The precise role played by HIV-specific cytotoxic T lymphocytes (CTL) in HIV infection remains controversial. Despite strong CTL responses being generated during the asymptomatic phase, the virus persists and AIDS ultimately develops. It has been argued that the virus is so variable, and the virus turnover so great that escape from CTL recognition would occur continually, but so far there is limited evidence for CTL escape. The opposing argument is that evidence for CTL escape is present but hard to find because multiple anti-HIV immune responses are acting simultaneously during the asymptomatic phase of infection. We describe six donors who make a strong CTL response to an immunodominant HLA-B27-restricted epitope. In the two donors who progressed to AIDS, CTL escape to fixation by the same mutation was observed, but only after 9-12 years of epitope stability. CTL escape may play an important role in the pathogenesis of HIV infection.
To establish the distribution of blood lipid concentrations and the prevalences of other risk factors for cardiovascular disease in Britain 12 092 men and women aged 25-59 in Glasgow, Leicester, London, and Oxford were studied. Subjects were selected by opportunistic case finding, in which patients consulting their general practitioner for any reason were offered a health check by appointment, or random selection from age-sex registers, in which an invitation for a health check was posted. The overall rate of response was 73%, being 91-94% by opportunistic case finding and 36-63% by random selection. At the health check subjects answered a brief questionnaire about risk factors for cardiovascular disease, and their height, weight, and blood pressure were recorded; a blood sample was taken for measuring plasma concentrations of cholesterol, triglyceride, high density lipoprotein cholesterol, and glucose.The mean cholesterol concentrations were 5-9 (SD 1.2) and 5-8 (1-2) mmol/l in men and women, respectively. In London the mean value was 5 5 (1-2) mmol/l for both men and women and was significantly lower than mean values in the three other centres, among which there were no significant differences. In men and women aged 25-29 concentrations were similar but they increased in men until the age of 45-49, after which they showed no further increase; in women concentrations did not increase until the age of 40-44 and by the age of 50-59 values were higher thair in men. Mean triglyceride concentrations were significantly higher in men than in women (1.8 (1-4) v 1-3 (0.9) mmol/l, respectively), and trends with age were similar to those for cholesterol concentrations, except that at no age were values higher in women than in men. Mean triglyceride values overall were higher in Glasgow and London than in Oxford and Leicester. Body mass index was higher in Glasgow and London than in the other two centres and correlated with systolic and diastolic blood pressures and triglyceride concentration. In addition, subjects in Glasgow smoked significantly more than those in the other centres. These observations could contribute to the higher rate of coronary heart disease in Glasgow. Plasma lipid concentrations and the prevalences of other risk factors for
A conformationally-biased, agonist of human C5a65–74 (EP67) was assessed for its adjuvant activities in vitro and in vivo. EP67 induced the release of the inflammatory (Th1) type cytokines from C5a receptor (CD88)-bearing antigen presenting cells (APC). Serum from mice immunized with EP67-ovalbumin (OVA) contained high OVA-specific antibody (Ab) titers [IgG1, IgG2a (IGg2c), IgG2b]. Mice receiving OVA alone produced only IgG1 Abs, indicating the ability of EP67 to induce a Th1-like antibody (A)b class switch. Spleen cell cultures from wild type mice but not CD88−/− mice showed an enhanced OVA-specific proliferative response in vitro. These results indicate the ability of EP67 to drive a Th1-mediated immune response and its potential use as a unique adjuvant
-Rathlou NH. Lithium clearance and renal tubular sodium handling during acute and longterm nifedipine treatment in essential hypertension. Clin Sci 1988;75:609-13 Results-2931 Patients (74% of those screened) had a total cholesterol concentration of <6-5 mmol/l. If the triglyceride concentration had not been measured in these patients isolated hypertriglyceridaemia (:2-3mmol/l) would have remained undetected in 185. Among these 185 patients, however, 123 were overweight or obese and only 18 (0-6% of those screened) had an increased risk associated with both a raised triglyceride concentration (>2-3 mmol/l) and a low HDL cholesterol concentration (<0-9 mmol/l). Conversely, in the 790 patients with predominant hypercholesterolaemia (cholesterol concentration -6-5 mmol/l and triglyceride concentration <2-3 mmol/l) measurement of HDL cholesterol concentration showed that 348 (9% of those screened) had only a moderately increased risk with a ratio oftotal to HDL cholesterol of <4-5
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