Possible dominant-negative mutation of the SHIP gene in acute myeloid leukemia.

The SH2 domain-containing inositol 5'-phosphatase (SHIP) is crucial in hematopoietic development. To evaluate the possible tumor suppressor role of the SHIP gene in myeloid leukemogenesis, we examined primary leukemia cells from 30 acute myeloid leukemia (AML) patients, together with eight myeloid leukemia cell lines. A somatic mutation at codon 684, replacing Val with Glu, was detected in one patient, lying within the signature motif 2, which is the phosphatase active site. The results of an in vitro inositol 5'-phosphatase assay revealed that the mutation reduced catalytic activity of SHIP. Leukemia cells with the mutation showed enhanced Akt phosphorylation following IL-3 stimulation. K562 cells transfected with the mutated SHIP-V684E cDNA showed a growth advantage even at lower serum concentrations and resistance to apoptosis induced by serum deprivation and exposure to etoposide. These results suggest a possible role of the mutated SHIP gene in the development of acute leukemia and chemotherapy resistance through the deregulation of the phosphatidylinositol-3,4,5-triphosphate (PI(3,4,5)P3)/Akt signaling pathway. This is the first report of a mutation in the SHIP gene in any given human cancer, and indicates the need for more attention to be paid to this gene with respect to cancer pathogenesis.     

恙虫病并发中毒性肝炎40例临床分析

目的探讨恙虫病并发中毒性肝炎的临床特点。方法按诊断标准选择病例进行临床分析。结果本组除了具有恙虫病特征性的临床表现外，同时出现黄疸占25％(总胆红素平均164μmol/L)，出血点和瘀斑占15％，肝大占76％，脾大占63％。ALT和AST升高，平均分别为295U/L和240U/L。使用特效抗茵药物和护肝退黄治疗有良效。结论恙虫病并发中毒性肝炎较常见，少数可出现严重的肝功能损害。     

ICR小鼠人工感染泰泽氏菌的组织病变观察

20只ICR小鼠经尾静脉途径人工感染泰泽氏菌。感染小鼠健康活泼,与对照小鼠无区别。感染后4-7天,lO只经醋酸可的松激发的小鼠其肝脏均表现出轻重不等的散在、灶性病变以至弥漫性灶性坏死,Gierasa染色镜检可见数量不等、典型的泰泽氏菌,细菌培养阴性。10只未经激发小鼠和5只对照小鼠均未见有病变,镜检也未查到泰泽氏菌。上述试验结果表明,泰泽氏菌在ICR小鼠体内的繁殖和形成肝脏病变与机体的免疫状态有密切关系。     

经去颧弓扩大颞下入路切除海绵窦,岩尖,上斜坡肿瘤

本文介绍采用改进的去颧弓扩大颞下入路手术治疗８例位于或累及海绵窦、岩骨尖部、上斜坡、天幕游离前外缘肿瘤患者。该方法的要点是断去颧弓，扇形形成颞肌瓣，翻向颧弓断段以下，咬除蝶骨嵴外侧部分，形成低位颞额骨窗，仅轻度上抬颞叶，则可充分暴露病变范围。由于手术空间扩大，更利于肿瘤切除。本组８例均达到全部或大部分切除，患者术后均得以康复，原有体征不同程度改善。     

Clinical effects and pharmacokinetics of the fusion protein PIXY321 in children receiving myelosuppressive chemotherapy

A hemopoietin with the ability to accelerate both platelet and granulocyte recovery after intensive chemotherapy would have great clinical utility. The recombinant fusion protein composed of human granulocyte-macrophage colony-stimulating factor and interleukin-3 (PIXY321), showed some promise in early adult trials. However, studies for pediatric patients are limited, and there are no systematic data on the pharmacokinetics of PIXY321 given over prolonged periods at current dosage levels. Purpose: To determine the safety, clinical effects and plasma concentrations of increasing doses of PIXY321 in children treated with myelosuppressive chemotherapy. Methods: A total of 39 children with relapsed or high-risk solid tumors were enrolled in this phase I/II study. PIXY321 was administered once or twice daily by subcutaneous injection in total doses of 500 to 1000 μg/m² per day for 14 days after each course of chemotherapy with ifosfamide, carboplatin, and etoposide (ICE). Pharmacokinetic studies were performed on day 1 of the first course in 33 patients and repeated on day 14 in 13 patients (once-daily schedule only). Results: Although mild local skin reactions and fever were frequent, no dose-limiting toxicity was identified at the maximum dose studied (1000 μg/m² per day). There were no statistically significant differences in chemotherapy-induced hematologic toxicity with increasing doses of PIXY321 or with twice-daily vs once-daily dosing. On day 1, the median PIXY321 clearance was 657 ml/min per m² (range 77–1804 ml/min per m²) and the median half-life was 3.7 h (range 2.1–20.8 h). On day 14, clearance increased in all patients studied (median increase 63%), with a corresponding decrease in the median 12-h concentration (from 1.2 to 0.25 ng/ml). Maximum concentrations were <1 ng/ml in 81% of patients, and only two patients had maximum plasma concentrations equivalent to those required for consistent activity in vitro. Conclusions: The recombinant fusion protein PIXY321 proved safe in children treated with myelosuppressive ICE chemotherapy but had no demonstrable clinical benefits. The pharmacokinetic studies suggest that the observed lack of hematologic benefit may be explained by low plasma concentrations resulting from increased clearance with prolonged administration. Moreover, the significant increase in PIXY321 systemic clearance in the absence of increased circulating myeloid cells suggests that the upregulation of either extravascular compartment hematopoietic progenitor cells or nonhematopoietic cells may play an important role in controlling circulating concentrations of this unique cytokine. These findings highlight the importance of a thorough assessment of the systemic disposition of cytokines when determining the dose and schedule necessary to achieve clinical activity in patients. Received: 29 January 1997 / Accepted: 9 May 1997     

T抗原单克隆抗体法在大肠癌筛检中的应用初探

目的 探讨T抗原单克隆抗体法在大肠癌筛检中的临床价值.方法 同时采用T抗原单克隆抗体法和半乳糖氧化酶法检测207例直肠粘液中的T抗原.结果 T抗原单克隆抗体法和半乳糖氧化酶法的敏感性和特异性分别为69.2%、67.3%和64.2%、65.6%,两者的筛检价值无明显差别.结论T抗原单克隆抗体法对大肠癌筛检有较大临床价值,且操作简便.     

维生素B12辅助治疗小儿急性肾小球肾炎40例

我院在常规治疗方法上加用维生素B12治疗小儿急性肾小球肾炎40例，取得很好疗效，现报道如下。     

孕激素与围绝经期情绪障碍相关性的探讨

目的：探索孕激素在女性围绝经期情绪障碍中的作用.方法：研究对象以抑郁为主伴或不伴焦虑的围绝经期女性57例,及参加体检的、经Zung氏焦虑抑郁自评量表筛选后无抑郁焦虑症状群的围绝经期健康女性37例,两组年龄范围均介于40～60岁.主要评定工具为HAMD、HAMA、SAS、SDS等量表,并于入院后次晨空腹抽血检测孕激素.结果：HAMD、HAMA评分在女性围绝经期情绪障碍组和健康对照组之间存在着统计学差异（P＜0.01）;情绪障碍组的孕激素水平虽然略高于健康对照组,但两者之间差异无统计学意义（P＞0.05）;情绪障碍组的孕激素与HAMD评分之间没有相关性,而与HAMA评分之间有低度相关性（P＜0.05）.结论：孕激素在女性围绝经期情绪障碍的发生、发展中可能发挥着一定的作用.     

柴莪退热栓治疗急性病毒性上呼吸道感染临床研究

目的观察柴莪退热栓治疗急性病毒性上呼吸道感染中医辨证属卫分证、卫气同病证的临床疗效,并探讨外感高热卫分证、卫气同病证证候与疗效间的关系.方法将患者 80例随机分为治疗组与对照组,分别予柴莪退热栓和消炎痛栓塞肛,并进行安全性评价.结果两组总体疗效相当,且未发现明显毒副作用.结论 柴莪退热栓治疗急性病毒性上呼吸道感染疗效满意.     

稳态强噪声暴露后听神经动作电位及神经丝蛋白表达的观察

目的 观察豚鼠暴露于稳态强噪声后听神经复合动作电位(CAP)及神经丝蛋白(NFP)的变化。方法 选用20只(40耳)Preyer反射正常的健康豚鼠，分为4组，噪声暴露后存活7天组(N-7d)、14天组(N-14d)和2个月组(N-2m)各5只，空白对照组(C)5只。噪声强度130dB(A)SPL，连续暴露5小时，于暴露前、暴露后3、7、14天、暴露后2个月分别测试CAP—N1波反应阈。免疫组化反应分别检测对照组、暴露后7、14天组、暴露后2个月组动物耳蜗内NFP的表达。结果稳态强噪声暴露后CAP—N1波反应阈明显增高，于暴露后7天基本稳定。暴露后7、14天NFP表达无明显变化，暴露后2月NFP表达显著减弱。结论 130dB(A)SPL稳态强噪声暴露5小时可以导致豚鼠CAP中重度永久性阈移，噪声损伤的早期NFP改变不明显，耳蜗NFP染色反应随着存活时间延长逐渐减弱，反映了损伤后神经纤维中骨架蛋白存在变性过程。