全血流動下でのフォンビルブランド因子依存性血栓形成における組織因子の機能特性

Von Willebrand factor (VWF) plays an important role in mediating platelet adhesion and aggregation under high shear rate conditions. Such platelet aggregates are strengthened by fibrin-network formation triggered by tissue factor (TF). However, little is known about the role of TF in VWF-dependent thrombus formation under blood flow conditions. We evaluated TF in thrombus formation on immobilized VWF under whole blood flow conditions in an in vitro perfusion chamber system. Surface-immobilized TF amplified intra-thrombus fibrin generation significantly under both low and high shear flow conditions, while TF in sample blood showed no appreciable effects. Furthermore, immobilized TF enhanced VWF-dependent platelet adhesion and aggregation significantly under high shear rates. Neutrophil cathepsin G and elastase increased significantly intra-thrombus fibrin deposition on immobilized VWF–TF complex, suggesting the involvement of leukocyte inflammatory responses in VWF/TF-dependent mural thrombogenesis under these flow conditions. These results reveal a functional link between VWF and TF under whole blood flow conditions, in which surface-immobilized TF and VWF mutually contribute to mural thrombus formation, which is essential for normal hemostasis. By contrast, TF circulating in blood may be involved in systemic hypercoagulability, as seen in sepsis caused by severe microbial infection, in which neutrophil inflammatory responses may be active.博士（医学）・乙第1388号・平成28年11月24日© The Japanese Society of Hematology 2016The original publication is available at www.springerlink.comThe final publication is available at Springer via http://dx.doi.org/10.1007/s12185-016-2086-

Coagulation potential of immobilised factor VIII in flow-dependent fibrin generation on platelet surfaces.

Coagulation factor VIII (FVIII) plays an essential role in haemostasis. To date, physiologic activity of FVIII circulating in the bloodstream (S-FVIII) is evaluated by classic coagulation assays. However, the functional relevance of FVIII (-von Willebrand factor complex) immobilised on thrombogenic surfaces (I-FVIII) remains unclear. We used an in vitro perfusion chamber system to evaluate the function of I-FVIII in the process of mural thrombus formation under whole blood flow conditions. In perfusion of either control or synthetic haemophilic blood, the intra-thrombus fibrin generation on platelet surfaces significantly increased as a function of I-FVIII, independent of S-FVIII, under high shear rate conditions. This I-FVIII effect was unvarying regardless of anti-FVIII inhibitor levels in synthetic haemophilic blood. Thus, our results illustrate coagulation potentials of immobilised clotting factors, distinct from those in the bloodstream, under physiologic flow conditions and may give a clue for novel therapeutic approaches for haemophilic patients with anti-FVIII inhibitors.博士（医学）・甲第602号・平成25年7月22日The definitive version is available at " http://dx.doi.org/10.1160/TH13-02-0159

Systematic review and meta-analysis: the relationship between the Helicobacter pylori dupA gene and clinical outcomes

<p>Abstract</p> <p>Background</p> <p>In 2005, the first disease-specific <it>Helicobacter pylori </it>virulence factor that induced duodenal ulcer and had a suppressive action on gastric cancer has been identified, and was named duodenal ulcer promoting gene (<it>dupA</it>). However, the importance of the <it>dupA </it>gene on clinical outcomes is conflicting in subsequent studies. The aim of this study was to estimate the magnitude of the risk for clinical outcomes associated with <it>dupA </it>gene.</p> <p>Methods</p> <p>A meta-analysis of case-control studies which provided raw data on the infection rates with the <it>dupA</it>-positive <it>H. pylori </it>detected by polymerase chain reaction was performed.</p> <p>Results</p> <p>Seventeen studies with a total of 2,466 patients were identified in the search. Infection with the <it>dupA</it>-positive <it>H. pylori </it>increased the risk for duodenal ulcer by 1.41-fold (95% confidence interval [CI], 1.12-1.76) overall. Subgroup analysis showed that the summary odds ratio (OR) was 1.57 (95% CI, 1.19-2.06) in Asian countries and 1.09 (95% CI, 0.73-1.62) in Western countries. There was no association between the presence of the <it>dupA </it>gene and gastric cancer and gastric ulcer. Publication bias did not exist.</p> <p>Conclusion</p> <p>Our meta-analysis confirmed the importance of the presence of the <it>dupA </it>gene for duodenal ulcer, especially in Asian countries.</p

Metabolic imaging using SPECT

金沢大学医学部附属病院核医学診療科Introduction: In normal condition, the heart obtains more than two-thirds of its energy from the oxidative metabolism of long chain fatty acids, although a wide variety of substrates such as glucose, lactate, ketone bodies and amino acids are also utilised. In ischaemic myocardium, on the other hand, oxidative metabolism of free fatty acid is suppressed and anaerobic glucose metabolism plays a major role in residual oxidative metabolism. Therefore, metabolic imaging can be an important technique for the assessment of various cardiac diseases and conditions. Materials and methods: In SPECT, several iodinated fatty acid traces have been introduced and studied. Of these, 123I-labelled 15-(p-iodophenyl)3-R, S-methylpentadecanoic acid (BMIPP) has been the most commonly used tracer in clinical studies, especially in some of the European countries and Japan. Results and discussion: In this review article, several fatty acid tracers for SPECT are characterised, and the mechanism of uptake and clinical utility of BMIPP are discussed in detail. © 2007 Springer-Verlag

看護系大学卒業の看護師の看護実践能力を測定する「看護実践能力自己評価尺度（CNCSS）」の妥当性の検討

目的：看護系大学卒業の看護師の看護実践能力を測定する「看護実践能力自己評価尺度（CNCSS）」の妥当性を検討した．方法：看護系大学を卒業した臨床経験１年目から５年目の看護師に，自記式質問票を配布し郵送にて回収した．CNCSS はコンピテンス13項目から構成されている．看護実践能力に関連する因子である経験年数，専門的成長の機会，職務満足，相談しやすい環境の各因子の違いから各コンピテンスの得点に差があることで妥当であるとした．有意水準は５％とした．結果：質問票5,021部配布し1,498部（回収率33.1％）の回答を得た．看護実践能力に関連する因子において，CNCSSのコンピテンス項目の得点に有意な差が認められた．経験年数と職務満足はすべてのコンピテンスでｐ＜0.001，および相談しやすい環境は全コンピテンス項目でｐ＜0.01であった．結論：本研究でCNCSSのすべてのコンピテンスの得点が看護実践能力を反映していた．CNCSSは，看護実践能力を測定するための有効な尺度であると考える．Purpose: The Clinical Nursing Competence Self-Assessment Scale (CNCSS) was developed for the purpose of evaluating the educational efforts that nursing universities have undertaken since 2005 to enhance the development of practical nursing skills (E.g. in2012). We examined the validity of CNCSS, which consists of 13 competence items and measures the nursing practice ability of nursing graduates. Method: A total of 5,021 copies CNCSS were distributed nurses with one to five years of clinical experience after graduation from nursing college, working in hospital facilities nationwide. The validity was determined whether the scores of the 13 competence items varied with factors related to nursing practice ability. The factors included years of experience, professional growth opportunities, job satisfaction, intention to continue working, and a good workplace relationships. One-way analysis of variance was used for score comparison. A p value <0.05 was considered a statistically significant difference. Result: We received 1,498 replies (response rate 33.1%). The scores of 13 competence items of the CNCSS significantly varied with factors related to nursing practice ability. In particular, the years of experience and the job satisfaction were p <0.001 for all competency items, and easy-to-consult environment was p <0.01for all competency items. Conclusion: In the present study, the scores of all competence items of the CNCSS reflected the nursing practice ability. We believe that the CNCSS is a valid tool to measure nursing practice ability

放射性ヨード標識metaiodobenzylguanidineによる心筋交感神経イメージングに関する研究

取得学位 : 博士（医学）, 学位授与番号 : 医博甲第1000号, 学位授与年月日：平成3年3月25日,学位授与年：199

Comparison of (18)F SPECT with PET in myocardial imaging: A realistic thorax-cardiac phantom study

BACKGROUND: Positron emission tomography (PET) imaging with fluorine-18 ((18)F) Fluorodeoxyglucose (FDG) and flow tracer such as Rubidium-82 ((82)Rb) is an established method for evaluating an ischemic but viable myocardium. However, the high cost of PET imaging restricts its wider clinical use. Therefore, less expensive (18)F FDG single photon emission computed tomography (SPECT) imaging has been considered as an alternative to (18)F FDG PET imaging. The purpose of the work is to compare SPECT with PET in myocardial perfusion/viability imaging. METHODS: A nonuniform RH-2 thorax-heart phantom was used in the SPECT and PET acquisitions. Three inserts, 3 cm, 2 cm and 1 cm in diameter, were placed in the left ventricular (LV) wall to simulate infarcts. The phantom acquisition was performed sequentially with 7.4 MBq of (18)F and 22.2 MBq of Technetium-99m ((99m)Tc) in the SPECT study and with 7.4 MBq of (18)F and 370 MBq of (82)Rb in the PET study. SPECT and PET data were processed using standard reconstruction software provided by vendors. Circumferential profiles of the short-axis slices, the contrast and viability of the inserts were used to evaluate the SPECT and PET images. RESULTS: The contrast for 3 cm, 2 cm and 1 cm inserts were for (18)F PET data, 1.0 ± 0.01, 0.67 ± 0.02 and 0.25 ± 0.01, respectively. For (82)Rb PET data, the corresponding contrast values were 0.61 ± 0.02, 0.37 ± 0.02 and 0.19 ± 0.01, respectively. For (18)F SPECT the contrast values were, 0.31 ± 0.03 and 0.20 ± 0.05 for 3 cm and 2 cm inserts, respectively. For (99m)Tc SPECT the contrast values were, 0.63 ± 0.04 and 0.24 ± 0.05 for 3 cm and 2 cm inserts respectively. In SPECT, the 1 cm insert was not detectable. In the SPECT study, all three inserts were falsely diagnosed as "viable", while in the PET study, only the 1 cm insert was diagnosed falsely "viable". CONCLUSION: For smaller defects the (99m)Tc/(18)F SPECT imaging cannot entirely replace the more expensive (82)Rb/(18)F PET for myocardial perfusion/viability imaging, due to poorer image spatial resolution and poorer defect contrast