アスコルビン酸ステアリン酸エステルを投与したマウスにおける鉛毒性の軽減

We aimed to evaluate roles of hepatic ascorbic acid in ddY strain mice after a single injection of lead acetate (100μmol/kg body weight, i.p.). Lead decreased glutathione content, inhibited glutathione S-transferase activity, and increased calcium content in the liver four days after the injection. These lead-induced alterations were significantly antagonized by the treatment of mice with a diet containing 1(w/w) % ascorbyl stearate ester (ASE) for three days before and four days after lead injection, whereas ascorbate content was largely elevated in the livers of animals treated with both lead and ASE. Furthermore, the production of NADPH was enhanced by not only lead injection but also ASE-feeding. These results suggest that ASE-feeding could ameliorate cell damage through the restoration of intracellular redox states

Cultural characteristics of Laetiporus sulphureus, producing an anti-thrombin substance

The clotting time for thrombin of the culture broth from Laetiporus sulphureus was more than 44 times that of the control (2% malt extract medium), whereas the culture broths of all other strains exhibited lower anti-coagulative activity. In experiments on the utilization of carbon sources, the mycelial growth of L. sulphureus was rapid with glucose as the sole carbon source. Casamino acid was the best source for the strain. Thiamine was required for the mycelial growth of L. sulphureus. The optimum temperature for efficient mycelial growth was recorded at 30℃. The initial pH 4 to 5 was the most favorable for L. sulphureus for growth

www.wjgnet.com World Journal of Gastroenterology ISSN 1007-9327

the stomach: Report of five case

Endoscopic enucleation of gastrointestinal stromal tumors of the stomach: Report of five cases

Gastrointestinal stromal tumor (GIST) of the stomach was treated by endoscopic enucleation in five patients. They were three men and two woman, aged 36-56 years. Tumors located in the cardia were completely enucleated endoscopically without any serious complication. The largest diameter of removed tumors ranged from 1.2 to 2.5 cm. Histopathological diagnosis was GIST with low risk of malignancy (mitotic index < 5/50 high power field) in all cases. The patients were disease-free for 10.5-42.2 mo after endoscopic enucleation

DNA damage enhanced by the attenuation of SLD5 delays cell cycle restoration in normal cells but not in cancer cells.

SLD5 is a member of the GINS complex composed of PSF1, PSF2, PSF3 and SLD5, playing a critical role in the formation of the DNA replication fork with CDC45 in yeast. Previously, we had isolated a PSF1 orthologue from a murine hematopoietic stem cell DNA library and were then able to identify orthologues of all the other GINS members by the yeast two hybrid approach using PSF1 as the bait. These GINS orthologues may also function in DNA replication in mammalian cells because they form tetrameric complexes as observed in yeast, and gene deletion mutants of both PSF1 and SLD5 result in a lack of epiblast proliferation and early embryonic lethality. However, we found that PSF1 is also involved in chromosomal segregation in M phase, consistent with recent suggestions that homologues of genes associated with DNA replication in lower organisms also regulate cellular events other than DNA replication in mammalian cells. Here we analyzed the function of SLD5 other than DNA replication and found that it is active in DNA damage and repair. Attenuation of SLD5 expression results in marked DNA damage in both normal cells and cancer cells, suggesting that it protects against DNA damage. Attenuation of SLD5 delays the DNA repair response and cell cycle restoration in normal cells but not in cancer cells. These findings suggest that SLD5 might represent a therapeutic target molecule acting at the level of tumor stromal cells rather than the cancerous cells themselves, because development of the tumor microenvironment could be delayed or disrupted by the suppression of its expression in the normal cell types within the tumor

Ganglioside Synthase Knockout Reduces Prion Disease Incubation Time in Mouse Models

Localization of the abnormal and normal isoforms of prion proteins to detergent-resistant membrane microdomains, lipid rafts, is important for the conformational conversion. Lipid rafts are enriched in sialic acid-containing glycosphingolipids (namely, gangliosides). Alteration in the ganglioside composition of lipid rafts can affect the localization of lipid raft-associated proteins. To investigate the role of gangliosides in the pathogenesis of prion diseases, we performed intracerebral transmission study of a scrapie prion strain Chandler and a Gerstmann-Straussler-Scheinker syndrome prion strain Fukuoka-1 using various knockout mouse strains ablated with ganglioside synthase gene (ie, GD2/GM2 synthase, GD3 synthase, or GM3 synthase). After challenge with the Chandler strain, GD2/GM2 synthase knockout mice showed 20% reduction of incubation time, reduced prion protein deposition in the brain with attenuated glial reactions, and reduced localization of prion proteins to lipid rafts. These results raise the possibility that the gangliosides may have an important role in prion disease pathogenesis by affecting the localization of prion proteins to lipid rafts

Impaired cell cycle restoration after DNA damage in SLD5^+/− MEFs.

<p>MEFs were treated with DMSO (<b>A</b>) or etoposide (<b>B</b>) as indicated in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0110483#pone-0110483-g002" target="_blank">Figure 2</a> and the same number of living cells as indicated were cultured with fresh medium for 72 h. Cells were counted at the indicated time. Data represent the mean ± SD. *, <i>P</i><0.05 (n = 3).</p

Delayed and prolonged Rad51 expression after DNA damage by etoposide in SLD5^+/− MEFs.

<p>(<b>A</b>) Western blot analysis of Rad51 expression in WT and SLD5^+/− MEFs. β-actin was the internal control. MEFs were treated with etoposide for 12 h (−12∼0) and lysed at the indicated times. (<b>B</b>) Quantitative evaluation of Rad51 expression as revealed in (<b>A</b>) based on densitometric analysis. Results are fold-change compared with the level seen in WT MEFs before treatment with etoposide. Data represent the mean ± SD.*, <i>P</i><0.05 (n = 3).</p