合成病毒多肽诱导实验性自身免疫性脑脊髓炎的行为学,免疫学和病理学研究

目的研究与髓鞘碱性蛋白（MBP）有相似氨基酸序列的4条病毒多肽免疫大鼠后能否诱导出实验性自身免疫性脑脊髓炎（EAE）模型，并探讨其可能的发生机制。方法66只Lewis雌性大鼠，随机分为6组，每组11只。A组用完全弗氏佐剂（cFA）免疫；B组用豚鼠MBP68-86免疫；C组-F组分别用乙型肝炎病毒、JC病毒、EB病毒和HHV-6病毒肽段免疫。EAE评分按国际标准。免疫后第15天处死大鼠，制备淋巴结细胞悬液和腰段脊髓冰冻切片。用MBP68-86和PBS分别刺激6组的淋巴结细胞，测定各组T淋巴细胞对MBP68-86的增殖反应，MBP68-86刺激下的IFN-Y分泌及每条病毒肽与MBP68-86诱导抗体间的交叉反应性。对脊髓切片进行细胞浸润的评级，并用免疫组化法对浸润细胞分类。结果B组（MBP68-86免疫组）和D组（JC病毒肽免疫组）分别有10只鼠和6只鼠出现EAE表现；MBP68-86显著刺激B组和D组大鼠的T淋巴细胞增殖，与cFA组比较有统计学差异（P〈0．05）；B组和D组的淋巴细胞在MBP68-86刺激下释放的IFN-γ量上升，明显高于CFA组（P％0．（）5）；MBP68-86免疫大鼠的血清与4条病毒肽之间无明显的交叉反应性；发病鼠脊髓内有大量浸润细胞，免疫组化显示为T细胞和巨噬细胞浸润并有小胶质细胞激活。结论JC病毒肽具有与MBP68-86相似、但较弱的致病原性；其可能具有与MBP68-86相似的T细胞表位，而缺乏相似的B细胞表位；提示病毒的分子模拟学说在多发性硬化（MS）发病中可能有一定的作用。     

双向分化肿瘤血管生成拟态的组织微阵列研究

目的　探讨在双向分化肿瘤中是否存在肿瘤细胞通过自身变形并模拟产生血管样通道而达到自身血液供应的方式 ,即血管生成拟态 (VM )。方法　采用免疫组化和PAS双重染色技术研究双向分化肿瘤内血管的生成模式 ,收集双向分化肿瘤恶性黑色素瘤 (高度恶性 30例、低度恶性 30例 ) ,滑膜肉瘤 (高度恶性 2 3例、低度恶性 13例 ) ,间皮肉瘤 (2 6例 ) ,上皮样肉瘤 (4例 )及具有双向分化倾向的腺泡型横纹肌肉瘤 (高度恶性 16例、低度恶性 16例 )共 15 8例 ,制作成组织芯片 ,进行CD31和PAS双重染色 ,通过网格计数法比较这些肿瘤中CD31和PAS阳性图案围成的管道面积 ,以其差异研究血管生成拟态。并且比较高度恶性肿瘤和低度恶性肿瘤血管生成拟态的差异。结果　双向分化肿瘤中CD31和PAS阳性图案围成的管道面积差异具有统计学意义 (P <0 .0 1)。同时观察到细胞异型性小的双向分化肿瘤形成血管生成拟态的例数明显少于瘤细胞异型性大的双向分化肿瘤形成血管生成拟态例数 ,其差异具有统计学意义 (P <0 .0 5 )。在明显具有血管生成拟态的点阵中见PAS阳性的血管样图案内无内皮细胞衬覆但有红细胞存在 ,并可见双向分化肿瘤的瘤细胞可表达CD31抗原和PAS阳性物质。结论　双向分化肿瘤内的肿瘤细胞可通过自身变形并且与细胞外基质     

Colour duplex Doppler ultrasonography evaluation of non‐vasculogenic male erectile dysfunction: An Indian perspective

We present the study of colour duplex Doppler ultrasonography on Indian patients with non‐vasculogenic erectile dysfunction. Patients with a history suggestive of psychogenic impotence along with a normal clinical response to intracavernosal papaverine were presumed to have non‐vasculogenic erectile dysfunction. In our patients, the incidence of psychogenic impotence was much higher and the mean age of patients presenting with erectile dysfunction was lower as compared to patients from developed countries reported in research. The Doppler flowmetry showed much higher mean peak systolic velocities (PSVs) with a negative correlation between age and PSV. End diastolic velocity, resistive index and acceleration time values conformed to the literature.     

Analysis of the herpes simplex virus type 1 UL6 gene in patients with stromal keratitis

Recent work suggests that herpes simplex virus (HSV) stromal keratitis in the mouse is caused by autoreactive T lymphocytes triggered by a 16 amino acid region of the HSV UL6 protein (aa299-314), Science 279, 1344-1347). In the present study we sought to determine whether genetic variation of this presumed autoreactive UL6 epitope is responsible for different pathogenic patterns of human HSV keratitis. To accomplish this, we sequenced the HSV UL6 gene from ocular isolates of 10 patients with necrotizing stromal keratitis, 7 patients with recurrent epithelial keratitis, and 8 patients with other forms of HSV keratitis. The sequences obtained predicted identical UL6(299-314) epitopes for all 25 viral isolates. Furthermore, the upstream sequence of all isolates was free of insertions, deletions, and stop codons. We conclude that different pathogenic patterns of human HSV keratitis occur independent of genetic variation of the HSV UL6 (299-314) epitope.     

骨肉瘤细胞体外培养中仿血管发生现象

目的 对骨肉瘤肿瘤血管产生机制进行初步的研究,观察骨肉瘤细胞是否有仿血管发生的能力。方法 应用Ⅰ型胶原蛋白凝胶的三维培养基对骨肉瘤细胞进行培养,观察骨肉瘤细胞在三维培养基中是否可形成血管样结构,并运用电镜、光镜观察这些血管样结构的形态学构成。结果 电镜、光镜下观察到骨肉瘤细胞在Ⅰ型胶原蛋白凝胶的三维培养基中能够形成血管样结构。结论 骨肉瘤细胞体外能够自身形成血管样结构,具有仿血管发生的能力。     

Helicobacter pylori and autoimmune diseases

It is now widely accepted that Helicobacter pylori may play a role in several extra-gastric diseases. In particular, H. pylori infection seems to be implicated in various autoimmune diseases. Many recent studies have shown a healing or an improvement in different autoimmune disorders after H. pylori eradication therapy in infected patients. The exact mechanisms behind this relationship remain under discussion, but molecular mimicry is a consistent hypothesis. This subject is particularly relevant taking into consideration the high prevalence of H. pylori infection, the existence of inexpensive and noninvasive diagnostic methods, as the urea breath test or the stool antigen test, and the low cost and toxicity of eradication treatment. If this connection becomes confirmed, it can change the diagnostic and therapeutic approach of some autoimmune diseases.     

Potential mechanisms involved in the absorptive transport of cadmium in isolated perfused rabbit renal proximal tubules

Lumen-to-cell transport, cellular accumulation, and toxicity of cadmium as ionic cadmium (Cd²⁺) or as the l-cysteine (Cys) or d,l-homocysteine (Hcy) S-conjugate of cadmium (Cys-S-Cd-S-Cys, Hcy-S-Cd-S-Hcy) were studied in isolated, perfused rabbit proximal tubular segments. When Cd²⁺ (0.73 μM) or Cys-S-Cd-S-Cys (0.73 μM) was perfused through the lumen of S₂ segments of the proximal tubule, no visual evidence of cellular pathological changes was detected during 30 min of study. Cd²⁺-transport was temperature-dependent and was inhibited by Fe²⁺, Zn²⁺, and elevated concentrations of Ca²⁺. Luminal uptake of Cys-S-Cd-S-Cys was also temperature-dependent and was inhibited by the amino acids l-cystine and l-arginine, while stimulated by l-methionine. Neither l-aspartate, l-glutamate, the synthetic dipeptide, Gly-Sar nor Zn²⁺ had any effect on the rate of Cys-S-Cd-S-Cys transport. Conclusions: When delivered to the luminal compartment, Cd²⁺ appears to be capable of utilizing certain transporter(s) of Zn²⁺ and some transport systems sensitive to Ca²⁺ and Fe²⁺. In addition, Cys-S-Cd-S-Cys and Hcy-S-Cd-S-Hcy appear to be transportable substrates of one or more amino acid transporters participating in luminal absorption of the amino acid l-cystine (such as system b^0,+). These findings indicate that multiple mechanisms could be involved in the luminal absorption of cadmium (Cd) in proximal tubular segments depending on its form. These findings provide a focus for future studies of Cd absorption in the proximal tubule.     

Identification and Characterization of Peptide Mimics of Blood Group A Antigen

In order to investigate peptide mimics of carbohydrate blood group A antigen, a phage display 12-mer peptide library was screened with a monoclonal antibody against blood group A antigen, NaM87-1F6. The antibody-binding properties of the selected phage peptides were evaluated by phage ELISA and phage capture assay. The peptides were co-expressed as glutathione S-transferase （GST） fusion proteins. RBC agglutination inhibition assay was performed to assess the natural blood group A antigen-mimicking ability of the fusion proteins. The results showed that seven phage clones selected bound to NaM87-1F6 specifically, among which, 6 clones bore the same peptide sequence, EYWYCGMNRTGC and another harbored a different one QIWYERTLPFTF. The two peptides were successfully expressed at the N terminal of GST protein. Both of the fusion proteins inhibited the RBC agglutination mediated by anti-A serum in a concentration-dependent manner. These results suggested that the fusion proteins based on the selected peptides could mimic the blood group A antigen and might be used as anti-A antibody-adsorbing materials when immunoabsorption was applied in ABO incompatible transplantation.