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181.
The Na+–Ca2+ exchange (NCX) system plays a pivotal role in regulating intracellular Ca2+ concentration in cardiomyocytes, neuronal cells, kidney and a variety of other cells. It performs a particularly important function in regulating cardiac contractility and electrical activity. One of the leading NCX inhibitors is KB‐R9743 (KBR) that appears to exhibit selectivity for Ca2+‐influx‐mode NCX activity (reverse mode of NCX). In this article we reviewed pharmacology of KBR and provide a brief summary of studies with other NCX inhibitors, such as SEA0400 (SEA) and SN‐6 (SN). Potential clinical usefulness of KBR and other NCX inhibitors is still controversial but the reviewed findings may be helpful in designing more selective and clinically useful NCX inhibitors for the treatment of cardiac, neuronal and kidney diseases. 相似文献
182.
目的 研究冠心病患者心肌缺血情况下循环中白细胞介素-6(IL-6)和脂蛋白(a)[LP(a)]水平的关系和临床意义。方法 用ELISA分析试剂盒检测62例冠心病患者和50例健康对照者血浆IL-6,用免疫透射比浊法检测血滑LP(a),并对心电图(EKG)ST段的情况进行比较。结果 冠心病组血浆IL-6和血清LP(a)水平均较健康对照组显著增高(P<0.01)。与健康对照组相比,ST段异常组和ST段正常组血浆IL-6水平均显著增高(P<0.01);ST段异常组血浆LP(a)水平显著增高(P<0.01),ST段正常组血清LP(a)水平有所增高,但无统计学意义(P>0.05)。ST段异常组血浆IL-6和血清LP(a)水平均显著高于ST段正常组(P<0.05,P<0.01)。冠心病患者血浆IL-6和血滑LP(a)水平存在显著的相关性(P<0.05)。结论 冠心病患者循环中IL-6和LP(a)水平显著升高,高水平IL-6和LP(a)可能反映血管和心肌损伤的发生,LP(a)的增加可能与IL-6刺激肝脏合成LP(a)增加有关。 相似文献
183.
乳腺癌组织中基质金属蛋白酶MMP-9和CD44v6表达及其意义 总被引:2,自引:2,他引:0
目的探讨基质金属蛋白酶MMP-9和CD44v6在乳腺癌中的表达及其与乳腺癌侵袭、转移的关系.方法采用免疫组化方法对46例乳腺癌(10例导管内癌,36例乳腺浸润癌),10例乳腺增生组织MMP-9、CD44v6进行标记和分析.结果MMP-9和CD44v6在乳腺增生组织中几乎不表达,导管内癌、乳腺浸润癌表达率显著增高,各组间差异有显著性(P<0.05),而且MMP-9与CD44v6过表达与淋巴结转移有关.结论MMP-9和CD44v6的过表达在乳腺癌侵袭和转移中发挥重要作用,可作为乳腺癌侵袭和转移的重要分子学标志. 相似文献
184.
大鼠坐骨神经慢性挤压性损伤后痛阈和血清IL-6的变化及相关性研究 总被引:2,自引:0,他引:2
目的:通过大鼠坐骨神经慢性挤压伤(CCI)神经性疼痛模型的热敏变化及血清中IL-6含量的变化,探讨血清IL-6在神经性疼痛形成中的作用及可能机制.方法:36只250~300g的健康雄性Wistar大鼠,在戊巴比妥钠麻醉下于大腿中部暴露坐骨神经并作结扎,取对侧大腿坐骨神经暴露作为模拟对照(B组).术后1,3,5,7,9,11,13,15 d测定大鼠(n=12)两侧后爪对热敏阈值的变化.于术后第15 d处死大鼠,取血清,ELISA法测定IL-6浓度.结果:大鼠双侧后爪(CCI和B)的收缩潜伏期在术后第3,5,7,9,11,13,15 d有显著差异;CCI组血清IL-6与对照组比较有显著差异.结论:IL-6与大鼠坐骨神经慢性挤压性损伤后出现的神经源性疼痛过敏有关. 相似文献
185.
B. Pfausler G. Grubwieser S. Bsch H. Vollert M. Herald E. Schmutzhard 《European journal of neurology》1995,2(6):570-572
A 37 year old male was admitted with the diagnosis of bacterial meningitis. Pneumococci were seen in the Gram stain of the cerebrospinal fluid. The clinical condition did not suggest severely raised intracranial pressure, there were no localizing signs and symptoms. CSF was turpid, with 20.100/3/mm3, mainly polymorphonuclear cells. Tumor necrosis factor alpha in CSp was greatly increased with 813 pg/ml. Parallel to the application of intravenous Penicillin G a CSF filtration was carried out. Within 214 h 225 ml CSF were filtrated through a Pall-filter, using a bidirectional pump. Cell count dropped to 720/3 cells/mm3, TNF-alpha to 39 pg/ml. The clinical course was uneventful, on day 12 the patient could be discharged without sequelae. CSF filtration may be a highly effective method to reduce from the CSF pathogenetically important cytokines, such as TNF-alpha, being responsible for intrathecal/meningeal inflammatory processes and triggered by cell-wall components of bacteria, e.g. pneumococci. 相似文献
186.
固定化酶裂解Pen-GK生产6-APA的实验设计及其工业化 总被引:1,自引:0,他引:1
本文通过研究固定化青霉素酰化酶裂解青霉素工业钾盐(Pen-GK)生产6-APA的反应机理,确定了最佳裂解实验流程,并对裂解罐的搅拌装置、pH自控装置、加氨装置、温度自控装置、过滤系统等进行了最佳设计。 相似文献
187.
Sigrid C. Schwarz Hansjörg Sauer Wolfgang H. Oertel Christopher D. Earl Andreas R. Kupsch 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1997,115(1):71-82
We employed intracerebral co-transplantation of foetal xenogeneic striatal mouse tissue and allogeneic rat substantia nigra
into the adult rat brain to elucidate the effects of xenogeneic mouse graft on the function and survival of an allogeneic
rat graft in 6-hydroxydopamine lesioned Sprague-Dawley rats. Foetal mouse striatum (STR) and rat substantia nigra (VM) were
transplanted as non-pooled separate deposits or a pooled cell suspension with or without cyclosporin A (Cy A). Immunosuppressed
recipients of pooled rat and mouse co-grafts showed a significantly better compensation of amphetamine-induced rotational
behaviour compared with non-immunosuppressed animals with pooled rat and mouse co-grafts 3 and 6 weeks post-grafting.Tyrosine
hydroxylase (TH) immunohistochemistry revealed a non-significant reduction in survival in pooled (1806.3±367.5 cells) rat
and mouse co-transplants without immunosuppression compared with immunosuppressed pooled (3383.3±732.7 cells) animals with
allo- and xenogeneic tissue and controls (3506.4±839.3 cells). Graft volumes were significantly reduced in pooled transplants
without immunosuppression (0.1±0.026 mm3; ANOVA post-hoc SchefféF-test, P<0.0001) compared with immunosuppressed recipients (0.7±0.1 mm3) and controls (0.6±0.1 mm3). In non-pooled allo- and xenogeneic grafts without immunosuppression the survival rate of the TH-immunoreactive cells and
graft volumes were reduced (2359.3±479.5 cells; 0.2±0.043 mm3) compared with immunosuppressed animals (2927.3±946.6 cells; 0.6±0.2 mm3) and controls (2701.1±693.8 cells; 0.3±0.1 mm3) without reaching a level of significance. Rejection of mouse tissue was observed in all non-immunosuppressed recipients.
In summary: (i) continued immunosuppression yielded significant beneficial effects on function and beneficial effects on survival
of pooled grafts with an immunogenetic disparity; (ii) the rejection of a xenogeneic graft component may compromise survival
and function of other, allogeneic graft components; and (iii) transplantation of non-pooled allo- and xenogeneic tissues may
result in a better survival of the graft compared with pooled cell suspensions.
Received: 25 March 1996 / Accepted: 1 December 1996 相似文献
188.
卵巢癌细胞多种细胞因子基因表达的研究 总被引:1,自引:0,他引:1
本文应用RT-PCR方法,检测5例刚分离的晚期上皮性卵巢癌患者肿瘤细胞和3例卵巢痛患者腹水中肿瘤细胞IL-2、IL-2R、TNF-a,IL-6、TGF-p、IL-10等细胞因子基因的表达,用免疫学方法检测卵巢癌细胞上清液中IL-6活性。结果发现:卵巢癌肿瘤细胞表达IL-6mRNA和抑制性细胞因子TGF-p、IL-10。腹水中存在较多量lL-6可能来自肿瘤细胞。 相似文献
189.
Manfred Kopf Suzanne Herren Michael V. Wiles Mark B. Pepys Marie H. Kosco-Vilbois 《The Journal of experimental medicine》1998,188(10):1895-1906
Mice rendered deficient for interleukin (IL) 6 by gene targeting were evaluated for their response to T cell–dependent antigens. Antigen-specific immunoglobulin (Ig)M levels were unaffected whereas all IgG isotypes showed varying degrees of alteration. Germinal center reactions occurred but remained physically smaller in comparison to those in the wild-type mice. This concurred with the observations that molecules involved in initial signaling events leading to germinal center formation were not altered (e.g., B7.2, CD40 and tumor necrosis factor R1). T cell priming was not impaired nor was a gross imbalance of T helper cell (Th) 1 versus Th2 cytokines observed. However, B7.1 molecules, absent from wild-type counterparts, were detected on germinal center B cells isolated from the deficient mice suggesting a modification of costimulatory signaling. A second alteration involved impaired de novo synthesis of C3 both in serum and germinal center cells from IL-6–deficient mice. Indeed, C3 provided an essential stimulatory signal for wild-type germinal center cells as both monoclonal antibodies that interrupted C3-CD21 interactions and sheep anti–mouse C3 antibodies caused a significant decrease in antigen-specific antibody production. In addition, germinal center cells isolated from C3–deficient mice produced a similar defect in isotype production. Low density cells with dendritic morphology were the local source of IL-6 and not the germinal center lymphocytes. Adding IL-6 in vitro to IL-6–deficient germinal center cells stimulated cell cycle progression and increased levels of antibody production. These findings reveal that the germinal center produces and uses molecules of the innate immune system, evolutionarily pirating them in order to optimally generate high affinity antibody responses. 相似文献
190.
MARION FRANKENBERGER BARBARA HOFMANN BERTOLD EMMERICH CHRISTOPH NERL RETO A. SCHWENDENER & H.W. LÖMS ZIEGLER -HEITBROCK 《British journal of haematology》1997,98(1):186-194
The vitamin D3 derived hormone 1,25 (OH)2 vitamin D3 (1,25 D3 ) is able to induce growth arrest and differentiation in myelomonocytic leukaemia cells. In order to allow for specific delivery to leukaemic cells the lipophilic compound was incorporated into the lipid membranes of liposomes. Liposomal 1,25 D3 reduced proliferation as measured by 3 H-thymidine incorporation in HL60 leukaemia cells by up to 60%. When liposomes were prepared at different concentrations of 1,25 D3 65% inhibition was achieved at 48 n M . The MC 1288 stereoisomer of 1,25 D3 was more potent and had the same activity at 48 n M .
The effect of the liposomal compounds was specific to myeloid cells as they reduced proliferation in myelomonocytic HL60, monoblastic U937 and monocytic Mono Mac 6 cells but not in the T-cell lines Jurkat and Molt 4.
The antiproliferative effect of liposomal 1,25 D3 was associated with an induction of differentiation since treated HL60 cells showed a monocytic morphology, increased expression of CD14 and decreased expression of CD33.
When peripheral blood leukaemic cells from M4 and M5 acute myeloid leukaemia (AML) patients were admixed with liposomal compounds an antiproliferative effect was seen in all five cases, including the two cases where free compounds led to enhanced growth. Liposomal delivery of 1,25 (OH)2 vitamin D3 may offer a novel approach to treatment of myelomonocytic leukaemia. 相似文献
The effect of the liposomal compounds was specific to myeloid cells as they reduced proliferation in myelomonocytic HL60, monoblastic U937 and monocytic Mono Mac 6 cells but not in the T-cell lines Jurkat and Molt 4.
The antiproliferative effect of liposomal 1,25 D
When peripheral blood leukaemic cells from M4 and M5 acute myeloid leukaemia (AML) patients were admixed with liposomal compounds an antiproliferative effect was seen in all five cases, including the two cases where free compounds led to enhanced growth. Liposomal delivery of 1,25 (OH)