Identification of human T cell epitopes in the Mycobacterium leprae heat shock protein 70-kD antigen.

In a number of pathogens, heat shock proteins (hsp) stimulate humoral and cellular immune responses despite significant sequence identity with host hsp. The 70-kD hsp of Mycobacterium leprae, which shares 47% identity with human hsp70 at the protein level, elicited a T cell response in most Myco. bovis (bacille Calmette-Guérin (BCG)) vaccinees as well as leprosy and tuberculosis patients and their contacts. In order to locate T cell epitopes, DNA fragments encoding portions of the 70-kD hsp were expressed in the vector pGEX-2T and tested for T cell reactivity in an in vitro proliferative assay. Cultures of peripheral blood mononuclear cells (PBMC) from BCG vaccinees indicated that the C-terminal half of the molecule contained multiple T cell epitopes, as the T cells from a majority of Myco. leprae hsp70-reactive individuals responded to C-344. Lower proportions of patients with paucibacillary leprosy (36%) and tuberculosis patients (16%) responded to C-344. The smaller C-142 fragment which includes the terminal 70 residues unique to Myco. leprae and is the target for the human antibody response elicited a cellular response in few patients and no vaccinees. In order to map T cell epitopes, two series of synthetic peptides encompassing the region 278-502 were prepared. Using overlapping 12mer and 20mer peptides, this region of the molecule was found to contain several potential T cell epitopes. The longer peptides gave a clearer indication of reactive sequences including regions of the molecule which were not identified with the 12mer peptides. Fine mapping of reactive peptide pools using the 12mer peptides identified two T cell epitopes. Although both were located in regions of the molecule shared with Myco. tuberculosis, one appeared to be cross-reactive with the equivalent human sequence, and thus has the potential to initiate autoimmune responses.     

Artificial adaptation to cold produced by noradrenalin

The state of muscular heat production 2–3 weeks after intravenous injection of noradrenalin was studied during exposure to cold. A single injection of noradrenalin was found to facilitate maintenance of temperature homeostasis for several weeks with a greatly reduced electrical activity of the muscles and before the noradrenalin was given. The phenomenon probably lies at the basis of adaptation of animals to cold.Laboratory of Temperature Regulation, I. P. Pavlov Institute of Physiology, Academy of Sciences of the USSR, Leningrad. (Presented by Academician V. N. Chernigovskii.) Translated from Byulleten', Éksperimental'noi Biologii i Meditsiny, Vol. 81, No. 3, pp. 286–289, March, 1976.     

Effects of luminal stimuli on polyamine metabolism in the small intestine of the rat: the role of enteric nerves

The aim of this study was to investigate to what extent polyamine metabolism in the small intestine of the rat is controlled by the enteric nervous system. Polyamine metabolism was followed by measuring the activity of ornithine decarboxylase (ODC) and in some instances also the content of polyamines (putrescine, spermidine and spermine). ODC activity in the intestine was increased when intraluminal pressure was increased and 3 h after placing cholera toxin in the intestinal lumen. Cholera toxin also increased the tissue putrescine content. Atropine or hexamethonium given i.v. did not influence the evoked changes of ODC activity. The pressure induced changes were not decreased by placing lidocaine on the serosal surface. On the other hand, the ODC activity of control segments were decreased by hexamethonium or atropine. The presence of glucose in the intestinal perfusate did not augment tissue ODC activity, neither did the heat stable enterotoxin from Escherichia coli (STa). It is concluded that the effect on polyamine metabolism evoked by luminal pressure or cholera toxin seems not to be mediated via nerves, while nerves seem to influence ODC activity during control conditions. The experiments with enterotoxins suggest that cAMP is the intracellular second messenger controlling intestinal ODC activity.     

Increase of fetal arterial blood temperature by reduction of umbilical blood flow in chronically instrumented fetal sheep

The effect of reduced umbilical blood flow rate on fetal core temperature was investigated in five chronically instrumented fetal sheep (gestational age 124 days). On average, fetal-maternal temperature difference increased 0.13±0.02 °C when blood flow rate was decreased to about 1/3 of normal (248±69 ml min^–1) for 30 min. The small temperature rise is the consequence of predominant heat dissipation through the placenta, and of diminished oxygen consumption.     

Emigration of selected subsets of {gamma}{delta}+ T cells from the adult murine thymus

Cells bearing the form of the TCR make up only 1–3% ofT cells in the adult murine thymus and peripheral lymphold organs.Evidence from studies of nude mice suggests that the developmentof at least some T cells is thymus dependent; however, untilnow it has not been directly demonstrated that cells are exportedfrom the thymus. In this paper we have used the technique oflabelling thymocytes in vivo with FITC, followed by flow cytometrlcanalysis to trace cells emigrating from the thymus to the spleen.Using this approach we have been able to demonstrate for thefirst time that T cells are exported from the adult murinethymus to the spleen. We also demonstrate that the cells emigratingto the spleen are a selected subset of thymocytes being heatstable antigen positive, Thy-1⁺, and expressing low levels ofCD44 (Pgp-1). In addition, investigation of TCR V; gene usageamong adult ⁺ thymocytes, recent emigrants, and spleen cells,indicated a selective emigration of cells expressing certainVgenes.     

脑室注射促甲状腺素释放激素对电针镇痛及脑内亮氨酸脑啡肽含量的影响

实验用大鼠76只,用辐射热-甩尾法测痛,以电针后痛阈变化的百分率评价镇痛效应;用放射免疫分析法测定脑内L-Enk含量。发现脑室注入三肽-促甲状腺素释放激素(TRH)后,能显著降低电针镇痛效果;提高丘脑内L-Enk含量,但痛阈与脑内L-Enk含量的变化无相关关系。本文证明,TRH在电针镇痛过程中是对抗作用。已知针刺镇痛与脑内多种神经质和肽类有关,在不利于针刺镇痛的因素中,TRH是新添的“一员”。     

整合“转录组-基因调控网络”探讨白虎加桂枝汤君药石膏的性-效关联内涵

目的 从“性-效”关联角度,采用“转录组-基因调控网络”整合研究策略,系统评价白虎加桂枝汤君药石膏在全方“热者寒之”药效作用中的贡献度和贡献形式。方法 20只雄性Lewis大鼠随机分为4组,每组5只：正常组、佐剂诱导型关节炎（AIA）热证模型组、AIA热证+白虎加桂枝汤组（BHGZT,21.4 g·kg^-1）、AIA热证+白虎加桂枝汤去石膏拆方组（BHGZT-GYP,10.7 g·kg^-1）。利用热痹经典动物模型-AIA热证大鼠来源的转录组表达谱数据,通过“病证基因-药物效应靶标”相互作用网络挖掘,预测石膏在白虎加桂枝汤干预热痹的主要作用环节。基于AIA热证大鼠模型从受累关节情况、关节临床积分、肿胀度、关节表面温度、疼痛阈值、关节损伤等疾病严重指标和病证结合指标情况,以及体内“免疫-炎症”失衡调节层面进行整体验证,并基于体外3T3-L1前脂肪细胞开展体外成脂实验验证。结果 白虎加桂枝汤君药石膏在干预热痹中的主要作用环节是调节机体能量代谢的紊乱和矫正“免疫-炎症”的失衡。动物实验观察可见,白虎加桂枝汤及其去石膏拆方均可显著缓解AIA热证大鼠受累关节红肿、畸变和疼痛等症状（P<0.01）,并抑制受累膝/踝关节损伤、滑膜炎症、骨破坏等病理改变（P<0.05）,且全方作用明显优于去石膏拆方（P<0.05）。机制研究表明,白虎加桂枝汤及其去石膏拆方可显著抑制AIA热证大鼠的胸腺/脾脏损伤和内脏指数（P<0.05）,并降低TLR4、TNF-α、IL-6、IL-1β及IL-18等炎症因子的表达（P<0.05）。体外3T3-L1前脂肪细胞实验表明,与去石膏拆方组相比,白虎加桂枝汤全方能够更加显著地抑制脂肪细胞成脂,且单纯石膏对脂滴含量的抑制作用显著增强,表明石膏在全方抑制成脂中的重要作用。结论 白虎加桂枝汤君药石膏在全方缓解热痹相关的能量代谢紊乱和矫正“免疫-炎症”失衡中发挥着重要作用,这与其寒药性及其清热泻火的作用特点密切相关。     

50例冠状动脉搭桥术的临床研究

目的：观察冠状动脉搭桥术的临床疗效。方法：选择经内科治疗仍反复心绞痛发作或不适于PTCA等治疗的冠心病人50例,均在体外循环,心脏停跳下行冠状动脉搭桥术,选用的血管桥包括大隐静脉,乳内动脉和桡动脉,共搭145根桥,平均每例2．9支桥,5例同时行室壁瘤切除或成形术。结果：治愈48例,死亡2例,48例长期随访,效果良好,结论：对有冠脉搭桥指征的病人行搭桥手术,疗效安全可靠, 远期效果好。     

温病热瘀证的病机及分期证治探讨

温病热瘀证是指在温病发生发展过程中,既有热毒炽盛又见血行瘀滞的一类急性发热性疾病,是温病学中一个独特证型,即热邪入侵体内,煎熬阴津血液,导致血液粘稠而成瘀血。热邪和瘀血相互交织,热瘀阻于脏腑经络,引起相关脏腑的病变,最终可致热瘀气脱,正气耗竭而死亡,而热毒和血瘀是整个热瘀证病变过程中始终贯穿的基本病理因素。     

肢体缺血/再灌注诱发大鼠心脏血红素氧合酶1的表达(英文)

目的　观察后肢体缺血 /再灌注是否诱发心脏血红素氧合酶 1(HO - 1)的表达。方法　在氨基甲酸乙脂麻醉大鼠行后肢体缺血 /再灌注后 ,测量心脏组织中丙二醛的含量和超氧歧化酶 (SOD)的活性 ;并应用Northern和Western杂交方法分别检测HO - 1mRNA和蛋白的表达情况。结果　在肢体缺血 /再灌注过程中 ,心脏中的丙二醛含量增加 ,而超氧歧化酶的活性降低 ;单纯肢体缺血并不引起心脏血红素氧合酶 1mR NA和蛋白表达的变化 ,但缺血 /再灌注增强心脏血红素氧合酶 1mRNA和蛋白表达。结论　肢体缺血 /再灌注不仅提高心脏中丙二醛的含量 ,降低超氧歧化酶的活性 ;而且上调血红素氧合酶 1在心脏的表达。