人颈动脉粥样硬化斑块环氧化物酶-2及Ⅰ型前列腺素合成酶的表达

目的探讨环氧化物酶-2(cyclooxygenase type 2,COX-2)及Ⅰ型前列腺素合成酶(membrane associated prostaglandin E-1,mPGES-1)在人颈动脉粥样硬化斑块中的表达变化及作用机制。方法收集24例人颈动脉粥样硬化斑块标本和10例肠系膜动脉标本做对照组,应用免疫组织化学及逆转录PCR方法测定COX-2及mPGES-1mRNA表达水平,Western印记方法检测COX-2及mPGES-1的蛋白表达水平。比较不同程度动脉粥样硬化组织间COX-2、mPGES-1 mRNA表达水平及蛋白表达水平。结果颈动脉粥样硬化斑块组的免疫组织化学染色检测COX-2和mPGES-1呈阳性表达,斑块组COX-2 mRNA和mPGES-1 mRNA表达与对照组相比上调,差异有统计学意义(P<0.05);COX-2及mPGES-1 mRNA上调水平相关(P<0.05);颈动脉粥样硬化斑块的COX-2蛋白表达上调水平与对照组相比差异有统计学意义(P<0.05);颈动脉粥样硬化斑块COX-2、mPGES-1 mRNA及蛋白表达水平与病理损害程度有关,差异有统计学意义(P<0.05)。结论COX-2及mPGES-1基因表达水平上调可能是进展性动脉粥样硬化损害的关键因素。     

肺鳞状细胞癌中死亡相关蛋白激酶的表达

目的　检测肺鳞状细胞癌中死亡相关蛋白激酶 (DAP K)mRNA表达及细胞凋亡 ,探讨DAP K与细胞凋亡的关系及其在肺鳞状细胞癌发生、发展中的作用。方法　用原位分子杂交法检测 6 0例肺鳞状细胞癌、9例癌旁肺组织DAP KmRNA表达 ;用原位末端标记TUNEL法检测相应组织中细胞凋亡 ,计算凋亡指数 (AI)。结果　肺鳞状细胞癌的DAP KmRNA阳性表达率为 4 6 7% ,癌旁肺组织为 6 7 7% ,其阳性率高于肿瘤组织 (P <0 0 1 )。在肺鳞状细胞癌中 ,高分化癌DAP KmRNA阳性率为 70 % ,低分化癌为 2 3 3% ,高分化癌的DAP KmRNA阳性率高于低分化癌 (P <0 0 1 )。肺鳞状细胞癌的细胞AI为(0 6 72 8± 0 4 2 6 1 ) % ,癌旁肺组织中支气管肺泡上皮细胞AI为 (1 0 2 89± 0 2 4 33) % ,癌旁肺组织的AI高于肿瘤组织 (P<0 0 1 )。在肺鳞状细胞癌中 ,高分化癌的AI为 (0 5 82 3± 0 1 92 2 ) % ,低分化癌为 (0 4 4 6 0± 0 1 92 5 ) % ,高分化癌的AI高于低分化癌 (P <0 0 1 )。DAP KmRNA呈阳性表达的肺癌 ,其AI为 (0 5 31 7± 0 2 0 97) % ;DAP KmRNA呈阴性者 ,其AI为 (0 4 872± 0 1 91 8) % ,两组间差异有显著性 (P <0 0 5 )。在连续切片上 ,DAP KmRNA阳性细胞的分布区域与凋亡阳性细胞的分布相似。DAP KmRNA呈阳性表达     

肿瘤相关糖蛋白-72抗原在原发性乳腺癌组织中的表达及其临床意义

目的:探讨抗肿瘤相关糖蛋白(TAG-72)抗原的表达与原发性乳腺癌病理特征及预后的关系.方法:随机选取原发性乳腺癌患者118例, 应用SABC免疫组化方法检测TAG-72抗原的表达.并对其中的92例原发性乳腺癌患者中作术后为期5年的随访, 分析TAG-72抗原与原发性乳腺癌患者预后的相关性.结果:TAG-72抗原在原发性乳腺癌组织中的阳性表达率为78.81% (93/118), 并与原发性乳腺癌组织的临床病理学特征及患者的预后均有密切的关系.在直径较大(P<0.05)、 TNM分期较高(P<0.05)、淋巴结转移(P<0.01)及组织学分级低(P<0.01)的肿瘤组织中, TAG-72抗原高表达.此外, TAG-72抗原阳性表达的原发性乳腺癌患者的生存率明显低于阴性表达的患者 (P<0.01).结论:TAG-72抗原的表达可能与原发性乳腺癌的发生、浸润、转移有关;TAG-72抗原可以作为一个肿瘤标志物在临床中应用, 检测其在原发性乳腺癌组织中的阳性表达率, 并结合临床病理学分级, 可提高对患者预后判断的准确性.     

胃粘膜相关淋巴组织型淋巴瘤形态学研究

目的：研究胃粘膜相关淋巴细胞（ＭＡＬＴ）型淋巴瘤及共与胃粘膜套细胞淋巴瘤和滤泡性淋巴瘤的鉴别诊断。方法：应用ＨＥ染色和免疫组化ＡＢＣ法检测胃ＭＡＬＴ型淋巴瘤，内镜作幽门螺杆菌培养基尿素试验检测ＨＰ感染。结果：３１例胃ＭＡＬＴ型淋巴瘤中低度恶性２７例，高度恶性４例。细胞类型以ＣＣＬ型最常见。免疫表型以ＩｇＭ为主，缺乏ＩｇＤ，３１例中２８例有ＨＰ感染（占９０．５２％），结论：（１）低恶ＭＡＬＴ型淋巴瘤     

The chemokine receptor CCR7 is expressed on epithelium of non-inflamed gastric mucosa, Helicobacter pylori gastritis, gastric carcinoma and its precursor lesions and up-regulated by H. pylori

CCR7 chemokine-receptor expression on tumour cells of gastric carcinoma has been associated with lymph-node metastasis and is thought to play an important role in metastasis. However, so far it is unknown whether CCR7 is newly up-regulated on gastric carcinoma or already expressed in non-neoplastic gastric epithelium. Therefore, epithelial CCR7 expression was investigated in the process of gastric carcinogenesis: non-inflamed mucosa --Helicobacter pylori gastritis -- intestinal metaplasia/dysplasia -- gastric carcinoma. CCR7 was expressed by gastric epithelium in non-inflamed gastric mucosa (n = 5), H. pylori gastritis (n = 17), intestinal metaplasia (n = 10), dysplasia (n = 3) and on tumour cells in 20 of 24 patients with gastric carcinoma (13/14 intestinal-type; 7/10 diffuse-type) as tested by immunohistochemistry. As CCR7 expression by gastric epithelium was significantly stronger in H. pylori gastritis than in non-infected mucosa, the influence of H. pylori on CCR7 receptor expression of gastric epithelial cells was investigated by fluorescence activated cell sorter analysis. H. pylori strains up-regulated the CCR7 chemokine-receptor in CCR7-positive cell lines. No difference in CCR7 up-regulation between cag(+) and cag(-)H. pylori strains was found. Epithelial CCR7 up-regulation by H. pylori may alter the metastatic fate of gastric carcinoma. Additionally, CCR7 expression not only on gastric carcinoma, but also on non-neoplastic gastric epithelium, suggests a novel biological function.     

Association of Helicobacter pylori-dependent gastritis with gastric carcinomas in young Japanese patients: histopathological comparison of diffuse and intestinal type cancer cases

AIMS: The causal relationship of H. pylori gastric colonization with gastric cancer development has not as yet been fully elucidated. The prevalence of H. pylori infection increases with age in the asymptomatic population in Japan, and reaches a high plateau in those older than 40 years. The objective of this study was to assess the link between H. pylori and gastric carcinomas in patients younger than 40 years. METHODS AND RESULTS: Detection of H. pylori and assessment of background mucosa based on the Sydney system was performed histopathologically for 40 Japanese gastric cancer cases younger than 40 years and compared with 40 age- and sex-matched controls. H. pylori infection in gastric mucosa was detected significantly more frequently (P < 0.001) in patients with cancer (29/40; 72.5%) than in controls (11/40; 27.5%). Additionally, by histopathological comparison between intestinal (18 cases) and diffuse (70 cases) types of young gastric cancer patients, mucosal atrophy and intestinal metaplasia were found to coexist with acute and chronic inflammation in the background mucosa of both intestinal and diffuse types, being significantly more prevalent than in young controls. CONCLUSIONS: As well as the high prevalence of H. pylori in young subjects with gastric cancer, it is clear that persistent infection induces mucosal damage, resulting in atrophy and intestinal metaplasia. Thus, acute/chronic gastritis could play an essential role in the early development of neoplasia in the stomach.     

A novel isoform of the smooth muscle cell differentiation marker smoothelin

Studies on smooth muscle cell differentiation and those on vascular development in mouse and humans have long been hampered by the lack of suitable markers. Here we describe a novel, large isoform of smoothelin, a structural protein of differentiated, contractile smooth muscle cells. The protein, which is highly conserved in mouse and humans, shows homology with other cytoskeleton-associated smooth muscle cell proteins and contains an actinin-type actin-binding domain. Northern blot analysis from various mouse organs identified short and long smoothelin mRNA forms, which exhibit distinct tissue expression patterns. The short form is highly expressed in visceral muscle tissues such as intestine and stomach and is not detectable in brain, while the long mRNA form is expressed in all vascularized organs. These results may provide new tools and approaches to study both smooth muscle cell differentiation and proliferative vascular disease. Received: 25 August 1998 / Accepted: 19 October 1998     

B cell epitope specificity in ANCA‐associated vasculitis: does it matter?

Pauci‐immune idiopathic small‐vessel vasculitis is strongly associated with the presence of antineutrophil cytoplasm autoantibodies (ANCA). Antibodies to PR3 predominate in patients with Wegener's granulomatosis; antibodies to myeloperoxidase (MPO) are found more frequently in patients with microscopic polyangiitis. There is increasing in vivo and in vitro evidence for a pathogenic role of ANCA in systemic vasculitis based on associations of ANCA with disease activity. If ANCA are pathogenic, why is the course of disease different from one patient to another? Antibodies can recognize different binding sites (epitopes) on their corresponding antigens. Differences in binding specificity may influence the pathogenic potential of the antibodies. Differences between epitope specificity of ANCA between patients or changes in epitope specificity of ANCA in time in an individual patient may, accordingly, result in differences in disease expression. This review will focus on epitope specificity of autoantibodies in systemic autoimmune diseases and especially on the epitope specificity of PR3– and MPO–ANCA. We will discuss whether PR3–ANCA or MPO–ANCA recognize different epitopes on PR3 and MPO, respectively, and whether the epitopes recognized by ANCA change in parallel with the disease activity of ANCA‐associated vasculitis. Finally, we will speculate if the direct pathogenic role of ANCA can be ascribed to one relapse‐ or disease‐inducing epitope. Characterization of relapse‐ or disease‐inducing epitopes bound by PR3–ANCA and MPO–ANCA is significant for understanding initiation and reactivation of ANCA‐associated vasculitis. Elucidating a disease‐inducing epitope bound by ANCA may lead to the development of epitope‐specific therapeutic strategies.     

Assessment of different methods for staining Helicobacter pylori in endoscopic gastric biopsies

The recent implication of Helicobacter pylori in the pathogenesis of gastritis-peptic ulcer syndrome and its relevance for the development of upper gastrointestinal malignancy warrant efficient methods for the detection and demonstration of the organism in biopsy specimens. We have compared 5 staining methods, namely, haematoxylin and eosin (H & E), immunohistochemistry (IHC), the silver staining HpSS, the alcian yellow-toluidine blue (Leung) method (A-Y) and Genta staining, for the demonstration of the organism in gastric biopsies taken from antrum, body and fundus of 118 patients who presented to our hospital with upper gastrointestinal symptoms. We found no significant differences in the efficacy of H & E, IHC, HpSS and A-Y in the demonstration of H. pylori in all 3 gastric sites. The least reproducible stain in our hands was the Genta stain. We conclude that H & E is adequate for the initial assessment of gastric biopsies in symptomatic upper gastrointestinal patients. This is because it is a well-tested, cheap and easy staining method, requiring a relatively short period of time to perform, with highly reproducible results. It has an added advantage of enabling simultaneous assessment of morphological changes accompanying H. pylori infection. When the density of the organism is expected to be low, we recommend addition of HpSS staining because of its high sensitivity and low cost. The disadvantages of the other staining methods (IHC, A-Y and Genta) are discussed.     

Immune aspects of intestinal metaplasia of the stomach: An immunohistochemical study

Summary Immune characteristics of intestinal metaplasia of the stomach were analyzed by the immunoperoxidase technique in frozen and paraffin-embedded specimens. In fetal and minimally inflamed adult gastric mucosa, secretory component (SC) was absent from epithelial cells. Non-intestinalized gastric mucosa with evident inflammatory changes showed weak SC immunoreactivity at the generative cell zone. Enhanced immunoreactivity of SC with evidence of transepithelial transport of IgA and IgM, but not of IgG, was demonstrated in intestinalized glands of either the complete or incomplete type. The number of inflammatory cells and lymphoid follicles was decreased in intestinalized mucosa when compared with that in non-intestinalized gastritic mucosa; J chain-negative IgG plasma cells and T cells, both of which were fairly abundant in the latter mucosa, were remarkably decreased in the former mucosa, whereas the decrease of J chain-positive IgA or IgM plasma cells was slight or equivocal. In either mucosa, IgA was the most popular immunoglobulin class in plasma cells. IgD plasma cells were very rare. In the germinal centers of lymphoid follicles which were preferentially distributed in non-intestinalized gastritic mucosa, IgM or IgG germinocytes predominated over IgA germinocytes, and a few T cells and NK cells also were present. Intraepithelial lymphoid cells with a T-suppressor phenotype were detected in intestinalized glands. The possibility that intestinal metaplasia is an adaptation to long-standing chronic gastritis is discussed.