应用免疫组化技术检测胃癌组织p53、c-erbB-2、p21、nm23基因表达产物及其临床意义

目的：为探讨胃癌组织p53、c-erbB-2、p21、nm23联合基因表达产物对胃癌诊断与治疗方面的价值。方法：应用免疫组化技术检测了手术切除胃癌组织p53、c-erbB-2、p21、nm23基因产物表达。结果：p53蛋白表达阳性率37．6％-46．2％，c-erbB-2为34．6％-56．8％，p21为37．8％。61．5％，nm23为30．8％-70．3％；非胃癌组织(胃、十二指肠溃疡、胃息肉、重度不典型增生)未见c-erbB-2、p21、nm23基因表达。c-erbB-2、p21的表达与胃癌的分化程度有关，p21、nm23基因表达与肿瘤浸润深度、肿瘤转移程度有关。p53、c-erbB-2、p21、nm23四种肿瘤蛋白在胃镜活检标本和手术切除标本中表达是一致的，无显著性差异。结论：对胃癌组织检测p53、c-erbB-2、p21、nm23基因表达产物在胃部的良恶性肿瘤鉴别、非手术临床分期的判断及指导胃癌的临床诊断与治疗等方面具有一定价值。     

Association of DAAO with schizophrenia in the Chinese population

Recently, the gene called DAAO was reported to be associated with schizophrenia in the French Canadian populations. Here, we report a result obtained in the study of our large collection of 547 schizophrenia cases and 536 controls in the Chinese population. Six single-nucleotide polymorphisms (SNPs) were genotyped at and around the DAAO locus, covering a 10-kb region entirely encompassing the complementary DNA sequences of DAAO. We found statistically significant differences in allele distributions on one marker: SNP rs3741775 (P = 0.0000001). In the haplotype analysis based on the information of linkage-disequilibrium block across this gene locus, we demonstrated a highly significant association between schizophrenia and a DAAO haplotype (P = 2.0173 x 10(-21)), which therefore provides an independent statistical support for association of the DAAO gene with schizophrenia and indicates that the DAAO gene may play a significant role in the etiology of schizophrenia in the Han Chinese.     

Expression of Wnt ligands and Frizzled receptors in colonic mucosa and in colon carcinoma.

AIMS: Signalling through the Wnt pathway is integrally associated with colon carcinogenesis. Although activating mutations in the genes for adenomatous polyposis coli (APC) and beta-catenin are clearly associated with colon cancer, less is understood about the role of the upstream secreted ligands (Wnts) and their receptors (frizzled, Fz) in this process. In other systems, increased Wnt signalling has been shown to alter the expression of components of this pathway. This study was designed to test the hypothesis that colon cancer is characterised by aberrant expression of specific Wnt genes and Fz receptors. METHODS: The expression of Wnt genes was assessed by in situ, antisense RNA hybridisation in paraffin wax embedded samples of normal and malignant human colon tissues with probes specific for the individual Wnt genes. The expression of Fz1 and Fz2 was determined by immunoperoxidase based antibody staining on human tissues. RESULTS: Changes in the expression of some ligands and receptors were seen in colon cancer. For example, Wnt2 mRNA was detected in colon cancer but was undetectable in normal colonic mucosa. Differential expression of Wnt5a in normal mucosa was also noted, with increased expression at the base of the crypts compared with the luminal villi and slightly increased expression in colon cancer. Wnt7a exhibited minimal expression in both normal and malignant colon tissues, whereas other Wnt ligands including Wnts 1, 4, 5b, 6, 7b, and 10b were expressed equally and strongly in both normal and malignant colon tissues. In defining cellular responses and phenotype, the type and distribution of Fz receptors may be as important as the pattern of Wnt ligand expression. No expression of Fz receptor 1 and 2 was seen in normal colonic mucosa and in well differentiated tumours. However, poorly differentiated tumours exhibited a high degree of Fz receptor expression, especially at the margin of cellular invasion. CONCLUSIONS: These data indicate that the expression of members of the Wnt signal transduction pathway, distinct from APC and beta-catenin, is integrally associated with the process of colon carcinogenesis. Wnt2, and possibly Wnt5a, may be involved in the progression from normal mucosa to cancer and the expression of Fz1/2 receptors may be involved in processes associated with tumour invasion. Altered expression of these Wnts and Fz receptors may prove useful as prognostic or diagnostic markers for patients with colon cancer.     

Treatment of resistant malignant lymphoma with cyclophosphamide, total body irradiation, and transplantation of cryopreserved autologous marrow

Twenty-seven patients with malignant lymphoma in whom primary chemotherapy had failed and the prognosis was poor were treated with cyclophosphamide, total body irradiation, and transplantation of cryopreserved autologous marrow. The median time to recovery of more than 500 neutrophils per microliter and more than 10,000 platelets per microliter was 18 and 24 days, respectively. Complete remission was achieved in 15 patients (56 per cent), five of whom were in continuous remission at this writing 19 to 71 months after transplantation without further therapy and one of whom was alive in a subsequent remission at 20 months. Fifteen patients died of lymphoma, three of interstitial pneumonitis, two of sepsis, and one of congestive heart failure. This experience shows that intensive therapy and autologous-marrow transplantation can produce prolonged remissions in patients with malignant lymphoma in whom conventional chemotherapy has failed.     

体外反搏对心肌缺血犬血流动力学的影响及内皮素机制的探讨

目的：探讨体外反搏改善心肌缺血犬血流动力学的作用和内皮素机制。 方法： 19只健康杂种犬随机分为对照组、缺血组和反搏组，分别于冠状动脉左前降支结扎前和结扎后60 min、120 min、180 min记录以下指标：①主动脉根部血压；②左心室收缩和舒张末压、+dp/dtmax和-dp/dtmax；③头臂干血流量；④放免法检测血浆和心肌内皮素-1（ET-1）的含量。 结果： 冠脉结扎1 h，缺血组和反搏组犬血压、左心室收缩和舒张功能、头臂干血流量明显低于正常组（P<0.05），而血浆ET-1水平明显高于正常组（P<0.05）。经过体外反搏2 h，反搏组犬的收缩压、舒张压和平均压、左心室收缩和舒张功能、头臂干血流量明显高于缺血组（P<0.05）；而反搏组犬的血浆和心肌ET-1水平明显低于缺血组（P<0.05）。 结论： 体外反搏可改善心肌缺血犬血流动力学指标，其机制可能与降低ET-1的产生有关。     

Cytochrome P450 1A1 and manganese superoxide dismutase genes polymorphisms in ankylosing spondylitis

OBJECTIVES: To investigate the associations of cytochrome p450 1A1 (CYP1A1) and manganese superoxide dismutase (MnSOD) genes polymorphisms with the susceptibility to AS in Taiwan. METHODS: The polymorphisms of CYP1A1 and MnSOD genes were determined in 70 patients with ankylosing spondylitis (AS) and 93 healthy controls by polymerase chain reaction (PCR)/restriction fragment length polymorphisms (RFLP) methods. RESULTS: The genotype frequency of CYP1A1 4887C/A was significantly lower in patients with AS than in controls. The phenotype frequency of CYP1A1 4887A also tended to be decreased in patients with AS. There were no significant differences in the genotype, allele, and phenotype frequencies of MnSOD gene polymorphisms between patients with AS and controls. CONCLUSION: CYP1A1 4887A may be a protective factor for the development of AS in Taiwan. However, MnSOD gene polymorphisms are not associated with the susceptibility to AS.     

Functional morphology and physiological properties of bronchopulmonary C-fiber afferents

Nonmyelinated (C-) fibers represent the majority of vagal afferents innervating the airways and lung, and play an important role in regulating the respiratory and cardiovascular functions under both normal and abnormal physiologic conditions. Studies of the relationship between the conduction velocities of the vagal afferents and their sensitivities to capsaicin and other chemical irritants reveal that C-fibers are the primary type of chemosensitive afferents in the rat lung. Furthermore, a distinct sensitivity to capsaicin and a weak response to lung inflation are the defining characteristics of these afferents. In cultured rat nodose and jugular ganglion neurons, capsaicin-sensitive cells were identified by measurement of the capsaicin-evoked calcium transients using the Fura-2-based ratiometric imaging technique. The percentage of capsaicin-sensitive neurons gradually decreases as the cell diameter increases. However, the capsaicin-sensitive neurons cannot be precisely identified solely on the basis of the cell size. Anandamide, an endogenous cannabinoid released from leukocytes and epithelial cells, consistently evokes a stimulatory effect on pulmonary C-fiber endings by activating vanilloid receptor type 1 (VR1). The discharge pattern of pulmonary C-fibers evoked by anandamide closely resembles that produced by a much lower ( approximately 1/600) dose of capsaicin in the same fibers. Whether anandamide acts as a potential endogenous ligand to VR1 at the C-fiber terminals is unclear, and the physiological role of VR1 in modulating the transduction properties of these afferents also remains to be determined.     

牛磺酸拮抗同型半胱氨酸诱导的线粒体呼吸链自由基生成和同型半胱氨酸抑制线粒体牛磺酸转运体

目的:观察同型半胱氨酸(Hcy)对心肌线粒体电子漏及自由基生成的影响,以及观察牛磺酸的拮抗效应。方法: 分离大鼠心肌线粒体,超声波破碎线粒体制备亚线粒体,纯化制备猪心肌线粒体琥珀酸细胞色素C还原酶(SCR)重组体。分别用Hcy和/或牛磺酸共同孵育心肌线粒体、亚线粒体、SCR;用化学发光法测定H₂O₂^- 及O₂^- 生成;并用滤膜抽滤法观察线粒体膜牛磺酸转运体的性质及Hcy对牛磺酸转运功能的影响。结果: Hcy呈浓度依赖性地刺激大鼠心肌线粒体、亚线粒体氧自由基生成及SCR电子漏增加,牛磺酸自身不影响心肌线粒体、亚线粒体及SCR氧自由基生成,但呈浓度依赖性地抑制Hcy诱导的线粒体、亚线粒体及呼吸链重组体氧自由基生成。线粒体膜上存在Na+依赖性的牛磺酸转运体,Hcy呈浓度依赖性地抑制牛磺酸转运体对牛磺酸的转运功能。结论: 牛磺酸抑制Hcy刺激的线粒体呼吸链电子漏增加及氧自由基生成。线粒体膜上存在Na+依赖性的牛磺酸转运体,Hcy抑制线粒体膜上牛磺酸转运体对牛磺酸的转运功能。