Selective sparing of a class of striatal neurons in Huntington's disease

A distinct subpopulation of striatal aspiny neurons, containing the enzyme nicotinamide adenine dinucleotide phosphate diaphorase, is preserved in the caudate nucleus in Huntington's disease. Biochemical assays confirmed a significant increase in the activity of this enzyme in both the caudate nucleus and putamen in postmortem brain tissue from patients with this disease. The resistance of these neurons suggests that the gene defect in Huntington's disease may be modifiable by the local biochemical environment. This finding may provide insight into the nature of the genetically programmed cell death that is a characteristic of the disease.     

NMDA receptor losses in putamen from patients with Huntington's disease

N-Methyl-D-aspartate (NMDA), phencyclidine (PCP), and quisqualate receptor binding were compared to benzodiazepine, gamma-aminobutyric acid (GABA), and muscarinic cholinergic receptor binding in the putamen and cerebral cortex of individuals with Huntington's disease (HD). NMDA receptor binding was reduced by 93 percent in putamen from HD brains compared to binding in normal brains. Quisqualate and PCP receptor binding were reduced by 67 percent, and the binding to other receptors was reduced by 55 percent or less. Binding to these receptors in the cerebral cortex was unchanged in HD brains. The results support the hypothesis that NMDA receptor-mediated neurotoxicity plays a role in the pathophysiology of Huntington's disease.     

Mental symptoms in Huntington's disease and a possible primary aminergic neuron lesion

Monoamine oxidase activity was higher in the cerebral cortex and basal ganglia of patients dying from Huntington's disease than in controls. Enzyme kinetics and multiple substrate studies indicated that the increased activity was due to elevated concentrations of monoamine oxidase type B. Concentrations of homovanillic acid were increased in the cerebral cortex but not in the basal ganglia of brains of patients with Huntington's disease. These changes may represent a primary aminergic lesion that could underlie some of the mental symptoms of this disease.     

Evidence for degenerative and regenerative changes in neostriatal spiny neurons in Huntington's disease

Golgi impregnations of neostriatum from deceased Huntington's disease patients and controls were examined. In all cases of Huntington's disease the morphology of dendrites of medium-sized spiny neurons was markedly altered by the appearance of recurved endings and appendages, a decrease or increase in the density of spines, and abnormalities in the size and shape of spines. Pathological changes were rarely observed in medium-sized and large aspiny neostriatal neurons. The findings provide evidence for simultaneous degeneration and growth of spiny neurons in Huntington's disease and support the view that a specific population of neostriatal neurons is selectively involved in its pathogenesis.     

A DNA segment encoding two genes very tightly linked to Huntington's disease

The discovery of D4S10, an anonymous DNA marker genetically linked to Huntington's disease (HD), introduced the capacity for limited presymptomatic diagnosis in this late-onset neurodegenerative disorder and raised the hope of cloning and characterizing the defect based on its chromosomal location. Progress on both fronts has been limited by the absence of additional DNA markers closer to the HD gene. An anonymous DNA locus, D4S43, has now been found that shows extremely tight linkage to HD. Like the disease gene, D4S43 is located in the most distal region of the chromosome 4 short arm, flanked by D4S10 and the telomere. In three extended HD kindreds, D4S43 displays no recombination with HD, placing it within 0 to 1.5 centimorgans of the genetic defect. Expansion of the D4S43 region to include 108 kilobases of cloned DNA has allowed identification of eight restriction fragment length polymorphisms and at least two independent coding segments. In the absence of crossovers, these genes must be considered candidates for the site of the HD defect, although the D4S43 restriction fragment length polymorphisms do not display linkage disequilibrium with the disease gene.     

Alzheimer's disease: cell-specific pathology isolates the hippocampal formation

Examination of temporal lobe structures from Alzheimer patients reveals a specific cellular pattern of pathology of the subiculum of the hippocampal formation and layers II and IV of the entorhinal cortex. The affected cells are precisely those that interconnect the hippocampal formation with the association cortices, basal forebrain, thalamus, and hypothalamus, structures crucial to memory. This focal pattern of pathology isolates the hippocampal formation from much of its input and output and probably contributes to the memory disorder in Alzheimer patients.     

SUMO1 haploinsufficiency leads to cleft lip and palate

The posttranslational modification sumoylation can have multiple effects on its substrate proteins. We studied a patient with isolated cleft lip and palate and a balanced chromosomal translocation that disrupts the SUMO1 (small ubiquitin-related modifier) gene, resulting in haploinsufficiency. In mouse, we found that Sumo1 is expressed in the developing lip and palate and that a Sumo1 hypomorphic allele manifests an incompletely penetrant orofacial clefting phenotype. Products of several genes implicated in clefting are sumoylated, and the Sumo1 hypomorphic allele interacts genetically with a loss-of-function allele for one of these loci. Thus, sumoylation defines a network of genes important for palatogenesis.     

Huntington's disease: two families with differing clinical features show linkage to the G8 probe

To test the hypothesis that interfamily variability in Huntington's Disease (HD) is due to mutation at different loci, linkage analysis was undertaken in two large HD kindreds that differed in ethnicity, age-at-onset, and neurologic and psychiatric features. Both families showed linkage of the HD locus to the G8 probe. Several recombinants were documented in each family, and the best estimate of the recombination fraction for the two families was 6 percent with a 95 percent confidence interval of 0 to 12 percent. Although the data support the existence of a single HD locus, use of the G8 probe for presymptomatic testing in these kindreds would have resulted in a 12 percent error rate in genotype assignment at the HD locus.     

仿刺参稚参"脱板病"超微病理的研究

利用电镜负染技术对2006年夏季大连地区养殖场患脱板病的仿刺参Apostichopus japonicus稚参组织匀浆液进行了检测。结果发现,提取液中存在大量病毒样粒子,该病毒粒子近似球形,具有囊膜。应用超薄切片电镜技术对患病刺参的超微病理进行研究,并与正常组进行了对照观察,结果发现:在病变细胞内存在大量直径80~100 nm的具有囊膜的球形病毒样粒子,该病毒粒子以团聚或散落形式存在于细胞质内,并由质膜包被;病变细胞内内质网肿胀,部分核糖体脱落,其周围散落着大量明显呈六边形的病毒核心结构,并出现大量溶酶体残余体形成的髓袢样结构;高尔基体明显肿胀、膨大,线粒体界限模糊,出现嵴脱落;在病变严重的细胞内,可见细胞器崩解后形成的大量空泡结构。但未发现细菌和其他类可疑病原。     

医学病理学的发展与我国近代兽医病理学

兽医病理学的发展同整个医学的发展密切相关。本文回顾了医学病理学的发展进程,着重叙述了我国近代兽医病理学的发展,特别是改革开放以来,我国兽医病理学事业的进步历程。     

Alterations in L-glutamate binding in Alzheimer's and Huntington's diseases

Brain sections from patients who had died with senile dementia of the Alzheimer's type (SDAT), Huntington's disease (HD), or no neurologic disease were studied by autoradiography to measure sodium-independent L-[3H]glutamate binding. In brain sections from SDAT patients, glutamate binding was normal in the caudate, putamen, and claustrum but was lower than normal in the cortex. The decreased cortical binding represented a reduction in numbers of binding sites, not a change in binding affinity, and appeared to be the result of a specific decrease in numbers of the low-affinity quisqualate binding site. No significant changes in cortical binding of other ligands were observed. In brains from Huntington's disease patients, glutamate binding was lower in the caudate and putamen than in the same regions of brains from control and SDAT patients but was normal in the cortex. It is possible that development of positron-emitting probes for glutamate receptors may permit diagnosis of SDAT in vivo by means of positron emission tomographic scanning.     

人SUMO1基因的真核表达载体构建及其RNA干扰靶点筛选

[目的]构建人SUMO1的真核表达载体,筛选SUMO1的有效干涉靶点。[方法]将SUMO1亚克隆至载体pCMV-HA中。寻找可能的干涉位点,合成上下游引物,退火后直接克隆入GFP-HU双启动子载体。用WesternBlot和细胞荧光的方法检测各载体对外源性SUMO融合蛋白表达的影响,其后检测对内源性SUMO1表达的敲降效果。[结果]构建的人SUMO1真核表达载体pCMV-HA-SUMO1测序正确。针对267、279、293、309、342、386等不同干涉靶点构建双启动子干扰载体,其中293位点的干涉载体在WesternBlot和荧光检测试验中均表现出稳定的敲降效果,抑制了SUMO1的表达。[结论]该研究成功构建了SUMO1的真核表达载体及具有明显敲降效果的干涉载体,可为后续研究奠定基础。