Single nucleotide variation analysis in 65 candidate genes for CNS disorders in a representative sample of the European population

The detailed investigation of variation in functionally important regions of the human genome is expected to promote understanding of genetically complex diseases. We resequenced 65 candidate genes for CNS disorders in an average of 85 European individuals. The minor allele frequency (MAF), an indicator of weak purifying selection, was lowest in radical amino acid alterations, whereas similar MAF was observed for synonymous variants and conservative amino acid alterations. In noncoding sequences, variants located in CpG islands tended to have a lower MAF than those outside CpG islands. The transition/transversion ratio was increased among both synonymous and conservative variants compared with noncoding variants. Conversely, the transition/transversion ratio was lowest among radical amino acid alterations. Furthermore, among nonsynonymous variants, transversions displayed lower MAF than did transitions. This suggests that transversions are associated with functionally important amino acid alterations. By comparing our data with public SNP databases, we found that variants with lower allele frequency are underrepresented in these databases. Therefore, radical variants obtain distinctively lower database coverage. However, those variants appear to be under weak purifying selection and thus could play a role in the etiology of genetically complex diseases.     

重复电刺激前肢神经引起成年大鼠运动皮层的可塑性改变

为了了解成年大鼠运动皮层的功能可塑性，利用皮层内微刺激方法测定ＭＩ代表区并观察重复电刺激前肢神经对ＭＩ代表区的影响。实验组大鼠（９例）持续１．２－２小时的前肢神经电刺激导致前肢运动区与面部触须运动区边界向ＶＩ方向，移动２６３．３±９０．９μｍ并同时伴有运动阈值的改变；ＦＬ内ＭＴ降低５．０±１３．３μＡ，而在ＶＩ内ＭＴ升高９．６±１１．６μＡ对照组大鼠间隔１．５－２小时的两次测定结果，ＦＬ－ＶＩ边界     

单克隆抗体2A7亲和层析法纯化红细胞膜表面的CD59分子

用抗ＣＤ５９单抗２Ａ７与ＣＮＢｒ－Ｓｅｐｈａｒｏｓｅ４Ｂ偶联制备亲和层析柱，从正常人红细胞膜蛋白抽提物中分离纯化出ＣＤ５９分子。本法纯化的ＣＤ５９分子量为１８－２０ＫＤａ对还原剂敏感，与ＭｃＡｂｓｓＭＥＭ４３和１Ｆ５有高亲和性，再掺入豚鼠红细胞后，能够抑制人体补体的反应性溶血，本文还对三株抗ＣＤ５９单抗２Ａ７，ＭＥＭ４３及１Ｆ５的抗原特异性进行了初步分析。     

Effects of transgenes for human and bovine growth hormones on age-related changes in ovarian morphology in mice

The expression of human growth hormone (GH) in female transgenic mice (TM) is accompanied by sterility, whereas females expressing the bovine GH gene are fertile. A light and electron microscopic study was conducted to examine whether expression of these foreign GH genes in mice is associated with structural changes in the ovaries of young adult (3-month-old) or middle-aged (7-month-old) mice. One ovary was serially sectioned for light microscopy, and the contralateral ovary was used for electron microscopy. The numbers of preantral (PAF) and antral (AF) follicles, with and without signs of atresia, as well as the number of corpora lutea (CL), were determined. As expected, body weights of both young and middle-aged TM of either kind were significantly increased over those of their normal littermates. However, the ovarian weights of TM and control mice did not differ. In the 3-month-old TM, the ovaries were grossly normal at the light microscopic level. However, significantly more CL were counted in the ovaries of human GH-TM than in those of the other two groups. The percentage of PAF with signs of atresia was significantly reduced in ovaries of bovine GH-TM compared with the other groups, while the percentages of AF undergoing atresia were significantly different in all groups, with the highest values in normal animals, intermediate ones in human GH-TM, and the lowest in bovine GH-TM. In the ovaries of 7-month-old human GH-TM, conspicuous clusters of large, foamy light cells were present in the cortex and the medulla. Ultrastructurally, these cells appeared as interstitial cells in various stages of degeneration, accumulating cholesterol crystal-like inclusions. Although degeneration of interstitial cells was observed also in the other types of animals, it involved usually only single cells and no cytoplasmic crystal inclusions. Moreover, in the ovaries of 7-month-old human GH-TM the percentages of PAF were significantly reduced and the percentages of AF significantly increased compared with those in the two other groups, which did not differ from each other with respect to these parameters. No significant differences in the numbers of CL were found between the groups. Percentages of atretic PAF were significantly reduced in bovine GH-TM and comparable in the other two groups, while percentages of atretic AF were not different between normal and bovine GH-TM, but were significantly increased in human GH-TM.(ABSTRACT TRUNCATED AT 400 WORDS)     

The link between T helper balance and lymphoproliferative disease

Lymphoproliferative disorders comprise a heterogeneous group of neoplasms whose behaviors range from indolent to very aggressive. The increased incidence seen in the context of immunodeficiency provides evidence that the host immune system plays a vital role in their pathogenesis. We believe that T-helper (Th)-2 dominant states favor development of lymphoproliferative disorders, including lymphoma, and conversely T-helper (Th)-1 immunity protects against lymphoproliferative disease. The age distribution of lymphomas favors childhood and post-reproductive senescence, suggesting that exposure to these periods of Th-2 bias constitutes a key risk factor for developing the disease. The tendency of lymphomas to arise in Th-2 biased locations such as mucosal interfaces, immunoprivileged sites, and regions of B-cell differentiation may likewise reflect a corresponding spatial predilection. Various clinical conditions or treatments that shift Th1/Th2 balance, including HIV infection, transplant-related immune suppression, and autoimmune disorders, can also influence the status of lymphoproliferative diseases.     

新生儿缺氧、缺血性脑病血中6-keto-PGF1α,NSE水平变化的临床研究

目的:探讨HIE患者血中6-keto-PGF1α、NSE水平变化及临床意义.方法:用RIA检测89例HIE患者和32例正常新生儿血中6-keto-PGF1α、NSE水平变化.结果:HIE轻、中、重度组6-keto-PGF1α水平与正常对照组比较,均存在显著性差异(p＜0.01),HIE患者轻度组NSE水平与对照组比较无显著性差异(p＞0.05),中、重度组NSE水平与对照组比较存在显著性差异(p＜0.01),6-keto-PGF1α、NSE二组血中浓度上升与HIE程度呈正相关.结论:HIE患者中6-keto-PGF1α、NSE水平检测,对判断HIE的脑损伤程度、治疗、预后观察,具有重要临床意义和应用价值.     

Identification of human antitumor cytotoxic T lymphocytes epitopes of recoverin, a cancer-associated retinopathy antigen, possibly related with a better prognosis in a paraneoplastic syndrome

Cancer-associated retinopathy (CAR) is a rare paraneoplastic syndrome, and the recoverin-specific autoantibody is suggested to contribute to the pathogenesis of retinopathy, including apoptosis of retinal cells. Because it is known that CAR(+) cancer patients have a preferable prognosis, we hypothesized that aberrantly expressed recoverin in cancer cells can become a target of cytotoxic T lymphocytes (CTL). Here we tested nine recoverin-derived HLA-A24-binding peptides for their capacity to elicit antitumor CTL. We observed recoverin-specific CTL responses in two HLA-A24(+) CAR(+) cancer patients. In addition, the CTL responses were obtained from three of ten CAR(-) cancer patients and two of six healthy individuals. The CTL precursor frequency of CAR(+) cancer patients and that of CAR(-) cancer patients was higher than that of healthy individuals. Of nine recoverin peptides, R49 (QFQSIYAKF), R49.2 (QFQSIYAKFF), and R64 (AYAQHVFRSF) were discovered to induce the peptide-specific CTL. Taken together, our present data suggest that peripheral activation of recoverin-specific antitumor CTL is likely to contribute to the preferable prognosis of CAR(+) cancer patients. Moreover, in cases other than CAR(+) cancer patients, recoverin may offer the opportunity to design epitope-based immunotherapeutic approaches for treating HLA-A24(+) cancer patients with a recoverin-expressing tumor.     

磷酸组织胺诱导的Ⅰ型超敏反应对肝损伤作用的研究

目的:通过观察与Ⅰ型超敏反应相关的生物活性介质--组织胺对家兔肝脏有无直接损伤作用,进一步论证Ⅰ型超敏反应对肝脏的损伤作用.方法:选择34只家兔随机分为对照组、实验Ⅰ组和实验Ⅱ组3组;对照组只进行正常饲料喂养,实验Ⅰ组在正常饲料喂养的同时每天给予0.4μg/kg耳静脉注射磷酸组胺注射液,实验Ⅱ组在正常饲料喂养的同时每天给予0.08 μg/kg耳静脉注射磷酸组胺注射液;动态观察以上3个组的血清谷丙转氨酶(ALT)及血清谷草转氨酶(AST)变化;利用光学显微镜观察以上3个组肝组织的病理变化.结果:无论是实验Ⅰ组或实验Ⅱ组,经过一段时间的观察,发现血清内ALT和AST含量均显着高于对照组(P＜0.01),但Ⅰ、Ⅱ组之间无显着性差异(P＞0.05);实验Ⅰ组和实验Ⅱ组在显微镜下观察,其肝脏均有不同程的损伤和病理改变,且实验Ⅱ组的损伤和变化大于实验Ⅰ组,而对照组的肝脏则无明显的病理变化.结论:组织胺对家兔肝脏确实有一定的损伤作用,而且随着投予剂量和时间的增加,肝脏的损伤和病理变化也越显著;通过本研究,可以得出Ⅰ型超敏反应导致肝脏病理变化及损伤的见解.     

A case of multiple schwannomas of the trigeminal nerves, acoustic nerves, lower cranial nerves, brachial plexuses and spinal canal: schwannomatosis or neurofibromatosis?

In most cases, while schwannoma is sporadically manifested as a single benign neoplasm, the presence of multiple schwannomas in one patient is usually indicative of neurofibromatosis 2. However, several recent reports have suggested that schwannomatosis itself may also be a distinct clinical entity. This study examines an extremely rare case of probable schwannomatosis associated with intracranial, intraspinal and peripheral involvements. A 63-year-old woman presented with a seven-year history of palpable lumps on both sides of the supraclavicular area and hearing impairment in both ears. On physical examination, no skin manifestations were evident. Facial sensory change, deafness in the left ear and decreased gag reflex were revealed by neurological examination. Magnetic resonance imaging revealed multiple lesions of the trigeminal nerves, acoustic nerves, lower cranial nerves, spinal accessory nerve, brachial plexuses, and spinal nerves. Pathological examination of tumors from the bilateral brachial plexuses, the spinal nerve in the T8 spinal position and the neck mass revealed benign schwannomas. Following is this patient case report of multiple schwannomas presenting with no skin manifestations of neurofibromatosis.     

The effect of beta adrenergic stimulation on QT and QTc interval in syncope children with or without coexisting ventricular arrhythmias

We investigated the effect of beta-adrenergic stimulation on the heart rate and QT interval in syncope children with or without coexisting ventricular arrhythmias (VA). Of the 24 children who presented with syncope or presyncope and showed negative tilt test, 13 were classified into a group with VA and the remaining 11 without VA. The provocative test was performed in bolus infusion and continuous infusion. RR, QT, and QTc intervals on routine 12-lead surface electrocardiogram were obtained during each stage of isoproterenol infusion. In all cases, malignant ventricular arrhythmia and syncope were not induced by isoproterenol provocative test. RR and QT intervals were shortened and QTc intervals were prolonged as the isoproterenol dose was increased in both groups and methods. The QTc interval reached its peak level after the bolus injection of 1.0 microgram and during the continuous infusion of 0.03 microgram/kg/min. The two groups showed no significant difference in the QTc interval change according to the infusion methods. This study indicates that changes in the heart rate and QT interval by beta-adrenergic stimulation were not different according to the coexisting ventricular arrhythmias in syncope children with negative head-up tilt test.