.3.- (Phosphoric Monoester Hydrolases); EC 3.1.3.48 (PTEN protein, human); EC 3.1.3.66 (phosphatidylinositol-3,4-bisphosphate 4-phosphatase); EC 3.1.3.67 (PTEN Phosphohydrolase); OID: NLM: PMC3248162; ppublish
United States
1949-2553; 1949-2553
Herbert Wertheim College of Medicine, Miami, FL, USA. email: iagoulni@fiu.edu
PMID: 21487159; 260 [pii]
eng
Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.; Review; IM
2319
21
Journal Article
Agoulnik,I. U.;Krause,W. C.;Bingman,W. E.,3rd;Rahman,H. T.;Amrikachi,M.;Ayala,G. E.;Weigel,N. L.
Repressors of androgen and progesterone receptor action
The Journal of biological chemistry
J.Biol.Chem.200315-Aug278333113631148
Animals;Binding Sites;Breast Neoplasms;COS Cells;DAX-1 Orphan Nuclear Receptor;DNA-Binding Proteins/genetics/metabolism;Female;Gene Expression Regulation, Neoplastic;HeLa Cells;Hormone Antagonists/pharmacology;Humans;Hydroxamic Acids/pharmacology;Male;Metribolone/pharmacology;Mifepristone/pharmacology;Nuclear Proteins/chemistry/metabolism;Nuclear Receptor Co-Repressor 1;Nuclear Receptor Co-Repressor 2;Promoter Regions, Genetic/physiology;Prostate/physiology;Prostatic Hyperplasia/metabolism/physiopathology;Protein Structure, Tertiary;Protein Synthesis Inhibitors/pharmacology;Receptors, Androgen/chemistry/metabolism;Receptors, Calcitriol/metabolism;Receptors, Interferon/metabolism;Receptors, Progesterone/chemistry/metabolism;Receptors, Retinoic Acid/genetics/metabolism;Repressor Proteins/chemistry/genetics/metabolism;Testosterone Congeners/pharmacology;Tumor Suppressor Protein p53/metabolism
Androgen and progesterone receptors (AR and PR) are two determining factors in gonadal differentiation that are highly expressed in developing and mature gonads. Loss of AR results in XY sex reversal and mutations causing reduced AR activity lead to varying degrees of defects in masculinization. Female PR knockout mice are infertile due to ovarian defects. While much has been discovered about positive regulation of these receptors by coactivators little is known about repression of the transcriptional activity of AR and PR in the presence of agonists. In this study we assessed the effect of SMRT and DAX-1 on AR and PR activity in the presence of both agonists and partial antagonists. We show that SMRT and DAX-1 repress agonist-dependent activity of both receptors, and the mechanism of repression includes disruption of the receptor dimer interactions rather than recruitment of histone deacetylases. We demonstrate that endogenous agonist-bound PR and DAX-1 in T47D breast cancer cells and endogenous AR and DAX-1 in LNCaP prostate cancer cells can be coimmunoprecipitated suggesting that the interaction is physiological. Surprisingly, although DAX-1 represses partial antagonist activity of AR, it was ineffective in repressing partial antagonist induced activity of PR. In contrast to most reported repressors, the expression of DAX-1 is restricted. We found that although DAX-1 is expressed in normal human prostate, its expression is strongly reduced in benign prostatic hyperplasia suggesting that DAX-1 plays a role in limiting AR activity in prostate.
LR: 20121115; GR: CA 58204/CA/NCI NIH HHS/United States; GR: HD 07165/HD/NICHD NIH HHS/United States; JID: 2985121R; 0 (DAX-1 Orphan Nuclear Receptor); 0 (DNA-Binding Proteins); 0 (Hormone Antagonists); 0 (Hydroxamic Acids); 0 (IFNGR2 protein, human); 0 (NCOR1 protein, human); 0 (NCOR2 protein, human); 0 (NR0B1 protein, human); 0 (Ncor1 protein, mouse); 0 (Ncor2 protein, mouse); 0 (Nr0b1 protein, mouse); 0 (Nuclear Proteins); 0 (Nuclear Receptor Co-Repressor 1); 0 (Nuclear Receptor Co-Repressor 2); 0 (Protein Synthesis Inhibitors); 0 (Receptors, Androgen); 0 (Receptors, Calcitriol); 0 (Receptors, Interferon); 0 (Receptors, Progesterone); 0 (Receptors, Retinoic Acid); 0 (Repressor Proteins); 0 (Testosterone Congeners); 0 (Tumor Suppressor Protein p53); 3X2S926L3Z (trichostatin A); 84371-65-3 (Mifepristone); 965-93-5 (Metribolone); 2003/05/27 [aheadofprint]; ppublish
United States
0021-9258; 0021-9258
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
PMID: 12771131; M305153200 [pii]
eng
Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.; IM
10.1074/jbc.M305153200
19
22
Journal Article
Agoulnik,I. U.;Tong,X. W.;Fischer,D. C.;Korner,K.;Atkinson,N. E.;Edwards,D. P.;Headon,D. R.;Weigel,N. L.;Kieback,D. G.
A germline variation in the progesterone receptor gene increases transcriptional activity and may modify ovarian cancer risk
The Journal of clinical endocrinology and metabolism
J.Clin.Endocrinol.Metab.
2004Dec891263406347
Animals;Binding, Competitive;COS Cells;Cercopithecus aethiops;DNA Transposable Elements;Female;Genetic Predisposition to Disease;Germ-Line Mutation;Hormones/metabolism;Humans;Introns;Osmolar Concentration;Ovarian Neoplasms/genetics;Receptors, Progesterone/genetics/metabolism;Transcription, Genetic;Transfection
Recently, we and others have detected a haplotype of the human progesterone receptor gene (PR). This haplotype consists of a 320-bp insertion in intron G together with point mutations in exons 4 and 5 and was named PROGINS. Whereas the exon 5 mutation is silent, the mutation in exon 4 results in a V660L substitution. Interestingly, this genetic polymorphism was seen to cosegregate with an increased risk of sporadic ovarian cancer in different ethnic groups. Our data provide evidence for the existence of an epidemiological link between a mutated progesterone receptor allele and ovarian cancer (odds ratio, 3.02; 95% confidence interval, 1.86-4.91). Functional characterization of the mutated receptor protein revealed a greater transcriptional activity compared with the wild-type receptor. By contrast, hormone binding and hormone dissociation rates were similar in both receptor proteins. We found that the increased transcriptional activity was due to increased stability resulting in higher expression of the mutant protein. Thus, the long-lasting hyperactivation of progesterone receptor-driven genes secondary to the increased transcriptional activity of the mutated progesterone receptor may participate in ovarian carcinogenesis. This is of special interest, because only a few genetic markers are available for the majority of women diagnosed with sporadic ovarian cancer.
JID: 0375362; 0 (DNA Transposable Elements); 0 (Hormones); 0 (Receptors, Progesterone); ppublish
United States
0021-972X; 0021-972X
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
PMID: 15579801; 89/12/6340 [pii]
eng
Journal Article; AIM; IM
10.1210/jc.2004-0114
19
23
Journal Article
Agoulnik,I. U.;Vaid,A.;Bingman,W. E.,3rd;Erdeme,H.;Frolov,A.;Smith,C. L.;Ayala,G.;Ittmann,M. M.;Weigel,N. L.
Role of SRC-1 in the promotion of prostate cancer cell growth and tumor progression
Cancer research
Cancer Res.20051-Sep651779597967
Androgens/physiology;Cell Growth Processes/physiology;Cell Line, Tumor;Disease Progression;HeLa Cells;Histone Acetyltransferases;Humans;Male;Nuclear Receptor Coactivator 1;Oligonucleotides, Antisense/genetics;Prostatic Neoplasms/genetics/metabolism/pathology;Receptors, Androgen/genetics/metabolism/physiology;Transcription Factors/biosynthesis/genetics/physiology;Transfection
Prostate cancer is initially androgen dependent and there is evidence that androgen receptor continues to play a role in androgen-independent prostate cancer. Androgen receptor activity depends both on the level of androgens and on the level of coactivators that interact with androgen receptor. Our goal was to evaluate the role of the androgen receptor coactivator SRC-1 in prostate cancer progression. Using tissue arrays to measure SRC-1 protein levels, we found that increased SRC-1 expression in clinically localized, androgen-dependent cancer is associated with clinical and pathologic variables of increased tumor aggressiveness. Interestingly, there was variable expression of SRC-1 in normal prostate tissue which correlated with the staining intensity of the corresponding cancer tissue. To test the contribution of SRC-1, we examined its role in androgen-dependent LNCaP and androgen-independent C4-2 prostate cancer cell lines. Using small interfering RNA to reduce expression of androgen receptor, we found that androgen receptor was required both for cell growth and for basal expression of prostate-specific antigen in the androgen-independent C4-2 cell line. Thus, although the cells can grow in an androgen-depleted medium, they remained androgen receptor dependent. Reduction of SRC-1 expression significantly reduced growth and altered androgen receptor target gene regulation in both LNCaP and C4-2 cell lines whereas it had no effect on the growth of the androgen receptor-negative PC-3 and DU145 prostate cancer cell lines. Although the requirement for androgens and androgen receptor in the development of prostate cancer is well established, our study implicates enhanced androgen receptor activity through elevated expression of SRC-1 in the development of more aggressive disease in men with prostate cancer.
LR: 20091119; GR: CA58204/CA/NCI NIH HHS/United States; GR: DK65252/DK/NIDDK NIH HHS/United States; GR: T32-DK07763/DK/NIDDK NIH HHS/United States; JID: 2984705R; 0 (Androgens); 0 (Oligonucleotides, Antisense); 0 (Receptors, Androgen); 0 (Transcription Factors); EC 2.3.1.48 (Histone Acetyltransferases); EC 2.3.1.48 (NCOA1 protein, human); EC 2.3.1.48 (Nuclear Receptor Coactivator 1); ppublish
United States
0008-5472; 0008-5472
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
PMID: 16140968; 65/17/7959 [pii]
eng
Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.; IM
10.1158/0008-5472.CAN-04-3541
19
24
Journal Article
Agoulnik,I. U.;Vaid,A.;Nakka,M.;Alvarado,M.;Bingman,W. E.,3rd;Erdem,H.;Frolov,A.;Smith,C. L.;Ayala,G. E.;Ittmann,M. M.;Weigel,N. L.
Androgens modulate expression of transcription intermediary factor 2, an androgen receptor coactivator whose expression level correlates with early biochemical recurrence in prostate cancer
Cancer research
Cancer Res.20061-Nov66211059410602
Androgens/pharmacology;Cell Line, Tumor;Cell Proliferation;Exons;Humans;Immunohistochemistry;Introns;Male;Metribolone/pharmacology;Neoplasm Recurrence, Local;Neoplasms, Hormone-Dependent/chemistry/pathology;Nuclear Receptor Coactivator 2/analysis/genetics/physiology;Prostatic Neoplasms/chemistry/pathology;Receptors, Androgen/metabolism;Thymidine/metabolism
Prostate cancer is an androgen-dependent disease; metastatic prostate cancer is typically treated by androgen receptor (AR) blockade. Recurrence after androgen ablation and evidence that AR continues to play a role in many prostate cancers has led to an examination of other factors that potentiate AR activity. AR is a ligand-activated transcription factor whose activity is regulated not only by hormone but also by the levels of coactivators recruited by AR to facilitate transcription. We sought to assess the consequences of reducing expression of the transcription intermediary factor 2 (TIF2) coactivator on prostate cancer cell growth and AR action in cell lines to examine TIF2 expression in prostate cancer and to correlate expression with clinical outcome. Depletion of TIF2 reduced expression of AR-induced target genes and slowed proliferation of AR-dependent and AR-independent prostate cancer cells. Remarkably, we found that TIF2 expression is directly repressed by high levels of androgens in multiple AR-expressing cell lines. Expression of a reporter containing 5'-flanking region of the TIF2 was repressed both by androgens and by the antagonist, Casodex. Expression of TIF2 correlates with biochemical (prostate-specific antigen) recurrence (P = 0.0136). In agreement with our in vitro findings, the highest expression of TIF2 was found in patients whose cancer relapsed after androgen ablation therapy, supporting the idea that AR blockade might activate pathways that lead to stimulation of AR-dependent and AR-independent proliferation of prostate epithelium. The elevated expression of TIF2 at low hormone levels likely aids in inducing AR activity under these conditions; treatment with Casodex has the potential to counteract this induction.
LR: 20071203; GR: CA58204/CA/NCI NIH HHS/United States; GR: DK65252/DK/NIDDK NIH HHS/United States; GR: T32-DK07763/DK/NIDDK NIH HHS/United States; JID: 2984705R; 0 (Androgens); 0 (NCOA2 protein, human); 0 (Nuclear Receptor Coactivator 2); 0 (Receptors, Androgen); 50-89-5 (Thymidine); 965-93-5 (Metribolone); ppublish
United States
0008-5472; 0008-5472
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
PMID: 17079484; 66/21/10594 [pii]
eng
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; IM
10.1158/0008-5472.CAN-06-1023
19
25
Book, Section
Agoulnik,I. U.;Weigel N.L.
Androgen Receptor Coactivators and Prostate Cancer
2006 5
Hormonal Carcinogenesis
International Symposium on Hormonal Carcinogenesis
19
26
Journal Article
Agoulnik,I. U.;Weigel,N. L.
Coactivator selective regulation of androgen receptor activity
SteroidsSteroids2009Aug748669674
Androgens;Animals;Cell Line, Tumor;Cell Proliferation;Cyproterone Acetate/metabolism;Gene Expression Regulation, Neoplastic;Histone Acetyltransferases/genetics/metabolism;Humans;Male;Nuclear Receptor Coactivator 1;Nuclear Receptor Coactivator 3;Prostatic Neoplasms/pathology;RNA, Long Untranslated;RNA, Untranslated/genetics/metabolism;Receptors, Androgen/genetics/metabolism;Substrate Specificity;Transcription Factors/deficiency/genetics/metabolism;Transcription, Genetic;Transcriptional Activation
The androgen receptor (AR) is a ligand activated nuclear receptor, which regulates transcription and stimulates growth of androgen dependent prostate cancer. To regulate transcription, AR recruits a series of coactivators that modify chromatin and facilitate transcription. However, information on ligand and target gene-specific requirements for coactivators is limited. We compared the actions of the p160 coactivators SRC-1 and SRC-3/RAC3 with SRA (steroid receptor RNA activator). All three coactivate AR in the presence of agonist as expected. However, overexpression of either SRC-1 or SRC-3 increased AR activity in response to the partial antagonist, cyproterone acetate, whereas SRA was unable to stimulate AR activity under these conditions. Using siRNA to reduce expression of these coactivators in LNCaP cells, we also found promoter specific requirement for these coactivators. SRC-3 is required for optimal androgen dependent induction of PSA, TMPRSS2, and PMEPA1 whereas SRA is required only for optimal induction of the TMPRSS2 gene. These data indicate that different groups of AR target genes have distinct requirements for coactivators and response to AR ligands.
LR: 20121115; GR: P50-CA58204/CA/NCI NIH HHS/United States; GR: R01 DK065252-04/DK/NIDDK NIH HHS/United States; GR: R01DK65252/DK/NIDDK NIH HHS/United States; GR: T32HD07165/HD/NICHD NIH HHS/United States; JID: 0404536; 0 (Androgens); 0 (RNA, Long Untranslated); 0 (RNA, Untranslated); 0 (Receptors, Androgen); 0 (Transcription Factors); 0 (steroid receptor RNA activator); 427-51-0 (Cyproterone Acetate); EC 2.3.1.48 (Histone Acetyltransferases); EC 2.3.1.48 (NCOA1 protein, human); EC 2.3.1.48 (Nuclear Receptor Coactivator 1); EC 2.3.1.48 (Nuclear Receptor Coactivator 3); NIHMS100819; OID: NLM: NIHMS100819; OID: NLM: PMC2687407; 2008/12/17 [received]; 2009/02/10 [revised]; 2009/02/22 [accepted]; 2009/03/09 [aheadofprint]; ppublish
United States
1878-5867; 0039-128X
Department of Molecular and Cellular Biology, Baylor College of Medicine, M130, One Baylor Plaza, Houston, TX 77030, United States.
PMID: 19463689; S0039-128X(09)00057-9 [pii]
eng
Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.; IM
10.1016/j.steroids.2009.02.007; 10.1016/j.steroids.2009.02.007
19
27
Journal Article
Agoulnik,I. U.;Weigel,N. L.
Androgen receptor coactivators and prostate cancer
Advances in Experimental Medicine and Biology
Adv.Exp.Med.Biol.
2008 617 245255
Histone Acetyltransferases/metabolism;Humans;Male;Nuclear Receptor Coactivator 1;Nuclear Receptor Coactivator 2/metabolism;Prostatic Neoplasms/drug therapy/metabolism;Receptors, Androgen/metabolism;Transcription Factors/metabolism
LR: 20091119; JID: 0121103; 0 (Nuclear Receptor Coactivator 2); 0 (Receptors, Androgen); 0 (Transcription Factors); EC 2.3.1.48 (Histone Acetyltransferases); EC 2.3.1.48 (NCOA1 protein, human); EC 2.3.1.48 (Nuclear Receptor Coactivator 1); RF: 45; ppublish
United States
0065-2598; 0065-2598
Dept. of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
PMID: 18497048
eng
Journal Article; Review; IM
10.1007/978-0-387-69080-3_23; 10.1007/978-0-387-69080-3_23
19
28
Journal Article
Agoulnik,I. U.;Weigel,N. L.
Androgen receptor action in hormone-dependent and recurrent prostate cancer
Journal of cellular biochemistry
J.Cell.Biochem.
20061-Oct992362372
Androgens/metabolism;Animals;Cell Proliferation;Gene Expression;Humans;Male;Models, Biological;Mutation;Neoplasm Recurrence, Local/genetics/metabolism/pathology;Neoplasms, Hormone-Dependent/genetics/metabolism/pathology;Prostatic Neoplasms/genetics/metabolism/pathology;Receptors, Androgen/chemistry/genetics/metabolism;Signal Transduction
The importance of androgens and androgen receptors (AR) in primary prostate cancer is well established. Metastatic disease is usually treated with some form of androgen ablation, which is effective for a limited amount of time. The role of AR in prostate cancers that recur despite androgen ablation therapy is less certain. Most of these tumors express prostate specific antigen (PSA), an androgen-regulated gene; moreover, AR is generally highly expressed in recurrent prostate cancer. We propose that AR continues to play a role in many of these tumors and that it is not only the levels of AR, ligands, and co-regulators, but also the changes in cell signaling that induce AR action in recurrent prostate cancer. These pathways are, therefore, potential therapeutic targets.
LR: 20071114; CI: Copyright 2006; GR: CA58204/CA/NCI NIH HHS/United States; GR: DK65252/DK/NIDDK NIH HHS/United States; JID: 8205768; 0 (Androgens); 0 (Receptors, Androgen); RF: 50; ppublish
Wiley-Liss, Inc
United States
0730-2312; 0730-2312
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
PMID: 16619264
eng
Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.; Review; IM
10.1002/jcb.20811
19
29
Journal Article
Agoulnik,I. Y.;Cho,Y.;Niederberger,C.;Kieback,D. G.;Cooney,A. J.
Cloning, expression analysis and chromosomal localization of the human nuclear receptor gene GCNF
FEBS lettersFEBS Lett.19986-Mar4242-Jan7378
Adult;Amino Acid Sequence;Chromosome Mapping;Chromosomes, Human, Pair 9;Cloning, Molecular;DNA-Binding Proteins/analysis/genetics/metabolism;Genomic Library;Humans;In Situ Hybridization;Male;Molecular Sequence Data;Nuclear Receptor Subfamily 6, Group A, Member 1;Receptors, Cytoplasmic and Nuclear/analysis/genetics/metabolism;Sequence Alignment;Sequence Homology, Amino Acid;Testis/chemistry/cytology/metabolism
Germ cell nuclear factor (GCNF) is an orphan member of the nuclear receptor gene superfamily. We report the cloning of a cDNA encoding a new variant of human GCNF from human testis and its expression analysis. Southern blot analysis of the human genomic DNA indicates that the GCNF gene is not closely related to other members within the nuclear receptor superfamily. Chromosomal localization of the GCNF gene shows that the gene is located on chromosome 9 at the locus q33-34.1. In situ hybridization analysis of GCNF expression in the testis shows that human GCNF is expressed exclusively in germ cells.
LR: 20091119; GENBANK/AF004291; JID: 0155157; 0 (DNA-Binding Proteins); 0 (NR6A1 protein, human); 0 (Nuclear Receptor Subfamily 6, Group A, Member 1); 0 (Receptors, Cytoplasmic and Nuclear); ppublish
NETHERLANDS
0014-5793; 0014-5793
Department of Obstetrics and Gynecology, Houston, TX 77005, USA.
PMID: 9537518; S0014-5793(98)00142-2 [pii]
eng
Journal Article; IM
19
30
Journal Article
Agudelo,M.;Gandhi,N.;Saiyed,Z.;Pichili,V.;Thangavel,S.;Khatavkar,P.;Yndart-Arias,A.;Nair,M.
Effects of alcohol on histone deacetylase 2 (HDAC2) and the neuroprotective role of trichostatin A (TSA)
Alcoholism, Clinical and Experimental Research
Alcohol.Clin.Exp.Res.
2011Aug35815501556
Cell Line;Central Nervous System Depressants/toxicity;Dose-Response Relationship, Drug;Ethanol/toxicity;Gene Expression/drug effects;Histone Deacetylase 2/drug effects/genetics/metabolism;Histone Deacetylase Inhibitors/pharmacology;Humans;Hydroxamic Acids/metabolism/pharmacology;Neuroprotective Agents/metabolism/pharmacology;Reactive Oxygen Species/analysis/metabolism
BACKGROUND: Previous studies have implicated histone deacetylases (HDACs) and HDAC inhibitors (HDIs) such as trichostatin A (TSA) in the regulation of gene expression during drug addiction. Furthermore, an increase in HDAC activity has been linked to neurodegeneration. Alcohol has also been shown to promote abundant generation of reactive oxygen species (ROS) resulting in oxidative stress. TSA inhibits HDACs and has been shown to be neuroprotective in other neurodegenerative disease models. Although HDACs and HDIs have been associated with drug addiction, there is no evidence of the neurodegenerative role of HDAC2 and neuroprotective role of TSA in alcohol addiction. Therefore, we hypothesize that alcohol modulates HDAC2 through mechanisms involving oxidative stress. METHODS: To test our hypothesis, the human neuronal cell line, SK-N-MC, was treated with different concentrations of ethanol (EtOH); HDAC2 gene and protein expression were assessed at different time points. Pharmacological inhibition of HDAC2 with TSA was evaluated at the gene level using qRT-PCR and at the protein level using Western blot and flow cytometry. ROS production was measured with a fluorescence microplate reader and fluorescence microscopy. RESULTS: Our results showed a dose-dependent increase in HDAC2 expression with EtOH treatment. Additionally, alcohol significantly induced ROS, and pharmacological inhibition of HDAC2 with TSA was shown to be neuroprotective by significantly inhibiting HDAC2 and ROS. CONCLUSIONS: These results suggest that EtOH can upregulate HDAC2 through mechanisms involving oxidative stress and HDACs may play an important role in alcohol use disorders (AUDs). Moreover, the use of HDIs may be of therapeutic significance for the treatment of neurodegenerative disorders including AUDs.
LR: 20130630; CI: Copyright (c) 2011; GR: R01 DA012366-01A1/DA/NIDA NIH HHS/United States; GR: R01 DA021537-01/DA/NIDA NIH HHS/United States; GR: R01 DA027049-04/DA/NIDA NIH HHS/United States; GR: R01 MH085259-03/MH/NIMH NIH HHS/United States; GR: R01DA012366/DA/NIDA NIH HHS/United States; GR: R01DA021537/DA/NIDA NIH HHS/United States; GR: R37 DA025576-01/DA/NIDA NIH HHS/United States; GR: R37 DA025576-04/DA/NIDA NIH HHS/United States; GR: R37DA025576/DA/NIDA NIH HHS/United States; JID: 7707242; 0 (Central Nervous System Depressants); 0 (Histone Deacetylase Inhibitors); 0 (Hydroxamic Acids); 0 (Neuroprotective Agents); 0 (Reactive Oxygen Species); 3X2S926L3Z (trichostatin A); 64-17-5 (Ethanol); EC 3.5.1.98 (Histone Deacetylase 2); NIHMS275767; OID: NLM: NIHMS275767; OID: NLM: PMC3128172; 2011/03/29 [aheadofprint]; ppublish
by the Research Society on Alcoholism
England
1530-0277; 0145-6008
Department of Immunology, Florida International University, Miami, FL 33199, USA.
PMID: 21447001
eng
Journal Article; Research Support, N.I.H., Extramural; IM
10.1111/j.1530-0277.2011.01492.x; 10.1111/j.1530-0277.2011.01492.x
80
31
Journal Article
Agudelo,M.;Newton,C.;Widen,R.;Sherwood,T.;Nong,L.;Friedman,H.;Klein,T. W.
Cannabinoid receptor 2 (CB2) mediates immunoglobulin class switching from IgM to IgE in cultures of murine-purified B lymphocytes
Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology
J.Neuroimmune Pharmacol.
2008Mar313542
Animals;B-Lymphocytes/drug effects/immunology/metabolism;Bornanes/pharmacology;Cannabinoids/pharmacology;Cyclohexanols/pharmacology;Enzyme-Linked Immunosorbent Assay;Flow Cytometry;Immunoglobulin Class Switching/drug effects/physiology;Immunoglobulin E/immunology;Immunoglobulin M/immunology;Mice;Piperidines/pharmacology;Pyrazoles/pharmacology;Receptor, Cannabinoid, CB2/drug effects/immunology/metabolism;Th2 Cells/immunology
Marijuana cannabinoid treatment increases Th2 activity, and previous reports showed that B cells express the highest level of CB(2) mRNA relative to other immune cells, suggesting that cannabinoids play a critical role in B cell activation and maturation. We previously reported evidence of Th2 biasing and class switching in cannabinoid-treated and antigen-challenged mice. We now explore the possibility that cannabinoids directly influence B cell antibody class switching. Mouse splenic B cells were purified by negative selection and cultured with IL4 and anti-CD40 in the presence or absence of the nonselective cannabinoid agonist, CP55940, or the CB(1) selective cannabinoid agonist, methanandamide, and analyzed at different days by flow cytometry for surface expression of either IgM or IgE. Cells treated with CP55940 showed an increase in expression of IgE by day 5 in culture; methanandamide had no effect. CP55940 also induced an increase in secreted IgE in culture supernatants as analyzed by ELISA. In addition, CB(2) receptors were increased on B cells after stimulation with IL-4 and anti-CD40, and the class switching effect of CP55940 was attenuated by the CB(2) antagonist, SR144528. These results suggest that cannabinoids bias toward Th2-type immunity by directly inducing B cell class switching from IgM to IgE through a mechanism involving CB(2) receptors.
LR: 20130606; GR: DA019824/DA/NIDA NIH HHS/United States; GR: R01 DA019824-02/DA/NIDA NIH HHS/United States; JID: 101256586; 0 (Bornanes); 0 (Cannabinoids); 0 (Cyclohexanols); 0 (Immunoglobulin M); 0 (Piperidines); 0 (Pyrazoles); 0 (Receptor, Cannabinoid, CB2); 0 (SR 144528); 158681-13-1 (rimonabant); 37341-29-0 (Immunoglobulin E); 83003-12-7 (3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol); NIHMS49271; OID: NLM: NIHMS49271; OID: NLM: PMC2423231; 2007/06/15 [received]; 2007/08/16 [accepted]; 2007/09/27 [aheadofprint]; ppublish
United States
1557-1904; 1557-1890
Department of Molecular Medicine, School of Biomedical Sciences, College of Medicine, University of South Florida, Tampa, FL 33612, USA.
PMID: 18247126
eng
In Vitro; Journal Article; Research Support, N.I.H., Extramural; IM
10.1007/s11481-007-9088-9; 10.1007/s11481-007-9088-9
80
32
Journal Article
Agudelo,M.;Yoo,C.;Nair,M. P.
Alcohol-induced serotonergic modulation: the role of histone deacetylases
Alcohol (Fayetteville, N.Y.)
Alcohol2012Nov467635642
Blotting, Western;Cell Line;Dose-Response Relationship, Drug;Enzyme-Linked Immunosorbent Assay;Ethanol/toxicity;Flow Cytometry;Fluorometry;Gene Expression Regulation, Enzymologic/drug effects;Histone Acetyltransferases/metabolism;Histone Deacetylase 1/genetics/metabolism;Histone Deacetylase Inhibitors/pharmacology;Histone Deacetylases/genetics/metabolism;Humans;Hydroxamic Acids/pharmacology;Ondansetron/pharmacology;Real-Time Polymerase Chain Reaction;Receptors, Serotonin, 5-HT3/drug effects/genetics/metabolism;Serotonergic Neurons/drug effects/enzymology;Serotonin/metabolism;Serotonin 5-HT3 Receptor Antagonists/pharmacology;Time Factors;Up-Regulation
Previous studies have demonstrated that alcohol use disorders (AUDs) are regulated by multiple mechanisms such as neurotransmitters and enzymes. The neurotransmitter, serotonin (5-hydroxytryptamine, 5-HT) may contribute to alcohol effects and serotonin receptors, including 5-HT3, play an important role in AUDs. Recent studies have also implicated histone deacetylases (HDACs) and acetyltransferases (HATS) in regulation of drug addiction, and HDAC inhibitors (HDACi) have been reported as transcriptional modulators of monoaminergic neurotransmission. Therefore, we hypothesize that HDACs may play a role in ethanol-induced serotonergic modulation. The effects of ethanol on serotonin and 5-HT3, and the role HDACs, HDAC activity and the HDACi, trichostatin A (TSA), play in alcohol-induced serotonergic effects were studied. Human SK-N-MC and neurons, were treated with ethanol (0.05, 0.1 and 0.2%), and/or TSA (50 nM), and 5-HT3 levels were assessed at 24-72 h. Gene expression was evaluated by qRT-PCR and protein by western blot and flow cytometry. Serotonin release was assessed by ELISA and HDAC activity by fluorometric assay. Our results show an increase in 5-HT3 gene after ethanol treatment. Further, ethanol significantly increased HDACs 1 and 3 genes accompanied by an increased in HDAC activity while TSA significantly inhibited HDACs. Studies with TSA show a significant upregulation of ethanol effects on 5-HT3, while surprisingly TSA inhibited ethanol-induced serotonin production. These results suggest that ethanol affects 5-HT3 and serotonin through mechanisms involving HDACs and HATs. In summary, our studies demonstrate some of the novel properties of HDAC inhibitors and contribute to the understanding of the mechanisms involve in alcohol-serotonergic modulation in the CNS.
LR: 20130416; CI: Published by Elsevier Inc.; GR: R01 DA021537-06/DA/NIDA NIH HHS/United States; GR: R01 MH085259/MH/NIMH NIH HHS/United States; GR: R01 MH085259-04/MH/NIMH NIH HHS/United States; GR: R01DA021537/DA/NIDA NIH HHS/United States; GR: R01MH085259/MH/NIMH NIH HHS/United States; GR: R37 DA025576-05/DA/NIDA NIH HHS/United States; JID: 8502311; 0 (Histone Deacetylase Inhibitors); 0 (Hydroxamic Acids); 0 (Receptors, Serotonin, 5-HT3); 0 (Serotonin 5-HT3 Receptor Antagonists); 3X2S926L3Z (trichostatin A); 50-67-9 (Serotonin); 64-17-5 (Ethanol); 99614-02-5 (Ondansetron); EC 2.3.1.48 (Histone Acetyltransferases); EC 3.5.1.98 (HDAC1 protein, human); EC 3.5.1.98 (Histone Deacetylase 1); EC 3.5.1.98 (Histone Deacetylases); EC 3.5.1.98 (histone deacetylase 3); NIHMS370298; OID: NLM: NIHMS370298 [Available on 11/01/13]; OID: NLM: PMC3455143 [Available on 11/01/13]; PMCR: 2013/11/01 00:00; 2011/10/28 [received]; 2012/03/21 [revised]; 2012/03/22 [accepted]; 2012/07/12 [aheadofprint]; ppublish
United States
1873-6823; 0741-8329
Florida International University, Miami, 33199, USA.
PMID: 22796363; S0741-8329(12)00064-X [pii]; S0741-8329(12)00064-X [pii]
eng
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; IM
10.1016/j.alcohol.2012.03.005; 10.1016/j.alcohol.2012.03.005
80
33
Journal Article
Agul'nik,A. I.;Agul'nik,S. I.;Ruvinskii,A. O.
Meiotic drive of t-haplotypes: segregation of chromosomes in mice with partial trisomy
GenetikaGenetika1990Oct261017761782
Animals;Chromosomes;Haplotypes;Male;Meiosis;Mice;Mutation;Translocation, Genetic;Trisomy
The properties of the t haplotypes, specific mutant states of the proximal region of chromosome 17 in the house mouse keep renewing interest. One such property is increased transmission of the t haplotype from heterozygous t/+ males to their offspring. By means of reciprocal translocation T (16; 17)43H, we have constructed males with tertiary trisomy 17 (+T43/++/RB7+) carrying Robertsonian translocation Rb(16.17)7Bnr. The offspring of these males was viable when sperm of +T43/++ and Rb7+ was used. The segregation patterns in the offspring of t-bearing trisomics were analysed on days 16-18 of embryonic development. It was found that in the case when the t haplotype is on the normal acrocentric (male male ++T43/+t12+/Rb7++), its presence in the gamete +t12+/++T43 does not produce meiotic drive. However, when t6 is on Rb7, meiotic drive was equal to 80%. It is concluded that the presence of a normal homolog and a t-bearing chromosome in sperm does not result in meiotic drive. Possible mechanisms of meiotic drive of the t haplotypes are discussed.
LR: 20061115; JID: 0047354; ppublish
USSR
0016-6758; 0016-6758
PMID: 2283048
rus
English Abstract; Journal Article; IM
Meioticheskii draiv t-gaplotipov: segregatsiia khromosom u myshei s chastichnoi trisomiei
49
34
Journal Article
Agulnik,A. I.;Agulnik,S. I.;Ruvinsky,A. O.
Two doses of the paternal Tme gene do not compensate the lethality of the Thp deletion
The Journal of heredity
J.Hered.1991Jul-Aug824351353
Animals;Chromosome Deletion;Crosses, Genetic;Dosage Compensation, Genetic;Female;Genes, Lethal;Male;Mice;Mutation;Tail;Trisomy
The hairpin-tail (Thp) deletion in chromosome 17 is lethal when it is inherited from the mother, whereas heterozygotes with Thp deletion that is paternal in origin are viable. The lethal effect of maternal Thp is due to a deficiency of the Tme gene that is located in the Thp-deleted region. In this article we describe analysis of the viability of mice with tertiary trisomy of chromosome 17, Ts(17(16]43H, with different doses of the paternal and maternal Tme alleles. We demonstrate that the presence of an additional copy of the region with the Tme gene in the female gamete entirely compensates maternal Thp lethality. We failed to compensate the absence of the Tme gene from the chromosome of maternal derivation by two doses of Tme derived from the father. Thus evidence was obtained indicating that there are significant differences between the activities of the paternal and maternal alleles of the Tme gene due to chromosome imprinting.
LR: 20051117; JID: 0375373; GS: Thp; GS: Tme; ppublish
UNITED STATES
0022-1503; 0022-1503
Institute of Cytology and Genetics, Siberian Branch of the Academy of Sciences of the USSR, Novosibirsk.
PMID: 1880396
eng
Journal Article; IM
49
35
Journal Article
Agulnik,A. I.;Agulnik,S. I.;Ruvinsky,A. O.
Meiotic drive of t haplotypes: chromosome segregation in mice with tertiary trisomy
Genetical research
Genet.Res.1991Feb5715154
Animals;Chromosomes/physiology;Crosses, Genetic;Female;Haplotypes;Male;Meiosis;Mice;Mice, Mutant Strains;Translocation, Genetic;Trisomy
The properties of the t haplotypes, specific mutant states of the proximal region of chromosomes 17 in the house mouse, are of continuing interest. One such property is increased transmission of the t haplotype by heterozygous t/+ males to offspring. Using the reciprocal translocation T(16;17)43H we have constructed males with tertiary trisomy of chromosome 17 (+T43/+ +/Rb7+) carrying the Robertsonian translocation Rb(16.17)7Bnr. Only the progeny of these males which had inherited either T43/+ or Rb7 from their male parent were viable. The segregation patterns in the offspring of t-bearing trisomics were analysed on days 16-18 of embryonic development. It was found that, when the t12 haplotype is in the normal acrocentric (males+ +T43/+ t12 + /Rb7+ +), its presence in the gamete +t12+/+ + T43 does not produce meiotic drive. However, when t6 is in Rb7, meiotic drive was observed: 80% of offspring carried the t haplotype. It is concluded that the meiotic drive is probably inhibited by the presence of a normal homologue of chromosome 17 in the same sperm. Possible mechanisms for the t haplotype effect are discussed.
LR: 20041117; JID: 0370741; EIN: Genet Res 1991 Apr;57(2):206; ppublish
ENGLAND 0016-6723
Institute of Cytology and Genetics, Academy of Sciences of the USSR, Novosibirsk.
PMID: 2040454
eng
Journal Article; IM
49
36
Journal Article
Agulnik,A. I.;Bishop,C. E.;Lerner,J. L.;Agulnik,S. I.;Solovyev,V. V.
Analysis of mutation rates in the SMCY/SMCX genes shows that mammalian evolution is male driven
Mammalian genome : official journal of the International Mammalian Genome Society
Mamm.Genome
1997Feb82134138
Amino Acid Sequence;Animals;Base Sequence;DNA, Complementary;Evolution, Molecular;Histone Demethylases;Histone-Lysine N-Methyltransferase;Horses;Humans;Male;Mice;Molecular Sequence Data;Mutation;Oxidoreductases, N-Demethylating;Proteins/genetics;Sequence Homology, Amino Acid;Sex Characteristics;X Chromosome;Y Chromosome
Mammalian evolution is believed to be male driven because the greater number of germ cell divisions per generation in males increases the opportunity for errors in DNA replication. Since the Y Chromosome (Chr) replicates exclusively in males, its genes should also evolve faster than X or autosomal genes. In addition, estimating the overall male-to-female mutation ratio (alpha m) is of great importance as a large alpha m implies that replication-independent mutagenic events play a relatively small role in evolution. A small alpha m suggests that the impact of these factors may, in fact, be significant. In order to address this problem, we have analyzed the rates of evolution in the homologous X-Y common SMCX/SMCY genes from three different species--mouse, human, and horse. The SMC genes were chosen because the X and Y copies are highly homologous, well conserved in evolution, and in all probability functionally interchangeable. Sequence comparisons and analysis of synonymous substitutions in approximately 1kb of the 5' coding region of the SMC genes reveal that the Y-linked copies are evolving approximately 1.8 times faster than their X homologs. The male-to-female mutation ratio alpha m was estimated to be 3. These data support the hypothesis that mammalian evolution is male driven. However, the ratio value is far smaller than suggested in earlier works, implying significance of replication-independent mutagenic events in evolution.
LR: 20120302; GENBANK/L25270; GENBANK/U52363; GENBANK/U52364; GENBANK/U52365; GENBANK/Z29651; GENBANK/Z29652; JID: 9100916; 0 (DNA, Complementary); 0 (Jarid1d protein, mouse); 0 (Proteins); EC 1.14.11.- (Histone Demethylases); EC 1.14.11.- (KDM5D protein, human); EC 1.5.- (KDM5C protein, human); EC 1.5.- (Kdm5c protein, mouse); EC 1.5.- (Oxidoreductases, N-Demethylating); EC 2.1.1.43 (Histone-Lysine N-Methyltransferase); ppublish
UNITED STATES
0938-8990; 0938-8990
Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas 77030, USA.
PMID: 9060413
eng
Journal Article; IM
49
37
Journal Article
Agulnik,A. I.;Harrison,W. R.;Bishop,C. E.
Smcy transgene does not rescue spermatogenesis in sex-reversed mice
Mammalian genome : official journal of the International Mammalian Genome Society
Mamm.Genome
2001Feb122112116
Animals;Chromosome Banding;Chromosomes, Artificial, Yeast;Disorders of Sex Development;Female;Genotype;In Situ Hybridization, Fluorescence;Male;Mice;Mice, Inbred Strains;Mice, Transgenic;Physical Chromosome Mapping;Polymorphism, Genetic;Proteins/genetics/metabolism;Spermatogenesis/genetics;Testis/anatomy & histology/cytology/growth & development;Transgenes;Y Chromosome/genetics
In mouse, the Sxr(b) deletion interval (delta Sxr(b)) maps to the small short arm of the Y chromosome and is known to contain gene(s) required for normal spermatogenesis; in particular, Spy, which is essential for the postnatal mitotic proliferation of spermatogonia. This deletion interval is approximately 1-2 Mb and contains eight known genes. In this paper we report the construction of YAC transgenic mice containing different regions of the delta Sxr(b) interval including Zfy1, Ube1y, Smcy, and Eif2s3. Two male and one female founder mice, transgenic for all four genes, were sterile. However, a fertile transgenic, carrying a full-length copy of the Smcy gene integrated into central Chr 12, was identified. Smcy is a highly conserved Y chromosome-located gene, encoding peptides corresponding to epitopes of the male-specific antigen, H-Y. The Smcy transgene was ubiquitously expressed in all organs and tissues tested in male and female carriers. Introduction of the transgene into an X Sxr(b)/O genetic background did not rescue the early arrest of spermatogenesis characteristic of these males. These data indicate that the presence of Smcy is not sufficient to restore spermatogenesis, making it a highly unlikely candidate for Spy.
LR: 20101118; JID: 9100916; 0 (Jarid1d protein, mouse); 0 (Proteins); ppublish
United States
0938-8990; 0938-8990
Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas 77030, USA. agoulnik@bcm.tmc.edu
PMID: 11210179
eng
Journal Article; Research Support, U.S. Gov't, P.H.S.; IM
49
38
Journal Article
Agulnik,A. I.;Longepied,G.;Ty,M. T.;Bishop,C. E.;Mitchell,M.
Mouse H-Y encoding Smcy gene and its X chromosomal homolog Smcx
Mammalian genome : official journal of the International Mammalian Genome Society
Mamm.Genome
1999Sep109926929
Alternative Splicing;Amino Acid Sequence;Animals;Base Sequence;DNA, Complementary/genetics;Exons;Female;Genetic Variation;H-Y Antigen/genetics;Histone Demethylases;Histone-Lysine N-Methyltransferase;Humans;Introns;Male;Mice;Molecular Sequence Data;Oxidoreductases, N-Demethylating;Proteins/genetics;Sequence Homology, Amino Acid;Species Specificity;X Chromosome/genetics;Y Chromosome/genetics
LR: 20120302; GENBANK/AF127244; GENBANK/AF127245; GR: HD27584/HD/NICHD NIH HHS/United States; JID: 9100916; 0 (DNA, Complementary); 0 (H-Y Antigen); 0 (Jarid1d protein, mouse); 0 (Proteins); EC 1.14.11.- (Histone Demethylases); EC 1.14.11.- (KDM5D protein, human); EC 1.5.- (KDM5C protein, human); EC 1.5.- (Kdm5c protein, mouse); EC 1.5.- (Oxidoreductases, N-Demethylating); EC 2.1.1.43 (Histone-Lysine N-Methyltransferase); ppublish
UNITED STATES
0938-8990; 0938-8990
Department of Obstetrics and Gynecology, 6550 Fannin St., Baylor College of Medicine, Houston, Texas 77030, USA.
PMID: 10441747; MGS2135 [pii]
eng
Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.; IM
49
39
Journal Article
Agulnik,A. I.;Mitchell,M. J.;Lerner,J. L.;Woods,D. R.;Bishop,C. E.
A mouse Y chromosome gene encoded by a region essential for spermatogenesis and expression of male-specific minor histocompatibility antigens
Human molecular genetics
Hum.Mol.Genet.
1994Jun36873878
Amino Acid Sequence;Animals;Base Sequence;Chromosome Mapping;Chromosomes, Artificial, Yeast;DNA/genetics;DNA Primers;Female;Gene Expression/genetics;H-Y Antigen/biosynthesis/genetics;Humans;Male;Mice/genetics;Molecular Sequence Data;Polymerase Chain Reaction/methods;RNA-Directed DNA Polymerase;Restriction Mapping;Sequence Deletion;Sequence Homology, Amino Acid;Sex Characteristics;Spermatogenesis/genetics;Testis/metabolism;Y Chromosome
A new mouse Y chromosome gene, Smcy, has been isolated from the region encoding Spy, a spermatogenesis gene and Hya and Sdma, the genes that, respectively, control the expression of the male specific minor histocompatibility antigen H-Y, as measured by specific T-cell assays and the serologically detected male antigen SDMA. Smcy is well conserved on the Y in mouse, man and even marsupials. It is expressed in all adult male tissues tested and can also be detected during mouse development from as early as two cells. In addition, its human Y homologue, SMCY, is expressed in multiple tissues and maps to the same Yq deletion interval as the human H-Y antigen controlling locus, HY.
LR: 20061115; GENBANK/Z29652; JID: 9208958; 0 (DNA Primers); 0 (H-Y Antigen); 9007-49-2 (DNA); EC 2.7.7.49 (RNA-Directed DNA Polymerase); GS: HY; GS: Hya; GS: Sdma; GS: Smcy; GS: Spy; ppublish
ENGLAND
0964-6906; 0964-6906
Department of Obstetrics and Gynecology, University of Tennessee, Memphis 38103.
PMID: 7524912
eng
Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; IM
49
40
Journal Article
Agulnik,A. I.;Mitchell,M. J.;Mattei,M. G.;Borsani,G.;Avner,P. A.;Lerner,J. L.;Bishop,C. E.
A novel X gene with a widely transcribed Y-linked homologue escapes X-inactivation in mouse and human
Human molecular genetics
Hum.Mol.Genet.
1994Jun36879884
Alleles;Animals;Base Sequence;Chromosome Mapping;Cloning, Molecular;DNA Primers;DNA, Complementary/analysis;Female;Hominidae/genetics;Humans;In Situ Hybridization;Male;Meiosis;Mice/genetics;Molecular Sequence Data;Polymerase Chain Reaction;Sequence Homology, Nucleic Acid;X Chromosome;Y Chromosome
A new gene, designated Smcx, was cloned from the mouse X chromosome by its homology to the Y located gene Smcy. Using direct in situ hybridisation Smcx was mapped to the distal end of the mouse X chromosome (XF2-XF4) and its human homologue, SMCX, was mapped to proximal Xp (Xp11.1-Xp11.2). Further meiotic mapping in the mouse placed Smcx in the Plp-Pdha1 interval. As Smcx/SMCX have widely expressed homologues on the Y chromosome, they appeared good candidates for genes that escape X-inactivation. In the human we show this to be the case as SMCX is expressed in hamster-human hybrids containing either an active or inactive human X chromosome. Two alleles of Smcx were found to be expressed in T(16;X)16H female mice despite the intact X chromosome being inactive in all cells. This indicates that Smcx is also not subject to X-inactivation and provides the first example of a gene that is expressed from inactive and active X chromosomes in the mouse.
LR: 20041117; GENBANK/Z29650; GENBANK/Z29651; JID: 9208958; 0 (DNA Primers); 0 (DNA, Complementary); GS: SMCX; GS: Smcx; GS: Smcy; ppublish
ENGLAND
0964-6906; 0964-6906
Department of Obstetrics and Gynecology, University of Tennessee, Memphis 38103.
PMID: 7951230
eng
Journal Article; IM
49
41
Journal Article
Agul'nik,A. I.;Ruvinskii,A. O.
Novel partial t-haplotypes of domestic mouse: characteristics of basic properties
GenetikaGenetika1989May255894901
Animals;Chromosome Mapping;Female;Genotype;Haplotypes;Male;Mice;Mice, Mutant Strains/genetics;Mutation;Phenotype
The paper concerns the description of new partial t-haplotypes. One of them, tN1, arose as a result of recombination from t12. The rest ones, tN2-tN5, arose from t6. All the haplotypes described are viable in homozygotic state and when present with T (Brachyury) cause the offspring to be tailless. The tN1-heterozygous males transmit the chromosome with this haplotype to their offspring at the rate of 33%, the t12/tN1 compounds being subfertile. Transmission of chromosome with tN2-tN5 haplotype from heterozygous males does not deviate from 1:1, the t6/tN2 (-tN5) being fertile. The data obtained point out to additional genes (distorters) in the model of t-haplotype, offered by M. Lyon (1984, 1986), that agrees with suggestion of L. Silver (1985). Recombination analysis showed that tN1-tN5 haplotypes suppress crossing over at the strech of 4-5 cM, distally to the T mutation. In tN1 homozygous stock the short-tailed mice appear at the rate of 6-7%. Manifestation of the fused gene is sufficiently modified in a greater part of the animals having genotype tN1Fu/tN1+. That is likely to be the result of gene interaction in early ontogenesis. It has been shown earlier, that penetrance of Fu gene is reduced in the progeny of Fu/t12 females. The results are in favor of the fact that this effect is connected with the distal part of t12-haplotype, the proximal tN1-haplotype having no such effect.
LR: 20061115; JID: 0047354; ppublish
USSR
0016-6758; 0016-6758
PMID: 2744437
rus
English Abstract; Journal Article; IM
Novye chastichnye t-gaplotipy domovoi myshi: kharakteristika osnovnykh svoistv
49
42
Journal Article
Agul'nik,A. I.;Ruvinskii,A. O.;Poliakov,A. V.
tctN-mutation causing taillessness in mice heterozygous for gene T
GenetikaGenetika1990Aug26814621468
Animals;Chromosome Mapping;Female;Haplotypes;Heterozygote;Male;Mice;Mice, Mutant Strains;Mutation;Recombination, Genetic;Tail
Screening of wild male mice trapped in Turkmenistan (Middle Asia) revealed a mouse with a mutation causing strong increase in expressivity of T mutation (Brachyury). A novel mutation was designated tctN-t complex tail interaction Novosibirsk. Compound heterozygotes T/tctN have tailless of extremely short tailed phenotype. Homozygotes tctN/tctN were completely viable and fertile. It was shown that the novel mutation was closely linked to T locus. Further genetic analysis showed that the chromosome with tct had no properties of t haplotypes: no lethal factors or the factors influencing fertility and segregation of homologoues; there was no effect on recombination frequency in the proximal part of chromosome 17 in tctN/+mice. The problems of t haplotype evolution are discussed.
LR: 20061115; JID: 0047354; GS: T; GS: tctN; ppublish
USSR
0016-6758; 0016-6758
PMID: 2258033
rus
English Abstract; Journal Article; IM
tctN-mutatsiia, vyzyvaiushchaia beskhvostost' u myshei, geterozigotnykh po genu T
49
43
Journal Article
Agulnik,A. I.;Zharkikh,A.;Boettger-Tong,H.;Bourgeron,T.;McElreavey,K.;Bishop,C. E.
Evolution of the DAZ gene family suggests that Y-linked DAZ plays little, or a limited, role in spermatogenesis but underlines a recent African origin for human populations
Human molecular genetics
Hum.Mol.Genet.
1998Sep7913711377
Africa;Animals;Base Sequence;Biological Evolution;Cercopithecidae/genetics;Conserved Sequence;DNA Primers/genetics;DNA Transposable Elements;Female;Genetic Linkage;Genetic Variation;Humans;Male;Models, Genetic;Multigene Family;Phylogeny;Polymorphism, Genetic;Primates/genetics;RNA-Binding Proteins/genetics;Spermatogenesis/genetics;Y Chromosome/genetics
The recent transposition to the Y chromosome of the autosomal DAZL1 gene, potentially involved in germ cell development, created a unique opportunity to study the rate of Y chromosome evolution and assess the selective forces that may act upon such genes, and provided a new estimate of the male-to-female mutation rate (alpham). Two different Y-located DAZ sequences were observed in all Old World monkeys, apes and humans. Different DAZ copies originate from independent amplification events in each primate lineage. A comparison of autosomal DAZL1 and Y-linked DAZ intron sequences gave a new figure for male-to-female mutation rates of alpham = 4. It was found that human DAZ exons and introns are evolving at the same rate, implying neutral genetic drift and the absence of any functional selective pressures. We therefore hypothesize that Y-linked DAZ plays little, or a limited, role in human spermatogenesis. The two copies of DAZ in man appear to be due to a relatively recent duplication event (55 000-200 000 years). A worldwide survey of 67 men from five continents representing 19 distinct populations showed that most males have both DAZ variants. This implies a common origin for the Y chromosome consistent with a recent 'out of Africa' origin of the human race.
LR: 20101118; JID: 9208958; 0 (DAZ1 protein, human); 0 (DNA Primers); 0 (DNA Transposable Elements); 0 (RNA-Binding Proteins); ppublish
ENGLAND
0964-6906; 0964-6906
Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX, USA.
PMID: 9700189; ddb197 [pii]
eng
Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; IM
49
44
Journal Article
Agul'nik,S. I.;Agul'nik,A. I.;Ruvinskii,A. O.
Meiotic drive of the aberrant chromosome 1 in the house mouse
GenetikaGenetika1990Apr264664669
Animals;Chromosome Aberrations;Female;Genotype;Male;Meiosis;Mice/genetics
Animals with aberrant chromosome 1 carrying one or two large insertions were earlier described in natural populations of Mus musculus. In the present work, inheritance of the aberrant chromosome 1 from the Yakutsk population was investigated. It was shown that 80-85% of the progeny from heterozygous females received chromosome 1 with insertions. From chromosomal analysis of blastocytes and oocytes at the MII stage, it was concluded that the preferential distribution of the aberrant chromosome into oocytes during the first and especially, the second meiotic divisions is relevant to the segregation distortion observed. The mechanism of this powerful meiotic drive is discussed.
LR: 20061115; JID: 0047354; ppublish
USSR
0016-6758; 0016-6758
PMID: 2373357
rus
English Abstract; Journal Article; IM
Meioticheskii draiv aberrantnoi 1-i khromosomy u domovoi myshi
49
45
Journal Article
Agulnik,S. I.;Agulnik,A. I.;Ruvinsky,A. O.
Meiotic drive in female mice heterozygous for the HSR inserts on chromosome 1
Genetical research
Genet.Res.1990Apr55297100
Animals;DNA Transposable Elements;Female;Gene Frequency;Meiosis;Mice/genetics
Chromosome 1 with one or two long insertions has been previously found in natural mouse populations. The inheritance of chromosome 1 with two insertions from the Yakutsk population is analysed in this paper. It was demonstrated that heterozygous females transmit this chromosome to 80-85% of offspring. The observations made at M II, in conjunction with the recombination data, allowed us to conclude that preferential passage of the chromosome 1 with insertions to the oocyte and egg, rather than to the first and second polar bodies at meiosis, is the causative factor of the distorted segregation. A meiotic drive of such potency has not been previously reported for female mammals. The possible mechanism of the drive is discussed.
LR: 20031114; JID: 0370741; 0 (DNA Transposable Elements); ppublish
ENGLAND 0016-6723
Institute of Cytology and Genetics, Academy of Sciences of the USSR, Novosibirsk.
PMID: 2164490
eng
Journal Article; IM
49
46
Journal Article
Ajees,A. A.;Marapakala,K.;Packianathan,C.;Sankaran,B.;Rosen,B. P.
Structure of an As(III) S-adenosylmethionine methyltransferase: insights into the mechanism of arsenic biotransformation
Biochemistry
Biochemistry
201210-Jul512754765485
Arsenic/metabolism;Biotransformation;Environmental Pollutants/metabolism;Humans;Methyltransferases/chemistry/metabolism;Models, Molecular;Protein Structure, Tertiary;Rhodophyta/enzymology;S-Adenosylmethionine/metabolism;Sequence Homology, Amino Acid
Enzymatic methylation of arsenic is a detoxification process in microorganisms but in humans may activate the metalloid to more carcinogenic species. We describe the first structure of an As(III) S-adenosylmethionine methyltransferase by X-ray crystallography that reveals a novel As(III) binding domain. The structure of the methyltransferase from the thermophilic eukaryotic alga Cyanidioschyzon merolae reveals the relationship between the arsenic and S-adenosylmethionine binding sites to a final resolution of approximately 1.6 A. As(III) binding causes little change in conformation, but binding of SAM reorients helix alpha4 and a loop (residues 49-80) toward the As(III) binding domain, positioning the methyl group for transfer to the metalloid. There is no evidence of a reductase domain. These results are consistent with previous suggestions that arsenic remains trivalent during the catalytic cycle. A homology model of human As(III) S-adenosylmethionine methyltransferase with the location of known polymorphisms was constructed. The structure provides insights into the mechanism of substrate binding and catalysis.
LR: 20130715; GR: GM55425/GM/NIGMS NIH HHS/United States; GR: R37 GM055425/GM/NIGMS NIH HHS/United States; GR: Howard Hughes Medical Institute/United States; JID: 0370623; 0 (Environmental Pollutants); 29908-03-0 (S-Adenosylmethionine); 7440-38-2 (Arsenic); EC 2.1.1.- (Methyltransferases); EC 2.1.1.137 (AS3MT protein, human); NIHMS390224; OID: NLM: NIHMS390224; OID: NLM: PMC3447999; 2012/06/29 [aheadofprint]; ppublish
United States
1520-4995; 0006-2960
Department of Cellular Biology and Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, 33199, United States.
PMID: 22712827
eng
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; IM
10.1021/bi3004632
9
47
Journal Article
Ajees,A. A.;Marapakala,K.;Packianathan,C.;Sankaran,B.;Rosen,B. P.
Structure of an As(III) S-adenosylmethionine methyltransferase: insights into the mechanism of arsenic biotransformation
Biochemistry
Biochemistry
201210-Jul512754765485
Arsenic/metabolism;Biotransformation;Environmental Pollutants/metabolism;Humans;Methyltransferases/chemistry/metabolism;Models, Molecular;Protein Structure, Tertiary;Rhodophyta/enzymology;S-Adenosylmethionine/metabolism;Sequence Homology, Amino Acid
Enzymatic methylation of arsenic is a detoxification process in microorganisms but in humans may activate the metalloid to more carcinogenic species. We describe the first structure of an As(III) S-adenosylmethionine methyltransferase by X-ray crystallography that reveals a novel As(III) binding domain. The structure of the methyltransferase from the thermophilic eukaryotic alga Cyanidioschyzon merolae reveals the relationship between the arsenic and S-adenosylmethionine binding sites to a final resolution of approximately 1.6 A. As(III) binding causes little change in conformation, but binding of SAM reorients helix alpha4 and a loop (residues 49-80) toward the As(III) binding domain, positioning the methyl group for transfer to the metalloid. There is no evidence of a reductase domain. These results are consistent with previous suggestions that arsenic remains trivalent during the catalytic cycle. A homology model of human As(III) S-adenosylmethionine methyltransferase with the location of known polymorphisms was constructed. The structure provides insights into the mechanism of substrate binding and catalysis.
LR: 20130715; GR: GM55425/GM/NIGMS NIH HHS/United States; GR: R37 GM055425/GM/NIGMS NIH HHS/United States; GR: Howard Hughes Medical Institute/United States; JID: 0370623; 0 (Environmental Pollutants); 29908-03-0 (S-Adenosylmethionine); 7440-38-2 (Arsenic); EC 2.1.1.- (Methyltransferases); EC 2.1.1.137 (AS3MT protein, human); NIHMS390224; OID: NLM: NIHMS390224; OID: NLM: PMC3447999; 2012/06/29 [aheadofprint]; ppublish
United States
1520-4995; 0006-2960
Department of Cellular Biology and Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, 33199, United States.
PMID: 22712827
eng
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; IM
10.1021/bi3004632
9
48
Journal Article
Al Mansouri,A. S.;Lorke,D. E.;Nurulain,S. M.;Ashoor,A.;Keun-Hang,S. Y.;Petroianu,G.;Isaev,D.;Oz,M.
Methylene blue inhibits the function of alpha7-nicotinic acetylcholine receptors
CNS & neurological disorders drug targets
CNS Neurol.Disord.Drug Targets
2012Sep116791800
Alzheimer Disease/drug therapy;Animals;Bungarotoxins/pharmacology;CA1 Region, Hippocampal/cytology/drug effects;Enzyme Inhibitors/pharmacology;GABA Agents/pharmacology;Humans;Male;Membrane Potentials/drug effects;Methylene Blue/pharmacology;Nicotinic Antagonists/pharmacology;Oocytes;Patch-Clamp Techniques;Pyramidal Cells/drug effects;Radioligand Assay;Rats;Rats, Sprague-Dawley;Receptors, Nicotinic/drug effects/physiology;Xenopus laevis;gamma-Aminobutyric Acid/pharmacology
Methylene Blue (MB) is being investigated in clinical studies for its beneficial effects in the treatment of Alzheimer disease. However, its exact mechanisms of action have not been fully elucidated. The modulation of nicotinic acetylcholine receptors (nAChRs) has been suggested to play a role in the pathogenesis of various neurodegenerative diseases. Therefore, in the present study, the effect of MB on the function of the cloned alpha7 subunit of the human nAChR expressed in Xenopus oocytes was investigated using the two-electrode voltage-clamp technique. MB reversibly inhibited ACh (100 muM)-induced currents in a concentration-dependent manner with an IC50 value of 3.4+/-0.3 muM. The effect of MB was not dependent on the membrane potential. MB did not affect the activity of endogenous Ca2+-dependent Cl- channels, since the inhibition by MB was unaltered in oocytes injected with the Ca2+ chelator 1,2-bis (o-aminophenoxy) ethane-N, N, N', N'-tetraacetic acid and perfused with Ca2+-free bathing solution containing 1.8 mM Ba2+. MB decreased the maximal ACh-induced responses without significantly affecting ACh potency. Furthermore, specific binding of [125I] alpha-bungarotoxin, a radioligand selective for the alpha7 nAChR, was not altered by MB (10 muM), indicating that MB acts as a noncompetitive antagonist on alpha7 nAChRs. In hippocampal slices, whole-cell recordings from CA1 pyramidal neurons indicated that the increases in the frequency and amplitudes of the gamma-aminobutyric acid-mediated spontaneous postsynaptic currents induced by bath application of 2 mM choline, a specific agonist for alpha7 nAChRs, were abolished after 10 min application of 3 muM MB. These results demonstrate that MB inhibits the function of human alpha7 nAChRs expressed in Xenopus oocytes and of alpha7 nAChR-mediated responses in rat hippocampal neurons.
JID: 101269155; 0 (Bungarotoxins); 0 (Enzyme Inhibitors); 0 (GABA Agents); 0 (Nicotinic Antagonists); 0 (Receptors, Nicotinic); 0 (alpha7 nicotinic acetylcholine receptor); 56-12-2 (gamma-Aminobutyric Acid); 61-73-4 (Methylene Blue); 2011/12/08 [received]; 2012/03/19 [revised]; 2012/03/20 [accepted]; ppublish
United Arab Emirates
1996-3181; 1871-5273
Functional Lipidomics Branch, Department of Pharmacology, Faculty of Medicine and Health Sciences, UAE University, Abu Dhabi, Al Ain, 17666, UAE.
PMID: 22483305; CDTCNSND-EPUB-20120404-015 [pii]
eng
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; IM
21
49
Journal Article
Apte-Deshpande,A.;Somani,S.;Mandal,G.;Soorapaneni,S.;Padmanabhan,S.
Over expression and analysis of O-glycosylated recombinant human granulocyte colony stimulating factor in Pichia pastoris using Agilent 2100 Bioanalyzer
Journal of Biotechnology
J.Biotechnol.
200910-Aug14314450
Antibodies, Monoclonal/chemistry;Biotechnology/methods;Cloning, Molecular;Detergents/pharmacology;Escherichia coli/metabolism;Fermentation;Glycoproteins/chemistry;Glycosylation;Granulocyte Colony-Stimulating Factor/biosynthesis/chemistry;Humans;Leukocyte Elastase/chemistry;Pichia/metabolism;Recombinant Proteins/chemistry;Saccharomyces cerevisiae/metabolism;Time Factors
Recombinant human granulocyte colony stimulating factor (rhGCSF) was expressed in methylotrophic yeast Pichia pastoris under the control of AOX1 promoter after integration of the GCSF gene into P. pastoris genome. Methanol induction of the Pichia integrants yielded only 2mgl(-1) of rhGCSF whereas inclusion of surfactants during induction enhanced the yields to the level of 200-250mgl(-1) in shake flask studies after 72h of induction. Preliminary studies in a bioreactor showed rhGCSF expression levels of 6mg rhGCSF g(-1) methanol day(-1) which is significantly higher to the reported value of 0.4mg rhGCSF g(-1) methanol day(-1) reported till date for Pichia derived rhGCSF. A single step purification protocol of shake flask derived rhGCSF yielded homogenous rhGCSF protein of >99% purity. Even though, purified rhGCSF showed a single band on reducing SDS-PAGE, examination of the same protein on Agilent 2100 Bioanalyzer, revealed two closely unresolved peaks. Such a pattern was also observed for crude rhGCSF preparations. Mutagenesis of the O-glycosylation site of rhGCSF (Thr(133) to Leu(133)) showed a single peak on bioanalyzer, which overlapped with the peak obtained for a non-glycosylated rhGCSF. Our data discloses for the first time the novel use of Agilent Bioanalyzer to detect glycoforms of proteins in crude and purified preparations and such a tool could be easily applied for glycoprotein profiling of monoclonal antibodies and other fusion proteins expressed in mammalian cells. This is the first report of a simple, rapid, sensitive and a cost-efficient tool for detection of glycoproteins.
JID: 8411927; 0 (Antibodies, Monoclonal); 0 (Detergents); 0 (Glycoproteins); 0 (Recombinant Proteins); 143011-72-7 (Granulocyte Colony-Stimulating Factor); EC 3.4.21.37 (Leukocyte Elastase); 2009/02/02 [received]; 2009/05/25 [revised]; 2009/06/04 [accepted]; 2009/06/13 [aheadofprint]; ppublish
Netherlands
1873-4863; 0168-1656
Biotechnology R & D, Lupin Limited, Pune, India.
PMID: 19527756; S0168-1656(09)00251-X [pii]
eng
Journal Article; IM
10.1016/j.jbiotec.2009.06.002; 10.1016/j.jbiotec.2009.06.002
108
50
Journal Article
Apte-Deshpnade,A.;Mandal,G.;Soorapaneni,S.;Prasad,B.;Kumar,J.;Padmanabhan,S.
High-level expression of non-glycosylated and active staphylokinase from Pichia pastoris
Biotechnology Letters
Biotechnol.Lett.
2009Jun316811817
Bacterial Proteins/biosynthesis/chemistry/genetics/isolation & purification;Chromatography, Ion Exchange/methods;Glycosylation;Metalloendopeptidases/biosynthesis/chemistry/genetics/isolation & purification;Molecular Weight;Pichia/genetics;Plasminogen/metabolism;Recombinant Proteins/biosynthesis/chemistry/genetics/isolation & purification
Staphylokinase (SAK) is a promising thrombolytic agent for treating blood-clotting disorders. Recombinant SAK (rSAK) was produced after integration of the gene into Pichia pastoris genome. The recombinant Pichia carrying multiple insertions of the SAK gene yielded high-level (approximately 1 g/l) of extracellular glycosylated rSAK (approximately 18 kDa) with negligible plasminogen activation activity. Addition of tunicamycin during the induction phase resulted in expression of non-glycosylated and highly active rSAK (approximately 15 kDa) from the same clone. Two simple steps of ion-exchange chromatography produced an homogenous rSAK of >95% purity which suitable for future structural and functional studies.
JID: 8008051; 0 (Bacterial Proteins); 0 (Recombinant Proteins); 9001-91-6 (Plasminogen); EC 3.4.24.- (Metalloendopeptidases); EC 3.4.24.29 (auR protein, Staphylococcus aureus); 2008/12/11 [received]; 2009/01/23 [accepted]; 2009/01/19 [revised]; 2009/02/12 [aheadofprint]; ppublish
Netherlands
1573-6776; 0141-5492
Biotechnology R & D, Lupin Limited, 46A/47A, Nande Village, Mulshi Taluka, Pune 411042, India.
PMID: 19214390
eng
Journal Article; IM
10.1007/s10529-009-9938-z; 10.1007/s10529-009-9938-z
108
51
Journal Article
Ashoor,A.;Lorke,D.;Nurulain,S. M.;Kury,L. A.;Petroianu,G.;Yang,K. H.;Oz,M.
Effects of phenothiazine-class antipsychotics on the function of alpha7-nicotinic acetylcholine receptors
European journal of pharmacology
Eur.J.Pharmacol.
201130-Dec6733-Jan2532
Animals;Antipsychotic Agents/administration & dosage/pharmacology;Calcium/metabolism;Chloride Channels/metabolism;Female;Hippocampus/drug effects/metabolism;Humans;Inhibitory Concentration 50;Male;Membrane Potentials/drug effects;Oocytes/drug effects/metabolism;Patch-Clamp Techniques;Phenothiazines/administration & dosage/pharmacology;Rats;Rats, Sprague-Dawley;Receptors, Nicotinic/drug effects/metabolism;Xenopus laevis
The effects of phenothiazine-class antipsychotics (chlorpromazine, fluphenazine, phenothiazine, promazine, thioridazine, and triflupromazine) upon the function of the cloned alpha(7) subunit of the human nicotinic acetylcholine receptor expressed in Xenopus oocytes were tested using the two-electrode voltage-clamp technique. Fluphenazine, thioridazine, triflupromazine, chlorpromazine, and promazine reversibly inhibited acetylcholine (100 muM)-induced currents with IC(5)(0) values of 3.8; 5.8; 6.1; 10.6 and 18.3 muM, respectively. Unsubstituted phenothiazine did not have a significant effect up to a concentration of 30 muM. Inhibition was further characterized using fluphenazine, the strongest inhibitor. The effect of fluphenazine was not dependent on the membrane potential. Fluphenazine (10 muM) did not affect the activity of endogenous Ca(2)(+)-dependent Cl(-) channels, since the extent of inhibition by fluphenazine was unaltered by intracellular injection of the Ca(2)(+) chelator BAPTA and perfusion with Ca(2)(+)-free bathing solution containing 2 mM Ba(2)(+). Inhibition by fluphenazine, but not by chlorpromazine was reversed by increasing acetylcholine concentrations. Furthermore, specific binding of [(1)(2)(5)I] alpha-bungarotoxin, a radioligand selective for alpha(7)-nicotinic acetylcholine receptor, was inhibited by fluphenazine (10 muM), but not by chlorpromazine in oocyte membranes. In hippocampal slices, epibatidine-evoked [(3)H] norepinephrine release was also inhibited by fluphenazine (10 muM) and chlorpromazine (10 muM). Our results indicate that phenothiazine-class typical antipsychotics inhibit, with varying potencies, the function of alpha(7)-nicotinic acetylcholine receptor.
CI: Copyright (c) 2011; JID: 1254354; 0 (Antipsychotic Agents); 0 (Chloride Channels); 0 (Phenothiazines); 0 (Receptors, Nicotinic); 0 (alpha7 nicotinic acetylcholine receptor); 7440-70-2 (Calcium); 2011/06/23 [received]; 2011/10/03 [revised]; 2011/10/11 [accepted]; 2011/10/25 [aheadofprint]; ppublish
Elsevier B.VNetherlands
1879-0712; 0014-2999
Laboratory of Functional Lipidomics, Department of Pharmacology, Faculty of Medicine and Health Sciences, UAE University, Al Ain, UAE.
PMID: 22044918; S0014-2999(11)01388-4 [pii]
eng
Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; IM
10.1016/j.ejphar.2011.10.020; 10.1016/j.ejphar.2011.10.020
21
52
Journal Article
Athauda,G.;Giubellino,A.;Coleman,J. A.;Horak,C.;Steeg,P. S.;Lee,M. J.;Trepel,J.;Wimberly,J.;Sun,J.;Coxon,A.;Burgess,T. L.;Bottaro,D. P.
c-Met ectodomain shedding rate correlates with malignant potential
Clinical cancer research : an official journal of the American Association for Cancer Research
Clin.Cancer Res.
200615-Jul1214 Pt 141544162
Animals;Cell Line, Tumor;Cell Transformation, Neoplastic;Disease Progression;Dose-Response Relationship, Drug;Electrochemistry;Humans;Luminescence;Mice;Neoplasm Metastasis;Neoplasm Transplantation;Protein Structure, Tertiary;Proto-Oncogene Proteins c-met/chemistry/metabolism;Recombinant Proteins/chemistry;Tumor Markers, Biological/chemistry
PURPOSE: Many proteins are proteolytically released from the cell surface by a process known as ectodomain shedding. Shedding occurs under normal physiologic conditions and can be increased in certain pathologies. Among the many receptors for which ectodomain shedding has been shown is c-Met, the hepatocyte growth factor (HGF) receptor tyrosine kinase. HGF stimulates mitogenesis, motogenesis, and morphogenesis in a variety of cellular targets during development, homeostasis, and tissue regeneration. Inappropriate HGF signaling resulting in unregulated cell proliferation, motility, and invasion occurs in several human malignancies. This can occur through paracrine signaling, autocrine loop formation, receptor mutation, gene amplification, or gene rearrangement, accompanied frequently with overexpression of ligand and/or receptor proteins. We hypothesized that c-Met overexpression in cancer might result in increased ectodomain shedding, and that its measure could be a useful biomarker of tumor progression. EXPERIMENTAL DESIGN: We developed a sensitive electrochemiluminescent immunoassay to quantitate c-Met protein in cell lysates, culture supernatants, and biological samples. RESULTS: A survey of cultured cell models of oncogenic transformation revealed significant direct correlations (P 0.92, linear regression). CONCLUSIONS: For a variety of human cancers, c-Met ectodomain shedding may provide a reliable and practical indicator of malignant potential and overall tumor burden.
LR: 20091119; JID: 9502500; 0 (Recombinant Proteins); 0 (Tumor Markers, Biological); EC 2.7.10.1 (Proto-Oncogene Proteins c-met); ppublish
United States
1078-0432; 1078-0432
Urologic Oncology Branch, Laboratory of Molecular Pharmacology, and Medical Oncology Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892-1107, USA.
PMID: 16857786; 12/14/4154 [pii]
eng
Journal Article; Research Support, N.I.H., Intramural; IM
10.1158/1078-0432.CCR-06-0250
13
53
Journal Article
Atluri,S. R.;Singhi,P.;Khandelwal,N.;Malla,N.
Evaluation of excretory secretory and 10-30 kDa antigens of Taenia solium Cysticerci by EITB assay for the diagnosis of neurocysticercosis
Parasite immunology
Parasite Immunol.
2009Mar313151155
Animals;Antibodies, Helminth/analysis/blood;Antigens, Helminth/chemistry/diagnostic use;Blood Chemical Analysis;Child;Humans;Immunoblotting/methods;Immunoenzyme Techniques/methods;Molecular Weight;Neurocysticercosis/diagnosis;Sensitivity and Specificity;Taenia solium/immunology;Urine/chemistry
Neurocysticercosis (NCC), caused by the presence of Taenia solium Cysticerci in the Central Nervous System is the most common neurological disease of parasite aetiology. The serodiagnostic methods available at present have variable sensitivity and specificity depending upon the antigen and technique used. The present study was aimed to assess the efficacy of T. solium Cysticerci excretory secretory (ES) and lower molecular mass (LMM) 10-30 kDa antigenic fractions for antibody detection in serum and urine samples by enzyme-linked immunoelectrotransfer blot (EITB) for the diagnosis of NCC. Serum and urine samples were collected from 125 clinically suspected and radiologically proven NCC children (111 patients with single lesion and 14 with multiple lesions) and 125 control subjects. With the use of ES and LMM antigenic fractions, the sensitivity of the EITB assay was 85.6% and 80.8% with serum and 76.8% and 50.4% with urine, respectively. The specificity was 64% and 61.6% with serum and 48% and 33.6% with urine samples, respectively. The study suggests that antibody detection to ES antigen in serum by EITB assay may serve better purpose for the serodiagnosis of human NCC.
JID: 7910948; 0 (Antibodies, Helminth); 0 (Antigens, Helminth); ppublish
England
1365-3024; 0141-9838
Department of Parasitology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
PMID: 19222787; PIM1085 [pii]
eng
Evaluation Studies; Journal Article; IM
10.1111/j.1365-3024.2008.01085.x; 10.1111/j.1365-3024.2008.01085.x
81
54
Journal Article
Atluri,S. R.;Singhi,P.;Khandelwal,N.;Malla,N.
Neurocysticercosis immunodiagnosis using Taenia solium cysticerci crude soluble extract, excretory secretory and lower molecular mass antigens in serum and urine samples of Indian children
Acta Tropica
Acta Trop.2009Apr11012227
Animals;Antibodies, Helminth/analysis/blood;Antigens, Helminth/diagnostic use;Child;Child, Preschool;Enzyme-Linked Immunosorbent Assay/methods;Female;Humans;India;Infant;Male;Neurocysticercosis/diagnosis/immunology;Sensitivity and Specificity;Serum/parasitology;Taenia solium/immunology/isolation & purification;Urine/parasitology
Neurocysticercosis (NCC), the most common neurological disorder of parasite etiology, results from lodgement of Taenia solium cysticerci in the central nervous system and is now increasingly being recognized in children. The confirmed diagnosis is based collectively on radiological findings and serodiagnostic techniques. The serodiagnostic techniques have variable sensitivity and specificity depending upon the technique, antigens used, location and number of cysts. Crude soluble extract (CSE), excretory secretory (ES) and lower molecular mass (LMM) (10-30 kDa) antigenic fraction of T. solium cysticerci were evaluated for antibody detection in serum and urine samples by ELISA. Serum and urine samples were collected each from 125 clinically suspected and radiologically proven NCC (111 with single Computed Tomography (CT) lesions and 14 with multiple CT lesions) and 125 control subjects (60 with neurological disorders other than NCC, 40 with other parasitic diseases and 25 apparently healthy subjects). The sensitivity of the ELISA with the use of CSE, ES and LMM antigenic fractions was 38.4%, 63.2% and 30.4% with serum (cut off dilution 400), 46.4%, 44% and 47.2% with neat urine and the specificity was 88%, 76.8% and 85.6% with serum (cut off dilution 400), 66.4%, 65.2% and 58.4% with neat urine samples, respectively. The study suggests that detection of antibody to ES antigen in serum samples may serve useful purpose for the serodiagnosis of human NCC.
JID: 0370374; 0 (Antibodies, Helminth); 0 (Antigens, Helminth); 2008/08/05 [received]; 2008/12/07 [revised]; 2008/12/19 [accepted]; 2008/12/27 [aheadofprint]; ppublish
Netherlands
1873-6254; 0001-706X
Department of Parasitology, Postgraduate Institute of Medical Education and Research, Chandigarh, India. atluripgi@yahoo.com
PMID: 19161966; S0001-706X(08)00367-7 [pii]
eng
Evaluation Studies; Journal Article; IM
10.1016/j.actatropica.2008.12.004; 10.1016/j.actatropica.2008.12.004
81
55
Journal Article
Atluri,V. S.;Kanthikeel,S. P.;Reddy,P. V.;Yndart,A.;Nair,M. P.
Human synaptic plasticity gene expression profile and dendritic spine density changes in HIV-infected human CNS cells: role in HIV-associated neurocognitive disorders (HAND)
PloS onePLoS One201319-Apr84e61399
HIV-associated neurocognitive disorders (HAND) is characterized by development of cognitive, behavioral and motor abnormalities, and occur in approximately 50% of HIV infected individuals. Our current understanding of HAND emanates mainly from HIV-1 subtype B (clade B), which is prevalent in USA and Western countries. However very little information is available on neuropathogenesis of HIV-1 subtype C (clade C) that exists in Sub-Saharan Africa and Asia. Therefore, studies to identify specific neuropathogenic mechanisms associated with HAND are worth pursuing to dissect the mechanisms underlying this modulation and to prevent HAND particularly in clade B infection. In this study, we have investigated 84 key human synaptic plasticity genes differential expression profile in clade B and clade C infected primary human astrocytes by using RT(2) Profile PCR Array human Synaptic Plasticity kit. Among these, 31 and 21 synaptic genes were significantly (>/=3 fold) down-regulated and 5 genes were significantly (>/=3 fold) up-regulated in clade B and clade C infected cells, respectively compared to the uninfected control astrocytes. In flow-cytometry analysis, down-regulation of postsynaptic density and dendrite spine morphology regulatory proteins (ARC, NMDAR1 and GRM1) was confirmed in both clade B and C infected primary human astrocytes and SK-N-MC neuroblastoma cells. Further, spine density and dendrite morphology changes by confocal microscopic analysis indicates significantly decreased spine density, loss of spines and decreased dendrite diameter, total dendrite and spine area in clade B infected SK-N-MC neuroblastoma cells compared to uninfected and clade C infected cells. We have also observed that, in clade B infected astrocytes, induction of apoptosis was significantly higher than in the clade C infected astrocytes. In conclusion, this study suggests that down-regulation of synaptic plasticity genes, decreased dendritic spine density and induction of apoptosis in astrocytes may contribute to the severe neuropathogenesis in clade B infection.
GR: R01DA021537/DA/NIDA NIH HHS/United States; GR: R01DA027049/DA/NIDA NIH HHS/United States; GR: R01MH085259/MH/NIMH NIH HHS/United States; GR: R37DA025576/DA/NIDA NIH HHS/United States; JID: 101285081; OID: NLM: PMC3631205; 2013 [ppublish]; 2013/01/10 [received]; 2013/03/08 [accepted]; 2013/04/19 [epublish]; epublish
United States
1932-6203; 1932-6203
Department of Immunology, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, Florida, USA.
PMID: 23620748; PONE-D-13-01650 [pii]
eng
Journal Article; Research Support, N.I.H., Extramural; IM
10.1371/journal.pone.0061399; 10.1371/journal.pone.0061399
81
56
Journal Article
Atluri,V. S.;Singhi,P. D.;Khandelwal,N.;Malla,N.
2D-PAGE analysis of Taenia solium metacestode 10-30 kDa antigens for the serodiagnosis of neurocysticercosis in children
Acta Tropica
Acta Trop.2011May1182165169
Animals;Antibodies, Helminth/blood;Antigens, Helminth/analysis;Child;Child, Preschool;Electrophoresis, Gel, Two-Dimensional;Female;Helminth Proteins/analysis;Humans;Infant;Male;Neurocysticercosis/diagnosis;Parasitology/methods;Sensitivity and Specificity;Serologic Tests/methods;Taenia solium/chemistry
Neurocysticercosis (NCC) caused by T. solium metacestode is an increasingly important health issue in Indian children. The sensitivity and specificity of available serological techniques were low in case of single cysticercus granuloma cases which is a more common feature in Indian patients who are children. Serum samples were collected from 13 clinically and radiologically suggestive NCC children and seropositive by ELISA, 25 clinically and radiologically suggestive NCC children and seronegative by ELISA and 25 control subjects. The 10-30 kDa antigens of T. solium metacestode were subjected to 2-dimensional gel electrophoresis (2D-PAGE) followed by enzyme-linked immunoelectrotransfer blot (EITB) assay to detect antibody in serum. Analysis of 10-30 kDa antigenic fraction 2D-PAGE map showed 31 proteins between 10 and 28 and 30 kDa with the Isoelectric point of 3-10. All the 13 (100%) NCC seropositive and 15 (60%) out of 25 NCC seronegative samples were reactive with 2D fraction antigens. In the control group, none of the serum was reactive except 2 hydatid samples (92% specificity). The sensitivity and specificity of 2D-PAGE EITB assay were significantly higher than the ELISA which is the routine diagnostic method used in the endemic countries for the serodiagnosis of neurocysticercosis.
CI: Copyright (c) 2011; JID: 0370374; 0 (Antibodies, Helminth); 0 (Antigens, Helminth); 0 (Helminth Proteins); 2010/07/27 [received]; 2011/01/12 [revised]; 2011/02/18 [accepted]; 2011/02/24 [aheadofprint]; ppublish
Elsevier B.VNetherlands
1873-6254; 0001-706X
Department of Parasitology, Postgraduate Institute of Medical Education and Research, Chandigarh, India. dratluri@aol.com
PMID: 21354092; S0001-706X(11)00034-9 [pii]
eng
Evaluation Studies; Journal Article; IM
10.1016/j.actatropica.2011.02.009; 10.1016/j.actatropica.2011.02.009
81
57
Journal Article
Bajpai,M.;Fiedler,S. E.;Huang,Z.;Vijayaraghavan,S.;Olson,G. E.;Livera,G.;Conti,M.;Carr,D. W.
AKAP3 selectively binds PDE4A isoforms in bovine spermatozoa
Biology of reproduction
Biol.Reprod.2006Jan741109118
3',5'-Cyclic-AMP Phosphodiesterases/metabolism;Adaptor Proteins, Signal Transducing/metabolism;Animals;Cattle;Cyclic AMP-Dependent Protein Kinases;Cyclic Nucleotide Phosphodiesterases, Type 1;Cyclic Nucleotide Phosphodiesterases, Type 4;Fluorescent Antibody Technique;Immunoprecipitation;Isoenzymes;Male;Phosphorylation;Solubility;Sperm Maturation/physiology;Sperm Motility/physiology;Spermatozoa/metabolism/physiology
Cyclic AMP plays an important role in regulating sperm motility and acrosome reaction through activation of cAMP-dependent protein kinase A (PKA). Phosphodiesterases (PDEs) modulate the levels of cyclic nucleotides by catalyzing their degradation. Although PDE inhibitors specific to PDE1 and PDE4 are known to alter sperm motility and capacitation in humans, little is known about the role or subcellular distribution of PDEs in spermatozoa. The localization of PKA is regulated by A-kinase anchoring proteins (AKAPs), which may also control the intracellular distribution of PDE. The present study was undertaken to investigate the role and localization of PDE4 during sperm capacitation. Addition of Rolipram or RS25344, PDE4-specific inhibitors significantly increased the progressive motility of bovine spermatozoa. Immunolocalization techniques detected both PDE4A and AKAP3 (formerly known as AKAP110) in the principal piece of bovine spermatozoa. The PDE4A5 isoform was detected primarily in the Triton X-100-soluble fraction of caudal epididymal spermatozoa. However, in ejaculated spermatozoa it was seen primarily in the SDS-soluble fraction, indicating a shift in PDE4A5 localization into insoluble organelles during sperm capacitation. AKAP3 was detected only in the SDS-soluble fraction of both caudal and ejaculated sperm. Immunoprecipitation experiments using COS cells cotransfected with AKAP3 and either Pde4a5 or Pde4d provide evidence that PDE4A5 but not PDE4D interacts with AKAP3. Pulldown assays using sperm cell lysates confirm this interaction in vitro. These data suggest that AKAP3 binds both PKA and PDE4A and functions as a scaffolding protein in spermatozoa to regulate local cAMP concentrations and modulate sperm functions.
LR: 20130524; GR: HD31544/HD/NICHD NIH HHS/United States; GR: HD36408/HD/NICHD NIH HHS/United States; GR: HD38520/HD/NICHD NIH HHS/United States; GR: R01 HD036408/HD/NICHD NIH HHS/United States; JID: 0207224; 0 (Adaptor Proteins, Signal Transducing); 0 (Isoenzymes); EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases); EC 3.1.4.17 (3',5'-Cyclic-AMP Phosphodiesterases); EC 3.1.4.17 (Cyclic Nucleotide Phosphodiesterases, Type 1); EC 3.1.4.17 (Cyclic Nucleotide Phosphodiesterases, Type 4); NIHMS7499; OID: NLM: NIHMS7499; OID: NLM: PMC1352331; 2005/09/21 [aheadofprint]; ppublish
United States
0006-3363; 0006-3363
Department of Medicine, Oregon Health and Sciences University and VA Medical Center, Portland, OR 97239, USA.
PMID: 16177223; biolreprod.105.043588 [pii]
eng
Journal Article; Research Support, N.I.H., Extramural; IM
10.1095/biolreprod.105.043588
52
58
Journal Article
Baker,W. P.;Dainer,P.;Lester,W. M.;Marty,A. M.;Blair,T. P.
Ischemic chest pain after 5-fluorouracil therapy for cancer
The American Journal of Cardiology
Am.J.Cardiol.
198615-Feb576497498
Angina Pectoris/etiology/pathology/physiopathology;Coronary Vessels/pathology;Fluorouracil/adverse effects;Hemodynamics;Humans;Male;Middle Aged;Myocardium/pathology
LR: 20071115; JID: 0207277; 51-21-8 (Fluorouracil); ppublish
UNITED STATES
0002-9149; 0002-9149
PMID: 3946274; 0002-9149(86)90788-5 [pii]
eng
Case Reports; Journal Article; AIM; IM
111
59
Journal Article
Balasubramanian,D.;Kong,K. F.;Jayawardena,S. R.;Leal,S. M.;Sautter,R. T.;Mathee,K.
Co-regulation of {beta}-lactam resistance, alginate production and quorum sensing in Pseudomonas aeruginosa
Journal of medical microbiology
J.Med.Microbiol.
2011Feb60Pt 2147156
Alginates;Animals;Anti-Bacterial Agents/metabolism;Bacterial Proteins/metabolism;Caenorhabditis elegans/microbiology;Disease Models, Animal;Drug Resistance, Bacterial;Gene Expression Profiling;Gene Expression Regulation, Bacterial;Glucuronic Acid/biosynthesis;Hexuronic Acids;Promoter Regions, Genetic;Pseudomonas Infections/pathology;Pseudomonas aeruginosa/pathogenicity/physiology;Quorum Sensing;Sigma Factor/metabolism;Virulence;Virulence Factors/biosynthesis;beta-Lactam Resistance;beta-Lactams/metabolism
Development of beta-lactam resistance, production of alginate and modulation of virulence factor expression that alters host immune responses are the hallmarks of chronic Pseudomonas aeruginosa infection in cystic fibrosis patients. In this study, we propose that a co-regulatory network exists between these mechanisms. We compared the promoter activities of ampR, algT/U, lasR, lasI, rhlR, rhlI and lasA genes, representing the beta-lactam antibiotic resistance master regulatory gene, the alginate switch operon, the las and rhl quorum-sensing (QS) genes, and the LasA staphylolytic protease, respectively. Four isogenic P. aeruginosa strains, the prototypic Alg(-) PAO1, Alg(-) PAOampR, the mucoid Alg(+) PAOmucA22 (Alg(+) PDO300) and Alg(+) PAOmucA22ampR (Alg(+) PDOampR) were used. We found that in the presence of AmpR regulator and beta-lactam antibiotic, the extracytoplasmic function sigma factor AlgT/U positively regulated P(ampR), whereas AmpR negatively regulated P(algT/U). On the basis of this finding we suggest the presence of a negative feedback loop to limit algT/U expression. In addition, the functional AlgT/U caused a significant decrease in the expression of QS genes, whereas loss of ampR only resulted in increased P(lasI) and P(lasR) transcription. The upregulation of the las QS system is likely to be responsible for the increased lasA promoter and the LasA protease activities in Alg(-) PAOampR and Alg(+) PDOampR. The enhanced expression of virulence factors in the ampR strains correlated with a higher rate of Caenorhabditis elegans paralysis. Hence, this study shows that the loss of ampR results in increased virulence, and is indicative of the existence of a co-regulatory network between beta-lactam resistance, alginate production, QS and virulence factor production, with AmpR playing a central role.
LR: 20130703; GR: R25 GM61347/GM/NIGMS NIH HHS/United States; GR: S06 GM08205/GM/NIGMS NIH HHS/United States; GR: SC1 AI081376-03/AI/NIAID NIH HHS/United States; GR: SC1 AI081376-04/AI/NIAID NIH HHS/United States; JID: 0224131; 0 (AlgU protein, Pseudomonas aeruginosa); 0 (Alginates); 0 (Anti-Bacterial Agents); 0 (Bacterial Proteins); 0 (Hexuronic Acids); 0 (Sigma Factor); 0 (Virulence Factors); 0 (beta-Lactams); 125267-46-1 (AmpR protein, Bacteria); 576-37-4 (Glucuronic Acid); 9005-32-7 (alginic acid); EIN: J Med Microbiol. 2011 May;60(Pt 5):696-7; OID: NLM: PMC3081088; 2010/10/21 [aheadofprint]; ppublish
England
1473-5644; 0022-2615
Department of Biological Sciences, College of Arts and Science, Florida International University, Miami, FL 33199, USA.
PMID: 20965918; jmm.0.021600-0 [pii]
eng
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; IM
10.1099/jmm.0.021600-0; 10.1099/jmm.0.021600-0
105
60
Journal Article
Balasubramanian,D.;Mathee,K.
Comparative transcriptome analyses of Pseudomonas aeruginosa
Human genomics
Hum.Genomics
2009Jul34349361
Biofilms;Humans;Oligonucleotide Array Sequence Analysis;Osmotic Pressure;Pseudomonas aeruginosa/genetics/pathogenicity;Quorum Sensing;RNA, Bacterial/genetics;RNA, Messenger/genetics;Virulence
One of the hallmarks of bacterial survival is their ability to adapt rapidly to changing environmental conditions. Niche adaptation is a response to the signals received that are relayed, often to regulators that modulate gene expression. In the post-genomic era, DNA microarrays are used to study the dynamics of gene expression on a global scale. Numerous studies have used Pseudomonas aeruginosa--a Gram-negative environmental and opportunistic human pathogenic bacterium--as the model organism in whole-genome transcriptome analysis. This paper reviews the transcriptome studies that have led to immense advances in our understanding of the biology of this intractable human pathogen. Comparative analysis of 23 P. aeruginosa transcriptome studies has led to the identification of a unique set of genes that are signal specific and a core set that is differentially regulated. The 303 genes in the core set are involved in bacterial homeostasis, making them attractive therapeutic targets.
LR: 20130311; GR: M083677/PHS HHS/United States; GR: SC1 AI081376-02/AI/NIAID NIH HHS/United States; GR: SC1 AI081376-03/AI/NIAID NIH HHS/United States; JID: 101202210; 0 (RNA, Bacterial); 0 (RNA, Messenger); RF: 90; NIHMS214230; OID: NLM: NIHMS214230; OID: NLM: PMC2897818; ppublish
England
1479-7364; 1473-9542
Department of Biological Sciences, College of Arts and Science, Florida International University, Miami, FL 33199, USA.
PMID: 19706365; F1512U6W113HT4L1 [pii]
eng
Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review; IM
105
61
Book, Section
Balasubramanian,D.;Murugapiran, S.K., Silva-Herzog, E.;Schenper,L.;Yang,X.;Tatke,G.;Narasimhan,G.;Mathee,K.
Transcriptional regulatory network in Pseudomonas aeruginosa
195-248 Babu,M.
In Bacterial Gene Regulation
Horizon Press
Philadelphia, PA
104105
62
Journal Article
Balasubramanian,D.;Schneper,L.;Kumari,H.;Mathee,K.
A dynamic and intricate regulatory network determines Pseudomonas aeruginosa virulence
Nucleic acids research
Nucleic Acids Res.
20137-Jan411120
Alginates;Biofilms/growth & development;Gene Expression Regulation, Bacterial;Gene Regulatory Networks;Glucuronic Acid/biosynthesis;Hexuronic Acids;Iron/metabolism;Pseudomonas aeruginosa/genetics/metabolism/pathogenicity;RNA, Small Untranslated/metabolism;Signal Transduction;Virulence/genetics;Virulence Factors/metabolism
Pseudomonas aeruginosa is a metabolically versatile bacterium that is found in a wide range of biotic and abiotic habitats. It is a major human opportunistic pathogen causing numerous acute and chronic infections. The critical traits contributing to the pathogenic potential of P. aeruginosa are the production of a myriad of virulence factors, formation of biofilms and antibiotic resistance. Expression of these traits is under stringent regulation, and it responds to largely unidentified environmental signals. This review is focused on providing a global picture of virulence gene regulation in P. aeruginosa. In addition to key regulatory pathways that control the transition from acute to chronic infection phenotypes, some regulators have been identified that modulate multiple virulence mechanisms. Despite of a propensity for chaotic behaviour, no chaotic motifs were readily observed in the P. aeruginosa virulence regulatory network. Having a 'birds-eye' view of the regulatory cascades provides the forum opportunities to pose questions, formulate hypotheses and evaluate theories in elucidating P. aeruginosa pathogenesis. Understanding the mechanisms involved in making P. aeruginosa a successful pathogen is essential in helping devise control strategies.
LR: 20130711; GR: 5SC1AI081376/AI/NIAID NIH HHS/United States; GR: S06 GM08205/GM/NIGMS NIH HHS/United States; JID: 0411011; 0 (Alginates); 0 (Hexuronic Acids); 0 (RNA, Small Untranslated); 0 (Virulence Factors); 576-37-4 (Glucuronic Acid); 7439-89-6 (Iron); 9005-32-7 (alginic acid); OID: NLM: PMC3592444; 2012/11/11 [aheadofprint]; ppublish
England
1362-4962; 0305-1048
Department of Biological Sciences, College of Arts and Science, Florida International University, Miami, FL 33199, USA.
PMID: 23143271; gks1039 [pii]
eng
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review; IM
10.1093/nar/gks1039; 10.1093/nar/gks1039
105
63
Journal Article
Balasubramanian,D.;Schneper,L.;Merighi,M.;Smith,R.;Narasimhan,G.;Lory,S.;Mathee,K.
The regulatory repertoire of Pseudomonas aeruginosa AmpC ss-lactamase regulator AmpR includes virulence genes
PloS onePLoS One2012 73e34067
Animals;Anti-Bacterial Agents/pharmacology;Bacterial Proteins/genetics/physiology;Biofilms;Caenorhabditis elegans;Drug Resistance, Bacterial;Gene Deletion;Gene Expression Regulation, Bacterial;Gene Transfer, Horizontal;Mutation;Oligonucleotide Array Sequence Analysis;Phenotype;Polymerase Chain Reaction/methods;Pseudomonas aeruginosa/genetics/pathogenicity;Transcriptome;Virulence;Virulence Factors/metabolism;beta-Lactamases/genetics/physiology
In Enterobacteriaceae, the transcriptional regulator AmpR, a member of the LysR family, regulates the expression of a chromosomal beta-lactamase AmpC. The regulatory repertoire of AmpR is broader in Pseudomonas aeruginosa, an opportunistic pathogen responsible for numerous acute and chronic infections including cystic fibrosis. In addition to regulating ampC, P. aeruginosa AmpR regulates the sigma factor AlgT/U and production of some quorum sensing (QS)-regulated virulence factors. In order to better understand the ampR regulon, we compared the transcriptional profile generated using DNA microarrays of the prototypic P. aeruginosa PAO1 strain with its isogenic ampR deletion mutant, PAODeltaampR. Transcriptome analysis demonstrates that the AmpR regulon is much more extensive than previously thought, with the deletion of ampR influencing the differential expression of over 500 genes. In addition to regulating resistance to beta-lactam antibiotics via AmpC, AmpR also regulates non-beta-lactam antibiotic resistance by modulating the MexEF-OprN efflux pump. Other virulence mechanisms including biofilm formation and QS-regulated acute virulence factors are AmpR-regulated. Real-time PCR and phenotypic assays confirmed the microarray data. Further, using a Caenorhabditis elegans model, we demonstrate that a functional AmpR is required for P. aeruginosa pathogenicity. AmpR, a member of the core genome, also regulates genes in the regions of genome plasticity that are acquired by horizontal gene transfer. Further, we show differential regulation of other transcriptional regulators and sigma factors by AmpR, accounting for the extensive AmpR regulon. The data demonstrates that AmpR functions as a global regulator in P. aeruginosa and is a positive regulator of acute virulence while negatively regulating biofilm formation, a chronic infection phenotype. Unraveling this complex regulatory circuit will provide a better understanding of the bacterial response to antibiotics and how the organism coordinately regulates a myriad of virulence factors in response to antibiotic exposure.
LR: 20130626; GR: 5SC1AI081376/AI/NIAID NIH HHS/United States; GR: S06 GM08205/GM/NIGMS NIH HHS/United States; JID: 101285081; 0 (Anti-Bacterial Agents); 0 (Bacterial Proteins); 0 (Virulence Factors); 125267-46-1 (AmpR protein, Bacteria); EC 3.5.2.6 (AmpC beta-lactamases); EC 3.5.2.6 (beta-Lactamases); OID: NLM: PMC3315558; 2011/11/08 [received]; 2012/02/27 [accepted]; 2012/03/29 [epublish]; ppublish
United States
1932-6203; 1932-6203
Department of Biological Sciences, College of Arts and Science, Florida International University, Miami, Florida, United States of America.
PMID: 22479525; PONE-D-11-22223 [pii]
eng
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; IM
10.1371/journal.pone.0034067; 10.1371/journal.pone.0034067
105
64
Journal Article
Bandyopadhyay,S.;Ganguly,S.;Mandal,G.;Sen,R.;Saha,P.;Ghosh,M. K.;Sarkar,M.;Chatterjee,M.
Cytotoxicity of Senecio in macrophages is mediated via its induction of oxidative stress
Research in veterinary science
Res.Vet.Sci.2009Aug8718590
Animals;Cells, Cultured;Female;Macrophages, Peritoneal/drug effects;Male;Mice;Oxidative Stress/drug effects;Plants, Toxic/toxicity;Reactive Nitrogen Species/metabolism;Reactive Oxygen Species/metabolism;Senecio/toxicity
In Arunachal Pradesh and other sub-Himalayan areas of India, accidental consumption of Senecio plants by yaks is often fatal as the plant contains toxic alkaloids like Seneciophylline. The present investigation was undertaken to demonstrate the pro-oxidant effects of an ethanolic extract of Senecio chrysanthemoides (S-EtOH). S-EtOH impaired viability in macrophages, the IC(50) being 13.8+/-1.11 microg/mL. The effect of S-EtOH (1 microg/mL) on generation of reactive oxygen species (ROS) in macrophages was measured by flow cytometry using 2',7'-dichlorofluorescein diacetate (H(2)DCFDA) where it caused a significant increase in the mean fluorescence channel (MFC) from 8.55+/-0.03 to 47.32+/-2.25 (p<0.001). S-EtOH also effected a 3.8-fold increase in extracellular nitric oxide (NO) generation from 4.90+/-0.72 microM to 18.79+/-0.32 microM (p<0.001), a 2.2-fold increase in intracellular NO production, the MFC increasing from 14.95+/-0.48 to 33.34+/-1.66 (p<0.001), and concomitantly depleted non protein thiols as analyzed by flow cytometry using mercury orange, with a reduction in MFC from 632.5+/-49.44 to 407.4+/-12.61 (p<0.01). Additionally, S-EtOH (14 microg/mL, 24h) caused apoptosis as evident by increased Annexin V binding and terminal deoxynucleotidyl transferase mediated dUTP DNA nick end labeling. Taken together, the cytotoxicity of S-EtOH can be partly attributed to its capacity to inflict oxidative damage via generation of both reactive oxygen and nitrogen species culminating in apoptosis.
JID: 0401300; 0 (Reactive Nitrogen Species); 0 (Reactive Oxygen Species); 2007/12/26 [received]; 2008/12/09 [revised]; 2008/12/16 [accepted]; 2009/02/04 [aheadofprint]; ppublish
England
1532-2661; 0034-5288
National Research Centre on Yak, Indian Council of Agricultural Research, Dirang, Arunachal Pradesh 790101, India.
PMID: 19195669; S0034-5288(08)00273-7 [pii]
eng
Journal Article; Research Support, Non-U.S. Gov't; IM
10.1016/j.rvsc.2008.12.007; 10.1016/j.rvsc.2008.12.007
108
65
Journal Article
Banerjee,S.;Salunkhe,S. S.;Apte-Deshpande,A. D.;Mandi,N. S.;Mandal,G.;Padmanabhan,S.
Over-expression of proteins using a modified pBAD24 vector in E. coli expression system
Biotechnology Letters
Biotechnol.Lett.
2009Jul31710311036
Escherichia coli/genetics/metabolism;Gene Expression;Genes, Bacterial;Genes, Viral;Genetic Vectors;Podoviridae/genetics;Promoter Regions, Genetic;Recombinant Proteins/biosynthesis/genetics
A modified pBAD24 vector (pBAD24M) was constructed with the araBAD promoter of the arabinose operon along with T7g10 sequence elements and a modified Shine-Dalgarno sequence. While both green fluorescent protein and granulocyte colony stimulating factor showed negligible expression under the original pBAD24 vector, they were expressed at >35% of total cellular protein with the modified vector. Similar results were obtained for staphylokinase wherein the pBAD24-SAK construct yielded 8 ng/10(6) c.f.u. of E. coli induced cells while the pBAD24M-SAK vector showed nearly 55 ng/10(6) c.f.u. induced bacterial cells as tested by ELISA. Interestingly, the expression levels using modified pBAD24 vector matched that achieved with T7 promoter based vector system. The modified pBAD24 vector therefore represents a simple and a useful prokaryotic expression system for efficient repression, modulation and elevated protein expression levels.
JID: 8008051; 0 (Recombinant Proteins); 2009/02/23 [received]; 2009/03/09 [accepted]; 2009/02/27 [revised]; 2009/03/29 [aheadofprint]; ppublish
Netherlands
1573-6776; 0141-5492
Biotechnology R & D, Lupin Limited, Lupin Research Park, 46A/47A, Nande Village, Mulshi Taluka, Pune, 411042, India.
PMID: 19330488
eng
Journal Article; IM
10.1007/s10529-009-9976-6; 10.1007/s10529-009-9976-6
108
66
Book, Section
Bauman,K.;Brown,D.
Gynecology in Primary Care
1997
Rudy,D. R.;Kurowski,K.
Family Medicine House Officer Series
William and Wilkins
Philadelphia, PA
56
67
Journal Article
Berrocal,Y.;Pearse,D. D.;Singh,A.;Andrade,C. M.;McBroom,J. S.;Puentes,R.;Eaton,M. J.
Social and environmental enrichment improves sensory and motor recovery after severe contusive spinal cord injury in the rat
Journal of neurotrauma
J.Neurotrauma
2007Nov241117611772
Animals;Contusions/complications/physiopathology/rehabilitation;Female;Hyperalgesia/etiology/prevention & control;Motor Activity/physiology;Neuronal Plasticity;Rats;Rats, Inbred F344;Recovery of Function/physiology;Social Environment;Spinal Cord Injuries/complications/physiopathology/rehabilitation;Thoracic Vertebrae
Neuropathic pain and motor dysfunction are difficult problems following spinal cord injury (SCI). Social and environmental enrichment (SEE), which models much of the clinical rehabilitation environment for post-SCI persons, is the focus of the current investigation which examines the effects of multiple-housing and the addition of climbing spaces, improved bedding and crawl toys on the sensory and motor recovery following a severe contusive SCI. Efficacy was determined with sensory testing, open-field motor behavioral testing, lesion volume analysis and quantification of brain-derived neurotrophic factor (BDNF) in the lumbar spinal cord with and without SEE provided during the recovery period. Sensory and motor testing were performed weekly for 12 weeks following SCI. SEE significantly and permanently reversed cutaneous allodynia, but not thermal hyperalgesia, to near normal levels. The gross locomotor performance (BBB [Basso, Beattie, and Bresnahan] motor scores) significantly improved about two points. In addition, the BBB subscale scores were significantly improved nearly seven points by the end of the study. SEE also significantly improved foot rotation to normal levels and reduced gridwalk footfall errors nearly 50%, but had no effect on stride length or base of support dysfunctions. SEE significantly increased the total volume of a thoracic segment of cord encompassing the injury site at 12 weeks, by reducing cavitation and increasing both the volume of grey and white matter spared, compared to SCI alone. When BDNF levels were examined in the injured lumbar spinal cord, SEE significantly returned BDNF levels to near-normal. These data suggest that immediate use of SEE after contusive SCI is able to improve overall spinal cell survival and prevent much of the sensory and motor dysfunction that accompanies contusive SCI.
JID: 8811626; ppublish
United States
0897-7151; 0897-7151
The Miami Project to Cure Paralysis, Miller School of Medicine at the University of Miami, Miami, Florida, USA.
PMID: 18001204
eng
Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; IM
10.1089/neu.2007.0327
24
68
Journal Article
Berrocal,Y. A.;Almeida,V. W.;Gupta,R.;Levi,A. D.
Transplantation of Schwann cells in a collagen tube for the repair of large, segmental peripheral nerve defects in rats.
Journal of neurosurgery
J.Neurosurg.
20137-Jun
Object Segmental nerve defects pose a daunting clinical challenge, as peripheral nerve injury studies have established that there is a critical nerve gap length for which the distance cannot be successfully bridged with current techniques. Construction of a neural prosthesis filled with Schwann cells (SCs) could provide an alternative treatment to successfully repair these long segmental gaps in the peripheral nervous system. The object of this study was to evaluate the ability of autologous SCs to increase the length at which segmental nerve defects can be bridged using a collagen tube. Methods The authors studied the use of absorbable collagen conduits in combination with autologous SCs (200,000 cells/mul) to promote axonal growth across a critical size defect (13 mm) in the sciatic nerve of male Fischer rats. Control groups were treated with serum only-filled conduits of reversed sciatic nerve autografts. Animals were assessed for survival of the transplanted SCs as well as the quantity of myelinated axons in the proximal, middle, and distal portions of the channel. Results Schwann cell survival was confirmed at 4 and 16 weeks postsurgery by the presence of prelabeled green fluorescent protein-positive SCs within the regenerated cable. The addition of SCs to the nerve guide significantly enhanced the regeneration of myelinated axons from the nerve stump into the proximal (p < 0.001) and middle points (p < 0.01) of the tube at 4 weeks. The regeneration of myelinated axons at 16 weeks was significantly enhanced throughout the entire length of the nerve guide (p < 0.001) as compared with their number in a serum-only filled tube and was similar in number compared with the reversed autograft. Autotomy scores were significantly lower in the animals whose sciatic nerve was repaired with a collagen conduit either without (p < 0.01) or with SCs (p < 0.001) when compared with a reversed autograft. Conclusions The technique of adding SCs to a guidance channel significantly enhanced the gap distance that can be repaired after peripheral nerve injury with long segmental defects and holds promise in humans. Most importantly, this study represents some of the first essential steps in bringing autologous SC-based therapies to the domain of peripheral nerve injuries with long segmental defects.
JID: 0253357; aheadofprint
1933-0693; 0022-3085
The Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida; and.
PMID: 23746104
ENG
JOURNAL ARTICLE
10.3171/2013.4.JNS121189
24
69
Journal Article
Berrocal,Y. A.;Almeida,V. W.;Levi,A. D.
Limitations of nerve repair of segmental defects using acellular conduits
Journal of neurosurgery
J.Neurosurg.
20137-Jun
The authors present the case of a 20-year-old man who, 3 months after his initial injury, underwent repair of a 1.7-cm defect of the ulnar nerve at the wrist; repair was performed with an acellular nerve allograft. Given the absence of clinical or electrophysiological recovery at 8 months postrepair, the patient underwent reexploration, excision of the "regenerated cable," and rerepair of the ulnar nerve with sural nerve autografts. Histology of the cable demonstrated minimal axonal regeneration at the midpoint of the repair. At the 6- and 12-month follow-ups of the sural nerve graft repair, clinical and electrophysiological evidence of both sensory and motor reinnervation of the ulnar nerve and associated hand muscles was demonstrated. In this report, the authors describe a single case of failed acellular nerve allograft and correlate the results with basic science and human studies reporting length and diameter limitations in human nerve repair utilizing grafts or conduits devoid of viable Schwann cells.
JID: 0253357; aheadofprint
1933-0693; 0022-3085
Department of Neurological Surgery and The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida.
PMID: 23746100
ENG
JOURNAL ARTICLE
10.3171/2013.4.JNS121938
24
70
Journal Article
Berrocal,Y. A.;Pearse,D. D.;Andrade,C. M.;Hechtman,J. F.;Puentes,R.;Eaton,M. J.
Increased spinal c-Fos expression with noxious and non-noxious peripheral stimulation after severe spinal contusion
Neuroscience letters
Neurosci.Lett.
20078-Feb41315862
Animals;Female;Formaldehyde/adverse effects;Functional Laterality;Gene Expression Regulation/physiology;Neurons, Afferent/metabolism;Peripheral Nerves/physiopathology;Physical Stimulation/methods;Proto-Oncogene Proteins c-fos/metabolism;Rats;Rats, Inbred F344;Spinal Cord Injuries/metabolism/pathology/physiopathology;Spinal Nerve Roots/pathology
The effects of severe contusive spinal cord injury (SCI), at thoracic level 8 (T8), on lumbar c-Fos expression in the spinal cord was investigated. As hypothesized, chronic SCI has a significant effect on expression of c-Fos in the dorsal spinal sensory areas with noxious and innocuous peripheral stimulation of the sciatic nerve. This alteration to stimulation effects was measured using counts of c-Fos immunoreactive cells in the dorsal horn of the L5 lumbar spinal cord in injured animals at 90 days post-injury and in uninjured controls. The number of c-Fos immunoreactive cells increased in SCI rats only after noxious peripheral stimulation (electrical and chemical) suggesting a general increase in excitability in spinal pathways (central sensitization) associated with chronic SCI. These altered responses may represent a functional anatomical reorganization of spinal cord circuitry leading to increased dorsal horn c-Fos expression as a response to severe chronic contusive damage to the spinal cord sensory pathways.
JID: 7600130; 0 (Proto-Oncogene Proteins c-fos); 50-00-0 (Formaldehyde); 2006/10/23 [received]; 2006/11/13 [revised]; 2006/11/13 [accepted]; 2006/12/11 [aheadofprint]; ppublish
Ireland
0304-3940; 0304-3940
The Miami Project to Cure Paralysis, Miami, FL 33136, United States.
PMID: 17161529; S0304-3940(06)01235-3 [pii]
eng
Journal Article; Research Support, Non-U.S. Gov't; IM
10.1016/j.neulet.2006.11.030
24
71
Book, Section
Bhattacharjee,H.;Ghosh,M.;Mukhopadhyay,R.;Rosen,B. P.
Arsenic transport systems from E. coli to humans in Transport of molecules across microbial membranes
1999 58-79
Broom-Smith,J. K.;Baumberg,S.;Sterling,C. J.;Ward,F. B.
Society for General Microbiology Symposia Series
Cambridge University Press
Cambridge 201075
72
Book, Section
Bhattacharjee,H.;Mukhopadhyay,R.;Thiyagarajan,S.;Rosen,B. P.
Aquaglyceroporins:  ancient Channels for Metalloids
2008 7:33
Journal of Biology
SpringerNew York 201075
73
Book, Section
Bhattacharjee,H.;Rosed,B.;Mukhopadhyay,R.
Aquaglyceroporins and metalloid  transport:  Implications in human diseases
2009 190 309-325 Beitz,E.
Handbook of Experimental Pharmacology
SpringerNew York 205107
74
Journal Article
Bhattacharjee,H.;Carbrey,J.;Rosen,B. P.;Mukhopadhyay,R.
Drug uptake and pharmacological modulation of drug sensitivity in leukemia by AQP9
Biochemical and biophysical research communications
Biochem.Biophys.Res.Commun.
200424-Sep3223836841
Aquaporins/genetics/metabolism;Arsenicals/pharmacokinetics;Biological Transport;Cloning, Molecular;HL-60 Cells;Humans;Ion Channels/genetics/metabolism;K562 Cells;Kinetics;Oxides/pharmacokinetics;Recombinant Proteins/metabolism;Transfection;Vitamin D/pharmacology
Leukemia is the most common childhood cancer. Trisenox, the active ingredient of which is trivalent arsenic, is the first line of treatment for acute promyelocytic leukemia. Since drug action usually requires uptake of the drug, it is of importance to determine the transport system responsible for Trisenox uptake. Recently, human aquaglyceroporin 9 (AQP9) has been shown to transport As(III) in Xenopus oocytes. In this study we report to show that AQP9 expression modulates the drug sensitivity of leukemic cells. AQP9 was transfected into the chronic myelogenous leukemia cell line K562. The transfectants became hypersensitive to Trisenox and Sb(III). The promyelocytic leukemia cell line HL60 treated with vitamin D showed higher expression of AQP9 and hypersensitivity to Trisenox and Sb(III). This sensitivity was due to higher rates of uptake of the trivalent metalloids by the cell lines overexpressing AQP9. Trisenox hypersensitivity results from increased expression of AQP9 drug uptake system. The possibility of using pharmacological agents to increase expression of AQP9 gene delivers the promise of new therapies for the treatment of leukemia. Thus, drug hypersensitivity can be correlated with increased expression of the drug uptake system. This is the first demonstration that AQP9 can modulate drug sensitivity in cancer.
LR: 20071114; GR: GM 52216/GM/NIGMS NIH HHS/United States; JID: 0372516; 0 (AQP9 protein, human); 0 (Aquaporins); 0 (Arsenicals); 0 (Ion Channels); 0 (Oxides); 0 (Recombinant Proteins); 1327-53-3 (arsenic trioxide); 1406-16-2 (Vitamin D); 2004/07/29 [received]; ppublish
United States
0006-291X; 0006-291X
Department of Biochemistry and Molecular Biology, Wayne State University, School of Medicine, Detroit, MI 48201, USA.
PMID: 15336539; S0006-291X(04)01718-8 [pii]
eng
Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; IM
10.1016/j.bbrc.2004.08.002
107
75
Journal Article
Bhattacharjee,H.;Sheng,J.;Ajees,A. A.;Mukhopadhyay,R.;Rosen,B. P.
Adventitious arsenate reductase activity of the catalytic domain of the human Cdc25B and Cdc25C phosphatases
Biochemistry
Biochemistry
20102-Feb494802809
Arsenate Reductases/metabolism;Binding Sites;Catalytic Domain;Humans;Isoenzymes/chemistry/metabolism;Protein Structure, Tertiary;cdc25 Phosphatases/chemistry/metabolism
A number of eukaryotic enzymes that function as arsenate reductases are homologues of the catalytic domain of the human Cdc25 phosphatase. For example, the Leishmania major enzyme LmACR2 is both a phosphatase and an arsenate reductase, and its structure bears similarity to the structure of the catalytic domain of human Cdc25 phosphatase. These reductases contain an active site C-X(5)-R signature motif, where C is the catalytic cysteine, the five X residues form a phosphate binding loop, and R is a highly conserved arginine, which is also present in human Cdc25 phosphatases. We therefore investigated the possibility that the three human Cdc25 isoforms might have adventitious arsenate reductase activity. The sequences for the catalytic domains of Cdc25A, -B, and -C were cloned individually into a prokaryotic expression vector, and their gene products were purified from a bacterial host using nickel affinity chromatography. While each of the three Cdc25 catalytic domains exhibited phosphatase activity, arsenate reductase activity was observed only with Cdc25B and -C. These two enzymes reduced inorganic arsenate but not methylated pentavalent arsenicals. Alteration of either the cysteine and arginine residues of the Cys-X(5)-Arg motif led to the loss of both reductase and phosphatase activities. Our observations suggest that Cdc25B and -C may adventitiously reduce arsenate to the more toxic arsenite and may also provide a framework for identifying other human protein tyrosine phosphatases containing the active site Cys-X(5)-Arg loop that might moonlight as arsenate reductases.
LR: 20130717; GR: AI58170/AI/NIAID NIH HHS/United States; GR: GM55425/GM/NIGMS NIH HHS/United States; GR: R37 GM055425/GM/NIGMS NIH HHS/United States; JID: 0370623; 0 (Isoenzymes); EC 1.20.- (Arsenate Reductases); EC 3.1.3.48 (cdc25 Phosphatases); ppublish
United States
1520-4995; 0006-2960
Department of Cellular Biology and Pharmacology, Florida International University, Herbert Wertheim College of Medicine, Miami, Florida 33199, USA. hbhatta@fiu.edu
PMID: 20025242
eng
Journal Article; Research Support, N.I.H., Extramural; IM
10.1021/bi9019127; 10.1021/bi9019127
107
76
Journal Article
Bishop,C. E.;Whitworth,D. J.;Qin,Y.;Agoulnik,A. I.;Agoulnik,I. U.;Harrison,W. R.;Behringer,R. R.;Overbeek,P. A.
A transgenic insertion upstream of sox9 is associated with dominant XX sex reversal in the mouse
Nature genetics
Nat.Genet.2000Dec264490494
Animals;Base Sequence;Chromosome Mapping;DNA Primers/genetics;Disorders of Sex Development;Female;Genes, Dominant;High Mobility Group Proteins/genetics;In Situ Hybridization;In Situ Hybridization, Fluorescence;Male;Mice;Mice, Transgenic;Molecular Sequence Data;Mutagenesis, Insertional;Pedigree;Phenotype;SOX9 Transcription Factor;Sequence Deletion;Transcription Factors/genetics
In most mammals, male development is triggered by the transient expression of the Y-chromosome gene, Sry, which initiates a cascade of gene interactions ultimately leading to the formation of a testis from the indifferent fetal gonad. Several genes, in particular Sox9, have a crucial role in this pathway. Despite this, the direct downstream targets of Sry and the nature of the pathway itself remain to be clearly established. We report here a new dominant insertional mutation, Odsex (Ods), in which XX mice carrying a 150-kb deletion (approximately 1 Mb upstream of Sox9) develop as sterile XX males lacking Sry. During embryogenesis, wild-type XX fetal gonads downregulate Sox9 expression, whereas XY and XX Ods/+ fetal gonads upregulate and maintain its expression. We propose that Ods has removed a long-range, gonad-specific regulatory element that mediates the repression of Sox9 expression in XX fetal gonads. This repression would normally be antagonized by Sry protein in XY embryos. Our data are consistent with Sox9 being a direct downstream target of Sry and provide genetic evidence to support a general repressor model of sex determination in mammals.
LR: 20101118; GENBANK/AC069019; JID: 9216904; 0 (DNA Primers); 0 (High Mobility Group Proteins); 0 (SOX9 Transcription Factor); 0 (Sox9 protein, mouse); 0 (Transcription Factors); ppublish
UNITED STATES
1061-4036; 1061-4036
Department of Obstetrics & Gynecology, Baylor College of Medicine, Houston, Texas, USA. bishop@bcm.tmc.edu
PMID: 11101852
eng
Journal Article; Research Support, U.S. Gov't, P.H.S.; IM
10.1038/82652
4919
77
Journal Article
Boettger-Tong,H. L.;Agulnik,A. I.;Ty,T. I.;Bishop,C. E.
Transposition of RhoA to the murine Y chromosome
GenomicsGenomics199815-Apr492180187
Animals;Blotting, Southern;Child;Chromosome Mapping;Chromosomes, Artificial, Yeast/genetics;Cloning, Molecular;Female;GTP-Binding Proteins/genetics;Humans;Male;Mice;Mice, Inbred C3H;Mice, Inbred C57BL;Phylogeny;Polymerase Chain Reaction;Sequence Analysis, DNA;Y Chromosome/genetics;rhoA GTP-Binding Protein
In an effort to produce a more complete transcription map of the short (approximately 5 Mb) arm of the mouse Y chromosome, we have initiated exon trapping from Yp-derived YACs. Sequence analysis of the trapped products has identified exons of previously cloned mouse Y-located genes Zfy and SSty and potential exons homologous to the human Y-located Tspy gene family. In addition, a family of three Yp-located transcripts that show close homology to human RHOA (locus designation ARHA), a member of the Ras family of small GTPases, has been identified. To determine whether these Yp sequences had been transposed from an autosomal ancestor, we used this trapped product to isolate a full-length autosomal mouse RhoA cDNA that is 80% identical at the nucleotide level and 98% identical at the amino acid level to human RHOA and maps to mouse Chromosome 2 (locus designation ArhA). Sequence analysis indicates that the Y-linked copies have diverged from the autosomal form, with small deletions precluding maintenance of a significant open reading frame in all Yp copies. Yet RT-PCR analysis indicates that two of these pseudogenes, RhoAy1 and 3, are expressed in a testis-specific manner, in sharp contrast to the nearly ubiquitous expression pattern of the autosomal ancestor. The data indicate that the Y copies of RhoA have been transposed from an autosome, followed by subsequent duplication, sequence divergence, and acquisition of a testis-specific promoter/enhancer.
LR: 20071114; GENBANK/AF014371; GENBANK/AF014372; GENBANK/AF014373; GENBANK/AF014374; GR: HD27584/HD/NICHD NIH HHS/United States; JID: 8800135; EC 3.6.1.- (GTP-Binding Proteins); EC 3.6.5.2 (rhoA GTP-Binding Protein); ppublish
UNITED STATES
0888-7543; 0888-7543
Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas 77030, USA.
PMID: 9598304; S0888-7543(98)95219-3 [pii]
eng
Journal Article; Research Support, U.S. Gov't, P.H.S.; IM
10.1006/geno.1998.5219
49
78
Journal Article
Boettger-Tong,H. L.;Rohozinski,J.;Agoulnik,A. I.;Dohmae,K.;Nishimune,Y.;Levy,N.;Bishop,C. E.
Identification and sequencing the juvenile spermatogonial depletion critical interval on mouse chromosome 1 reveals the presence of eight candidate genes
Biochemical and biophysical research communications
Biochem.Biophys.Res.Commun.
200116-Nov288511291135
Animals;Cell Cycle Proteins/genetics;Chromosome Mapping;Chromosomes;Cullin Proteins;Genetic Complementation Test;Genetic Linkage;Male;Mice;Mice, Inbred C3H;Mice, Inbred C57BL;Mice, Mutant Strains;Mutation;Sequence Analysis, DNA;Spermatogenesis;Spermatogonia/physiology;Testis/anatomy & histology;Transcription, Genetic
In mice, the recessive, non-pleiotropic, juvenile spermatogonial depletion (jsd) mutation results in a single wave of spermatogenesis, followed by failure of type A spermatogonial stem cells to differentiate, rendering adult males sterile. As part of an effort to identify the gene underlying this mutation, we report here the construction of a high-resolution genetic map involving more than 1000 meioses and 24 polymorphic loci. Our data define a critical jsd interval of approximately 0.4 cM at 49 cM on mouse chromosome 1, between D1Mit215 and 257SP6. We have constructed a physical map spanning the region comprising 24 overlapping BACs. Eighteen of these BACs have been fully sequenced, or are in draft form, allowing us to annotate approximately 2.5 Mb of DNA surrounding the jsd locus. The critical 0.4 cM jsd interval corresponds to a physical distance of approximately 1.5 Mb. Eight genes have been identified in this interval, two of which appear to be possible candidates for the jsd mutation.
LR: 20101118; CI: Copyright 2001; JID: 0372516; 0 (Cell Cycle Proteins); 0 (Cul3 protein, mouse); 0 (Cullin Proteins); ppublish
Academic Press
United States
0006-291X; 0006-291X
Department of Obstetrics and Gynecology, Baylor College of Medicine, 6550 Fannin, Suite 861, Houston, TX 77030, USA.
PMID: 11700028; S0006-291X(01)95899-1 [pii]
eng
Journal Article; IM
10.1006/bbrc.2001.5899
49
79
Journal Article
Bogatcheva,N. V.;Agoulnik,A. I.
INSL3/LGR8 role in testicular descent and cryptorchidism
Reproductive biomedicine online
Reprod.Biomed.Online
2005Jan1014954
Cryptorchidism/metabolism;Humans;Infertility, Male/genetics/metabolism;Insulin/genetics/metabolism;Male;Mutation;Proteins/genetics/metabolism;Testis/anatomy & histology/physiology
Cryptorchidism, generally referred to a failure of testicular descent into the scrotum, is the most frequent (up to 3-4% at birth) congenital anomaly in newborn boys. Cryptorchidism is closely associated with impaired fertility, and represents an established risk factor for testicular cancer. Like other genital defects, cryptorchidism is believed to be caused by either endocrine or genetic abnormalities, or both. Recent elucidation of the molecular mechanism of the rodent testicular descent, and, in particular, the critical role of Insl3 (insulin-like 3) and its receptor Great/Lgr8 encouraged the search for naturally occurring mutations in the human homologues of these genes in the affected patient population. Genetic analysis revealed several functionally deleterious mutations in both INSL3 and GREAT/LGR8 genes. However, although some of mutations were found only in cryptorchid patients, it remains to be verified whether there is a causative link between the presence of mutations in INSL3 or GREAT/LGR8 and the undescended testis phenotype in men. The data and analysis of published studies indicate that mutations in these two genes might account for only a small portion of all cases of this disease in the human population.
LR: 20111117; GR: R01 HD037067-05/HD/NICHD NIH HHS/United States; JID: 101122473; 0 (Insulin); 0 (Leydig insulin-like protein); 0 (Proteins); RF: 48; ppublish
England
1472-6483; 1472-6483
Department of Obstetrics and Gynecology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
PMID: 15705294
eng
Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Review; IM
49
80
Journal Article
Bogatcheva,N. V.;Ferlin,A.;Feng,S.;Truong,A.;Gianesello,L.;Foresta,C.;Agoulnik,A. I.
T222P mutation of the insulin-like 3 hormone receptor LGR8 is associated with testicular maldescent and hinders receptor expression on the cell surface membrane
American journal of physiology.Endocrinology and metabolism
Am.J.Physiol.Endocrinol.Metab.
2007Jan2921E13844
Adult;Amino Acid Sequence;Antigens, Surface/metabolism;Cells, Cultured;Cryptorchidism/genetics;DNA Mutational Analysis;Genetic Testing;Humans;Male;Middle Aged;Models, Biological;Molecular Sequence Data;Mutant Proteins/metabolism;Point Mutation;Protein Structure, Tertiary;Receptors, G-Protein-Coupled/genetics/metabolism;Tissue Distribution;Transfection
Insulin-like 3 (INSL3) hormone plays a crucial role in testicular descent during embryonic development. Genetic ablation of Insl3 or its G protein-coupled receptor (GPCR) Lgr8 causes cryptorchidism in mice. Previously, we identified a nonfunctional T222P mutation of LGR8 in several human patients with testicular maldescent. Using a large population of patients and healthy controls from Italy, we have demonstrated that T222P LGR8 mutation is present only in affected patients (19 T222P/+ of 598 vs. 0/450, P < 0.0001). We have also identified a novel allele of LGR8 (R223K) found in one patient with retractile testes. Both mutations are located in the leucine-rich repeats (LRRs) of GPCR ectodomain. The expression analysis of T222P mutant receptor transfected into 293T cells revealed that the mutation severely compromised GPCR cell membrane expression. The substitution of Thr(222) with the neutral Ser or Ala, or the R223K mutation, did not alter receptor cell membrane expression or ligand-induced cAMP increase. Additional mutations, affecting first leucine in a signature LxxLxLxxN/CxL stretch of LRR (L283F), or the amino acid residues, forming the disulfide bond or coordinating calcium ion in the LDLa module (C71Y and D70Y), also rendered proteins with reduced cell surface expression. The structural alterations of both LRRs and LDLa of the ligand-binding part of LGR8 cause the inability of receptor to express on the cell surface membrane and might be responsible for the abnormal testicular phenotype in patients.
LR: 20110922; GR: R01 HD037067-10/HD/NICHD NIH HHS/United States; GR: R01-HD-037067/HD/NICHD NIH HHS/United States; JID: 100901226; 0 (Antigens, Surface); 0 (Mutant Proteins); 0 (RXFP2 protein, human); 0 (Receptors, G-Protein-Coupled); 2006/08/22 [aheadofprint]; ppublish
United States
0193-1849; 0193-1849
Dept. of Ob/Gyn, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
PMID: 16926383; 00228.2006 [pii]
eng
Journal Article; Research Support, N.I.H., Extramural; IM
10.1152/ajpendo.00228.2006
49
81
Journal Article
Bogatcheva,N. V.;Truong,A.;Feng,S.;Engel,W.;Adham,I. M.;Agoulnik,A. I.
GREAT/LGR8 is the only receptor for insulin-like 3 peptide
Molecular endocrinology (Baltimore, Md.)
Mol.Endocrinol.
2003Dec171226392646
Amino Acid Sequence;Animals;Cryptorchidism/genetics;Female;Gene Deletion;Genotype;Insulin;Litter Size;Male;Mice;Mice, Knockout;Molecular Sequence Data;Mutagenesis;Pregnancy;Proteins/genetics/metabolism;Receptors, G-Protein-Coupled/deficiency/genetics/metabolism;Receptors, Peptide/deficiency/genetics/physiology;Swine
During male development testes descend from their embryonic intraabdominal position into the scrotum. Two genes, encoding the insulin-like 3 peptide (INSL3) and the GREAT/LGR8 G protein-coupled receptor, control the differentiation of gubernaculum, the caudal genitoinguinal ligament critical for testicular descent. It was established that the INSL3 peptide activates GREAT/LGR8 receptor in vitro. Mutations of Insl3 or Great cause cryptorchidism (undescended testes) in mice. Overexpression of the transgenic Insl3 causes male-like gubernaculum differentiation, ovarian descent into lower abdominal position, and reduced fertility in females. To address the question whether Great deletion complements the mutant female phenotype caused by the Insl3 overexpression, we have produced Insl3 transgenic mice deficient for Great. Such females had a wild-type phenotype, demonstrating that Great was the only cognate receptor for Insl3 in vivo. We have established that pancreatic HIT cells, transfected with the INSL3 cDNA, produce functionally active peptide. Analysis of five INSL3 mutant variants detected in cryptorchid patients showed that P49S substitution renders functionally compromised peptide. Therefore, mutations in INSL3 might contribute to the etiology of cryptorchidism. We have also showed that synthetic insulin-like peptides (INSL4 and INSL6) were unable to activate LGR7 or GREAT/LGR8.
LR: 20111117; GR: P01 HD36289/HD/NICHD NIH HHS/United States; GR: R01 HD037067-03/HD/NICHD NIH HHS/United States; GR: R01 HD37067/HD/NICHD NIH HHS/United States; JID: 8801431; 0 (Insulin); 0 (Leydig insulin-like protein); 0 (Proteins); 0 (Receptors, G-Protein-Coupled); 0 (Receptors, Peptide); 0 (relaxin receptor 2, mouse); 0 (relaxin receptors); 2003/08/21 [aheadofprint]; ppublish
United States
0888-8809; 0888-8809
Department of Obstetrics and Gynecology, 6550 Fannin Street, Baylor College of Medicine, Houston, Texas 77030, USA.
PMID: 12933905; me.2003-0096 [pii]
eng
Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; IM
10.1210/me.2003-0096
49
82
Journal Article
Bonnin,Rodolfo;Brown,Chris
The Cuban Diaspora: A Comparative Analysis of the Search for Meaning Among Recent Cuban Exiles and Cuban Americans
Hispanic Journal of Behavioral Sciences
200211244465478
Acculturation;Cuban Americans;Cuban American families;Family relations
A study was conducted to investigate the relations between acculturation, family dimensions, and purpose in life among recent Cuban exiles and Cuban Americans. Findings revealed that family adaptability, family cohesion, and acculturation were significant predictors of purpose in life. In addition, several of the variables examined were significantly related, especially the significant relationship discovered between purpose in life and the two family dimension variables for both groups.
M3: Article 7399863 507785603
http://search.ebscohost.com/login.aspx?direct=true&db=ssf&AN=507785603&site=ehost-live
10.1177/0739986302238215
EBSCO 1
83
Journal Article
Borodin,P. M.;Gorlov,I. P.;Agul'nik,A. I.;Agul'nik,S. I.;Rubinskii,A. O.
Synapsis and chiasma distribution in mice heterozygous for translocations in chromosomes 16 and 17
GenetikaGenetika1991Feb272252262
Animals;Chromosomes/ultrastructure;Crossing Over, Genetic/genetics;Haplotypes/genetics;Heterozygote;Male;Mice;Prophase/genetics;Translocation, Genetic/genetics
Electron microscopic analysis of synaptonemal complexes and analysis of chiasmata distribution in male mice heterozygous for Robertsonian translocation T(16; 17)7Bnr - (Rb7), for synaptonemal reciprocal translocation T(16;17)43H - (T43), in double heterozygotes for these translocations and in males with partial trisomy of the proximal region of chromosome 17 was carried out. Synaptic disturbances around the breakpoints of the translocations, such as asynapsis of homologous regions of partners and non-homologous synapsis of centromeric regions of acrocentric chromosomes, were revealed. Synaptic regularity in the proximal part of the chromosome 17 appeared to be affected by no t12 haplotype. Good coincidence between sizes of mitotic chromosomes and corresponding lateral elements of synaptonemal complexes was found for all chromosomes, with the exception of Rb7 in trisomics. In the latter karyotype, the proximal part of chromosome 17 involved in Robertsonian fusion seems to be shortened in the course of zygotene and never synapted with homologous segment of neither the acrocentric chromosome 17 nor large product of reciprocal translocation. Drastic increase in chiasmata frequency in the proximal part of chromosome 17 was revealed in heterozygotes for T43H and in trisomics, as compared with the double heterozygotes Rb7/T43. The latter finding was explained by the existence of two independent pairing segments in the former karyotypes.
LR: 20061115; JID: 0047354; ppublish
USSR
0016-6758; 0016-6758
PMID: 1874435
rus
English Abstract; Journal Article; IM
Sinapsis i raspredelenie khiazm u myshei, geterozigotnykh po translokatsiiam 16-i i 17-i khromosom
49
84
Journal Article
Borodin,P. M.;Gorlov,I. P.;Agulnik,A. I.;Agulnik,S. I.;Ruvinsky,A. O.
Chromosome pairing and recombination in mice heterozygous for different translocations in chromosomes 16 and 17
Chromosoma
Chromosoma
1991Dec1014252258
Animals;Haplotypes;Heterozygote;Meiosis;Mice;Recombination, Genetic;Synaptonemal Complex;Translocation, Genetic;Trisomy
In order to clarify the relationship between meiotic pairing and recombination, an electron microscopic (EM) study of synaptonemal complexes (SC) and an analysis of chiasma frequency and distribution were made in male mice singly and doubly heterozygous for Robertsonian [Rb(16.17)7Bnr] and reciprocal [T(16:17)43H] translocations and also in tertiary trisomics for the proximal region of chromosome 17. In all these genotypes an extensive zone of asynapsis/desynapsis around the breakpoints was revealed. At the same time a high frequency of non-homologous pairing was observed in precentromeric regions of acrocentric chromosomes. The presence in the proximal region of chromosome 17 of the t haplotype did not affect the synaptic behaviour of this region. Chiasma frequency in the proximal region of chromosome 17 in the T(16:17)43H heterozygotes and trisomics was increased when compared with that in Robertsonian heterozygotes.
LR: 20041117; JID: 2985138R; ppublish
GERMANY
0009-5915; 0009-5915
Institute of Cytology and Genetics, Novosibirsk, USSR.
PMID: 1773663
eng
Journal Article; IM
49
85
Book, Section
Brown,D.;Bauman,K.
Soar throat and nasal congestion
1999 Weiss,B. D.
20 Common Problems in Primary Care
McGraw HillNew York 56
86
Book, Section
Brown,D.;Jennings,A.
The Overtown Cookbook
2009 Miami, FL 56
87
Journal, Electronic
Brown,D.;Mechaber,A.;Trapido,E.;Mites Campbell,M.;Marcus,E.;Aftab,A.;Hernandez,R.;OConnell,M.
Tobacco cessation objective structured clinical examination (OSCE).
MedEdPORTAL
2009 5102 56
88
Journal Article
Brown,D. R.;Celestin,M. J.;Hernandez,A.;Brewster,L. G.;Spruill,T. E.;Nierenberg,B.;Brewster,C. D.;Akal,S.;Page,J. B.
The development of a cultural competency observational tool
Medical teacher
Med.Teach.2010 326536537
Checklist;Cultural Competency;Humans;Physician-Patient Relations;Prejudice
JID: 7909593; ppublish
England
1466-187X; 0142-159X
PMID: 20527687
eng
Letter; Research Support, U.S. Gov't, P.H.S.; IM
563571
89
Journal Article
Brown,D. R.;Hernandez,A.;Saint-Jean,G.;Evans,S.;Tafari,I.;Brewster,L. G.;Celestin,M. J.;Gomez-Estefan,C.;Regalado,F.;Akal,S.;Nierenberg,B.;Kauschinger,E. D.;Schwartz,R.;Page,J. B.
A participatory action research pilot study of urban health disparities using rapid assessment response and evaluation
American Journal of Public Health
Am.J.Public Health
2008Jan9812838
Community Health Workers/education;Community Networks/organization & administration;Consumer Participation;Florida;Focus Groups;Healthcare Disparities/statistics & numerical data;Humans;Pilot Projects;Poverty;Quality of Health Care;Urban Health Services/economics/statistics & numerical data;Urban Population
Healthy People 2010 made it a priority to eliminate health disparities. We used a rapid assessment response and evaluation (RARE) to launch a program of participatory action research focused on health disparities in an urban, disadvantaged Black community serviced by a major south Florida health center. We formed partnerships with community members, identified local health disparities, and guided interventions targeting health disparities. We describe the RARE structure used to triangulate data sources and guide intervention plans as well as findings and conclusions drawn from scientific literature and epidemiological, historic, planning, clinical, and ethnographic data. Disenfranchisement and socioeconomic deprivation emerged as the principal determinants of local health disparities and the most appropriate targets for intervention.
LR: 20130606; GR: 1 D54 HP05464-02/PHS HHS/United States; GR: 1 D58HP03198-03/PHS HHS/United States; JID: 1254074; OID: NLM: PMC2156052; 2007/11/29 [aheadofprint]; ppublish
United States
1541-0048; 0090-0036
Department of Family Medicine and Community Health, Leonard M. Miller School of Medicine, University of Miami, PO Box 016700, Miami, FL 33101, USA. dbrown@med.miami.edu
PMID: 18048802; AJPH.2006.091363 [pii]
eng
Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; AIM; IM
10.2105/AJPH.2006.091363
5671
90
Journal Article
Burka,G.;Mather,F. J.;Acuna,J. M.;Tran,T.
Race-specific trends in infant mortality: contributions of birth-weight distribution and birth-weight-specific mortality, Louisiana 1991-2002
The Journal of the Louisiana State Medical Society : official organ of the Louisiana State Medical Society
J.La.State Med.Soc.
2009Jul-Aug1614199205
African Americans/statistics & numerical data;Birth Weight;European Continental Ancestry Group/statistics & numerical data;Health Status Disparities;Humans;Infant;Infant Mortality/ethnology/trends;Infant, Low Birth Weight;Infant, Newborn;Louisiana/epidemiology
OBJECTIVES: To assess the race-specific trends in infant mortality rate (IMR) in Louisiana and identify changes in the birth weight distribution (BWD) and birth weight specific mortality (BWSM) and their effect on the overall infant mortality rate. METHODS: We used the state of Louisiana's period-linked birth/infant death file, 1991-2002. The difference in race-specific mortality between our study population and the reference population was partitioned into two components, BWD and BWSM, using the method developed by Kitagawa. RESULTS: The IMR among black infants was at least twice as high as that of white infants for every year except 1991. The difference in BWD is responsible for much of the differences between the IMR among blacks and whites. On average, 80% of the excess deaths among black infants were attributed to BWD; the great majority of the infants who died weighed less than 2500 grams. CONCLUSIONS: There was a significant decline in excess mortality attributable to BWSM among both blacks and whites. But despite this decline, the overall IMR for Louisiana remained high because of the higher proportion of low birth weight infants among blacks.
JID: 7505618; ppublish
United States
0024-6921; 0024-6921
Centers for Disease Control and Prevention, District of Columbia Department of Health, USA.
PMID: 19785310
eng
Journal Article; IM
30
91
Journal Article
Canovas,D.;Mukhopadhyay,R.;Rosen,B. P.;de Lorenzo,V.
Arsenate transport and reduction in the hyper-tolerant fungus Aspergillus sp. P37
Environmental microbiology
Environ.Microbiol.
2003Nov51110871093
Arsenates/metabolism/pharmacology;Arsenic/metabolism;Aspergillus/drug effects/metabolism;Biological Transport/physiology;Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone/pharmacology;Drug Resistance, Fungal;Oxidation-Reduction;Phosphates/metabolism;Uncoupling Agents/pharmacology;Valinomycin/pharmacology;Verapamil/pharmacology
Aspergillus sp. P37 is able to grow at arsenate concentrations of 0.2 M--more than 20-fold higher than that withstood by reference microorganisms such Escherichia coli, Saccharomyces cerevisiae and Aspergillus nidulans. This paper examines the transport of arsenate and phosphate and the reduction of arsenate in Aspergillus sp. P37. These properties were compared with the corresponding properties of the archetype strain Aspergillus nidulans TS1. Both uptake and efflux of arsenate were inhibited by carbonyl cyanide-p-trifluoromethoxyphenylhydrazone, suggesting that the transport system(s) is(are) membrane-potential dependent. As uptake of arsenate and phosphate are higher in Aspergillus sp. P37 than in A. nidulans, the increase in arsenate resistance cannot be accounted for by a change in uptake. Cells of both strains loaded with arsenic slowly released the oxyanion. Speciation of the arsenic in the medium showed an enhanced level of arsenate reduction in Aspergillus sp. P37. These data suggest that increased arsenate reduction is at least in part responsible for the hyper-tolerant phenotype of this fungus.
LR: 20071114; GR: GM52216/GM/NIGMS NIH HHS/United States; JID: 100883692; 0 (Arsenates); 0 (Phosphates); 0 (Uncoupling Agents); 2001-95-8 (Valinomycin); 370-86-5 (Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone); 52-53-9 (Verapamil); 7440-38-2 (Arsenic); ppublish
England
1462-2912; 1462-2912
Centro Nacional de Biotecnologia-CSIC, Campus UAM-Cantoblanco, Madrid 28049, Spain.
PMID: 14641588; 508 [pii]
eng
Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; IM
107
92
Journal Article
Carbrey,J. M.;Song,L.;Zhou,Y.;Yoshinaga,M.;Rojek,A.;Wang,Y.;Liu,Y.;Lujan,H. L.;DiCarlo,S. E.;Nielsen,S.;Rosen,B. P.;Agre,P.;Mukhopadhyay,R.
Reduced arsenic clearance and increased toxicity in aquaglyceroporin-9-null mice
Proceedings of the National Academy of Sciences of the United States of America
Proc.Natl.Acad.Sci.U.S.A.
200915-Sep106371595615960
Animals;Aquaporins/deficiency/genetics/metabolism;Arsenic/pharmacokinetics/toxicity;Arsenites/pharmacokinetics/toxicity;Electrocardiography;Heart Conduction System/drug effects/physiopathology;Immunohistochemistry;Lethal Dose 50;Male;Metabolic Clearance Rate;Mice;Mice, Inbred C57BL;Mice, Knockout;Myocardium/metabolism;Sodium Compounds/pharmacokinetics/toxicity;Tissue Distribution
Expressed in liver, aquaglyceroporin-9 (AQP9) is permeated by glycerol, arsenite, and other small, neutral solutes. To evaluate a possible protective role, AQP9-null mice were evaluated for in vivo arsenic toxicity. After injection with NaAsO(2), AQP9-null mice suffer reduced survival rates (LD(50), 12 mg/kg) compared with WT mice (LD(50), 15 mg/kg). The highest tissue level of arsenic is in heart, with AQP9-null mice accumulating 10-20 times more arsenic than WT mice. Within hours after NaAsO(2) injection, AQP9-null mice sustain profound bradycardia, despite normal serum electrolytes. Increased arsenic levels are also present in liver, lung, spleen, and testis of AQP9-null mice. Arsenic levels in the feces and urine of AQP9-null mice are only approximately 10% of the WT levels, and reduced clearance of multiple arsenic species by the AQP9-null mice suggests that AQP9 is involved in the export of multiple forms of arsenic. Immunohistochemical staining of liver sections revealed that AQP9 is most abundant in basolateral membrane of hepatocytes adjacent to the sinusoids. AQP9 is not detected in heart or kidney by PCR or immunohistochemistry. We propose that AQP9 provides a route for excretion of arsenic by the liver, thereby providing partial protection of the whole animal from arsenic toxicity.
LR: 20130531; GR: AI58170/AI/NIAID NIH HHS/United States; GR: DK065098/DK/NIDDK NIH HHS/United States; GR: HL48268/HL/NHLBI NIH HHS/United States; GR: R37 GM055425-29/GM/NIGMS NIH HHS/United States; JID: 7505876; 0 (Aqp9 protein, mouse); 0 (Aquaporins); 0 (Arsenites); 0 (Sodium Compounds); 48OVY2OC72 (sodium arsenite); 7440-38-2 (Arsenic); OID: NLM: PMC2747225; 2009/09/08 [aheadofprint]; ppublish
United States
1091-6490; 0027-8424
Department of Cell Biology, Duke University School of Medicine, Durham, NC 27710, USA. jennifer.carbrey@duke.edu
PMID: 19805235; 0908108106 [pii]
eng
Journal Article; Research Support, N.I.H., Extramural; IM
10.1073/pnas.0908108106; 10.1073/pnas.0908108106
107
93
Journal Article
Cardenas,S.;Scuri,M.;Samsell,L.;Ducatman,B.;Bejarano,P.;Auais,A.;Doud,M.;Mathee,K.;Piedimonte,G.
Neurotrophic and neuroimmune responses to early-life Pseudomonas aeruginosa infection in rat lungs
American journal of physiology.Lung cellular and molecular physiology
Am.J.Physiol.Lung Cell.Mol.Physiol.
2010Sep2993L33444
Aging;Animals;Animals, Newborn;Antibodies/pharmacology;Capillary Permeability;Carbazoles/pharmacology;Chemokines/metabolism;Cytokines/metabolism;Enzyme Inhibitors/pharmacology;Indole Alkaloids/pharmacology;Inflammation Mediators/metabolism;Lung/immunology/innervation/microbiology/pathology;Lung Diseases/microbiology/pathology/physiopathology;Microvessels/metabolism;Nerve Growth Factors/antagonists & inhibitors/immunology/metabolism;Neurogenic Inflammation/microbiology;Neuroimmunomodulation;Pseudomonas Infections/complications/pathology/physiopathology;Pseudomonas aeruginosa;Pulmonary Circulation;Rats;Rats, Inbred F344;Up-Regulation;Weaning
Early-life respiratory infection with Pseudomonas aeruginosa is common in children with cystic fibrosis or immune deficits. Although many of its clinical manifestations involve neural reflexes, little information is available on the peripheral nervous system of infected airways. This study sought to determine whether early-life infection triggers a neurogenic-mediated immunoinflammatory response, the mechanisms of this response, and its relationship with other immunoinflammatory pathways. Weanling and adult rats were inoculated with suspensions containing P. aeruginosa (PAO1) coated on alginate microspheres suspended in Tris-CaCl(2) buffer. Five days after infection, rats were injected with capsaicin to stimulate nociceptive nerves in the airway mucosa, and microvascular permeability was measured using Evans blue as a tracer. PAO1 increased neurogenic inflammation in the extra- and intrapulmonary compartments of weanlings but not in adults. The mechanism involves selective overexpression of NGF, which is critical for the local increase in microvascular permeability and for the infiltration of polymorphonuclear leukocytes into infected lung parenchyma. These effects are mediated in part by induction of downstream inflammatory cytokines and chemokines, especially IL-1beta, IL-18, and leptin. Our data suggest that neurogenic-mediated immunoinflammatory mechanisms play important roles in airway inflammation and hyperreactivity associated with P. aeruginosa when infection occurs early in life.
LR: 20130529; GR: GM-061347/GM/NIGMS NIH HHS/United States; GR: HL-61007/HL/NHLBI NIH HHS/United States; GR: NCS-07-11/PHS HHS/United States; JID: 100901229; 0 (Antibodies); 0 (Carbazoles); 0 (Chemokines); 0 (Cytokines); 0 (Enzyme Inhibitors); 0 (Indole Alkaloids); 0 (Inflammation Mediators); 0 (Nerve Growth Factors); 97161-97-2 (staurosporine aglycone); OID: NLM: PMC2951071; 2010/06/11 [aheadofprint]; ppublish
United States
1522-1504; 1040-0605
Department of Pediatrics and Pediatric Research Institute, West Virginia University School of Medicine, Morgantown, West Virginia 26506-9214, USA.
PMID: 20543002; ajplung.00017.2010 [pii]
eng
Journal Article; Research Support, N.I.H., Extramural; IM
10.1152/ajplung.00017.2010; 10.1152/ajplung.00017.2010
105
94
Journal Article
Casamassima,A. C.;Hess,L. W.;Marty,A.
TC-83 Venezuelan equine encephalitis vaccine exposure during pregnancy
TeratologyTeratology1987Dec363287289
Adult;Edema;Encephalomyelitis, Equine/immunology;Encephalomyelitis, Venezuelan Equine/embryology/immunology;Female;Fetal Death;Humans;Pregnancy;Pregnancy Complications, Infectious/immunology;Vaccines, Attenuated
A human pregnancy exposed to TC-83 live attenuated Venezuelan equine encephalitis (VEE) virus vaccine resulted in hydrops fetalis and fetal demise. Maternal seroconversion and the finding of a diffuse mononuclear cell infiltrate on postmortem examination are suggestive of a causative role for TC-83 vaccine.
LR: 20041117; JID: 0153257; 0 (Vaccines, Attenuated); ppublish
UNITED STATES
0040-3709; 0040-3709
Department of Pediatrics, New York Medical College and Westchester County Medical Center, Valhalla, New York 10595.
PMID: 3424216
eng
Journal Article; IM
10.1002/tera.1420360303
111
95
Journal Article
Castrucci,B. C.;Echegollen Guzman,A.;Saraiya,M.;Smith,B. R.;Lewis,K. L.;Coughlin,S. S.;Gossman,G. L.;McDonald,J. A.;Foulkes,H.;Mirchandani,G.;Correa-Nieto Canedo,L.;Garcia,I. M.;Acuna,J.
Cervical cancer screening among women who gave birth in the US-Mexico border region, 2005: the Brownsville-Matamoros Sister City Project for Women's Health
Preventing chronic disease
Prev.Chronic Dis.
2008Oct54A116
Cross-Sectional Studies;Dihydroergotamine;Education;Female;Health Behavior;Health Knowledge, Attitudes, Practice;Hispanic Americans;Humans;Mexico;Multivariate Analysis;Parturition;Pregnancy;Prenatal Care;Socioeconomic Factors;Texas;Uterine Cervical Neoplasms/diagnosis;Vaginal Smears;Women's Health Services/organization & administration
INTRODUCTION: The objective of this study was to examine correlates of ever having had a Papanicolaou (Pap) test among women who recently delivered a live infant and who resided near the US-Mexico border. METHODS: This cross-sectional study included women who delivered a live infant in Matamoros, Mexico (n = 488) and Cameron County, Texas (n = 453). Women were interviewed in the hospital before discharge between August 21 and November 9, 2005. Multivariable logistic regression was used to estimate the odds of ever having had a Pap test. RESULTS: Significantly fewer Matamoros women (62.1%) than Cameron County women (95.7%) reported ever having had a Pap test. Only 12% of Matamoros women said they received their most recent Pap test during prenatal care, compared with nearly 75% of Cameron County women. After adjusting for potential confounders, the odds of ever having had a Pap test were 7.41 times greater in Cameron County than in Matamoros (95% confidence interval, 4.07-13.48). CONCLUSION: The Healthy Border 2010 goals are to cut cervical cancer mortality by 20% to 30% in the border region. The significant difference in Pap test prevalence among our survey respondents may reflect that routine prenatal Pap testing is more common in the United States than in Mexico. Because women who are receiving prenatal care have increased interaction with health care providers, Matamoros providers may need to be educated about the need to screen for cervical cancer during this time.
LR: 20091118; GR: U65 CCU 623699-01-2/PHS HHS/United States; JID: 101205018; 511-12-6 (Dihydroergotamine); CIN: Prev Chronic Dis. 2008 Oct;5(4):A111. PMID: 18793499; CIN: Prev Chronic Dis. 2008 Oct;5(4):A110. PMID: 18793498; CIN: Prev Chronic Dis. 2008 Oct;5(4):A109. PMID: 18793497; CIN: Prev Chronic Dis. 2008 Oct;5(4):A107. PMID: 18793495; OID: NLM: PMC2578779; 2008/09/15 [epublish]; ppublish
United States
1545-1151
Texas Department of State Health Services, 1100 West 49th St, Austin, TX 78756, USA. brian.castrucci@dshs.state.tx.us
PMID: 18793504; A116 [pii]
eng
Journal Article; Research Support, U.S. Gov't, P.H.S.; IM
30
96
Journal Article
Castrucci,B. C.;Pina Carrizales,L. E.;D'Angelo,D. V.;McDonald,J. A.;Foulkes,H.;Ahluwalia,I. B.;Gossman,G. L.;Acuna,J.;Erickson,T.;Clatanoff,K.;Lewis,K.;Mirchandani,G.;Smith,B.
Attempted breastfeeding before hospital discharge on both sides of the US-Mexico border, 2005: the Brownsville-Matamoros Sister City Project for Women's Health
Preventing chronic disease
Prev.Chronic Dis.
2008Oct54A117
Adult;Breast Feeding;Female;Health Policy;Hospitals;Humans;Mexico;Parturition;Postnatal Care;Pregnancy;Prenatal Care;Social Support;Texas;Women's Health Services/organization & administration
INTRODUCTION: The US-Mexico border region has a growing population and limited health care infrastructure. Preventive health behaviors such as breastfeeding ease the burden on this region's health care system by reducing morbidity and health care costs. We examined correlates of attempted breastfeeding before hospital discharge on each side of the US-Mexico border and within the border region. METHODS: The cross-sectional study included women who delivered a live infant in Matamoros, Tamaulipas, Mexico (n = 489), and Cameron County, Texas (n = 457), which includes Brownsville, Texas. We interviewed women before hospital discharge from August 21 through November 9, 2005. We used multivariate logistic regression to estimate the odds of attempted breastfeeding before hospital discharge in Cameron County, Texas, the municipality of Matamoros, Mexico, and the 2 communities combined. RESULTS: Prevalence of attempted breastfeeding before hospital discharge was 81.9% in Matamoros compared with 63.7% in Cameron County. After adjusting for potential confounders, the odds of attempted breastfeeding before hospital discharge were 90% higher in Matamoros than in Cameron County (adjusted odds ratio [AOR], 1.93; 95% confidence interval [CI], 1.31-2.84 for the combined model). In the 2 communities combined, odds of attempted breastfeeding before hospital discharge were higher among women who had a vaginal delivery than among women who had a cesarean delivery (AOR, 1.98; 95% CI, 1.43-2.75) and were lower among women who delivered infants with a low birth weight than among women who delivered infants with a normal birth weight (AOR, 0.26; 95% CI, 0.15-0.44). CONCLUSION: The rate of attempted breastfeeding in Matamoros was significantly higher than in Cameron County. Additional breastfeeding support and messages on the US side of the US-Mexico border are needed.
LR: 20091118; GR: U65 CCU 623699-01-2/PHS HHS/United States; JID: 101205018; CIN: Prev Chronic Dis. 2008 Oct;5(4):A110. PMID: 18793498; CIN: Prev Chronic Dis. 2008 Oct;5(4):A111. PMID: 18793499; CIN: Prev Chronic Dis. 2008 Oct;5(4):A108. PMID: 18793496; CIN: Prev Chronic Dis. 2008 Oct;5(4):A107. PMID: 18793495; OID: NLM: PMC2578764; 2008/09/15 [epublish]; ppublish
United States
1545-1151
Office of Title V, Division of Family and Community Health Services, Texas Department of State Health Services, 1100 West 49th St, Austin, TX 78756, USA. brian.castrucci@dshs.state.tx.us
PMID: 18793505; A117 [pii]
eng
Journal Article; Research Support, U.S. Gov't, P.H.S.; IM
30
97
Journal Article
Chan,K. G.;Atkinson,S.;Mathee,K.;Sam,C. K.;Chhabra,S. R.;Camara,M.;Koh,C. L.;Williams,P.
Characterization of N-acylhomoserine lactone-degrading bacteria associated with the Zingiber officinale (ginger) rhizosphere: co-existence of quorum quenching and quorum sensing in Acinetobacter and Burkholderia
BMC microbiology
BMC Microbiol.
20118-Mar11 512180-11-51
Acinetobacter/growth & development/isolation & purification/metabolism;Acyl-Butyrolactones/metabolism;Burkholderia/growth & development/isolation & purification/metabolism;Culture Media;Ginger/microbiology;Malaysia;Quorum Sensing;Rhizosphere
BACKGROUND: Cell-to-cell communication (quorum sensing (QS)) co-ordinates bacterial behaviour at a population level. Consequently the behaviour of a natural multi-species community is likely to depend at least in part on co-existing QS and quorum quenching (QQ) activities. Here we sought to discover novel N-acylhomoserine lactone (AHL)-dependent QS and QQ strains by investigating a bacterial community associated with the rhizosphere of ginger (Zingiber officinale) growing in the Malaysian rainforest. RESULTS: By using a basal growth medium containing N-(3-oxohexanoyl)homoserine lactone (3-oxo-C6-HSL) as the sole source of carbon and nitrogen, the ginger rhizosphere associated bacteria were enriched for strains with AHL-degrading capabilities. Three isolates belonging to the genera Acinetobacter (GG2), Burkholderia (GG4) and Klebsiella (Se14) were identified and selected for further study. Strains GG2 and Se14 exhibited the broadest spectrum of AHL-degrading activities via lactonolysis while GG4 reduced 3-oxo-AHLs to the corresponding 3-hydroxy compounds. In GG2 and GG4, QQ was found to co-exist with AHL-dependent QS and GG2 was shown to inactivate both self-generated and exogenously supplied AHLs. GG2, GG4 and Se14 were each able to attenuate virulence factor production in both human and plant pathogens. CONCLUSIONS: Collectively our data show that ginger rhizosphere bacteria which make and degrade a wide range of AHLs are likely to play a collective role in determining the QS-dependent phenotype of a polymicrobial community.
LR: 20130630; JID: 100966981; 0 (Acyl-Butyrolactones); 0 (Culture Media); OID: NLM: PMC3062576; 2010/12/31 [received]; 2011/03/08 [accepted]; 2011/03/08 [aheadofprint]; epublish
England
1471-2180; 1471-2180
Division of Genetics and Molecular Biology, Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia. kokgan@um.edu.my
PMID: 21385437; 1471-2180-11-51 [pii]
eng
Journal Article; Research Support, Non-U.S. Gov't; IM
10.1186/1471-2180-11-51; 10.1186/1471-2180-11-51
105
98
Journal Article
Chan,W. Y.;Lorke,D. E.;Tiu,S. C.;Yew,D. T.
Proliferation and apoptosis in the developing human neocortex
The Anatomical Record
Anat.Rec.20021-Aug2674261276
Apoptosis/physiology;Cell Division;Gestational Age;Humans;Neocortex/cytology/embryology;Organogenesis/physiology
The cell kinetics of the developing central nervous system (CNS) is determined by both proliferation and apoptosis. In the human neocortex at week 6 of gestation, proliferation is confined to the ventricular zone, where mitotic figures and nuclear immunoreactivity for proliferating cell nuclear antigen (PCNA) are detectable. Cell division is symmetric, with both daughter cells reentering mitosis. At week 7, the subventricular zone, a secondary proliferative zone, appears. It mainly gives rise to local circuit neurons and glial cells. Around week 12, the ventricular and subventricular zones are thickest, and the nuclear PCNA label is strongest, indicating that proliferation peaks at this stage. Thereafter, asymmetric division becomes the predominant mode of proliferation, with one daughter cell reentering mitosis and the other one migrating out. Towards late gestation, the ventricular and subventricular zones almost completely disappear and proliferation shifts towards the intermediate and subplate zones, where mainly glial cells are generated. A remnant of the subventricular zone with proliferative activity persists into adulthood. In general, proliferation follows a latero-medial gradient in the neocortex lasting longer in its lateral parts. Apoptotic nuclei have been detected around week 5, occurring in low numbers in the ventricular zone at this stage. Apoptotic cell death increases around midgestation and then spreads throughout all cortical layers, with most dying cells located in the ventricular and subventricular zones. This spatial distribution of apoptosis extends into late gestation. During the early postnatal period, most apoptotic cells are still located in the subcortical layers. During early embryonic development, proliferation and apoptosis are closely related, and are probably regulated by common regulators. In the late fetal and early postnatal periods, when proliferation has considerably declined in all cortical layers, apoptosis may occur in neurons whose sprouting axons do not find their targets.
LR: 20061115; CI: Copyright 2002; JID: 0370540; RF: 242; ppublish
Wiley-Liss, Inc
United States
0003-276X; 0003-276X
Department of Anatomy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
PMID: 12124904
eng
Journal Article; Research Support, Non-U.S. Gov't; Review; IM
10.1002/ar.10100
21
99
Journal Article
Chen,C. Z.;Southall,N.;Xiao,J.;Marugan,J. J.;Ferrer,M.;Hu,X.;Jones,R. E.;Feng,S.;Agoulnik,I. U.;Zheng,W.;Agoulnik,A. I.
Identification of Small-Molecule Agonists of Human Relaxin Family Receptor 1 (RXFP1) by Using a Homogenous Cell-Based cAMP Assay
Journal of biomolecular screening
J.Biomol.Screen.
2013Jul186670677
GPCR;RXFP1;agonist;qHTS;relaxin;small molecule
The relaxin hormone is involved in a variety of biological functions, including female reproduction and parturition, as well as regulation of cardiovascular, renal, pulmonary, and hepatic functions. It regulates extracellular matrix remodeling, cell invasiveness, proliferation, differentiation, and overall tissue homeostasis. The G protein-coupled receptor (GPCR) relaxin family receptor 1 (RXFP1) is a cognate relaxin receptor that mainly signals through cyclic AMP second messenger. Although agonists of the receptor could have a wide range of pharmacologic utility, until now there have been no reported small-molecule agonists for relaxin receptors. Here, we report the development of a quantitative high-throughput platform for an RXFP1 agonist screen based on homogenous cell-based HTRF cyclic AMP (cAMP) assay technology. Two small molecules of similar structure were independently identified from a screen of more than 365 677 compounds. Neither compound showed activity in a counterscreen with HEK293T cells transfected with an unrelated GPCR vasopressin 1b receptor. These small-molecule agonists also demonstrated selectivity against the RXFP2 receptor, providing a basis for future medicinal chemistry optimization of selective relaxin receptor agonists.
JID: 9612112; OTO: NOTNLM; 2012/12/04 [aheadofprint]; ppublish
United States
1552-454X; 1087-0571
1National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA.
PMID: 23212924; 1087057112469406 [pii]
eng
Journal Article; IM
10.1177/1087057112469406; 10.1177/1087057112469406
4919
100
Journal Article
Crawford,D. C.;Acuna,J. M.;Sherman,S. L.
FMR1 and the fragile X syndrome: human genome epidemiology review
Genetics in medicine : official journal of the American College of Medical Genetics
Genet.Med.2001Sep-Oct35359371
European Continental Ancestry Group/genetics;Female;Fragile X Mental Retardation Protein;Fragile X Syndrome/epidemiology/genetics;Gene Frequency/genetics;Genetic Testing;Genome, Human;Heterozygote;Humans;Male;Mutation/genetics;Nerve Tissue Proteins/genetics;RNA-Binding Proteins;Trinucleotide Repeats/genetics
The fragile X syndrome, an X-linked dominant disorder with reduced penetrance, is one of the most common forms of inherited mental retardation. The cognitive, behavioral, and physical phenotype varies by sex, with males being more severely affected because of the X-linked inheritance of the mutation. The disorder-causing mutation is the amplification of a CGG repeat in the 5' untranslated region of FMR1 located at Xq27.3. The fragile X CGG repeat has four forms: common (6-40 repeats), intermediate (41-60 repeats), premutation (61-200 repeats), and full mutation (>200-230 repeats). Population-based studies suggest that the prevalence of the full mutation, the disorder-causing form of the repeat, ranges from 1/3,717 to 1/8,918 Caucasian males in the general population. The full mutation is also found in other racial/ethnic populations; however, few population-based studies exist for these populations. No population-based studies exist for the full mutation in a general female population. In contrast, several large, population-based studies exist for the premutation or carrier form of the disorder, with prevalence estimates ranging from 1/246 to 1/468 Caucasian females in the general population. For Caucasian males, the prevalence of the premutation is approximately 1/1,000. Like the full mutation, little information exists for the premutation in other populations. Although no effective cure or treatment exists for the fragile X syndrome, all persons affected with the syndrome are eligible for early intervention services. The relatively high prevalence of the premutation and full mutation genotypes coupled with technological advances in genetic testing make the fragile X syndrome amenable to screening. The timing as well as benefits and harms associated with the different screening strategies are the subject of current research and discussion.
LR: 20091119; GR: R01 HD29909/HD/NICHD NIH HHS/United States; JID: 9815831; 0 (FMR1 protein, human); 0 (Nerve Tissue Proteins); 0 (RNA-Binding Proteins); 139135-51-6 (Fragile X Mental Retardation Protein); RF: 155; ppublish
United States
1098-3600; 1098-3600
Centers for Disease Control and Prevention, Epidemic Intelligence Service, Division of Applied Public Health Training, Epidemiology Program Office, Atlanta, Georgia, USA.
PMID: 11545690
eng
Journal Article; Research Support, U.S. Gov't, P.H.S.; Review; IM
10.109700125817-200109000-00006
30
Loading...
 
 
 
120231379353383328-Reflist-api.