No evidence for preservation of somatostatin-containing neurons after intrastriatal injections of quinolinic acid

Intrastriatal injections of excitotoxic amino acids and their analogues (for example kainate and ibotenate) elicit a pattern of neuronal degeneration that is similar in many respects to that observed in Huntington's disease. In this disease there is a progressive degeneration of most types of intrinsic neuron but somatostatin and neuropeptide Y levels are increased 3-5-fold. This may be attributed to the selective preservation of a sub-class of striatal aspiny neurons, in which these two peptides are co-localized together with the enzyme NADPH-diaphorase. Beal et al. reported recently that following intrastriatal injections of quinolinic acid in rats, medium-sized aspiny neurons were selectively preserved and they suggested that quinolinic acid which is found in human brain might cause the neuronal degeneration seen in Huntington's disease. We have used immunocytochemical and enzyme histochemical techniques to examine this selective toxicity but find no evidence to support this finding. We conclude that there are substantial differences between the immunocytochemical changes detected in postmortem Huntington's disease brain and those following quinolinic-acid-induced degeneration.     

A highly polymorphic locus very tightly linked to the Huntington's disease gene

The genetic defect in Huntington's disease (HD), an inherited neuropsychiatric disorder of unknown etiology, has not been defined. The discovery of linkage between HD and the DNA marker D4S10(G8) raised the possibility of isolating the disease gene on the basis of its chromosomal location, in addition to providing a limited presymptomatic test for the late onset disorder. But it has been difficult to isolate other DNA markers nearer to the HD gene, and this has hampered attempts to identify the disease locus and limited the applicability and accuracy of predictive testing. Recently, several new DNA markers from the region of the genome near the HD gene have been isolated using a directed cloning strategy. We describe here the characterization of one of these new markers, D4S95, a highly polymorphic locus which displays no recombination with the HD gene in the families tested. The high degree of polymorphism at this locus and its proximity to the HD gene make it extremely useful for predictive testing and as a new starting point for attempts to clone the disease gene.     

Inhibition of caspase-1 slows disease progression in a mouse model of Huntington's disease.

Huntington's disease is an autosomal-dominant progressive neurodegenerative disorder resulting in specific neuronal loss and dysfunction in the striatum and cortex. The disease is universally fatal, with a mean survival following onset of 15-20 years and, at present, there is no effective treatment. The mutation in patients with Huntington's disease is an expanded CAG/polyglutamine repeat in huntingtin, a protein of unknown function with a relative molecular mass of 350,000 (M(r) 350K). The length of the CAG/polyglutamine repeat is inversely correlated with the age of disease onset. The molecular pathways mediating the neuropathology of Huntington's disease are poorly understood. Transgenic mice expressing exon 1 of the human huntingtin gene with an expanded CAG/polyglutamine repeat develop a progressive syndrome with many of the characteristics of human Huntington's disease. Here we demonstrate evidence of caspase-1 activation in the brains of mice and humans with the disease. In this transgenic mouse model of Huntington's disease, expression of a dominant-negative caspase-1 mutant extends survival and delays the appearance of neuronal inclusions, neurotransmitter receptor alterations and onset of symptoms, indicating that caspase-1 is important in the pathogenesis of the disease. In addition, we demonstrate that intracerebroventricular administration of a caspase inhibitor delays disease progression and mortality in the mouse model of Huntington's disease.     

Towards a transgenic model of Huntington's disease in a non-human primate

Non-human primates are valuable for modelling human disorders and for developing therapeutic strategies; however, little work has been reported in establishing transgenic non-human primate models of human diseases. Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized by motor impairment, cognitive deterioration and psychiatric disturbances followed by death within 10-15 years of the onset of the symptoms. HD is caused by the expansion of cytosine-adenine-guanine (CAG, translated into glutamine) trinucleotide repeats in the first exon of the human huntingtin (HTT) gene. Mutant HTT with expanded polyglutamine (polyQ) is widely expressed in the brain and peripheral tissues, but causes selective neurodegeneration that is most prominent in the striatum and cortex of the brain. Although rodent models of HD have been developed, these models do not satisfactorily parallel the brain changes and behavioural features observed in HD patients. Because of the close physiological, neurological and genetic similarities between humans and higher primates, monkeys can serve as very useful models for understanding human physiology and diseases. Here we report our progress in developing a transgenic model of HD in a rhesus macaque that expresses polyglutamine-expanded HTT. Hallmark features of HD, including nuclear inclusions and neuropil aggregates, were observed in the brains of the HD transgenic monkeys. Additionally, the transgenic monkeys showed important clinical features of HD, including dystonia and chorea. A transgenic HD monkey model may open the way to understanding the underlying biology of HD better, and to the development of potential therapies. Moreover, our data suggest that it will be feasible to generate valuable non-human primate models of HD and possibly other human genetic diseases.     

腐殖酸对超滤膜污染特性的研究

对超滤膜受腐殖酸污染的特性进行了研究,比较了不同质量浓度的腐殖酸对膜通量的影响以及添加钙离子后对膜污染的综合影响,同时考查了在膜过滤过程中的UV254变化规律.结果表明,质量浓度为1、2、5、10 mg/L腐殖酸对50 ku的膜通量影响较显著,在相同的过滤时间内,膜通量分别下降了25.5%、32.7%、48.3%和56.1%.添加钙离子后,膜通量下降更严重,但膜滤出水的UV254明显降低,提高了对腐殖酸的去除率.     

醋酸调质钙基吸收剂的循环碳酸化特性

提出了采用醋酸溶液调质石灰石和白云石的方法来提高它们在循环煅烧-碳酸化过反应过程中吸收CO2的能力.在不同反应条件下分别研究了石灰石和白云石的醋酸化产物醋酸钙和醋酸钙镁在循环煅烧-碳酸化过程中的碳酸化转化率.结果表明:碳酸化温度在600～700℃时,醋酸钙和醋酸钙镁的转化率分别明显高于石灰石和白云石,经过15次循环和20次循环后其碳酸化转化率分别可达0.54和0.6.当煅烧温度从920℃增加到1 050℃时,醋酸钙和醋酸钙镁转化率和抗烧结性能明显优于石灰石和白云石.随着碳酸化气氛中CO2浓度的增加,醋酸钙和醋酸钙镁转化率的增量小于石灰石和白云石.存在最佳的粒径范围使醋酸钙和醋酸钙镁的碳酸化能力最大.虽然醋酸钙镁的碳酸化转化率高于醋酸钙,但单位质量煅烧后的醋酸钙的CO2吸收量大于醋酸钙镁.     

cAMP依赖蛋白激酶(PKA)磷酸化Nef蛋白对HIV复制的影响

目的:研究Nef PKA磷酸化位点对HIV复制的影响。方法:在全长HIVNL4-3中,通过将Nef Ser9突变为丙氨酸,构建一个单突变HIV DNA。接着用野生型HIV或单突变型HIV产生病毒,然后用病毒去感染外周血单核细胞(PBMC)。结果:与亲代病毒比较,单突变Ser9为丙氨酸的病毒下调了HIV在静息PBMC中的复制。结论 :该突变在消除静息原代细胞中Nef对HIV复制的影响起重要作用。研究结果显示,PKA对Nef磷酸化是静息细胞中病毒生命周期的重要步骤。     

硝酸改性竹炭理化性质变化的研究

采用质量分数分别为17%、34%和68%的硝酸溶液对竹炭进行8 h的表面改性处理,测定了改性前后竹炭的碘值、灰分和水分含量。结果表明:3种改性条件下竹炭的碘值和灰分含量均比改性之前有小幅度下降,而水分含量则比改性之前有明显上升,其中,以68%硝酸改性的竹炭其各项指标变化幅度最大。使用Boehm滴定法和傅里叶变换红外光谱FTIR对硝酸改性前后的竹炭进行了结构表征,结果发现硝酸改性后的竹炭表面含氧官能团数量有不同程度的增加;比表面积和孔径分析表明,硝酸改性后竹炭的比表面积显著下降,平均孔径显著增大;SEM-EDS分析表明硝酸改性后竹炭的表面粗糙程度增加,同时含碳量降低,含氧官能团数量增加;TG-DSC分析结果同样表明硝酸改性后的竹炭表面有大量水分子和表面官能团生成,进而造成失重率显著增加。     

甜叶菊斑枯病病原菌的生物学特性

甜叶菊斑枯病病原菌经鉴定为Septoria steviae Ishiba Yokoyama et Tani．,病菌分离菌株生长慢,在8种不同培养基上生长速度、产生分生孢子器和分生孢子的能力相差很大．光照对菌体产孢影响显,但对菌丝生长没有影响．降低马铃薯葡萄糖琼脂培养基中葡萄糖的含量,菌体生长慢,但可提高单位面积菌体产孢量．微量元素硼在一定范围内有促进产孢的作用．菌体在pH值3～10范围内均可生长,生长最适pH值是5．0～6．0．     

乙酸光氯化合成三氯乙酸宏观动力学研究

针对乙酸光氯化制备三氯乙酸反应过程，采用带有溢流的环流反应器，在半连续条件下测定乙酸、氯乙酸、二氯乙酸和三氯乙酸浓度随时间的变化规律。建立了乙酸光氯化反应过程的宏观动力学方程，考虑到Cl2与乙酸、氯乙酸和二氯乙酸的反应存在竞争性，通过引入“竞争因子”提高备组分浓度模型计算值与实验值的拟合度，并估计出动力学参数。结果表明，加入“竞争因子”的平行-连串宏观动力学模型能准确地反映己酸光氯化合成三氯乙酸的反应动力学规律。     

草酸分子结构与性质的量子化学计算研究

采用量子化学的MP2,B3LYP,HF计算方法在6311 G水平上,对草酸可能存在的13种构型进行完全放开的全几何优化及振动频率分析,得到8种稳定构型和5种内转动过渡态构型.并对最稳定构型Ⅰ在MP2/6311 G水平上作了NBO和MO分析,讨论了C-C键对草酸稳定性的影响以及草酸的结构与性质之间的关系.     

2,5-噻吩二羧酸锌配合物的合成及表征

采用加热回流的方法,以2,5-噻吩二羧酸和邻菲咯啉为配体,合成了锌的二元和三元配合物,并用元素分析、红外光谱、热重分析进行了表征.     

通过载体表达siRNAs抑制禽流感病毒复制的研究

禽流感病毒是养禽业危害最严重的病原微生物之一。为探讨小干涉RNA(siRNA)对A型禽流感病毒复制的干扰作用,以H5亚型AIV PB2基因为靶序列,设计合成了4对编码siRNAs的DNA序列,将其克隆到psiRNA-hH1neo载体中,构建siRNAs表达载体,鉴定正确后将重组质粒转染MDCK细胞,采用G418筛选建立抗性细胞系,用血凝(HA)试验和real time RT-PCR试验检测抑制效果, 在细胞水平筛选出具有高效抑制AIV复制的2个靶位点PB2-1154、PB2-342、为AIV的基因功能研究,抗病毒药物的开发和转基因动物的研究奠定了基础。     

硝酸甘油治疗心血管疾病的护理体会

目的探讨硝酸甘油治疗心血管疾病出现不同程度不良反应的原因和护理效果。方法对本院1997年来应用硝酸甘油治疗心血管疾病580例病人的资料进行回顾性分析。结果120例出现不同程度的不良反应,其中出现休克2例,体位性低血压54例,颜面潮红、胸闷、头晕头痛39例,静脉炎15例,尿潴留l0例。结论硝酸甘油浓度,滴速未掌握,健康宣教未到位是造成不良反应的原因,严格控制硝酸甘油浓度、滴速,有效健康教育,是提高硝酸甘油治疗心血疾病疗效,减少不良反应的主要手段。