Messenger RNA expression profile of sleep-related genes in peripheral blood cells in patients with chronic kidney disease

13301乙第2071号博士（医学）金沢大学博士論文本文Full 以下に掲載：Clinical and Experimental Nephrology Apr;20(2) pp.218-225 2016. Springer. 共著者：Shinji Kitajima, Yasunori Iwata, Kengo Furuichi, Akihiro Sagara, Yasuyuki Shinozaki, Tadashi Toyama, Norihiko Sakai, Miho Shimizu, Takeshi Sakurai, Shuichi Kaneko, Takashi Wad

Effect of the primary cooling rate on the motility and fertility of frozen-thawed rabbit spermatozoa

[EN] In the present study, we examined the effect of primary cooling rates on the motility and fertility of frozen-thawed rabbit spermatozoa. Rabbit semen diluted with an egg-yolk acetamide extender was cooled from room temperature to 5°C at four different rates (-0.1, -0.2, -0.4, -0.8°C/min) as a primary cooling step, then semen was frozen in liquid nitrogen vapour. After thawing, sperm cooled at -0.1°C/min showed the highest motility (40.7 ± 7.3%); there were no significant differences between the motilities of the -0.1, -0.2, and -0.4°C/min groups. The motility of frozen-thawed sperm cooled at -0.8°C/min (29.2 ± 6.8%) was significantly lower than that of sperm cooled at -0.1 and -0.2°C/min. The viability (-0.1°C/min, 38.1 ± 4.0%; -0.8°C/min, 24.3 ± 7.3%) of frozen-thawed sperm was closely related to its motility (-0.1°C/min, 36.7 ± 7.2%; -0.8°C/min, 22.3 ± 4.7%). Quality of post-thaw motile sperm cooled at different rates was estimated by comparing the fertilisation ability of the -0.1 and -0.8°C/min groups following artificial insemination. There were no significant differences in pregnancy rates and mean litter sizes. These data suggest that cooling rabbit semen at rates ranging from -0.1 to -0.8°C/min affects the viability but not the fertilisation capacity of motile spermatozoa after thawing.The authors thank Ms. T. Shimazaki, Ms. R. Tsuneyoshi, and Ms. R. Eriguchi for their technical assistance. This study was partly supported by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (No. 22500386).Maeda, T.; Liu, E.; Nishijima, K.; Tanaka, M.; Yamaguchi, S.; Morimoto, M.; Watanabe, T.... (2012). Effect of the primary cooling rate on the motility and fertility of frozen-thawed rabbit spermatozoa. World Rabbit Science. 20(2):65-70. doi:10.4995/wrs.2012.1080SWORD657020

Enhanced Nox1 expression and oxidative stress resistance in c-kit-positive hematopoietic stem/progenitor cells

Although stem cells are generally thought to be resistant to oxidative stress, the fact and in detail molecular mechanism are still to be clearly identified. We herein tried to understand the overall characterization of redox regulatory signaling in hematopoietic stem cells. We purified c-kit-positive hematopoietic stem/progenitor cells from the bone marrow of healthy mice, and then evaluated their redox regulatory property. Compared to the c-kit-negative matured mononuclear cells, c-kit-positive stem/progenitor cells showed lower basic levels of intracellular reactive oxygen species, faster clearance of the accumulated intracellular reactive oxygen species, and higher resistant to oxidative stress. An overall view on the gene expression profile associated with redox regulation showed to be widely differed between cell types. We confirmed that the c-kit-positive stem/progenitor cells expressed significantly higher of Nox1 and catalase, but less of lactoperoxidase than these matured mononuclear cells. Our data suggests that stem cells keep specific redox regulatory property for defensing against oxidative stress

Combined pure red cell aplasia and autoimmune hemolytic anemia in systemic lupus erythematosus with anti-erythropoietin autoantibodies

金沢大学医薬保健研究域医学系A 42-year-old woman with systemic lupus erythematosus was admitted to our hospital because of severe anemia. Her bone marrow was almost normocellular and erythroblasts were nearly absent. Laboratory data showed elevated levels of lactate dehydrogenase and positive findings on Coombs\u27 tests. On the basis of these findings, her anemia was diagnosed as the overlap of pure red cell aplasia with autoimmune hemolytic anemia. Radioimmunoprecipitation assay revealed that her serum was positive for anti-erythropoietin antibodies before therapy. Furthermore, the autoantibodies inhibited proliferation of an erythropoietin-dependent cell line in a dose-dependent manner. Immunosuppressive treatment improved the anemia accompanied with disappearance of the autoantibodies. © 2008 Wiley-Liss, Inc

A case of neurosarcoidosis with necrotizing granuloma expressing angiotensin-converting enzyme

金沢大学医薬保健研究域医学系We described a case of neurosarcoidosis with necrotizing sarcoid granulomatosis in a 22-year-old man. Contrast-enhanced brain computed tomography scan and magnetic resonance imaging showed intracerebral multiple nodular lesions. Noncaseating and partial necrotizing granulomas were detected in the specimen resected by neurosurgery. In addition, immunohistochemical examination revealed the expression of angiotensin-converting enzyme in necrotizing granuloma. Thus, these findings were consistent with neurosarcoidosis. Clinical and pathological presentation, immunological features, and treatment modalities of neurosarcoidosis are discussed. © 2010 Japan College of Rheumatology.This is the pre-peer reviewed version of the following article: [Full cite], which has been published in final form at [link to final article]

Fibrocytes are involved in the pathogenesis of human chronic kidney disease

金沢大学医薬保健研究域医学系The presence of chronic kidney disease in humans is associated with a risk of kidney function loss as well as the development of cardiovascular disease. Fibrocytes have been shown to contribute to organ fibrosis. In this study, the presence of fibrocytes was investigated immunohistochemically in kidney biopsy specimens from 100 patients with chronic kidney disease. In addition, 6 patients with thin basement membrane disease were studied as a disease control. In patients with chronic kidney disease, the infiltration of fibrocytes was observed mainly in the interstitium. The number of interstitial fibrocytes in patients with chronic kidney disease was higher than that in patients with thin basement membrane disease. The number of infiltrated fibrocytes in the interstitium correlated well with the severity of tubulointerstitial lesions, such as interstitial fibrosis, in patients with chronic kidney disease. In addition, there were significant correlations between the number of interstitial fibrocytes and the number of CD68-positive macrophages in the interstitium as well as urinary monocyte chemoattractant protein-1/CCL2 levels. In particular, there was an inverse correlation between the number of interstitial fibrocytes and kidney function at the time of biopsy. Finally, the numbers of interstitial fibrocytes and macrophages as well as urinary CCL2 levels were significantly decreased during convalescence induced by glucocorticoid therapy. These results suggest that fibrocytes may be involved in the pathogenesis of chronic kidney disease through the interaction with macrophages as well as CCL2. © 2010 Elsevier Inc. All rights reserved

Collagen adhesion gene is associated with blood stream infections caused by methicillin-resistant Staphylococcus aureus

Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) causes hospital- and community-acquired infections. It is not clear whether genetic characteristics of the bacteria contribute to disease pathogenesis in MRSA infection. We hypothesized that whole genome analysis of MRSA strains could reveal the key gene loci and/or the gene mutations that affect clinical manifestations of MRSA infection. Methods: Whole genome sequences (WGS) of MRSA of 154 strains were analyzed with respect to clinical manifestations and data. Further, we evaluated the association between clinical manifestations in MRSA infection and genomic information. Results: WGS revealed gene mutations that correlated with clinical manifestations of MRSA infection. Moreover, 12 mutations were selected as important mutations by Random Forest analysis. Cluster analysis revealed strains associated with a high frequency of bloodstream infection (BSI). Twenty seven out of 34 strains in this cluster caused BSI. These strains were all positive for collagen adhesion gene (cna) and have mutations in the locus, those were selected by Random Forest analysis. Univariate and multivariate analysis revealed that these gene mutations were the predictor for the incidence of BSI. Interestingly, mutant CNA protein showed lower attachment ability to collagen, suggesting that the mutant protein might contribute to the dissemination of bacteria. Conclusions: These findings suggest that the bacterial genotype affects the clinical characteristics of MRSA infection. (c) 2019 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases