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  1 / 1374 MEDLINE  
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[PMID]:26936971
[Au] Autor:Brewer PD; Habtemichael EN; Romenskaia I; Coster AC; Mastick CC
[Ad] Endereço:Department of Biochemistry and Molecular Biology, and Department of Pharmacology, University of Nevada, Reno, NV 89557, U.S.A.
[Ti] Título:Rab14 limits the sorting of Glut4 from endosomes into insulin-sensitive regulated secretory compartments in adipocytes.
[So] Source:Biochem J;473(10):1315-27, 2016 May 15.
[Is] ISSN:1470-8728
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Insulin increases glucose uptake by increasing the rate of exocytosis of the facilitative glucose transporter isoform 4 (Glut4) relative to its endocytosis. Insulin also releases Glut4 from highly insulin-regulated secretory compartments (GSVs or Glut4 storage vesicles) into constitutively cycling endosomes. Previously it was shown that both overexpression and knockdown of the small GTP-binding protein Rab14 decreased Glut4 translocation to the plasma membrane (PM). To determine the mechanism of this perturbation, we measured the effects of Rab14 knockdown on the trafficking kinetics of Glut4 relative to two proteins that partially co-localize with Glut4, the transferrin (Tf) receptor and low-density-lipoprotein-receptor-related protein 1 (LRP1). Our data support the hypothesis that Rab14 limits sorting of proteins from sorting (or 'early') endosomes into the specialized GSV pathway, possibly through regulation of endosomal maturation. This hypothesis is consistent with known Rab14 effectors. Interestingly, the insulin-sensitive Rab GTPase-activating protein Akt substrate of 160 kDa (AS160) affects both sorting into and exocytosis from GSVs. It has previously been shown that exocytosis of GSVs is rate-limited by Rab10, and both Rab10 and Rab14 are in vitro substrates of AS160. Regulation of both entry into and exit from GSVs by AS160 through sequential Rab substrates would provide a mechanism for the finely tuned 'quantal' increases in cycling Glut4 observed in response to increasing concentrations of insulin.
[Mh] Termos MeSH primário: Adipócitos/metabolismo
Endossomos/metabolismo
Proteínas rab de Ligação ao GTP/metabolismo
[Mh] Termos MeSH secundário: Células 3T3-L1
Adipócitos/efeitos dos fármacos
Animais
Endocitose/genética
Endocitose/fisiologia
Citometria de Fluxo
Insulina/farmacologia
Macroglobulinas/genética
Macroglobulinas/metabolismo
Camundongos
Transporte Proteico/fisiologia
Transferrina/metabolismo
Proteínas rab de Ligação ao GTP/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Insulin); 0 (Macroglobulins); 0 (Transferrin); EC 3.6.1.- (Rab14 protein, mouse); EC 3.6.5.2 (rab GTP-Binding Proteins)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170515
[Lr] Data última revisão:
170515
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160304
[St] Status:MEDLINE
[do] DOI:10.1042/BCJ20160020


  2 / 1374 MEDLINE  
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[PMID]:26845597
[Au] Autor:Bignulin S; Falleti E; Cmet S; Cappello D; Cussigh A; Lenisa I; Dissegna D; Pugliese F; Vivarelli C; Fabris C; Fabris C; Toniutto P
[Ad] Endereço:Department of Medical Sciences Experimental and Clinical, Medical Liver Transplant Section, Udine, Italy.
[Ti] Título: Usefulness of acoustic radiation force impulse and fibrotest in liver fibrosis assessment after liver transplant.
[So] Source:Ann Hepatol;15(2):200-6, 2016 Mar-Apr.
[Is] ISSN:1665-2681
[Cp] País de publicação:Mexico
[La] Idioma:eng
[Ab] Resumo:UNLABELLED:  Background and rationale. Acoustic radiation force impulse (ARFI) is a non-invasive tool used in the evaluation of liver fibrosis in HCV positive immune-competent patients. This study aimed to assess the accuracy of ARFI in discriminating liver transplanted patients with different graft fibrosis severity and to verify whether ARFI, eventually combined with non-invasive biochemical tests, could spare liver biopsies. This prospective study included 51 HCV positive liver transplanted patients who consecutively underwent to annual liver biopsy concomitantly with ARFI and blood chemistry tests measurements needed to calculate several non-invasive liver fibrosis tests. RESULTS: Overall ARFI showed an AUC of 0.885 in discriminating between patients without or with significant fibrosis (Ishak score 0-2vs. 3-6). Using a cut-off of 1.365 m/s, ARFI possesses a negative predictive value of 100% in identifying patients without significant fibrosis. AUC for Fibrotest was 0.848 in discriminating patients with Ishak fibrosis score 0-2 vs. 3-6. The combined assessment of ARFI and Fibro-test did not improve the results obtained by ARFI alone. CONCLUSION: ARFI measurement in HCV positive liver transplanted patients can be considered an easy and accurate non-invasive tool in identify patients with a benign course of HCV recurrence.
[Mh] Termos MeSH primário: Hepatite C Crônica/diagnóstico por imagem
Cirrose Hepática/diagnóstico por imagem
Transplante de Fígado
Fígado/diagnóstico por imagem
[Mh] Termos MeSH secundário: Idoso
Alanina Transaminase/sangue
Apolipoproteína A-I/sangue
Área Sob a Curva
Aspartato Aminotransferases/sangue
Bilirrubina/sangue
Biópsia
Técnicas de Imagem por Elasticidade
Feminino
Haptoglobinas/metabolismo
Hepatite C Crônica/metabolismo
Hepatite C Crônica/patologia
Hepatite C Crônica/cirurgia
Seres Humanos
Fígado/patologia
Cirrose Hepática/metabolismo
Cirrose Hepática/patologia
Cirrose Hepática/cirurgia
Macroglobulinas/metabolismo
Masculino
Meia-Idade
Valor Preditivo dos Testes
Estudos Prospectivos
Recidiva
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Apolipoprotein A-I); 0 (Haptoglobins); 0 (Macroglobulins); EC 2.6.1.1 (Aspartate Aminotransferases); EC 2.6.1.2 (Alanine Transaminase); RFM9X3LJ49 (Bilirubin)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160205
[St] Status:MEDLINE
[do] DOI:10.5604/16652681.1193710


  3 / 1374 MEDLINE  
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[PMID]:25488663
[Au] Autor:Rodriguez E; Nan R; Li K; Gor J; Perkins SJ
[Ad] Endereço:From the Department of Structural and Molecular Biology, Division of Biosciences, Darwin Building, University College London, Gower Street, London WC1E 6BT, United Kingdom.
[Ti] Título:A revised mechanism for the activation of complement C3 to C3b: a molecular explanation of a disease-associated polymorphism.
[So] Source:J Biol Chem;290(4):2334-50, 2015 Jan 23.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The solution structure of complement C3b is crucial for the understanding of complement activation and regulation. C3b is generated by the removal of C3a from C3. Hydrolysis of the C3 thioester produces C3u, an analog of C3b. C3b cleavage results in C3c and C3d (thioester-containing domain; TED). To resolve functional questions in relation to C3b and C3u, analytical ultracentrifugation and x-ray and neutron scattering studies were used with C3, C3b, C3u, C3c, and C3d, using the wild-type allotype with Arg(102). In 50 mm NaCl buffer, atomistic scattering modeling showed that both C3b and C3u adopted a compact structure, similar to the C3b crystal structure in which its TED and macroglobulin 1 (MG1) domains were connected through the Arg(102)-Glu(1032) salt bridge. In physiological 137 mm NaCl, scattering modeling showed that C3b and C3u were both extended in structure, with the TED and MG1 domains now separated by up to 6 nm. The importance of the Arg(102)-Glu(1032) salt bridge was determined using surface plasmon resonance to monitor the binding of wild-type C3d(E1032) and mutant C3d(A1032) to immobilized C3c. The mutant did not bind, whereas the wild-type form did. The high conformational variability of TED in C3b in physiological buffer showed that C3b is more reactive than previously thought. Because the Arg(102)-Glu(1032) salt bridge is essential for the C3b-Factor H complex during the regulatory control of C3b, the known clinical associations of the major C3S (Arg(102)) and disease-linked C3F (Gly(102)) allotypes of C3b were experimentally explained for the first time.
[Mh] Termos MeSH primário: Ativação do Complemento
Complemento C3/metabolismo
Complemento C3b/metabolismo
Complemento C3c/metabolismo
Complemento C3d/metabolismo
[Mh] Termos MeSH secundário: Arginina/química
Cristalografia por Raios X
Seres Humanos
Macroglobulinas/metabolismo
Mutagênese
Mutação
Conformação Proteica
Multimerização Proteica
Espalhamento de Radiação
Ressonância de Plasmônio de Superfície
Ultracentrifugação
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Complement C3); 0 (Macroglobulins); 80295-43-8 (Complement C3b); 80295-44-9 (Complement C3c); 80295-45-0 (Complement C3d); 94ZLA3W45F (Arginine)
[Em] Mês de entrada:1504
[Cu] Atualização por classe:151028
[Lr] Data última revisão:
151028
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:141210
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M114.605691


  4 / 1374 MEDLINE  
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[PMID]:24868914
[Au] Autor:Kit IuIa; Kornii N; Kril' II; Mahorivs'ka IB; Tkachenko V; Bilyi RO; Stoika RS
[Ti] Título:[Proteolytic activity of IgG-antibodies of mice, immunized by calf thymus histones].
[So] Source:Ukr Biochem J;86(2):79-88, 2014 Mar-Apr.
[Is] ISSN:2409-4943
[Cp] País de publicação:Ukraine
[La] Idioma:ukr
[Ab] Resumo:The main goal of the study was to determine the ability of histones to induce production of the proteolytically active IgG-antibodies in BALB/c mice. In order to perform this study 8 mice were immunized with the fraction of total calf thymus histones. IgGs were isolated from the serum of the immunized and not immunized animals by means of precipitation with 33% ammonium sulfate, followed by affinity chromatography on protein G-Sepharose column. Histones, myelin basic protein (MBP), lysozyme, BSA, ovalbumin, macroglobulin, casein and cytochrome c served as substrates for determining the proteolytic activity. It was found that IgGs from the blood serum of immunized mice are capable of hydrolyzing histone H1, core histone and MBP. On the contrary, the proteolytic activity of IgGs from the blood serum of not immunized mice was not detected. The absence of proteolytical enzymes in the fraction of IgGs was proven by HPLC chromatography. High levels of proteolytic activity toward histones have been also detected in affinity purified IgGs from blood serum of patients with rheumatoid arthritis, but not in healthy donors. These data indicate that eukaryotic histones may induce production of protabzymes in mammals. The possible origin of these protabzymes and their potential biological role in mammalians is discussed.
[Mh] Termos MeSH primário: Anticorpos Catalíticos/química
Artrite Reumatoide/sangue
Histonas/administração & dosagem
Soros Imunes/química
Imunoglobulina G/química
[Mh] Termos MeSH secundário: Animais
Artrite Reumatoide/imunologia
Artrite Reumatoide/patologia
Caseínas/química
Bovinos
Cromatografia de Afinidade
Cromatografia Líquida de Alta Pressão
Citocromos c/química
Histonas/imunologia
Histonas/isolamento & purificação
Seres Humanos
Imunização
Macroglobulinas/química
Masculino
Camundongos
Camundongos Endogâmicos BALB C
Muramidase/química
Proteína Básica da Mielina/química
Ovalbumina/química
Proteólise
Especificidade por Substrato
Timo/química
[Pt] Tipo de publicação:ENGLISH ABSTRACT; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antibodies, Catalytic); 0 (Caseins); 0 (Histones); 0 (Immune Sera); 0 (Immunoglobulin G); 0 (Macroglobulins); 0 (Myelin Basic Protein); 9006-59-1 (Ovalbumin); 9007-43-6 (Cytochromes c); EC 3.2.1.17 (Muramidase)
[Em] Mês de entrada:1406
[Cu] Atualização por classe:150504
[Lr] Data última revisão:
150504
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140530
[St] Status:MEDLINE


  5 / 1374 MEDLINE  
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[PMID]:23578179
[Au] Autor:Spicknall KE; Dubas LE; Mutasim DF
[Ti] Título:Cutaneous macroglobulinosis with monotypic plasma cells: a specific manifestation of Waldenström macroglobulinemia.
[So] Source:J Cutan Pathol;40(5):440-4, 2013 May.
[Is] ISSN:1600-0560
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Plasmócitos/patologia
Púrpura Hiperglobulinêmica/diagnóstico
Dermatopatias/diagnóstico
Macroglobulinemia de Waldenstrom/diagnóstico
[Mh] Termos MeSH secundário: Adulto
Seres Humanos
Macroglobulinas/metabolismo
Masculino
Púrpura Hiperglobulinêmica/metabolismo
Dermatopatias/metabolismo
Macroglobulinemia de Waldenstrom/metabolismo
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Macroglobulins)
[Em] Mês de entrada:1310
[Cu] Atualização por classe:130412
[Lr] Data última revisão:
130412
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130413
[St] Status:MEDLINE
[do] DOI:10.1111/cup.12150


  6 / 1374 MEDLINE  
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[PMID]:23413684
[Au] Autor:Zorin NA; Zorina VN
[Ti] Título:[Macroglobulin signaling system].
[So] Source:Biomed Khim;58(4):400-10, 2012 Jul-Aug.
[Is] ISSN:2310-6972
[Cp] País de publicação:Russia (Federation)
[La] Idioma:rus
[Ab] Resumo:This review will focus on the systematization of knowledge about structure of macroglobulin signaling system, which includes macroglobulin family proteins (alpha-2-macroglobulin, alpha-2-glycoprotein, pregnancy associated plasma protein A), their receptors (LRP, grp78), ligands (proteinases, cytokines, hormones, lipids, et al.) transforming and transcriptional factors for regulation of macroglobulins synthesis. After reviewing the functions of macroglobulin signaling system, and mechanisms of their realization, we discuss the complex and significant role of this system in different physiological and pathological processes.
[Mh] Termos MeSH primário: Macroglobulinas/metabolismo
Transdução de Sinais/fisiologia
[Mh] Termos MeSH secundário: Animais
Transporte Biológico/fisiologia
Citocinas/metabolismo
Feminino
Proteínas de Choque Térmico/metabolismo
Hormônios/metabolismo
Seres Humanos
Ligantes
Masculino
Peptídeo Hidrolases/metabolismo
[Pt] Tipo de publicação:ENGLISH ABSTRACT; JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Cytokines); 0 (Heat-Shock Proteins); 0 (Hormones); 0 (Ligands); 0 (Macroglobulins); 0 (molecular chaperone GRP78); EC 3.4.- (Peptide Hydrolases)
[Em] Mês de entrada:1303
[Cu] Atualização por classe:140401
[Lr] Data última revisão:
140401
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130219
[St] Status:MEDLINE


  7 / 1374 MEDLINE  
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[PMID]:22366155
[Au] Autor:Shannahan JH; Alzate O; Winnik WM; Andrews D; Schladweiler MC; Ghio AJ; Gavett SH; Kodavanti UP
[Ad] Endereço:Curriculum in Toxicology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA.
[Ti] Título:Acute phase response, inflammation and metabolic syndrome biomarkers of Libby asbestos exposure.
[So] Source:Toxicol Appl Pharmacol;260(2):105-14, 2012 Apr 15.
[Is] ISSN:1096-0333
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Identification of biomarkers assists in the diagnosis of disease and the assessment of health risks from environmental exposures. We hypothesized that rats exposed to Libby amphibole (LA) would present with a unique serum proteomic profile which could help elucidate epidemiologically-relevant biomarkers. In four experiments spanning varied protocols and temporality, healthy (Wistar Kyoto, WKY; and F344) and cardiovascular compromised (CVD) rat models (spontaneously hypertensive, SH; and SH heart failure, SHHF) were intratracheally instilled with saline (control) or LA. Serum biomarkers of cancer, inflammation, metabolic syndrome (MetS), and the acute phase response (APR) were analyzed. All rat strains exhibited acute increases in α-2-macroglobulin, and α1-acid glycoprotein. Among markers of inflammation, lipocalin-2 was induced in WKY, SH and SHHF and osteopontin only in WKY after LA exposure. While rat strain- and age-related changes were apparent in MetS biomarkers, no LA effects were evident. The cancer marker mesothelin was increased only slightly at 1 month in WKY in one of the studies. Quantitative Intact Proteomic profiling of WKY serum at 1 day or 4 weeks after 4 weekly LA instillations indicated no oxidative protein modifications, however APR proteins were significantly increased. Those included serine protease inhibitor, apolipoprotein E, α-2-HS-glycoprotein, t-kininogen 1 and 2, ceruloplasmin, vitamin D binding protein, serum amyloid P, and more 1 day after last LA exposure. All changes were reversible after a short recovery regardless of the acute or long-term exposures. Thus, LA exposure induces an APR and systemic inflammatory biomarkers that could have implications in systemic and pulmonary disease in individuals exposed to LA.
[Mh] Termos MeSH primário: Reação de Fase Aguda/induzido quimicamente
Amiantos Anfibólicos/toxicidade
Inflamação/induzido quimicamente
Síndrome Metabólica/induzido quimicamente
[Mh] Termos MeSH secundário: Reação de Fase Aguda/imunologia
Adiponectina/sangue
Animais
Biomarcadores/sangue
Inflamação/imunologia
Leptina/sangue
Lipocalina-2
Lipocalinas/sangue
Macroglobulinas/metabolismo
Masculino
Síndrome Metabólica/imunologia
Orosomucoide/metabolismo
Osteopontina/sangue
Proteômica
Ratos
Ratos Endogâmicos F344
Ratos Endogâmicos SHR
Ratos Endogâmicos WKY
Estudos Retrospectivos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Adiponectin); 0 (Asbestos, Amphibole); 0 (Biomarkers); 0 (Lcn2 protein, rat); 0 (Leptin); 0 (Lipocalin-2); 0 (Lipocalins); 0 (Macroglobulins); 0 (Orm1 protein, rat); 0 (Orosomucoid); 0 (Spp1 protein, rat); 106441-73-0 (Osteopontin)
[Em] Mês de entrada:1208
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:120228
[St] Status:MEDLINE
[do] DOI:10.1016/j.taap.2012.02.006


  8 / 1374 MEDLINE  
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[PMID]:21913005
[Au] Autor:Lu XC; Yang B; Yu RL; Chi XH; Tuo S; Tuo CW; Zhu HL; Wang Y; Jiang CG; Fu XB; Yang Y; Liu Y; Yao SQ; Dai HR; Cai L; Li BJ; Han WD
[Ad] Endereço:Department of Geriatric Hematology, Chinese PLA General Hospital, Beijing, China. xuechun1111@126.com
[Ti] Título:Clinical study of autologous cytokine-induced killer cells for the treatment of elderly patients with diffuse large B-cell lymphoma.
[So] Source:Cell Biochem Biophys;62(1):257-65, 2012 Jan.
[Is] ISSN:1559-0283
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:To evaluate the effectiveness and safety of autologous cytokine-induced killer (CIK) cells in elderly patients with diffuse large B-cell lymphoma. Peripheral blood mononuclear cells (PBMC) were isolated from nine elderly patients with diffuse large B-cell lymphoma. PBMCs were augmented by priming with interferon gamma (IFN-γ) followed by IL-2 and monoclonal antibody (mAb) against CD3. Autologous CIK cells (range 5 × 10(9)-1 × 10(10)) were then infused back to individual patients; infusion was repeated every 4 weeks for 32 weeks (eight cycles). Patients were assessed for changes in lymphocyte subgroup, tumor-related biological parameters, imaging characteristics, the condition of remission, quality of life (QOL), and survival. Prior to CIK infusion, two patients were in complete remission and seven patients were in partial remission. After autologous CIK cell transfusions, the proportion of CD3+, CD3+CD8+, and CD3+CD56+ cells were significantly increased compared with baseline (P < 0.05); whereas serum levels of ß2-microglobulin and LDH were significantly decreased (P < 0.05). The lymphoma symptoms were reduced and QOL was improved (P < 0.05) in all patients. All patients achieved complete remission at study endpoint. No adverse reactions were reported. Autologous CIK cell immunotherapy is safe and efficacious for the treatment of elderly patients with diffuse large B-cell lymphoma.
[Mh] Termos MeSH primário: Células Matadoras Induzidas por Citocinas/transplante
Imunoterapia
Linfoma Difuso de Grandes Células B/terapia
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Anticorpos Monoclonais/imunologia
Anticorpos Monoclonais/farmacologia
Complexo CD3/imunologia
Complexo CD3/metabolismo
Antígeno CD56/metabolismo
Antígenos CD8/metabolismo
Células Cultivadas
Células Matadoras Induzidas por Citocinas/imunologia
Feminino
Seres Humanos
Interferon gama/farmacologia
Interleucina-2/farmacologia
L-Lactato Desidrogenase/sangue
Linfoma Difuso de Grandes Células B/diagnóstico por imagem
Linfoma Difuso de Grandes Células B/metabolismo
Linfoma Difuso de Grandes Células B/mortalidade
Macroglobulinas/análise
Masculino
Meia-Idade
Imagem Multimodal
Tomografia por Emissão de Pósitrons
Análise de Sobrevida
Tomografia Computadorizada por Raios X
Transplante Autólogo
Resultado do Tratamento
[Pt] Tipo de publicação:CLINICAL TRIAL; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (CD3 Complex); 0 (CD56 Antigen); 0 (CD8 Antigens); 0 (Interleukin-2); 0 (Macroglobulins); 82115-62-6 (Interferon-gamma); EC 1.1.1.27 (L-Lactate Dehydrogenase)
[Em] Mês de entrada:1205
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:110914
[St] Status:MEDLINE
[do] DOI:10.1007/s12013-011-9273-6


  9 / 1374 MEDLINE  
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[PMID]:21978460
[Au] Autor:Lim W; Jeong W; Kim JH; Lee JY; Kim J; Bazer FW; Han JY; Song G
[Ad] Endereço:Department of Agricultural Biotechnology, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 151-921, Korea.
[Ti] Título:Differential expression of alpha 2 macroglobulin in response to dietylstilbestrol and in ovarian carcinomas in chickens.
[So] Source:Reprod Biol Endocrinol;9:137, 2011 Oct 07.
[Is] ISSN:1477-7827
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Alpha 2 macroglobulin (A2M; also known as ovostatin), a homotetrameric protein with four disulfide-linked subunits, has the unique feature of inactivating/inhibiting most known proteases including serine-, threonine-, cysteine-, aspartic- and metalloproteases. In chickens, A2M has been identified and characterized biochemically, but little is known of its functional role(s) in the oviduct, hormonal regulation of expression or its expression in ovarian carcinomas in chickens. Therefore, we investigated estrogen regulation of A2M gene expression during development of the chicken oviduct, and its expression in normal and cancerous ovaries from chickens. METHODS: To determine tissue-specific expression of A2M in chickens, we collected various organs from male and female chickens and performed RT-PCR analyses. To examine A2M gene expression in the oviduct of 1-week-old female chicks that received a subcutaneous implant of 15 mg DES in the abdominal region for 20 days, we performed RT-PCR, qPCR and in situ hybridization analyses using cDNAs from control- (n=5) and DES-treated oviducts (n=5), and then each segment of the oviduct from DES-treated chicks. To determine if A2M is a biomarker of ovarian cancer in hens, we collected cancerous (n=10) ovaries from a total of 136 chickens which had completely stopped egg-laying and performed RT-PCR and in situ hybridization analyses. RESULTS: We found that A2M is most abundant in the chicken oviduct, specifically luminal (LE) and glandular epithelia (GE), but it was not detected in any other tissues of either sex. We then determined that DES (dietylstilbestrol, a synthetic nonsteroidal estrogen) increased A2M mRNA only in LE and GE of the oviduct of chicks. Further, expression of A2M was most abundant in GE of endometrioid adenocarcinoma of cancerous, but not normal ovaries of hens. CONCLUSIONS: Collectively, results of the present study indicate that A2M is novel estrogen-stimulated gene expressed in LE and GE of the chicken oviduct and may be used for monitoring effects of therapies for ovarian cancer in laying hens.
[Mh] Termos MeSH primário: Carcinoma/veterinária
Galinhas
Dietilestilbestrol/farmacologia
Estrogênios não Esteroides/farmacologia
Macroglobulinas/metabolismo
Neoplasias Ovarianas/veterinária
Doenças das Aves Domésticas/metabolismo
alfa-Macroglobulinas/metabolismo
[Mh] Termos MeSH secundário: Animais
Proteínas Aviárias/genética
Proteínas Aviárias/metabolismo
Biomarcadores Tumorais/química
Biomarcadores Tumorais/genética
Biomarcadores Tumorais/metabolismo
Carcinoma/metabolismo
Carcinoma/patologia
Células Epiteliais/metabolismo
Células Epiteliais/patologia
Feminino
Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos
Macroglobulinas/química
Macroglobulinas/genética
Masculino
Proteínas de Neoplasias/química
Proteínas de Neoplasias/genética
Proteínas de Neoplasias/metabolismo
Especificidade de Órgãos
Neoplasias Ovarianas/metabolismo
Neoplasias Ovarianas/patologia
Ovário/crescimento & desenvolvimento
Ovário/metabolismo
Ovário/patologia
Oviductos/citologia
Oviductos/crescimento & desenvolvimento
Oviductos/metabolismo
Filogenia
Doenças das Aves Domésticas/patologia
RNA Mensageiro/metabolismo
Homologia de Sequência de Aminoácidos
alfa-Macroglobulinas/química
alfa-Macroglobulinas/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Avian Proteins); 0 (Biomarkers, Tumor); 0 (Estrogens, Non-Steroidal); 0 (Macroglobulins); 0 (Neoplasm Proteins); 0 (RNA, Messenger); 0 (alpha-Macroglobulins); 731DCA35BT (Diethylstilbestrol); 86697-40-7 (ovomacroglobulin)
[Em] Mês de entrada:1202
[Cu] Atualização por classe:151119
[Lr] Data última revisão:
151119
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:111008
[St] Status:MEDLINE
[do] DOI:10.1186/1477-7827-9-137


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[PMID]:21833999
[Au] Autor:Thompson D; Develter W; Cairns DA; Barrett JH; Perkins DA; Stanley AJ; Mooney A; Selby PJ; Banks RE
[Ad] Endereço:Clinical Biochemistry and Immunology, The General Infirmary, Leeds, UK. Douglas.Thompson@leedsth.nhs.uk
[Ti] Título:A pilot study to investigate the potential of mass spectrometry profiling in the discovery of novel serum markers in chronic renal disease.
[So] Source:Proteomics Clin Appl;5(9-10):523-31, 2011 Oct.
[Is] ISSN:1862-8354
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:PURPOSE: There has been significant criticism of how technologies such as SELDI have been used in biomarker discovery and how the data have been analysed. We initiated a proof-of-principle pilot study using SELDI with stringent pre-analytic and analytical procedures with robust statistical analysis, to determine whether, under such conditions, using different degrees of renal dysfunction as a model, useful data could be obtained. EXPERIMENTAL DESIGN: SELDI-TOF-MS profiling with stringent quality control measures was used to examine the proteomic profile of serum from healthy controls (n=30), patients with end-stage renal failure being treated by dialysis (n=30) and renal transplant patients (n=50) with varying degrees of graft stability. RESULTS: Principal component analysis of the data suggests that the continuum from normality to end-stage renal failure through 'stable' and 'unstable' transplant may be detected by SELDI profiling. Serum ß2 microglobulin was identified as a major component and this was validated using immunonephelometry. CONCLUSIONS AND CLINICAL RELEVANCE: This pilot study suggests that stringently controlled SELDI analysis is able to detect proteins which may be useful in the stratification of patients post-renal transplant. Further studies using a larger cohort of patients with chronic allograft dysfunction, defined by protocol biopsies, are indicated.
[Mh] Termos MeSH primário: Biomarcadores/sangue
Insuficiência Renal Crônica/sangue
Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Feminino
Seres Humanos
Transplante de Rim
Macroglobulinas/análise
Macroglobulinas/imunologia
Masculino
Meia-Idade
Nefelometria e Turbidimetria
Projetos Piloto
Análise de Componente Principal
Diálise Renal
Insuficiência Renal Crônica/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Biomarkers); 0 (Macroglobulins)
[Em] Mês de entrada:1201
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:110812
[St] Status:MEDLINE
[do] DOI:10.1002/prca.201100009



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