Th‐17 Alloimmune Responses in Renal Allograft Biopsies From Recipients of Kidney Transplants Using Extended Criteria Donors During Acute T Cell–Mediated Rejection

Although renal transplantation using expanded criteria donors has become a common practice, immune responses related to immunosenescence in those kidney allografts have not been studied yet in humans. We performed a retrospective molecular analysis of the T cell immune response in 43 kidney biopsies from patients with acute T cell–mediated rejection including 25 from recipients engrafted with a kidney from expanded criteria donor and 18 from recipients grafted with optimal kidney allograft. The clinical, transplant and acute T cell–mediated rejection characteristics of both groups were similar at baseline. The expression of RORγt, Il‐17 and T‐bet mRNA was significantly higher in the elderly than in the optimal group (p = 0.02, p = 0.036, and p = 0.01, respectively). Foxp3 mRNA levels were significantly higher in elderly patients experiencing successful acute T cell–mediated rejection reversal (p = 0.03). The presence of IL‐17 mRNA was strongly associated with nonsuccessful reversal in elderly patients (p = 0.008). Patients with mRNA IL17 expression detection and low mRNA Foxp3 expression experienced significantly more treatment failure (87.5%) than patients with no mRNA IL17 expression and/or high mRNA Foxp3 expression (26.7%; p = 0.017). Our study suggests that the Th17 pathway is involved in pathogenesis and prognosis of acute T cell–mediated rejection in recipients of expanded criteria allograft.     

The Concept of Diminished Responsibility in Supranational Criminal Law (Psychiatric Approach)

The role of the community management order (CMO) in the management of mental illness has been associated with controversy. There is uncertainty as to the effectiveness of such involuntary treatment. Review of outcomes of involuntary community treatment has shown varied results, and in the remote areas of Australia the issue becomes more complex, and outcomes more difficult to measure. The Northern Territory's Mental Health Act 2000 has broadened criteria for detention. The decision to impose follow-up and case management on an individual (who may reside in a community several hundred kilometres from an in-patient facility) requires careful consideration of its ethical, professional and psychosocial implications. The trend toward increasing use of mental health legislation in the Northern Territory — particularly for Indigenous people — deserves close scrutiny in order that culturally appropriate and sensitive treatment plans are developed.     

人表皮细胞与角膜上皮细胞蛋白质组的差异表达初步研究

目的：应用蛋白质组技术比较人表皮细胞与角膜上皮细胞之间的蛋白质表达差异。方法：实验于2005-11，2006-10在中山大学中山眼科中心国家眼科学重点实验室完成。分别培养人表皮细胞与角膜上皮细胞，裂解原代细胞抽提总蛋白，精确定量后进行双向电泳，扫描电泳凝胶获得二维总蛋白图谱。图谱使用软件辅助比较分析，找出差异表达点，从凝胶中抠取差异点，胶内酶解后用基质辅助激光解吸附，电离飞行时间串级质谱法鉴定差异蛋白。结果：人表皮细胞与角膜上皮细胞蛋白质凝胶分析获得600余个清晰的蛋白质斑点，在比较分析出的26个差异点中初步鉴定出4个差异表达蛋白，分别是细胞内氯离子通道1、Psodasin、乳酸脱氢酶B和丝氨酸蛋白酶抑制因子。结论：人表皮细胞与角膜上皮细胞在蛋白质表达上有较高的相似性以及较好的可比性，为探索表皮细胞横向分化成角膜上皮细胞的分子机制做出了有益的尝试，并提供了具有一定可操作性的实验方法。     

Acquired resistance to TRAIL-induced apoptosis in human ovarian cancer cells is conferred by increased turnover of mature caspase-3

Little is known on how cancer cells can acquire resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). In this study, we established TRAIL-resistant cells from the TRAIL-sensitive human ovarian carcinoma cell line OVCAR3 to evaluate the potential mechanisms of acquired resistance to TRAIL. The selected resistant cells were cross-resistant to Fas ligand but remained sensitive to drug-induced apoptosis. Expression of TRAIL receptors was not altered in TRAIL-resistant OVCAR3 cells. Cleavage of caspase-8 and caspase-3 occurred in both TRAIL-resistant and TRAIL-sensitive cells. However, mature caspase-3 fragments were not detected by immunoblot in TRAIL-resistant cells and caspase-3 activity was significantly inhibited in these cells. The addition of proteasome inhibitors significantly increased TRAIL-induced apoptosis in resistant cells and enhanced the accumulation of mature caspase-3 fragments. Pretreatment with cycloheximide showed that active caspase-3 fragments have a high turnover rate in OVCAR3 R350 cells. X-linked inhibitor of apoptosis down-regulation by RNA interference also increased the accumulation of cleaved caspase-3 intermediates and resensitized TRAIL-resistant cells. Our findings show that altered turnover of mature caspase-3 may lead to acquired TRAIL resistance in ovarian cancer cells. Proteasome and X-linked inhibitor of apoptosis inhibitors could have a role in clinical situations to potentiate the cytotoxic effects of TRAIL in resistant tumor cells.     

A look at the thoracic surgery workforce in Canada: how demographics and scope of practice may impact future workforce needs

Background

The purpose of this study is to describe the demographics, training and practice characteristics of physicians performing thoracic surgery across Canada to better assess workforce needs.

Methods

We developed a questionnaire using a modified Delphi process to generate questionnaire items. The questionnaire was administered to all Canadian thoracic surgeons via email (n = 102) or mail (n = 35).

Results

In all, 97 surgeons completed the survey (71% response rate). The mean age of respondents was 47.7 (standard deviation 9.1) years; 10.3% were older than 60. Ninety respondents (88.7%) were men, 95 (81.1%) practised in English and 93 (76%) were born in Canada. Most (90.4%) had a medical school affiliation, with an equal proportion practising in community or university teaching hospitals. Only 18% of respondents reported working fewer than 60 hours per week, and 34% were on call more than 1 in 3. Three-quarters of work hours were devoted to clinical care, with the remaining time split among research, administration and teaching. Malignant lung disease accounted for 61.2% of practice time, with the remaining time equally split between benign and malignant thoracic diseases. Preoperative testing (49.4%) and insufficient operating time (49.5%) were the most common factors delaying delivery of care. More than 80% of respondents reported being satisfied with their careers, with 62.1% planning on retiring after age 60.

Conclusion

This survey characterizes Canadian thoracic surgeons by providing specific demographic, satisfaction and scope of practice information. Despite challenges in obtaining adequate resources for providing timely care, job satisfaction remains high, with a balanced workforce supply and demand anticipated for the foreseeable future.