Synergistic convergence of microbiota-specific systemic IgG and secretory IgA

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抗人DR5抗体mDRA- 6细胞毒作用机制分析

目的:探讨鼠抗人DR5单克隆抗体(mAb)mDRA-6对Jurkat细胞的细胞毒作用及其机制。方法:以流式细胞术测定mAbmDRA-6对Jurkat细胞的细胞毒作用和细胞凋亡作用,以及caspase8、9的抑制剂对mAbmDRA-6诱导的Jurkat细胞凋亡的影响。在荧光显微镜下,观察mAbmDRA-6对Jurkat细胞形态的影响。以琼脂糖凝胶电泳检测Jurkat细胞中的DNA片段化。结果:mAbmDRA-6对Jurkat细胞具有显著的细胞毒作用,并呈剂量和时间依赖性。经mAbmDRA-6处理后,Jurkat细胞可出现典型的细胞凋亡的形态特征:细胞膜皱缩,出泡,染色质浓缩,形成凋亡小体等。经mAbmDRA-6处理后,Jurkat细胞膜表面高表达丝氨酸磷脂,并可导致Jurkat细胞中的DNA片段化。caspase8的抑制剂可明显抑制mAbmDRA-6诱导的Jurkat细胞凋亡,caspase9的抑制剂的影响很小。结论:mAbmDRA-6可通过死亡受体信号传导途径诱导Jurakt细胞凋亡,对Jurkat细胞产生细胞毒作用,其在以TRAIL/DR5系统进行的肿瘤治疗和探讨DR5功能结构域方面具有广阔的应用前景。     

Maternal death associated with ovum donation twin pregnancy.

A case of maternal death due to sub-arachnoid haemorrhage in an ovum donation twin pregnancy complicated by hypertension is described. Attention is drawn to a forecasted increase in maternal morbidity and mortality in in-vitro fertilization (IVF) pregnancies, which occur in older women and are often multiple.     

p38应急信号通路参与一氧化氮诱导PC12细胞死亡

目的:探讨一氧化氮诱导PC12细胞死亡的信号转导途径。方法:将亚硝基铁氰化钠(sodiumnitroprusside,SNP)、caspase-3拮抗剂(caspase-3inhibitorⅡ)加SNP或p38拮抗剂(SB203580)加SNP与传代培养的PC12细胞一起孵育,观测细胞的存活率和caspase-3的活性;用MTT法测细胞存活率,caspase-3检测试剂盒测caspase-3活性。结果:SNP以浓度和时间依赖性方式诱导PC12细胞死亡,并增加caspase-3的活性;caspase-3拮抗剂Ⅱ和p38拮抗剂均明显减少细胞死亡且p38拮抗剂明显降低caspase-3的活性。结论:一氧化氮可能通过激活p38、caspase-3信号分子诱导PC12细胞死亡。     

“Dark” (compacted) neurons may not die through the necrotic pathway

Dark neurons were produced in the cortex of the rat brain by hypoglycemic convulsions. In the somatodendritic domain of each affected neuron, the ultrastructural elements, except for disturbed mitochondria, were remarkably preserved during the acute stage, but the distances between them were reduced dramatically (ultrastructural compaction). Following a 1-min convulsion period, only a few neurons were involved and their environment appeared undamaged. In contrast, 1-h convulsions affected many neurons and caused swelling of astrocytic processes and neuronal dendrites (excitotoxic neuropil). A proportion of dark neurons recovered the normal structure in 2 days. The non-recovering dark neurons were removed from the brain cortex through two entirely different pathways. In the case of 1-h convulsions, their organelles swelled, then disintegrated and finally dispersed into the neuropil through large gaps in the plasma membrane (necrotic-like removal). Following a 1-min convulsion period, the non-recovering dark neurons fell apart into membrane-bound fragments that retained the compacted interior even after being engulfed by astrocytes or microglial cells (apoptotic-like removal). Consequently, in contrast to what is generally accepted, the dark neurons produced by 1-min hypoglycemic convulsions do not die as a consequence of necrosis. As regards the case of 1-h convulsions, it is assumed that a necrotic-like removal process is imposed, by an excitotoxic environment, on dark neurons that previously died through a non-necrotic pathway. Apoptotic neurons were produced in the hippocampal dentate gyrus by intraventricularly administered colchicine. After the biochemical processes had been completed and the chromatin condensation in the nucleus had reached an advanced phase, the ultrastructural elements in the somatodendritic cytoplasm of the affected cells became compacted. If present in an apparently undamaged environment such apoptotic neurons were removed from the dentate gyrus through the apoptotic sequence of morphological changes, whereas those present in an impaired environment were removed through a necrotic-like sequence of morphological changes. This suggests that the removal pathway may depend on the environment and not on the death pathway, as also assumed in the case of the dark neurons produced by hypoglycemic convulsions.     

Immunologic defects as possible causes of therapeutic failures in children with transposition of the great arteries

Summary Recurrent and severe infections and absence of thymic shadow in X-ray examination were observed in children with the transposition of the great arteries (TGA). Among 45 children (29 boys and 16 girls) with TGA whose age ranged from 3 days to 16 years and who were hospitalized during 1 year, infectious diarrhea was observed in 77.7% cases, urinary tract infections in 44.5%, respiratory tract infections in 42.2%, sepsis in 17.5%, and meningitis in 8.8%. Nine of the children died, sepsis was a cause of death in seven children, and there were postsurgical complications in two children. Immunologic abnormalities in children with TGA included a decreased level of T-lymphocytes and T_29° subpopulation, impaired mitogen-induced lymphoproliferation in vitro, and increased nitro blue tetrazolium (NBT) reduction activity of monocytes. Impaired parameters of cellular immunity correlated with worst clinical status. No disorders of humoral immunity were observed. These observations may be important for forming opinion about proper therapy and the cause of death in children with TGA.All results have been included in T. Marek-Szydowska's doctoral dissertation and were communicated at the 65th Annual Meeting of Deutsche Gesellschaft für Rechtsmedizin, St. Gallen, Switzerland, Sept. 9–13, 1986     

Brain death

Summary Following the research of Giessen Neurosurgery on primary and secondary lesions of the hypothalamo-pituitary system and the brainstem over a period of more than 30 years, cerebral failure and death does not represent a uniform syndrome but consists of several, well characterized syndromes of irreversible hypothalamo-pituitary, mesencephalic and bulbar failure. The specific syndromes are described in detail. The diagnosis is based on establishing complete irreversible damage of specific vital basal functions such as hypothalamo-pituitary transmission, water-and electrolyte metabolism, temperature regulation, circulation and respiration. The common feature of all types is the irreversible break-down of the complex central neurogenous and/or neurohumoral regulatory system. The permanent and irreversible loss of central regulation and modulation means at the same time the complete cessation of the specific human cortical function, the death of the whole brain. Only in bulbar failure with primary irreversible cessation of respiration artificial respiration can maintain the autonomous functions of the heart for a limited time. It is indicated when organ explantation is to be considered. Complete and irreversible isolated loss of cortical function abolishes the normal human life, but does not mean death of the remaining vegetating human being.Presented at the meeting of the Working Group of the Pontificia Academia Scientiarum on The artificial prolongation of life and the exact determination of the moment of death, Vatican City, October 19–21, 1985.Dedicated to Prof. Dr. Jean Brihaye at the occasion of his 65th anniversary.     

Growth,regression and cell death in rat liver as related to tissue levels of the hepatomitogen cyproterone acetate

Previous studies have shown that xenobiotic compounds such as the environmental pollutant -hexa-chlorocyclohexane (-HCH) and the synthetic sex steroid cyproterone acetate (CPA) induce growth of rat liver by hypertrophy and hyperplasia. After withdrawal of the growth stimuli, liver hypertrophy was usually found to be readily reversible. Conflicting observations were made concerning the fate of liver hyperplasia: hepatic hyperplasia persisted when induced by -HCH but was found to be partially reversible when induced by CPA. The present study confirms the reversibility of hepatic hyperplasia induced by CPA in rats: about 30% of liver DNA present at maximal liver enlargement disappeared within 6 days after cessation of CPA treatment. Simultaneously, a dramatic increase in the rate of cell elimination by apoptosis was found. Glutamate-pyruvate transaminase and alkaline phosphatase in serum did not show major increases, suggesting that cell death was not due to lytic membrane damage. Furthermore, if treatment with CPA was continued or resumed, the enhanced DNA content persisted and the number of apoptotic bodies was greatly reduced. These observations suggest that the occurrence of cell death is due to withdrawal of the growth stimulus CPA. It may reflect a regulatory phenomenon serving to maintain homeostasis of cell number.Further studies showed that CPA is rapidly eliminated from rat liver and serum: t 1/2 in the liver is about 11 h. In contrast, -HCH was previously found to be eliminated more slowly: t 1/2 approximately 144 h. The present study revealed that -HCH, CPA and nafenopin lower the number of apoptotic bodies. This suggests that inducers of liver growth can inhibit hepatocellular death by apoptosis. It is concluded that the regression of hyperplasia after CPA withdrawal may be due to its rapid elimination. On the other hand the relatively long persistence of -HCH may result in inhibition of cell death and thereby stabilize hepatic hyperplasia.Abbreviations CPA cyproterone acetate - -HCH -hexachlorocyclohexane - PB phenobarbital - NAF nafenopin - AB apoptotic body - b.w. body weight - p. admin. post-administration - GPT glutamate-pyruvate transaminase - ALP alkaline phosphatase Dedicated to Professor W. Koransky on the occasion of his 65th birthday