AIM： To determine whether body weight and/or serum leptin were independent predictors of response to antiviral treatment in patients with chronic hepatitis C. METHODS： A retrospective evaluation was performed in 139...AIM： To determine whether body weight and/or serum leptin were independent predictors of response to antiviral treatment in patients with chronic hepatitis C. METHODS： A retrospective evaluation was performed in 139 patients with chronic hepatitis C treated with interferon （IFN） from 1996 to 2000. Sustained response was defined as negative by hepatitis C virus （HCV） RNA analysis using PCR and normal transaminase at 24 wk after cessation of IFN therapy. Patients who remained positive for HCV RNA at the end of IFN treatment were defined as resistant to IFN therapy. Sex, age, body mass index （BMI） （≥ 25 vs 〈 25）, complication of diabetes mellitus, serum leptin level （≥ 8.0μg/L vs 〈8.0μg/L）, and the stage of liver fibrosis by needle biopsy （F1/F2 vs F3/F4） were examined. RESULTS： Sustained response was achieved in 33 patients （23.7%）, while others failed to show a response to IFN therapy. Overall, the factors associated with sustained antiviral effects were HCV-RNA load, HCV genotype, serum leptin level, and stage of liver fibrosis evaluated by univariate analysis. BMI was not associated with any therapeutic effect of IFN. Multivariate analysis indicated that HCV-RNA load was a significant risk factor, but among the patients with low viremia （HCV-RNA 〈 100 MU/L）, leptin level was an independent risk factor for IFN resistance. Namely, a high level of serum leptin attenuated the effect of IFN on both male and female patients with low viremia. CONCLUSION： High serum leptin level is a negative predictor of response to antiviral treatment in chronic hepatitis C with low viremia.展开更多
While severe acute respiratory syndrome coronavirus （SARS-CoV）~as initially thought to enter cells through direct fusion with the plasma membrane, more recent evidence suggests that yirus entry may also involve endo...While severe acute respiratory syndrome coronavirus （SARS-CoV）~as initially thought to enter cells through direct fusion with the plasma membrane, more recent evidence suggests that yirus entry may also involve endocytosis. We have found that SARS-CoV enters cells viapH- and receptor-dependent endocytosis. Treatment of cells with either SARS-COV spike protein or spike-bearing pseudoviruses resulted in the translocation of angiotensin-converting enzyme 2 （ACE2）, the functional receptor of SARS-CoV, from the cell surface to endosomes. In addition, the spike-bearing pseudoviruses and early endosome antigen 1 were found to colocalize in endosomes. Further analyses using specific endocytic path- way inhibitors and dominant-negative Epsl5 as well as caveolin-1 colocalization study suggested that virus entry was mediated by a clathrin- and caveolae-independent mechanism. Moreover, cholesterol- and sphingolipid-rich lipid raft microdomains in the plasma membrane, which have been shown to act as platforms for many physiological signaling pathways, were shown to be involved in virus entry. Endocytic entry of SARS-CoV may expand the cellular range of SARS-CoV infection, and our findings here contribute to the understanding of SARS-CoV pathogenesis, providing new information for anti-viral drug research.展开更多
AIM: To assess the clinical significance of Hepatitis B virus (HBV) DNA localization in the liver tissue of patients with positive HBsAg and negative viremia.METHODS: HBV virological parameters of 33 HBsAg positive ch...AIM: To assess the clinical significance of Hepatitis B virus (HBV) DNA localization in the liver tissue of patients with positive HBsAg and negative viremia.METHODS: HBV virological parameters of 33 HBsAg positive chronic hepatitis patients, including seromarkers and HBV DNA amplification in both sera and liver biopsies, were evaluated.RESULTS: Ten patients had negative viremia and positive HBV DNA in their liver biopsies. Most of them had HBeAg-negative/HBeAb-positive chronic hepatitis.Their liver biochemical and histopathological profiles were different from the viremic patients. Their disease pattern was designated as 'hepatitis B in situ'.CONCLUSION: Hepatitis B in situ is a consequential entity which can be missed in clinical practice. It is a new clinical pattern of chronic HBV infection that considers HBV in liver biopsy and adds a new indication for antiviral therapy.展开更多
The present work aimed to investigate the microscopic and ultramicro- scopic structure of the liver to assess the level of hepatic impairment during preg- nancy toxemia. Seven pregnant small-tailed Han sheep of negati...The present work aimed to investigate the microscopic and ultramicro- scopic structure of the liver to assess the level of hepatic impairment during preg- nancy toxemia. Seven pregnant small-tailed Han sheep of negative urine ketone bodies were assessed in this study. Toxemia was induced by limiting food and movement tate in pregnancy. Three sheep developed obvious clinical symptoms with motor weakness, depression, anorexia, locomotion disturbances, blindness and lan- guishment. We harvested their liver tissues as pathological material, and used rou- tine histological and electronic microscopy methods to observe the histopathological changes in small-tailed Han sheep induced by pregnancy toxemia. Autopsy of the livers of the sheep revealed deep yellow coloration, intumescence and hemorrhage on the surface. Microstructural features indicated fatty degeneration, which is a main characteristic of fatty liver. Hepatocellular ultrastructural changes were observed un- der an electronic microscope. The characteristic findings were nucieolus concentra- tion, vacuolation of mitochondria and excessive glycogen granules in the cytoplasm. Via this experimental protocol, pregnancy toxemia of sheep was successfully in- duced, providing a pathological model for the study of this disease. After the experi- mental induction of pregnancy toxemia, the clinical symptoms of pathogenic sheep and pathological changes to their livers exhibited obvious characteristics of pregnan- cy toxemia.展开更多
基金Supportecl by a Grant-in-Aid from the Ministry of Education,Culture,Sports,Science and Technology,Japan,for Scientific Research,No.16590606(TM)
文摘AIM： To determine whether body weight and/or serum leptin were independent predictors of response to antiviral treatment in patients with chronic hepatitis C. METHODS： A retrospective evaluation was performed in 139 patients with chronic hepatitis C treated with interferon （IFN） from 1996 to 2000. Sustained response was defined as negative by hepatitis C virus （HCV） RNA analysis using PCR and normal transaminase at 24 wk after cessation of IFN therapy. Patients who remained positive for HCV RNA at the end of IFN treatment were defined as resistant to IFN therapy. Sex, age, body mass index （BMI） （≥ 25 vs 〈 25）, complication of diabetes mellitus, serum leptin level （≥ 8.0μg/L vs 〈8.0μg/L）, and the stage of liver fibrosis by needle biopsy （F1/F2 vs F3/F4） were examined. RESULTS： Sustained response was achieved in 33 patients （23.7%）, while others failed to show a response to IFN therapy. Overall, the factors associated with sustained antiviral effects were HCV-RNA load, HCV genotype, serum leptin level, and stage of liver fibrosis evaluated by univariate analysis. BMI was not associated with any therapeutic effect of IFN. Multivariate analysis indicated that HCV-RNA load was a significant risk factor, but among the patients with low viremia （HCV-RNA 〈 100 MU/L）, leptin level was an independent risk factor for IFN resistance. Namely, a high level of serum leptin attenuated the effect of IFN on both male and female patients with low viremia. CONCLUSION： High serum leptin level is a negative predictor of response to antiviral treatment in chronic hepatitis C with low viremia.
文摘While severe acute respiratory syndrome coronavirus （SARS-CoV）~as initially thought to enter cells through direct fusion with the plasma membrane, more recent evidence suggests that yirus entry may also involve endocytosis. We have found that SARS-CoV enters cells viapH- and receptor-dependent endocytosis. Treatment of cells with either SARS-COV spike protein or spike-bearing pseudoviruses resulted in the translocation of angiotensin-converting enzyme 2 （ACE2）, the functional receptor of SARS-CoV, from the cell surface to endosomes. In addition, the spike-bearing pseudoviruses and early endosome antigen 1 were found to colocalize in endosomes. Further analyses using specific endocytic path- way inhibitors and dominant-negative Epsl5 as well as caveolin-1 colocalization study suggested that virus entry was mediated by a clathrin- and caveolae-independent mechanism. Moreover, cholesterol- and sphingolipid-rich lipid raft microdomains in the plasma membrane, which have been shown to act as platforms for many physiological signaling pathways, were shown to be involved in virus entry. Endocytic entry of SARS-CoV may expand the cellular range of SARS-CoV infection, and our findings here contribute to the understanding of SARS-CoV pathogenesis, providing new information for anti-viral drug research.
文摘AIM: To assess the clinical significance of Hepatitis B virus (HBV) DNA localization in the liver tissue of patients with positive HBsAg and negative viremia.METHODS: HBV virological parameters of 33 HBsAg positive chronic hepatitis patients, including seromarkers and HBV DNA amplification in both sera and liver biopsies, were evaluated.RESULTS: Ten patients had negative viremia and positive HBV DNA in their liver biopsies. Most of them had HBeAg-negative/HBeAb-positive chronic hepatitis.Their liver biochemical and histopathological profiles were different from the viremic patients. Their disease pattern was designated as 'hepatitis B in situ'.CONCLUSION: Hepatitis B in situ is a consequential entity which can be missed in clinical practice. It is a new clinical pattern of chronic HBV infection that considers HBV in liver biopsy and adds a new indication for antiviral therapy.
基金Supported by Natural Science Foundation of Ningxia(BA002-2004)
文摘The present work aimed to investigate the microscopic and ultramicro- scopic structure of the liver to assess the level of hepatic impairment during preg- nancy toxemia. Seven pregnant small-tailed Han sheep of negative urine ketone bodies were assessed in this study. Toxemia was induced by limiting food and movement tate in pregnancy. Three sheep developed obvious clinical symptoms with motor weakness, depression, anorexia, locomotion disturbances, blindness and lan- guishment. We harvested their liver tissues as pathological material, and used rou- tine histological and electronic microscopy methods to observe the histopathological changes in small-tailed Han sheep induced by pregnancy toxemia. Autopsy of the livers of the sheep revealed deep yellow coloration, intumescence and hemorrhage on the surface. Microstructural features indicated fatty degeneration, which is a main characteristic of fatty liver. Hepatocellular ultrastructural changes were observed un- der an electronic microscope. The characteristic findings were nucieolus concentra- tion, vacuolation of mitochondria and excessive glycogen granules in the cytoplasm. Via this experimental protocol, pregnancy toxemia of sheep was successfully in- duced, providing a pathological model for the study of this disease. After the experi- mental induction of pregnancy toxemia, the clinical symptoms of pathogenic sheep and pathological changes to their livers exhibited obvious characteristics of pregnan- cy toxemia.
