61 research outputs found

    The Study of MASPs Knockout Mice

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    ダイ46ジ ナンキョク チイキ カンソクタイ キショウブモン ホウコク 2005

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    この報告は,第46次南極地域観測隊気象部門が,2005年2月1日から2006年1月31日まで昭和基地において行った気象観測結果をまとめたものである.観測方法,測器,統計方法等は第45次隊とほぼ同様である. 越冬期間中,特記される気象現象として,次のものが挙げられる.1) 地上気象観測において,2005年の年平均相対湿度73は高い方から,年平均雲量7.5は多い方からの極値を更新し,年平均風速7.2m/sは大きい方から,年合計雪日数228日は多い方から第2位の記録となった.2) ブリザードの回数は,A級6回,B級9回,C級15回の計30回で平年並みだったが,5月は過去最多の5回を記録した.3) 昭和基地上空のオゾン全量日代表値は,8月下旬から10月中旬までオゾンホールの目安となる220m atm-cm以下の値を継続的に下回り,9月の月平均値は173m atm-cmで,過去4番目に少なかった.10月4日には越冬中の最低値である136m atm-cmを記録した.This report describes the results of meteorological observations at Syowa Station from February 1st, 2005 to January 31st, 2006, carried out by the Meteorological Observation Team of the 46th Japanese Antarctic Research Expedition (JARE-46). The observation methods, instruments and statistical methods used by the JARE-46 were almost the same as those used by the JARE-45 observation team. Remarkable weather phenomena observed during the period of JARE-46 are as follows.1) Annual mean relative humidity and cloud amount in 2005 at Syowa Station were 73 and 7.5, both records for Syowa Station. Annual mean wind speed and number of snow days were 7.2m/s and 228 days, both second highest values.2) There were 30 blizzards of which 6 were class A, 9 class B and, 15 class C, typical of a normal year.3) The amount of total ozone over Syowa Station became lower than or equal to 220m atm-cm from the end of August to mid-October. Monthly mean amount of total ozone in September was 173m atm-cm, which was the 4th lowest value in the historical record. On 4th October, the amount of total ozone was 136m atm-cm, which was the lowest value during JARE-46

    Physical features of spondylolysis patients

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    The purpose of this study was to evaluate the physical features of pediatric patients with lumbar spondylolysis (LS), factors that increase the load during compensatory movements at the lumbar spine, and the outcomes of rehabilitation. Twenty patients were included. Fifteen items were used : fingertip-to-floor distance (FFD), straight leg raising (SLR), heel-to-buttock distance (HBD), tightness of the rectus femoris, the lateral and medial rotator muscles, iliopsoas, tensor fascia lata, adductor muscles, soleus muscle, and latissimus dorsi, and trunk rotation, sit-ups and endurance of the abdominal and back muscles. Initial findings were judged as positive or negative using previously reported cut-off values and were re-evaluated 2 or 3 months later. Positive tests were found for HBD and tightness of the rectus femoris in 85% of the patients, for endurance of the abdominal muscles in 75%, SLR and sit-ups in 70%, and FFD and tightness of the external rotator muscles in 60%. The physical features varied according to the type of sport played, and some patients were refractory to rehabilitation. Only 17.6%, 33.3%, and 40.0% of patients with initially positive findings for HBD, tightness of the external rotator muscles, and endurance of the abdominal muscles, respectively, achieved improvements after rehabilitation

    Essential role of Mannose-binding lectin-associated serine protease-1 in activation of the complement factor D

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    The complement system is an essential component of innate immunity, participating in the pathogenesis of inflammatory diseases and in host defense. In the lectin complement pathway, mannose-binding lectin (MBL) and ficolins act as recognition molecules, and MBL-associated serine protease (MASP) is a key enzyme; MASP-2 is responsible for the lectin pathway activation. The function of other serine proteases (MASP-1 and MASP-3) is still obscure. In this study, we generated a MASP-1– and MASP-3–deficient mouse model (Masp1/3−/−) and found that no activation of the alternative pathway was observed in Masp1/3−/− serum. Mass spectrometric analysis revealed that circulating complement factor D (Df) in Masp1/3−/− mice is a zymogen (pro-Df) with the activation peptide QPRGR at its N terminus. These results suggested that Masp1/3−/− mice failed to convert pro-Df to its active form, whereas it was generally accepted that the activation peptide of pro-Df is removed during its secretion and factor D constitutively exists in an active form in the circulation. Furthermore, recombinant MASP-1 converted pro-Df to the active form in vitro, although the activation mechanism of pro-Df by MASP-1 is still unclear. Thus, it is clear that MASP-1 is an essential protease of both the lectin and alternative complement pathways

    Development of a real-time quantitative PCR assay for detection of a stable genomic region of BK virus

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    <p>Abstract</p> <p>Background</p> <p>BK virus infections can have clinically significant consequences in immunocompromised individuals. Detection and monitoring of active BK virus infections in certain situations is recommended and therefore PCR assays for detection of BK virus have been developed. The performance of current BK PCR detection assays is limited by the existence of viral polymorphisms, unknown at the time of assay development, resulting in inconsistent detection of BK virus. The objective of this study was to identify a stable region of the BK viral genome for detection by PCR that would be minimally affected by polymorphisms as more sequence data for BK virus becomes available.</p> <p>Results</p> <p>Employing a combination of techniques, including amino acid and DNA sequence alignment and interspecies analysis, a conserved, stable PCR target region of the BK viral genomic region was identified within the VP2 gene. A real-time quantitative PCR assay was then developed that is specific for BK virus, has an analytical sensitivity of 15 copies/reaction (450 copies/ml) and is highly reproducible (CV ≤ 5.0%).</p> <p>Conclusion</p> <p>Identifying stable PCR target regions when limited DNA sequence data is available may be possible by combining multiple analysis techniques to elucidate potential functional constraints on genomic regions. Applying this approach to the development of a real-time quantitative PCR assay for BK virus resulted in an accurate method with potential clinical applications and advantages over existing BK assays.</p

    Overexpression of a Minimal Domain of Calpastatin Suppresses IL-6 Production and Th17 Development via Reduced NF-κB and Increased STAT5 Signals

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    Calpain, a calcium-dependent cysteine protease, is reportedly involved in the pathophysiology of autoimmune diseases such as rheumatoid arthritis (RA). In addition, autoantibodies against calpastatin, a natural and specific inhibitor of calpain, are widely observed in RA. We previously reported that E-64-d, a membrane-permeable cysteine protease inhibitor, is effective in treating experimental arthritis. However, the exact role of the calpastatin-calpain balance in primary inflammatory cells remains unclear. Here we investigated the effect of calpain-specific inhibition by overexpressing a minimal functional domain of calpastatin in primary helper T (Th) cells, primary fibroblasts from RA patients, and fibroblast cell lines. We found that the calpastatin-calpain balance varied during Th1, Th2, and Th17 development, and that overexpression of a minimal domain of calpastatin (by retroviral gene transduction) or the inhibition of calpain by E-64-d suppressed the production of IL-6 and IL-17 by Th cells and the production of IL-6 by fibroblasts. These suppressions were associated with reductions in RORγt expression and STAT3 phosphorylation. Furthermore, inhibiting calpain by silencing its small regulatory subunit (CPNS) suppressed Th17 development. We also confirmed that overexpressing a minimal domain of calpastatin suppressed IL-6 by reducing NF-κB signaling via the stabilization of IκBα, without affecting the upstream signal. Moreover, our findings indicated that calpastatin overexpression suppressed IL-17 production by Th cells by up-regulating the STAT5 signal. Finally, overexpression of a minimal domain of calpastatin suppressed IL-6 production efficiently in primary fibroblasts derived from the RA synovium. These findings suggest that inhibiting calpain by overexpressing a minimal domain of calpastatin could coordinately suppress proinflammatory activities, not only those of Th cells but also of synovial fibroblasts. Thus, this strategy may prove viable as a candidate treatment for inflammatory diseases such as RA

    Meteorological observations at Syowa Station in 2005 by the 46th Japanese Antarctic Research Expedition

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    This report describes the results of meteorological observations at Syowa Station from February 1st, 2005 to January 31st, 2006, carried out by the Meteorological Observation Team of the 46th Japanese Antarctic Research Expedition (JARE-46). The observation methods, instruments and statistical methods used by the JARE-46 were almost the same as those used by the JARE-45 observation team. Remarkable weather phenomena observed during the period of JARE-46 are as follows.1) Annual mean relative humidity and cloud amount in 2005 at Syowa Station were 73 and 7.5, both records for Syowa Station. Annual mean wind speed and number of snow days were 7.2m/s and 228 days, both second highest values.2) There were 30 blizzards of which 6 were class A, 9 class B and, 15 class C, typical of a normal year.3) The amount of total ozone over Syowa Station became lower than or equal to 220m atm-cm from the end of August to mid-October. Monthly mean amount of total ozone in September was 173m atm-cm, which was the 4th lowest value in the historical record. On 4th October, the amount of total ozone was 136m atm-cm, which was the lowest value during JARE-46

    Mouse Ficolin B Has an Ability to Form Complexes with Mannose-Binding Lectin-Associated Serine Proteases and Activate Complement through the Lectin Pathway

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    Ficolins are thought to be pathogen-associated-molecular-pattern-(PAMP-) recognition molecules that function to support innate immunity. Like mannose-binding lectins (MBLs), most mammalian ficolins form complexes with MBL-associated serine proteases (MASPs), leading to complement activation via the lectin pathway. However, the ability of murine ficolin B, a homologue of human M-ficolin, to perform this function is still controversial. The results of the present study show that ficolin B in mouse bone marrow is an oligomeric protein. Ficolin B, pulled down using GlcNAc-agarose, contained very low, but detectable, amounts of MASP-2 and small MBL-associated protein (sMAP) and showed detectable C4-deposition activity on immobilized N-acetylglucosamine. These biochemical features of ficolin B were confirmed using recombinant mouse ficolin B produced in CHO cells. Taken together, these results suggest that like other mammalian homologues, murine ficolin B has an ability to exert its function via the lectin pathway
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