Über Sexualhormone bei den Haustieren

Ohne ZusammenfassungNach einem Vortrag, gehalten am 26. Juni in der Medizinischen Gesellschaft Gießen.     

Comparative study on antibodies to human and bacterial 60 kDa heat shock proteins in a large cohort of patients with coronary heart disease and healthy subjects

BACKGROUND: Recent observations indicate an association between antibodies against mycobacterial heat shock protein (hsp65) and coronary heart disease (CHD). Previously, we reported on marked differences in antigen specificity and complement activating ability of anti-hsp65 antibodies and auto-antibodies against human heat shock protein, hsp60. Here, we investigated whether there are differences between antih-sp65 and anti-hsp60 antibodies in their association with CHD. DESIGN: We measured by ELISA the levels of antibodies to hsp65, hsp60 and E. coli-derived GroEL in three groups: Group I, 357 patients with severe CHD who underwent by-pass surgery; Group II, 67 patients with negative coronary angiography; Group III, 321 healthy blood donors. Antibodies against Helicobacter pylori were also measured by commercial ELISA. RESULTS: As calculated by multiple regression analysis, the levels of anti-hsp60 auto-antibodies were significantly higher in Group I compared to Group II (P = 0.007) or Group III (P < 0.0001). By contrast, although concentrations of anti-hsp65 and anti-GroEL antibodies in Group I were higher than in Group III, no significant differences between Group I and Group II were found. Antibodies to the two bacterial hsp strongly correlated to each other, but either did not correlate or weakly correlated to hsp60. In Group I, serum concentrations of anti-H.pylori antibodies significantly correlated with those of anti-hsp65 and anti-GroEL antibodies but they did not correlate with the anti-hsp60 antibodies. CONCLUSIONS: As to their clinical relevance, a remarkable difference become evident between antibodies to human hsp60 and antibodies against bacterial hsp in the extent of association with CHD. On the basis of these findings and some pertinent literature data, an alternative explanation for the association between high level of anti-hsp antibodies and atherosclerotic vascular diseases is raised.     

高压氧对脑缺血再灌注海马神经元Bcl-2和Bax蛋白表达的影响

目的观察高压氧(HBO)作用下脑缺血再灌注海马CA1区神经元Bcl-2和Bax蛋白表达的变化情况,进一步研讨高压氧治疗脑缺血再灌注损伤、减轻神经元凋亡从而发挥保护作用的机制。方法沙土鼠20只,采用随机数字法将实验动物分为正常对照组、缺血组、0.15MPaHBO治疗组、0.25MPaHBO治疗组,0.25MPa压力空气(hyperbaricair,HBA)对照组,每组4只动物。采用“双侧颈总动脉阻断法”前脑缺血模型,缺血20min后再灌注3d,并用0.15MPa和0.25MPa压力的高压氧治疗(60min/d,连续3d)后,应用免疫组化LSAB方法,观察高压氧对海马CA1区神经元凋亡相关基因Bcl-2和Bax的蛋白表达的影响。结果沙土鼠脑缺血再灌注3d组海马CA1区大量神经元表达Bax蛋白,并且神经元发生凋亡,未见神经元表达Bcl-2蛋白;高压氧治疗组则大量神经元表达Bcl-2蛋白,并且0.25MPa高压氧治疗组比0.15MPa高压氧治疗组变化更显著,而各组表达Bax蛋白的神经元数目无明显变化,但高压氧治疗组Bax蛋白阳性的神经元形态正常。结论HBO暴露可诱导大量神经元表达Bcl-2蛋白,对Bax蛋白表达则无明显作用,使Bcl-2和Bax蛋白表达的比值增高,从而起到保护神经元的作用,这可视为HBO治疗脑缺血性损伤减少神经元凋亡的机制之一。     

Mucosal dysplasia and DNA content in ulcerative colitis patients with ileorectal anastomosis

In a follow-up study of an epidemiologically defined patient group comprising 1,274 patients with ulcerative colitis diagnosed in Stockholm County during 1955–1979, 55 patients had undergone colectomy with ileorectal anastomosis (IRA). Nine of these were found to have Crohn's disease after histopathologic review of the colectomy specimens. Of the 46 patients with ulcerative colitis remaining for evaluation, two died postoperatively. Twenty-five patients were subsequently reoperated with rectal excision owing to intractable inflammatory activity (n=22, one postoperative death) or owing to dysplasia (n=3). Of 19 patients with their IRA still intact at time of follow-up, 15 patients (median disease duration 23 years) had a flexible sigmoidoscopy with multiple biopsies performed. The average length of the remaining rectum and sigmoid colon was 26 cm. No patient had findings of dysplasia, carcinoma, or DNA aneuploidy. None of the four remaining patients had developed dysplasia or carcinoma at the time of the latest regular rigid sigmoidoscopy. The risk of malignant transformation in this selected group of patients with ulcerative colitis operated upon with colectomy and IRA derived from an epidemiologically defined population seems to be low.This study was supported by grants from the Cancer Society in Stockholm.     

Global test for high-dimensional mediation: Testing groups of potential mediators

We address the problem of testing whether a possibly high-dimensional vector may act as a mediator between some exposure variable and the outcome of interest. We propose a global test for mediation, which combines a global test with the intersection-union principle. We discuss theoretical properties of our approach and conduct simulation studies that demonstrate that it performs equally well or better than its competitor. We also propose a multiple testing procedure, ScreenMin, that provides asymptotic control of either familywise error rate or false discovery rate when multiple groups of potential mediators are tested simultaneously. We apply our approach to data from a large Norwegian cohort study, where we look at the hypothesis that smoking increases the risk of lung cancer by modifying the level of DNA methylation.