Monoclonal antibodies to mammalian heat shock proteins impair mouse embryo development in vitro

Two-cell mouse embryos (B6D2F1) were cultured in the presence or absence of 100 microg/ml monoclonal antibodies specific for the mammalian 60 kDa (HSP60), 70 kDa (HSP70) and 90 kDa (HSP90) heat shock proteins. Embryo development was evaluated after 3, 5 and 7 days in culture by determining the number of blastocysts, hatched blastocysts and outgrown trophoblasts at the successive time points. At day 3, only 29% (22/75) of the embryos cultured with anti-HSP60 antibody developed to the blastocyst stage (P < 0.0001) as compared to 67% (31/46) of the embryos cultured with anti-HSP70, 72% (43/60) cultured with anti-HSP90, and 79% (49/62) in medium plus mouse IgG1. By day 5, hatched embryos were present in 28% (13/ 46) of the cultures containing anti-HSP70 (P < 0.0001), as opposed to 57% (34/60) containing anti-HSP90 and 73% (45/62) containing IgG1. At day 7, outgrown trophoblasts were observed in 9% (4/46) of cultures containing anti-HSP70 (P < 0.0001), 45% (27/60) containing anti-HSP90 (P < 0.01) and 66% (41/62) cultured in medium plus IgG1. Antibodies to different heat shock proteins exerted a detrimental effect on mouse embryo development at unique development stages. Immune sensitization to heat shock proteins may be a cause of reproductive failure.      

Tonabersat, a gap-junction modulator: efficacy and safety in two randomized, placebo-controlled, dose-ranging studies of acute migraine

Tonabersat is a novel benzopyran derivative that blocks the cortical spreading depression proposed to be associated with migraine attacks. The ability of single oral doses of 15, 25, 40 and 80 mg of tonabersat to relieve the symptoms of moderate to severe migraine was evaluated in 859 migraineurs enrolled in two dose-ranging, double-blind, randomized, placebo-controlled, parallel-group trials, one international and the other North American. In the international study, significantly more patients given tonabersat than given placebo experienced relief of headache pain at 2 h (15 mg, 36.8%; 40 mg, 40.7%), the principal efficacy variable, and at 4 h (40 mg, 63.0%) and complete abolition of headache at 4 h (40 mg, 34.3%). None of the primary or secondary efficacy variables indicated significant differences between tonabersat and placebo in the North American study. Tonabersat was generally well tolerated, with dizziness and nausea the most common side-effects. Serious adverse events were uncommon, and no patient withdrew from either study because of adverse events. These results suggest a possible interplay between tonabersat pharmacokinetics (the relatively long time required to reach maximum plasma concentrations) and patient characteristics (previous triptan exposure) in the management of acute migraine attacks. Based on the pharmacokinetics and actions on cortical spreading depression, tonabersat may have potential value in migraine prophylaxis.     

乙型肝炎病毒感染

急性乙型肝炎感染乙型肝炎病毒(HBV)是非细胞致病性的。肝脏的损害是感染的肝细胞免疫溶解所致。在炎性浸润性细胞中,有自然杀伤(NK)和细胞毒性T细胞。在肝细胞表面有、病毒抗原。这些抗原协同Ⅰ类主要组织相容复合体(MHC)蛋白质,使这些细胞成为细胞毒性T细胞溶解的靶细胞。对慢性HBV感染病人的研究提示,乙型肝炎核心(C)和e抗原是免疫系统主要的靶抗原。肝细胞通常只表达微量Ⅰ类MHC糖蛋白,但在急性HBV感染早期,随着干扰素     

Recombinant vaccinia viruses for the characterization of Plasmodium falciparum-specific cytotoxic T lymphocytes: recognition of processed antigen despite limited re-stimulation efficacy

Cytotoxic T lymphocytes (CTL) have been implicated in immunity to Plasmodium falciparum infection and disease. We have previously described the use of peptides to define malaria-specific CTL epitopes. To determine whether these peptide epitopes are processed intracellularly from the whole antigen we have developed recombinant vaccinia viruses (rVV) expressing three malaria antigens: thrombospondin-related adhesive protein (TRAP), Pfs16 and the C- terminal half of liver-stage antigen (LSA)-1. Target cells infected with recombinant viruses were lysed by malaria-specific CTL from semi- immune African donors. We also tested the ability of cells infected with these recombinant vaccinia viruses to re-stimulate malaria- specific CTL in peripheral blood lymphocytes from malaria immune adults. Two other pox virus recombinants, NYVAC, an attenuated vaccinia virus, and ALVAC, a canarypox virus, both expressing malaria antigens were also evaluated for their ability to stimulate malaria-specific CTL in contrast to peptide, none of these viruses successfully re- stimulated CTL from the peripheral blood lymphocytes of semi-immune donors. The ability of human CTL from naturally exposed individuals to recognize processed antigen supports the relevance of these cells in protective immunity to malaria.      

Cross sectional study of use of alternative medicines in Chinese cancer patients

The aim of this study was to ascertain the prevalence of alternative medicine consumption in Chinese cancer patients on active conventional treatment. A cross sectional survey of 100 consecutive advanced cancer patients admitted to a cancer clinical trial referral unit were personally interviewed by their assigned oncology research nurse using a specially designed questionnaire. The results showed that 64% of our patients used indigenous Chinese medication. In all age groups except the over-70s (P = 0.043), > 50% took such medication, more female (76%) than male (57.6%) patients (P = 0.323). Patients of all educational levels (P = 0.062) and religious backgrounds (P = 0.08) consumed alternative medicines. Duration of alternative medication consumption was less than three months in 50% of patients, with costs between US$40 and 2000/month for 70% of patients. Reasons cited for alternative medication consumption was hope that it might be of some benefit to their well being or disease control, and maybe even result in a miracle cure. Sources of advice on medication were mostly from strangers (by word of mouth), family, friends, the media, and infrequently from qualified professional Chinese doctors. Reasons for discontinuing such treatment were mostly given as lack of positive effect. In conclusion, Chinese cancer patients, willingly, rampantly and non-selectively seek out and consume alternative medications, with almost total ignorance of the medication consumed, oblivious to any potential side effects, and with little subjective benefit.