Association analysis of cytotoxic T-lymphocyte antigen 4 gene polymorphisms with primary biliary cirrhosis in Japanese patients

Background & Aims: Primary biliary cirrhosis (PBC) is an organ-specific autoimmune disease of still unidentified genetic etiology that is characterized by chronic inflammation of the liver. Since cytotoxic T-lymphocyte antigen 4 (CTLA4) polymorphisms have recently been linked with PBC susceptibility in studies on Caucasians, we investigated the genetic association between CTLA4 polymorphisms and PBC in a Japanese population. Methods: Five single nucleotide polymorphisms (SNPs) in the CTLA4 gene (rs733618, rs5742909, rs231775, rs3087243, and rs231725) were genotyped in 308 patients with PBC and 268 healthy controls using a TaqMan assay. Results: One CTLA4 gene SNP (rs231725) was significantly associated with susceptibility to anti-mitochondrial antibody (AMA)-positive PBC, but clinical significance disappeared after correction for multiple testing. Moreover, CTLA4 gene SNPs did not influence AMA development or disease progression to orthotopic liver transplantation in our Japanese cohort. In haplotype analyses, one haplotype [haplotype 1 (CGGA)] at rs5742909, rs231775, rs3087243, and rs231725, was significantly associated with susceptibility to both AMA-positive PBC and overall PBC. Conclusions: This study showed that CTLA4 gene polymorphisms had a modest, but significant association with susceptibility to PBC in the Japanese population. The connection between genetic variants and the function of the CTLA4 gene remains to be addressed in future investigations.ArticleJOURNAL OF HEPATOLOGY. 53(3):537-541 (2010)journal articl

Serum amyloid A-induced IL-6 production by rheumatoid synoviocytes

AbstractIn this study, we investigated the role of serum amyloid A protein (SAA) in the production of interleukin-6 (IL-6) using rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS). Recombinant SAA stimulation induced the production of pro-inflammatory cytokine, IL-6, from RA-FLS. The signaling events induced by SAA included the activation of the mitogen-activated protein kineases, p38 and JNK1/2 and the activation of nuclear factor-kappa B (NF-κB). Inhibitor studies have shown SAA-induced IL-6 production to be down-regulated by NF-κB inhibition and partially inhibited by p38 or JNK inhibitors. Our findings demonstrate that SAA is a significant inducer of IL-6, which is critically involved in RA pathogenesis

Population history of deep-sea vent and seep Provanna snails (Mollusca: Abyssochrysoidea) in the northwestern Pacific

Background Gastropods of the genus Provanna are abundant and widely distributed in deep-sea chemosynthetic environments with seven extant species described in the northwestern Pacific. Methods We investigated the population history and connectivity of five Provanna species in the northwestern Pacific through population genetic analyses using partial sequences of the cytochrome c oxidase subunit I gene. Results We found that P. subglabra, the most abundant and genetically diverse species, is genetically segregated by depth. Among the five species, the three comparatively shallower species (P. lucida, P. kuroshimensis, P. glabra) had a more constant demographic history compared to the deeper species (P. subglabra, P.  clathrata). Discussion Environmental differences, especially depth, appears to have a role in the segregation of Provanna snails. The population of P. clathrata in the Irabu Knoll appears to have expanded after P. subglabra population. The remaining three species, P. lucida, P. kuroshimensis, and P. glabra, are only known from a single site each, all of which were shallower than 1,000 m. These data indicate that Provanna gastropods are vertically segregated, and that their population characteristics likely depend on hydrothermal activities

The role of IL-18 in the modulation of matrix metalloproteinases and migration of human natural killer (NK) cells

AbstractIn this study, we examined whether interleukin-18 (IL-18) affects natural killer (NK) cells' migration and matrix metalloproteinases (MMPs) production. We demonstrated that chemotaxis of human NK cells through basement membrane-like Matrigel was augmented by IL-18. As well, IL-18 stimulation induces the production of activated forms of matrix metalloproteinase-2 (MMP-2) as well as the production of pro-MMP-2 from NK cells. We also demonstrated that MT1-MMP expression on human NK cells, which is a major activator of MMP-2, was induced by IL-18 stimulation coordinated with MMP-2 activation. These data suggest that the MT1-MMP/MMP-2 system participates in the degradation of basement membrane components and thus contributes to NK cell migration

Myocardial Impairment Detected by Late Gadolinium Enhancement in Hypertrophic Cardiomyopathy: Comparison with 99mTc-MIBI/Tetrofosmin and 123I-BMIPP SPECT

Purpose: Myocardial fibrosis is considered to be an important factor in myocardial dysfunction and sudden cardiac death in hypertrophic cardiomyopathy (HCM). The purpose of this study was to compare myocardial fibrosis detected by late gadolinium enhancement (LGE) on cardiac MRI with myocardial perfusion and fatty acid metabolism assessed by single photon emission computed tomography in HCM.Materials and Methods: We retrospectively evaluated 20 consecutive HCM patients (female, 7; mean age, 53.4 years) who underwent LGE, technetium-99m methoxyisobutylisonitrile/tetrofosmin (99mTc-MIBI/tetrofosmin), and iodine-123 beta-methyl-iodophenylpentadecanoic acid (123I-BMIPP) imaging. We calculated the myocardium-to-lumen signal ratio (M/L) for LGE in 17 segments based on the American Heart Association statement. Scoring of 99mTc-MIBI/tetrofosmin (PI) and 123I-BMIPP (BM) was performed for each segment using a 5-point scale (0, normal; 4, highly decreased).Results: Nineteen of 20 patients (95%) and 153 of 340 segments (45%) showed LGE. M/Ls were 0.42ｱ・.16, 0.55ｱ・.17, and 0.65ｱ・.24 in PI0/BM0, PI0/BM1-4 and PI1-4/BM1-4, respectively. All M/Ls were significantly higher than that of a normal control (0.34ｱ・.14) (p<0.001).Conclusions: Myocardial fibrosis in HCM can occur despite normal perfusion and fatty acid metabolism, and is more strongly associated with disorders of fatty acid metabolism than with perfusion abnormalities. M/L may be a useful indicator of disease severity

Skin Perfusion Pressure Is a Prognostic Factor in Hemodialysis Patients

Peripheral arterial disease (PAD) is common in hemodialysis patients and predicts a poor prognosis. We conducted a prospective cohort study to identify risk factors for PAD including skin perfusion pressure (SPP) in hemodialysis patients. The cohort included 373 hemodialysis patients among 548 patients who received hemodialysis at Oyokyo Kidney Research Institute, Hirosaki, Japan from August 2008 to December 2010. The endpoints were lower limb survival (peripheral angioplasty or amputation events) and overall survival of 2 years. Our results showed that <70 mmHg SPP was a poor prognosis for the lower limb survival and overall survival. We also identified age, history of cardiovascular disease, presence of diabetes mellitus, smoking history, and SPP < 70 mmHg as independent risk factors for lower limb survival and overall survival. Then, we constructed risk criteria using the significantly independent risk factors. We can clearly stratify lower limb survival and overall survival of the hemodialysis patients into 3 groups. Although the observation period is short, we conclude that SPP value has the potential to be a risk factor that predicts both lower limb survival and the prognosis of hemodialysis patients

コロナ禍における大学生のストレスと ソーシャル・キャピタルの関連

コロナ禍における大学生のストレスとソーシャル・キャピタル（以下，SC）の関連を明らかにし，コロナ禍における SC を高めるための取り組みについて検討することを目的に，A 大学の大学生 2,124 名を対象に，無記名 WEB 調査を実施した。調査時期は，COVID-19 第６波と第７波の狭間の比較的感染者数が落ち着いている 2022 年６月の一週間とし，調査内容は，Kessler 6 scale 日本語版（以下，K6）を用いたストレス状況と，基本属性，COVID-19 に対する不安，認知的 SC，構造的 SC とした。K6 ≧５点をストレスあり群，K6＜５点をストレスなし群とし，居住形態と共に，COVID-19 に対する不安，認知的 SC ９項目，構造的 SC ８項目について二項ロジスティック回帰分析を行った（有意水準５％）。結果，回答者数は 257 名（回収率 12.1％）であり，ストレスあり群は131 名（51.0％），ストレスなし群は 126 名（49.0％）であった。ストレス状況に関連する要因は，一人暮らしまたは寮生活といった住居環境，認知的 SC では「教員を信頼している」にあてはまらない，構造的 SC では，サークル活動の未実施，COVID-19 に対する感染の不安であった。大学生の半数以上がストレスを有する状況であり，メンタルヘルス対策の強化が課題となった。大学の行事やサークル活動が希薄になる中，所属や帰属意識，組織から守られ大切にされているといった雰囲気の醸成が，大学生一人ひとりの健康につながっていくと考えられた