B cell-intrinsic MyD88 signaling prevents the lethal dissemination of commensal bacteria during colonic damage

The Toll-like receptor adaptor protein MyD88 is essential for the regulation of intestinal homeostasis in mammals. In this study, we determined that Myd88-deficient mice are susceptible to colonic damage that is induced by dextran sulfate sodium (DSS) administration resulting from uncontrolled dissemination of intestinal commensal bacteria. The DSS-induced mortality of Myd88-deficient mice was completely prevented by antibiotic treatment to deplete commensal bacteria. By using cell type-specific Myd88-deficient mice, we established that B cell-intrinsic MyD88 signaling plays a central role in the resistance to DSS-induced colonic damage via the production of IgM and complement-mediated control of intestinal bacteria. Our results indicate that the lack of intact MyD88 signaling in B cells, coupled with impaired epithelial integrity, enables commensal bacteria to function as highly pathogenic organisms, causing rapid host death.     

The survival motor neuron protein in spinal muscular atrophy

The 38 kDa survival motor neuron (SMN) protein is encoded by two ubiquitously expressed genes: telomeric SMN (SMN(T)) and centromeric SMN (SMN(C)). Mutations in SMN(T), but not SMN(C), cause proximal spinal muscular atrophy (SMA), an autosomal recessive disorder that results in loss of motor neurons. SMN is found in the cytoplasm and nucleus. The nuclear form is located in structures termed gems. Using a panel of anti-SMN antibodies, we demonstrate that the SMN protein is expressed from both the SMN(T) and SMN(C) genes. Western blot analysis of fibroblasts from SMA patients with various clinical severities of SMA showed a moderate reduction in the amount of SMN protein, particularly in type I (most severe) patients. Immunocytochemical analysis of SMA patient fibroblasts indicates a significant reduction in the number of gems in type I SMA patients and a correlation of the number of gems with clinical severity. This correlation to phenotype using primary fibroblasts may serve as a useful diagnostic tool in an easily accessible tissue. SMN is expressed at high levels in brain, kidney and liver, moderate levels in skeletal and cardiac muscle, and low levels in fibroblasts and lymphocytes. In SMA patients, the SMN level was moderately reduced in muscle and lymphoblasts. In contrast, SMN was expressed at high levels in spinal cord from normals and non- SMA disease controls, but was reduced 100-fold in spinal cord from type I patients. The marked reduction of SMN in type I SMA spinal cords is consistent with the features of this motor neuron disease. We suggest that disruption of SMN(T) in type I patients results in loss of SMN from motor neurons, resulting in the degeneration of these neurons.      

Malaysian Dialysis and Transplant Registry Report

SUMMARY: This report summarizes data for dialysis and transplant patients up to the end of 1995. We estimate coverage to be about 30% of dialysis patients and near complete ascertainment of transplant patients. On the 31 December 1995, there were 2224 patients on renal replacement therapy (RRT), comprising 50% on haemodialysis (HD), 12% on continuous ambulatory peritoneal dialysis (CAPD) and 38% with functioning transplants. the prevalence rate for dialysis was 68 per million population (p.m.p.) and that of transplant 42 p.m.p. the new dialysis acceptance rate was 15 p.m.p. and transplant 5 p.m.p. Forty-seven per cent of new patients had unknown primary renal disease and 30% was due to non-insulin dependent diabetes mellitus. Mean age of prevalent HD patients was 42 years, CAPD 46 years and 34 years for transplant. Patient survival on CAPD was 85% at 1 year and for HD was 88%. One year transplant patient survival was 94% and graft survival 91%.