Calcium-activated proteolysis of intracellular domains in the cell adhesion molecules NCAM and N-cadherin.

One of the consequences of increased intracellular calcium in response to a variety of physiological stimuli is the calcium activation of cytosolic proteases. Unlike lysosomal proteases with broad specificity, these calcium-activated neutral proteases show limited proteolysis of a restricted set of substrate proteins suggesting they may play a regulatory role in cellular physiology. In this study we show that the neural cell adhesion molecules NCAM-180 and N-cadherin are substrates for such endogenous calcium-activated neutral proteases. In contrast, a third neural cell adhesion molecule G4/L1 was not susceptible to calcium-activated proteolysis. The threshold for activation of NCAM and N-cadherin proteolysis is in the micromolar range of calcium suggesting that NCAM and N-cadherin are substrates for a mu-type calpain (calpain I). The site recognized by this protease is within intracellular domains of NCAM-180 and N-cadherin which are important for their interaction with cytoskeletal components. These results suggest that calcium-activated proteolysis at these sites in vivo could disrupt the linkage between extracellular ligand binding to these adhesion molecules and the normal intracellular effectors of such extracellular binding events.     

Intracellular Ca2+ suppressed a transient potassium current in hippocampal neurons

The effects of intracellular Ca2+ (Ca2+i) on K+ currents in hippocampal cells were examined using acutely isolated cells obtained from adult guinea pigs. Whole-cell voltage-clamp recordings were carried out in a configuration that allowed a continuous perfusion of the intracellular medium. Recording media were made to block inward currents and allowed selective activation of K(+)-dependent outward currents. Voltage-dependent outward currents consisted of an initial rapidly decaying component followed by a sustained component. The time constant of decay of the transient current was about 25 msec, and previous studies (Numann et al., 1987) showed that the kinetic and pharmacological properties of this current closely resembled the A current recorded in invertebrate neurons (Connor and Stevens, 1971; Thompson, 1982). Intracellular perfusion of hippocampal cells with a solution containing elevated Ca2+ (about 4.5 x 10(-4) M) elicited outward currents at the holding potential (-45 to -55 mV) and produced changes in voltage-dependent K+ currents. The transient outward current (IA) activated by depolarization was suppressed with increases in Ca2+i. Delayed, sustained K+ currents were greatly potentiated. Data also showed that, among the 3 effects elicited by Ca2+i, suppression of IA was most sensitive to Ca2+i elevation. Previous results (Numann et al., 1987) showed that IA had a lower threshold (about -45 mV) than sustained currents (about -40 mV). By using low levels of depolarization (-40 mV), IA can be selectively activated, and the suppressive effect of Ca2+i on IA was confirmed on the kinetically isolated IA.(ABSTRACT TRUNCATED AT 250 WORDS)     

Treatment of ulcerative colitis by traditional Chinese medicine and dynamic study of immune functions

The effect of the traditional Chinese medicinal herbs enema and enteric-coated capsules in the treatment of ulcerative colitis (UC) were compared in 260 cases. The immune complexes and the dynamic change of autoantibodies were monitored in 28 out of the 260 cases before and after treatment. The following results were observed. (1) There was no significant difference in the total effective rate between the enema group and the oral capsule group (93.3% and 87.5% respectively), but the recovery rates of purulent hemafecia, mucusfecia and erosion accompanying colitis, etc. in the former group were higher than those in the latter (P less than 0.01). (2) The circulating immune complexes were found 43 times above the normal range in 17 cases with positive rate 60.7%, and tended to decrease as the condition became better after treatment. Antinuclear antibodies were determined by the indirect fluorescent immune method and the indirect enzyme labelling method and the positive rates were 53.6% and 64.7% respectively, both being much higher than those in the controls (P less than 0.01).     

Chronic fatigue of the small enterprise workers participating in an occupational health checkup center in southern Taiwan

Purpose  There has been increasing interest in the occupational health of workers in small enterprises, especially in developing countries. This study examines the association between psychosocial job characteristics and fatigue, and attempts to identify risk factors for fatigue among workers of small enterprises in southern Taiwan. Methods  A structured questionnaire was administered to workers receiving regular health examinations between August 2005 and January 2006. The questionnaire collected demographic information and data on working conditions, personal health status and life styles. It also collected information on psychosocial job characteristics, fatigue and psychological distress using three instruments. Results  A total of 647 workers with mean age of 43.7 were completed. Probable fatigue was found in 34.6% of the sample. Fatigue was found by multiple logistic regressions to be associated with the lack of exercise, working in shifts, depression score and lack of social support at workplace. Conclusions  This study found associations between life style, psychosocial job characteristics and fatigue. Because the high prevalence of probable fatigue was found in such small enterprises, the authors suggest that a short interview with some quick questionnaires in health checkup for these small enterprise workers are helpful to early detect psychosocial and fatigue problems.     

Delta hepatitis virus infection in China

To assess the prevalence, epidemiological features and prognostic implications of hepatitis D (Delta) in Sichuan Province, The People's Republic of China, 649 sera (515 from HBsAg positive patients and 134 from HBsAg negative subjects) were tested by radioimmunoassay (RIA) for antibody to the hepatitis D virus (anti-HD). Forty-seven sera (7.2%) showed some degree of reactivity. Serial dilutions of these sera indicated that prozoning was not responsible for the equivocal results. Thirty-four of the 47 sera were submitted under code to a second laboratory for independent analysis. According to those results anti-HD antibodies were detected in four of these sera. The overall prevalence of anti-HD in the HBsAg positive patients therefore was 0.8% (4/515). On the basis of clinical, biochemical and histological data 427 HBsAg positive sera were further divided into acute Type B hepatitis, chronic Type B hepatitis, healthy carrier state and hepatocellular carcinoma (HCC) subgroups. Two of 65 (3.1%) anti-HD positive sera belonged to the acute Type B hepatitis group; one of 104 (0.9%), the chronic Type B hepatitis group and one of 246 (0.4%), the healthy carrier group. No antibody was detected in sera from 12 HBsAg positive HCC patients. All HBsAg negative patients were negative for anti-HD antibody. The results of this study indicate that despite a high prevalence of hepatitis B virus infection, positive serology for delta virus is uncommon in Sichuan Province, The People's Republic of China.