胃癌细胞增殖与腹腔灌洗液中端粒酶活性及腹膜转移的相关性研究

目的 研究胃癌增殖细胞核抗原（proliferating cell nuclear antigen，PCNA）表达与腹腔灌洗液端粒酶活性及腹膜转移的相关性，并比较腹腔灌洗液中端粒酶活性和细胞学检测游离癌细胞预测腹膜转移的应用价值。方法 应用免疫组化SP法检测60例胃癌患者胃癌组织中PCNA表达，PCR—TRAP-ELISA法检测腹腔灌洗液中端粒酶活性，同时行腹腔灌洗液脱落细胞学（peritoneal lavage cytology．PLC）检测；并分析其与相关临床病理因素的关系。结果 胃癌患者腹腔灌洗液中端粒酶活性的阳性率为41．7％；与浆膜侵犯、组织学类型、浸润深度、浆膜受累面积及腹膜转移密切相关，并随着浸润深度及浆膜受累面积的增加而升高（P〈0．05）。PLC检测阳性率为25．0％；在伴肉眼可见腹膜转移灶（P1-3）者明显增高，也随着浸润深度及浆膜受累面积的增加而升高。两种方法检测的阳性率总体上差异无统计学意义。但在未分化型癌、pT1、伴肉眼可见腹膜转移灶（P1-3）者端粒酶活性阳性率明显高于PLC。PCNA增殖指数（PI）在腹腔灌洗液端粒酶活性表达阳性者明显高于表达阴性者，伴肉眼可见腹膜转移灶（P1-3）者明显高于无肉眼可见腹膜转移灶（P0）者，浆膜受侵者明显高于浆膜未受侵者（P均〈0．05）。结论 两种方法均适用于胃癌腹腔脱落癌细胞的诊断或腹膜转移的预测，端粒酶活性检测微量癌细胞的灵敏度优于PLC法检测；胃癌端粒酶活性与恶性增殖活性密切相关；胃癌高增殖活性是浆膜受侵及腹膜转移的重要原因。     

基因芯片筛选尿道下裂雌激素敏感基因的研究

目的 寻找与尿道下裂发病密切相关的基因,探讨尿道下裂形成机制.方法 ①实验组为12例尿道下裂患儿,年龄6～12个月,平均8个月.尿道下裂中度5例,重度7例.组织标本取自尿道成形手术时切取的尿道板组织.②对照组为6例年龄匹配的男性患儿,留取包皮环切时的正常表皮组织.用Tri-Reagent分别提取总RNA,与含22 000个人类基因的寡核苷酸基因芯片杂交、洗脱、染色、扫描,基因强度变化行方差分析(ANOVA,P＜0.01)和Tukey分析,基因表达强度变化＞2倍作为有意义的基因,比较尿道下裂和正常组织之间基因表达差异.从上调表达的基因中选择雌激素敏感基因行RT-PCR,标本除上述患儿RNA外,再增加年龄配对的3例中度、1例重度尿道下裂和2例年龄配对的RNA作为对照,即对照、中度和重度尿道下裂患者RNA标本各8例,验证芯片结果.结果 尿道下裂组织与正常组织之间存在明显的基因表达差异,共筛选出表达强度变化＞2倍的基因94个,其中中度尿道下裂与正常比较,47个基因上调表达(P＜0.01);重度尿道下裂与正常比较,68个基因上调表达(P＜0.001);重度与中度比较,17个基因上调表达(P＞0.05).上调表达的基因中发现了4个雌激素敏感基因CYR61、结缔组织生长因子、ATF3和GADD45β,基因芯片和RT-PCR均证实其在尿道下裂组织中的表达明显高于正常对照.结论 异常表达的基因与尿道下裂的发生有关,尿道下裂组织中雌激素敏感基因上调表达参与了尿道下裂的发病机制.     

Cystic fibrosis and the phenotypic expression of autosomal dominant polycystic kidney disease

Recent experiments in cultured cyst epithelial cells from kidneys of patients with autosomal dominant polycystic kidney disease (ADPKD) have shown that the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) is present in the apical surface of these cells and mediates chloride (Cl-) and fluid secretion in vitro. To determine whether the presence of CF with the expression of mutated CFTR proteins modifies cyst formation in ADPKD, we studied a large family with both inherited diseases. ADPKD in this family is linked to PKD1. The family is composed of 26 members; 11 members with ADPKD, 4 members with CF, and 2 members with both diseases. Renal volumes measured by computerized tomography (CT), calculated creatinine clearances, and other clinical parameters in the family members with ADPKD and CF were compared with those in the family members with ADPKD alone, as well as to a large population of patients with ADPKD. The patients with CF and ADPKD, but not the CF heterozygote carriers with ADPKD, had less severe polycystic kidney and liver disease, as indicated by normal renal function; smaller renal volume, even when corrected for height and body surface area; and the absence of hypertension and liver cysts. These observations suggest that the coexistence of CF may reduce the severity of ADPKD.     

Charcot-Marie-Tooth病患者血清PMP22抗体、IL-6和TNF-α水平的研究

目的检测Charcot-Marie-Tooth(CMT)病患者血清周围髓鞘蛋白22(PMP22)抗体、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)水平,以探讨是否有免疫学机制参与CMT的病理生理过程。方法以人工合成PMP22胞外片段作为多肽抗原,用双抗体酶标法检测9名CMT1A患者和7名CMTX1患者血清PMP22抗体,同时检测IL-6和TNF-α水平;11名吉兰-巴雷综合征(GBS)患者和20名性别、年龄相匹配的正常人作对照。结果55.6%CMT1A患者和57.1%CMTX1患者PMP22抗体阳性,63.6%GBS患者和10%正常对照PMP22抗体阳性。正常对照组和CMT患者血清IL-6和TNF-α水平差异无统计学意义(P>0.05)。结论CMT1A患者PMP22抗体阳性与性别、年龄和病程均无关,但在CMTX1家系中,该抗体与性别相关(男性患者阳性),这可能是导致CMTX1家系中男性患者临床症状明显重于女性患者的原因之一。在CMT1A中,PMP22抗体的存在可能是对神经损伤的继发性反应而不是原发性病理过程,在CMTX1家系中存在继发性的免疫过程。此症可能不存在细胞因子介导的免疫损害。     

Potential ethnic modifiers in the assessment and treatment of Alzheimer's disease: challenges for the future

OBJECTIVE: Despite numerous clinical trials, it is unknown whether ethnicity affects treatment response to cognitive enhancers in Alzheimer's disease (AD). There is convincing evidence of ethnic and genetic variability in drug metabolism. This article reviews the available data on ethnicity in clinical trials for AD to answer two questions: (1) what are the challenges to diagnose and treat AD across different ethnic groups, and (2) are there differences in response to pharmacologic interventions for AD across these different ethnic groups? METHOD: Available data from Alzheimer's Disease Cooperative Study (ADCS) randomized controlled clinical trials and from randomized controlled industry-sponsored trials for four cognitive enhancers (donepezil, galantamine, rivastigmine and sabeluzole) were pooled to assess the numbers of non-Caucasian participants. RESULTS: The participation of ethnic minority subjects in clinical trials for AD was dependent on the funding source, although Caucasian participants were over-represented and non-Caucasian participants were under-represented in the clinical trials. Because of the low participation rate of ethnic minorities, there were insufficient data to assess any differences in treatment outcome among different ethnic groups. Strategies to improve diversity in clinical trials are discussed. CONCLUSION: Greater participation of ethnically diverse participants in clinical trials for AD would generate additional information on possible differences in metabolism, treatment response, adverse events to therapeutic agents, and could foster the investigation of genetic variability among ethnic groups.     

The stability of coping strategies in older adults with osteoarthritis and the ability of these strategies to predict changes in depression,disability, and pain

Objectives: Given the chronically painful, incurable nature of osteoarthritis, effective cognitive and behavioral coping strategies may be critical for older adults with the disease. Little is known about how and why coping changes over time, nor about stability of coping strategies in persons with osteoarthritis. The aims of this work were to examine the structure of coping in older adults with osteoarthritis, the association of coping strategies with well-being, the stability of coping over time, and its association with changes in well-being over the same period.

Method: In a cross-sectional study, 199 older adults with osteoarthritis of the knee were assessed at baseline and two-years’ follow-up. Items from two coping scales were factor analyzed, and Pearson's correlations and paired-samples t-tests assessed relative and absolute stability of the resultant coping strategies. CFA assessed the stability of the factor structure itself. Ordinary least-squares regression analyses examined the impact of change in coping on well-being.

Results: A five-factor coping solution emerged: stoicism, refocusing, problem-solving, wishful-thinking, and emotion-focused coping. The factor structure showed stability over the two-year period. Absolute stability of strategies varied, indicating that change in coping styles was possible.

Conclusion: Changes in coping style predicts future well-being; however, coping remains malleable with age and maladaptive strategies can be effectively targeted. Greater knowledge of the utility or maladaptive nature of a given strategy may help guide decisions about interventions for patients with osteoarthritis and encourage more adaptive coping styles.