Association of HLA antigens with differential responsiveness toMycobacterium w vaccine in multibacillary leprosy patients

Leprosy patients undergoing phase II trials in two hospitals of New Delhi, India, were HLA typed to see the association of HLA with differential responsiveness toMycobacterium w vaccine. The vaccine comprises an atypical, nonpathogenic mycobacterium,Mycobacterium w, which has cross-reactive antigens withM. leprae. Multibacillary patients who are lepromin negative are vaccinated at an interval of 3 months. Considerable improvement is evident in the patients in terms of a decline in bacterial indices and histopathological and immunological upgrading. But all the patients do not respond to the vaccine in the same manner; some are slow responders, while others are good responders. HLA-A28 and DQw3 (DQw8+9) were found to be associated with slow responsiveness, while DQw1 and DQw7 were found to be associated with a more rapid responsiveness to theM. w vaccine. However, these associations were not significant afterP correction for the number of antigens tested for each locus except for HLA-DQw3 (DQw8 and DQw9) and DQw7. DQw7, a new defined split of HLA-DQw3, seems to be associated with the responsiveness toM. w vaccine.     

Autonomous histopathological regression of primary tumours associated with specific immune responses to cancer antigens

Spontaneous histopathological regression of cancer has been reported. The involvement of the immune system in such regression has been advocated, leading to the theory of immunological surveillance against cancer. A prediction of this theory is that common tumour antigens can be recognized upon repeated exposure by cell-mediated immunity, which leads to tumour regression and the subsequent appearance of tumour antigen-loss variants. However, no direct evidence has been provided in non-viral-induced experimental animal models of primary malignancy or in human primary cancer. This study examined two groups of melanoma patients where histopathological regression of the primary tumour was observed. Many of the 23 patients with multiple (> or =3) primary melanomas showed significant regression of their last melanoma (median 33%, mean 40) compared with matched melanomas from patients with a single primary melanoma (median 0%, mean 12) (p=0.0080), or compared with their first primary melanoma (p=0.0013). Regression was consistent with an 'immunization effect' seen in murine tumour transplantation studies, where inoculation with > or =3 asynchronous tumours induces transplantation rejection on subsequent challenge. A significant decrease in the expression of the melanoma common tumour antigen MART-1 in the last primary tumour from multiple melanoma patients (median 8%, mean 24) versus matched single melanoma patients (median 79%, mean 68) (p=0.0041) and in the last versus first tumour in multiple primary patients was found (p=0.0083). Metastases from 17 patients whose primary skin melanomas had completely regressed (occult primary melanoma) also showed significant MART-1 loss (median 0%, mean 11) compared with matched metastases from patients with non-regressing primary melanoma (median 51%, mean 50) (p=0.0013). MART-1 antigen-loss variants observed in the multiple primary and occult primary patients correlated with the presence of peripheral blood MART-1-specific cytotoxic T lymphocytes (CTLs) (p=0.03). No similar effects were observed with two other melanoma antigens, gp100 and CD63. Thus, in two groups of human melanoma patients, evidence is provided for histopathological tumour regression associated with cancer immune surveillance.     

Mutations of p53 Tumor Suppressor Gene, Apoptosis, and Proliferation in Intrahepatic Cholangiocellular Carcinoma of the Liver

This study was performed to examine the correlation between mutations of the p53 tumor suppressor gene, the occurrence of apoptosis, and proliferation in cholangiocellular carcinoma of the liver. The results obtained were compared with pathohistological stage (according to UICC) and grade and with disease related survival rate. In 41 curatively (R0–) resected intrahepatic cholangiocellular carcinomas, the status of the p53 gene was determined by direct sequencing of exons 4–9 and immunohistochemically. Apoptosis was assessed using the in situ end labeling (ISEL) technique in combination with morphological criteria. Proliferation was analyzed by immunohistochemistry of MIB-1 (Ki-67), Proliferating cell nuclear antigen (PCNA), and silver-stained nucleolar organizer regions (AgNOR). The results obtained were compared with pathohistological stage (according to UICC), grade, several other histopathological factors, and survival rate. Mutations of p53 were detected in 15/41 carcinomas examined (37%). The most common change was a GC and CT transition, changing the hot spot amino acid determined by exons 4–8. Of these 15 tumors, 14 were also p53-positive by immunohistochemistry. In each carcinoma examined, we could demonstrate MIB-1, PCNA, and AgNOR dots and also apoptotic cells in variable proportions. The proliferation markers showed a significant correlation among themselves. In univariate survival analysis, the extent of the primary tumor, lymph node status, grade, and p53 were significant factors influencing patient survival. Performing multivariate Cox regression survival analysis, however, only the extent of primary tumor and lymph node status had an independent prognostic impact. Apoptosis was not related to patient prognosis or to other parameters examined. In conclusion, these results indicated that p53 could serve as an additional prognostic parameter that could provide auxiliary information for patient outcome. However, tumor stage and lymph node involvement were the strongest prognostic factors. We failed to establish apoptosis or other pathological parameters as factors predicting the prognosis of patients with cholangiocellular carcinoma.     

Effect of nano copper on visceral organs and the contents of trace elements in weanling pigs

We determine the effect of nano copper on visceral organs and contents of trace elements in organs and serum in weanling pigs. Our results showed that following supplementary concentration with 25, 50 and 200?mg/kg/day of nano copper, contents of copper shows trend of increasing in liver, kidney and intestinal; and ferrum shows gradually decreasing. The histopathological examination showed hemolysis, degeneration, nucleus pycnosis in liver, while renal tubular epithelial cell exfoliation and lymphocyte infiltration were found in kidney on supplementation of high concentration of nano-copper. Therefore, dietary supplementation of nano-copper 25?mg/kg b.wt could be a potential substitute for weaning piglets.     

The first histopathological evidence of trimetazidine for the prevention of contrast-induced nephropathy

Aim: We aimed to investigate the prophylactic effects of trimetazidine (TMZ) against contrast-induced nephropathy (CIN) in rat kidneys. Methods and results: 28 Wistar rats were divided into 4 groups of 7 rats each (control (C), contrast media (CM) TMZ, trimetazidin?+?contrast media groups (TMZ?+?CM). The administration of TMZ solution was done on d2, d3 and d4. Fifth day, contrast media was administered at a single dose. On d6 scarification was performed. The oxidant/antioxidant parameters were measured and histopathological scores were performed in kidney tissues. Most of the histopathological scores were significantly higher in the CM group as compared to other groups. Moreover, the scores of the TMZ?+?CM and C groups were not statistically different. CM group, had significantly higher levels of MDA compared to the C and CM?+?TMZ groups (562.82?±?38.15 vs. 419.15?±?49.01 and 507.34?±?14.16 01?nmol/mg protein respectively) (p?0.001). CM group had significantly lower levels of SOD as compared to C, CM?+?TMZ and TMZ groups (p?0.05). Conclusion: To the best of our knowledge, this study for the first time, histopathologically demonstrated the effectiveness of TMZ for the prevention of CIN.     

基于数字组织病理图像的肿瘤与微环境相互作用风险模型在口咽癌症中的预后研究

数字组织病理学全幅图像为计算机化的定量分析提供新的机遇。越来越多的研究表明,肿瘤微环境中的免疫细胞与癌变细胞的相互作用是一项重要的预后指标。HPV+口咽癌症是头颈部常见的恶性肿瘤,目前对其没有很好的预后指标。利用计算机图像处理和模式识别技术,从数字组织病理学全幅图像中定量提取细胞核形态,并利用其特征去度量肿瘤微环境与癌变区域相互作用的程度,构建口咽癌症复发风险模型。实验数据来自华盛顿大学医学中心的病理学档案,是连续回顾性收集的234名口咽癌患者手术切除的组织病理学切片及其相应的跟踪数据。研究发现:利用图像定量分析构建口咽癌症复发风险模型,能够显著地区分复发与非复发病患,其100次5折交叉验证的分类结果的平均AUC达到0.67±0.02;对病患分别进行单变量(HR(95%CI)=1.76(0.99～3.13),P=0.0352)及多变量生存分析((HR(95%CI)=3.27(1.12～5.46),P=0.039)),结果说明肿瘤微环境与癌变区域相互作用高的口咽癌症病患相比于相互作用低的病患,有更低的复发风险及更长的生存期。研究揭示计算机定量度量的肿瘤微环境中的免疫细胞与癌变细胞的相互作用,有望作为一个独立的预后指标来指导口咽癌症病患的治疗疗程。     

活检术前应用皮质醇对原发性中枢神经系统淋巴瘤病理诊断的影响

目的研究活检术前应用皮质醇是否会影响原发性中枢神经系统淋巴瘤的病理诊断。方法回顾分析2005年2月至2011年2月期间73例经立体定向活检诊断为原发性中枢神经系统淋巴瘤患者的资料。结果 73例淋巴瘤患者中,39例（53.4%）在活检术前应用皮质醇;10例（73;13.7%）未得出阳性结果,再次行立体定向活检或开颅被证实为原发性中枢神经系统淋巴瘤,其中5例（39例）术前应用过皮质醇（12.8%）,5例（34例）未使用皮质醇（14.7%）（P=1.0）。结论活检术前应用皮质醇对大部分原发性中枢神经系统淋巴瘤患者而言不影响其病理诊断。