Role of cortical filamentous actin in the melanotrope cell of Xenopus laevis

In secretory cells filamentous actin (f-actin) is mostly present subjacent to the plasma membrane, referred to as cortical actin. While the function of cortical actin in the secretory processes has been extensively studied, little attention has been given to the role of actin in signal transduction and intracellular second messenger dynamics. Analysis with the fluorescent f-actin probe Alexa-phalloidin shows that Xenopus laevis pituitary melanotrope cells possess a thick cortical actin ring. This cell is a good model to study the possible function(s) of f-actin in signal transduction processes. Regulation of the release of alpha-MSH from this cell involves a convergence of various receptor mechanisms to regulate the activity of voltage-operated Ca2+ channels. We have considered three potential functions for the cortical actin ring in the signaling process of the melanotrope: (1) it functions as a barrier for access of secretory granules to the membrane for exocytosis, (2) it is involved in anchoring components of the Ca2+ signalling machinery of the cell, and/or (3) it helps to form a scaffold for components of the signal transduction machinery used by the various neurotransmitters and neuropeptides that regulate the activity of the cell. To test these possibilities we have examined the effect of the f-actin depolymerising toxin latrunculin B on Ca2+ signaling, signal transduction and alpha-MSH secretion in the melanotrope. We show that while the toxin is effective in disrupting the cortical actin ring, this treatment has no effect on either Ca2+ signaling or the signal transduction processes studied. The toxin does induce an increase in alpha-MSH release, indicating that the cortical actin ring acts as a barrier for secretory granule access to the membrane.     

An investigation of enterococcal bacteremia

Records of all 34 patients with positive blood cultures for enterococcus at Mount Sinai Medical Center of Greater Miami in 1981 were reviewed. Twenty-four true bacteremias were identified from sources including the pelvis/abdomen (9), urinary tract (6), wounds (2), IV catheter (2), contaminated needle (1), endocarditis (1), and primary bacteremia (3). Sixteen of the 24 true bacteremias were hospital acquired, and these infectious accounted for 7 of 9 (78%) fatal outcomes. Fourteen of 16 patients with hospital-acquired infection received prior antibiotic therapy. Eight (24%) of the original 34 patients had positive blood cultures for enterococcus as a result of cross-contamination from an automated blood culture analyzer. The rate of cross-contamination per positive blood culture for enterococcus in 1981 was 22%. Two remaining patients in the original series could not be placed in a category of true infection of cross-contamination. Although there was a real increase in the number of enterococcal bacteremias in 1981, a much larger apparent increase was explained by several episodes of pseudobacteremia.     

溃疡性结肠炎的免疫机制

溃疡性结肠炎（Ulcerativecolitis，UC）与克罗恩病（Crohn’s disease，CD）同属炎症性肠疾病（Inflammatory bowel disease，IBD），是一种主要累及直肠、结肠黏膜的慢性非特异性炎症，以腹痛、腹泻、粘液血便、里急后重为主要临床表现；迁延不愈，长达几十年，亦有发生癌变的可能性。UC患者肠黏膜固有层中有大量炎性细胞浸润并伴有局部体液或细胞免疫激活；本病多并发结节性红斑、关节炎等自身免疫性病的肠外表现；     

Rheumatoid vasculitis: Experience with 13 patients and review of the literature

Rheumatoid vasculitis is an uncommon but potentially catastrophic complication of RA. There are few current extensive experiences and no consensus regarding the clinical, laboratory, histologic features, and management or prognosis of rheumatoid vasculitis. We therefore reviewed selected observations in 13 patients followed over the past decade and compared them with patients reported and with results of a survey of North American Rheumatologists. Our patients were seven men and six women (age, 33 to 70 years) who had had active RA for 4 to 36 years. They exhibited sensory neuropathy, mononeuritis multiplex, Felty syndrome, cutaneous lesions, leg ulcers, gangrene, anemia, leukocytosis, eosinophilia, high titers of RF, hypocomplementemia, and CICs or cryoglobulinemia approximately as frequently as other reported patients with rheumatoid vasculitis, but they displayed constitutional symptoms, subcutaneous nodules, ischemic changes, and proteinuria rather less consistently than in other series. These observations were not necessarily as expected by survey respondents. We, as in other series and suggested by survey respondents, tended to select penicillamine or cytotoxic drugs (or plasmapheresis) for patients with mononeuritis, gangrene, or leg ulcers, and nonsteroidal antiinflammatory drugs, antimalarials, gold, or penicillamine for sensory neuropathy or digital lesions. Four patients died, two deteriorated, and seven were stable or improved, a finding that was also similar to the experiences of others. Rheumatoid vasculitis is an uncommon, potentially catastrophic syndrome with varying clinico-pathologic features that have different prognostic implications and should be managed individually.     

sp600125对乙醛刺激的大鼠肝星状细胞增殖及bcl-2、c-myc蛋白表达的影响

肝星状细胞（HSC）的活化与增殖是肝纤维化发生的关键环节。乙醛刺激HSC活化与增殖，是导致酒精性肝纤维化发生的关键因素。研究表明，丝裂原活化蛋白激酶（MAPK），包括细胞外信号调节激酶（ERK）、JNK、P38是HSC活化与增殖导致肝纤维化发生的主要信号传导通路之一。乙醛刺激HSC中JNK磷酸化水平随sp600125（JNK信号传导通路特异性阻断剂）浓度增加而减少。本实验用sp600125处理乙醛刺激的HSC，观察sp600125对HSC增殖以及bcl-2、c-myc蛋白表达的影响，以探讨酒精性肝纤维化的发生机制。     

中枢神经系统Slit/Robo GTPase激活蛋白信号通路研究进展

中枢神经系统的Slit蛋白可与其跨膜受体Roundabout(Robo)蛋白结合,二者相互作用激活细胞内与Robo胞内结构域耦联的Slit-RoboGTP酶激活蛋白(Slit/Robo GTPase activating protein,sr-GAP)分子,进而触发一系列细胞信号转导产生多方面效应。此信号通路不仅参与调节中枢神经系统的发育,而且与神经元再生、胶质瘤发生和精神发育迟缓等有关。     

Sodium-Hydrogen Exchange and Platelet Function

On stimulation of platelets with agonists, for example, thrombin, a rapid rise in intracellular pH is observed. This alkalinization is mediated by an increase in transport activity of the Na⁺/H⁺ exchanger isoform NHE1. In addition to this Na⁺/H⁺ exchange mechanism, platelets express bicarbonate/chloride exchangers, which also contribute to pH_i homeostasis. The main functions of NHE1 in platelets include pH_i control, volume regulation, and participation in cell signaling. The isoform NHE1 is highly sensitive toward inhibition by EIPA, Hoe694, and Hoe642. The regulation of NHE1 activity is complex and is not completely understood. It includes the MAP kinase cascade, the Ca/calmodulin system, several heterotrimeric G proteins (G12, G13, Gq, and Gi), small G proteins (ras, cdc42, rhoA), and downstream kinases (e.g., p160ROCK). Volume challenges stimulate tyrosine phosphorylation of cytoplasmic proteins, which ultimately activate NHE1. Thrombin, thromboxane, platelet-activating factor, angiotensin II, endothelin, phorbol ester, and Ca²⁺ ionophors stimulate NHE1 activity in platelets. Blockade of platelet NHE1 can inhibit platelet activation. With the development of highly specific NHE1 inhibitors, detailed investigation of the relationships between NHE1 activity and platelet activation now becomes feasible.     

Janus激酶/信号传导子和转录激活子信号通路重建对MHCC97细胞干扰素α应答的影响

目的阐明原发性肝癌MHCC97细胞中Janus激酶/信号传导子和转录激活子信号通路对干扰素α抗肿瘤增殖作用的影响.方法用Dosper转染干扰素调节因子9（IRF9）表达质粒入MHCC97细胞;用Western blot和寡核苷酸迁移率实验分别检测肝癌细胞中IRF9、细胞周期调控蛋白和干扰素刺激基因因子3的表达;用四甲基偶氮唑盐和流式细胞术分别检测细胞的增殖水平及各期细胞的分布情况. 结果通过高表达IRF9因子可恢复MHCC97细胞对干扰素α抗增殖的应答能力,同时阻滞细胞由S期过渡到G 2期.结论完整的Janus激酶/信号传导子和转录激活子信号通路对介导干扰素α抗肝癌MHCC97细胞的增殖作用至关重要.