Background/Aims: The presence of antibodies to the 210- kDa glycoprotein of the nuclear pore complex (gp210) is highly indicative of primary biliary cirrhos is (PBC). However, the significance of anti- gp210 antibody ...Background/Aims: The presence of antibodies to the 210- kDa glycoprotein of the nuclear pore complex (gp210) is highly indicative of primary biliary cirrhos is (PBC). However, the significance of anti- gp210 antibody titers for monitori ng PBC remains unresolved. Methods: We used an ELISA with a gp210 C- terminal p eptide as an antigen to assess serum antibody titers in 71 patients with PBC. Re sults: Patients were classified into three groups: Group A in whom anti- gp210 titers were sustained at a high level, Group B in whom anti- gp210 status chang ed from positive to negative under ursodeoxycholic acid (UDCA) therapy, Group C in whom anti- gp210 antibodies were negative at the time of diagnosis. The rate of progression to end- stage hepatic failure was significantly higher in group A (60% ) as compared to groups B (0% ) and C (4.2% ). The sustained antibody response to gp210 was closely associated with the severity of interface hepatit is. The significance of anti- gp210 antibody was confirmed by National Hospital Organization Study Group for Liver Disease in Japan. Conclusions: The serial qu antitation of serum anti- gp210- C- terminal peptide antibodies is useful for monitoring the effect of UDCA and for the early identification of patients at h igh risk for end- stage hepatic failure.展开更多
Although there have been significant advances in understanding the clinical and biochemical features of primary biliary cirrhosis (PBC), there is still a paucity of data on the usefulness of biomarkers as prognostic i...Although there have been significant advances in understanding the clinical and biochemical features of primary biliary cirrhosis (PBC), there is still a paucity of data on the usefulness of biomarkers as prognostic indicators. This is particularly important at the time of initial diagnosis. Indeed, the widespread use of antimitochondrial antibody testing has led to an earlier diagnosis of asymptomatic PBC and it is difficult to predict which patients will experience a benign versus a rapidly progressive course. To address this issue, we examined a unique population of 127 newly diagnosed patients with PBC during a 15-year period of observation that began in January 1990. Sera from these patients were analyzed for antimitochondrial, antinuclear, and anti-smooth muscle antibodies, and immunoblotting was performed for nuclear pore complex (NPC). The patients were then followed up longitudinally using biochemical liver function tests. No patient was under any medical therapy for PBC at the time of the initial sera collection. Data were analyzed based not only on the clinical features, but also the Mayo score and specific outcome measures, including time to death, need for liver transplantation, and complication free survival. Among patients with early disease, bilirubin increased to >2 mg/dL in the anti-NPC(+) patients(26%vs. 5%, P = .019). Anti-NPC antibodies remained stable or slightly increased over the period of observation. In conclusion, anti-NPC identifies patients likely to experience an unfavorable clinical course and more rapid disease progression.展开更多
Molecules can enter the nucleus by passive diffusion or active transport mechanisms, depending on their size. Small molecules up to size of 50-60 kDa or less than 10 nm in diameter can diffuse passively through the nu...Molecules can enter the nucleus by passive diffusion or active transport mechanisms, depending on their size. Small molecules up to size of 50-60 kDa or less than 10 nm in diameter can diffuse passively through the nuclear pore complex （NPC）, while most proteins are transported by energy driven transport mechanisms Active transport of viral proteins is mediated by nuclear localization signals （NLS）, which were first identified in Simian Virus 40 large T antigen and had subsequently been identified in a large number of viral they contain short stretches of lysine or arginine residues. These signals are recognized proteins. Usually by the importin super-family （importin α and β） proteins that mediate the transport across the nuclear envelope through Ran-GTP In contrast, only one class of the leucine-rich nuclear export signal （NES） on viral proteins is known at present. Chromosome region maintenance 1 （CRM1） protein mediates nuclear export of hundreds of viral proteins through the recognition of the leucine-rich NES.展开更多
文摘Background/Aims: The presence of antibodies to the 210- kDa glycoprotein of the nuclear pore complex (gp210) is highly indicative of primary biliary cirrhos is (PBC). However, the significance of anti- gp210 antibody titers for monitori ng PBC remains unresolved. Methods: We used an ELISA with a gp210 C- terminal p eptide as an antigen to assess serum antibody titers in 71 patients with PBC. Re sults: Patients were classified into three groups: Group A in whom anti- gp210 titers were sustained at a high level, Group B in whom anti- gp210 status chang ed from positive to negative under ursodeoxycholic acid (UDCA) therapy, Group C in whom anti- gp210 antibodies were negative at the time of diagnosis. The rate of progression to end- stage hepatic failure was significantly higher in group A (60% ) as compared to groups B (0% ) and C (4.2% ). The sustained antibody response to gp210 was closely associated with the severity of interface hepatit is. The significance of anti- gp210 antibody was confirmed by National Hospital Organization Study Group for Liver Disease in Japan. Conclusions: The serial qu antitation of serum anti- gp210- C- terminal peptide antibodies is useful for monitoring the effect of UDCA and for the early identification of patients at h igh risk for end- stage hepatic failure.
文摘Although there have been significant advances in understanding the clinical and biochemical features of primary biliary cirrhosis (PBC), there is still a paucity of data on the usefulness of biomarkers as prognostic indicators. This is particularly important at the time of initial diagnosis. Indeed, the widespread use of antimitochondrial antibody testing has led to an earlier diagnosis of asymptomatic PBC and it is difficult to predict which patients will experience a benign versus a rapidly progressive course. To address this issue, we examined a unique population of 127 newly diagnosed patients with PBC during a 15-year period of observation that began in January 1990. Sera from these patients were analyzed for antimitochondrial, antinuclear, and anti-smooth muscle antibodies, and immunoblotting was performed for nuclear pore complex (NPC). The patients were then followed up longitudinally using biochemical liver function tests. No patient was under any medical therapy for PBC at the time of the initial sera collection. Data were analyzed based not only on the clinical features, but also the Mayo score and specific outcome measures, including time to death, need for liver transplantation, and complication free survival. Among patients with early disease, bilirubin increased to >2 mg/dL in the anti-NPC(+) patients(26%vs. 5%, P = .019). Anti-NPC antibodies remained stable or slightly increased over the period of observation. In conclusion, anti-NPC identifies patients likely to experience an unfavorable clinical course and more rapid disease progression.
基金The Startup Fund of the Hundred Talents Program of the Chinese Academy of Science (20071010-141)National Natural Science Foundation of China(30870120)+1 种基金Open Research Fund Program of the State Key Laboratory of Virology of China (2007003,2009007)Hubei Province Natural Science Foundation of Innovation Groups Project (2008CDA013)
文摘Molecules can enter the nucleus by passive diffusion or active transport mechanisms, depending on their size. Small molecules up to size of 50-60 kDa or less than 10 nm in diameter can diffuse passively through the nuclear pore complex （NPC）, while most proteins are transported by energy driven transport mechanisms Active transport of viral proteins is mediated by nuclear localization signals （NLS）, which were first identified in Simian Virus 40 large T antigen and had subsequently been identified in a large number of viral they contain short stretches of lysine or arginine residues. These signals are recognized proteins. Usually by the importin super-family （importin α and β） proteins that mediate the transport across the nuclear envelope through Ran-GTP In contrast, only one class of the leucine-rich nuclear export signal （NES） on viral proteins is known at present. Chromosome region maintenance 1 （CRM1） protein mediates nuclear export of hundreds of viral proteins through the recognition of the leucine-rich NES.
