他克莫司与环孢菌素A对肝移植受者CD4/CD8 T淋巴细胞亚群及共刺激分子的调节作用

目的:探讨他克莫司(Tacrolimus, FK506)与环孢菌素A(CsA)对肝移植受者T淋巴细胞亚群共刺激分子的调节作用.方法:采用荧光标记单克隆抗体(mAb)结合流式细胞技术, 测定移植术后使用FK506或CsA治疗2月末的肝移植受者外周血T细胞亚群及其表面共刺激分子CD28、CD152 和ICOS的表达情况.以健康志愿者(健康对照组)和患终末期肝脏疾病拟进行肝移植者(疾病对照组)为对照.结果:疾病对照组T细胞亚群平衡紊乱、共刺激分子表达异常(P＜0.05).治疗组肝移植受者T淋巴细胞亚群表达恢复至健康对照水平, T细胞表面CD28和ICOS分子表达显著降低(P＜0.05)而CD152分子表达明显升高(P＜0.05).比较不同药物治疗组:CsA治疗组CD4 T细胞表达和CD8 T细胞表面CD28、CD152分子表达均明显高于FK506治疗组(P＜0.05);其他指标无统计学意义(P＞0.05).结论:在常规血药浓度条件下FK506和CsA的对CD4/CD8T细胞亚群及共刺激分子的免疫调节作用存在差异.FK506对T细胞亚群的调节作用强于CsA.FK506可同时抑制正性共刺激分子CD28和ICOS表达并促进负性共刺激分子CD152表达, 而CsA对T细胞免疫抑制作用主要是通过促进CD152分子的高表达介导.     

CD4+ICOS+ T lymphocytes inhibit T cell activation 'in vitro' and attenuate autoimmune encephalitis 'in vivo'

The inducible co-stimulator (ICOS, CD278) is essential to theefficient development of normal and pathological immune reactions.Since ICOS-deficient mice have enhanced susceptibility to experimentalallergic encephalomyelitis (EAE), we have functionally analyzeda CD4⁺ICOS⁺ population comprising 6–15% of all CD4⁺ Tcells in secondary lymphoid organs of unmanipulated wild-typemice and checked for their ability to suppress EAE. In C57BL/6mice, CD4⁺ICOS⁺ cells were a major source of cytokines includingIFN-, IL-2, IL-4, IL-10 or IL-17A. Upon activation, these cellsshowed preferentially enhanced production of IL-4 or IL-10 butinhibited IFN- production. In contrast, CD4⁺ICOS^– cellsmainly produced IFN-. Interestingly, CD4⁺ICOS⁺ cells partiallysuppressed the proliferation of CD4⁺ICOS^– or CD4⁺CD25^–lymphocytes ‘in vitro’ by an IL-10-dependent mechanism.Furthermore, CD4⁺ICOS⁺ activated and expanded under appropriateconditions yielded a population enriched in cells producingIL-10 and T_h2 cytokines that also suppressed the proliferationof CD4⁺CD25^– lymphocytes. CD4⁺ICOS⁺ cells, before or afterexpansion in vitro, reduced the severity of EAE when transferredto ICOS-deficient mice. In the same EAE model, lymph node cellsfrom ICOS-deficient mice receiving ICOS⁺ cells showed reducedIL-17A production and enhanced IL-10 secretion upon antigenactivation in vitro. Thus, naturally occurring CD4⁺ICOS⁺ cells,expanded or not in vitro, are functionally relevant cells ableof protecting ICOS-deficient mice from severe EAE.     

AILIM/ICOS signaling induces T-cell migration/polarization of memory/effector T-cells

AILIM/ICOS has critical roles in the regulation of T-cell differentiation and effector T-cell function in various immune responses. The counter-ligand for AILIM/ICOS, B7h, is widely expressed in not only lymphoid tissue and antigen-presenting cells, but also in fibroblast and endothelial cells in various organs. Here, we demonstrate that activated human T-cells migrate beneath TNF-alpha-treated HUVEC and display morphological polarization via AILIM/ICOS signaling. AILIM/ICOS stimulation, in the absence of antigen stimulation, also induced T-cell polarization. Importantly, AILIM/ICOS-mediated polarization was evident in CD4+CD45RO+ memory T-cells and generated Th1 cells, but not in CD4+CD45RA+ naive T-cells and generated Th2 cells. Furthermore, AILIM/ICOS signaling is involved in transendothelial migration of Th1 cells, but not Th2 cells. Our data suggest that AILIM/ICOS-B7h interactions play an important role in the endothelium in controlling the entry of memory/effector T-cells into inflamed tissues in the periphery.     

Association studies of CTLA-4, CD28, and ICOS gene polymorphisms with B-cell chronic lymphocytic leukemia in the Polish population

Abnormal expression of the costimulatory molecules cytotoxic T-lymphocyte antigen 4 (CTLA-4), CD28, and inducible co-stimulator (ICOS) leads to disturbances of immune response and an increased risk of cancer. An extended study was undertaken to evaluate the association among the polymorphisms CTLA-4c.49A>G, CTLA-4g.319C>T, CTLA-4g.*642AT(8_33), CD28c.17+3T>C, and ICOSc.1554+4GT(8_15) and susceptibility to B-cell chronic lymphocytic leukemia (B-CLL) in the Polish population. The study revealed increased frequency of the CTLA-4g.319C>T [T] allele and the CTLA-4g.319C>T [T] phenotype in B-CLL patients compared with healthy controls (p = 0.003, odds ratio [OR] = 1.73; and p = 0.009, OR = 1.74, respectively). The presence of the CD28c.17+3T>C [C] allele and the CD28c.17+3T>C [C] phenotype increased the OR of B-CLL to 1.59 (p = 0.007) and 1.74 (p = 0.007), respectively. Either CTLA-4g.319C>T or CD28c.17+3T>C was associated with time to Rai stage progression. The distributions of the alleles and genotypes of the ICOS gene significantly differed between patients and controls (p = 0.0009 and p = 0.006, respectively). Individuals possessing short alleles were 2.02 times more prone to B-CLL than others (p = 0.001), whereas carriers of long alleles were protected from B-CLL (p = 0.02, OR = 0.62). The haplotype association study and multivariate analysis confirmed the association of CTLA-4g.319C>T and ICOSc.1554+4GT(8_15) gene polymorphisms with B-CLL. The polymorphic sites CTLA-4c.49A>G and CTLA-4g.*642AT(8_33) did not correlate with B-CLL. Our results are the first in the literature to report that gene polymorphism of the costimulatory molecules CTLA-4, CD28, and ICOS contributes to susceptibility to B-CLL.     

CTLA-4, CD28, and ICOS gene polymorphism associations with non-small-cell lung cancer

Polymorphisms in genes encoding CD28, ICOS, and CTLA-4 were demonstrated to be associated with susceptibility to malignancies. To the best of our knowledge, no study on this association has been performed in a Caucasian population for non-small-cell lung cancer (NSCLC). In the present work, we investigated the polymorphisms CTLA-4c.49A>G (rs231775), CTLA-4g.319C>T (rs5742909), CTLA-4g.*642AT(8_33), CTLA-4g.*6230G>A (CT60) (rs3087243), CTLA-4g.*10223G>T (Jo31) (rs11571302), CD28c.17+3T>C (rs3116496), and ICOSc.1554+4GT(8_15) in 208 NSCLC patients and 326 controls. The distributions of the allele and genotype were similar in both groups for CTLA-4, CD28, and ICOS gene polymorphisms. However, we noted a tendency toward overrepresentation of individuals possessing the CTLA-4c.49A>G[A] allele in NSCLC patients compared with controls (0.84 vs 0.79, p = 0.09). The association became significant compared with controls in women for the CTLA-4c.49A>G[A] allele and CTLA-4c.49A>G[AA] genotype (0.67 vs 0.54, p = 0.01, and 0.47 vs 0.30, p = 0.02; respectively). Moreover, the constellation of alleles CTLA-4c.49A>G[A]/CT60[G]/CD28c.17+3T>C[T]/ICOSc.1554+4GT(8_15)[>10] increased the risk of NSCLC about 2-fold (p = 0.002). The same constellation of alleles combined with smoking, CTLA-4g.319C>T[T], and ICOSc.1554+4GT(8_15)[>10] was associated with a decreased overall survival rate. In conclusion, the constellation of specific alleles in CTLA-4, CD28, and ICOS genes contributes to the susceptibility and clinical course of NSCLC.     

L1 cell adhesion molecule as a novel independent poor prognostic factor in gallbladder carcinoma

Gallbladder carcinoma is a lethal malignancy and is hard to cure by current treatment. Thus, identification of molecular prognostic markers to predict gallbladder carcinoma as therapeutic targets is urgently needed. Recent studies have demonstrated that L1 cell adhesion molecule is associated with the prognosis of variable malignancy. Here, we investigated L1 cell adhesion molecule expression in gallbladder carcinoma and its prognostic significance. In this study, we examined L1 cell adhesion molecule expression in tumor specimens from 69 patients with gallbladder carcinoma by immunohistochemistry and analyzed the correlation between L1 cell adhesion molecule expression and clinicopathologic factors or survival. L1 cell adhesion molecule was not expressed in the normal epithelium of the gallbladder but in 63.8% of gallbladder carcinomas, remarkably at the invasive front of the tumors. In addition, L1 cell adhesion molecule expression was significantly associated with high histologic grade, advanced pathologic T stage and clinical stage, and positive venous/lymphatic invasion. Multivariate analyses showed that L1 cell adhesion molecule expression (hazard ratio, 3.503; P = .028) and clinical stage (hazard ratio, 3.091; P = .042) were independent risk factor for disease-free survival. L1 cell adhesion molecule expression in gallbladder carcinoma was significantly correlated with tumor progression and unfavorable clinicopathologic features. L1 cell adhesion molecule expression was an independent poor prognostic factor for disease-free survival in patients with gallbladder carcinoma. Taken together, our findings suggest that L1 cell adhesion molecule expression could be used as a novel prognostic factor for patient survival and might be a potential therapeutic target in gallbladder carcinomas.     

ICOS/GL50信号在T细胞依赖性体液免疫应答中的作用

研究ICOS/GL5 0信号在T细胞体外增殖、细胞因子分泌以及B细胞抗体分泌中的作用 ,进一步探讨该信号途径在机体体液免疫应答中的作用机制。采用3 H TdR检测GL5 0 L92 9转染细胞和特异性鼠抗人GL5 0单抗对T细胞体外增殖的作用 ;ELISA法检测GL5 0 L92 9转染细胞和抗人GL5 0单抗对T细胞分泌IL 2、IL 10以及ICOS L92 9转染细胞和特异性鼠抗人GL5 0单抗对PWM介导的B细胞分泌抗体的效应。结果提示GL5 0 L92 9转染细胞能够促进经抗CD3单抗活化的T细胞增值和分泌IL 10 ,而抗GL5 0单抗可以阻断这些效应。ICOS分子与B细胞上GL5 0分子的结合上调PWM介导的B细胞分泌抗体而抗GL5 0单抗则下调这一效应。这些表明 ,ICOS/GL5 0信号途径在机体T细胞依赖的体液免疫应答反应中发挥着重要的调节作用     

ICOS is required for the generation of both central and effector CD4+ memory T‐cell populations following acute bacterial infection

Interactions between ICOS and ICOS ligand (ICOSL) are essential for the development of T follicular helper (Tfh) cells and thus the formation and maintenance of GC reactions. Given the conflicting reports on the requirement of other CD4⁺ T‐cell populations for ICOS signals, we have employed a range of in vivo approaches to dissect requirements for ICOS signals in mice during an endogenous CD4⁺ T‐cell response and contrasted this with CD28 signals. Genetic absence of ICOSL only modestly reduced the total number of antigen‐specific CD4⁺ T cells at the peak of the primary response, but resulted in a severely diminished number of both T central memory and T effector memory cells. Treatment with blocking anti‐ICOS mAb during the primary response recapitulated these effects and caused a more substantial reduction than blocking CD28 signals with CTLA4Ig. During the memory phase of the response further signals through ICOS or CD28 were not required for survival. However, upon secondary challenge only Tfh cell expansion remained heavily ICOS‐dependent, while CD28 signals were required for optimal expansion of all subsets. These data demonstrate the importance of ICOS signals specifically for memory CD4⁺ T‐cell formation, while highlighting the potential of therapeutically targeting this pathway.     

Abrogation of ICOS/ICOS ligand costimulation in NOD mice results in autoimmune deviation toward the neuromuscular system

NOD mice spontaneously develop insulin‐dependent diabetes around 10–40 wk of age. Numerous immune gene variants contribute to the autoimmune process. However, genes that direct the autoimmune response toward β cells remain ill defined. In this study, we provide evidence that the Icos and Icosl genes contribute to the diabetes process. Protection from diabetes in ICOS^?/? and ICOSL^?/? NOD mice was unexpectedly associated with the development of an autoimmune disorder of the neuro‐muscular system, characterized by myositis, sensory ganglionitis and, to a reduced extent, inflammatory infiltrates in the CNS. This syndrome was reproduced upon adoptive transfer of CD4⁺ and CD8⁺ T cells from diseased donors to naïve NOD.scid recipients. Our data further show that protection from diabetes results from defective activation of autoimmune diabetogenic effector T cells in ICOS^?/? NOD mice, whereas acceleration of diabetes in BDC2.5 ICOS^?/? NOD mice is induced by a dominant defect in Treg. Taken together, our findings indicate that costimulation signals play a key role in regulating immune tolerance in peripheral tissues and that the ICOS/ICOSL costimulatory pathway influences the balance between Treg and diabetogenic effector T cells.     

Expression of E-selectin, intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 in non-small-cell lung carcinoma

Vascular cell adhesion molecules (VCAM) play an important part in the regulation of inflammation and are considered to be important in the process of malignant tumour growth. The present study describes the immunohistochemical staining patterns of E-selectin, intercellular adhesion molecule (ICAM)-1 and VCAM-1 on endothelial cells of the vessels in tumour stroma and other cell types in non-small-cell lung carcinoma (NSCLC; n=43) in association with inflammatory cells. Expression of E-selectin was dominant on endothelial cells in the stromal areas of the tumour, especially at the borders, and was confined to endothelial cells. Moderate to strong staining for ICAM-1 was demonstrated on endothelial cells irrespective of size or localization of the vessels. Compared with ICAM-1, fewer vessels were positive for VCAM-1, and stained with lesser intensity. ICAM-1 expression was demonstrated on NSCLC cells, the basal cells of bronchial epithelium, type II pneumocytes, lymphocytes and fibroblasts. VCAM-1 was clearly expressed on NSCLC cells in 4 of the 43 cases and on lymphocytes and fibroblasts. The staining patterns observed on endothelial cells support the idea of an active status of NSCLC vessels. This phenotypic pattern looks similar to the vascular component of inflammation. The presence of ICAM-1 and VCAM-1 on NSCLC cells suggests a functional role in the process of chemotaxis for tumour cells.     

细胞粘附分子CD15在肝癌组织中的表达

目的：观察细胞粘附分子ＣＤ１５在肝癌组织中的表达情况及肝脏良恶性病变的鉴别价值，方法：应用免疫组化ＳＰ法观察细胞粘附人子ＣＤ１５在７例正常肝组织，１３例肝硬变（５例伴轻－中度不典型增生）和４９例肝细胞癌组织中的表达。结果：正常肝组织和肝硬变组织中均无ＣＤ１５表达，仅肝癌组织中出现ＣＤ１５阳性表达，阳性率为３０．６％（１５／４９），ＣＤ１５表达与患者性别，年龄，肝癌肉眼形态，组织分化程度无明显关系（     

Stem cell therapy targets the neointimal smooth muscle cells in experimentally induced atherosclerosis: involvement of intracellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM)

Smooth muscle cells (SMCs) are currently considered a central pivotal player in pathogenesis and development of atherosclerotic lesions. As consequence of vascular injury, SMCs migrate from the tunica media into the tunica intima layers where they contribute to neointimal formation by converting into foam cells and producing pro-inflammatory and oxidative stress markers. We targeted the replacement of neointimal SMCs by using the mesenchymal stem cells (MSCs) therapy in experimentally induced atherosclerosis in an attempt to improve the atherosclerotic lesion and its concomitant complications. Rats were divided into 4 groups (n=20). Control group: rats kept on a standard chow diet; atherosclerotic group: rats received the atherogenic diet; stem cells-treated group: rats were injected with CD34⁺ stem cells (6×10⁶ cells in 0.5 mL PBS in rat tail vein) and maintained on the atherogenic diet; and resveratrol-treated group: rats were supplemented orally with resveratrol at a dose level 3 mg/kg per day and the atherogenic diet. After 12 weeks, rats were euthanized, blood samples were collected for separation of serum, and abdominal aortas were excised for further biochemical, molecular, and histopathological investigations. We used resveratrol, the well-established anti-atherosclerotic drug, as a benchmark to assess the efficacy of stem cell therapy. MSCs treatment revealed significant amelioration in both histopathological and biochemical patterns as evidenced by decreased foam cells formation, ICAM-1, VCAM, M-CSF, iNOS, COX-2, and TNF-α. We concluded that MSCs therapy significantly replaced the neointimal SMCs and decreased adhesion molecules as well as the oxidative and inflammatory markers in atherosclerosis.     

Neural cell adhesion molecule expression in renal cell carcinomas: relation to metastatic behavior

Neural cell adhesion molecule (NCAM), a member of the immunoglobulin superfamily, is expressed by a subgroup of renal cell carcinomas (RCCs) and by a limited number of adult organs, including the central nervous system (CNS) and adrenal gland. Because the major function of NCAM is homophilic adhesion between homotypic and heterotypic cells, we hypothesized that NCAM-expressing RCCs should preferentially metastasize to the CNS and adrenal gland. We did a retrospective immunohistochemical analysis of NCAM expression both in 338 primary renal tumors, including 249 conventional RCCs and 31 metastases of conventional RCCs. In primary renal tumors, NCAM was expressed by only 38 (15.2%) conventional RCCs and by no other histological subtypes of renal tumor. This expression correlated with a higher risk of adrenal and CNS metastases (P <0.001). NCAM expression also correlated with tumor size (P <0.001), renal vein involvement (P = 0.02), perirenal invasion (P = 0.02), and Fuhrman grading (P < 0.001). Finally, patients with NCAM-expressing RCCs had a lower survival rate (P = 0.006), especially in the first 2 years after surgery. NCAM expression is of interest both for evaluating the prognosis of patients with conventional RCCs and for determining a subgroup of patients at high risk for adrenal and CNS metastases.     

Sialomucin CD43 regulates T helper type 17 cell intercellular adhesion molecule 1 dependent adhesion,apical migration and transendothelial migration

T helper type 17 lymphocytes (Th17 cells) infiltrate the central nervous system (CNS), induce inflammation and demyelination and play a pivotal role in the pathogenesis of multiple sclerosis. Sialomucin CD43 is highly expressed in Th17 cells and mediates adhesion to endothelial selectin (E-selectin), an initiating step in Th17 cell recruitment to sites of inflammation. CD43^−/− mice have impaired Th17 cell recruitment to the CNS and are protected from experimental autoimmune encephalomyelitis (EAE), the mouse model of multiple sclerosis. However, E-selectin is dispensable for the development of EAE, in contrast to intercellular and vascular cell adhesion molecules (ICAM-1 and VCAM-1). We report that CD43^−/− mice have decreased demyelination and T-cell infiltration, but similar up-regulation of ICAM-1 and VCAM-1 in the spinal cord, compared with wild-type (WT) mice, at the initiation of EAE. CD43^−/− Th17 cells have impaired adhesion to ICAM-1 under flow conditions in vitro, despite having similar expression of LFA-1, the main T-cell ligand for ICAM-1, as WT Th17 cells. Regardless of the route of integrin activation, CD43^−/− Th17 cell firm arrest on ICAM-1 was comparable to that of WT Th17 cells, but CD43^−/− Th17 cells failed to optimally apically migrate on immobilized ICAM-1-coated coverslips and endothelial cells, and to transmigrate under shear flow conditions in an ICAM-1-dependent manner. Collectively, these findings unveil novel roles for CD43, facilitating adhesion of Th17 cells to ICAM-1 and modulating apical and transendothelial migration, as mechanisms potentially responsible for Th17 cell recruitment to sites of inflammation such as the CNS.     

共刺激信号分子表达异常与自身免疫性疾病的关系

目的 分析类风湿性关节炎（RA）和系统性红斑狼疮（SLE）细胞免疫异常中共刺激活化信号途径的异同点,探讨细胞活化的共刺激信号途径对于RA和SLE发病的意义。方法 采用流式细胞术分析SLE和RA患者T细胞表面共刺激分子CD28、CD152／CTLA-4、CD154／CD40L和ICOS表达情况。结果 ①RA患者CD4^＋T细胞比例明显增加,SLE患者以CD8^＋T细胞增加显著。②SLE患者CD4^＋和CD8^＋T细胞上CD28和CD152的表达增加;RA患者T细胞亚群上CD28分子的表达减少,CD152分子的表达增加。③RA患者CD4^＋T细胞上CD154分子表达增加,CD8^＋T细胞上CD154分子表达减少,T细胞亚群上可诱导共刺激分子（ICOS）的表达无明显变化;SLE患者CD4^＋和CD8^＋T细胞上CD1254或ICOS分子的表达均减少。结论 RA和SLE患者机体的免疫异常中存在着明显的分子信号途径差异。     

SLE患者外周血T细胞亚群ICOS与CD28共表达水平与疾病的关系

目的观察系统性红斑狼疮(systemic lupus erythematosus，SLE)病人外周血CD4^ 及CD8^ T细胞表面可诱导共刺激分子(inducible co-stimulator，ICOS)及CD28共表达水平，探讨ICOS和CD28共表达水平与SLE疾病的关系。方法采用三色流式细胞术检测SLE病人(n=51)及正常人(n=30)外周血CD4^ 及CD8^ T细胞表面ICOS与CD28共表达水平，并结合SLE病人疾病活动程度、临床表现等进行分析。结果与正常人相比，SLE活动期和稳定期病人外周血CD4^ T细胞中仅表达ICOS不表达CD28(即CD28^-ICOS^ )的细胞比例明显升高，但活动期病人和稳定期病人之间并无差异；活动期病人外周血CD8^ T细胞上同时表达CD28和ICOS的细胞(即CD28^ ICOS^ 细胞)和CD28^-ICOS^ 细胞比例都明显升高；同一SLE病人在疾病活动期CD4^ 和CD8^ T细胞中CD28^ ICOS^ 的细胞比例和CD8^ T细胞中CD28-ICOS^ 细胞比例明显高于该病人经过治疗病情稳定时；初发未治疗SLE病人仅CD4^ T细胞中CD28^ ICOS^ 细胞的比例比复发病人明显升高；血清抗dsDNA抗体( )病人和血清免疫球蛋白含量(IsG、IgA和IgM中任何一种)异常升高的病人外周血CD4^ T细胞中CD28^ ICOS^ 细胞和CD8^ T细胞中CD28-ICOS^ 细胞比例分别明显高于血清抗dsDNA抗体(-)和血清免疫球蛋白含量正常的病人。结论CD28和ICOS在SLE病人外周血CD4^ 和CD8^ T细胞上共表达水平与SLE疾病的活动程度、病程及临床表现等存在一定的关联。     

Hyalin is a cell adhesion molecule involved in mediating archenteron-blastocoel roof attachment

The US National Institutes of Health has designated the sea urchin embryo as a model organism because around 25 discoveries in this system have led to insights into the physiology of higher organisms, including humans. Hyalin is a large glycoprotein in the hyaline layer of sea urchin embryos that functions to maintain general adhesive relationships in the developing embryo. It consists of the hyalin repeat domain that has been identified in organisms as diverse as bacteria, worms, flies, mice, sea urchins and humans. Here we show, using a polyclonal antibody raised against the 11.6 S species of hyalin, that it localizes at the tip of the archenteron and on the roof of the blastocoel exactly where these two structures bond in an adhesive interaction that has been of interest for over a century. In addition, the antibody blocks the interaction between the archenteron tip and blastocoel roof. These results, in addition to other recent findings from this laboratory that will be discussed, suggest that hyalin is involved in mediating this cellular interaction. This is the first demonstration that suggests that hyalin functions as a cell adhesion molecule in many organisms, including humans.     

Neural cell adhesion molecule is upregulated in nerves with prostate cancer invasion

Currently postulated mechanisms of perineural invasion (PNI) include interaction between tumor cells and nerves. Neural cell adhesion molecule (N-CAM), one of the well-known members of the immunoglobulin super-family of adhesion molecules, was implicated in PNI and metastasis in various types of cancer. Tissue microarray technology was used to build 2 sets of tissue array (with versus without PNI) from 50 prostate cancers (PCa). The slides were stained immunohistochemically, and the results were evaluated semiquantitatively using a 0 to 3+ scoring system. N-CAM staining was observed in all nerves with variable intensity. N-CAM expression was upregulated in 73% (31 of 42) of the nerves with PNI compared with nerves without PNI (P >.001). The results suggested that N-CAM is probably involved in PNI in PCa. It is conceivable that cancer cells, through a yet-to-be-established paracrine loop, signal the nerve to increase N-CAM production and increase adhesion. N-CAM upregulation in nerves may also facilitate cancer cells to migrate toward nerves and promote the process of perineural spread through increased survival using the nuclear factor kappa B pathway.     

Rapid detection of intercellular adhesion molecule 1 (G241R and K469E) polymorphisms by a novel PCR-SSP assay

Intercellular adhesion molecule 1 (ICAM-1) is a cell surface glycoprotein member of the immunoglobulin superfamily and is actively involved in immune and inflammatory responses. We introduce a novel polymerase chain reaction-sequence-specific primers (PCR-SSP) method for rapid and simultaneous genotyping of ICAM-1 G241R and K469E polymorphisms. In a total of 184 DNA samples that have been previously analyzed for these polymorphisms using polymerase chain reaction-restriction fragment length polymorphism technique, re-genotyping of all samples with this new assay showed accurate and reproducible results. As PCR-SSP-based genotyping protocols are more convenient and cost-effective to do, it could therefore offer a valuable tool for assessment of ICAM-1 polymorphisms to which more confirmatory studies are needed.     

神经黏附分子NB-3在中枢神经系统中的功能

神经黏附分子属于免疫球蛋白超家族，它不仅在发育中与形成轴突生长方向和突触连接有关，而且在成体的突触可塑性和记忆中也发挥重要的作用。NB-3是1996年发现的神经黏附分子，属于免疫球蛋白超家族的Contactin亚家族，集中表达于神经系统。NB-3可促进神经元轴突的生长，参与少突胶质细胞的分化与成熟，促进小脑发育及功能维持。