Spatial and temporal pattern of purkinje cell degeneration in shaker mutant rats with hereditary cerebellar ataxia

Temporal-spatial patterns of surviving Purkinje cells were studied quantitatively in a rat mutant (shaker) with differential hereditary cerebellar ataxia and Purkinje cell degeneration. Shaker rat mutants are characterized behaviorally as mild if they are ataxic or as strong if they have ataxia and tremor. Purkinje cells degenerate in both mild and strong shaker mutants, but the temporal and spatial patterns of cell death are strikingly different. In mild shaker mutants, Purkinje cell death is temporally restricted, with 31-46% of the Purkinje cells in lobules I-IX dying by 3 months of age. Very few Purkinje cells degenerate after this age. Purkinje cell death is spatially random. In lobules I-IX, every second, third, or fourth Purkinje cell degenerates. Purkinje cells in lobule X do not degenerate. In strong shaker mutants, Purkinje cell degeneration is temporally protracted and spatially restricted. By 3 months of age, most Purkinje cells in lobules I-VIa, -b, and -d, and -d have degenerated. Numerous Purkinje cells in the paravermis of lobules VIIb-VIII have also degenerated. Surviving Purkinje cells in the vermis and lateral hemisphere of lobules VIIb-VIII are aligned in parasagittally oriented stripes or transversely oriented bands. Purkinje cells continue to degenerate in localized areas of the posterior lobe such that, by 18 months of age, surviving Purkinje cells are limited primarily to lobules VIc, VIIa, IXd, and X. Quantitative analysis indicates that none of the Purkinje cells in these lobules degenerate.     

Glial cell line-derived neurotrophic factor (GDNF) gene expression in the human brain: A post mortem in situ hybridization study with special reference to Parkinson's disease

Summary Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor for dopaminergic neurons. Since dopaminergic neurons degenerate in Parkinson's disease, this factor is a potential therapeutical tool that may save dopaminergic neurons during the pathological process. Moreover, a reduced GDNF expression may be involved in the pathophysiology of the disease. In this study, we tested whether altered GDNF production may participate in the mechanism of cell death in this disease. GDNF gene expression was analyzed by in situ hybridization using riboprobes corresponding to a sequence of the exon 2 human GDNF gene. Experiments were performed on tissue sections of the mesencephalon and the striatum from 8 patients with Parkinson's disease and 6 control subjects matched for age at death and for post mortem delay. No labelling was observed in either group of patients. This absence of detectable expression could not be attributed to methodological problems as a positive staining was observed using the same probes for sections of astroglioma biopsies from human adults and for sections of a newborn infant brain obtained at post-mortem. These data suggest that GDNF is probably expressed at a very low level in the adult human brain and its involvement in the pathophysiology of Parkinson's disease remains to be demonstrated. GDNF may represent a powerful new therapeutic agent for Parkinson's disease, however.     

住院皮肤病患者88例死亡原因回顾性分析

目的：探讨住院皮肤病患者的主要致死疾病和死亡原因。方法：回顾性分析华山医院皮肤科1992～2001年88例住院患者的死亡原因。结果：88例死亡患者中，药疹25例，大疱性疾病16例，皮肌炎17例，系统性红斑狼疮(SLF)9例，合计67例，占死亡总数的76．14％。主要死亡原因是继发感染47例，多器官功能衰竭10例，消化道出血9例。结论：药疹、大疱性疾病、皮肌炎和SLE是皮肤科的主要致死疾病，继发感染是重要死亡原因。     

脑静脉血栓病人的死亡因素分析(附5例分析)

目的分析脑静脉血栓(CVT)病人的死亡原因。方法回顾分析136例CVT病人中5例死亡病例的病因、临床表现、影像学资料、治疗经过及死亡原因。结果病死率为3.7%。2例在急性期死亡,3例在慢性期死亡。直接死亡因素均为脑疝;间接死亡因素为颅内多发性出血和多个部位的脑静脉血栓形成,死亡组(3.20±0.84)支静脉受累,存活组(2.09±1.00)支静脉受累(P=0.016)。而性别、年龄、确诊时间、癫疒间发作、病灶部位及治疗前颅内压等没有显著增加死亡的危险性。某些临床表现,如失语、运动障碍、精神症状及意识障碍与死亡有关,但其系多发性颅内出血及多个部位脑静脉血栓所致。结论CVT病人的直接死亡原因为脑疝,间接原因为多发性脑静脉血栓和颅内多发性出血。死亡不仅可以发生在急性期,也可以出现在慢性期。     

Early onset of autoimmunity in MRL/++ mice following immunization with beta 2 glycoprotein I.

Antiphospholipid antibodies (aPL) are associated with thrombosis, thrombocytopenia and recurrent fetal loss in humans and in some animal models. Immunization with beta 2 glycoprotein I (beta 2GPI) induced aPL production in normal rabbits and mice. However, the association of these antibodies with disease manifestations remains controversial. To determine whether induction of aPL by beta 2GPI immunization in an autoimmune strain of mice (MRL/++) would result in acceleration of clinical and serological autoimmune disease manifestations, three groups of 8-week-old female mice were studied. One group was immunized with beta 2GPI, and one with ovalbumin (OVA); the third was not immunized. After two booster injections, sera were analysed for the presence of anticardiolipin (aCL) and anti-DNA by ELISA and anti-nuclear antibody (ANA) by immunofluorescence. Mice were studied for thrombocytopenia, proteinuria, fecundity rates, litter sizes and the development of central nervous system dysfunction. Elevated levels of aCL, anti-DNA and ANA were detected in all beta 2GPI-immunized, in three OVA-immunized, and in none of the unimmunized mice. The anti-DNA antibodies were inhibited by CL micelles, suggesting cross-reactivity between aCL and anti-DNA. Platelet counts, fecundity rates and litter size were reduced in beta 2GPI-immunized but not in OVA-immunized or unimmunized mice. None of the mice developed neurological dysfunction or significant proteinuria over a 10-week period post-immunization. These findings suggest that beta 2GPI immunization induces aPL in MRL/++ mice associated with accelerated autoimmune manifestations resembling the antiphospholipid syndrome.     

QT及JT离散度对心性猝死预测价值的探讨

测定３２例心性猝死和３０例非猝死性心性死亡病人入院后的首次心电图ＱＴ离散度（ＱＴｄ）和ＪＴ离散度（ＪＴｄ），产以３０例存活病人作对照，结果显示：（１）心性猝死组ＱＴｄ，ＪＴｄ较存活组和非猝死性心性死亡组显著增大（前者Ｐ均〈０．０１，后者Ｐ均〈０．０５，而非猝死性心性死亡组与存活组ＱＴｄ，ＪＴｄ比较差异均无统计学意义。（２）在心性猝死病人中，死亡直接原因为快速室性心律失常组（２３例）的ＱＴｄ，ＪＴｄ     

Prediction of Arrhythmic Events After Acute Myocardial Infarction Using Two Methods for Late Potentials Recording

One hundred consecutive patients recovering from an acute myocardiai infarction underwent, prior to home discharge, signal-averaged electrocardiography (ECG), left ventriculography. and 24-hour Holter ECG recording. The signal-averaged ECG was recorded and analyzed using two procedures: the orthogonal bipolar XYZ lead configuration with a bidirectional filter: and a precordial unipolar lead configuration with a uonrecursive digital filter. An abnormal signal-averaged ECG was seen in 40% of patients with the XYZ system and in 30% of patients in the precordial method, abnormal ejection fraction (< 40%) in 24% of patients and high grade ectopy activity in 22%. During the 24-month follow-up period, 12 patients (12%) had an arrhythmic event defined as either sudden death (11 patients) or sustained ventricular tachycardia (1 patient). Neither the signal-averaged ECG with the XYZ configuration, the abnormal ejection fraction, nor the high grade ectopy were able to statistically predict a higher arrhythmic event rate. The signal-averaged ECG with the precordial configuration was able to statistically predict a higher arrhythmic event rate, P < 0.03; odds ratio = 3.96. The combination of the orthogonal XYZ configuration signal-averaged ECG with the ejection fraction (P < 0.01, odds ralio = 7.33), or with ejection fraction and Holter monitoring (P < 0.06. odds ratio = 6.17) was able to predict a higher arrhythmic event rate. The combination of the precordial configuration signal-averaged ECG with the ejection fraction (P < 0.002, odds ratio = 14.4), or with ejection fraction and Holter monitoring (P < 0.06. odds ratio =10) was able to better predict a higher arrhythmic event rate. The combination of a normal or abnormal signal-averaged ECG and ejection fraction gave a sensitivity, specificity, positive, or negative value prediction of arrhythmic events of 60%, 90.6%, 37.5%, and 96%, respectively. It must be emphasized that the number of arrhythmic events during the 2-year follow-up was small and further study is required to determine the true predictive value of each method for arrhythmic events.     

中国农村地区5岁以下儿童肺炎死亡社会危险因素研究

目的 调查农村5岁以下儿童肺炎死亡相关的社会危险因素.方法1995年11月—1997年2月在湖北恩施和建始两个贫困地区对5岁以下儿童肺炎死亡的危险因素进行病例—对照研究,死亡病例组226例,肺炎对照组 452例.结果 引起儿童肺炎死亡的社会-经济危险因素有:家庭的人均年收入少于 450元、母亲没有立即带孩子看病的理由是没钱看病或交通不便、家中曾有过一个孩子死亡、家长和村医生的文化程度低、父亲的职业是农民、居室内有火炉、母亲对疾病的认识不够、医生的专业培训不足等.结论 除生物相关因素外,社会危险因素同样是农村5岁以下儿童肺炎死亡的重要因素.它们中某些因素是可以借助对父母的健康教育和急性呼吸道感染病例标准管理而得到控制.     

NGF Augmentation rescues trigeminal ganglion and principalis neurons,but not brainstem or cortical whisker patterns,after infraorbital nerve injury at birth

Prior studies indicate that neonatal nerve injury kills many trigeminal (V) first- and second-order cells, and interrupts pattern formation in the brainstem and cerebral cortex. Yet it is not known whether effects upon cell survival and pattern formation are causally related. To determine whether axotomized V ganglion cells can be rescued by an exogenous trophic agent, rats received 5 mg/kg of nerve growth factor (NGF) prior to, and every day after, infraorbital nerve section on the day of birth until sacrifice on postnatal day (PND) 1, 3, 5, 7, or 14. Other animals received identical lesions without NGF. Ganglion cell numbers were significantly reduced by PNDl in pups not given NGF, while NGF-treated rats displayed no significant cell loss through PND7. However, NGF did not permanently rescue V neurons because ganglion cell numbers were reliably reduced by PND14. Cell numbers in V nucleus principalis were reduced by PNDl in pups not given NGF, while NGF-treated animals displayed no cell loss through PND14. NGF's rescue of second-order cells is probably an indirect effect of NGF actions upon V ganglion cells because, in other newborns, NGF failed to maintain principalis cells after direct lesion of the left V ganglion. To determine whether preventing cell death permits whisker-related pattern formation, other rats also received NGF prior to and after infraorbital nerve section at birth. After 3–14 days, patterns were assessed in the brainstem and cortex with cytochrome oxidase histochemistry and serotonin immunocytochemistry. Whisker-related patterns failed to develop as in cases not given NGF. These data indicate that communication with the periphery is necessary for the maintenance of central whisker-related patterns. They also suggest that V ganglion cells can be rescued, albeit temporarily, from rapid injury-induced death by NGF, thereby delaying injury-induced cell death in nucleus principalis. However, the mechanism(s) responsible for injury-induced pattern alterations in the developing V system remains to be elucidated. © 1993 Wiley-Liss, Inc.