Dystrobrevin deficiency at the sarcolemma of patients with muscular dystrophy

Mutations in the genes encoding dystrophin or dystrophin-associated proteins are responsible for Duchenne muscular dystrophy or various forms of limb-girdle muscular dystrophies respectively. We have recently cloned the gene for the murine 87 kDa postsynaptic protein dystrobrevin, a dystrophin-associated protein. Anti-dystrobrevin antibodies stain the sarcolemma in normal skeletal muscle indicating that dystrobrevin co-localises with dystrophin and the dystrophin- associated protein complex. By contrast, dystrobrevin membrane staining is severely reduced in muscles of Duchenne muscular dystrophy patients, consistent with dystrobrevin being a dystrophin-associated protein. Interestingly, dystrobrevin staining at the sarcolemma is dramatically reduced in patients with limb-girdle muscular dystrophy arising from the loss of one or all of the sarcoglycan components. Normal dystrobrevin staining is observed in patients with other forms of limb- girdle muscular dystrophy where dystrophin and the rest of the dystrophin-associated protein complex are normally expressed and in other neuromuscular disorders. Our results show that dystrobrevin- deficiency is a generic feature of dystrophies linked to dystrophin and the dystrophin-associated proteins. This is the first indication that a cytoplasmic component of the dystrophin-associated protein complex may be involved in the pathogenesis of limb-girdle muscular dystrophy.      

On duodenal stump leakage caused by adult human Taenia

To the editor： Shao Xinxin and colleagues recently described a case of duodenal stump leakage caused by Taenia saginata （T.saginata）. Apparently, they did not identify the discharged adult tapeworm recovered after the treatment neither morphologically nor molecularly. The authors concluded that the species responsible for the symptoms was T. saginata based on the fact that the patient mentioned that he had been infected by T. saginata two years ago.     

Prevalence of Candida co-infection in patients with pulmonary tuberculosis

Background

Candida species are emerging as a potentially pathogenic fungus in patients with broncho-pulmonary diseases. The synergistic growth promoting association of Candida and Mycobacterium tuberculosis has raised increased concern for studying the various Candida spp . and its significance in pulmonary tuberculosis patients during current years.

Aims

This study was undertaken with the objective of discovering the prevalence of co-infection caused by different Candida species in patients with pulmonary tuberculosis.

Method

A total of 75 patients with pulmonary tuberculosis diagnosed by sputum Ziehl-Neelsen staining were included in the study. Candida co-infection was confirmed using the Kahanpaa et al. criteria. Candida species were identified using gram stain morphology, germ tube formation, morphology on cornmeal agar with Tween-80, sugar fermentation tests and HiCrome Candida Agar.

Results

Candida co-infection was observed in 30 (40%) of patients with pulmonary tuberculosis. Candida albicans was the most common isolate observed in 50% of the patients with co-infection, followed by C. tropicalis (20%) and C. glabrata (20%). Candida co-infection was found in 62.5% of female patients, while it was observed in only 29.4% of the male patients (P value 0.0133). Mean ± SD age of the patients with C. glabrata infection was 65.83 ± 3.19, while the mean ± SD age of the patients with other Candida infections was 43.25 ± 20.44 (P value 0.0138).

Conclusion

Many patients with pulmonary tuberculosis have co-infection with Candida spp. The prevalence of non-albicans Candida species is increasing and may be associated with inadequate response to anti-tubercular drugs. C. glabrata infection has a strong association with old age.     

Effects of recombinant human erythropoietin on megakaryocytes and on platelet production in the rat

The contention that erythropoietin (Epo) affects platelet production was investigated in the rat with recombinant human Epo (rHuEpo). In normal rats, Epo caused a dose-dependent increase in both reticulocyte and platelet numbers, the reticulocyte response preceding that of platelets. Withdrawal of Epo resulted in reticulocytes and platelets returning to control levels. [75Se]-selenomethionine incorporation into platelets was also enhanced in response to Epo. Chronic daily administration of rHuEpo resulted in steady state erythrocyte levels after 12 to 14 days, which were elevated 20% above controls. Attainment of this steady state was associated with both reticulocytes and platelets returning to control levels despite continued administration of Epo, an effect not associated with a change in the half-life of circulating Epo. In polycythemic rats a platelet response was observed before an effect on reticulocytes. Erythropoietin caused a 2.4-fold increase in the frequency of small acetylcholinesterase-positive cells within 24 hours, and increased the mean megakaryocyte diameter within 48 hours. Furthermore, the [3H]-thymidine labeling index of megakaryocytes from rats treated for 24 hours with rHuEpo was increased for all stages of megakaryocyte maturation. These results support the proposal of an effect of Epo on rat megakaryocytes causing increased platelet production.     

Partial protein S gene deletion in a family with hereditary thrombophilia

Familial thrombophilia, the hereditary predisposition to venous thromboembolic disease, is associated with a protein S deficiency in approximately 8% of the cases. Laboratory measurements of total protein S antigen in affected families have indicated that heterozygotes, ie, individuals carrying both a normal and a defective protein S gene, are severely at risk of developing venous thrombosis at a young age. The recent isolation of protein S cDNA has enabled us to start a search for genetic defects in the protein S gene of heterozygotes. Using Southern blotting on probands of six unrelated families with hereditary protein S deficiency, one proband was found to have a grossly abnormal gene pattern. The abnormality appears to involve at least the deletion of the middle portion of the protein S coding sequence. Family analysis showed that the defect cosegregates with the protein S deficiency. These data agree with the notion that hereditary thrombophilia associated with protein S deficiency is indeed directly the result of a defect in the protein S gene.