抗棘球蚴药物研究:3-取代苯基-5-取代-1,2,4-噁二唑的合成

合成了3-取代苯基-5-取代-1,2,4-(口恶)二唑类化合物50个,经感染棘球蚴的小鼠初筛,部分化合物对棘球蚴有不同程度的作用,化合物13、28和30对棘球蚴的囊重抑制率分别为70、75.6和71.6%,其中化合物13对棘球蚴的生发层有损害作用。     

屈膝过程中的胫股运动特性分析

本文采用三维位移测量方法，测试１０例离体人膝标本的胫股关节三维运动特性。发现屈膝过程中，胫股运动也具有典型的三维运动特点。其中在屈膝初期的３０°内，胫骨内旋最明显并伴有胫骨内翻现象，平均内旋８°，内翻６－７ｍｍ，膝关节完全伸直时胫股扣锁使膝关节稳定，屈曲时胫股“解锁”使膝关节松弛，具重要的临床意义，同时提示，在解释传统的胫股扣锁现象时不应遗漏伴随发生的胫骨内／外翻现象。     

精氨酸加压素（AVP）的衍生物AVP4—8不能作用于AVPV1a受体而诱发电流反应

在微量注射大量肝脏ｍＲＮＡ之后，通过电压箝方法进行功能鉴定，两栖类卵母细胞成功地表达了ＡＶＰＶ１ａ受体。但在灌流ＡＶ４－８溶液时，却不能诱导卵母细胞产生内向振荡电流反应。提示ＡＶＰ４－８不能通过ＡＶＰＶ１ａ受体而介导生理学效应。     

X-刀立体定向放射治疗颅内肿瘤的近期疗效分析

目的:分析立体定向X-刀放射治疗颅内肿瘤后的近期疗效,并进行阶段性工作总结。材料和方法:53例不同类型脑瘤患者,以CT、MR、DSA图像资料作为定位依据,用德国Brain LAB治疗计划系统设计三维优化方案,西门子MD-2型直线加速器旋转照射。结果:53例患者经X-刀治疗后,近期均取得了满意效果,诸如以卡氏评分法评价,临床症状有所改善;以CT增强扫描复查观察,肿瘤大小趋于缩小或消失。结论:立体定向放射治疗后的追踪观察表明,只要严格掌握适应症,精确定位,精确计划,精心治疗,X-刀是一种安全、有效、无痛苦的治疗脑肿瘤的方法。它可起到改善临床症状,提高患者生活质量,延长生存期限的作用。     

A New Serum Tumor Marker, CAM 123-6, Highly Specific to Pulmonary Adenocarcinoma

KL-6, a circulating mucin-like glycoprotein, is a pulmonary adenocarcinoma-associated antigen and is also regarded as an indicator of disease activity of interstitial pneumonitis. KL-6 has extensive heterogeneous antigenic determinants and consists of multiple heterogeneous antigen molecules. We have searched for circulating KL-6-associated glycoproteins with superior diagnostic value to KL-6 as a tumor marker for pulmonary adenocarcinoma. A new murine monoclonal antibody EH-123 reacting with an asialosugar chain on KL-6 was established. A new KL-6-associated molecule detected by a bimonoclonal bideterminant sandwich assay using the EH-123 antibody as a catcher and horseradish peroxidase-labeled KL-6 as a tracer was designated as CAM 123-6. In 59% (22 of 37) of patients with pulmonary adenocarcinoma, serum levels of CAM 123-6 were abnormally elevated and the positive rate increased with the progression of clinical stage. Elevated levels were not detected in normal individuals or in patients with benign lung diseases, other histologic types of lung cancer, gastric cancer, colon cancer or breast cancer. CAM 123-6 was more specific to pulmonary adenocarcinoma than carcinoembryonic antigen (CEA), but the sensitivity of CAM 123-6 for pulmonary adenocarcinoma was similar to that of CEA. CAM 123-6 is a promising candidate as a serum tumor marker for pulmonary adenocarcinoma.     

TGFβ-1 regulation of VEGF production by breast cancer cells

Background: Angiogenesis is essential for tumor growth and metastasis. Vascular endothelial growth factor (VEGF) is the most potent angiogenic factor identified to date. TGFβ-1 acts as an indirect angiogenic agent. Methods: VEGF and TGFβ-1 were measured in the serum of breast cancer patients and agematched controls and in tumor tissue of cancer patients by ELISA. VEGF protein and mRNA expression by breast tumor cell lines were examined, and the effect of TGFβ-1 on VEGF production in these cells was assessed. Results: VEGF levels were significantly higher (P=.03) in the serum of patients with breast cancer compared to age-matched controls. A positive correlation was found between serum (r=0.539) and tumor tissue (r=0.688) levels of VEGF and TGFβ-1. Metastatic MDA-MB-231 breast cancer cells produce more VEGF than do the primary BT474 cells. TGFβ-1 significantly (P<.05) increased production of VEGF. Conclusions: Breast cancer cells constitutively produce VEGF protein and mRNA. There is a relationship between VEGF and TGFβ-1 levels in breast cancer patients, and TGFβ-1 regulates VEGF expression by breast cancer cells. Presented at the 50th Annual Cancer Symposium of the Society of Surgical Oncology, Chicago, Illinois, March 20–23, 1997.     

An experimental model for canine visceral leishmaniasis

Seven mixed-breed dogs were challenged with either promastigotes or amastigotes of Leishmania donovani infantum strains recently isolated from naturally infected dogs. Different routes and numbers of parasites were utilized and each dog was monitored for at least 1 year post-infection. Anti-parasite specific antibody levels were measured by enzyme-linked immunosorbence, immunofluorescence, crossed-immune electrophoresis and Western blotting on crude antigen. Western blotting on two pure parasite proteins, dp72 and gp70-2, was also done. Mitogenic and antigen-specific stimulation of peripheral blood lymphocytes was monitored; and the haematological, clinical and parasitological parameters measured. Dogs challenged with amastigotes exhibited a more pronounced humoral response to leishmanial antigens. Only in one case was strong antigen-specific proliferation detected. Clinical signs of disease, including hypergammaglobulinaemia, enlarged lymph nodes and the presence of parasites, were also more apparent in the dogs challenged with amastigotes. None of the seven dogs died. Serum antibodies to leishmanial antigens were apparent between 1.5 to 3 months following challenge and correlated with the appearance of enlarged lymph nodes, hypergammaglobulinaemia and the presence of parasites in tissue biopsies. Serum antibodies remained chronically high in these dogs throughout the period of the study. Only one dog (1/3) challenged intravenously with promastigotes and the dog challenged intradermally with amastigotes produced transient antibody responses to leishmanial antigen.     

Altered enzyme activities of xenobiotic biotransformation in kidneys after subchronic administration of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) to rats

Activities of the xenobiotic metabolizing enzymes were measured in the liver, kidney, duodenum and lung microsomes and cytosol fractions of Wistar rats after subchronic administration of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a potent bacterial mutagen in chlorinated drinking water. MX was administered by gavage at the dose level of 30 mg/kg for 18 weeks (low dose), or at the dose level which was raised gradually from 45 mg/kg for 7 weeks via 60 mg/kg for 2 weeks to a clearly toxic dose of 75 mg/kg for 5 weeks (high dose). Microsomal and cytosolic preparations were made and the activities of 7-ethoxyresorufin-O-deethylase (EROD), pentoxyresorufin-O-dealkylase (PROD), NADPH-cytochrome-c-reductase, UDP-glucuronosyltransferase (UDPGT) and glutathione-S-transferase (GST) were measured. Kidneys were affected most. A dose-dependent decrease was observed in EROD (90% in males, 80% in females at the high dose) and in PROD (58% in females, at the high dose) in kidneys. An increase was, however, detected in kidney NADPH-cytochrome-c-reductase (66% in females at high dose), UDPGT (89% in males and 97% in females at high dose) and GST activities (56% in males and 50% in females at high dose). MX caused only a few changes in the enzyme activities of the liver. The EROD activity was decreased 25% to 37%, both in the livers of males and females, but the total content of P450s was not altered. Hepatic GST activity was elevated in females in a dose-dependent manner (31% and 44%). GST activity was elevated in duodenum in females (59%) at the high dose. There were no marked changes in the enzyme activities in the lungs. MX was a weak inhibitor of EROD activity both in the liver and kidney microsomes in vitro, decreasing the EROD activity by 53% and 43%, respectively at the concentration of 0.9 mM. The results indicate that MX decreases the activity of phase I metabolism enzymes, but induces phase II conjugation enzyme activities, particularly in kidneys in vivo. It is possible that these changes contribute to metabolism of MX in kidneys and renders them susceptible to MX in the course of repeated exposure.     

超声心动图定量犬冬眠心肌的方法学研究

目的:建立经胸小剂量多巴酚丁胺超声心动图激发试验(Dobu-UCG)评价犬冬眠心肌定量的方法学。材料和方法:成功建立冬眠心肌犬7条3～6个月后进行DoBu-UCG试验,测量Dobu-UCG后的心肌梗死区运动幅度(wall motion amplitude of area with myocardium infarction,MMI)和非梗死区心内膜运动幅度(wall mo-tion amplititude of areas with non myocardium infarction,MNMI)的比值(MMI/MNMI),以及试验后MMI/MNMI与试验前MMI/MNMI的差值(D值);并与实验后测量组织切片的冬眠心肌面积(the area oftotal alive myocardium,ATAM)和梗死区总面积(the area of total infarction myocardium,ATIM)的比值(ATAM/ATIM)进行比较。结果:Dobu-UCG激发试验后MMI/MNMI比值、D值分别与ATAM/ATIM进行对比分析,显示两者均高度相关(r=0.83～0.90,P分别为<0.05和<0.001)。结论:测量Dobu-UCG激发试验后MMI/MNMI比值,以及试验后、前MMI/MNMI差值(D)是定量梗死区内冬眠心肌的较好方法。