Working With Human Research Protections

PURPOSE: To provide a primer for novice nurse scientists about the increasingly regulated human research environment. ORGANIZING CONSTRUCTS: Federal regulations and international guidelines about protection of human research participants are discussed, with particular attention to institutional review boards for human research. CONCLUSION: Understanding the processes used by institutional review boards to foster ethical human research promotes collaborative interactions and supports compliant research work.     

BKV in Simultaneous Pancreas-Kidney Transplant Recipients: A Leading Cause of Renal Graft Loss in First 2 Years Post-Transplant

With the introduction of more potent immunosuppressive agents, rejection has decreased in simultaneous pancreas/kidney transplant (SPK) recipients. However, as a consequence, opportunistic infections have increased. The purpose of this report is to outline the course of SPK patients who developed polyomavirus-associated nephropathy (PVAN). A retrospective review of 146 consecutive SPK recipients from January 1, 1996 to December 31, 2002 was performed. Immunosuppression, rejection and development of PVAN were reviewed. Nine patients were identified. All received induction with either OKT3 or thymoglobulin. Immunosuppression included tacrolimus/cyclosporine, MMF/azathioprine and sirolimus/prednisone. Two patients were treated for kidney rejection prior to the diagnosis of PVAN. Time to diagnosis was an average of 359.3 days post-transplantation. Immunosuppression was decreased but five ultimately lost function. However, none developed pancreatic abnormalities as demonstrated by normal glucose and amylase. Two underwent renal retransplantation after PVAN diagnosis and both have normal kidney function. PVAN was the leading cause of renal loss in SPK patients in the first 2 years after transplantation and is a serious concern for SPK recipients. The pancreas, however, is spared from evidence of infection, and no pancreatic rejection occurred when immunosuppression was decreased.     

The comparative evaluation of cellular localization of viral antigens with microscopic changes in the ileum of cattle infected with bovine viral diarrhea

The correlation between microscopic changes with cellular localization of viral antigens was studied in the ileum of 16 cases infected with bovine viral diarrhea virus (BVDV). Microscopic lesions in the ileum included multifocal erosive and ulcerative ileitis, severe congestion and hemorrhage, crypt dilation and mucus engorgement, epithelial debris and leukocytes, lymphoid depletion of Peyer’s patches, herniation of mucosal epithelium into depleted Peyer’s patches, and fibrinoid vasculitis of submucosal vessels. BVDV antigen was detected by immunohistochemistry in macrophages, dendritic cells, smooth muscle cells, endothelial cells, epithelial cells of crypts, and mucosal epithelium, together with other mononuclear cells including lymphocytes, plasma cells, fibroblasts, and intramural ganglial cells. No consistent correlation between the presence of BVDV antigen and vascular lesions in the ileum was identified. The intensity and distribution of the immunoperoxidase stain in the ileum was graded as highly positive (18.7%), moderately positive (56.3%), and mildly positive (25%). In conclusion, the pattern and density of distribution and localization of BVDV antigen in the ileum was not consistently correlated with the severity of microscopic lesions.     

The nocturnal jejunal migrating motor complex: defining normal ranges by study of 51 healthy adult volunteers and meta-analysis

Interdigestive human small bowel motility is characterized by the migrating motor complex (MMC). The aims of this study were to: (i) establish the normal range of variables of the nocturnal jejunal MMC and (ii) incorporate these data in a subsequent meta-analysis. Eighty-one recordings were performed by prolonged (24 h) ambulatory manometry in 51 subjects in two centres. Quantitative analysis was undertaken of 419 Phase III and 332 Phase II episodes. Adjusted mean values of seven variables were calculated using a mixed-effects model. Meta-analysis of pooled published data to generate a reliable 95% reference range was also performed. Adjusted mean values and confidence intervals are presented for all seven variables. Intrasubject variances were large in comparison with intersubject. Meta-analysis of 19 studies (356 pooled patients) meeting inclusion criteria produced wide reference ranges. At least five such ranges are useful for the detection of abnormality in the individual. This is the largest study of normal volunteers presented to date, with ranges for many variables produced using appropriate statistical methodology. A model for definition of abnormality has been proposed. We recommend that these data may be used by investigators in this field as a complement to other existing indicators of small bowel dysmotility.     

Clinical characteristics and imaging manifestations of AIDS complicated with disseminated Penicillium marneffei infection

Objective To investigate the clinical characteristics and imaging manifestations of AIDS complicated with disseminated Penicillium marneffei （PM） infection. Methods A total of 12 patients with AIDS complicated with disseminated PM infection were collected and the symptoms, signs, laboratory examination results and image manifestations of these patients were analyzed retrospectively. Results （1） The diagnosis of PM infection in all the 12 cases were confirmed by peripheral blood culture. All the 12 cases （100%） had irregular fever （38-41℃） and enlarged lymph nodes, 8 cases （66%） had skin rashes; 8 cases （66%） had hepatomegaly; 9 cases （75%） had splenomegaly while 8 cases （66%） had anemia. （2） Imaging manifestation： Five cases manifested bilateral pulmonary disseminated miliary nodular shadows or lattice signs; 1 case showed enlarged hilar lymph node and 2 cases showed patchy shadow with pleuritis. One case presented sub-pleural curve line shadow at the posterior part of the right lower lung, and adhesion between the intestinal wall and intestinal mesentery in mass form in the abdomen by CT examination. Conclusion Patients suffering from AIDS （CD4 T lymphocytes 〈50/μ L） with impaired immunity might be susceptible to complication of disseminated PM infection, which presents mainly damage of multiple organs and symptoms such as fever; enlargement of liver, spleen and lymph nodes, as well as specific skin maculopapular rashes. Imaging manifestations in the lungs were revealed as miliary nodular shadows and lattice-like shadows. Intensified abdominal CT might reveal presence of several enlarged postperitoneal lymph nodes and intestinal adhesion in shape of ＂cakes＂.     

Epstein-Barr virus DNA in Reed-Sternberg cells of Hodgkin''s disease is frequently associated with CR2 (EBV receptor) expression

We studied 44 cases of Hodgkin's disease for the presence of Epstein-Barr virus (EBV) DNA, its localization and the expression of the EBV receptor on the tumour cells. EBV DNA was found in 52% (16/31) of the Hodgkin's lymphomas using the polymerase chain reaction. With a very sensitive non-radioactive DNA in situ hybridization technique in combination with immunohistochemistry for CD 30 or CD 15 antigens, EBV DNA was localized to Reed-Sternberg cells and its mononuclear variants. The relationship between the presence of EBV DNA and the expression of the EBV-receptor CR2 (CD 21) on Reed-Sternberg cells was studied using the same techniques and two different monoclonal anti-CD 21 antibodies. CR2 could be detected on a substantial number of the Reed-Sternberg cells in EBV DNA positive Hodgkin's lymphomas (9/12; 75%), whereas in EBV negative cases positivity with anti-CD 21 was rare (1/13; 8%). The results indicate that CR2 expression on Reed-Sternberg cells and the presence of EBV DNA sequences are frequently associated in Hodgkin's lymphomas.     

D2-43病毒E蛋白在酵母细胞表面的展示

目的：在酵母细胞表面展示登革2型病毒43株(D2—43)的E基因，探索利用酵母表面展示系统建立DNA改组筛选平台的可行性。方法：通过RT-PCR扩增获得D2-43的E基因，将该基因亚克隆至T载体后，再克隆至酵母表面展示载体pYDI，于酿酒酵母EBY100中利用半乳糖进行诱导表达。表达产物采用间接免疫荧光法和FACS进行检测。结果：酵母表面展示产物可与D2-43的腹水抗体特异性地结合；在半乳糖诱导后24h，展示E蛋白的酵母细胞百分数达22．07％。结论：本研究为建立基于酵母表面展示系统的DNA改组筛选平台奠定了基础。     

Chronic delta hepatitis in haemophiliacs

The seroepidemiological profile of HBV and HDV was investigated in 640 male haemophiliacs. Twenty-seven of forty-four HBsAg carriers were anti-HDV-IgG positive, 22 were also anti-HDV-IgM positive. A markedly lower prevalence of HDV infection was found in patients with anti-HBc in the absence of HBsAg and anti-HBs (6/41). Repeated detection of anti-HDV-IgM in 5/41 individuals of this group indicates that circulating HBsAg is not an absolute prerequisite for chronic HDV infection. Overall, chronically active HDV infection was detected more frequently in quiescent than in active chronic HBV infections. Anti-HDV-IgM was not detected in the absence of anti-HDV-IgG antibodies. Anti-HDV-IgG may disappear after resolution of HDV infection, as indicated by the low prevalence (1/42) in such individuals with past HBV infection as well as by loss of anti-HDV-IgG observed in two patients.     

网络化人类精子库管理信息系统的建立与应用

目的 :建立网络化人类精子库管理信息系统。　方法 :用SQLServer2 0 0 0和PowerBuilder 8.0开发人类精子库管理信息系统。　结果 :系统形成了档案管理、体检与检查管理、检验与冷冻管理、供应与随访管理 4个模块 ,系统以远程传输与实时监控的方法控制和管理供应点。　结论 :本系统具有数据容量大、安全性能好、保密性能强 ,具有远程传输与实时监控功能     

应用激光显微分离技术在骨肉瘤组织原位筛选噬菌体肽库

目的将激光显微分离(laser capture microdissection, LCM) 技术应用于噬菌体表面呈现肽库的筛选过程,建立一种可以直接在天然组织中筛选肽库的方法。方法将新鲜人骨肉瘤组织块在噬菌体肽库溶液振荡孵育后制成组织冰冻切片,免疫组化染色检测噬菌体在组织中的浸润扩散。改进常规LCM切片处理方法,以冻干法替代酒精/二甲苯法脱水,以期在LCM操作过程中提高切片上噬菌体的存活率。LCM法分离摄取骨肉瘤切片上的肿瘤靶细胞,转染回收这些细胞上特异结合的噬菌体。滴定法检测所筛选的噬菌体对特异性细胞的亲和力。结果利用LCM技术,可以由肿瘤冰冻切片上收集到足够的与特异性噬菌体短肽,应用于噬菌体表面呈现肽库筛选。经过3轮筛选后所获得的噬菌体与人骨肉瘤组织的特异性亲和力提高16倍。结论本研究首次将LCM技术应用于噬菌体表面呈现肽库的筛选,可以使我们直接在新鲜人肿瘤组织中筛选与特定细胞群甚至单个细胞亲合的短肽;同时又避免了天然组织中其他杂质细胞的污染,为研制细胞特异性导向载体提供了一个新的途径。