BcL-2、Bax、CD44V6在乳腺癌表达及预后的研究

目的探讨影响乳腺癌患者预后的因素,协助临床制定手术方式及术后治疗方案。方法选择80例各型乳腺癌患者的标本,应用免疫组化SP方法,检测乳腺癌组织中癌基因BcL-2、Bax及黏附因子CD44V6的表达情况。结果乳腺癌中BcL-2、Bax及CD44V6的表达情况与肿瘤组织学分级、瘤体直径。有无转移及患者术后存活时间均有显著性相关(P<0.05或0.01)。结论BcL-2高表达、Bax低表达、CD44V6低表达的患者组织学分级好,肿瘤体积小,淋巴结转移少,术后存活时间长,这部分患者可做肿物扩大切除而保留乳房或即使已做乳房切除,术后也可减少放疗及化疗剂量。     

Effects of recombinant humanen dothelial-derived interleukin-8 on hemorhagic shock in rats

目的：研究重组人内皮细胞衍生的白细胞介素－８（ＩＬ８）对失血性休克的作用．方法：大鼠股动脉放血至ＭＡＢＰ５３２ｋＰａ，维持９０ｍｉｎ，复制晚期失血性休克模型．输血后，静脉注射ＩＬ８２５０μｇ·ｋｇ－１．放免法测定血浆ＥＴ１和６ＫＰＧＦ１α含量．结果：给予ＩＬ８后，ＭＡＢＰ显著提高，休克状态改善，２ｈ存活率相应提高；休克晚期血浆ＥＴ１水平比正常明显升高（２１±４ｖｓ８２±１８ｎｇ·Ｌ－１，Ｐ＜００１），血浆６ＫＰＧＦ１α含量明显降低（１０７±１２ｖｓ１５７±１１ｎｇ·Ｌ－１，Ｐ＜００１）．ＩＬ８显著降低血浆ＥＴ１水平（１０±４ｎｇ·Ｌ－１，Ｐ＜００１），提高血浆６ＫＰＧＦ１α含量（３６８±１６ｎｇ·Ｌ－１，Ｐ＜００１）．结论：ＩＬ８具有较好的抗休克作用．     

N-ω-Carbethoxypentyl-4-quinolones: A New Class of Leukotriene Biosynthesis Inhibitors

6-[(4-Quinolinyl)oxy]hexanoic acids and the corresponding esters were designed and synthesized as inhibitors of the production of arachidonic acid metabolites. The inhibitory activities were assayed in vitro by evaluation of serum leukotriene B₄ and thromboxane B₂ production. While all 6-[(4-quinolinyl)oxy]hexanoic acids and their esters proved to be inactive, the N-alkyl-4-quinolones, obtained as by-products in their synthesis, were found to be a new class of leukotriene biosynthesis inhibitors.     

Characterization of the human cytochrome P450 enzymes involved in the metabolism of dihydrocodeine

Aims Using human liver microsomes from donors of the CYP2D6 poor and extensive metabolizer genotypes, the role of individual cytochromes P-450 in the oxidative metabolism of dihydrocodeine was investigated.
Methods The kinetics of formation of N- and O -demethylated metabolites, nordihydrocodeine and dihydromorphine, were determined using microsomes from six extensive and one poor metabolizer and the effects of chemical inhibitors selective for individual P-450 enzymes of the 1A, 2A, 2C, 2D, 2E and 3A families and of LKM1 (anti-CYP2D6) antibodies were studied.
Results Nordihydrocodeine was the major metabolite in both poor and extensive metabolizers. Kinetic constants for N -demethylation derived from the single enzyme Michaelis-Menten model did not differ between the two groups. Troleandomycin and erythromycin selectively inhibited N -demethylation in both extensive and poor metabolizers. The CYP3A inducer, α-naphthoflavone, increased N -demethylation rates. The kinetics of formation of dihydromorphine in both groups were best described by a single enzyme Michaelis-Menten model although inhibition studies in extensive metabolizers suggested involvement of two enzymes with similar K _m values. The kinetic constants for O -demethylation were significantly different in extensive and poor metabolizers. The extensive metabolizers had a mean intrinsic clearance to dihydromorphine more than ten times greater than the poor metabolizer. The CYP2D6 chemical inhibitors, quinidine and quinine, and LKM1 antibodies inhibited O -demethylation in extensive metabolizers; no effect was observed in microsomes from a poor metabolizer.
Conclusions CYP2D6 is the major enzyme mediating O -demethylation of dihydrocodeine to dihydromorphine. In contrast, nordihydrocodeine formation is predominantly catalysed by CYP3A.     

Inadequate Erythropoietin Response to Anaemia in HIV Patients: Relationship to Serum Levels of Tumour Necrosis Factor-Alpha, Interleukin-6 and Their Soluble receptors

Severe anaemia is a frequent complication in advanced HIV infection. In our study we investigated the interaction between cytokine network, HIV infection and erythropoietin (Epo) response with increasing anaemia levels. No correlations could be established between circulating tumour necrosis factor (TNF)-alpha and any of the examined parameters. However, a negative correlation was found between haemoglobin values and soluble TNF receptor levels (sTNF-R-I: r  = −0.54; P  < 0.001; sTNF-R II: r  = −0.47; P  < 0.001) as well as interleukin-6 levels ( r  = −0.29; P  < 0.001). In contrast, no significant increase in log[Epo], counterbalancing haemoglobin decline and paralleling the rise in sTNF receptors, was found. In patients classified as stage III, according to the Centers for Disease Control (CDC) classification, the erythropoietin response was significantly more impaired than in patients from CDC groups I and II ( P  < 0.001). The results of this study suggest that similar to its action in vitro , activation of the TNF/TNF-R system may impair erythropoietin production in HIV-associated anaemia. Due to the brief half-life of TNF-α, this activation is particularly reflected by elevations of soluble TNF receptor levels.     

白细胞介素1α对鼠甲状腺细胞增殖的影响

采用四氮唑蓝（MTT）比色法检测TSH存在和缺乏时白细胞介素1α（IL－1α）对鼠FRTL-5细胞增殖的影响。结果提示，在无TSH条件下IL-1α20～2000kU／L对FRTL－5细胞无明显促增殖作用；在TSH存在时IL－1α20和200kU／L对FRTL－5细胞增殖亦无明显抑制作用，IL－1α2000kU／L则可显著抑制TSH介导的FRTL－5细胞增殖。     

Spatially and Temporally Regulated Modification of the Receptor-like Protein Tvrosine Phosphatase ζ/β isoforms with Keratan Sulphate in the Developing Chick Brain

Protein tyrosine phosphatase ζ (PTPζRPTPβ) is a proteoglycan-type receptor-like protein tyrosine phosphatase specifically expressed in the brain. In addition to the transmembrane form (PTPζ-A), the extracellular splice variant (PTPζ-S) occurs as a major soluble chondroitin sulphate proteoglycan in the brain. We prepared antibodies which specifically recognize PTPζ-A and -S, and analysed the carbohydrate structures on the two PTPζ isoforms in the developing chick brain. lmmunoprecipitation experiments using these antibodies revealed that almost all of the keratan sulphate recognized by a monoclonal antibody (5D4) was exclusively bound to PTPζ-A and PTPζ-S. Addition of keratan sulphate to these proteoglycans markedly increased from embryonic day (E) 11, in contrast to the addition of Le^X and HNK-1 carbohydrates, which gradually increased during development in accordance with expression of the core proteins, suggesting that keratan sulphate modification plays some specific roles. Moreover, at the early embryonic stage keratan sulphate was observed only in several restricted regions, especially at boundary regions such as the roof plate of the tectum, the zona limitans intrathalamica in the diencephalon, and the mesencephalon-metencephalon boundary. At the mesencephalon-metencephalon boundary, keratan sulphate modification of PTPζ isoforms was specifically observed from E3 to E6 on a ring of cells encircling the neural tube and their radially oriented processes, which were identified as radial glial fibres. This expression pattern of keratan sulphate spatiotemporally corresponded well to the formation of the fovea isthmi, a groove separating the mesencephalon from the metencephalon. These results suggest that carbohydrates including keratan sulphate on PTPζ isoforms play important roles in brain development by modulating the cell-cell and/or cell-substrate interactions mediated by these molecules.     

Reciprocal regulation of the nitric oxide synthase/arginase balance in mouse bone marrow-derived macrophages by TH 1 and TH 2 cytokines

Activation with lipopolysaccharide induces macrophages to produce the enzymes arginase and nitric oxide (NO) synthase. Both enzymes use as a substrate the amino acid L-arginine, which can be either hydrolyzed by arginase to urea and ornithine or oxidized by NO synthase to NO and citrulline. NO is important in the bactericidal and cytotoxic activities of macrophages. An equivalent functional role of arginase and its products is not known. We tested the induction of arginase in bone marrow-derived macrophages by endogenous mediators that are known to induce NO synthase, such as interferon-γ (IFN-γ), or suppress the induction of this enzyme, such as interleukin (IL)-4, IL-10, and prostaglandin E₂ (PGE₂). We find that PGE₂ and the TH2 cytokines IL-4 and IL-10 are potent inducers of arginase. In contrast, the TH 1 cytokine IFN-γ does not induce arginase. Simultaneous application of both types of mediators leads to reduced induction of both arginase and NO synthase. Exposure of macrophage cultures to inducers of NO synthase exhausts their ability to respond subsequently to inducers of arginase. Conversely, exposure of the cells to inducers of arginase exhausts their ability to respond subsequently to inducers of NO synthase. The results are consistent with a competition of both enzymes for their substrate, L-arginine, with a reciprocal inhibition in the induction of both enzymes, or a combination of both phenomena. The enzymes NO synthase and arginase appear to define two alternate functional states of macrophages, induced by TH 1 and TH 2 cytokines, respectively.     

雌、孕激素对IL-6基因在子宫内膜表达的影响

为了进一步了解白介素－６（ＩＬ－６）在生殖过程中的作用，应用斑点杂交和原位杂交方法，研究ＩＬ－６在小鼠子宫内膜的基因表达和雌、孕激素对这种表达的影响。实验证明，正常动情前期子宫内膜间质细胞有ＩＬ－６ｃＲＮＡ基因表达，切除动物卵巢，即可消除这种表达。如给去卵巢动物２ｍｇ孕激素加１０ｎｇ雌激素或２０ｍｇ孕激素加１００ｎｇ雌激素，它们的光密度（ＩＯＤ）值分别可达到２．３和２．５。结果证明，子宫内膜间质细胞是产生细胞因子ＩＬ－６的主要细胞之一，并受卵巢激素的调控。     

Case Report: Gianotti-Crosti Syndrome Associated with Human Herpesvirus-6 Infection

We report a case of Gianotti-Crosti syndrome associated with human herpesvirus-6 (HHV-6) infection. An eight-month-old girl developed monomorphous papules on her cheeks, buttocks, and extremities after the subsidence of exanthema subitum. Viral antibody analysis confirmed primary HHV-6 infection. HHV-6 may be added to the list of causative agents of Gianotti-Crosti syndrome.