Morphologic change and the DNA contents of the testicular cell of rabbits treated with the fatty acid ex­tracted from the irradiated animals

1. The unsaturated fatty acid fraction (OX) from the liver of irradiated rabbits contains substance which has the same effects as X-ray irradiation on the testicular cells. 2. This substance introduced intravenously causes the degeneration of the germinal cells with the formation of giant cells or multi-nucleated cells and the mitotic abnormalities. 3. The DNA content of the cell also shows the changes exactly identical with that seen after X-ray irradiation. 4. From these results we conclude that the X-ray injury will be mainly due to the production of some toxic substance which is found in the unsaturated fatty acid fraction and severely affects the cells in mitosis and DNA metabolism.</p

Copy number loss of (src homology 2 domain containing)-transforming protein 2 (SHC2) gene: discordant loss in monozygotic twins and frequent loss in patients with multiple system atrophy

<p>Abstract</p> <p>Background</p> <p>Multiple system atrophy (MSA) is a sporadic disease. Its pathogenesis may involve multiple genetic and nongenetic factors, but its etiology remains largely unknown. We hypothesized that the genome of a patient with MSA would demonstrate copy number variations (CNVs) in the genes or genomic regions of interest. To identify genomic alterations increasing the risk for MSA, we examined a pair of monozygotic (MZ) twins discordant for the MSA phenotype and 32 patients with MSA.</p> <p>Results</p> <p>By whole-genome CNV analysis using a combination of CNV beadchip and comparative genomic hybridization (CGH)-based CNV microarrays followed by region-targeting, high-density, custom-made oligonucleotide tiling microarray analysis, we identified disease-specific copy number loss of the (Src homology 2 domain containing)-transforming protein 2 (<it>SHC2</it>) gene in the distal 350-kb subtelomeric region of 19p13.3 in the affected MZ twin and 10 of the 31 patients with MSA but not in 2 independent control populations (<it>p </it>= 1.04 × 10^-8, odds ratio = 89.8, Pearson's chi-square test).</p> <p>Conclusions</p> <p>Copy number loss of <it>SHC2 </it>strongly indicates a causal link to MSA. CNV analysis of phenotypically discordant MZ twins is a powerful tool for identifying disease-predisposing loci. Our results would enable the identification of novel diagnostic measure, therapeutic targets and better understanding of the etiology of MSA.</p

NMR and mutational identification of the collagen-binding site of the chaperone Hsp47.

Heat shock protein 47 (Hsp47) acts as a client-specific chaperone for collagen and plays a vital role in collagen maturation and the consequent embryonic development. In addition, this protein can be a potential target for the treatment of fibrosis. Despite its physiological and pathological importance, little is currently known about the collagen-binding mode of Hsp47 from a structural aspect. Here, we describe an NMR study that was conducted to identify the collagen-binding site of Hsp47. We used chicken Hsp47, which has higher solubility than its human counterpart, and applied a selective (15)N-labeling method targeting its tryptophan and histidine residues. Spectral assignments were made based on site-directed mutagenesis of the individual residues. By inspecting the spectral changes that were observed upon interaction with a trimeric collagen peptide and the mutational data, we successfully mapped the collagen-binding site in the B/C β-barrel domain and a nearby loop in a 3D-homology model based upon a serpin fold. This conclusion was confirmed by mutational analysis. Our findings provide a molecular basis for the design of compounds that target the interaction between Hsp47 and procollagen as therapeutics for fibrotic diseases

Oyygen uptake of adriamycin resistant cells of Ehrlich ascites tumor

エールリッヒ腹水癌細胞を用いアドリアマイシンに対する耐性細胞（ADR耐性細胞）を樹立した。電子顕微鏡を用い撮影写真から細胞質当たりのミトコンドリア（MT）の割合を面積比で求めた。親株に比較して1μg/ml ADR耐性細胞では1.32倍、10μg/ml ADR耐性細胞では1.47倍であった。これらの細胞の呼吸を測定した。耐性細胞の内発呼吸は親株に比較して増加していた。1μg/ml ADR耐性細胞では1.45倍、10μg/ml ADR耐性細胞では1.49倍であり、MTの増加量とほぼ同じ割合であった。これらのことから、細胞が耐性になるとエネルギー消費が高まるために細胞内MTが増加し、その結果呼吸（酸素消費）が増加することが推察された。Adriamycin-resistant cells of Ehrlich ascites tumor cells were established in our laboratory. Using electron microscope, the area of mitochondria (MT) per cytoplasm of ADR-resistant cells were measured with planimeter. The values of wild-type cells, 1μg/ml ADR-resistant cells and 10μg/ml ADR-resistant cells were 39.3, 51.8 and 57.7 μ(2) per 1,000 μ(2) of cytoplasm, respectively. Oxygen consumption of 1 μg/ml ADR-resistant cells and 10 μg/ml ADR-resistant cells were 1.45-fold and 1.49-fold compared to that of wild-type cells, respectively. These results indicate that ADR-resistant cells require more energy to work efflux pump than wild-type cells