DNA analysis of two patients with a non-fluorescent y chromosome

Summary Results of DNA study on two patients of gonadal dysgenesis with a 45,X/46,X,Ynf (non-fluorescent Y chromosome) karyotype are described. In one patient who developed gonadoblastoma, all 12 loci on the non-fluorescent part of Yq were detected. Another patient did not have gonadoblastoma at 20 years, and only the proximal 6 loci out of 12 were detected.     

Neuronal loss and neurofibrillary degeneration in the hippocampal cortex in late-onset sporadic Alzheimer's disease

To explore more fully the relationship between neuronal death and neurofibrillary degeneration, unaffected neurons, intracellular neurofibrillary tangles (i-NFT) and extracellular NFT (e-NFT) in 22 patients with late-onset sporadic Alzheimer's disease (AD) were morphometrically evaluated in eight subdivisions of the hippocampal cortex, using the Gallyas hematoxylin-eosin stain. The subdivisions examined included CA4, CA3, CA2, CA1 (CA: cornu ammonis), prosubiculum (PRO), subiculum and presubiculum (PRE), parasubiculum (PARA) and the entorhinal cortex (ENT). The unaffected neuron density was significantly lower and both i-NFT and e-NFT densities were significantly higher in subdivisions other than CA4 and CA3 in AD patients compared with those in the aged controls. Unaffected neuron density was significantly, inversely correlated with e-NFT density and with total NFT density in all subdivisions except for PRE in AD patients. Especially in CA2, CA1, PRO and ENT, there were strong correlations between the neuron density and these NFT densities. Both unaffected neuron and e-NFT densities in CA1 and ENT were significantly correlated with the disease duration. The i/e-NFT ratio, an index of the degree and/or rate of progress of neuronal death via neurofibrillary degeneration, showed the lowest value in ENT in AD patients. The findings suggest that neuronal death via neurofibrillary degeneration starts earliest and/or most rapidly progresses in ENT. Furthermore, the i/e-NFT ratios in both ENT and CA1 were significantly correlated with the disease duration, suggesting that the neuronal death pattern in the two subdivisions parallels disease progression.     

Are there sequential morphometrical changes in the nucleus basalis in Alzheimer's disease?

Degenerated neurons of the nucleus basalis of Meynert (nbM) were quantitatively analyzed in 3 normal and 3 Alzheimer's disease (AD) subjects. In this study, the Ch4 of the nbM was examined using the indirect immunoperoxidase method with a monoclonal antibody to acetylcholinesterase (AChE) counterstained with cresyl violet. AChE-rich neurons were designated as the cholinergic neurons. The cross-sectional area of all the Ch4 neurons with clearly visible nucleoli in one preparation was measured using a computer image analyzing system. Furthermore, we compared these data with the numbers of neurofibrillary tangles (NFTs) and neuritic plaques (NPs) in the temporal cortex by Gallyas silver stain. The cholinergic neurons decreased in number and size according to the length of the disease duration but the surviving cholinergic neurons in the size range from 800 to 1,000 micron 2 in a case with short clinical duration were increased in number. The non-cholinergic neurons showed only atrophy without definite neuronal cell depletion. The 400- to 1,000-microns 2-sized non-cholinergic neurons were markedly decreased in number, and the number of 300-microns 2-sized non-cholinergic neurons remained unchanged. Although there was an inverse correlation between the degree of atrophy and depletion of the cholinergic neurons with the number of NFTs and NPs in 2 AD cases with 3 and 6 years of disease duration, this correlation was not found in an AD case with 12 years of disease duration, probably due to extensive and profound grey matter degeneration.     

Association of tumor necrosis factor and human leukocyte antigen DRB1 alleles with Graves' ophthalmopathy

Tumor necrosis factor (TNF)-alpha plays a central role in the development of ophthalmopathy in patients with Graves' disease (GD). The aim of this study was to investigate the association of TNF promoter polymorphisms at positions -1031 (T-1031C), -863 (C-863A), -857 (C-857T), -308 (G-308A), and -238 (G-238A) with Graves' ophthalmopathy (GO). We studied the distribution of TNF and human leukocyte antigen (HLA) DRB1 alleles in 228 Polish white patients with GD, 106 of whom had ophthalmopathy (NOSPECS class > or = III) and 248 healthy subjects. TNF -308A and HLA-DRB1*03 alleles were significantly increased in patients with GD compared with healthy subjects. Stratification analysis revealed no independent association of -308A with GD when the DRB1*03 status was considered. Subdividing GD according to eye involvement revealed that the distribution of TNF promoter haplotypes differed significantly in patients with or without ophthalmopathy. The haplotype containing the -238A allele was absent in GO. The association of G-238A with GO was independent of DRB1 alleles. These results indicate that TNF G-308A is associated with susceptibility to GD (however, this association is not independent of HLA-DRB1*03) and that TNF G-238A is associated with the development of ophthalmopathy, suggesting that G-238A or a gene in linkage disequilibrium may be disease modifying in GD.     

Association of phosphorylation site of tau protein with neuronal apoptosis in Alzheimer's disease

In addition to neuritic changes and amyloid deposits, neuronal and glial cell apoptosis is an important pathological feature of Alzheimer's disease (AD). Several factors have been postulated as causes or triggers of cellular apoptotic change. This study focused on a quantifiable relationship between phosphorylation sites of tau protein in the neurofibrillary tangles (NFT) and neuronal apoptosis. Five monoclonal anti-tau antibodies (AT180, AT8, HT7, Tau2 and Tau5) for NFT labeling and TdT-mediated UTP nick-end labeling (TUNEL) for localizing apoptotic change were employed. TUNEL-stained neuronal nuclei showed significantly high density in the entorhinal cortex, cornu ammonis (CA) and the parietal cortex. In all regions, density of TUNEL-stained neuronal nuclei showed significantly direct correlation with that of AT8-, AT180- and Tau2-positive neurons. Correlation of TUNEL-stained neuronal nuclei with tau-positive neurons differed depending on the cerebral regions. Density of TUNEL-stained neuronal nuclei showed inverse correlation with that of both AT8-positive and Gallyas-stained NFT in the CA and showed significantly direct correlation with AT8- and HT7-positive neurons in the frontal cortex. Density of tau-positive and Gallyas-stained NFT was higher than that of TUNEL-stained nuclei. We conclude that phosphorylation sites of tau, 159-163 and 202-205, are probably associated with neuronal apoptosis and apoptotic change follows abnormal phosphorylation of tau.     

Feasibility study of quality of life (QOL) instrument in patients with advanced lung cancer

We have studied the feasibility of the QOL measurement for the group of patients with advanced lung cancer using the QOL questionnaires modified from FLIC (Functional Living Index Cancer). The 16-items instrument showed that the Cronbach's alpha of all categories were over 0.6. as the quality of reliability. Using the principal component method of multivariate analysis, four major factors were identified as a part of the construct validity. We concluded that the QOL of patients with advanced lung cancer under the clinical research setting can be evaluated using this questionnaires even in Japan which has different cultural background from the Western Countries.