AIM： Pancreatic regenerating protein （reg Ⅰ ） stimulates pancreatic regeneration after pancreatectomy and is mitogenic to ductal and 13-cells. This suggests that reg Ⅰand its receptor may play a role in recovery ...AIM： Pancreatic regenerating protein （reg Ⅰ ） stimulates pancreatic regeneration after pancreatectomy and is mitogenic to ductal and 13-cells. This suggests that reg Ⅰand its receptor may play a role in recovery after pancreatic injury. We hypothesized that reg Ⅰ and its receptor are induced in acute pancreatitis. METHODS： Acute pancreatitis was induced in male Wistar rats by retrograde injection of 3% sodium taurocholate into the pancreatic duct. Pancreata and serum were collected 12, 24, and 36 hours after injection and from normal controls （4 rats/group）. Reg Ⅰ receptor mRNA, serum reg Ⅰ protein, and tissue reg Ⅰ protein levels were determined by Northern analysis, enzymelinked immunosorbent assay （ELISA）, and Western analysis, respectively. Immunohistochemistry was used to localize changes in reg Ⅰ and its receptor. RESULTS： Serum amylase levels and histology confirmed necrotizing pancreatitis in taurocholate treated rats. There was no statistically significant change in serum reg Ⅰ concentrations from controls. However, Western blot demonstrated increased tissue levels of reg Ⅰ at 24 and 36 h. This increase was localized primarily to the acinar cells and the ductal cells by immunohistochemistry. Northern blot demonstrated a significant increase in reg Ⅰ receptor mRNA expression with pancreatitis. Immunohistochemistry localized this increase to the ductal cells, islets, and acinar cells. CONCLUSION： Acute pancreatitis results in increased tissue reg Ⅰ protein levels localized to the acinar and ductal cells, and a parallel threefold induction of reg Ⅰ receptor in the ductal cells, islets, and acinar cells. These changes suggest that induction of reg Ⅰand its receptor may be important for recovery from acute pancreatitis.展开更多
To compare the clinical and pathological manifestations of patients with antineutrophil cytoplasmic autoantibodies (ANCA) directed against proteinas e 3 (anti PR3) or myeloperoxidase (anti MPO). Methods. One hundred a...To compare the clinical and pathological manifestations of patients with antineutrophil cytoplasmic autoantibodies (ANCA) directed against proteinas e 3 (anti PR3) or myeloperoxidase (anti MPO). Methods. One hundred and forty patients with ANCA were detected for anti PR3 a nd anti MPO by ELISA. The clinical features at presentation, histopathological characteristics and outcome of all patients who were tested positive for anti P R3 or anti MPO were analysed.Results. In anti PR3 group (n=21), 16 cases (76.2%) had systemic vasculitis , in which Wegener’s granulomatosis prevailed (13 cases, 61.9%). In anti MPO g roup (n=31), 19 cases (61.3%) were diagnosed as systemic vasculitis and 12 case s (38.7%) as microscopic angiitis. For vasculitic patients with anti PR3 and a nti MPO, the disease duration at diagnosis was 9.6±2.0m and 4.4±0.9m respecti vely, P< 0.05;vasculitis activity index (BVAS) and mean number of affected organ were 22.5±2.1, 5.0±0.4 and 25.1±1.7, 4.8±0.4 respectively, P >0.05;upper r espiratory tract, eye and joint involvements were 11(68.8%), 7(43.8%), 11(68.8 %) and 7(36.8%), 2(10.5%), 5(26.3%) respectively, P< 0.05.Although there was no statistical difference in renal involvement between these two groups, patien ts with serum creatine >500 μmol/L were more commonly seen in anti MPO group t han in anti PR3 group, which were 8(42.1%) and 2(12.5%) respectively, P< 0.05 . Ten relapses were seen in anti PR3 group and only 2 in anti MPO group, but t he acute mortality rate in anti MPO group (5/19, 27.4%) was much higher than t hat in anti PR3 group (1/16, 6.3%). Conclusions. Anti PR3 and anti MPO occurred mainly in systemic vasculitis. A large divergence was seen in the disease spectrum between patients with anti PR 3 and those with anti MPO. In particular, upper respiratory tract, eye and join t involvements, granuloma formation and relapse were more prominent in anti PR3 patients. By contrast, the anti MPO patients had a more acute disease onset, m ore rapid progressive renal involvement and a higher acute mortality rate.展开更多
Mammalian cells express four different plasma membrane Ca2+ ATPases.Two of them(PMCA1 and PMCA4) are expressed ubiquitously,and are considered housekeeping isoforms.Two(PMCA2 and PMCA4) have tissue restricted distribu...Mammalian cells express four different plasma membrane Ca2+ ATPases.Two of them(PMCA1 and PMCA4) are expressed ubiquitously,and are considered housekeeping isoforms.Two(PMCA2 and PMCA4) have tissue restricted distribution.They are abundantly expressed in the brain and in nervous tissue-derived cell types.The primary transcripts of all PMCAs undergo alternative splicing,generating a large number of additional isoforms.Splicing occurs at site A,in the N-terminal moiety of the pump,and at site C,within the C-terminal calmodulin binding domain:The pumps are canonical targets of calmodulin stimu-lation.The site C insertion leads to a truncation of the pump about 50 residues short of the original C-terminal.One of the pumps(PMCA2) has special properties:It displays high activity even in the absence of the natural activator calmodulin,and has a particularly complex pattern of alternative splicing at both sites A and C.A variant of the PMCA2 pump containing an insert at site A and truncated C-terminally is the resident isoform of the pump in the stereocilia of hair cells of the inner ear.It exports Ca2+to the endolymph that bathes the stereocilia less efficiently than the full length,non-inserted PMCA2 pump.The proper functioning of hair cells demands the precise maintenance of the Ca2+balance between hair cells and the endolymph. Disturbances in the balance affect the process of mechano-electrical transduction,which depends on the ability of the stereo-ciliar bundle to deflect in response to sound waves.The tip links that organize the bundle are formed by the Ca2+binding pro-tein cadherin 23 and by protocadherin 15:Disturbances of the Ca2+binding by cadherin 23 and/or of the ability of the PMCA2 variant of the stereocilia to export Ca2+to the endolymph generate hearing loss phenotypes.Such phenotypes have now been described in mice and humans.In some cases they are linked to mutations of both cadherin 23 and the PMCA2 pump,but in other cases they may be generated by mutations of particular severity in only one of the two proteins.The PMCA2 defect that leads to deafness has now been analyzed molecularly:It affects the long range,unstimulated ability of PMCA2 to export Ca2+.展开更多
基金Supported by NIDDK R01 DK.54511 (MZ), R01 DK060106 (BD) NIH Digestive Disease Research Core Center (DDRCC) grant P30 DK52574 (BD)
文摘AIM： Pancreatic regenerating protein （reg Ⅰ ） stimulates pancreatic regeneration after pancreatectomy and is mitogenic to ductal and 13-cells. This suggests that reg Ⅰand its receptor may play a role in recovery after pancreatic injury. We hypothesized that reg Ⅰ and its receptor are induced in acute pancreatitis. METHODS： Acute pancreatitis was induced in male Wistar rats by retrograde injection of 3% sodium taurocholate into the pancreatic duct. Pancreata and serum were collected 12, 24, and 36 hours after injection and from normal controls （4 rats/group）. Reg Ⅰ receptor mRNA, serum reg Ⅰ protein, and tissue reg Ⅰ protein levels were determined by Northern analysis, enzymelinked immunosorbent assay （ELISA）, and Western analysis, respectively. Immunohistochemistry was used to localize changes in reg Ⅰ and its receptor. RESULTS： Serum amylase levels and histology confirmed necrotizing pancreatitis in taurocholate treated rats. There was no statistically significant change in serum reg Ⅰ concentrations from controls. However, Western blot demonstrated increased tissue levels of reg Ⅰ at 24 and 36 h. This increase was localized primarily to the acinar cells and the ductal cells by immunohistochemistry. Northern blot demonstrated a significant increase in reg Ⅰ receptor mRNA expression with pancreatitis. Immunohistochemistry localized this increase to the ductal cells, islets, and acinar cells. CONCLUSION： Acute pancreatitis results in increased tissue reg Ⅰ protein levels localized to the acinar and ductal cells, and a parallel threefold induction of reg Ⅰ receptor in the ductal cells, islets, and acinar cells. These changes suggest that induction of reg Ⅰand its receptor may be important for recovery from acute pancreatitis.
文摘To compare the clinical and pathological manifestations of patients with antineutrophil cytoplasmic autoantibodies (ANCA) directed against proteinas e 3 (anti PR3) or myeloperoxidase (anti MPO). Methods. One hundred and forty patients with ANCA were detected for anti PR3 a nd anti MPO by ELISA. The clinical features at presentation, histopathological characteristics and outcome of all patients who were tested positive for anti P R3 or anti MPO were analysed.Results. In anti PR3 group (n=21), 16 cases (76.2%) had systemic vasculitis , in which Wegener’s granulomatosis prevailed (13 cases, 61.9%). In anti MPO g roup (n=31), 19 cases (61.3%) were diagnosed as systemic vasculitis and 12 case s (38.7%) as microscopic angiitis. For vasculitic patients with anti PR3 and a nti MPO, the disease duration at diagnosis was 9.6±2.0m and 4.4±0.9m respecti vely, P< 0.05;vasculitis activity index (BVAS) and mean number of affected organ were 22.5±2.1, 5.0±0.4 and 25.1±1.7, 4.8±0.4 respectively, P >0.05;upper r espiratory tract, eye and joint involvements were 11(68.8%), 7(43.8%), 11(68.8 %) and 7(36.8%), 2(10.5%), 5(26.3%) respectively, P< 0.05.Although there was no statistical difference in renal involvement between these two groups, patien ts with serum creatine >500 μmol/L were more commonly seen in anti MPO group t han in anti PR3 group, which were 8(42.1%) and 2(12.5%) respectively, P< 0.05 . Ten relapses were seen in anti PR3 group and only 2 in anti MPO group, but t he acute mortality rate in anti MPO group (5/19, 27.4%) was much higher than t hat in anti PR3 group (1/16, 6.3%). Conclusions. Anti PR3 and anti MPO occurred mainly in systemic vasculitis. A large divergence was seen in the disease spectrum between patients with anti PR 3 and those with anti MPO. In particular, upper respiratory tract, eye and join t involvements, granuloma formation and relapse were more prominent in anti PR3 patients. By contrast, the anti MPO patients had a more acute disease onset, m ore rapid progressive renal involvement and a higher acute mortality rate.
文摘Mammalian cells express four different plasma membrane Ca2+ ATPases.Two of them(PMCA1 and PMCA4) are expressed ubiquitously,and are considered housekeeping isoforms.Two(PMCA2 and PMCA4) have tissue restricted distribution.They are abundantly expressed in the brain and in nervous tissue-derived cell types.The primary transcripts of all PMCAs undergo alternative splicing,generating a large number of additional isoforms.Splicing occurs at site A,in the N-terminal moiety of the pump,and at site C,within the C-terminal calmodulin binding domain:The pumps are canonical targets of calmodulin stimu-lation.The site C insertion leads to a truncation of the pump about 50 residues short of the original C-terminal.One of the pumps(PMCA2) has special properties:It displays high activity even in the absence of the natural activator calmodulin,and has a particularly complex pattern of alternative splicing at both sites A and C.A variant of the PMCA2 pump containing an insert at site A and truncated C-terminally is the resident isoform of the pump in the stereocilia of hair cells of the inner ear.It exports Ca2+to the endolymph that bathes the stereocilia less efficiently than the full length,non-inserted PMCA2 pump.The proper functioning of hair cells demands the precise maintenance of the Ca2+balance between hair cells and the endolymph. Disturbances in the balance affect the process of mechano-electrical transduction,which depends on the ability of the stereo-ciliar bundle to deflect in response to sound waves.The tip links that organize the bundle are formed by the Ca2+binding pro-tein cadherin 23 and by protocadherin 15:Disturbances of the Ca2+binding by cadherin 23 and/or of the ability of the PMCA2 variant of the stereocilia to export Ca2+to the endolymph generate hearing loss phenotypes.Such phenotypes have now been described in mice and humans.In some cases they are linked to mutations of both cadherin 23 and the PMCA2 pump,but in other cases they may be generated by mutations of particular severity in only one of the two proteins.The PMCA2 defect that leads to deafness has now been analyzed molecularly:It affects the long range,unstimulated ability of PMCA2 to export Ca2+.
