キョウト センニュウジ コモンジョ サイホウキ 3 センニュウジ チュウセイ ブンショ モクロク

調査報告(Report

キョウトセンニュウジ コモンジョ サイホウキ

調査報告(Report

キョウトセンニュウジ コモンジョ サイホウキ 2

調査報告(Report

Thymic Alterations in GM2 Gangliosidoses Model Mice

BACKGROUND: Sandhoff disease is a lysosomal storage disorder characterized by the absence of β-hexosaminidase and storage of GM2 ganglioside and related glycolipids. We have previously found that the progressive neurologic disease induced in Hexb(-/-) mice, an animal model for Sandhoff disease, is associated with the production of pathogenic anti-glycolipid autoantibodies. METHODOLOGY/PRINCIPAL FINDINGS: In our current study, we report on the alterations in the thymus during the development of mild to severe progressive neurologic disease. The thymus from Hexb(-/-) mice of greater than 15 weeks of age showed a marked decrease in the percentage of immature CD4(+)/CD8(+) T cells and a significantly increased number of CD4(+)/CD8(-) T cells. During involution, the levels of both apoptotic thymic cells and IgG deposits to T cells were found to have increased, whilst swollen macrophages were prominently observed, particularly in the cortex. We employed cDNA microarray analysis to monitor gene expression during the involution process and found that genes associated with the immune responses were upregulated, particularly those expressed in macrophages. CXCL13 was one of these upregulated genes and is expressed specifically in the thymus. B1 cells were also found to have increased in the thy mus. It is significant that these alterations in the thymus were reduced in FcRγ additionally disrupted Hexb(-/-) mice. CONCLUSIONS/SIGNIFICANCE: These results suggest that the FcRγ chain may render the usually poorly immunogenic thymus into an organ prone to autoimmune responses, including the chemotaxis of B1 cells toward CXCL13

Expression of Calmodulin and Myosin Light Chain Kinase during Larval Settlement of the Barnacle Balanus amphitrite

Barnacles are one of the most common organisms in intertidal areas. Their life cycle includes seven free-swimming larval stages and sessile juvenile and adult stages. The transition from the swimming to the sessile stages, referred to as larval settlement, is crucial for their survivor success and subsequent population distribution. In this study, we focused on the involvement of calmodulin (CaM) and its binding proteins in the larval settlement of the barnacle, Balanus ( = Amphibalanus) amphitrite. The full length of CaM gene was cloned from stage II nauplii of B. amphitrite (referred to as Ba-CaM), encoding 149 amino acid residues that share a high similarity with published CaMs in other organisms. Quantitative real-time PCR showed that Ba-CaM was highly expressed in cyprids, the stage at which swimming larvae are competent to attach and undergo metamorphosis. In situ hybridization revealed that the expressed Ba-CaM gene was localized in compound eyes, posterior ganglion and cement glands, all of which may have essential functions during larval settlement. Larval settlement assays showed that both the CaM inhibitor compound 48/80 and the CaM-dependent myosin light chain kinase (MLCK) inhibitor ML-7 effectively blocked barnacle larval settlement, whereas Ca2+/CaM-dependent kinase II (CaMKII) inhibitors did not show any clear effects. The subsequent real-time PCR assay showed a higher expression level of Ba-MLCK gene in larval stages than in adults, suggesting an important role of Ba-MLCK gene in larval development and competency. Overall, the results suggest that CaM and CaM-dependent MLCK function during larval settlement of B. amphitrite

精巣腫瘍におけるカルボプラチンを含む多剤併用化学療法:投与量, 腎機能と骨髄抑制について

6例の精巣腫瘍患者に対し計22コースのカルボプラチンを基本とした多剤併用療法を施行した.AUC(曲線下面積)は, カルバートにより示された以下の公式により算出した.カルボプラチン投与量=AUC×(GFR+25), GFR; 糸球体濾過率.骨髄抑制の程度をいくつかのカテゴリーにより検討した.化学療法のコースを体表面積当たり投与量により2群に分けた.白血球及び血小板の減少率, 最低値はこの2群の間で有意差を認めなかった.AUCにより3群に分けた場合, AUCの高い群は骨髄抑制の程度が高かったCarboplatin (CBDCA), a derivative of cis-diamminedichloroplatinum, has low renal and neural toxicity. The dose-limiting factor of this agent is myelosuppression. We experienced various degrees of myelosuppression, when the dose of CBDCA was determined by the body surface area (BSA) in CBDCA-based combination chemotherapy for testicular cancer. Calvert demonstrated that the dose of CBDCA administered should be adjusted by renal function, because CBDCA was excreted through the glomerulus. We report the relationship among 3 factors; the administration dose of CBDCA, renal function and the degree of myelosuppression. We treated 6 patients with testicular cancer. A total of 22 courses of CBDCA-based combination chemotherapy was performed. The area under the curve (AUC) was calculated by the following formula, which was demonstrated in Calvert's study. CBDCA dose = AUC x (GFR + 25), GFR; glomerular filtration rate. The degree of myelosuppression was examined. All chemotherapy courses were divided into 2 and 3 groups according to BSA and AUC, respectively. WBC and Plt reduction rates and nadir counts were significantly correlated with AUC, and showed no significant relationship to the dose determined by BSA. This study revealed that the degree of myelosuppression was closely related with AUC, which reflects the renal function

Farm use of calcium hydroxide as an effective barrier against pathogens

Livestock farming is affected by the occurrence of infectious diseases, but outbreaks can be prevented by proper sanitary control measures. Calcium hydroxide (Ca(OH)(2)), commonly called slaked lime, powder is traditionally used as a disinfectant to prevent infectious diseases in livestock. Since Ca(OH)(2) can inactivate a wide variety of pathogens, has a small environmental impact, does not require a disinfection tank (i.e., can be spread directly on the ground) and is produced inexpensively worldwide, it is used for the prevention of epidemics on farms worldwide. Water is essential for the strong alkalinity that underlies its disinfecting effect, but it is unknown how much water is required under field conditions. In addition, Ca(OH)(2) reacts with carbon dioxide in the environment, reducing its pH, but it is unclear how long its degradation takes under actual field use. Thus, we measured the water adsorption ability of Ca(OH)(2)-based disinfectants and its relation to disinfectant activity, as assessed by colony counts and live/dead staining and observation. We found that 15-20% (w/w) water in Ca(OH)(2) was necessary for disinfection to occur in practice. Moreover, we found that the pH of Ca(OH)(2) decreased within about two weeks to one month under actual use in practical conditions and lost its ability to disinfect. We further showed that granules prepared from Ca(OH)(2) and zeolite maintained high alkalinity more than twice as long as calcium powder. These findings will help to establish a suitable method of applying Ca(OH)(2) to protect farms from infectious diseases