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1.
BMC Infect Dis ; 18(1): 253, 2018 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-29866104

RESUMO

BACKGROUND: Spontaneous bacterial peritonitis (SBP) and bacterascites (BA) represent frequent and serious complications in cirrhosis patients with ascites. However, few detailed data are available regarding the clinical and bacteriological feature of SBP or BA patients in China. METHODS: We retrospectively analyzed bacteriological and clinical characteristics of patients with SBP and BA at Beijing 302 Hospital in China from January 2012 to December 2015. RESULTS: A total of 600 patients with SBP (n = 408) or BA (n = 192) were enrolled. Patients with BA appeared to have a less severe clinical manifestation and lower mortality rate than patients with SBP. Gram-negative bacteria formed the majority of pathogens in SBP (73.9%) and BA (55.8%) cases. Higher ascitic fluid polymorphonuclear leucocytes (PMN) count and hepatocellular carcinoma were independent risk factors for BA episode progressing to SBP. The concentration of blood urea nitrogen (BUN) was independent risk factor for 30-day mortality of BA patients. For patients with SBP, the independent risk factors for 30-day mortality were age, Model for End-Stage Liver Disease (MELD) score, septic shock and hepatocellular carcinoma. Patients with third-generation cephalosporin or carbapenems resistant infection had a significantly lower survival probability. There were significant differences in clinical characteristics and outcome among the major bacteria. Multivariate analysis showed that patients infected with Klebsiella spp. had higher hazard ratio of 30-day mortality. CONCLUSION: Our study reported the bacteriological and clinical characteristics of patients with SBP and BA. Higher ascitic fluid PMN count and hepatocellular carcinoma were found to be independent risk factors for BA episode progressed to SBP. Outcome of ascitic fluid infection in patients with cirrhosis was influenced by the type of bacteria and antimicrobial susceptibility.


Assuntos
Ascite/microbiologia , Infecções Bacterianas/etiologia , Peritonite/etiologia , Adulto , Idoso , Ascite/tratamento farmacológico , Ascite/etiologia , Ascite/mortalidade , Líquido Ascítico/microbiologia , Líquido Ascítico/patologia , Grupo com Ancestrais do Continente Asiático , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/mortalidade , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/microbiologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Feminino , Bactérias Gram-Negativas/isolamento & purificação , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/microbiologia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/microbiologia , Masculino , Pessoa de Meia-Idade , Peritonite/tratamento farmacológico , Peritonite/mortalidade , Prognóstico , Estudos Retrospectivos , Fatores de Risco
2.
Microbiol Immunol ; 61(6): 239-246, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28500746

RESUMO

To date, there have been no reports characterizing HIV-1 in the semen of Chinese men who have sex with men (MSM) with early infection. In this study, genetic diversity and viral load of HIV-1 in the seminal compartments and blood of Chinese MSM with early HIV-1 infection were examined. Viral load and genetic diversity of HIV-1 in paired samples of semen and blood were analyzed in seven MSM with early HIV-1 infection. HIV-1 RNA and DNA were quantitated by real-time PCR assays. Through sequencing the C2-V5 region of the HIV-1 env gene, the HIV-1 genotype and genetic diversity based on V3 loop amino acid sequences were determined by using Geno2pheno and PSSM programs co-receptor usage. It was found that there was more HIV-1 RNA in seminal plasma than in blood plasma and total, and more 2-LTR circular and integrated HIV-1 DNA in seminal cells than in peripheral blood mononuclear cells from all seven patients with early HIV-infection. There was also greater HIV-1 genetic diversity in seminal than in blood compartments. HIV-1 in plasma displayed higher genetic diversity than in cells from the blood and semen. In addition, V3 loop central motifs, which present some key neutralizing antibody epitopes, varied between blood and semen. Thus, virological characteristics in semen may be more representative when evaluating risk of transmission in persons with early HIV infection.


Assuntos
Variação Genética , Infecções por HIV/sangue , Infecções por HIV/transmissão , Infecções por HIV/virologia , HIV-1/genética , Homossexualidade Masculina , Sêmen/virologia , Carga Viral , Adolescente , Adulto , Motivos de Aminoácidos , Sequência de Aminoácidos , Anticorpos Neutralizantes , Anticorpos Antivirais , Grupo com Ancestrais do Continente Asiático , Contagem de Linfócito CD4 , DNA Viral/análise , Vetores Genéticos , Genótipo , Proteína gp120 do Envelope de HIV , HIV-1/classificação , Humanos , Leucócitos Mononucleares/virologia , Masculino , Fragmentos de Peptídeos , Filogenia , RNA Viral/análise , Reação em Cadeia da Polimerase em Tempo Real , Doenças Sexualmente Transmissíveis/sangue , Doenças Sexualmente Transmissíveis/virologia , Sequências Repetidas Terminais/genética , Adulto Jovem , Produtos do Gene env do Vírus da Imunodeficiência Humana/classificação , Produtos do Gene env do Vírus da Imunodeficiência Humana/genética
3.
Plant Mol Biol ; 94(1-2): 97-107, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28321650

RESUMO

KEY MESSAGE: This research is the first to demonstrate that OsSAUR45 is involved in plant growth though affecting auxin synthesis and transport by repressing OsYUCCA and OsPIN gene expression in rice. Small auxin-up RNAs (SAURs) comprise a large multigene family and are rapidly activated as part of the primary auxin response in plants. However, little is known about the role of SAURs in plant growth and development, especially in monocots. Here, we report the biological function of OsSAUR45 in the model plant rice (Oryza sativa). OsSAUR45 is expressed in a tissue-specific pattern and is localized to the cytoplasm. Rice lines overexpressing OsSAUR45 displayed pleiotropic developmental defects including reduced plant height and primary root length, fewer adventitious roots, narrower leaves, and reduced seed setting. Auxin levels and transport were reduced in the OsSAUR45 overexpression lines, potentially because of decreased expression of Flavin-binding monooxygenase family proteins (OsYUCCAs) and PIN-FORMED family proteins (OsPINs). Exogenous auxin application rapidly induced OsSAUR45 expression and partially restored the phenotype of rice lines overexpressing OsSAUR45. These results demonstrate that OsSAUR45 is involved in plant growth by affecting auxin synthesis and transport through the repression of OsYUCCA and OsPIN gene expression in rice.


Assuntos
Regulação da Expressão Gênica de Plantas/fisiologia , Ácidos Indolacéticos/metabolismo , Oryza/metabolismo , RNA de Plantas/metabolismo , Transporte Biológico , Oryza/genética , Plantas Geneticamente Modificadas , RNA de Plantas/genética
4.
Mil Med Res ; 4: 2, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28116112

RESUMO

BACKGROUND: Hepatitis B is a disease that affects the liver and is caused by the hepatitis B virus (HBV). Hepatitis B is a serious public health problem in China. The objective of this study was to assess knowledge of and behaviours towards the transmission and prevention of hepatitis B of new military recruits in China. METHODS: A cross-sectional study was conducted among 800 new military recruits. A self-administered, structured questionnaire was used to collect information, and 727 questionnaires were returned completed. Analysis was performed using SPSS 18.0, and P < 0.05 was considered statistically significant. RESULTS: Of the respondents, 665 (91.5%) were male and 62 (8.5%) were female. The mean age was 18.9 ± 1.7 years. A total of 608 respondents (83.6%) demonstrated poor knowledge and 119 (16.4%) adequate knowledge about HBV. Older age, female and higher education level were statistically associated with a higher mean knowledge score. Multivariate logistic regression showed that age (OR = 3.040, 95%CI 1.724-5.359, P < 0.001) and gender (OR = 1.791, 95%CI 1.325-2.421, P < 0.001) were significantly associated with appropriate behavioural practices towards prevention of HBV. CONCLUSION: Against a backdrop of high HBV prevalence in China, new military recruits had poor knowledge of HBV. New recruits need better education about HBV to assist in reducing and preventing HBV infection.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Hepatite B/complicações , Militares/psicologia , Adolescente , China , Estudos Transversais , Feminino , Hepatite B/diagnóstico , Vírus da Hepatite B/patogenicidade , Humanos , Masculino , Inquéritos e Questionários , Adulto Jovem
5.
Jpn J Clin Oncol ; 44(8): 711-7, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24855686

RESUMO

OBJECTIVE: Clinical trials suggest that combining transcatheter arterial chemoembolization with sorafenib in patients with advanced hepatocellular carcinoma shows a superior safety and tolerability profile. Our study aimed to retrospectively analyze the utility and prognostic factors of this combined therapy in these patients. METHODS: Patients with advanced hepatocellular carcinoma, treated by transcatheter arterial chemoembolization and sorafenib subsequently, between February 2010 and September 2012 in our hospital, were retrospectively analyzed. After sorafenib treatment for 12 weeks, abdominal enhanced computed tomography or magnetic resonance imaging was used to evaluate short-term outcomes and clinical benefit rate. Overall survival and adverse events were recorded during follow-up. Univariate and multivariate analyses were used to identify relationships between baseline characteristics and overall survival. RESULTS: Fifty-one advanced hepatocellular carcinoma patients were included. Common adverse events for sorafenib were hand-foot skin reaction, alopecia, diarrhea, anorexia and fatigue. The clinical benefit rate was 64% and the median survival time was 7.5 months. Median survival of patients with and without portal vein tumor thrombi was 6.0 months and 10.3 months (P < 0.001), respectively. Median survival of patients with cholinesterase ≥5000 U/l and < 5000 U/l was 10.6 months and 6.1 months (P < 0.001), respectively. Multivariate analysis identified the presence of portal vein tumor thrombi and low cholinesterase level as independent negative predictors of survival. CONCLUSIONS: Combining sorafenib and transcatheter arterial chemoembolization was safe and effective for advanced hepatocellular carcinoma patients with extrahepatic spread but without portal vein tumor thrombi. Portal vein tumor thrombi and cholinesterase level are independent predictors of prognosis following this combined therapy.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Neoplasias Hepáticas/terapia , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Adulto , Alopecia/etiologia , Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/efeitos adversos , Esquema de Medicação , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Niacinamida/efeitos adversos , Niacinamida/uso terapêutico , Compostos de Fenilureia/efeitos adversos , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Sorafenibe , Tromboembolia Venosa/etiologia
6.
Zhonghua Gan Zang Bing Za Zhi ; 21(2): 125-8, 2013 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-23663885

RESUMO

OBJECTIVE: To characterize the clinical, laboratory, imaging and pathological features of primary sclerosing cholangitis (PSC) and investigate the impact of ursodeoxycholic acid (UDCA) therapy on patient prognosis. METHODS: The medical records of 22 patients diagnosed with PSC between 2002 and 2011 were retrospectively reviewed. The PSC diagnosis had been made in patients with suspect biochemical abnormalities following evaluation by magnetic resonance cholangiopancreatography (MRCP) and/or endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic cholangiography (PTC). Fibrosis and inflammation were assessed by immunohistochemical analyses of tissue biopsies. Outcome of patients treated with UDCA (13-15 mg/kg/day, oral) were compared to that of patients without UDCA treatment by the X2 or corrected X2 tests. RESULTS: Among the 22 PSC patients, the majority was male (n=15) and presented with fatigue, dark urine, and body weight loss (n=15). Four cases had ulcerative colitis. At admission, all 22 cases showed elevated levels of alkaline phosphatase[ALP: (348+/-184) U/L], 19 cases showed elevated alanine aminotransferase [ALT: (94.0+/-67.0) U/L] and aspartate aminotransferase [AST: (98.0+/-67.0) U/L], and 15 cases showed elevated levels of total bilirubin (99.0+/-115.0) mumol/L and direct bilirubin (74.4+/-92.4 mumol/L. ERCP examination showed segmental intrahepatic bile duct stenosis with expansion, and stiff and enlarged gallbladder bile ducts, but unclear findings for the common bile ducts and pancreatic ducts. MRCP showed beading of the intrahepatic bile duct, stiffness of the bile duct wall, and dilation of the common bile duct. Fibrosis and inflammation were observed in the bile ducts, along with hyperplasia and the typical features of "onion skin" fibrosis and fibrous obliterative cholangitis. Five of the 10 patients treated with UDCA improved, and seven of the 12 patients in the non-UDCA treatment group improved. There was no statistically significant difference in outcome between the groups (paired X2=0.333, corrected X2=0.083, P more than 0.05). CONCLUSION: PSC patients were predominantly male and the common clinical manifestations were fatigue, dark urine, and body weight loss. At admission, serum biochemical indicators of cholangitis were increased significantly and subsequent imaging studies confirmed the suspected diagnosis by showing obvious characteristic changes. UDCA treatment did not significantly improve patient prognosis.


Assuntos
Colangite Esclerosante/diagnóstico por imagem , Colangite Esclerosante/patologia , Adulto , Colangiografia/métodos , Colangiopancreatografia Retrógrada Endoscópica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
7.
Beijing Da Xue Xue Bao Yi Xue Ban ; 45(2): 233-7, 2013 Apr 18.
Artigo em Chinês | MEDLINE | ID: mdl-23591343

RESUMO

OBJECTIVE: To investigate the autoantibody profile and its clinical implication in the patients with primary biliary cirrhosis. METHODS: During the period of 2008 to 2010,123 patients with primary biliary cirrhosis (PBC) in our hospital were enrolled in this study, of whom, 70 patients were with cirrhosis and 53 without cirrhosis, The autoantibody profile was tested for each patient by using immunoblotting and indirect immunofluorescence. RESULTS: Of the 123 PBC patients with liver cirrhosis, 49% were positive with serum ANA positive; 47%, 51%, 54%, 31% and 49% were positive with serum anti-nuclear antibodies (ANA), anti-mitochondrial antibodies-M2 (AMA-M2), anti-promyelocytic leukemia (anti-PML), anti-sp100 antibodies (anti-sp100), anti-Ro-52 antibody (anti-52KD), respectively. By contrast, of the PBC patients without liver cirrhosis, only 38%, 37%, 51%, 60%, 30% and 51% were positive with serum ANA, AMA, AMA-M2, anti-PML, anti-sp100 and anti-52KD, respectively.There was the statistical difference between the two groups. In addition, it was also found that the anti-gp210 antibody positive group had a higher Mayo risk score,lower serum albumin and severe cholestasis and impaired liver function when compared with anti-gp210 antibody negative patients. CONCLUSION: Our data indicate that serum AMA is helpful for early diagnosis of PBC, and in particular, serum ANA positivity can help make a diagnosis for the AMA-negative patients. These indicate that anti-gp210 antibodies appear in the late course of PBC.Anti-gp210 positive PBC patients have more severe cholestasis and liver dysfunction.


Assuntos
Anticorpos Antinucleares/sangue , Autoanticorpos/sangue , Cirrose Hepática Biliar/imunologia , Mitocôndrias Hepáticas/imunologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complexo de Proteínas Formadoras de Poros Nucleares/imunologia , Estudos Retrospectivos
8.
Zhonghua Gan Zang Bing Za Zhi ; 20(7): 487-91, 2012 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-23044231

RESUMO

OBJECTIVE: To evaluate the safety of human umbilical cord derived-mesenchymal stem cell (UC-MSC) transplantation therapy in patients with decompensated liver cirrhosis. METHODS: UC-MSCs were transplanted intravenously into patients with decompensated liver cirrhosis. Serum levels of glucose (GLU), total cholesterol (TC), blood urea nitrogen (BUN), alpha fetoprotein (AFP), white blood cells (WBC), and prothrombin activity (PA) were detected at different time points after UC-MSCs transplantation. RESULTS: Most UC-MSC transplanted patients experienced an improvement in quality of life, to varying degrees. With the exception of low-grade fever in a few patients, side effects and oncogenic events were rare (treatment group: 1/38 vs. control group: 1/16; P more than 0.05). The UC-MSCs transplantation showed no effect on GLU, TC, BUN, AFP, WBC, or PA. CONCLUSION: UC-MSCs transplantation in patients with decompensated liver cirrhosis is safe and may improve the patient's quality of life.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Cirrose Hepática/cirurgia , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Adulto , Idoso , Feminino , Humanos , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
9.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 27(6): 668-70, 2011 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-21651872

RESUMO

AIM: This study attempted to investigate the features of Treg cells in peripheral blood and liver of patients with primary hepatocellular carcinoma (HCC). METHODS: Peripheral blood samples were obtained from 30 HCC patients and 30 healthy control subjects, then were quantitatively analyzed for Treg cells by using flow cytometry. Liver infiltrating lymphocytes (LIL) isolated from resected tumor samples of 7 HCC patients were simultaneously analyzed. RESULTS: There was a significant increase in the frequency of peripheral Treg cells in HCC patients compared with healthy controls (P < 0.01). Furthermore, we also found that there was a higher frequency of infiltrated Treg within tumor samples than the counterpart in non-tumor region (P < 0.05). In addition, CD4(+) CD25(low) and CD4(+) CD25(-) T cells isolated from resected tumor samples were found to express higher level of FOXP3 molecules. CONCLUSION: Our findings showed that a dramatic increasing increase of Treg in peripheral blood and liver tissue of HCC patients may be associated with the significant increased development of Treg, which favors the disease progression through the suppressive effect of Treg on host immune response in these patients.


Assuntos
Carcinoma Hepatocelular/patologia , Fatores de Transcrição Forkhead/metabolismo , Neoplasias Hepáticas/patologia , Fígado/patologia , Linfócitos do Interstício Tumoral/patologia , Linfócitos T Reguladores/patologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/patologia , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/cirurgia , Progressão da Doença , Feminino , Fatores de Transcrição Forkhead/sangue , Hepatectomia , Humanos , Fígado/metabolismo , Fígado/cirurgia , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/cirurgia , Contagem de Linfócitos , Masculino , Linfócitos T Reguladores/metabolismo , Regulação para Cima
10.
PLoS One ; 6(3): e17484, 2011 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-21390263

RESUMO

BACKGROUND: Extensive mononuclear cell infiltration is strongly correlated with liver damage in patients with chronic hepatitis B virus (CHB) infection. Macrophages and infiltrating monocytes also participate in the development of liver damage and fibrosis in animal models. However, little is known regarding the immunopathogenic role of peripheral blood monocytes and intrahepatic macrophages. METHODOLOGY/PRINCIPAL FINDINGS: The frequencies, phenotypes, and functions of peripheral blood and intrahepatic monocyte/macrophage subsets were analyzed in 110 HBeAg positive CHB patients, including 32 immune tolerant (IT) carriers and 78 immune activated (IA) patients. Liver biopsies from 20 IA patients undergoing diagnosis were collected for immunohistochemical analysis. IA patients displayed significant increases in peripheral blood monocytes and intrahepatic macrophages as well as CD16(+) subsets, which were closely associated with serum alanine aminotransferase (ALT) levels and the liver histological activity index (HAI) scores. In addition, the increased CD16(+) monocytes/macrophages expressed higher levels of the activation marker HLA-DR compared with CD16(-) monocytes/macrophages. Furthermore, peripheral blood CD16(+) monocytes preferentially released inflammatory cytokines and hold higher potency in inducing the expansion of Th17 cells. Of note, hepatic neutrophils also positively correlated with HAI scores. CONCLUSIONS: These distinct properties of monocyte/macrophage subpopulations participate in fostering the inflammatory microenvironment and liver damage in CHB patients and further represent a collaborative scenario among different cell types contributing to the pathogenesis of HBV-induced liver disease.


Assuntos
Hepatite B Crônica/imunologia , Inflamação/imunologia , Cirrose Hepática/imunologia , Fígado/patologia , Monócitos/imunologia , Receptores de IgG/metabolismo , Índice de Gravidade de Doença , Adolescente , Adulto , Proliferação de Células , Feminino , Hepatite B Crônica/sangue , Hepatite B Crônica/complicações , Humanos , Inflamação/complicações , Fígado/imunologia , Cirrose Hepática/sangue , Cirrose Hepática/complicações , Macrófagos/imunologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/imunologia , Células Th17/citologia , Células Th17/imunologia , Adulto Jovem
11.
PLoS One ; 5(11): e13869, 2010 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-21079784

RESUMO

BACKGROUND: Treatment with nucleotide analogs is known to be effective in inhibiting HBV replication; however, patients with chronic hepatitis B (CHB) often show a wide range of clinical responses to these drugs. Therefore, the identification of an early immunologic marker associated with the clinical outcomes in such cases is critical for the improved clinical management. In our study, we aimed to investigate whether the viral load in CHB patients affected the ratio of the number of regulatory T cells (Tregs) to the number of interleukin-17-producing helper (Th17) cells. Further, we evaluated the clinical implications of the alterations in this ratio. METHODOLOGY/PRINCIPAL FINDINGS: Nine patients seropositive for hepatitis B e antigen received entecavir monotherapy for 12 months and the percentages of Tregs and Th17 cells as well as the HBV-specific IL-17 productions in these patients were longitudinally analyzed. The entecavir-induced suppression of HBV replication was accompanied by a rapid increase in the number of Th17 cells, together with a decrease in Treg cells, which lead to a significant reduction of Treg/Th17 ratios. In addition, peripheral blood mononuclear cells (PBMCs) exhibited a decreased IL-17 production upon stimulation with the HBV core antigen in vitro. CONCLUSIONS: The inhibition of viral replication results in an increase in Th17 cells and concomitant decrease in Treg cells. This imbalance of Treg cells to Th17 cells might have an important role in HBV persistence during entecavir treatment.


Assuntos
Guanina/análogos & derivados , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Linfócitos T Reguladores/efeitos dos fármacos , Células Th17/efeitos dos fármacos , Adolescente , Adulto , Alanina Transaminase/sangue , Antivirais/uso terapêutico , DNA Viral/sangue , DNA Viral/genética , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Seguimentos , Guanina/uso terapêutico , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Hepatite B Crônica/imunologia , Hepatite B Crônica/virologia , Humanos , Interleucina-17/sangue , Interleucina-17/metabolismo , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Linfócitos T Reguladores/citologia , Linfócitos T Reguladores/imunologia , Células Th17/citologia , Células Th17/imunologia , Fatores de Tempo , Resultado do Tratamento , Carga Viral/efeitos dos fármacos , Adulto Jovem
12.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 26(6): 536-8, 2010 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-20487644

RESUMO

AIM: To investigate phenotypical and functional characteristics of the CD39(+);FoxP3(+);regulatory T (Treg) cells in humans. METHODS: We collected peripheral blood from 10 healthy volunteers and separated PBMC by using density gradient centrifugation, and then detected the expression of CTLA-4, HLA-DR, CD45RO and Ki-67 on CD39(+);FoxP3(+); and CD39(-);FoxP3(+);Treg cells by using flow cytometric analysis. [(3);H]-thymidine incorporation assay and ELISA were used to monitor the suppressive capacity of CD39(+); FoxP3(+); Treg cells on proliferation and IFN-gamma secretion of Treg-depleted PBMC. RESULTS: The expression of CTLA-4, HLA-DR, CD45RO and Ki-67 was significantly higher in CD39(+);FoxP3(+); Treg cells than those in CD39(-);FoxP3(+); Treg cells. The suppressive capacity of CD39(+);FoxP3(+); Treg cells on proliferation and IFN-gamma secretion of Treg-depleted PBMC was significantly higher than those of FoxP3(+);CD39(-);Treg cells. CONCLUSION: CD39(+);Fxop3(+);Treg subset may play an essential role in immune regulation of Treg, and CD39 can be used as a surface marker to identify the functional Treg cells.


Assuntos
Antígenos CD/metabolismo , Apirase/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Adulto , Antígeno CTLA-4 , Proliferação de Células , Células Cultivadas , Feminino , Antígenos HLA-DR/metabolismo , Humanos , Interferon gama/metabolismo , Antígeno Ki-67/metabolismo , Antígenos Comuns de Leucócito/metabolismo , Masculino , Linfócitos T Reguladores/citologia
13.
J Gastroenterol ; 45(9): 968-78, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20411280

RESUMO

BACKGROUND: We carried out this study to evaluate the association between regulatory T cells (Treg) and prognosis and progression after cryoablation in patients with hepatitis-B virus-related hepatocellular carcinoma. METHODS: Peripheral Treg frequency in 111 patients with hepatocellular carcinoma (HCC) was detected by flow cytometry. Treg frequency and function were re-examined during patient follow up. A possible association between Treg and α-fetoprotein (AFP) was also analyzed, and the distribution of resident CD4(+) and CD8(+) T cells and FoxP3(+) T cells in the liver tissue of patients with HCC was examined by immunohistochemistry. RESULTS: Treg frequency significantly increased with disease progression. Our longitudinal study showed that Treg frequency had significantly decreased in 17 patients with HCC regression following cryoablation, but the frequency had dramatically increased in 14 patients with HCC recurrence or progression. Furthermore, AFP levels varied in a way comparable with Treg frequency in patients with elevated AFP recorded before therapy. Significantly increased suppressive effects of Treg on proliferation and cytokine secretion of CD8(+) and CD4(+) T cells were observed during follow up in patients with tumor progression, but not in patients with tumor response. Moreover, the numbers of CD8(+), CD4(+), and FoxP3(+) cells infiltrating the tumors around the cryotherapeutic zones were significantly decreased after argon-helium cryoablation, and this was associated with a reduction in the FoxP3/CD8 ratio. Importantly,increased quantities of circulating CD4(+)CD25(+)FoxP3(+) Treg and tumor infiltrating FoxP3(+) cells before cryoablation were associated with high recurrence or risk of progression in HCC patients after cryoablation. CONCLUSIONS: Treg variation is associated with tumor regression or progression in HCC following cryoablation and may be used as a marker to estimate HCC progression.


Assuntos
Carcinoma Hepatocelular/cirurgia , Criocirurgia/métodos , Neoplasias Hepáticas/cirurgia , Linfócitos T Reguladores/imunologia , Adulto , Idoso , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/virologia , Progressão da Doença , Feminino , Citometria de Fluxo , Seguimentos , Hepatite B/complicações , Humanos , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/virologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Prognóstico , Resultado do Tratamento
14.
Hepatology ; 51(1): 81-91, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19842207

RESUMO

UNLABELLED: Interleukin-17 (IL-17)-producing CD4(+) T cells (Th17)-mediated immune response has been demonstrated to play a critical role in inflammation-associated disease; however, its role in chronic hepatitis B virus (HBV) infection remains unknown. Here we characterized peripheral and intrahepatic Th17 cells and analyzed their association with liver injury in a cohort of HBV-infected patients including 66 with chronic hepatitis B (CHB), 23 with HBV-associated acute-on-chronic liver failure (ACLF), and 30 healthy subjects as controls. The frequency of circulating Th17 cells increased with disease progression from CHB (mean, 4.34%) to ACLF (mean, 5.62%) patients versus healthy controls (mean, 2.42%). Th17 cells were also found to be largely accumulated in the livers of CHB patients. The increases in circulating and intrahepatic Th17 cells positively correlated with plasma viral load, serum alanine aminotransferase levels, and histological activity index. In vitro, IL-17 can promote the activation of myeloid dendritic cells and monocytes and enhance the capacity to produce proinflammatory cytokines IL-1beta, IL-6, tumor necrosis factor (TNF)-alpha, and IL-23 in both CHB patients and healthy subjects. In addition, the concentration of serum Th17-associated cytokines was also increased in CHB and ACLF patients. CONCLUSION: Th17 cells are highly enriched in both peripheral blood and liver of CHB patients, and exhibit a potential to exacerbate liver damage during chronic HBV infection.


Assuntos
Linfócitos T CD4-Positivos/patologia , Hepatite B Crônica/patologia , Interleucina-17/biossíntese , Adolescente , Adulto , Células Dendríticas/imunologia , Feminino , Hepatite B Crônica/imunologia , Humanos , Fígado/citologia , Fígado/imunologia , Masculino , Pessoa de Meia-Idade
15.
Eur J Immunol ; 39(5): 1425-34, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19350559

RESUMO

Chronic HIV-1 infection can induce a significant decrease in CD127 expression on CD8 T cells, but the underlying mechanisms and immunological consequences are unclear. In this study, we investigated CD127 expression on CD8 T cells from a total of 51 HIV-1-infected subjects and 16 healthy individuals and analyzed the association between CD127 expression and CD8 T-cell apoptosis in these HIV-1-infected subjects. We found that CD127 expression on total CD8 T cells was significantly down-regulated, which was correlated with the increased CD8 T-cell apoptosis and disease progression of chronic HIV-1 infection. The in vitro addition of IL-7 efficiently rescued the spontaneous apoptosis of CD8 T cells from HIV-1-infected individuals. IL-7 stimulation also transiently down-regulated CD127 expression, whereas some of the CD127(-) CD8 T cells regained CD127 expression soon after IL-7 was retracted from the incubation medium. Thus, IL-7 stimulation reduced apoptosis of both CD127(+) and CD127(-)CD8 T cells to some degree. These data indicate that CD127 loss might impair IL-7 signaling and increase CD8 T-cell apoptosis during HIV-1 infection. This study, therefore, will extend the notion that IL-7 could be a good candidate for immunotherapy in HIV-1-infected patients.


Assuntos
Apoptose/imunologia , Linfócitos T CD8-Positivos/imunologia , Infecções por HIV/imunologia , HIV-1/imunologia , Subunidade alfa de Receptor de Interleucina-7/imunologia , Interleucina-7/farmacologia , Adulto , Estudos de Coortes , Regulação para Baixo/imunologia , Feminino , Citometria de Fluxo , Humanos , Memória Imunológica/imunologia , Imunoterapia/métodos , Técnicas In Vitro , Interleucina-7/uso terapêutico , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Adulto Jovem
16.
Immunology ; 128(1 Suppl): e366-75, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19016904

RESUMO

Persistent HIV infection results in a decrease in absolute counts of CD4(+) CD25(+) regulatory T cells (Treg). To investigate the role of decreased Treg counts in the regulation of excessive activation and apoptosis of CD8(+) T cells in human immunodeficiency virus (HIV)-1 infection, we characterized Treg in 83 HIV-1-infected individuals, including 19 long-term non-progressors (LTNPs) and 51 typical progressors (TPs) who were treatment-naïve, and 13 AIDS patients on highly active antiretroviral therapy (HAART), of whom nine were complete responders (CRs) and the remaining four were non-responders (NRs) to the treatment. TPs but not LTNPs had a significant decrease in absolute counts of circulating Treg, which was inversely correlated with the activation and apoptosis of CD8(+) T cells. Efficient HAART was found to increase Treg counts in CR patients and temper the excessive activation and apoptosis of CD8(+) T cells. Moreover, isolated Treg significantly inhibited the spontaneous and anti-CD3-induced apoptosis of CD8(+) T cells in a dose-dependent manner in vitro. Thus, our findings indicate that the decrease in Treg closely correlates with the increase in apoptotic CD8(+) T cells and disease progression in chronic HIV-1 infection, and that Treg may play a key role in maintaining the balance between the amount and quality of CD8(+) T cells in HIV-1 infection. Manipulation of Treg function may be a promising strategy for immune therapy of this disease.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Infecções por HIV/imunologia , HIV-1 , Linfócitos T Reguladores/imunologia , Adulto , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Apoptose/imunologia , Contagem de Linfócito CD4 , Linfócitos T CD8-Positivos/virologia , Doença Crônica , Progressão da Doença , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Ativação Linfocitária/imunologia , Masculino , Pessoa de Meia-Idade , RNA Viral/imunologia , Linfócitos T Reguladores/virologia
17.
J Immunol ; 181(6): 3741-4, 2008 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-18768824

RESUMO

Attrition of heterologous virus-specific CD8(+) T cells has been demonstrated in murine viral infection; however, little is known regarding this phenomenon in human viral infections. In this study, we observed that CMV-specific CD8(+) T cells displayed numerical decline and functional impairment in the early phase of acute infection, whereas programmed death-1 (PD-1) expression was significantly up-regulated by these CMV-specific CD8(+) T cells. This early PD-1 up-regulation was found to be closely associated with the increased apoptotic sensitivity of CMV-specific CD8(+) T cells. The in vitro addition of anti-PD-1 further enhanced the spontaneous apoptosis of CMV-specific CD8(+) T cells; however, blockade of the PD-1-mediated pathway with anti-PD-L1 significantly restored the CMV-specific CD8(+) T cell proliferation and IFN-gamma production. Thus, PD-1 plays a crucial role in the attrition of CMV-specific CD8(+) T cells in acute hepatitis B virus infection, which in turn, influences the preexisting homeostatic virus-specific CD8(+) T cell pool.


Assuntos
Antígenos CD/biossíntese , Proteínas Reguladoras de Apoptose/biossíntese , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/virologia , Citomegalovirus/imunologia , Epitopos de Linfócito T/imunologia , Hepatite B/imunologia , Hepatite B/metabolismo , Regulação para Cima/imunologia , Doença Aguda , Adulto , Antígenos CD/fisiologia , Apoptose/imunologia , Proteínas Reguladoras de Apoptose/fisiologia , Linfócitos T CD8-Positivos/patologia , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/metabolismo , Infecções por Citomegalovirus/patologia , Feminino , Hepatite B/patologia , Homeostase/imunologia , Humanos , Contagem de Linfócitos , Masculino , Receptor de Morte Celular Programada 1
18.
J Hepatol ; 49(3): 396-406, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18644645

RESUMO

BACKGROUND/AIMS: Functionally impaired dendritic cells (DCs) play important roles in suppressing host immune responses and facilitating viral persistence in chronic hepatitis B virus (HBV) infection. However, little is known regarding the status of intrahepatic DCs in HBV infection. METHODS: Based on availability, 11 recipient liver samples were obtained from acute-on-chronic hepatitis B liver failure (ACHBLF) patients who had undergone liver transplantation. The frequencies, phenotypes, and functions of intrahepatic DC subsets were analyzed. RESULTS: Both plasmacytoid dendritic cells (pDCs) and myeloid dendritic cells (mDCs) extensively infiltrated the liver of the ACHBLF patients and expressed mature phenotypes therein. In particular, activated hepatic pDCs produced interferon (IFN)-alpha, which subsequently induced interleukin (IL)-12 and IL-10 production via toll-like receptor-9 ligation in liver-infiltrating lymphocytes cultured in vitro. However, blockade of IFN-alpha production significantly reduced the cytokine production of the LILs. Further, a significantly low frequency of peripheral pDCs and highly reduced IFN-alpha production were observed in a large cohort of the ACHBLF patients, particularly in the non-survivors. Moreover, a persistently upregulated expression of hepatic IFN-alpha-associated genes was observed in the ACHBLF patients during disease progression. CONCLUSIONS: Activated pDCs accumulated in large numbers in the liver of the ACHBLF patients and regulated local immune responses in chronic HBV infection.


Assuntos
Células Dendríticas/patologia , Hepatite B Crônica/complicações , Hepatite B Crônica/patologia , Falência Hepática Aguda/patologia , Falência Hepática Aguda/virologia , Fígado/patologia , Adulto , Idoso , Estudos de Casos e Controles , Contagem de Células , Células Dendríticas/metabolismo , Progressão da Doença , Feminino , Humanos , Interferon-alfa/metabolismo , Interleucina-10/metabolismo , Interleucina-12/metabolismo , Lectinas Tipo C/metabolismo , Fígado/metabolismo , Fígado/cirurgia , Transplante de Fígado , Masculino , Glicoproteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Fenótipo , Prognóstico , Receptores Imunológicos/metabolismo
19.
Zhonghua Yi Xue Za Zhi ; 87(34): 2416-9, 2007 Sep 11.
Artigo em Chinês | MEDLINE | ID: mdl-18036321

RESUMO

OBJECTIVE: To investigate the frequencies of immunologically competent cells (ICCs) in the liver-infiltrating lymphocytes (LILs) and peripheral blood and their possible role in pathogenesis in patients with chronic severe hepatitis B (CSHB). METHODS: LILs were isolated from the liver tissue samples from 11 CSHB patients and 5 normal controls (NCs) by the method of combined grinding with semi-frosted microscopic slides and sedimentation of hepatic cells. The frequency of isolated ICCs, including CD3(+), CD4(+), and CD8(+) T-cells, NK cells, NKT cells, and B cells was examined and compared with that of the circulating ICCs in the CSHB patients. Comparison was conducted between the CSHB patients and the controls. RESULTS: (1) In the CSHB patients, the frequencies of CD4(+) T cells and B cells in LILs were 17% +/- 6% and 3.0% +/- 1.0% respectively, both significantly lower than those in the circulating blood (32% +/- 8% and 21.4% +/- 12.2% respectively, both P < 0.01); however, the frequencies of CD8(+) T cells, NK cells, and NKT cells in LILs were 38% +/- 13%, 34% +/- 18%, and 10% +/- 4% respectively, all significantly lower than those in the circulating blood (26% +/- 6%, 15% +/- 9%, and 6% +/- 4%, all P < 0.05). (2) The frequencies of infiltrating CD3(+) T cells and CD4(+) T cells of the CSHB patients were both significantly higher than those of the NCs (P = 0.042 and P = 0.001); and the frequency of infiltrating CD8(+) T cells of the CSHB patients was higher than that of the NCs, and the and the frequencies of infiltrating NK cells and NKT cells in LILs were lower than those of the NCs, however, not significantly. (3) Compared with the liver tissues from the NCs, the liver tissues from the CSHB patients exhibited a significantly higher ratio of liver-infiltrating CD4(+) T cells to peripheral blood CD4(+) T-cell subsets (P = 0.001), and significantly lower ratios of liver-infiltrating NKT cells and B cells to the peripheral blood NKT-cells and B cells (P = 0.029 and P = 0.001 respectively). CONCLUSION: The abundant infiltrating immune active cells, especially the CD4(+) T cells, CD8(+) T cells, and NK cells, may be the causal factors that drive the progressive development of CSHB.


Assuntos
Hepatite B Crônica/imunologia , Fígado/imunologia , Linfócitos/imunologia , Adulto , Idoso , Linfócitos B/imunologia , Linfócitos B/patologia , Relação CD4-CD8 , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/patologia , Feminino , Hepatite B Crônica/patologia , Humanos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/patologia , Fígado/patologia , Transplante de Fígado , Contagem de Linfócitos , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Linfócitos T/imunologia , Linfócitos T/patologia
20.
Artigo em Chinês | MEDLINE | ID: mdl-17429522

RESUMO

OBJECTIVE: To investigate the difference in the CD4+T lymphocytes activation between long term non progressors (LTNP) and typical progressors (TP) of HIV-1 infected patients. METHODS: Twenty-four HIV-1 infected patients and 15 heathy control adults were tested and flow cytometry was used to detect the activation marker CD38 and CD4 count in blood samples taken from the patients and control. bDNA method was used to test the virus load in the plasma of patients. RESULTS: The activation of CD4+T cells was positively correlated with virus load and negatively correlated with CD4 counts. Compared with normal controls, the activation of CD4+T cells was obviously increased in TP patients but not obviously changed in LTNP patients. CONCLUSION: Compared with healthy controls, the activation of CD4+T cells in LTNP did not obviously increase. This maybe partially accounts for LTNP patients keeping a good state for a long time.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Infecções por HIV/imunologia , HIV-1/fisiologia , Ativação Linfocitária/imunologia , ADP-Ribosil Ciclase 1/análise , Adulto , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/citologia , Feminino , Citometria de Fluxo , Infecções por HIV/sangue , Infecções por HIV/virologia , HIV-1/genética , Interações Hospedeiro-Patógeno , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Fatores de Tempo , Carga Viral , Adulto Jovem
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