Age-related progression of tau pathology in brains of baboons

Recently, cytoskeletal changes associated with abnormally phosphorylated tau protein were demonstrated in neurons and glial cells of two aged baboons (Papio). The present study examines the effects of age on the development of tau pathology in baboons. Brains of 50 baboons ranging in age from 1 to 30 years were categorized into four age groups: Group I: 1–10 years [n = 9], group II: 11–20 years [n = 13], group III: 21–25 years [n = 17], group IV: 26–30 years [n = 11]). Whole hemisphere sections (100 μm) were examined using phosphorylation-dependent anti-tau antibodies. Cytoskeletal changes were completely absent in animals of group I. In group II four animals (31%) exhibited cytoskeletal changes which were rated as mild or moderate. In group III abnormal tau was found in 12 brains (71%) ranging in severity from mild to severe. Finally, in group IV 10 out of 11 animals (91%) exhibited some degree of tau pathology which was rated as severe in 4 animals (36%). A statistically significant relationship was found between advancing age and progression of tau pathology in baboons. In conclusion, the present findings underline the value of the baboon as a potential nonhuman primate model for age-related tau pathology afflicting the human brain.     

帕金森病模型大鼠中脑腹侧被盖区多巴胺能神经元改变的实验研究

目的：探讨帕金森病（Parkinson’s disease，PD）大鼠模型中脑腹侧被盖区（ventral tegmentalarea，VTA）多巴胺能神经元的改变。方法：应用6-羟基多巴胺（6-hydroxydopamine，6-OHDA）注射右侧黑质致密区（substantia nigra compacta，SNc）制作PD大鼠模型，进行阿朴吗啡（apomorphine，APO）诱发行为学观察、电镜、尼氏染色观察中脑VTA神经元的改变、酪氨酸羟化酶（tyrosine hydroxylase，TH）免疫组织化学ABC观察其DA能神经元的改变并进行图像分析。结果：APO诱发PD大鼠模型异常旋转行为，尼氏染色见PD大鼠中脑VTA有神经细胞肿胀、坏死等变化，VTA TH阳性神经元数量减少，形态学改变。结论：中脑VTA DA能神经参与PD模型大鼠的改变；APO能诱导6-OHDAPD模型大鼠的旋转行为，其强弱可能与TH^＋神经元数量直接相关。     

Genetic analysis of the CD28/CTLA4/ICOS (CELIAC3) region in coeliac disease

Abstract:  In order to extend our previous findings of genetic linkage to the CD28/CTLA4/ICOS region on chromosome 2q33 ( CELIAC3 ) in coeliac disease (CD), we have investigated 22 genetic markers in 325 Norwegian/Swedish multiplex and simplex CD families. We found both linkage and association with several markers, primarily in the multiplex material. We observed strong linkage disequilibrium (LD) between SNPs (Single Nucleotide Polymorphisms) within an LD block delimited by MH30 and D2S72. A haplotype of this region marked by the alleles −1147*T: + 49*A:CT60*G:CT61*A was significantly associated with CD, suggesting that one or more polymorphisms of this haplotype, possibly −1147*T, are involved in CD susceptibility. The CT60 SNP, a polymorphism found to be most strongly associated with some other immune-mediated diseases, was not associated with CD, as this SNP was part of both associated and non-associated haplotypes. Moreover, our results suggest that CELIAC3 harbours several independent loci contributing to CD susceptibility.     

Abnormal distribution of cathepsins in the brain of patients with Alzheimer's disease

Formalin-fixed paraffin-embedded hippocampal sections of brains with early-onset and late-onset Alzheimer's disease were studied immunohistochemically with antisera against cathepsin D and cathepsin B. In addition to the staining of neuronal perikarya, some of the senile plaques visualized by Bielshowsky silver staining and some of reactive astrocytes were positively stained with the antisera against cathepsin D and cathepsin B in brains with Alzheimer's disease. Abnormal localization of cathepsin D and cathepsin B immunoreactivity in neuronal perikarya was observed in brains with early-onset Alzheimer's disease. These findings demonstrate that the distribution of lysosomal proteases was altered in brains with Alzheimer's disease, suggesting the primary and/or secondary involvement of the lysosomal proteases in the pathological process of Alzheimer's disease.     

锂与缺碘性甲状腺肿发病关系的实验研究

实验用Wistar大鼠125只。随机分成五组。动物实验期为20周。结果显示:单纯低碘或单纯高锂的大鼠均表现为增生性甲状腺肿的组织学改变及血清T_4降低、T_3升高;前者甲状腺上皮细胞增生较后者显著,后者甲状腺滤泡腔内胶质含量较多。低碘合并高锂摄入的大鼠,其甲状腺病变较单纯低碘或单纯高锂大鼠严重,并呈明显的胶性甲状腺肿组织学改变,血清T_4降低、T_3正常。可见高锂不仅有致甲肿作用,而且当它与低碘并存时,将加重甲状腺的病变,并使其向胶性甲状腺肿发展。     

Skin deposits in hereditary cystatin C amyloidosis

Summary Clinically normal skin from 47 individuals aged 9–70 years was investigated. Cystatin C amyloid deposits were found in various locations of the skin by light and/or electron microscopy, in all 12 patients with a clinical history of hereditary cystatin C amyloidosis (HCCA). Six asymptomatic individuals, who had the Alu 1 restriction fragment length polymorphism (RFLP) marker reported to cosegregate with the disease, also had cystatin C amyloid deposits in the skin. Three asymptomatic individuals (age 17–46) belonging to the HCCA families were without amyloid in the skin but had Alu 1 RFLP marker. Skin from 12 individuals who served as controls and skin from 14 close relatives of the patients was negative for amyloid. Punch biopsy of the skin is a simple procedure which is of value for the diagnosis of HCCA, even before the appearance of clinical symptoms. This method might also be of use in following progression of the disease.     

Incidence of severe ovarian hyperstimulation syndrome after GnRH agonist/HMG superovulation for in-vitro fertilization

In 1673 treatment cycles stimulated with buserelin and HMG, for IVF, GIFT or ZIFT, the severe ovarian hyperstimulation syndrome (OHSS) occurred in 10 cycles (0.6%). Eight patients were hyperandrogenic and showed an increased ovarian response to HMG. After replacement of a maximum of three embryos or zygotes, seven women became pregnant. Three women had a multiple gestation. All patients recovered uneventfully with conservative treatment. Support with progesterone or continuation of the agonist during the luteal phase did not prevent OHSS, confirming that the ovulatory HCG dose is the most important factor in inducing this severe complication. Luteal supplementation with HCG and/or HCG production during implantation could exacerbate OHSS.     

Electron microscopic evidence of a viral nature for osteoclast inclusions in Paget's disease of bone

Circumstantial evidence from electron microscopic and immunological studies support the view that Paget's disease of bone represents a slow virus infection. However, there is only limited information available regarding its electron microscopic, enzyme and immunocytochemical characteristics. Two cases were studied using electron microscopy with particular emphasis on the inclusions in osteoclasts. Detailed ultrastructural and cytochemical studies including immuno-electron microscopy were performed. Some osteoclasts demonstrated specific virus-like structures composed of aggregations of microtubules in the nucleus and cytoplasm. The structures were easily digested by trypsin or protease, and were sensitive to RNase, which provided substantial evidence of a proteinaceous nature and inclusion of ribonucleic acid. Immunocytochemical examination identified binding of anti-respiratory syncytial virus and anti-measles virus antibodies in the tissue obtained from one of the two cases examined. The presence of viral antigens in structures in the cytoplasm of Pagetic osteoclasts supports the theory of paramyxovirus involvement in this disease.