Human T-cell receptor BV6 gene polymorphism in relation to expression level and CD4/CD8 skewness

Using 50 samples of umbilical cord blood lymphocytes from Japanese donors, we analysed two human T-cell receptor beta variable (TCRBV) genes, BV6S4 and BV6S5, for their polymorphism, usage frequencies and CD4/CD8 skewness. They showed contrasting CD4/CD8 skewness, BV6S4 to CD8+ T cells and BV6S5 to CD4+ T cells. Genotyping of the BV6S4 alleles (A1, A2 and A3) revealed two of the six possible BV6S4 genotypes, A1/A2 and A2/A2. Among the two BV6S4 genotypes, no significant difference was detected in usage frequency or CD4/CD8 skewness. On the other hand, genotyping of the BV6S5 alleles (A1 and A2) revealed all three possible BV6S5 genotypes, A1/A1, A1/A2 and A2/A2, and the gene usage frequency was high, in the order A1/A1 > A1/A2 > A2/A2. These results indicate that the amino acid substitutions in BV6S5 (S36R and G70E) are in some way associated with the expression level of this gene. In the analysis of CD4/CD8 skewness, the three BV6S5 genotypes had similar skewness, indicating that A1 alleles are expressed more frequently than A2 alleles in both CD4+ and CD8+ T-cell populations. Although BV6S5 exhibits marked skewness to CD4+ T cells, our results indicate that the higher expression of A1 alleles is not associated with the increased ratio of CD4+ T cells.     

Vacuolated cell mesothelioma of the pericardium resembling liposarcoma: a case report

We report a case of localized pericardial mesothelioma with unusual histological features in a 44-year-old woman. Her radiological imagings showed an 11-cm pericardial tumor, between the heart and aortic arch. Microscopically, the tumor was predominantly composed of vacuolated cells and vaguely reminiscent of well differentiated "lipoma-like" liposarcoma, but only small foci of the tumor showed the papillotubular configuration. Histochemically, the tumor cells contained hyaluronic acid in the vacuoles but no lipids. Immunohistochemically, they showed immunoreactivity for cytokeratin, calretinin, vimentin, and epithelial membrane antigen. Ultrastructural study showed that the vacuoles of the tumor cells were intracytoplasmic lumina. The intracytoplasmic lumina and the surface membranes of the tumor cells had many long and slender microvilli with focal bush-like appearance. Desmosomes between adjacent cells were occasionally observed. To our knowledge, this is the first case report of epithelial type mesothelioma predominantly composed of vacuolated tumor cells, microscopically mimicking liposarcoma.     

Fundamental morphological changes in human olivary hypertrophy.

Morphological features of neurons in human inferior olivary nuclei were studied in 6 autopsied patients with dentato-olivary pathway lesions, who had survived for between 6 days and 15 months. Central chromatolysis-like neuronal enlargements were already present in the acute cases. Electron microscopy revealed round, homogeneous and electron-dense granules, varying in diameter from 0.15 micron to 2.5 microns, occurring frequently within the rough endoplasmic reticulum (ER) in the chromatolytic neurons of all 6 patients. No similar granules were observed in 6 controls. The vacuoles were due to dilatation of the rough ER, and often contained floccular materials. Neurofilamentous hyperplasia in the neurons was more frequently seen in the chronic cases. These findings suggest that the fundamental changes in the neurons in olivary hypertrophy occur within the rough ER.     

Temporal profile of potassium channel dysfunction in cerebrovascular smooth muscle after experimental subarachnoid haemorrhage

The pathogenesis of cerebral vasospasm after subarachnoid haemorrhage (SAH) involves sustained contraction of arterial smooth muscle cells that is maximal 6–8 days after SAH. We reported that function of voltage-gated K⁺ (K_V) channels was significantly decreased during vasospasm 7 days after SAH in dogs. Since arterial constriction is regulated by membrane potential that in turn is determined predominately by K⁺ conductance, the compromised K⁺ channel dysfunction may cause vasospasm. Additional support for this hypothesis would be demonstration that K⁺ channel dysfunction is temporally coincident with vasospasm. To test this hypothesis, SAH was created using the double haemorrhage model in dogs and smooth muscle cells from the basilar artery, which develops vasospasm, were isolated 4 days (early vasospasm), 7 days (during vasospasm) and 21 days (after vasospasm) after SAH and studied using patch-clamp electrophysiology. We investigated the two main K⁺ channels (K_V and large-conductance voltage/Ca²⁺-activated (K_Ca) channels). Electrophysiologic function of K_Ca channels was preserved at all times after SAH. In contrast, function of K_V channels was significantly decreased at all times after SAH. The decrease in cell size and degree of K_V channel dysfunction was maximal 7 days after SAH. The results suggest that K_V channel dysfunction either only partially contributes to vasospasm after SAH or that compensatory mechanisms develop that lead to resolution of vasospasm before K_V channels recover their function.     

Skeletal muscle sodium channel gating in mice deficient in myotonic dystrophy protein kinase

Myotonic dystrophy, a progressive autosomal dominant disorder, is associated with an expansion of a CTG repeat tract located in the 3'-untranslated region of a serine/threonine protein kinase, DMPK. DMPK modulates skeletal muscle Na channels in vitro, and thus we hypothesized that mice deficient in DMPK would have altered muscle Na channel gating. We measured macroscopic and single channel Na currents from cell-attached patches of skeletal myocytes from mice heterozygous (DMPK(+/-)) and homozygous (DMPK(-/-)) for DMPK loss. In DMPK(-/-) myocytes, Na current amplitude was reduced because of reduced channel number. Single channel recordings revealed Na channel reopenings, similar to the gating abnormality of human myotonic muscular dystrophy (DM), which resulted in a plateau of Na current. The gating abnormality deteriorated with increasing age. In DMPK(+/-) muscle there was reduced Na current amplitude and increased Na channel reopenings identical to those in DMPK(-/-) muscle. Thus, these mouse models of complete and partial DMPK deficiency reproduce the Na channel abnormality of the human disease, providing direct evidence that DMPK deficiency underlies the Na channel abnormality in DM.     

16例染色体异常核型分析

目的与方法本文对189例自然流产、闭经、发育不全患者进行细胞遗传学检查,结果发现异常核型16例,异常核型涉及1、3、4、5、6、7、8、9、10、 15、X、Y染色体.其中平衡易位10例,性染色体异常3例,大Y染色体3例.结论染色体异常是导致流产、闭经、性发育异常的重要遗传因素,应引起临床医师的高度重视.     

A new haplogroup pattern displayed in Fujian Han in China

Human Y-chromosomal binary polymorphisms have been considered to preserve the paternal genetic legacy and provide evidence on human evolution and the genetic relationships among and demographic history of different populations. To reveal the genetic origin and immigration of the Fujian Han, 13 binary markers on the Y chromosome were used to screen Fujian Han by allele-specific polymerase chain reaction. The results indicated that the M₉G marker was highly prevalent (96.20%), suggesting a significant genetic drift. In addition, M₁₂₂C frequency was only 22.78%, and M₄₅A and M₁₀₃T were default. The distinctive haplogroup frequencies (H₁, H₅, and H_6/7/8) imply that the haplogroup pattern is a relatively ancestral and interim type. Received: October 13, 2001 / Accepted: December 3, 2001