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Biomedical subjects

H Oya

Publications and source records attributed to H Oya.

At least 37 records · Page 2Linked to original sources
PubMed2001

Elevated circulating level of ghrelin in cachexia associated with chronic heart failure: relationships between ghrelin and anabolic/catabolic factors.

BACKGROUND: Ghrelin is a novel growth hormone (GH)-releasing peptide, isolated from the stomach, that may also cause a positive energy balance by stimulating food intake and inducing adiposity. We sought to investigate the pathophysiology of ghrelin in the cachexia associated with chronic heart failure (CHF). METHODS AND RESULTS: Plasma ghrelin was measured in 74 patients with CHF and 12 control subjects, together with potentially important anabolic and catabolic factors, such as GH and tumor necrosis factor (TNF-alpha). Patients with CHF were divided into two groups, those with cachexia (n=28) and those without cachexia (n=46). Plasma ghrelin did not significantly differ between all CHF patients and controls (181+/-10 versus 140+/-14 fmol/mL, P=NS). However, plasma ghrelin was significantly higher in CHF patients with cachexia than in those without cachexia (237+/-18 versus 147+/-10 fmol/mL, P<0.001). Circulating GH, TNF-alpha, norepinephrine, and angiotensin II were also significantly higher in CHF patients with cachexia than in those without cachexia. Interestingly, plasma ghrelin correlated positively with GH (r=0.28, P<0.05) and TNF-alpha (r=0.31, P<0.05) and negatively with body mass index (r=-0.35, P<0.01). CONCLUSIONS: Plasma ghrelin was elevated in cachectic patients with CHF, associated with increases in GH and TNF-alpha and a decrease in body mass index. Considering ghrelin-induced positive energy effects, increased ghrelin may represent a compensatory mechanism under catabolic-anabolic imbalance in cachectic patients with CHF.

Adolescent↗
PubMed2001

K(ATP) channels predominantly regulate conduit vessel tone in normoxic cat pulmonary arteries in vivo.

Through our investigations of the intact pulmonary circulation, we aimed to find out whether K(ATP) channels contribute to regulating basal vascular tone and to clarify which vascular segments dilate during K(ATP) channel activation under basal tone conditions. Using an X-ray television system on anesthetized cat lungs, we measured internal diameter (ID) responses to two K(ATP) channel inhibitors (glibenclamide and 4-morpholinecarboximidine-N-1-adamantyl-N'-cyclohexyl-hydrochloride (U-37883A)) and to an activator (levcromakalim) in normoxic pulmonary arteries. In conduit arteries (800-3000 microm ID), the inhibitors and activator induced larger ID constrictions (14-17%) and dilatations (29-32%), respectively. However, in resistance arteries (<500 microm), the constriction response was negligible and the dilatation response relatively small (5-10%). The data suggest that K(ATP) channels are active and capable of regulating basal vascular tone primarily within conduit pulmonary arteries even though these channels are present in all pulmonary arteries.

Adamantane↗
PubMed2001

Limited association between a catechol-O-methyltransferase (COMT) polymorphism and breast cancer risk in Japan.

BACKGROUND: Catechol-O-methyltransferase (COMT) inactivates the estradiol metabolites, 2-hydroxy estradiol and 4-hydroxy estradiol. To date, three studies in Caucasians and one study in Chinese have been conducted to determine the association with breast cancer risk of a functional polymorphism (G-to-A, Val158Met) of this enzyme, but the results were inconsistent. In order to examine the impact of this polymorphism on breast cancer risk in Japan, a case-control study was conducted, at Aichi Cancer Center Hospital. METHODS: The cases were 150 patients with histologically confirmed breast cancer who had been diagnosed within 4 years before enrollment at this hospital. The controls were 165 non-cancer patients, mainly from the gastroenterology and breast surgery clinics at the hospital. COMT-H (Val) is the wild-type allele, with high enzyme activity, while the COMT-L (Met) allele has low activity. Genotyping was conducted by a polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method. RESULTS: The allele frequency of COMT-L was 36.0% for cases and 33.0% for controls. Age-adjusted odds ratios relative to the COMT-HH genotype were 1.46 (95% confidence interval [CI], 0.90-2.36) for COMT-HL, and 0.99 (95% CI, 0.49-2.02) for the COMT-LL genotype. Significant odds ratios were not observed for any subgroup stratified by menopausal status, age at menarche, age at birth of first child, body mass index, and breast cancer history of mother and/or sister(s). CONCLUSION: The present study suggested that any association of the COMT polymorphism with breast cancer risk is limited in Japanese.

Adult↗
PubMed2001

Hemodynamic and hormonal effects of human ghrelin in healthy volunteers.

To investigate hemodynamic and hormonal effects of ghrelin, a novel growth hormone (GH)-releasing peptide, we gave six healthy men an intravenous bolus of human ghrelin (10 microg/kg) or placebo and vice versa 1-2 wk apart in a randomized fashion. Ghrelin elicited a marked increase in circulating GH (15-fold). The elevation of GH lasted longer than 60 min after the bolus injection. Injection of ghrelin significantly decreased mean arterial pressure (-12 mmHg, P < 0.05) without a significant change in heart rate (-4 beats/min, P = 0.39). Ghrelin significantly increased cardiac index (+16%, P < 0.05) and stroke volume index (+22%, P < 0.05). We also examined ghrelin receptor [GH secretagogues receptor (GHS-R)] gene expression in the aortas, the left ventricles, and the left atria of rats by RT-PCR. GHS-R mRNA was detectable in the rat aortas, left ventricles, and left atria, suggesting that ghrelin may cause cardiovascular effects through GH-independent mechanisms. In summary, human ghrelin elicited a potent, long-lasting GH release and had beneficial hemodynamic effects via reducing cardiac afterload and increasing cardiac output without an increase in heart rate.

Adult↗
PubMed2001

Short-term oral administration of L-arginine improves hemodynamics and exercise capacity in patients with precapillary pulmonary hypertension.

We sought to assess the effects of oral supplementation of L-arginine, the precursor of nitric oxide (NO), on hemodynamics and exercise capacity in patients with pulmonary hypertension. Acute hemodynamic responses to oral L-arginine (0.5 g/10 kg body weight) or placebo were examined in 19 patients with primary or precapillary secondary pulmonary hypertension. Cardiopulmonary exercise tests were performed to measure peak oxygen consumption (peak V O(2)) and the ventilatory response to carbon dioxide production (V E-V CO(2) slope) before and 1 wk after treatment with L-arginine (1.5 g/10 kg body weight/d) or placebo. Oral supplementation of L-arginine significantly increased plasma L-citrulline, which indicated enhancement of NO production. Supplemental L-arginine produced a 9% decrease in mean pulmonary arterial pressure (53 +/- 4 to 48 +/- 4 mm Hg, p < 0.05) and a 16% decrease in pulmonary vascular resistance (14.8 +/- 1.5 to 12.4 +/- 1.4 Wood units, p < 0.05). L-arginine modestly decreased mean systemic arterial pressure (92 +/- 4 to 87 +/- 3 mm Hg, p < 0.05). A 1-wk supplementation of L-arginine resulted in a slight increase in peak V O(2) (831 +/- 88 to 896 +/- 92 ml/min, p < 0.05) and a significant decrease in the V E- V CO(2) slope (43 +/- 4 to 37 +/- 3, p < 0.05) without significant systemic hypotension. Hemodynamics and exercise capacity remained unchanged during placebo administration. These results suggest that oral supplementation of L-arginine may have beneficial effects on hemodynamics and exercise capacity in patients with precapillary pulmonary hypertension.

Administration, Oral↗
PubMed2001

Hemodynamic, renal, and hormonal effects of ghrelin infusion in patients with chronic heart failure.

Ghrelin is a novel GH-releasing peptide that may also induce vasodilation and a positive energy balance through GH-independent mechanisms. However, the hemodynamic, renal, and hormonal effects of ghrelin in patients with chronic heart failure (CHF) remain unknown. Accordingly, 12 patients with CHF were given an iv infusion of human ghrelin (0.1 microg/kg.min) or placebo. Ghrelin significantly decreased mean arterial pressure (-9 mm Hg, P < 0.05) without a significant change in heart rate. Ghrelin significantly increased cardiac index (+25%, P < 0.05) and stroke volume index (+30%, P < 0.05), although it did not significantly alter mean pulmonary arterial pressure or pulmonary capillary wedge pressure. Infusion of ghrelin induced a marked increase in serum GH level (15-fold), associated with slight increases in circulating epinephrine, ACTH, cortisol, and PRL. Infusion of ghrelin did not significantly alter urine volume, urinary sodium excretion, or creatinine clearance. These hemodynamic, renal and hormonal parameters remained unchanged during placebo infusion. In summary, iv infusion of ghrelin, a potent GH-releasing peptide, had beneficial hemodynamic effects in patients with CHF in the absence of renal effects.

Aged↗
PubMed2001

Two-week, but not 1-week, hypoxic exposure enhances nitric oxide-mediated basal tone regulation in rat resistance pulmonary arteries.

We measured internal diameter (ID) changes in resistance and conduit pulmonary arteries of 1- and 2-week hypoxic rats and normoxic control rats in response to nitric oxide synthase (NOS) inhibitors in vivo. At 2 weeks of hypoxic exposure, the ID reduction as a result of NOS inhibition was enhanced within the resistance arteries, but not at 1 week of hypoxia.

Animals↗
PubMed2000

Increased plasma P-selectin and decreased thrombomodulin in pulmonary arterial hypertension were improved by continuous prostacyclin therapy.

BACKGROUND: Thrombosis in situ related to endothelial cell injury may contribute to the development of pulmonary hypertension (PH). P-selectin, a leukocyte adhesion receptor present in endothelial cells and platelets, reflects endothelial injury and platelet activation, and thrombomodulin (TM), a receptor for thrombin and a major anticoagulant proteoglycan on the endothelial membrane, reflects the anticoagulant activity of the endothelium. METHODS AND RESULTS: To assess abnormal coagulation due to endothelial injury in patients with PH, plasma levels of soluble P-selectin and TM were measured in 32 patients with primary PH (PPH), 25 with secondary pulmonary arterial hypertension (sPAH), 31 with pulmonary venous hypertension (PVH), and 17 healthy subjects (Control). These measurements were repeated after continuous infusion of prostacyclin in 15 patients with PPH and 3 with sPAH. P-selectin levels in both the sPAH and PPH groups were significantly higher than those in the Control and PVH groups (P<0.05). Plasma TM level in the PPH group was significantly lower than those in the other groups (P<0.01). After prostacyclin therapy, the lower TM level was increased and the higher P-selectin level was decreased (P<0.05). CONCLUSIONS: Decreased TM and increased P-selectin in PPH and sPAH may reflect in situ thrombosis due to endothelial injury. Prostacyclin may act not only as a vasodilator but also as an agent that improves endothelial injury and altered hemostasis in pulmonary arterial injury.

Adult↗
PubMed2000

Hemodynamic, renal, and hormonal effects of adrenomedullin infusion in patients with congestive heart failure.

BACKGROUND: Experimental studies have shown that adrenomedullin (AM) causes vasodilatation, diuresis, and a positive inotropic effect. In humans, however, whether infusion of AM has beneficial effects in congestive heart failure (CHF) remains unknown. METHODS AND RESULTS: Hemodynamic, renal, and hormonal responses to intravenous infusion of human AM (0.05 microg. kg(-1). min(-1)) were examined in 7 patients with CHF and 7 normal healthy subjects (NL). In NL group, AM significantly decreased mean arterial pressure (-16 mm Hg, P<0. 05) and increased heart rate (+12 bpm, P<0.05). In CHF group, AM also decreased mean arterial pressure (-8 mm Hg, P<0.05) and increased heart rate (+5 bpm, P<0.05), but to a much lesser degree (P<0.05 versus NL). AM markedly increased cardiac index (CHF, +49%; NL, +39%, P<0.05) while decreasing pulmonary capillary wedge pressure (CHF, -4 mm Hg; NL, -2 mm Hg, P<0.05). AM significantly decreased mean pulmonary arterial pressure only in CHF (-4 mm Hg, P<0.05). AM increased urine volume (CHF, +48%; NL, +62%, P<0.05) and urinary sodium excretion (CHF, +42%; NL, +75%, P<0.05). Only in CHF, plasma aldosterone significantly decreased during (-28%, P<0.05) and after (-36%, P<0.05) AM infusion. These parameters remained unchanged in 7 patients with CHF and 6 healthy subjects who received placebo. CONCLUSIONS: Intravenous infusion of AM has beneficial hemodynamic and renal effects in patients with CHF.

Adrenomedullin↗
PubMed2000

Organ specificity of c-kit+ lymphoid precursors in the liver, thymus, and bone marrow.

c-kit+Lin- cells are present in various immune organs, including the liver, thymus, and bone marrow, where lymphoid, myeloid, or erythroid cells are generated. To compare their properties as lymphoid precursors, c-kit+Lin- cells purified from various organs of B6.Ly5.1 mice were injected into 6.5 Gy-irradiated B6.Ly5.2 mice. Depending on the source of the c-kit cells, the degree of entrance and expansion of lymphoid cells differed in the liver and thymus of recipient mice. c-kit+ cells isolated from the bone marrow entered and expanded prominently in both the liver and thymus, whereas c-kit+ cells from the thymus did not do so at all. On the other hand, c-kit+ cells isolated from the liver and spleen showed an intermediate pattern, namely, they took a long time to enter and expand in the liver and thymus of recipient mice. All of these c-kit+ cells had the potential to give rise to lymphoid cells, which were specific to the liver and thymus, respectively. We previously showed that progenitor cells for extrathymic T cells in the liver and those for conventional T cells in the thymus are not always supplied by the bone marrow, as shown by experiments using parabiosis. Taken together with those previous data, the present results suggest that c-kit+Lin- cells isolated from various immune organs have organ specific properties.

Animals↗
PubMed2000

The differential effect of stress on natural killer T (NKT) and NK cell function.

When C57Bl/6 mice were exposed to restraint stress for 12 h or 24 h, lymphocytopenia was induced in the liver, spleen, and thymus. We examined which types of lymphocytes were sensitive or resistant to such stress by a immunofluorescence test. T cells of thymic origin were sensitive while NKT and NK cells were resistant. In contrast to the increase in the proportion of NK cells, NK activity of liver lymphocytes against YAC-1 targets decreased at 24 h after stress. On the other hand, their NKT cytotoxicity against syngeneic thymocytes increased in parallel with an increase in their proportion. In perforin -/- B6 mice and B6-gld/gld (Fas ligand-) mice, NK cells were found to mediate cytotoxicity through perforin while NKT cells mediated self-reactive cytotoxicity through Fas ligand. These results suggest that stress increases the proportion of both NK and NKT cells, but that NK cytotoxicity is suppressed while self-reactive NKT cytotoxicity is not, due to a diversity of their functional mechanisms.

Animals↗
PubMed2000

Disparate effect of beige mutation on cytotoxic function between natural killer and natural killer T cells.

Beige mice lack natural killer (NK) cytotoxicity, although NK cells are normally present. In recent studies, NK T cells have been newly identified. We therefore examined the number and function of NK T cells in beige mice. The number of NK T cells was at a normal level in the liver of beige mice. NK cytotoxicity was decreased in the liver of these mice, whereas NK T cytotoxicity was intact. When immunochemical staining for perforin was conducted, the majority of NK cells and the minority of NK T cells in beige mice carried a giant granule, containing perforin, in the cytoplasm. In the case of control B6 mice, the majority of NK cells and the minority of NK T cells had multiple, dispersed granules containing perforin. These results suggest that NK T cytotoxicity is unaffected by the beige mutation, owing to their cytotoxicity being mediated without the secretion system of perforin.

Animals↗
PubMed2000

Resistance of extrathymic T cells to stress and the role of endogenous glucocorticoids in stress associated immunosuppression.

When mice were exposed to restraint stress for 12 or 24 h, severe lymphopenia was induced in all immune system organs, including the liver and the thymus. However, in adrenalectomized mice, this response was completely absent. Phenotypic characterization revealed that interleukin (IL)-2Rbeta+CD3int cells (i.e. extrathymic T cells) with CD4+ phenotype and the NK1.1+ subset of CD3int cells (i.e. NKT cells) in the liver as well as the mature conventional T cells in the thymus were resistant to such stress. In adrenalectomized mice, there was no significant change in the distribution of lymphocyte subsets in all tested organs before stress. Interestingly, the number of lymphocytes in the liver and spleen and the proportion of NKT cells in the liver rather increased after stress in these adrenalectomized mice. Therefore, endogenous steroid hormones were indicated to be important in the induction of immunosuppressive states after stress. Among stress associated cytokines, the secretion of tumour necrosis factor (TNF)-alpha was completely suppressed while that of IL-6 was partially suppressed in adrenalectomized mice. These results suggest that endogenous steroid hormones are important for the induction of the stress associated immunosuppression and that NKT cells are resistant to stress, namely, resistant to exposure to endogenous steroid hormones.

Adrenalectomy↗
PubMed2000

Intensive expansion of natural killer T cells in the early phase of hepatocyte regeneration after partial hepatectomy in mice and its association with sympathetic nerve activation.

When C57BL/6 mice were partially hepatectomized (PHx), severe lymphocytosis was induced in the liver in the early phase of hepatocyte regeneration (4 to 12 hours after PHx). A major lymphocyte subset expanding in this organ was estimated to be natural killer 1.1(+) (NK1.1(+)) intermediate CD3 (CD3(int)) cells (i.e., NKT cells). CD3(int) cells are extrathymic T cells generated in situ in the liver. These changes were suppressed when mice with PHx were pretreated with a beta-adrenergicD antagonist (i.e., beta-blocker), propranolol (PPL). This might have been caused by sympathetic nerve stimulation during hepatocyte regeneration. An alpha-blocker showed a similar effect, although the magnitude of suppression was lower than that of the beta-blocker. We previously showed that NK and NKT cells express surface beta-adrenergic receptors and are activated in number by sympathetic nerve stimulation. In the present study, NK cytotoxicity mediated by liver lymphocytes obtained from mice with PHx decreased, whereas NKT cytotoxicity against syngeneic thymocytes increased. Purified CD3(int) cells were also found to be able to mediate NKT cytotoxicity against regenerating hepatocytes. These results suggest that sympathetic nerve stimulation after PHx results in subsequent activation of NKT cells and that these NKT cells might be associated with immunologic surveillance during hepatocyte regeneration.

Adrenergic alpha-Antagonists↗
PubMed2000

Haemodynamic correlates and prognostic significance of serum uric acid in adult patients with Eisenmenger syndrome.

OBJECTIVE: To assess haemodynamic correlates and prognostic significance of serum uric acid in adult patients with Eisenmenger syndrome. DESIGN: Retrospective observational study. SETTING: Tertiary referral centre. PATIENTS: 94 adult patients with Eisenmenger syndrome who were diagnosed between September 1982 and July 1998. MAIN OUTCOME MEASURES: Serum uric acid was measured in all patients, together with clinical and haemodynamic variables related to mortality. RESULTS: Serum uric acid was raised in patients with Eisenmenger syndrome compared with age and sex matched control subjects (7.0 v 4.7 mg/dl, p < 0.0001) and increased in proportion to the severity of New York Heart Association functional class. Serum uric acid was positively correlated with mean pulmonary arterial pressure (r = 0.30, p = 0.0052) and total pulmonary resistance index (r = 0.55, p < 0.0001), and negatively correlated with cardiac index (r = -0.50, p < 0.0001). During a mean follow up period of 97 months, 38 patients died of cardiopulmonary causes. Among various clinical, echocardiographic, and laboratory variables, serum uric acid remained predictive in multivariate analysis. Kaplan-Meier survival curves based on median serum uric acid showed that patients with high values had a significantly worse survival rate than those with low values (log-lank test: p = 0.0014 in male patients, p = 0.0034 in female patients). CONCLUSIONS: Serum uric acid increases in proportion to haemodynamic severity in adult patients with Eisenmenger syndrome and is independently associated with long term mortality.

Adolescent↗
PubMed2000

Haemodynamic and hormonal effects of adrenomedullin in patients with pulmonary hypertension.

OBJECTIVE: To investigate whether infusion of adrenomedullin, a potent vasorelaxant peptide, has beneficial haemodynamic and hormonal effects in patients with pulmonary hypertension. PATIENTS AND DESIGN: The haemodynamic and hormonal responses to intravenous infusion of adrenomedullin (0.05 microgram/kg/min) or placebo were examined in 13 patients with precapillary pulmonary hypertension. RESULTS: Infusion of adrenomedullin produced a 44% increase in cardiac index (mean (SD) 1.8 (0.2) to 2.6 (0.3) l/min/m(2), p < 0. 05) and a 32% decrease in pulmonary vascular resistance (19.7 (1.4) to 13.4 (1.3) units, p < 0.05), with a 4% reduction in mean pulmonary arterial pressure (62 (4) to 59 (4) mm Hg, NS). Adrenomedullin also decreased mean systemic arterial pressure (81 (3) to 72 (4) mm Hg, p < 0.05) and increased heart rate (73 (4) to 79 (4) beats/min, p < 0.05). Adrenomedullin decreased plasma aldosterone (9.8 (2.5) to 7.1 (1.5) ng/dl, p < 0.05) without significant changes in plasma renin activity. Plasma atrial and brain natriuretic peptides tended to decrease with adrenomedullin, although these changes did not reach significance. The haemodynamic and hormonal variables remained unchanged during placebo infusion. CONCLUSIONS: Intravenous adrenomedullin has beneficial haemodynamic and hormonal effects in patients with precapillary pulmonary hypertension.

Adrenomedullin↗
PubMed2000

Correlation between severity of pulmonary arterial hypertension and 123I-metaiodobenzylguanidine left ventricular imaging.

UNLABELLED: It remains unclear whether cardiac sympathetic nervous function is disturbed in patients with pulmonary arterial hypertension (PH) and how sympathetic dysfunction is related to PH. METHODS: In this study, (123)I-metaiodobenzylguanidine (MIBG) imaging of the heart, which reveals the sympathetic innervation of the left ventricle, was performed in 7 healthy volunteers without cardiopulmonary disease (control subjects); 55 patients with PH, including 27 with chronic thromboembolic pulmonary hypertension (CTEPH) of major vessels; and 28 patients with primary pulmonary hypertension (PPH). RESULTS: Cardiac (123)I-MIBG uptake, assessed as the heart-to-mediastinum activity ratio (H/M), was significantly lower in the CTEPH and PPH groups compared with that in the control group (P < 0.01). Myocardial MIBG turnover, expressed as the washout rate (WR [%]) from 15 to 240 min, was significantly higher in the CTEPH and PPH groups than that in the control group (P < 0.01). In the PPH group, H/M and WR values of MIBG correlated with the severity of pulmonary hypertension (represented by total pulmonary vascular resistance determined by right heart catheterization), the right ventricular ejection fraction determined by electron beam CT, and other variables but did not correlate well in the CTEPH group. In both groups, patients with H/M > or = 2.0 showed better cumulative survival than did those with H/M < 2.0 (P < 0.05). CONCLUSION: Patients with PH have significant left ventricular myocardial sympathetic nervous alteration. (123)I-MIBG imaging of the heart is useful for assessing the severity of pulmonary hypertension caused by PPH or CTEPH.

3-Iodobenzylguanidine↗