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Id: biblio-830067
Autor: Canto, Luisa Matos do; Farias, Ticiana Della Justina; Medeiros, Mayara Delagnelo; Coêlho, Cíntia Callegari; Sereia, Aline Fernanda Rodrigues; Back, Lia Kubelka Fernandes de Carlos; Mello, Filipe Martins de; Zimmermann, Adriana Fontes; Pereira, Ivânio Alves; Souza, Ilíada Rainha de.
Título: Association of PDCD1 polymorphism to systemic lupus erythematosus and rheumatoid arthritis susceptibility / Associação entre o polimorfismo do gene PDCD1 e a susceptibilidade ao lúpus eritematoso sistêmico e à artrite reumatoide
Fonte: Rev. bras. reumatol;56(6):483-489, Nov.-Dec. 2016. tab.
Idioma: en.
Resumo: ABSTRACT Objective: This study aims to analyze the relationship of programmed cell death 1 (PDCD1) gene polymorphism (PD1.3G/A - rs11568821) with features of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in a Southern Brazilian population. Methods: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed in 95 SLE and 87 RA patients and 128 control group individuals from Santa Catarina, Southern Brazil. The Hardy-Weinberg equilibrium (HWE) test, and odds ratio (OR) were analyzed, considering CI 95% and p ≤ 0.05. Results: The PD1.3A allele frequencies were 0.095 (SLE), 0.115 (RA) and 0.078 (controls). The genotypes of the control group were in HWE, while those of SLE and RA patients were not. However, we found no association between PD1.3 polymorphism and the SLE or RA susceptibility, nor clinical or epidemiological data. Conclusion: There was no significant association between PD1.3 polymorphism and SLE or RA susceptibility in this Southern Brazilian population.

RESUMO Objetivo: Este estudo teve como objetivo analisar a relação entre o polimorfismo do gene PDCD1 (programmed cell death 1) (PD1.3G/A - rs11568821) com características do lúpus eritematoso sistêmico (LES) e da artrite reumatoide (AR) em uma população do sul do Brasil. Métodos: A técnica de PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Lenght Polymorphism) foi utilizada para analisar amostras de 95 pacientes com LES e 87 com AR, assim como em 128 indivíduos do grupo controle de Santa Catarina, sul do Brasil. Foi analisada a probabilidade de equilíbrio de Hardy-Weinberg (EHW) e a odds ratio (OR), considerando um IC 95% e p ≤ 0,05. Resultados: As frequências alélicas PD1.3 A foram de 0,095 (LES), 0,115 (AR) e 0,078 (controles). Os genótipos do grupo controle estavam em EHW, enquanto aqueles dos pacientes com LES e AR não estavam. No entanto, não foi encontrada associação entre o polimorfismo PD1.3 e a suscetibilidade ao LES ou à AR, nem com dados clínicos ou epidemiológicos. Conclusão: Não foi encontrada associação significativa entre o polimorfismo PD1.3 e a susceptibilidade ao LES ou à AR nessa população do sul do Brasil.
Descritores: Artrite Reumatoide/genética
Predisposição Genética para Doença
Proteínas Reguladoras de Apoptose/genética
Lúpus Eritematoso Sistêmico/genética
-Polimorfismo de Fragmento de Restrição
Brasil
Estudos de Casos e Controles
Receptor de Morte Celular Programada 1
Frequência do Gene
Limites: Humanos
Tipo de Publ: Research Support, Non-U.S. Gov't
Responsável: BR1.1 - BIREME


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Id: biblio-887132
Autor: Linck, Rudinei Diogo Marques; Costa, Rômulo Leopoldo de Paula; Garicochea, Bernardo.
Título: Cancer immunology and melanoma immunotherapy
Fonte: An. bras. dermatol;92(6):830-835, Nov.-Dec. 2017.
Idioma: en.
Resumo: Abstract: The stimulation of the immune system, in order to generate an attack against cancer cells, similarly to that which occurs in infectious disease, has long been matter of interest in oncology; however, only limited success has been achieved, with different treatment strategies tested in recent years. The development of new immune checkpoint inhibitors is currently changing this scenario, and immunotherapy is becoming a real choice among traditional cytotoxic treatments to fight cancer. Recent reports have shown efficacy and safety with the use of pembrolizumab, nivolumab, and ipilimumab for the treatment of different neoplasms, especially melanoma. In this article, we propose a review of the mechanisms of action involved in cancer immunology, the response evaluation of immunotherapies, and its toxicity profile, as well as a summary of the main clinical trials that led to the adoption of these new drugs for melanoma treatment.
Descritores: Antineoplásicos Imunológicos/uso terapêutico
Imunoterapia/métodos
Melanoma/imunologia
Melanoma/tratamento farmacológico
Neoplasias/imunologia
Neoplasias/tratamento farmacológico
-Protocolos de Quimioterapia Combinada Antineoplásica
Resultado do Tratamento
Anticorpos Monoclonais Humanizados/uso terapêutico
Antígeno CTLA-4/antagonistas & inibidores
Receptor de Morte Celular Programada 1/antagonistas & inibidores
Ipilimumab/uso terapêutico
FRUCTOSE-BISPHOSPHATE ALDOLASE1
Anticorpos Monoclonais/uso terapêutico
Limites: Humanos
Tipo de Publ: Revisão
Responsável: BR1.1 - BIREME


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Id: biblio-912068
Autor: Barreta, Amilcar.
Título: Carcinomas de ovário associados à endometriose: expressão de marcadores proteicos de terapia alvo e prognóstico / Endometriosis-associated ovarian carcinomas: expression of protein biomarkers associated to target therapies and prognosis.
Fonte: Campinas; s.n; 2018. 162 p. ilus, tab.
Idioma: pt.
Tese: Apresentada a Universidade Estadual de Campinas para obtenção do grau de Doutor.
Resumo: Resumo: Introdução: endometriose é uma doença benigna, capaz de progredir extensamente e gerar clones atípicos. Considerada precursora dos carcinomas de células claras (CCOC) e endometrióide (EOC) de ovário, atualmente chamados carcinomas de ovário associados à endometriose (EAOC). Objetivos: comparar o perfil epidemiológico, a associação com endometriose e a expressão de marcadores imuno-histoquímicos para ARID1A, VEGF, PD-L1 e PARP-1 em mulheres com CCOC e EOC, e sua correlação com a sobrevida livre de progressão (SLP) e sobrevida global (SG). Métodos: estudo de coorte reconstituída, com 50 casos incluídos de CCOC e EOC tratados no CAISM-UNICAMP entre 1995 até 2016, acompanhados até 02/2017. Microarranjos de tecido com amostras de CCOC, EOC e endometriose foram corados com anticorpos monoclonais contra ARID1A, e para os biomarcadores proteicos VEGF, PD-L1, PARP-1 através de imuno-histoquímica. A expressão de ARID1A foi classificada (0 a 100) conforme a porcentagem de células não coradas. A expressão de VEGF, PD-L1 e PARP-1 foi classificada (0 a 300) conforme a multiplicação da porcentagem de células coradas por um fator da intensidade de expressão (ausente=0; fraco=1; moderado=2; forte=3). Idade ao diagnóstico; menopausa; índice de massa corpórea (IMC); CA-125; diagnóstico de endometriose; datas do diagnóstico, da progressão, do óbito e da última consulta foram recuperados dos prontuários. Comparação entre grupos foi realizada através de testes T e de ?2. A SLP (diferença de tempo entre o diagnóstico e a data de progressão) e a SG (diferença de tempo entre o diagnóstico e o óbito ou data da última data de consulta) foi avaliada através de curvas de Kaplan-Meyer e teste de Log-Rank ou regressão de COX. Resultados: 23 mulheres com CCOC (46%), e 27 com EOC (54%) foram incluídas; 80% tinham endometriose associada, 42% eram nulíparas, 42% eram pré-menopausa e CA125 foi elevado em todos estádios (FIGO I-II= média 614.7Ui/mL; FIGO III-IV= media 2361.2Ui/mL). A média de idade ao diagnóstico foi 7 anos menor em mulheres com EOC do que naquelas com CCOC. O CCOC foi mais diagnosticado em estágios iniciais quando associado à endometriose (p=0,03). O prognóstico dos EOC e CCOC em estádios iniciais foi semelhante (p=0,96). Os CCOC não associado à endometriose tiveram menor SG (p=0,04). A expressão de todos os biomarcadores esteve presente nos EAOC e na endometriose. O aumento da expressão de VEGF entre endometriose e câncer foi significativo (p=0,0002). A hiperexpressão de PARP-1 correlacionou-se negativamente com a SLP (p=0,03) e SG (p=0,01) em estádios iniciais. Conclusão: Os CCOC e EOC são comumente diagnosticados em estádios iniciais (FIGO I-II= 68%) e estão frequentemente associados à endometriose (80% dos casos). Quando associados à endometriose, os CCOC foram mais diagnosticados em estádios iniciais e tiveram SG maior. Houve elevada porcentagem de células com ARID1A mutado nos EAOC (>40%). VEGF se expressou mais intensamente nos CCOC e EOC que na endometriose, já a expressão de PD-L1 e de PARP-1 foi similar. Apenas a hiperexpressão de PARP-1 reduziu significativamente a SLP e a SG nos CCOC e EOC nos estádios iniciais(AU)

Abstract: Introduction: Endometriosis is a benign disease, able to progress widely and generate atypical clones. It is a precursor of clear cell ovarian carcinomas (CCOC) and endometrioid ovarian carcinomas (EOCs), now called endometriosis-associated ovarian carcinomas (EAOC). Objectives: To compare the epidemiological profile, association with endometriosis and the expression of immunohistochemical markers for ARID1A, VEGF, PD-L1 and PARP-1 in women with CCOC and EOC, and its correlation with progression-free survival (PFS) and overall survival (OS). Methods: A reconstituted cohort study with 50 cases of CCOC and EOC included. Cases were treated at CAISM-UNICAMP between 1995 and 2016, followed up until 02/2017. Tissue microarrays with CCOC, EOC and endometriosis samples were stained with monoclonal antibodies against ARID1A, and for VEGF, PD-L1, PARP-1 biomarkers by immunohistochemistry. The expression of ARID1A was classified (0 to 100) according to the percentage of unstained cells. The expression of VEGF, PD-L1 and PARP-1 was classified (0 to 300) multiplying the percentage of stained cells by an intensity of expression factor (absent=0, weak=1, moderate=2, strong=3). Age at diagnosis; menopause; BMI (body mass index); CA-125 levels; diagnosis of endometriosis; date of diagnosis, date of progression, date of death and date of last consultation were retrieved from the medical records. Comparison between groups was performed through T and ?2 tests. The PFS (difference in time between diagnosis and progression date) and OS (difference in time between diagnosis and death or the last date of consultation) was assessed using Kaplan-Meyer curves and Log-Rank test or COX multivariate models. Results: twenty-three women with CCOC (46%), and 27 with EOC (54%) were included; 80% had associated endometriosis, 42% were nulliparous, 42% were premenopausal, and CA125 was elevated at all stages (FIGO I-II = mean 614.7Ui / mL; FIGO III-IV = mean 2361.2Ui / mL). The mean age at diagnosis was 7 years lower in women with EOC than in those with CCOC. CCOC when associated with endometriosis were more diagnosed at early stages (p=0.03). The prognosis of EOC and CCOC at early stages was similar (p=0.96). CCOCs not associated with endometriosis had shorter OS (p=0.04). Expression of all biomarkers was present in the EAOC and endometriosis. The increase in VEGF expression between endometriosis and cancer was significant (p=0.0002). The overexpression of PARP-1 correlated negatively with PFS (p=0.03) and OS (p=0.01) at FIGO I-II stages. Conclusion: The diagnosis of women with EOC was made earlier than in those with CCOC. CCOC and EOC are commonly diagnosed in early stages (FIGO I-II - 68%) and were associated with endometriosis (80% of cases). When associated with endometriosis, clear cell carcinomas are more likely diagnosed at early stages, and the association of endometriosis with CCOC improves OS. There was a high percentage of cells with mutated ARID1A gene in EAOC (> 40%). VEGF was expressed more intensely in CCOC and EOC than in endometriosis, whereas expression of PD-L1 and PARP-1 was similar. Only the overexpression of PARP-1 significantly reduced PFS and OS in CCOC and EOC at early stages(AU)
Descritores: Prognóstico
Carcinoma Endometrioide
Endometriose
-Taxa de Sobrevida
Adenocarcinoma de Células Claras
Fatores de Crescimento do Endotélio Vascular
Endometriose/epidemiologia
Receptor de Morte Celular Programada 1
Poli(ADP-Ribose) Polimerase-1
Limites: Humanos
Feminino
Responsável: BR25.1 - Biblioteca
BR25.1; T/UNICAMP, B275c


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Id: lil-751312
Autor: Jalalvand, Fatemeh; Amoli, Mahsa M.; Yaghmaei, Parichehreh; Kimiagar, Masoud; Ebrahim-Habibi, Azadeh.
Título: Acarbose versus trans-chalcone: comparing the effect of two glycosidase inhibitors on obese mice
Fonte: Arch. endocrinol. metab. (Online);59(3):202-209, 06/2015. tab, graf.
Idioma: en.
Resumo: Objective Acarbose and trans-chalcone are glucosidase inhibitors whose beneficial effects have been demonstrated in diabetes. The present study aimed at investigating their potential effects in obesity.Materials and methods NMRI male mice (n = 48) were subjected to a high fat diet for four weeks, which induced an initial state of obesity. One control group was given normal rodent diet. Obese animals were then switched to normal rodent diet, and divided to four groups (n = 12 in each): untreated, sham (receiving grape seed oil), and experimental groups receiving acarbose and trans-chalcone (12 mg/kg) during eight weeks. Body weight, blood glucose and other biochemical parameters including triglycerides (TG), cholesterol, HDL, AST, and ALT were measured, as well as leptin, adiponectin, TNF-α, and total antioxidant capacity (TAC). Histological studies were performed on adipose cells and liver tissue samples.Results All factors were affected in a positive manner by acarbose, save for body weight, blood sugar and leptin levels, on which acarbose effects, although observable, were not statistically significant. Grape seed oil, used as a solvent for trans-chalcone was found to possess significant effect on TG and TAC, and had beneficial effects on other factors including liver enzymes and cholesterol. Trans-chalcone effects were significant on HDL, leptin and ALT. All compounds seemed to be able to affect fat deposition in liver tissue, and decrease the size of adipose tissue cells to some extent.Conclusion In conclusion, the tested compounds were able to affect lipid accumulation in tissues and influence adipokines, which may result in an enhanced state with regard to inflammation and oxidative stress. Arch Endocrinol Metab. 2015;59(3):202-9.
Descritores: /metabolismo
ANTIGENS, CDTISSUE ADHESIONS/metabolismo
Carcinoma Pulmonar de Células não Pequenas/imunologia
Citocinas/metabolismo
Neoplasias Pulmonares/imunologia
Receptor de Morte Celular Programada 1/metabolismo
Receptores ErbB/metabolismo
Linfócitos T/imunologia
Evasão Tumoral
-/genética
ANTIGENS, CDTISSUE ADHESIONS/genética
Linhagem Celular
Carcinoma Pulmonar de Células não Pequenas/metabolismo
Regulação Neoplásica da Expressão Gênica
Ativação Linfocitária
Neoplasias Pulmonares/metabolismo
Camundongos Transgênicos
MICE, INBRED CABDOMENABDOMINAL INJURIESBL
Oncogenes
Receptor de Morte Celular Programada 1/genética
Receptores ErbB/genética
Transdução de Sinais
Microambiente Tumoral
Limites: Animais
Humanos
Camundongos
Tipo de Publ: Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Responsável: BR1.1 - BIREME


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Id: lil-726575
Autor: Vásquez O., Karla; Soto S., Johana; Pizarro A., Carolina; Salas P., Francisca; Pérez B., Francisco.
Título: Frecuencia del polimorfismo PD-1.3 del gen del receptor de muerte celular programada 1 (PD-1) y su asociación con diabetes tipo 1 / Frequency of polymorphism PD-1.3 of programmed cell death 1 (PD-1) and their association with type 1 diabetes
Fonte: Rev. chil. endocrinol. diabetes;6(2):55-58, abr. 2013. tab.
Idioma: es.
Projeto: FONDECYT.
Resumo: Background: The programmed cell death 1 (PDCD-1) immune-receptor is a key element in the negative regulation of peripheral tolerance in T cells. The gene has several polymorphisms and can be associated with susceptibility to autoimmune diseases. Aim: To analyze the frequency and distribution of PD-1.3 polymorphism of PDCD-1 gene and explore its possible contribution as a susceptibility gene for type 1 diabetes (T1D). Patients and Methods: We analyzed 248 cases with T1D with recent diagnosis and 160 control children under 15 years of Santiago. Genetic polymorphism in PD-1 gene variant for PD-1.3 (rs 11568821) was analyzed by polymerase chain reaction and restriction fragment length polymorphism. Comparison of genotype, allele frequency and consistency with respect to Hardy-Weinberg were analyzed using X2 tests and Fisher exact test. Results: There was a very low frequency of the genotype A/A, both in T1D patients and in controls (< 2 percent). The A/G genotype was more common in diabetic patients than in controls (41.6 and 18.8 percent respectively, p < 0.04). G/G genotype was more common in controls than in patients (79.4 and 56.8 percent respectively, p < 0.02). T1D patients carrying genotype G/G had a higher frequency of anti-GAD65 and anti-A-2 antibodies (81 and 67 percent respectively). Conclusions: The distribution of PD-1.3 genotype frequencies are similar to that reported elsewhere. Possibly, this genetic variant (rs 11568821) does not have an important marker role in Chilean T1D patients.
Descritores: Diabetes Mellitus Tipo 1/genética
Polimorfismo Genético
Receptor de Morte Celular Programada 1/genética
-Autoimunidade
Anticorpos/análise
Diabetes Mellitus Tipo 1/imunologia
Frequência do Gene
Marcadores Genéticos
Genótipo
Limites: Humanos
Adolescente
Criança
Responsável: CL1.1 - Biblioteca Central


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Id: lil-716275
Autor: Mesquita Júnior, D.; Cruvinel, W.M.; Araujo, J.A.P.; Salmazi, K.C.; Kallas, E.G.; Andrade, L.E.C..
Título: Imbalanced expression of functional surface molecules in regulatory and effector T cells in systemic lupus erythematosus
Fonte: Braz. j. med. biol. res = Rev. bras. pesqui. méd. biol;47(8):662-669, 08/2014. tab, graf.
Idioma: en.
Projeto: FAPESP.
Resumo: Regulatory T (TREG) cells play an important role in maintaining immune tolerance and avoiding autoimmunity. We analyzed the expression of membrane molecules in TREG and effector T cells in systemic lupus erythematosus (SLE). TREG and effector T cells were analyzed for the expression of CTLA-4, PD1, CD28, CD95, GITR, HLA-DR, OX40, CD40L, and CD45RO in 26 patients with active disease, 31 with inactive disease, and 26 healthy controls. TREG cells were defined as CD25+/highCD127Ø/lowFoxP3+, and effector T cells were defined as CD25+CD127+FoxP3Ø. The ratio of TREG to effector T cells expressing GITR, PD1, HLA-DR, OX40, CD40L, and CD45RO was determined in the three groups. The frequency of TREG cells was similar in patients with SLE and controls. However, SLE patients had a decreased frequency of CTLA-4+TREG and CD28+TREG cells and an increased frequency of CD40L+TREG cells. There was a decrease in the TREG/effector-T ratio for GITR+, HLA-DR+, OX40+, and CD45RO+ cells, and an increased ratio of TREG/effector-T CD40L+ cells in patients with SLE. In addition, CD40L+TREG cell frequency correlated with the SLE disease activity index (P=0.0163). In conclusion, our findings showed several abnormalities in the expression of functionally critical surface molecules in TREG and effector T cells in SLE that may be relevant to the pathogenesis of this disease.
Descritores: Antígenos de Superfície/metabolismo
Leucócitos Mononucleares/metabolismo
Lúpus Eritematoso Sistêmico/imunologia
Linfócitos T Reguladores/imunologia
-Análise de Variância
/análise
ANTIGENS, CDABORTION, HABITUAL/análise
/análise
ANTIGENS, CDABSORPTION/análise
/análise
ANTIGENS, CDACETIC ANHYDRIDES/análise
/análise
CDABRUPTIO PLACENTAE LIGAND/análise
/análise
CTLA-ABBREVIATIONS AS TOPIC ANTIGEN/análise
Citometria de Fluxo
Fatores de Transcrição Forkhead/análise
Proteína Relacionada a TNFR Induzida por Glucocorticoide/análise
Antígenos HLA-DR/análise
/análise
INTERLEUKIN-ABDOMINAL INJURIES RECEPTOR ALPHA SUBUNIT/análise
/análise
INTERLEUKIN-TEMEFOS RECEPTOR ALPHA SUBUNIT/análise
Lúpus Eritematoso Sistêmico/metabolismo
Lúpus Eritematoso Sistêmico/fisiopatologia
Receptor de Morte Celular Programada 1/análise
/análise
RECEPTORS, OXABRUPTIO PLACENTAE/análise
Estatísticas não Paramétricas
Limites: Adulto
Feminino
Humanos
Masculino
Pessoa de Meia-Idade
Tipo de Publ: Research Support, Non-U.S. Gov't
Responsável: BR1.1 - BIREME


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Id: lil-659755
Autor: Palermo, Maria de Lourdes; Trindade, Maria Ângela Bianconcini; Duarte, Alberto José da Silva; Cacere, Camila Rodrigues; Benard, Gil.
Título: Differential expression of the costimulatory molecules CD86, CD28, CD152 and PD-1 correlates with the host-parasite outcome in leprosy
Fonte: Mem. Inst. Oswaldo Cruz;107(supl.1):167-173, Dec. 2012. ilus, graf.
Idioma: en.
Resumo: Leprosy is a spectral disease exhibiting two polar sides, namely, lepromatous leprosy (LL) characterised by impaired T-cell responses and tuberculoid leprosy in which T-cell responses are strong. Proper T-cell activation requires signalling through costimulatory molecules expressed by antigen presenting cells and their ligands on T-cells. We studied the influence of costimulatory molecules on the immune responses of subjects along the leprosy spectrum. The expression of the costimulatory molecules was evaluated in in vitro-stimulated peripheral blood mononuclear cells of lepromatous and tuberculoid patients and healthy exposed individuals (contacts). We show that LL patients have defective monocyte CD86 expression, which likely contributes to the impairment of the antigen presentation process and to patients anergy. Accordingly, CD86 but not CD80 blockade inhibited the lymphoproliferative response to Mycobacterium leprae. Consistent with the LL anergy, there was reduced expression of the positive signalling costimulatory molecules CD28 and CD86 on the T-cells in these patients. In contrast, tuberculoid leprosy patients displayed increased expression of the negative signalling molecules CD152 and programmed death-1 (PD-1), which represents a probable means of modulating an exacerbated immune response and avoiding immunopathology. Notably, the contacts exhibited proper CD86 and CD28 expression but not exacerbated CD152 or PD-1 expression, suggesting that they tend to develop a balanced immunity without requiring immunosuppressive costimulatory signalling.
Descritores: /imunologia
ANTIGENS, CDABORTION, HABITUAL/imunologia
/imunologia
ANTIGENS, CDACETAMINOPHEN/imunologia
/imunologia
CTLA-ABBREVIATIONS AS TOPIC ANTIGEN/imunologia
Hanseníase/microbiologia
Mycobacterium leprae/imunologia
Receptor de Morte Celular Programada 1/imunologia
Linfócitos T/imunologia
-/metabolismo
ANTIGENS, CDABORTION, HABITUAL/metabolismo
/metabolismo
ANTIGENS, CDACETAMINOPHEN/metabolismo
Estudos de Casos e Controles
/metabolismo
CTLA-ABBREVIATIONS AS TOPIC ANTIGEN/metabolismo
Interações Hospedeiro-Parasita
Hanseníase/imunologia
Mycobacterium leprae/fisiologia
Receptor de Morte Celular Programada 1/metabolismo
Limites: Adulto
Feminino
Humanos
Masculino
Tipo de Publ: Research Support, Non-U.S. Gov't
Responsável: BR1.1 - BIREME



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