Human interleukin 4 regulates the phenotype of lymphocytes generated during mixed lymphocyte culture and inhibits the IL-2-induced development of LAK function in normal and leukaemic cells

This study examined the immunoregulatory role of recombinant interleukin 4 (IL-4), also known as B-cell stimulating factor 1, on the generation of cytotoxic effector cells from normal and leukaemic human blood mononuclear cells. When tested on cells from normal individuals, the addition of IL-4 to mixed lymphocyte cultures led to a dose-dependent proliferation of T-helper cells (CD3, 4 positive) with a concomitant decrease in phenotypic and functional cytotoxic T cells and natural killer (NK) cells. IL-4 also inhibited the interleukin-2 (IL-2)-induced generation of lymphokine-activated killer (LAK) activity when added at the beginning of mixed lymphocyte culture. When tested on mature leukaemic NK cells, IL-4 also inhibited the ability of IL-2 to induce LAK function using a short-term culture system. These results show that IL-4 acts on both normal and leukaemic cells and suggests that it acts at more than one level during the development of LAK function.     

460例胃癌纤维胃镜活检标本的病理观察

本文分析了460例胃癌胃粘膜活检资料,结果:男:女为2.36:1:51～60岁年龄组发病率最岛(37.17％);发生部位以胃窦部最多见,占46.74％;组织学分类以低分化腺癌最多,占51 52％;在伴随病变中,畅化生的检出率为21.74％,胃腺囊为35％,胃粘膜上皮异型增生为32.61％。本组材料提示,不完全性大肠型肠化生、异型胃腺囊及胃粘膜中度以上异型增生与胃癌有密切关系。     

细胞凋亡抑制因子（Fas／APO-1）与抗β2-肾上腺素能受体自身抗体的关系

目的 检测并比较心肌梗死急性期不同时间点，β2自身抗体阳性组与阴性组，患者血清中Fas／APO-1水平差异，了解β2自身抗体对Fas／APO-1的影响。方法 41例急性心肌梗死患者，分别于发病24h、7天、2～4周时取血，采用ELISA的方法，检测血清中β2自身抗体的阳性率以及Fas／APO-1的水平；另外取34位性别、年龄匹配的健康人的血同法检测Fas／APO-1作为对照。结果心肌梗死急性期Fas／APO-1的水平均高于对照组（P〈0．05），以梗死后24hFas／APO-1的水平为最高；心肌梗死急性期不同时间点，β2自身抗体阳性组Fas／APO-1的水平均高于阴性组，但两组的结果差异无显著性（P〉0．05）。结论 血清Fas／APO-1水平可以在一定程度上反映心肌细胞凋亡的变化趋势，β2自身抗体对Fas／APO-1的确切影响，有待更大规模的实验来证实。     

Effect of gradual rise in plasma calcium concentration on the impairment of atrioventricular nodal conduction due to verapamil

The possible reversal by calcium of the inhibitory action of verapamil on the atrioventricular (AV) node was investigated in anesthetized, atropinized dogs, with cardiac pacing. The His bundle potentials were recorded by endocavitory electrode and the AV node effective refractory period measured by the extrastimulus method. Calcium infusion was effective against the impairment of AV nodal conduction induced by verapamil, provided it remained moderate: the gradual rise in the plasma calcium concentration counteracted the effects of an infusion of verapamil on conduction time and effective refractory period in the AV node, as long as it did not exceed 5 mmol/L. However, beyond this level, calcium appeared less and less capable of reversing the effects of verapamil. Thus, the protective action of calcium had a bell-shaped dose-response curve, with the optimum at 5 mmol/L. This biphasic influence is consistent with the opposite opinions previously given concerning the antagonism between calcium and calcium blockers, depending on whether hypercalcemia brought into play was mild or major. In any case, the prominent role played by calcium in the slow inward current in the AV node accounts for the antagonism, observed in vivo, between calcium and verapamil. The pacemaker activity of the sinoatrial (SA) node was less influenced by both calcium blocker and calcium.     

Functional recognition of the neuronal tyrosine hydroxylase cAMP regulatory element in different cell types.

Transient transfection of pLB2CAT constructs bearing short synthetic oligonucleotides derived either from the tyrosine hydroxylase (TH) promoter or other sources was used to examine functional cAMP regulatory element (CRE) activity in a variety of cell lines. The region containing only the putative TH CRE was found to be as or more effective in conferring cAMP responsiveness onto pLB2CAT (which employs the TK promoter) than the immediate 272 bp region of the TH promoter. Increases in CAT activity of 10- to 20-fold were observed in JEG-3 cells with a single insert of the TH CRE region (-31 to -54) in pLB2CAT, and the presence of a second insert generated only a modest further increase. This construct also responded to cAMP in 4 other cell lines tested but the degree of increase was less dramatic. Inserts containing the consensus 8 bp CRE motif embedded in other natural or artificial contexts served generally as weak functional CREs in all cell lines tested. In vitro analysis revealed that a specific protein-DNA complex apparently containing a single protein with a MW of 45-50 kDa was formed equally well with JEG-3 cell nuclear extract and CRE-bearing-TH and other fragments which produced dramatically different cAMP effects in vivo. These results suggest specificity in the effects of cAMP on different CREs which are dictated by contextual differences.     

Calcium-activated proteolysis of intracellular domains in the cell adhesion molecules NCAM and N-cadherin.

One of the consequences of increased intracellular calcium in response to a variety of physiological stimuli is the calcium activation of cytosolic proteases. Unlike lysosomal proteases with broad specificity, these calcium-activated neutral proteases show limited proteolysis of a restricted set of substrate proteins suggesting they may play a regulatory role in cellular physiology. In this study we show that the neural cell adhesion molecules NCAM-180 and N-cadherin are substrates for such endogenous calcium-activated neutral proteases. In contrast, a third neural cell adhesion molecule G4/L1 was not susceptible to calcium-activated proteolysis. The threshold for activation of NCAM and N-cadherin proteolysis is in the micromolar range of calcium suggesting that NCAM and N-cadherin are substrates for a mu-type calpain (calpain I). The site recognized by this protease is within intracellular domains of NCAM-180 and N-cadherin which are important for their interaction with cytoskeletal components. These results suggest that calcium-activated proteolysis at these sites in vivo could disrupt the linkage between extracellular ligand binding to these adhesion molecules and the normal intracellular effectors of such extracellular binding events.