Transmembrane signalling associated with ganglioside-induced CD4 modulation

Ganglioside (GM1) treatment of CD4+ human CEM lymphoma cells stimulated transient phosphoinositide (PI) breakdown, production of inositol phosphates (IP), protein phosphorylation and rapid decrease of CD4 surface expression. A comparison between the actions of GM1 and other agents that affect these signal transduction pathways demonstrated a distinct mechanism for GM1-induced decrease of CD4. GM1 stimulated both phospholipase C activity and protein phosphorylation but had no effect on either cellular cAMP levels or tyrosine kinase activity. Phorbol myristate acetate (PMA) stimulated protein phosphorylation and caused a significant decrease in surface display of CD4. Both of these processes were blocked by pretreating cells with the protein kinase C (PKC) inhibitor H7. These results demonstrate that GM1 stimulates PI turnover and induces a rapid decrease of CD4 surface expression by processes that do not activate adenylate cyclase or tyrosine kinase. They further demonstrate that the mechanism for GM1-induced decrease of CD4 is distinct from the CD4 internalization processes mediated by PKC activity.     

Ontogeny and thymus-dependence of T cell surface antigens in Xenopus : flow cytometric studies on monoclonal antibody-stained thymus and spleen

Recently generated anti-Xenopus T cell monoclonal antibodies (mAbs) to the 120 kDA XTLA-1 determinant and against the putative CD5 and CD8 homologues, together with anti-IgM and anti-MHC class II mAbs, are used in dual colour flow cytometric experiments to characterize cell surface antigenic expression on lymphocytes in thymus and spleen of Xenopus laevis during larval and early adult life and also in metamorphosis-inhibited animals. Histological confirmation of T cell emergence early in larval ontogeny is supplied by cryostat sections stained for CD8. Five-day thymectomy i.e. prior to T-lineage cell differentiation in the thymus, abolishes T cell marker expression in the spleen for up to 1 year. Moreover, late larval (20 days) or early adult (3 months) thymectomy (i.e. removal after peripheralization of T cells has occurred) also leads to severe depletion of mAb-defined T cells in the spleen.     

Cardiac tamponade.

Cardiac tamponade is a cardiological emergency requiring prompt treatment in order to avoid a fatal outcome. It can complicate a number of medical conditions and it is important, therefore, that all practitioners are aware of its presentation, diagnosis and management. These are outlined. We suggest that, with certain specific and important exceptions, percutaneous catheter pericardiocentesis is to be recommended in the management of cardiac tamponade. We include a review of 51 consecutive cases treated at our own institution. Catheter pericardiocentesis was successful in 49 (96%) cases and 36 (80%) patients did not require any further intervention. There were no major and only two minor complications which required no additional treatment. We review previous literature concerning percutaneous pericardiocentesis. Using recommended procedures, pericardiocentesis is successful in 90-100% of cases and major complications are rare.     

Effects of age and age-related hearing loss on the neural representation of speech cues.

OBJECTIVE: To examine the effects of aging and age-related hearing loss on the perception and neural representation of a time-varying speech cue. METHODS: P1, N1 and P2 cortical responses were recorded from younger and older normal-hearing adults, as well as older adults with age-related hearing loss. Synthetic speech tokens representing 10 ms increments along a /ba/-/pa/ voice-onset-time (VOT) continuum were used to evoke the responses. Each participant's ability to discriminate the speech tokens was also assessed. RESULTS: Compared with younger participants, older adults with and without hearing loss had more difficulty discriminating 10 ms VOT contrasts. In addition, both older groups elicited abnormal neural response patterns. There were no significant age-related findings for P1 latency; however, N1 latencies were prolonged for both older groups in response to stimuli with increased VOT durations. Also, P2 latencies were delayed for both older groups. The presence of age-related hearing loss resulted in a significant increase in N1 amplitude in response to voiceless stimuli. CONCLUSIONS: Aging and age-related hearing loss alter temporal response properties in the central auditory system. Because both older groups had difficulty discriminating these same speech stimuli, we conclude that some of the perceptual difficulties described by older adults might be due to age-related changes regulating excitatory and inhibitory processes. SIGNIFICANCE: Some of the speech understanding difficulties expressed by elderly adults may be related to impaired temporal precision in the aging auditory system. This might explain why older adults frequently complain that wearing a hearing aid makes speech louder, but does not necessarily improve their ability to understand speech.     

Discordant repeat size and phenotype in Kennedy syndrome

Previous reports in the literature have described correlation of increasing repeat length with severity of the phenotype, in Kennedy syndrome. We describe male siblings with different repeat lengths, with lack of expression of the phenotype in the sibling with the longer repeat length. The phenotype was identical to motor neurone disease. There is variability of expression in Kennedy syndrome and repeat length even in siblings cannot be taken as a conclusive indicator of severity. CAG repeat length cannot be used to predict the natural history of Kennedy disease. The diagnosis of Kennedy syndrome should be considered in male patients presenting with atypical motor neurone disease.     

Search for retrovirus in the chronic fatigue syndrome.

AIM: To examine peripheral blood and skeletal muscle from patients with chronic fatigue syndrome for exogenous retrovirus. METHODS: Blood samples from 30 patients and muscle biopsy specimens of 15 patients were examined for retroviral sequences by DNA extraction, polymerase chain reaction (PCR), and Southern blotting hybridisation. Sera were examined for human foamy virus by western immunoblotting and indirect immunofluorescence techniques. RESULTS: No differences between the patient and control populations was found for any of the PCR primer sets used (gag, pol, env, and tax regions of HTLV I/II). An endogenous gag band was observed in both the patient and control groups. All sera were negative for antibody to human foamy virus. CONCLUSION: The results indicate that there is no evidence of retroviral involvement in the chronic fatigue syndrome.     

Chloroquine attenuates hemorrhagic shock-induced immunosuppression and decreases susceptibility to sepsis.

Hemorrhagic shock causes a severe suppression of cellular immunity and an increased susceptibility to sepsis that may be due to increased release of prostaglandin E2 by macrophages. Since chloroquine inhibits the secretion of prostaglandin E2 by macrophages in vitro, the effects of chloroquine administration in vivo following hemorrhagic shock on macrophage prostaglandin E2 secretion and on depressed cellular immunity were examined. Inbred C3H/HeN male mice, aged 6 to 8 weeks, were bled to a mean blood pressure of 35 mm Hg, which was maintained for 60 minutes, and adequately, resuscitated. Mice then received intramuscular injections of either saline (vehicle) or chloroquine (10 mg/kg of body weight). Prostaglandin E2 in macrophage supernatants (radioimmunoassay) concanavalin A-dependent splenocyte proliferation, and interleukin 2 in splenocyte supernatants (CTLL 20 interleukin 2-dependent proliferation) were determined 2 or 24 hours later. Hemorrhage caused a significant decrease of splenocyte proliferation (47%) and interleukin 2 release (49%) at 24 hours, while prostaglandin E2 secretion from macrophages was elevated at 2 hours. Chloroquine treatment attenuated depression of splenocyte functions and reduced prostaglandin E2 release. Furthermore, chloroquine treatment decreased the mortality of septic mice after hemorrhage to levels comparable with those of sham-operated mice. Thus, chloroquine may be a useful adjunct in the clinical setting for the treatment of shock-induced immunodepression and increased susceptibility to sepsis following hemorrhage.