TGF-β1 Null Mutation Leads to CD154 Upregulated Expression in Affected Tissues

The TGF-1(–/–) mouse is a murine model for systemic autoimmune disease. The aim of this study is to elucidate the immunological mechanism that leads to multifocal tissue inflammation and autoantibody production in TGF-1(–/–) mice. Heart, lung, liver, and salivary gland from TGF-1(–/–) were assessed for CD154 expression by RT-PCR and immunohistochemistry. Compared to wild-type littermates, CD154 expression was elevated in all tissues studied. Furthermore, IL-12 mRNA was expressed in the salivary gland and heart of TGF-1(–/–) mice and not in wild-type littermates. This suggests that the CD154 pathway is activated in these tissues. This shows that TGF-1 regulates CD154 expression leading to spontaneous IL-12 production and autoimmunity.     

Direct evidence for clonal destruction of allo-reactive T cells in the mice treated with cyclophosphamide after allo-priming.

It has previously been reported that a single i.p. injection of 200 mg/kg cyclophosphamide (CP) 2 days after priming with 10(8) donor spleen cells (SC) leads to donor-specific skin allograft tolerance in H-2 compatible, multiminor antigen incompatible murine strain combinations. It is speculated that the i.v. injection of donor cells may result in synchronized proliferation of donor-reactive host T cells and subsequently administered CP may specifically destroy these proliferating T cells in the periphery. Although this unique action of CP is considered to be a principal mechanism in this method, direct evidence has not yet been obtained. In the present article, this in vivo destructive effect of CP is clearly demonstrated by assessing detailed kinetics of host-derived blastoid T cells and donor (Mls-1a)-reactive V beta 6+ T cells in the model system of C3H mice rendered tolerant to AKR. Frequencies of the blastoid cells and V beta 6+ cells, which increased as a result of AKR priming, decreased rapidly with the administration of CP. C3H mice, which received AKR SC alone, also exhibited partial deletion of V beta 6+ T cells, but both tempo and magnitude of decrease in the frequency of V beta 6+ cells were quite different from those of the C3H mice given AKR SC and CP, which showed more rapid and profound elimination of V beta 6+ T cells. In accordance with these kinetic studies, in vitro proliferative response to Mls-1a antigens was greatly impaired in mice treated with SC and CP, whereas a low but appreciable response was detected in mice given SC alone.(ABSTRACT TRUNCATED AT 250 WORDS)     

针刺过程中有衣小泡的形成、形态特征及其数量变化的研究

针刺大鼠“人中”、“四白”穴使之产生明显镇痛效果后,再将针刺时间分别延长至1、2、4、6、8、10、12h,到预定时间立即将动物灌流杀死取材,采用定量电镜方法观察计数了三叉神经尾侧脊束核胶状质亚核内各种有衣小泡的数量、形态以及在不同针刺时间内数量的变化。结果发现:大单壁有衣小泡的形成与针刺时间无明显正比例关系;而双壁有衣小泡则显然与之不同,它不仅形态多样,数目也随针刺时间而改变。本文将观察到的双壁有衣小泡归纳为以下五种类型:1、尚未与相邻两终末质膜脱离的孤立存在者。2、游离于终末内孤立存在者。3、与终末质膜相连且融合而成簇存在者;4、游离于终末内融合成簇者;5、树突棘凸入另一轴突或树突内并与之共同形成的不典型的双壁有衣小泡簇。本研究还发现,在针刺过程中双壁有衣小泡在1～8h内的形成与时间成正比,即1h时开始增多,4h显著增多,8h达高峰;以后开始下降,10h已恢复到4h的水平,到12h恢复到针刺前的状态。对照组仅见少数孤立的双壁有衣小泡,其形成基本上不随时间而变化。本文认为双壁有衣小泡的形成,是较大单壁有衣小泡的形成更为有效地继大致密核心小泡非突触部位胞吐之后膜再循环的一条新途径。     

Relationships among genotypes, virulence and clinical forms of Sporothrix schenckii infection

This study explored the relationships among genotypes, virulence and clinical forms of Sporothrix schenckii. Genomic DNA from isolates of S. schenckii, collected from different clinical forms of sporotrichosis, was amplified by randomly amplified polymorphic DNA (RAPD). Suspensions of different isolates of S. schenckii were inoculated into healthy BALB/c mice to compare their virulence, and the numbers and distribution of spores were determined by histological analysis. RAPD analysis indicated that the isolates from different clinical forms of sporotrichosis belonged to different genotypes. The mice inoculated with isolates from disseminated sporotrichosis showed an earlier onset of illness and more severe lesions than those inoculated with isolates from lymphocutaneous sporotrichosis, which, in turn, showed an earlier onset of illness and more severe lesions than those inoculated with isolates from fixed cutaneous sporotrichosis. Healthy BALB/c mice injected with isolates from disseminated sporotrichosis died within 10 days, whereas isolates from lymphocutaneous sporotrichosis and fixed cutaneous sporotrichosis failed to cause death. Histologically, mice inoculated with isolates from disseminated sporotrichosis had more spores than those inoculated with isolates from lymphocutaneous sporotrichosis and fixed cutaneous sporotrichosis. Thus, different genotypes may be associated closely with the virulence of different clinical forms of S. schenckii infection.     

单宁酸—金属盐联用媒染脑血管的研究

用２％多聚甲醛，２％戊二醛配伍不同浓度的单宁酸媒染固定液灌流大鼠，取服切片，放入２％氯化铁溶液中呈色，成功地显示了脑内各级血管及毛细血管网的形貌。高倍镜下可见各级血管呈空心管道状，基僻赤多条细纤维丝状结构编织或呈同心圆状排列而成，具有较强的立体感。     

左结肠动脉的应用解剖

在88例左半结肠标本上,观察了左结肠动脉。根据其行走位置不同,分为内侧型和外侧型。按左结肠动脉分叉点的高度不同又分为高位组、中位组和低位组。左结肠动脉分支中有一种直血管,向左连于降结肠的缘动脉,这些血管在作肠修复时,对促进左半结肠的血供有重要意义。根据左结肠动脉的解剖特点,提出了裁剪左半结肠时,切断左结肠动脉的要点。     

雷公藤红素对人肥大细胞系粘附能力和粘附分子表达的影响

雷公藤红素是雷公藤单体之一.本文研究雷公藤红素对人肥大细胞系HMC-1细胞粘附及粘附分子表达的影响.结果发现:HMC-1细胞能自发地表达β1、β3型整合素和CD44,不表达β2型整合素,具有迅速粘附于鼠尾胶的能力,在粘附过程中细胞由圆形、椭圆形变成梭形、多极形.雷公藤红素与HMC-1细胞在粘附前或粘附后共育均能以剂量和时间依赖方式抑制粘附和粘附过程中细胞形态的变化,并可下调粘附分子的表达.提示:雷公藤红素能抑制HMC-1细胞的粘附,这一作用与其抑制粘附分子表达和细胞形态的改变有关.     

酵母双杂合系统AD端阴离子交换蛋白C-末端表达质粒的构建

利用PCR方法，从阴离子交换蛋白1（AE1）全长cDNA中扩增出约350bp c末端cDNA片段，测序后将其克隆至pGADT7载体上，用醋酸锂法构建好的pADT7-AE1-c末端转染酵母菌HA109，观察其在选择性培养基上的表达情况。结果表明，获得了530bp AE1c－末端cDNA,pGADT7-AE1-c末端对酵母无毒性，不能激活检测基因，可作为酵母双杂合系统中的靶基因。     

CYFIP2 is highly abundant in CD4+ cells from multiple sclerosis patients and is involved in T cell adhesion

DNA microarray profiling of CD4(+) and CD8(+) cells from non-treated relapsing and remitting multiple sclerosis (MS) patients determined that the cytoplasmic binding partner of fragile X protein (CYFIP2, also called PIR121) was increased significantly compared to healthy controls. Western analysis confirmed that CYFIP2 protein was increased approximately fourfold in CD4(+) cells from MS compared to inflammatory bowel disorder (IBD) patients or healthy controls. Because CYFIP2 acts as part of a tetrameric complex that regulates WAVE1 activation we hypothesized that high levels of CYFIP2 facilitate T cell adhesion, which is elevated in MS patients. Several findings indicated that increased levels of CYFIP2 facilitated adhesion. First, adenoviral-mediated overexpression of CYFIP2 in Jurkat cells increased fibronectin-mediated adhesion. Secondly, CYFIP2 knock-down experiments using antisense oligodeoxynucleotides reduced fibronectin-mediated binding in Jurkat and CD4(+) cells. Thirdly, inhibition of Rac-1, a physical partner with CYFIP2 and regulator of WAVE1 activity, reduced fibronectin-mediated adhesion in Jurkat and CD4(+) cells. Finally, inhibition of Rac-1 or reduction of CYFIP2 protein decreased fibronectin-mediated adhesion in CD4(+) cells from MS patients to levels similar to controls. These studies suggest that overabundance of CYFIP2 protein facilitates increased adhesion properties of T cells from MS patients.     

Cribriform-morular variant of papillary carcinoma: the sporadic counterpart of familial adenomatous polyposis-associated thyroid carcinoma. A case report with clinical and molecular genetic correlation

The increased incidence of thyroid carcinomas in familial adenomatous polyposis (FAP) patients is well recognised. These thyroid neoplasms display distinctive clinicopathological features and generally show good prognostic outcome. Recently, unusual sporadic tumours that share the morphological features of FAP-associated thyroid carcinomas have also been described. In this report, we document a case of a thyroid tumour in a previously well, 46-year-old female. Histology revealed a circumscribed neoplasm composed of tubular, papillary, cribriform and solid areas. The pseudostratified columnar tumour cells showed occasional nuclear grooves and rare nuclear inclusions. Immunohistochemistry showed positive staining with antibodies to cytokeratin AE1/AE3, oestrogen and progesterone receptor proteins. Focal immunoreactivity was also noted with antibodies to thyroglobulin, epithelial membrane antigen, 34betaE12 and cytokeratin CK7. The absence of polyps on colonoscopy and germline mutation in the adenomatous polyposis coli (APC) gene provides evidence that this tumour represents the sporadic counterpart of FAP-associated thyroid carcinoma. The patient is well with no evidence of disease 7 months following resection of the tumour. The differential diagnoses and molecular genetics of this unusual tumour are discussed.