記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objectives: We explore the prevalence and characteristics of burnout among Japanese resident physicians and identifies factors associated with burnout. Methods: A cross-sectional study was conducted three times between April 2017 and March 2018 at a Japanese teaching hospital. Resident physicians were invited to answer an online survey that included existing valid instruments related to burnout, depression, and empathy. Demographic, background, occupational, and socioeconomic data were also collected. Participants were prompted to report the average daily work hours and the specialty they wish to pursue. Results: Overall, 39/76 (51%), 27/76 (36%), and 21/76 (28%) resident physicians responded to surveys in April 2017, October 2017, and March 2018, respectively. The percentages of participants with burnout for surveys in April 2017, October 2017, and March 2018 were 7/39 (18%), 6/27 (22%), and 7/21 (33.3%). Emotional exhaustion (EE) was the only burnout component strongly correlated with the severity of depression (r = .615, p < .001; r = .706, p < .001; r = .601, p < .01). EE and depersonalization (DP) had no significant correlation with average daily working hours (β = .156, p = .343 for EE; β = .061, p = .711 for DP). Conclusions: The results suggest that capping working hours alone may not be effective in reducing burnout in Japanese resident physicians. Medical educators might need to consider not only working hours but also individual job quality and satisfaction to address burnout. Future studies may need to incorporate qualitative methods to explore the characteristics of burnout.

DOI： 10.5116/ijme.5caf.53ad

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2169/internalmedicine.1589-18

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Empathy is an important component of overall clinical competence; thus, enhancing empathy in medical education is essential for quality patient care. AIM: This longitudinal study was designed to address the following questions: 1. Can a targeted educational program in communication skills training enhance empathy in medical students? and 2. Can such a program have a sustained effect? METHODS: Study participants included 116 students who entered Okayama University Medical School in 2011. Students participated in a communication skills training program aimed to enhance their empathy, and completed the Jefferson Scale of Empathy (JSE) five times: at the beginning of medical school, prior to participation in the program, immediately after the program, and in last years of medical school. A total of 69 students, representing 59% of the cohort, completed the JSE in all five test administrations. RESULTS: Students' total scores on the JSE and its two factors (Perspective Taking and Compassionate Care) increased significantly (p < 0.001) after participation in the communication skills training program. However, the program did not have a sustained effect. CONCLUSIONS: Targeted educational programs to enhance empathy in medical students can have a significant effect; however, additional reinforcements may be needed for a sustained effect.

DOI： 10.1080/0142159X.2018.1460657

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

To clarify potential relationships between chief complaints of patients and laboratory data with a focus on aging-related changes, we retrospectively analyzed the data of 843 patients who visited a general medicine department for the first time. Their chief complaints were classified into 8 major symptoms: visceral pain, somatic pain, fever, cough, dizziness, fatigue, appetite loss, and edema. We compared the laboratory data obtained from the patients with complaints with the data of symptom-free (control) patients. The serum sodium and potassium levels in the fever group were decreased compared to those in the control group. In the fever group, the serum sodium level was inversely correlated with age. The ratio of serum urea nitrogen to creatinine (UN/Cr) was increased in the appetite-loss group. There were significant age-dependent increases in the UN/Cr ratio in the appetite-loss and edema groups. Of note, serum levels of free thyroxin were lower in the dizziness group compared to the control group. In addition, the free thyroxin level was inversely correlated with age in the dizziness group but not in the asymptomatic control group. Collectively, the results indicated that osmolality-related laboratory data are strongly associated with individual primary symptoms at the first visit regardless of the final diagnosis. The consideration of age-dependent changes of these markers is helpful for diagnosing latent disorders based on various primary symptoms.

DOI： 10.18926/AMO/56372

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Atherosclerosis is a chronic inflammatory disease characterized by formation of lipid-rich plaques on the inner walls of arteries. ADAMTS4 (a disintegrin-like and metalloproteinase with thrombospondin motifs-4) is a secreted proteinase that regulates versican turnover in the arterial wall and atherosclerotic plaques. Recent reports indicated elevated ADAMTS4 level in human atherosclerotic plaques and in the plasma of acute coronary syndrome patients. Nevertheless, whether increased ADAMTS4 is a consequence of atherosclerosis or ADAMTS4 has a causal role in atherogenesis remains unknown. In this work, we investigated the role of ADAMTS4 in diet induced atherosclerosis using apolipoprotein E deficient (ApoE(-/-)) and Adamts4 knockout mice. We show that ADAMTS4 expression increases in plaques as atherosclerosis progresses in ApoE(-/-) mice. ApoE(-/-)Adamts4(-/-) double knockout mice presented a significant reduction in plaque burden at 18 weeks of age. Loss of ADAMTS4 lead to a more stable plaque phenotype with a significantly reduced plaque vulnerability index characterized by reduced lipid content and macrophages accompanied with a significant increase in smooth muscle cells, collagen deposition and fibrotic cap thickness. The reduced atherosclerosis is accompanied by an altered plasma inflammatory cytokine profile. These results demonstrate for the first time that ADAMTS4 contributes to diet induced atherosclerosis in ApoE(-/-) mice.

DOI： 10.1038/srep31130

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

A 68-year-old man with persistent bacteremia accompanying a large iliopsoas abscess, vertebral osteomyelitis, discitis and central venous port infection caused by methicillin-resistant Staphylococcus aureus (MRSA) was admitted to our hospital. During the course of treatment, the emergence of a daptomycin (DAP)-resistant MRSA strain was confirmed; the minimum inhibitory concentration was 1 to 2 μg/mL for vancomycin and more than 1 μg/mL for DAP. Although the bacterial cell wall was not significantly thickened, an increased positive surface charge and single-nucleotide polymorphism within mprF have been confirmed in DAP-resistant strains. Still rare, but clinicians need to be cautious of the emergence of DAP-resistant MRSA during treatment.

DOI： 10.2169/internalmedicine.55.4763

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We report a case of nephrostomy-associated urinary tract infection caused by Elizabethkingia meningoseptica that occurred in a patient with retroperitoneal fibrosis. Though conventional identification methods failed to detect the causative organism, it was identified on the basis of the complete sequencing of 16S rRNA. Four weeks of levofloxacin and minocycline administration successfully eradicated the infection. E. meningoseptica rarely causes urinary tract infections, and we believe that this is the first such case in which the isolate was genetically confirmed. The accurate identification of the organism is necessary for the provision of appropriate treatment and to obtain a better understanding of its epidemiology and pathogenicity.

DOI： 10.2169/internalmedicine.54.4998

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We herein report a case of Klebsiella oxytoca-producing IMP-1 that was detected as a first isolate of carbapenem-resistant Enterobacteriaceae (CRE) at our facility. Since K. oxytoca is an uncommon strain for CRE, we speculated that the resistant organism had already spread out inside the hospital. Metallo-β-lactamases promotes antibiotic resistance in Enterobacteriaceae, which potentially yields problematic issues in clinical settings. Active surveillance of antibiotic resistant strains is important and should be repeatedly highlighted. Furthermore, appropriate methods should be established to detect highly resistant strains.

DOI： 10.2169/internalmedicine.54.4965

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We herein present a rare case of Actinomyces turicensis bacteremia that was caused by pyometra. The patient was successfully treated with transvaginal drainage and antibiotic therapy. A literature review in MEDLINE showed that there have been only 8 previously reported cases of A. turicensis bacteremia. This infection frequently occurs in patients with visceral abscesses, and blood culture examinations usually reveal a polymicrobial pattern. However, the prognosis of such patients has been reported to generally be benign. Due to difficulties in performing bacterial identification and the wide-spectrum clinical pictures associated with this bacteremia, no comprehensive understanding of the clinical features of each Actinomyces species has yet been established.

DOI： 10.2169/internalmedicine.54.4637

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

A 67-year-old man with a persistent high fever was diagnosed to have an infective aneurysm in his left internal iliac artery. A blood culture detected a gram-negative spiral rod that was first identified as Campylobacter fetus subsp. venerealis based on a matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) analysis. However, the strain was finally confirmed to be Campylobacter fetus subsp. fetus based on a genetic analysis. The infection was successfully treated with emergency resection of the aneurysm, followed by 4 weeks of antibiotic therapy. Involvement of the peripheral artery is uncommon in cases of C. fetus-infective aneurysm. To figure out the epidemiology and pathogenicity of C. fetus infection, the accurate identification of the responsible organisms is essential.

DOI： 10.2169/internalmedicine.54.4845

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2169/internalmedicine.54.4262

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

A 53-year-old man with a past medical history of total arch replacement surgery and severe aortic regurgitation presented with a 1-month history of persistent general malaise, anorexia, body weight loss and night sweats. His recent history included gingival hyperplasia for 6 years, gingivitis after tooth extraction 3 years before, prolonged inflammatory status for 4 months, fundal hemorrhage and leg tenderness for 2 months. A pathogen was detected from blood culture, but conventional microbiological examination failed to identify the pathogen. The organism was eventually identified as Cardiobacterium valvarum by 16S rRNA analysis, and the patient was diagnosed with infective endocarditis and prosthetic vascular graft infection. The patient received intravenous antibiotic therapy using a combination of ceftriaxone and levofloxacin for 5 weeks and was discharged with a good clinical course. C. valvarum is a rare human pathogen in clinical settings. Only 10 cases have been reported to date worldwide, and therefore, the clinical characteristics of C. valvarum infection are not fully known. This is a first well-described case of C. valvarum infection in Japan, and further, a first report of aortic prosthetic vascular graft infection worldwide. Identification of C. valvarum is usually difficult due to its phenotypic characteristics, and molecular approaches would be required for both clinicians and microbiologists to facilitate more reliable diagnosis and uncover its clinical picture more clearly.

DOI： 10.1016/j.jiac.2014.07.008

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Angiogenesis and lymphangiogenesis play roles in malignant tumor progression, dissemination, and metastasis. ADAMTS1, a member of the matrix metalloproteinase family, is known to inhibit angiogenesis. Recombinant ADAMTS1 was shown to strongly inhibit angiogenesis. We investigated whether ADAMTS1 inhibited lymphangiogenesis in the present study. We examined cell proliferation and cell migration in normal human dermal lymphatic microvascular endothelial cells (HMVEC-dLy) transduced with or without adenoviral human ADAMTS1 gene therapy. We then examined the VEGFC/VEGFR3 signal transduction pathway in ADAMTS1-transduced HMVEC-dLy. Cell proliferation and tube formation in Matrigel were significantly lower with transduced ADAMTS1 than with control (non-transduced HMVEC-dLy). The phosphorylation of VEGFR3 was also attenuated by ADAMTS1 gene therapy in HMVEC-dLy. Immunoprecipitation assays revealed that ADAMTS1 formed a complex with VEGFC. Our results demonstrated that ADAMTS1 inhibited lymphangiogenesis in vitro. The data highlight the new function of ADAMTS1 in the regulation of lymphangiogenesis and the therapeutic potential of ADAMTS1 in cancer therapy.

DOI： 10.1016/j.yexcr.2014.03.002

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We describe a rare case of recurrent Stenotrophomonas maltophilia bacteremia in a previously healthy 45-year-old man. The infection was caused by osteomyelitis at the site of an iliac crest bone graft harvest. A genetic analysis using enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR) revealed that the blood isolates and pathogens obtained from the surgical wound were identical. Initial treatment with levofloxacin and cefozopran was ineffective, but the patient's infection was successfully treated by long-term administration of latamoxef and trimethoprim-sulfamethoxazole. The present case suggests that attention should be given to the possibility of S. maltophilia infection in any situations.

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記述言語：英語   出版者・発行元：OXFORD UNIV PRESS INC  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Angiogenesis plays an important role in tumor progression. Several reports have demonstrated that a disintegrin and metalloproteinase with thrombospondin motifs1 (ADAMTS1) inhibited angiogenesis via multiple mechanisms. The aim of this study was to investigate the effect of ADAMTS1 on endothelial cells in vitro and on tumor growth with regard to angiogenesis in vivo. We examined the effects of the transfection of ADAMTS1 using two constructs, full-length ADAMTS1 (full ADAMTS1) and catalytic domain-deleted ADAMTS1 (delta ADAMTS1). Transfection of both the full ADAMTS1 and delta ADAMTS1 gene constructs demonstrated the secretion of tagged-ADAMTS1 protein into the conditioned medium, so we examined the effects of ADAMTS1-containing conditioned medium on endothelial cells. Both types of conditioned media inhibited endothelial tube formation, and this effect was completely abolished after immunoprecipitation of the secreted protein from the medium. Both types of conditioned media also inhibited endothelial cell migration and proliferation. We then examined the impact of ADAMTS1 on endothelial cell apoptosis. Both conditioned media increased the number of Annexin V-positive endothelial cells and caspase-3 activity and this effect was attenuated when z-vad was added. These results indicated that ADAMTS1 induced endothelial cell apoptosis. We next examined the effects of ADAMTS1 gene transfer into tumor-bearing mice. Both full ADAMTS1 and delta ADAMTS1 significantly inhibited the subcutaneous tumor growth. Collectively, our results demonstrated that ADAMTS1 gene transfer inhibited angiogenesis in vitro and in vivo, likely as a result of the induction of endothelial cell apoptosis by ADAMTS1 that occurs independent of the protease activity.

DOI： 10.1111/j.1349-7006.2012.02381.x

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記述言語：英語   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Adipocyte fatty acid binding protein (A-FABP) has been reported to be involved in insulin resistance, lipid metabolism, and atherosclerosis; however, little is known about the effect of medication on the change in circulating A-FABP in human subjects. We evaluated the effects of angiotensin II type 1 receptor blocker (ARB) on arterial stiffness and its association with serum A-FABP in patients with hypertension. Thirty patients newly diagnosed with essential hypertension were treated with olmesartan (20 mg/day), an ARB, for 6 months. Serum levels of A-FABP and high-sensitivity C-reactive protein (hsCRP) were examined and the cardio-ankle vascular index (CAVI), which is a marker of arterial stiffness, was also determined. Serum A-FABP at baseline was significantly correlated with the body mass index (r = 0.45, P = 0.01), homeostasis model assessment as a marker of insulin resistance (r = 0.53, P < 0.01), and systolic blood pressure (r = 0.37, P = 0.047), and tended to be correlated with low-density lipoprotein cholesterol, triglyceride, and CAVI. Olmesartan treatment resulted in a significant decrease in CAVI, serum A-FABP levels, and hsCRP, besides a significant reduction of blood pressure. Multiple regression analysis revealed that the change in CAVI was independently correlated with the change in serum A-FABP. Olmesartan ameliorated arterial stiffness in patients with hypertension, which may be involved in the reduction of serum A-FABP.

DOI： 10.1007/s00380-010-0060-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

ADAMTS1 (a disintegrin and metalloproteinase with thrombospondin motifs 1) is an early immediate gene. We have previously reported that ADAMTS1 was strongly induced by hypoxia. In this study, we investigated whether ADAMTS1 promoter-driven reporter signal is detectable by acute hypoxia. We constructed the GFP (green fluorescent protein) expression vector [AHR (acute hypoxia-response sequence)-GFP] under the control of ADAMTS1 promoter and compared it with the constitutive GFP-expressing vector under the control of CMV (cytomegalovirus promoter-GFP). We transduced AHR-GFP and examined whether GFP signals can be detected under the acute hypoxia. When the human umbilical vein [HUVEC (human umbilical vein endothelial cells)] was transduced under normoxia, there were few GFP signals, while CMV-GFP showed considerable GFP signals. When HUVEC was stimulated with hypoxia, GFP signals from AHR-GFP gene were induced under hypoxic conditions. Notably, the GFP signals peaked at 3 h under hypoxia. In ischaemic hind limb model, transduced AHR-GFP showed hypoxic induction of GFP signals. In summary, we have demonstrated that the AHR system induced the reporter gene expression by acute hypoxia, and its induction is transient. This is the first report showing the unique acute hypoxia-activated gene expression system.

DOI： 10.1042/CBI20100290

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Even high-normal albuminuria is reportedly associated with cardiovascular events. OBJECTIVE: We determined the urine albumin creatinine ratio (UACR) in spot urine samples and analyzed the UACR distribution and the prevalence of high-normal levels. PATIENTS AND METHODS: The UACR was determined using immunoturbidimetry in 332 untreated asymptomatic non-diabetic Japanese patients with hypertension and in 69 control subjects. The microalbuminuria and macroalbuminuria levels were defined as a UCAR ≥30 and <300 µg/mg·creatinine and a UCAR ≥300 µg/mg·creatinine, respectively. RESULTS: The distribution patterns showed a highly skewed distribution for the lower levels, and a common logarithmic transformation produced a close fit to a Gaussian distribution with median, 25th and 75th percentile values of 22.6, 13.5 and 48.2 µg/mg·creatinine, respectively. When a high-normal UACR was set at >20 to <30 µg/mg·creatinine, 19.9% (66/332) of the hypertensive patients exhibited a high-normal UACR. Microalbuminuria and macroalbuminuria were observed in 36.1% (120/336) and 2.1% (7/332) of the patients, respectively. UACR was significantly correlated with the systolic and diastolic blood pressures and the pulse pressure. A stepwise multivariate analysis revealed that these pressures as well as age were independent factors that increased UACR. CONCLUSION: The UACR distribution exhibited a highly skewed pattern, with approximately 60% of untreated, non-diabetic hypertensive patients exhibiting a high-normal or larger UACR. Both hypertension and age are independent risk factors that increase the UACR. The present study indicated that a considerable percentage of patients require anti-hypertensive drugs with antiproteinuric effects at the start of treatment.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Connective tissue growth factor (CTGF) is a secreted protein that regulates fibrosis. We hypothesized that CTGF is induced in a pressure-overloaded (PO) heart and that blocking the angiotensin II type 1 receptor would reduce CTGF expression. Accordingly, we administered olmesartan and compared its effects with other antihypertensive drugs in a PO heart. CTGF induction was determined in a rat PO model, and olmesartan, hydralazine or saline was continuously administered. The effects of olmesartan on CTGF induction, myocyte hypertrophy and fibrosis were evaluated. The effect of olmesartan on cardiac function was also examined in CTGF- and transforming growth factor-beta 1 (TGF-β1)-infused rats. CTGF was increased in the PO heart 3 days after aortic banding and was markedly distributed around the perivascular fibrotic area. After 28 days, blood pressure was not significantly different in the olmesartan and hydralazine groups, but olmesartan treatment reduced CTGF distribution in PO hearts. Olmesartan was associated with a significantly reduced myocyte hypertrophy index (4.77±0.48 for olmesartan and 6.05±1.45 for saline, P<0.01), fibrosis area (32.0±15.5% compared with the saline group, P<0.05) and serum TGF-β1 level (62.6±10.6 ng ml⁻¹ for olmesartan and 84.4±7.2 ng ml⁻¹ for hydralazine, P<0.05). In addition, cardiac function was significantly preserved in the olmesartan group compared with the saline group. Finally, olmesartan ameliorated the cardiac dysfunction in CTGF- and TGF-β1-infused rats. Olmesartan attenuated CTGF induction, reduced perivascular fibrosis and ameliorated cardiac dysfunction in a PO heart. Our results provide insight into the beneficial effects of olmesartan on PO hearts, independent of blood-pressure lowering.

DOI： 10.1038/hr.2010.189

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: Based on well-established physiological theories, we studied correlations between changes in brachial-ankle pulse wave velocity (baPWV) relative to blood pressure (BP) elevation (elasticity of large-to-medium-sized arteries), and coronary artery disease (CAD). METHODS: The baPWV (in centimeters/second) and BP (in millimeters of mercury) were determined in 101 patients before, during, and/or after a cold pressor test using a volume-plethysmographic system. RESULTS: Significantly higher rates of increase in PWV relative to changes in BP were observed in the CAD(+) group than in the CAD(-) group when mean BP [median (25th-75th percentiles): 14.8 (8.3-24.9) vs. 8.6 (5.7-11.4) cm/s/mmHg, P<0.0001], and systolic [10.1 (6.0-17.5) vs. 6.4 (4.4-10.6) cm/s/mmHg, P=0.0023] and diastolic BP [21.0 (14.0-34.4) vs. 10.8 (6.8-16.1) cm/s/mmHg, P<0.0001] were used as BP indices. Similarly, the rates of increase in baPWV showed a significant correlation with the extent of CAD. The rate of increase in baPWV obtained using the mean, systolic and diastolic BP as indices showed an area under the receiver operating characteristic curve of 0.68-0.76, sensitivity of 65-75%, and specificity of 65-75% for the detection of CAD. The area under the receiver operating characteristic curve, sensitivity, and specificity for the rate of increase were slightly higher than those for baseline baPWV and baseline baPWV/baseline BP ratio, but not to a significant degree. CONCLUSION: The rate of increase in baPWV relative to BP elevation determined by cold pressor test is significantly and moderately correlated with CAD. To identify patients with CAD, the rate of increase in baPWV relative to changes in BP can provide considerable, but limited, information.

DOI： 10.1097/MCA.0b013e32833e1c19

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: The optimal combination treatment for hypertension has not been established. We investigated the effect of a calcium channel blocker or a diuretic added to angiotensin II receptor blockers (ARBs) on the augmentation index (AI), as a marker of arterial stiffness and wave reflection, in hypertensive patients. METHODS: Thirty-seven patients treated with ARBs were randomly allocated to either of the 2 groups receiving an ARB plus azelnidipine (AZ group) or trichlormethiazide (TCM group). Changes in brachial blood pressure (BP), AI, high-sensitive C-reactive protein (hsCRP), and serum asymmetric dimethylarginine, as an endogenous nitric oxide synthase inhibitor, were determined. RESULTS: Systolic and diastolic blood pressure after 6 months were significantly reduced in both the groups similarly; however, after adjustment for baseline covariates, the extent of the reduction in AI (%) in the AZ group was significantly greater than in the TCM group (between-group difference was 3.2; 95%CI: 0.2-6.3; P = 0.03). The reduction of high-sensitive C-reactive protein (mg/L) and serum asymmetric dimethylarginine (micromol/L) was significantly greater in the AZ group than in the TCM group (between-group difference was 0.18 and 0.05; 95%CI: -0.01 to 0.36 and -0.01 to 0.11; P = 0.04 and 0.02, respectively). Further, when patients were analyzed according to age younger than 60 years or older than 60 years, the reduction in AI in the AZ group aged older than 60 years was significantly greater than in the TCM group. CONCLUSION: The results suggest that azelnidipine has a more beneficial effect on vascular properties in combination therapy with ARB than trichlormethiazide.

DOI： 10.1097/MAJ.0b013e3181d658c4

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: The purpose of this study was to investigate the profile of histone deacetylase (HDAC) expression in the synovial tissue of rheumatoid arthritis (RA) compared with that of normal control and osteoarthritis (OA), and to examine whether there is a link between HDAC activity and synovial inflammation. METHODS: HDAC activity and histone acetyltransferase (HAT) activity were determined in nuclear extracts of total synovial tissue surgically obtained from normal, OA and RA joints. The level of cytoplasmic tumor necrosis factor a (TNFα) fraction was measured by ELISA. Total RNA of synovial tissue was used for RT-PCR of HDAC1-8. In synovial fibroblasts from RA (RASFs), the effects of TNFα on nuclear HDAC activity and class I HDACs (1, 2, 3, 8) mRNA expressions were examined by quantitative real-time PCR. The protein expression and distribution of class I HDACs were examined by Western blotting. RESULTS: Nuclear HDAC activity was significantly higher in RA than in OA and normal controls and correlated with the amount of cytoplasmic TNFα. The mRNA expression of HDAC1 in RA synovial tissue was higher than in OA and normal controls, and showed positive correlation with TNFα mRNA expression. The protein level of nuclear HDAC1 was higher in RA synovial tissue compared with OA synovial tissue. Stimulation with TNFα significantly increased the nuclear HDAC activity and HDAC1 mRNA expression at 24 hours and HDAC1 protein expression at 48 hours in RASFs. CONCLUSIONS: Our results showed nuclear HDAC activity and expression of HDAC1 were significantly higher in RA than in OA synovial tissues, and they were upregulated by TNFα stimulation in RASFs. These data might provide important clues for the development of specific small molecule HDAC inhibitors.

DOI： 10.1186/ar3071

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: High-normal urinary albumin excretion has been reported to have clinical significance with respect to progression of proteinuria and hypertension. OBJECTIVE: We analysed the effect of cilnidipine (10 mg/day) on morning systolic blood pressure (SBP) and urine albumin-creatinine ratio (UACR) in 16 non-diabetic hypertensive patients with a normal to marginally elevated UACR (mean +/- SD 29.4 +/- 21.7; range 7.5-72.9 mg/g creatinine). METHODS: Sequential home BP and UACR data were fitted to a simple exponential function as follows: where y is SBP (mmHg) or UACR (mg/g creatinine); alpha is the extent of the SBP (mmHg)- or UACR (mg/g creatinine)-lowering effect; beta (days) is the time-constant for SBP or UACR decrease; t is the number of days after the start of cilnidipine administration; and gamma is the finally stabilized SBP (mmHg) or UACR (mg/g creatinine). RESULTS: Mean +/- SD morning SBP and UACR decreased by 20.4 +/- 11.4 mmHg and 15.2 +/- 13.1 mg/g creatinine, respectively, as determined by coefficient alpha. The mean +/- SD time-constant for UACR decrease was significantly longer than that for BP decrease (43.5 +/- 22.9 vs 15.4 +/- 7.1 days). UACR reduction correlated with pre-treatment UACR values (correlation coefficient [R] = 0.88, p < 0.01) but not with BP decrease. CONCLUSIONS: The present study demonstrated that cilnidipine reduced UACR in hypertensive patients with normal to marginally elevated UACR independent of its BP-lowering effect.

DOI： 10.2165/11538510-000000000-00000

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記述言語：英語   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SAGE PUBLICATIONS LTD  

Helicobacter pylori (H. pylori) is a predominant pathogen that causes not only gastroduodenal diseases but also extra-alimentary tract diseases. In this study, we demonstrated that H. pylori infection promoted atherogenesis in heterozygous apoe(+/-) ldlr(+/-) mice. The male mice were fed with high fat diet from the age of 6 weeks. At the age of 16 weeks, development of atherosclerotic lesions was observed in the H. pylori-infected mice, and it seemed to be associated with an elevation of Th1-immune response against H. pylori origin-heat shock protein 60 (Hp-HSP60) and an increment of transendothelial migration of T cells. Subcutaneous immunisation with Hp-HSP60 or H. pylori eradication with antibiotics significantly reduced the progression of atherosclerosis, accompanied by a decline of Th1 differentiation and reduction of their chemotaxis beyond the endothelium. Thus, oral infection with H. pylori accelerates atherosclerosis in mice and the active immunisation with Hp-HSP60 or the eradication of H. pylori with antibiotics can moderate/prevent cellular immunity, resulting in a reduction of atherosclerosis. Lupus (2009) 18, 1154-1168.

DOI： 10.1177/0961203309106600

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

ADAMTS1 (a disintegrin and metalloproteinase with thrombospondin motifs 1) is a member of the matrix metalloproteinase family. We have previously reported that ADAMTS1 was strongly expressed in myocardial infarction. In this study, we investigated whether hypoxia induced ADAMTS1 and investigated its regulatory mechanism. In hypoxia, the expression level of ADAMTS1 mRNA and protein rapidly increased in endothelial cells, but not in other cell types. Interestingly, the induction of ADAMTS1 by hypoxia was transient, whereas vascular endothelial growth factor induction by hypoxia in human umbilical vein endothelial cells (HUVEC) increased in a time-dependent manner. CoCl2, a transition metal that mimics hypoxia, induced ADAMTS1 in HUVEC. The phosphatidylinositol 3-kinase inhibitor LY294002 dose-dependently inhibited the increase of ADAMTS1 mRNA expression in hypoxia. We characterized the promoter region of ADAMTS1, and the secreted luciferase assay system demonstrated that hypoxia induced luciferase secretion in the culture medium 4.6-fold in HUVEC. In the promoter region of ADAMTS1, we found at least three putative hypoxia-inducible factor (HIF) binding sites, and the chromatin immunoprecipitation assay revealed HIF-1 binding to HIF binding sites in the promoter region of ADAMTS1 under hypoxia. Recombinant ADAMTS1 protein promoted the migration of HUVEC under hypoxic conditions. In summary, we found that ADAMTS1 is transiently induced by hypoxia in endothelial cells, and its transcription is mediated by HIF-1 binding. Our data indicate that ADAMTS1 is a novel acute hypoxia-inducible gene.

DOI： 10.1074/jbc.M109.001313

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Activin A, a member of the transforming growth factor-beta cytokine family, has been suggested to have a role in inflammation. We examined the serum level of activin A in patients with acute myocardial infarction (AMI) undergoing successful primary percutaneous coronary intervention (PCI). METHODS: The subjects were 30 AMI patients, 20 stable angina pectoris (AP) patients and 20 normal subjects. The serum levels of activin A in AMI patients were measured before PCI and on days 1, 2, 7, and 14. RESULTS: Activin A levels before PCI in AMI patients (557+/-255 pg/ml) showed a significantly higher value than those in AP patients (364+/-159 pg/ml) and control subjects (316+/-144 pg/ml). Increased serum activin A level before PCI was decreased on day 2, and then gradually re-elevated on days 7 and 14. The serum activin A level before PCI was correlated with log-transformed peak creatine kinase (CK) as a surrogate of infarct size (r=0.48, p=0.008). Stepwise multiple regression analysis demonstrated that the serum activin A level before PCI was an independent predictor of peak CK. CONCLUSIONS: The serum activin A level, increased in AMI, was positively correlated with peak CK and CK-MB levels which are measures of infarction size.

DOI： 10.1016/j.cca.2008.10.027

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

During inflammation, lower molecular weight fragments of hyaluronan accumulate, and this is known to be inflammatory and immune-stimulatory. In diseases such as inflammatory bowel disease, inflammatory cells bind to hyaluronan; however, the cellular response and molecular mechanism of hyaluronan-hyaluronan receptor interactions in mononuclear cells are not well understood. The expression of hyaluronan receptors in peripheral blood mononuclear cells (PBMC) was examined. PBMC were stimulated with lower and higher molecular weight hyaluronan (molecular weight 100-150 kDa and 2700 kDa) and the induction of proinflammatory cytokines (interleukin-6 (IL-6) and monocyte chemoattractant protein (MCP-1)) was compared by enzyme-linked immunoabsorbant assay (ELISA). Cells were coincubated with various signaling pathway inhibitors. In addition, neutralizing antibodies against CD44 and TLR4 were added and the effects on PBMC were investigated. Finally, mononuclear cells from CD44-null and toll-like receptor 4 (TLR4) mutant mice were both stimulated with lower molecular weight hyaluronan. Among the hyaluronan receptors, TLR4 and CD44 were markedly expressed on PBMC. Hyaluronan-stimulated PBMC enhanced the attachment to the extracellular matrix. Lower molecular weight hyaluronan induced IL-6 and MCP-1 production in PBMC, but high-molecular-weight hyaluronan did not induce IL-6 and MCP-1 production. An anti-CD44 antibody attenuated the induction of both IL-6 and MCP-1 in lower molecular weight hyaluronan-stimulated PBMC. In both TLR4 mutant and CD44-null mice, the induction of IL-6 by lower molecular weight hyaluronan stimulation was decreased. SB203580 completely abolished IL-6 production in both TLR4 mutant and CD44-null mononuclear cells, while PD98059 abolished IL-6 production in CD44-null mononuclear cells. Hyaluronan receptors, CD44 and TLR4, play distinct roles in cytokine induction in hyaluronan-stimulated mononuclear cells.

DOI： 10.1093/glycob/cwn109

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: Pulse wave velocity has been used as an index of aortic stiffness. Recently, the cardio-ankle vascular index (CAVI), which reflects the stiffness of the aorta independently of blood pressure, has been developed. In this study, we analyzed the relationship between CAVI and left ventricular (LV) diastolic dysfunction. METHODS: A total of 119 patients were referred for echocardiography to evaluate ventricular function. Patients with reduced systolic function were excluded. Patients were divided on the basis of normal or reduced LV diastolic function determined by echocardiography. CAVI was measured using an automatic waveform analyzer. RESULTS: CAVI was significantly higher in patients with reduced LV diastolic function than those with normal LV diastolic function (9.0+/-1.1 and 8.5+/-1.1, p=0.009). Multiple linear regression analysis revealed that CAVI was independently associated with the ratio of peak early diastolic velocity to peak atrial diastolic velocity and left atrial diameter. When patients were classified on the basis of CAVI quartiles, multiple logistic regression analysis demonstrated that the highest quartile of CAVI showed an increased odds ratio for the presence of LV diastolic dysfunction. CONCLUSION: The present study revealed that an increased CAVI was independently associated with LV diastolic dysfunction in patients with preserved systolic function.

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Cardiac resynchronization therapy (CRT) is theoretically expected to affect repolarization as well as depolarization. We studied the effects of CRT on corrected QT (QTc) dispersion in association with symptomatic improvement. QTc dispersion was analyzed in 26 consecutive patients (67 +/- 6 years old, 18 men and 8 women) who underwent CRT. CRT responders and nonresponders were defined as patients showing and not showing > or = 1 class New York Heart Association symptomatic improvement 3 months after CRT, respectively. QTc interval, QRS width, and QTc dispersion were measured automatically from digital data using an analyzing system. There were 18 CRT responders and 8 nonresponders among the patients. CRT responders showed significantly larger QTc dispersion than CRT nonresponders before CRT (102 +/- 26 vs 40 +/- 12 ms, P < 0.01). A significant decrease in QTc dispersion by CRT was observed in responders (102 +/- 26 to 52 +/- 15 ms, P < 0.01). In contrast, QTc dispersion was not decreased by CRT in nonresponders (40 +/- 12 to 39 +/- 11 ms, not significant). The difference observed before CRT was thus abolished after CRT (52 +/- 15 vs 39 +/- 11 ms, not significant). Baseline values and changes in QRS width or QTc, as well as asynchrony of wall motion determined by tissue Doppler imaging, were not different between CRT responders and nonresponders before CRT. The present study with a small number of patients shows the potential utility of QTc dispersion for distinguishing CRT responders from CRT nonresponders before CRT, and warrants further study with a greater number of patients.

DOI： 10.1007/s00380-008-1056-7

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We examined the hemodynamic responses to exercise and symptoms in 37 male patients with untreated essential hypertension, and compared the findings with those in 32 age-matched healthy male volunteers by performing a graded symptom-limited exercise test using a bicycle ergometer. The subjective feeling of intensity of exercise was determined using the Borg scale. In the relationship between Borg scores and blood pressure (BP), patients with hypertension showed higher systolic BP and diastolic BP relative to the Borg scores than the controls. Consequently, patients with hypertension showed significantly higher systolic BP with Borg scores < or = 3 (subjective symptoms < or = moderately hard) than the controls (177.8 +/- 27.0 vs. 143.7 +/- 17.9 mmHg, p < 0.0001). Similarly, significantly higher diastolic BP with Borg scores < or = 3 was observed in patients with hypertension than in the controls (101.6 +/- 12.0 vs. 82.6 +/- 11.6 mmHg, p < 0.0001). The pulse pressure with Borg scores < or = 3 was also significantly higher in patients with hypertension than in the controls (76.2 +/- 20.6 vs. 61.0 +/- 13.6 mmHg, p < 0.0001). Hypertensive patients showed a decrease in the high-frequency power of heart rate variability at initial low-load exercise. In conclusion, the present study revealed that there was a greater BP response relative to the Borg score in patients with hypertension than in the controls. Autonomic nerve activity may contribute to some extent to these different relations. A determination of the relationship between the subjective feeling of intensity of the exercise and BP levels caused by a given intensity of load is essential before exercise training in patients, at least in males, with hypertension to avoid increasing the risk of cardiovascular events in association with excessive exercise training.

DOI： 10.1080/10641960802068436

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: The augmentation index of the radial pulse wave has been reported to be a sensitive aortic stiffness marker in relatively young but not in older individuals. We studied the relationship between augmentation index and the diurnal blood pressure profiles. PATIENTS AND METHODS: Twenty-four-hour ambulatory blood pressure monitoring was performed in 90 untreated patients with uncomplicated essential hypertension. The patients were classified into four groups: dippers, extreme dippers, nondippers, and risers. Augmentation index was calculated as the percentage of the second systolic peak relative to the first systolic peak. RESULTS: No significant differences in the averaged whole 24-h systolic or diastolic blood pressure were observed in the whole set of patients or in subgroup patients with age 60 years or under. In the whole set of patients (58.7 +/- 12.9 years), there were significant differences in augmentation index between patients with abnormal (other than dippers) and normal diurnal blood pressure profiles (dippers). In subgroup patients with age 60 years or below (49.1 +/- 9.1 years, n = 48), the abnormal diurnal blood pressure profile group showed significantly higher augmentation index (89.6 +/- 10.3%) than dippers (80.5 +/- 11.8%). The area under the curve in the receiver operating characteristics curve for distinguishing between dippers than other dippers was 0.73 (P < 0.01). Multivariate analysis demonstrated that abnormal diurnal blood pressure profile was independently associated with increase in augmentation index. In contrast, these relationships were not significant in the over 60 years subgroup patients (69.8 +/- 5.6 years old, n = 42). CONCLUSIONS: The present study revealed that augmentation index was associated with dipping blood pressure patterns in untreated hypertensive patients aged 60 years or younger. Augmentation index determination would be useful for initial assessment in connection with possible abnormal diurnal blood pressure variability in patients with age 60 years or younger.

DOI： 10.1097/HJH.0b013e3282f2fdb6

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: We examined the serum levels of interferon-gamma-inducible protein 10 (IP-10), an inflammation-induced chemokine, in acute myocardial infarction (AMI). DESIGN AND METHODS: The subjects were 33 AMI patients, 20 stable angina pectoris patients (AP) and 20 normal subjects. In AMI patients, blood samples were collected before percutaneous coronary intervention (PCI) and on days 3, 7 and 28. RESULTS: Patients with AMI showed significantly higher serum IP-10 levels (137.5+/-79.8 pg/mL) than control subjects (91.2+/-40.1 pg/mL) and patients with AP (93.3+/-41.1 pg/mL). The serum IP-10 level before PCI was negatively correlated with infarct size, as indicated by cumulative release of creatine kinase (CK) and peak CK and its isoenzyme CK-MB. Stepwise multiple regression analysis revealed that the serum IP-10 level before PCI was an independent predictor of cumulative CK release. CONCLUSIONS: The serum IP-10 level was increased in AMI, and a higher level of serum IP-10 before PCI may be informative regarding infarct size.

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We examined the relationship between plasma B-type natriuretic peptide (BNP) level and diurnal variability pattern of blood pressure (BP). Twenty-four-hour ambulatory BP monitoring was performed in 98 patients with asymptomatic essential hypertension, and the patients were classified into four groups according to their circadian BP variation profiles: dippers (n=29), nondippers (n=36), extreme dippers (n=19), and risers (n=14). Plasma BNP was measured by enzyme immunoassay. Based on the distribution pattern of BNP values, the values were analyzed after logarithmic transformation. Significant differences in plasma BNP levels among the types of circadian BP variations were demonstrated by analysis of variance (p<0.0005). Nondippers and risers showed significantly higher plasma BNP levels (mean [range: -1 SD and +1 SD]: 16.1 [6.3, 41.6] pg/mL and 29.2 [15.9, 53.4] pg/mL, respectively) than dippers (8.4 [3.7, 19.1] pg/mL). The area under the receiver operating characteristics curve for distinguishing patients with abnormal circadian BP variation from those with normal variation was 0.72, indicating that plasma BNP levels were useful for distinguishing between these patients. Specificity of 69% and sensitivity of 72% were obtained with a cut-off value of 10.5 pg/mL (log plasma BNP, 1.02) for distinguishing the abnormal diurnal BP profile group from the normal group. In conclusion, hypertensive patients with abnormal diurnal BP variation patterns (nondippers, extreme dippers, and risers) showed higher plasma BNP levels than those with normal circadian BP variation (dippers). Plasma BNP level is clinically useful for the identification of hypertensive patients who have abnormal circadian BP variability, which increases the risk of cardiovascular events.

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Automatic Doppler flow signal detection systems can provide beat-to-beat information for large blood vessels. We have developed new equipment for automatic measurement of Doppler flow signals. The reliability of the system was examined, and the variability of aortic and pulmonary peak flow velocity was determined. METHODS: We measured peak flow velocity using a newly developed system in healthy volunteers and patients with atrial fibrillation. Analysis of variability of peak flow velocity was performed with maximal entropy methods. RESULTS: In Bland-Altman plots, the mean and standard deviation (SD) of differences in aortic peak flow velocities between the automatic and manual measurements were 0.22 ± 0.75 cm/s and 0.85 ± 0.38 cm/s, respectively, in five normal volunteers. Moreover, less than 5% of the plotted points were beyond ± 2 SD of the differences. Furthermore, good reproducibility was demonstrated using Bland-Altman plots and Pearson's correlation analysis. Identical reliability was obtained in patients with atrial fibrillation. The same results were obtained for pulmonary peak flow velocity. In five healthy subjects, aortic and pulmonary peak flow showed standard deviations of 7.2 ± 2.4 and 3.8 ± 0.6 cm/s, respectively, and coefficients of variation of 6.1% ± 1.0% and 5.1% ± 1.1%, respectively, in time-domain variability. Similarly, frequency-domain variability was obtained for both peak flow velocities. CONCLUSION: The present study demonstrated the reliability of a newly developed automatic Doppler flow signal detection system. Using this system, the present study demonstrated for the first time aortic and pulmonary peak flow velocity variability. The present analytical methods may have considerable potential for studying aortic and/or pulmonary flow variability in connection with cardiac performance and prognosis of cardiac disease.

DOI： 10.1007/s10396-006-0126-7

PubMed

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記述言語：英語   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Web of Science

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記述言語：英語   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Web of Science

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Angiogenesis plays an essential role in tumor growth. This study investigated expression of the noncollagenous domain of alpha3(IV) collagen (alpha3(IV)NC1) transduced into tumors and its inhibition of tumor growth. We hypothesized that if a human telomerase reverse transcriptase (hTERT) promoter-driven RGD motif containing alpha3(IV)NC1 (hTERT/RGD-alpha3(IV)NC1) were expressed in telomerase-expressing tumor cells, it would inhibit tumor growth by its anti-angiogenic property. Adenoviral transduction of hTERT/RGD-alpha3(IV)NC1 expressed RGD-alpha3(IV)NC1 in hTERT-positive tumor cell lines. However, hTERT/RGD-alpha3(IV)NC1 did not express RGD-alpha3(IV)NC1 in hTERT-negative cells such as keratinocytes and fibroblasts. The secreted RGD-alpha3(IV)NC1 in the conditioned medium from tumor cells inhibited cell proliferation as well as tube formation in cultured endothelial cells, but had no effect on other types of cells. In an in vivo model, adenoviral hTERT/RGD-alpha3(IV)NC1 gene therapy showed limited expression of RGD-alpha3(IV)NC1 in tumors and resulted in a significant decrease of vessel density in tumors. The growth of subcutaneous (s.c.) tumors in nude mice was significantly suppressed by treatment with hTERT/RGD-alpha3(IV)NC1. In addition, long-term inhibition of tumor growth was achieved by intermittent administration of hTERT/RGD-alpha3(IV)NC1. In conclusion, our findings demonstrate that tumor-specific anti-angiogenic gene therapy utilizing RGD-alpha3(IV)NC1 under the hTERT promoter inhibited angiogenesis in tumors, resulting in an antitumor effect.

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Versican, a large chondroitin sulfate proteoglycan, plays a role in conditions such as wound healing and tissue remodelling. To test the hypothesis that versican expression is transiently upregulated and plays a role in the infarcted heart, we examined its expression in a rat model of myocardial infarction. Northern blot analysis demonstrated increased expression of versican mRNA. Quantitative real-time RT-PCR analysis revealed that versican mRNA began to increase as early as 6 h and reached its maximal level 2 days after coronary artery ligation. Versican mRNA then gradually decreased, while the mRNA of decorin, another small proteoglycan, increased thereafter. Versican mRNA was localized in monocytes, as indicated by CD68-positive staining, around the infarct tissue. The induction of versican mRNA was accelerated by ischemia/reperfusion (I/R), which was characterized by massive cell infiltration and enhanced inflammatory response. To examine the alteration of versican expression in monocytes/macrophages, we isolated human peripheral blood mononuclear cells and stimulated them with granulocyte/macrophage colony-stimulating factor (GM-CSF). Stimulation of mononuclear cells with GM-CSF increased the expression of versican mRNA as well as cytokine induction. The production of versican by monocytes in the infarct area represents a novel finding of the expression of an extracellular matrix gene by monocytes in the infarcted heart. We suggest that upregulation of versican in the infarcted myocardium may have a role in the inflammatory reaction, which mediates subsequent chemotaxis in the infarcted heart.

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Extracellular matrix (ECM)-degrading enzymes such as matrix metalloproteases (MMPs) play an essential role in the repair of infarcted tissue, which affects ventricular remodeling after myocardial infarction. ADAMTS1 (A disintegrin and metalloprotease with thrombospondin motifs), a newly discovered metalloprotease, was originally cloned from a cancer cell line, but little is known about its contribution to disease. To test the hypothesis that ADAMTS1 appears in infarcted myocardial tissue, we examined ADAMTS1 mRNA expression in a rat myocardial infarction model by Northern blotting, real-time RT-PCR and in situ hybridization. Normal endothelium expressed little ADAMTS1 mRNA, while normal myocardium expressed no detectable ADAMTS1 mRNA. Up-regulation of ADAMTS1 was demonstrated by Northern blot analysis and real-time RT-PCR at 3 h after coronary artery ligation. In situ hybridization revealed strong ADAMTS1 mRNA signals in the endothelium and myocardium in the infarcted heart, mainly in the infarct zone, at 3 h after myocardial infarction. The rapid and transient up-regulation of the ADAMTS1 gene in the ischemic heart was distinct from the regulatory patterns of other MMPs. Our study demonstrated that the ADAMTS1 gene is a new early immediate gene expressed in the ischemic endothelium and myocardium.

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Link proteins (LPs) belong to the link-module superfamily, which can stabilize and enhance the binding of lecticans to hyaluronan. We report here the identification and characterization of a novel rat link protein gene (Lp3/Hapln3). The deduced protein sequence shares the typical modular elements of link proteins and has an estimated mass of 39 kDa. Examination of the rat genomic DNA sequence revealed that Lp3/Hapln3 and aggrecan genes were paired on chromosome 1q31. Another LP gene and the lectican gene were also paired at a different locus, as they are in the human and mouse genomes. Immunohistochemical analysis showed the prominent expression of Lp3/Hapln3 in the smooth muscle tissues of the vascular wall and gastrointestinal tract. Further comparative studies revealed that Lp3/Hapln3 was well co-localized with versican around the smooth muscle cells of blood vessels but not around endothelial cells. In vitro experiments using primary cultured rat arterial smooth muscle cells (ASMCs) demonstrated the coordinated up-regulation of Lp3/Hapln3 and versican by platelet-derived growth factor (PDGF). These data were supported by in vivo studies of a mechanical vascular injury model in mice. Altogether, our results suggest that Lp3/Hapln3 is involved, together with versican and hyaluronan, in the formation of the pericellular matrix of vascular smooth muscle cells.

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Osteogenic protein, a member of the transforming growth factor-beta superfamily, has been reported to decrease the expression of intercellular adhesive molecules and prevent neutrophil accumulation and activity in tissue injury. OBJECTIVE: To examine the effects of osteogenic protein on ischemia/reperfusion in rat hearts. METHODS: Reperfusion was established after a 90 min ligation of the proximal left coronary artery in rats. Recombinant human osteogenic protein-1 (200 mug/kg) was administered via the femoral vein just before reperfusion. Intercellular adhesion molecule-1 (ICAM-1) messenger RNA (mRNA) expression and infarct size were evaluated using Northern blotting and triphenyl tetrazolium chloride staining, respectively. Terminal deoxynucleotidyl transferase mediated biotin-16-2'-deoxyuridine-5'-triphosphate nick end labeling (TUNEL) staining was also performed. RESULTS: In osteogenic protein-1 treated rats, the expression of ICAM-1 mRNA in ischemia/reperfusion hearts rapidly increased 4 h after reperfusion, although, the increase was lower than that observed in the vehicle-treated hearts (7.4+/-1.6-fold versus 14.6+/-3.7-fold increase compared to the increase observed in preligation control hearts, respectively). Similarly, in day 1 and day 7 hearts, the increase in ICAM-1 mRNA expression was significantly lower in ischemia/reperfusion hearts from rats treated with osteogenic protein-1 than in vehicle-treated rats (2.5+/-0.1-fold versus 5.8+/-2.3-fold and 1.5+/-0.3-fold versus 3.5+/-0.2-fold, respectively). Infarct size in rats treated with osteogenic protein-1 was significantly smaller than that observed in rats treated with vehicle (13.1+/-1.2% versus 28.5+/-5.7% of the left ventricle, P<0.01). The percentage of TUNEL-positive cardiomyocytes in ischemia/reperfusion hearts in rats treated with osteogenic protein-1 was significantly lower than in rats treated with vehicle (17.1+/-5.3% versus 31.1+/-4.5%, P<0.01). CONCLUSION: The present study demonstrated that recombinant human osteogenic protein-1 suppressed ICAM-1 mRNA expression, reduced infarct size and decreased TUNEL-positive cardiomyocytes in ischemic/reperfused rat hearts.

PubMed

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本医学教育学会  

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記述言語：日本語   出版者・発行元：(一社)日本プライマリ・ケア連合学会  

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

J-GLOBAL

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J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本医学教育学会  

背景:本邦の臨床研修病院で研修医メンター制度が導入されてきているが、制度の詳細や効果については明らかにされていない。目的:当院で運用している研修医メンター制度を紹介し、2018年度に本制度を利用した研修医(メンティ)からのメンター制度に対する評価を明らかにする。方法:制度を利用した研修医に無記名のwebアンケート調査を実施した。結果:2018年度採用研修医の78.0%(32名)が本制度を利用した。調査の回答率は87.5%(28名)で、制度に対する満足度は高かった。考察:今後はメンターも対象に、より詳細なアンケート調査を実施し、さらなる制度改善へとつなげたい。(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本医学教育学会  

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記述言語：日本語   出版者・発行元：(一社)日本医学教育学会  

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記述言語：日本語   出版者・発行元：(一社)日本医学教育学会  

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記述言語：日本語   出版者・発行元：(一社)日本医学教育学会  

J-GLOBAL

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J00050&link_issn=&doc_id=20200708060054&doc_link_id=%2Fed9jmded%2F2020%2F005103%2F056%2F0324-0325%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fed9jmded%2F2020%2F005103%2F056%2F0324-0325%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：岡山医学会  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J00175&link_issn=&doc_id=20191204120004&doc_link_id=10.4044%2Fjoma.131.159&url=https%3A%2F%2Fdoi.org%2F10.4044%2Fjoma.131.159&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

記述言語：日本語   出版者・発行元：(一社)日本臨床検査医学会  

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：日本語   出版者・発行元：(一社)日本医学教育学会  

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記述言語：日本語   出版者・発行元：(一社)日本病院総合診療医学会  

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記述言語：日本語   出版者・発行元：(一社)日本病院総合診療医学会  

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記述言語：日本語   出版者・発行元：(一社)日本病院総合診療医学会  

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：日本語   出版者・発行元：岡山医学会  

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：日本語   出版者・発行元：(一社)日本医学教育学会  

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記述言語：日本語   出版者・発行元：(一社)日本医学教育学会  

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記述言語：日本語   出版者・発行元：(一社)日本医学教育学会  

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記述言語：日本語   出版者・発行元：(一社)日本医学教育学会  

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記述言語：日本語   出版者・発行元：(一社)日本医学教育学会  

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：日本語   出版者・発行元：間脳・下垂体・副腎系研究会  

40歳代男性。他院で頭蓋咽頭腫に対する腫瘍摘出開頭術を受けるも、2ヵ月後、腰痛と39℃台の発熱が出現したため再入院となった。髄液培養にてAcinetobacterが検出され、細菌性髄膜炎として抗生剤加療されたが、解熱せず、当院へ転院となった。当初、本症例は細菌性髄膜炎として薬剤をMEPMからABPC/SBTに変更し対処した。だが、奏効はせず、腰痛精査のため行った脊椎CTにてTh7/8・L4/5に骨破壊像が認められ、更にL4/5の椎体培養からCandida albicansが検出され、Candida椎体炎と診断した。診断後は抗真菌薬を併用したが効果は得られず、頭部MRIを行ったところ、髄膜炎が示唆され、髄液異常の原因は化学性髄膜炎と考えられた。治療は副腎不全に対する補充療法の継続ほか、汎下垂体機能症に対してはヒドロコルチゾン投与を行った。9ヵ月後の外来検査ではMRI-FLAIRの高信号は消失し、髄液所見は改善傾向にあった。

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：日本語   出版者・発行元：(一社)日本医学教育学会  

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記述言語：日本語   出版者・発行元：(一社)日本病院総合診療医学会  

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記述言語：日本語   出版者・発行元：(一社)日本病院総合診療医学会  

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記述言語：日本語   出版者・発行元：(一社)日本病院総合診療医学会  

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記述言語：日本語   出版者・発行元：(一社)日本病院総合診療医学会  

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記述言語：日本語   出版者・発行元：(一社)日本病院総合診療医学会  

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：日本語   出版者・発行元：間脳・下垂体・副腎系研究会  

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記述言語：日本語   出版者・発行元：(一社)日本病院総合診療医学会  

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記述言語：日本語   出版者・発行元：(一社)日本医学教育学会  

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記述言語：日本語   出版者・発行元：(一社)日本病院総合診療医学会  

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記述言語：日本語   出版者・発行元：(一社)日本医学教育学会  

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記述言語：日本語   出版者・発行元：(一社)日本医学教育学会  

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記述言語：日本語   出版者・発行元：日本結合組織学会・マトリックス研究会  

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記述言語：日本語   出版者・発行元：(一社)日本内分泌学会  

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記述言語：日本語   出版者・発行元：(一社)日本病院総合診療医学会  

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記述言語：日本語   出版者・発行元：(一社)日本病院総合診療医学会  

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記述言語：日本語   出版者・発行元：(一社)日本病院総合診療医学会  

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記述言語：日本語   出版者・発行元：(一社)日本医学教育学会  

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記述言語：日本語   出版者・発行元：(一社)日本医学教育学会  

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記述言語：日本語   出版者・発行元：(一社)日本医学教育学会  

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記述言語：日本語   出版者・発行元：(公社)日本生化学会  

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記述言語：日本語   出版者・発行元：(一社)日本臨床検査医学会  

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記述言語：日本語   出版者・発行元：(一社)日本臨床検査医学会  

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記述言語：日本語   出版者・発行元：(一社)日本臨床検査医学会  

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記述言語：日本語   出版者・発行元：(一社)日本臨床検査医学会  

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記述言語：日本語   出版者・発行元：(一社)日本臨床検査医学会  

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記述言語：日本語   出版者・発行元：(公社)日本生化学会  

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記述言語：日本語   出版者・発行元：(一社)日本医学教育学会  

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記述言語：日本語   出版者・発行元：日本結合組織学会・マトリックス研究会  

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記述言語：日本語   出版者・発行元：日本結合組織学会・マトリックス研究会  

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記述言語：英語   出版者・発行元：(公社)日本生化学会  

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記述言語：英語   出版者・発行元：社団法人日本循環器学会  

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記述言語：英語   出版者・発行元：社団法人日本循環器学会  

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記述言語：英語   出版者・発行元：社団法人日本循環器学会  

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記述言語：英語   出版者・発行元：社団法人日本循環器学会  

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記述言語：英語   出版者・発行元：社団法人日本循環器学会  

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記述言語：日本語   出版者・発行元：(公社)日本薬学会  

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記述言語：英語   出版者・発行元：社団法人日本循環器学会  

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記述言語：英語   出版者・発行元：社団法人日本循環器学会  

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記述言語：英語   出版者・発行元：社団法人日本循環器学会  

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記述言語：日本語   出版者・発行元：日本結合組織学会・マトリックス研究会  

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記述言語：日本語   出版者・発行元：日本結合組織学会・マトリックス研究会  

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記述言語：英語   出版者・発行元：社団法人日本循環器学会  

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記述言語：英語   出版者・発行元：社団法人日本循環器学会  

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記述言語：英語   出版者・発行元：社団法人日本循環器学会  

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記述言語：日本語   出版者・発行元：(一社)日本動脈硬化学会  

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記述言語：英語   出版者・発行元：社団法人日本循環器学会  

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記述言語：英語   出版者・発行元：社団法人日本循環器学会  

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記述言語：日本語   出版者・発行元：(一社)日本循環器学会  

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記述言語：日本語   出版者・発行元：(一社)日本動脈硬化学会  

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記述言語：英語   出版者・発行元：社団法人日本循環器学会  

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記述言語：英語   出版者・発行元：社団法人日本循環器学会  

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記述言語：英語   出版者・発行元：社団法人日本循環器学会  

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記述言語：日本語   出版者・発行元：(一社)日本循環器学会  

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記述言語：英語   出版者・発行元：(一社)日本動脈硬化学会  

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記述言語：日本語   出版者・発行元：日本結合組織学会  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2002&ichushi_jid=J04666&link_issn=&doc_id=20020312510102&doc_link_id=%2Fcc0conti%2F2002%2F003401%2F102%2F0087-0087%26dl%3D2&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcc0conti%2F2002%2F003401%2F102%2F0087-0087%26dl%3D2&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_5.gif

記述言語：日本語   出版者・発行元：(一社)日本循環器学会  

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記述言語：日本語   出版者・発行元：(一社)日本循環器学会  

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記述言語：日本語   出版者・発行元：マトリックス研究会  

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記述言語：日本語   出版者・発行元：(一社)日本循環器学会  

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記述言語：日本語   出版者・発行元：(一社)日本肝臓学会  

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記述言語：日本語   出版者・発行元：広島医学会  

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記述言語：日本語   出版者・発行元：(一社)日本循環器学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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