Pathological and biochemical studies on a case of Pick disease with severe white matter atrophy

We report on a male patient with Pick disease who had shown severe white matter atrophy and dilatation of the lateral ventricle in the frontal lobe from an early stage. Upon admission to our hospital 2 years after disease onset, the patient showed apathy, and MRI revealed severe atrophy of the cortex and white matter of the frontal lobe. He died at age 74, 11 years after disease onset. Autopsy revealed severe atrophy of the frontal and temporal lobes, severe loss of white matter in the frontal lobe, dilatation of the lateral ventricles, and cortical thinning. Histopathological examination showed severe loss of myelinated fibers in the frontal white matter and severe neuronal loss with gliosis in the frontal and temporal cortices. Many Pick bodies were seen. Our patient had a rare case of Pick disease predominantly affecting the frontal lobe with severe involvement of the white matter from an early stage. This case suggests that myelinated fibers in the white matter as well as cerebral neurons are primarily affected in Pick disease.     

血管性勃起功能障碍动物模型的建立

目的探索建立血管性勃起功能障碍(ED)动物模型。方法雄性新西兰大白兔给予胆固醇及高脂饮食,同时用球囊导管损伤双侧髂内动脉内皮。测定术后4周、8周血脂并观察阴茎勃起情况、交配情况,同时用阴茎海绵体注射盐酸罂粟碱、阴茎血管双核素检查、髂内动脉数字减影造影(DSA)等方法研究勃起功能。结果与对照组相比,术后4周、8周模型组动物出现明显高脂血症,勃起程度明显下降,交配实验的各项观察指标均显著降低(P＜0.01),动脉造影显示双侧髂内动脉管腔直径明显缩小,双核素检查动脉显像指数(PIA)及静脉显像指数(PIV)明显降低,但第4周的模型组与对照组PIV结果没有统计学差异(P＞0.05)。结论高脂、高胆固醇饮食同时用球囊导管扩张动物髂内动脉,可以加速模型的形成,从而用于血管性ED的进一步研究。     

Structural white matter abnormalities in patients with idiopathic dystonia

We investigated whether structural white matter abnormalities, in the form of disruption of axonal coherence and integrity as measured with diffusion tensor imaging (DTI), constitute an underlying pathological mechanism of idiopathic dystonia (ID), independent of genotype status. We studied seven subjects with ID: all had cervical dystonia as their main symptom (one patient also had spasmodic dysphonia and two patients had concurrent generalized dystonia, both DYT1‐negative). We compared DTI MR images of patients with 10 controls, evaluating differences in mean diffusivity (MD) and fractional anisotropy (FA). ID was associated with increased FA values in the thalamus and adjacent white matter, and in the white matter underlying the middle frontal gyrus. ID was also associated with increase in MD in adjacent white matter to the pallidum and putamen bilaterally, left caudate, and in subcortical hemispheric regions, including the postcentral gyrus. Abnormal FA and MD in patients with ID indicate that abnormal axonal coherence and integrity contribute to the pathophysiology of dystonia. These findings suggest that ID is not only a functional disorder, but also associated with structural brain changes. Impaired connectivity and disrupted flow of information may contribute to the impairment of motor planning and regulation in dystonia. © 2006 Movement Disorder Society     

基质金属蛋白酶与肺癌转移的关系

基质金属蛋白酶(matrix metalloproteinases，MMPs)是一组锌离子依赖的蛋白水解酶，在ECM降解中起着重要作用。目前研究表明，MMPs活性异常不仅能促进肿瘤血管形成，还是人类多种肿瘤侵袭和转移的必要条件。本文就与肺癌侵袭和转移有关的MMPs研究作一综述。     

深部脑白质缺血影像表现与MTHFR基因多态性关系的探讨

目的：探讨MTHFR的纯合突变TT型基因是否为诱发皮层下深部脑白质缺血的危险因子，并证实皮层下深部脑白质缺血影像表现与MTHFR基因C／T多态性的关系。资料与方法：选择影像表现符合皮层下深部脑白质缺血诊断标准者30例，对照组30例为影像表现正常者，运用多聚酶链反应－限制性内切酶片段长度多态性技术（PCR－RFLP）检测两组MTHFR基因多态性。结果：采用χ^2检验，得出MTHFR基因纯合突变TT型在病变组与对照组比较差异有显著性（χ^2=5.0794,P＜0．05），病变组TT型较对照组显著升高，说明MTHFR的纯合突变TT型可能是诱发深部脑白质缺血的危险因素。运用成组设计两样本比较的秩和检验，得出TT型和非TT型患者在影像表现的分级程度上有差别，携带TT型基因者影像表现分级重。结论：MTHFR纯合突变TT型基因是深部脑白质缺血发病的危险因子，且TT型基因与深部脑白质缺血的易感性和影像表现呈明显正相关。     

Brain tissue microarrays in dementia research: White matter microvascular pathology in Alzheimer's disease

Tissue microarrays (TMA) consist of up to 1000 cylindrical tissue cores from different donor paraffin blocks relocated into one recipient block, allowing for efficient histopathological studies by fluorescence in situ hybridization, RNA in situ hybridization or immunohistochemistry. On the background of the increasing interest of the TMA technique in cancer research and the suggestion of its application also in studies of non‐neoplastic intracranial disorders, the technique was applied to pathologic white matter in AD brains. Eight cases with AD and concomitant white matter pathology were neuropathologically diagnosed on whole brain coronal slides. The TMA technique was used to grade severity of white matter pathology and to quantify small vessels with traditional staining and immunohistochemical markers. These measurements were compared with the whole brain neuropathological assessment. The technique produced good results with preserved tissue structures as confirmed by the whole brain evaluation. Severity of white matter pathology evaluated on the TMA cores correlated negatively with small vessel quantities, and statistically significant differences in vessel quantities paralleled different grades of white matter pathology. It is concluded that the TMA technique could be further utilized in studies of dementing disorders, and may have its advantages in large, clinically well‐characterized materials (e.g. in quantitative mapping of white matter changes).     

血液流变学因素对缺血心肌冠脉流量的影响

选用长白猪８只于麻醉下开胸，于在体猪心上探讨心肌缺血时冠脉仍保留有部分扩张储备，而未被充分利用的机理。实验结果表明：降低左冠状动脉前降支（ＬＡＤ）内压至４．６７ｋＰａ时，由ＬＡＤ分别输入腺苷、山莨菪碱、生理盐水（２ｍｌ／ｍｉｎ），皆能诱发出明显的ＬＡＤ流量增加（Ｐ＜０．０５）。在维持ＬＡＤ内压不变，并持续分别输入上述三种溶液的同时，从ＬＡＤ远端取血测血液流变学指标，结果显示，输入生理盐水和山莨菪碱使红细胞压积降低，血浆粘度和全血粘度下降；心肌缺血时，冠脉内输注药物所诱发出的“冠脉扩张储备”部分是由于此种给药方式所引起的血液稀释及血液粘度下降的结果。它提示在冠脉狭窄时，血液粘度对狭窄远端的心肌血供可能是一个相当重要的因素，降低血液粘度可能并不亚于扩血管药物的作用。     

Self-directed learning in anatomy: incorporation of case-based studies into a conventional medical curriculum

This paper reports an attempt to develop self-directed learning skills in second-year medical students by introducing case-based projects into the gross anatomy course at a long-established medical school. The programme and students' responses to a questionnaire completed at the end of the year are presented. Information on the various resources used by students to find information is given. The performance of students in the case-based components of the course has been evaluated and also in the more traditional end-of-year written examination. The data confirm that students have recognized that the projects were about obtaining a deeper understanding of the anatomy, and the programme appears to have promoted the use and study of library texts.     

The long-term effect of pinealectomy on the crypts of the rat gastrointestinal tract

Abstract: Previously it has been found that rat small bowel crypt cell hyperplasia occurred several weeks after pinealectomy. To determine if this effect was longer-lasting (because of the possible role of the pineal in bowel malignancy) the crypt cell proliferation rate was determined in rat small bowel and colon 6 months after pinealectomy, using a stathmokinetic technique. Although the hyperproliferative effect of pinealectomy was well maintained in the small bowel crypts after 6 months, the hyper proliferative effect in the colonic crypts was much less marked. There is no obvious explanation for these findings, although it is possible that regional differences in levels of gut neuropeptides or melatonin are involved. The mechanism of the effect of pinealectomy on the crypts remains unexplained—in particular, why the effect is so prolonged.