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Biomedical subjects
Publications and source records attributed to D Salmon.
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Previous observations suggested a concomitant relationship between the release of the variant surface glycoprotein (VSG) and the activation of adenylate cyclase in the bloodstream form of the parasitic protozoan Trypanosoma brucei. In order to evaluate this hypothesis, adenylate cyclase activity was measured in live trypanosomes subjected to different treatments known to induce the shedding of the VSG coat, namely low pH and trypsin digestion. In both cases adenylate cyclase activation occurred in parallel with the release of the VSG. The latter was found to be mediated by the glycosylphosphatidylinositol-specific phospholipase C that cleaves the glycosylphosphatidylinositol anchor of the protein (VSG lipase). Furthermore, both adenylate cyclase and VSG release were activated by the incubation of trypanosomes with specific inhibitors of protein kinase C, suggesting a repressive role for protein kinase C on both VSG lipase and adenylate cyclase activities. Significantly, in mutant trypanosomes lacking VSG lipase, adenylate cyclase was activated under conditions where VSG release did not occur. Moreover,VSG release was also found to occur in the absence of activation of the cyclase, as observed in the presence of low concentration of the thiol modifying reagent p-chloromercuriphenylsulfonic acid. These observations provide the first demonstration that release of the VSG in response to cellular stress is mediated by the VSG lipase and that while both release of the VSG and activation of adenylate cyclase occur in response to the same stimuli they are not obligatorily coupled.
Cytomegalovirus multifocal neuropathies (CMV-MN) in patients with AIDS are much less frequent than meningoradiculitis. We report here the case of a patient with AIDS hospitalized because of severe motor weakness and paralyzed left true vocal cord (PVC), related to a multifocal neuropathy. CSF analysis was normal with a negative PCR for CMV, but neuromuscular biopsy showed typical CMV inclusions. The patient's condition improved with high dose foscarnet therapy, followed by a combination of ganciclovir plus foscarnet, during a five-month follow-up period. Twenty three case reports of CMV-MN have been published in the literature, only 2 of them presenting with a PVC. Extraneurological CMV involvement was usually documented. PCR for CMV in CSF was most often positive. However CMV inclusions were not frequently observed. The patients were usually improved under therapy with usually ganciclovir but relapse was observed in fifty percent within 3 to 6 months despite secondary prophylaxis.
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We report the case of a 23 year-old Caribbean woman with sarcoidosis who developed specific skin ulcerations. Ulcerative lesions in sarcoidosis are distinctly unusual, generally multiple, painless, with preponderant location on the lower limbs. The diagnosis is difficult. The pathogenesis is discussed. The most successful therapy is hydrochloroquine with corticosteroids.
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In T. brucei, a transferrin-binding protein has been found to share sequence homology with pESAG-7 and -6, the products of two related genes present in the VSG gene polycistronic transcription unit. When expressed in Xenopus oocytes, they appear as N-glycosylated proteins secreted in the medium (pESAG-7) and GPI anchored to the membrane (pESAG-6). These proteins are able to homo- or heterodimerize, probably through association in the same orientation. Only heterodimers can bind Tf, possibly two molecules per dimer. A comparison of Tf binding to pESAG-7/6-expressing oocytes and trypanosomes suggests that pESAG-7/6 is the Tf receptor of the parasite. In trypanosomes, the majority of pESAG-7/6 is released from the membrane and associates, together with Tf, with a glycosylated matrix present in the lumen of the flagellar pocket. Both pESAG-7/6 and Tf are internalized via coated pits and vesicles. These observations suggest a novel mode of Tf binding and uptake in trypanosomes.
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Following contamination with HIV, the majority of patients develop AIDS after several years (65% at 12 years), although a small percentage remain asymptomatic for a long time. The clinical manifestations of HIV infection are currently classified into 4 stages: primo-infection (stage I), asymptomatic phase (stage II), persistent generalised lymphadenopathy (stage III), other manifestations (stage IV), among which the following substages are distinguished: systemic signs (IVA), HIV-specific neurological signs (IVB), opportunistic or minor infections (IVA), HIV-specific neurological signs (IVB), opportunistic or minor infections (IVC), cancers (IVD) and other manifestations (IVE). The principal manifestations of AIDS appear when the CD4 count falls to below 200/mm3 and consist of opportunistic infections, primarily oesophageal candidiasis, pneumocystosis and toxoplasmosis. The management of patients with a combination of prophylaxis against opportunistic infections and antiviral treatment has significantly delayed the onset of AIDS, but has had little effect on the course of AIDS, which remains about 18 months.
PURPOSE: To evaluate the long-term efficacy and safety of inhaled pentamidine as primary prophylaxis against Pneumocystis carinii pneumonia (PCP) in patients infected with human immunodeficiency virus (HIV). PATIENTS: Two hundred thirty-two HIV-infected patients with a CD4 cell count below 20% of the total lymphocyte count were given aerosolized pentamidine once every 4 weeks for more than 3 months. Pentamidine aerosols were administered at the hospital under medical supervision. Prevention of bronchospasm was carried out using inhaled salbutamol. RESULTS: Mean duration of prophylaxis was 15.9 months. Eleven patients (4.7%; [95% confidence interval 2% to 7.4%]) developed PCP. Probability to remain free of PCP is 95.6% at 12 months, 94% at 18 months, and 88% at 24 months. Mean delay between the onset of the prophylaxis and the occurrence of PCP for the 11 patients was 12.9 months (range: 4 to 26 months). No major side effect was observed, and minor side effects (cough, acute dyspnea) were infrequent. CONCLUSION: The efficacy and tolerance of aerosolized pentamidine as shown in our study support its use as primary prophylaxis against P. carinii in HIV-infected patients.
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Clinical course of HIV infection was studied among 156 intravenous drug users (IVDU). Mean follow up was 22.7 months. Characteristics of HIV infection in IVDU were frequent oral candidiasis and bacterial infections (BI), more frequent progression to AIDS after a second BI, rapid decline of CD4+ in a group of current IVDU. Progression to AIDS was 14.5% per year, not different among current and former IVDU. Twenty five IVDU died.
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