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Yasuyoshi Ouchi

Publications and source records attributed to Yasuyoshi Ouchi.

84 records · Page 5Linked to original sources
PubMed2002

Molecular mechanisms underlying human beta-defensin-2 gene expression in a human airway cell line (LC2/ad).

OBJECTIVE: Recently, human beta-defensin-2 (hBD-2), an inducible defensin, has been reported to be involved in innate immunity and host defence. To examine the exact roles of hBD-2 in the respiratory system, we examined the molecular mechanisms of hBD-2 gene expression in vitro. METHODOLOGY: Using a human airway cell line (LC-2/ad), lipopolysaccharide (LPS)-induced gene expression of hBD-2 was studied in the absence or the presence of (i) dexamethasone, (ii) inhibition of NF-kappaB and AP-1, (iii) intracellular calcium chelator, and (iv) cyclooxygenase (COX) inhibitors. RESULTS: Lipopolysaccharide-induced gene expression of hBD-2 was down-regulated by (i) dexamethasone, (ii) inhibition of NF-kappaB and AP-1, and (iii) intracellular calcium chelator. However, COX inhibitors had no effect on LPS-induced mRNA expression of hBD-2. CONCLUSION: These findings suggest that glucocorticoids (GC), but not COX inhibitors, reduce hBD-2 gene expression, while NF-kappaB, AP-1 and intracellular calcium are essential for hBD-2 expression. Glucocorticoid-induced down-regulation of hBD-2 might be involved in the GC-induced suppression of respiratory host defence associated with hBD-2.

Blotting, Northern↗
PubMed2002

Attenuation of antigen-induced airway hyperresponsiveness in CGRP-deficient mice.

Bronchial hyperresponsiveness and eosinophilia are major characteristics of asthma. Calcitonin gene-related peptide (CGRP) is a neuropeptide that has various biological actions. In the present study, we questioned whether CGRP might have pathophysiological roles in airway hyperresponsiveness and eosinophilia in asthma. To determine the exact roles of endogenous CGRP in vivo, we chose to study antigen-induced airway responses using CGRP gene-disrupted mice. After ovalbumin sensitization and antigen challenge, we assessed airway responsiveness and measured proinflammatory mediators. In the sensitized CGRP gene-disrupted mice, antigen-induced bronchial hyperresponsiveness was significantly attenuated compared with the sensitized wild-type mice. Antigen challenge induced eosinophil infiltration in bronchoalveolar lavage fluid, whereas no differences were observed between the wild-type and CGRP-mutant mice. Antigen-induced increases in cysteinyl leukotriene production in the lung were significantly reduced in the CGRP-disrupted mice. These findings suggest that CGRP could be involved in the antigen-induced airway hyperresponsiveness, but not eosinophil infiltration, in mice. The CGRP-mutant mice may provide appropriate models to study molecular mechanisms underlying CGRP-related diseases.

Animals↗
PubMed2002

Questionnaire survey on the Japanese guidelines for treatment of hypertension in the elderly: 1999 revised version.

A questionnaire survey was administered to Japanese clinical specialists in hypertension in order to gauge their opinions on the 1999 revised version of the Guidelines for Hypertension in the Elderly prepared by the Comprehensive Research Project on Aging and Health of the Ministry of Health and Welfare. Out of 162 council members of the Japanese Society of Hypertension, 122 (75%) replied. The majority (93%) of respondents approved of the guidelines in general, and 72% of them approved of the age-related setting of a therapeutic goal for blood pressure. Sixty-five percent of respondents selected long-acting Ca antagonists, ACE inhibitors and low-dose diuretics as first-line agents for hypertension without complications in the elderly. The results of the questionnaire survey should be reflected in the next version of the guidelines.

Aged↗
PubMed2002

[Questionnaire on the attitude of the physicians in educating the elderly patients with chronic obstructive pulmonary disease about smoking cessation].

Smoking status, the extent of recognition of the relationship between smoking and COPD, and actual nature of education for smoking cessation by physicians have not yet been fully elucidated. To investigate perceptions about education for smoking cessation in the elderly by physicians who work in the clinic, questionnaires were sent to the 1,012 physicians who belong to the Yokohama City Medical Association. Of these, 311 respond and their data (31%) were included in the analysis. The questionnaire included questions on the importance of smoking cessation in the elderly, on the perception about the relationship between smoking and various diseases, and actual education for smoking cessation. The smoking status of the physicians themselves was also investigated. The distribution of current smokers, ex-smokers, and non-smokers among the physicians was 13%, 33%, and 54%, respectively. Seventy-five percent of ex-smokers answered that their experience of smoking cessation influenced their patient education for smoking cessation, and 39% of smokers answered that their smoking status did not influence it. Only 53% of the physicians replied that they actually performed education for smoking cessation to the elderly, and 8% of them replied that they hardly perform any or do not perform it. Smoking cessation is thought to be the only way to prevent the development of COPD. However, only a half of physicians recognized the importance of smoking cessation for the treatment and control of COPD in the elderly. In addition, less than one third of physicians perform nicotine replacement therapy for smoking cessation. Enlightenment for physicians should be needed to make them perform education for smoking cessation more aggressively.

Aged↗
PubMed2002

[Chronic obstructive pulmonary disease (COPD) in the elderly: analysis from questionnaire about attitudes to the COPD guideline of the Japanese Respiratory Society and actual therapy for COPD used by physicians].

We have conducted a survey of attitudes to chronic obstructive pulmonary disease (COPD) in the elderly, a survey of attitudes to the COPD guideline prepared by the Japanese Respiratory Society, and a survey of the therapies actually used for this disease among physicians belonging to the Yokohama Medical Association. The results showed that most respondents thought that physicians, mainly except for respiratory physicians, miss the COPD patients because of failure to recognize COPD. The spread of the COPD guideline among physicians and the amount of therapy conducted according to this guideline were also insufficient. However, most physicians who know this guideline have used it well, and have also appreciated the contents. Thus, the results of our surveys suggested that this COPD guideline, with its step-by-step pharmacologic therapy, should be more widely disseminated, mainly among clinics and physicians that are not respiratory specialists. This would enable them to follow the guideline and improve their treatment of COPD. In addition, it was also supposed that the comprehensive respiratory rehabilitation should be more executed in the hospitals.

Aged↗
PubMedDate not supplied

Pleiotropic actions of vitamin K: protector of bone health and beyond?

Vitamin K is a nutrient that was originally identified as an essential factor for blood coagulation. Recently, vitamin K has emerged as a potential protector against osteoporosis, atherosclerosis, and hepatocarcinoma. Accumulated evidence indicates that subclinical non-hemostatic vitamin K deficiency in extrahepatic tissues, particularly in bone and possibly in vasculature, exists widely in the otherwise healthy adult population. Vitamins K1 and K2 have been shown to exert protective effects against osteoporosis, although it is important that the beneficial effects will be further confirmed by large-scale, randomized, clinical trials. Increasing evidence implicates a role for vitamin K in calcification of arteries and atherogenesis. Moreover, the therapeutic potential of vitamin K2 as an antihepatoma drug has recently been highlighted. Most of the new biological functions of vitamin K in bone, vasculature, and hepatoma cells are considered attributable to promotion of gamma-carboxylation of glutamic acid residues in vitamin K-dependent proteins, which is shared by vitamins K1 and K2. In contrast, vitamin K2-specific, gamma-carboxylation-unrelated functions have also been demonstrated. Thus, biological differences between vitamins K1 and K2 and potential involvement of gamma-carboxylation-independent actions in the new roles of vitamin K remain open issues. Molecular bases of coagulation-unrelated pleiotropic actions of vitamin K and its implications in human health deserve further investigations.

Animals↗
PubMedDate not supplied

Depletion of glutathione S-transferase P1 induces apoptosis in human lung fibroblasts.

Glutathione S-transferase P1 (GSTP1) is one of the xenobiotic-metabolizing and antioxidant enzymes, identified in the peripheral lungs. Recently, the authors reported the association between GSTP1 gene polymorphism and susceptibility to chronic obstructive pulmonary disease (COPD), and protective effect of GSTP1 against cigarette smoke in human lung fibroblasts in vitro. In this study, the authors investigated that depletion of GSTP1 by itself could induce cell death, including apoptosis, in human lung fibroblast-derived HFL-1 cells. The level of apoptosis and necrosis was increased significantly with GSTP1 antisense vector transfection. It was also observed that the transfection efficiency and the expression level of the vector were weaker in the transfectant of the antisense vector than in those of the sense and control vectors, which is also thought to indicate that inhibition of GSTP1 expression by the antisense vector alone affects cellular viability. However, there was no difference among these transfectants neither on glutathione (GSH) level nor on c-Jun NH2-terminal kinase (JNK) activation. Therefore, the authors report here that underexpression of GSTP1 appeared to induce apoptosis on lung fibroblasts, which suggests that GSTP1 may have protective effects against apoptosis in the airway cells, though the mechanism of this apoptotic pathway is still to be elucidated.

Apoptosis↗
PubMedDate not supplied

Effects of long-term and reduced-dose hormone replacement therapy on endothelial function and intima-media thickness in postmenopausal women.

OBJECTIVE: Short-term estrogen therapy improves endothelial function in postmenopausal women. However, there are few reports on its long-term effects on endothelial function and carotid intima-media thickness. Further, we determined whether a reduced dosage of estrogen may maintain its beneficial effects. DESIGN: Eighteen postmenopausal women (53.7+/-1.1 years) who had been diagnosed as having osteoporosis were enrolled. Among them, 11 women were prescribed oral conjugated estrogen 0.625 mg and medroxyprogesterone acetate 2.5 mg per day, and 7 women were prescribed an oral calcium supplement as the control group. Each patient decided whether she would take hormone replacement therapy or a calcium supplement. We performed ultrasound measurement of endothelial function of the brachial artery and carotid intima-media thickness. Examinations were scheduled to be performed pre-therapy and after 3, 6, 12, 18, 24, and 36 months of therapy. RESULTS: After three years of therapy, 6 women in the hormone replacement therapy group agreed to take half the dose of oral conjugated estrogen. Improvement of flow-mediated dilatation was observed at 3 months and the improvement was preserved up to 36 months. A similar improvement was also observed while women were on hormone replacement therapy even at the reduced dosage. Intima-media thickness of the common carotid artery in the control group increased after 12 months, which was not observed in the hormone replacement therapy group. CONCLUSIONS: Our results indicate that even at half the dose of estrogen, hormone replacement therapy may improve endothelial function and prevent the progression of carotid intima-media thickening in postmenopausal women.

Brachial Artery↗