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Yasunobu Hirata

Publications and source records attributed to Yasunobu Hirata.

At least 19 recordsLinked to original sources
PubMed2006

Three-vessel coronary artery disease complicated with congestive heart failure in a highly aged patient with tetralogy of Fallot having undergone palliative surgeries.

An increasing number of patients with tetralogy of Fallot (TOF) are reaching older age. We encountered a 75-year-old woman with uncorrected TOF and concomitant severe coronary artery disease (CAD) with congestive heart failure. Her CAD risk factor was hyperlipidemia, which had been untreated. Successful percutaneous coronary interventions have improved her clinical condition and provided long-term survival. Although CAD is considered to be a rare complication in adults with TOF, both strict modification of CAD risk factors and early detection of CAD would be also required in this population, given the residual TOF lesions relating to acute exacerbation of clinical presentation.

Aged↗
PubMed2006

The beneficial effect of coronary-artery-bypass surgery on survival in patients with diabetic retinopathy.

OBJECTIVE: The presence of retinopathy is a predictor of mortality following coronary revascularization in diabetics. We studied whether revascularization by coronary-artery-bypass surgery (CABG), as compared with percutaneous coronary intervention (PCI), influences the prognosis in diabetics with retinopathy. METHODS: Between April 1996 and March 2004, 1489 patients underwent revascularization as an initial procedure. Among these a total of 319 diabetics underwent retinal examination prior to the initial revascularization. These patients were classified according to whether they had retinopathy and whether they had undergone CABG, either initially or after PCI. Mortality rates were estimated from the time of initial revascularization procedure. RESULTS: The average follow-up from the time of initial revascularization was 48.2+/-28.6 months. In 153 diabetics with retinopathy, 59 eventually underwent CABG. During the entire follow-up period, there were 2 (3.4%) deaths in diabetics with retinopathy who underwent CABG and 14 (14.9%) deaths in those who did not have CABG. Mortality curves differed significantly between the two groups (P = 0.007). After adjustment for risk factors, the relative risk of death was 0.13 afforded by CABG (95% CI, 0.03-0.62; P = 0.011). In 166 diabetics without retinopathy, mortality curves were similar between the patients who underwent CABG and those who did not have CABG (P = 0.94). CONCLUSIONS: CABG conferred a survival advantage in diabetics with retinopathy. In contrast, no survival advantage was evident in diabetics without retinopathy undergoing CABG. Retinal status should be taken into consideration when considering revascularization strategy for diabetics who have coronary artery disease.

Aged↗
PubMed2006

Molecular mechanism of the inhibitory effect of aldosterone on endothelial NO synthase activity.

Although the proinflammatory and profibrotic actions of aldosterone (Aldo) on the vasculature have been reported, the effects and molecular mechanisms of Aldo on endothelial function are yet to be determined. We investigated how Aldo regulates endothelial NO synthase (eNOS) function in human umbilical vein endothelial cells (HUVECs). HUVECs were incubated for 16 hours with Aldo 10(-7) mol/L. The concentration of reactive oxygen species was estimated by measuring 2',7'-dichlorodihydrofluorescein diacetate chemiluminescence. Signal transduction was estimated by Western immunoblots. Real-time RT-PCR was performed to measure expression of transcripts of endogenous GTP cyclohydrolase-1 and components of reduced nicotinamide-adenine dinucleotide phosphate oxidase. To eliminate the possible effect of the glucocorticoid receptor (GR) and to emphasize the role of mineralocorticoid receptor, we used GR small interfering RNA and knocked down GR expression in several experiments. NO output was estimated by intracellular cGMP concentration. Reactive oxygen species production increased significantly in Aldo-treated HUVECs but was abolished by pretreatment with eplerenone. Transcripts of p47(phox) were increased by Aldo treatment. Vascular endothelial growth factor-induced eNOS Ser 1177 but not Akt Ser 473 phosphorylation levels were reduced significantly by pretreatment with Aldo. Pretreatment with either eplerenone or okadaic acid restored phosphorylation levels of eNOS Ser 1177 in Aldo-treated cells, suggesting that protein phosphatase 2A was upregulated by Aldo via mineralocorticoid receptor. The decrease in NO output caused by Aldo pretreatment was reversed significantly by 5,6,7,8-tetrahydrobiopterin, GTP cyclohydrolase-1 overexpression, or p47(phox) knockdown. These results suggest that Aldo inhibits eNOS function through bimodal mechanisms of 5,6,7,8-tetrahydrobiopterin deficiency and protein phosphatase 2A activation.

Aldosterone↗
PubMed2006

Modulation of luminescence intensity of lanthanide complexes by photoinduced electron transfer and its application to a long-lived protease probe.

Luminescent lanthanide complexes (Tb(3+), Eu(3+), etc.) have excellent properties for biological applications, including extraordinarily long lifetimes and large Stokes shifts. However, there have been few reports of lanthanide-based functional probes, because of the difficulty in designing suitable complexes with a luminescent on/off switch. Here, we have synthesized a series of complexes which consist of three moieties: a lanthanide chelate, an antenna, and a luminescence off/on switch. The antenna is an aromatic ring which absorbs light and transmits its energy to the metal, and the switch is a benzene derivative with a different HOMO level. If the HOMO level is higher than a certain threshold, the complex emits no luminescence at all, which indicates that the lanthanide luminescence can be modulated by photoinduced electron transfer (PeT) from the switch to the sensitizer. This approach to control lanthanide luminescence makes possible the rational design of functional lanthanide complexes, in which the luminescence property is altered by a biological reaction. To exemplify the utility of our approach to the design of lanthanide complexes with a switch, we have developed a novel protease probe, which undergoes a significant change in luminescence intensity upon enzymatic cleavage of the substrate peptide. This probe, combined with time-resolved measurements, was confirmed in model experiments to be useful for the screening of inhibitors, as well as for clinical diagnosis.

Chemistry, Clinical↗
PubMed2006

New insights in the treatment strategy for pulmonary arterial hypertension.

INTRODUCTION: Recent advances in our understanding of the pathophysiological and molecular mechanisms involved in pulmonary arterial hypertension have led to the development of novel and rational pharmacological therapies. In addition to conventional therapy (i.e., supplemental oxygen and calcium channel blockers), prostacyclin or endothelin receptor antagonists have been recommended as a first-line therapy for pulmonary arterial hypertension. However, these treatments have potential limitations with regard to their long-term efficacy and improvement in survival. Furthermore, intravenous prostacyclin (epoprostenol) therapy, which is recommended by most experts for patients with New York Heart Association (NYHA) functional class IV, is complicated, uncomfortable for patients, and expensive because of the cumbersome administration system. Considering these circumstances, it is necessary to develop additional novel therapeutic approaches that target the various components of this multifactorial disease. CASE REPORT: In this short review, we present an overview of the current treatment options for pulmonary arterial hypertension and describe a case report with primary pulmonary hypertension. A male patient with NYHA functional class IV and showing no response to calcium channel blockers and prostacyclin exhibited significantly improved exercise tolerance and hemodynamics and long-term survival for more than 2.5 years after receiving an oral combination therapy of a phosphodiesterase type 5 inhibitor (sildenafil), phosphodiesterase type 3 inhibitor (pimobendan), and nicorandil. FUTURE PERSPECTIVE: We also discuss the background and plausible potential mechanisms involved in this case, as well as future perspectives in the treatment of pulmonary arterial hypertension.

Anticoagulants↗
PubMed2006

Urinary liver-type fatty acid binding protein as a useful biomarker in chronic kidney disease.

BACKGROUND: We reported that urinary L-FABP reflected the progression of chronic kidney disease (CKD). This study is aimed to evaluate the clinical significance of urinary liver type fatty acid binding protein (L-FABP) as a biomarker for monitoring CKD. METHODS: Urinary L-FABP was measured using human L-FABP ELISA kit (CMIC.Co., Ltd., Tokyo, Japan). The relations between urinary L-FABP and clinical parameters were evaluated in non-diabetic CKD (n = 48) for a year. In order to evaluate the influence of serum L-FABP derived from liver upon urinary L-FABP, both serum and urinary L-FABP were simultaneously measured in patients with CKD (n = 73). RESULTS: For monitoring CKD, the cut-off value in urinary L-FABP was determined as 17.4 microg/g.cr. by using a receiver operating characteristics (ROC) curve. Renal function deteriorated significantly more in patients with 'high' urinary L-FABP (n = 36) than in those with 'low' L-FABP (n = 12). The decrease in creatinine clearance was accompanied by an increase in urinary L-FABP, but not in urinary protein. Serum L-FABP in patients with CKD was not correlated with urinary L-FABP. CONCLUSION: Urinary excretion of L-FABP increases with the deterioration of renal function. Serum L-FABP did not influence on urinary L-FABP. Urinary L-FABP may be a useful clinical biomarker for monitoring CKD.

Adult↗
PubMed2006

Effects of adrenomedullin on acute ischaemia-induced collateral development and mobilization of bone-marrow-derived cells.

Adrenomedullin exerts not only vasodilatory effects, but also angiogenic effects. In the present study, we investigated the effects of adrenomedullin on collateral formation and circulating bone-marrow-derived cells after acute tissue ischaemia. Bone marrow of 8-10-week-old female C57BL/6J mice was replaced with that from GFP (green fluorescent protein) transgenic mice (GFP mice). At 8 weeks after transplantation, hindlimb ischaemia was induced by resecting the right femoral artery and a plasmid expressing human adrenomedullin (50 mug) was injected into the ischaemic muscle, followed by in vivo electroporation on a weekly basis. Overexpression of adrenomedullin significantly enhanced the blood flow recovery compared with controls (blood flow ratio, 1.0+/-0.2 compared with 0.6+/-0.3 respectively, at week 4; P<0.05) and increased capillary density in the ischaemic leg as determined by anti-CD31 immunostaining of the ischaemic muscle (567+/-40 compared with 338+/-65 capillaries/mm(2) respectively, at week 5; P<0.05). There were more GFP-positive cells in the thigh muscle of the mice injected with adrenomedullin than in that of the control mice (29.6+/-4.5 compared with 16.5+/-3.3 capillaries/mm(2) respectively, at week 5; P<0.05). We repeated the same experiments using LacZ-knock-in mice instead of GFP mice, and obtained similar results. These findings suggest that adrenomedullin may augment ischaemia-induced collateral formation with some effects on circulating bone-marrow-derived cells.

Adrenomedullin↗
PubMed2006

A case of cholesterol embolism confirmed by skin biopsy and successfully treated with statins and steroids.

Although cholesterol embolism syndrome was recognized as a clinicopathologic entity more than 50 years ago, it is attracting growing attention recently. It is a multisystemic disorder in which cholesterol crystals released from atherosclerotic plaques obstruct small arterioles, resulting in local ischemia and end-organ damage. There are no established treatments, and with the limited treatment options available, it is important to make the diagnosis as early as possible. We present the case of a 68-year-old man with cholesterol embolism who had a few fluttering atheromas in the aorta, as demonstrated by transesophageal ultrasonography. The diagnosis was confirmed by skin biopsy, and treatment with statins and steroids proved effective, as renal failure progressively improved. This case emphasizes the importance of early diagnosis and shows the possible therapeutic effects of statins and steroids for patients with this syndrome.

Aged↗
PubMed2006

18F-fluorodeoxyglucose positron emission tomography in a case of retroperitoneal fibrosis.

A patient with recurrent abdominal pain was admitted to our hospital. Computed tomography showed a soft dense mass surrounding the abdominal aorta at the infrarenal level, which was compatible with retroperitoneal fibrosis. (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography showed abnormal uptake of (18)F-FDG into these lesions. Two months after the initiation of corticosteroid therapy, the abnormal uptake of (18)F-FDG had ceased along with a reduction in the fibrous mass surrounding the abdominal aorta.

Abdominal Pain↗
PubMed2006

[Nitric oxide].

Explore the source record for details and available documents.

Adiponectin↗
PubMed2005

Ghrelin improves renal function in mice with ischemic acute renal failure.

Growth hormone and IGF-1 have been suggested to have tissue-protective effects. Ghrelin is a stomach-derived growth hormone secretagogue. The effects of ghrelin on ischemia/reperfusion-induced renal failure in mice were examined. Ischemic acute renal failure was induced by bilateral renal artery clamping for 45 min and reperfusion for 24 h. Ghrelin (100 microg/kg mouse) or vehicle was injected subcutaneously six times before surgery and three times after surgery every 8 h. Twenty-four hours after reperfusion, the right kidney was isolated and perfused. Acetylcholine (ACh)- and adrenomedullin-induced endothelium-dependent vasorelaxation of renal vessels significantly improved in ghrelin-pretreated mice (%Delta renal perfusion pressure by 10(-7) M ACh -63.5 +/- 3.7 versus -41.2 +/- 5.5%; P < 0.05). This change was associated with significant increases of nitric oxide release in the kidneys of ghrelin-treated mice (10(-7) M ACh 35.5 +/- 5.8 versus 16.9 +/- 3.5 fmol/g kidney per min; P < 0.05). Serum concentration of urea nitrogen (53 +/- 7 versus 87 +/- 15 mg/dl; P < 0.05) and renal injury score were significantly lower in the ghrelin group (2.5 +/- 0.8 versus 5.3 +/- 1.5; P < 0.01). Tubular apoptotic index was significantly lower in the ghrelin group (5 +/- 5 versus 28 +/- 4; P < 0.05). Furthermore, the survival rate after the 60-min ischemic period was higher in the ghrelin group (80 versus 20%; P < 0.05). Ghrelin treatment significantly increased the serum level of IGF-1. However, such renal protective effects of ghrelin on ischemia/reperfusion injury were not observed in insulin receptor substrate-2 knockout mice. These results suggest that ghrelin may protect the kidneys from ischemia/reperfusion injury and that this effect is related to an improvement of endothelial function through an IGF-1-mediated pathway.

Acute Kidney Injury↗
PubMed2005

Age-associated aortic stenosis in apolipoprotein E-deficient mice.

OBJECTIVES: The present study was designed to assess aortic valve morphology and function in mice of advanced age. We also evaluated the potential contribution of bone-marrow-derived cells to the pathogenesis of aortic stenosis. BACKGROUND: Age-associated valvular degeneration is characterized by lipid accumulation, collagen deposition, and calcification containing smooth muscle-like cells and osteoblast-like cells. Cellular and molecular factors that mediate these changes remain unknown. METHODS: We extensively examined the aortic valves of senile wild-type and apolipoprotein E (ApoE)-/- mice with echocardiography. The aortic valves were analyzed by immunohistochemistry and electron microscopy. The bone marrow of wild-type and ApoE-/- mice was reconstituted with that of green fluorescent protein (GFP) or beta-galactosidase (LacZ) mice, which expressed GFP or LacZ ubiquitously. RESULTS: Transaortic flow velocity was correlated with age in wild-type and ApoE-/- mice. The aortic valves of old ApoE-/- mice showed sclerosis that resembled the pathology of human aortic stenosis. A significant number of GFP-positive cells (10.7 +/- 4.1%) in the sclerotic valves of ApoE-/- mice expressed alpha-smooth muscle actin, whereas most of the GFP-positive cells were identified as endothelial cells or macrophages in wild-type mice. There were bone-marrow-derived cells that were positive for osteoblast-related proteins near the sites of ectopic calcification. The sclerotic valves displayed frequent apoptotic cell death and chemokine expression. CONCLUSIONS: Senile ApoE-deficient mice display aortic valve sclerosis that is similar to that observed in humans. The sclerotic valves displayed frequent apoptotic cell death and chemokine expression. Smooth muscle-like cells observed in degenerative valves might derive, at least in part, from bone marrow.

Age Factors↗
PubMed2005

Hemodynamic and hormonal responses to a short-term low-intensity resistance exercise with the reduction of muscle blood flow.

We investigated the hemodynamic and hormonal responses to a short-term low-intensity resistance exercise (STLIRE) with the reduction of muscle blood flow. Eleven untrained men performed bilateral leg extension exercise under the reduction of muscle blood flow of the proximal end of both legs pressure-applied by a specially designed belt (a banding pressure of 1.3 times higher than resting systolic blood pressure, 160-180 mmHg), named as Kaatsu. The intensity of STLIRE was 20% of one repetition maximum. The subjects performed 30 repetitions, and after a 20-seconds rest, they performed three sets again until exhaustion. The superficial femoral arterial blood flow and hemodynamic parameters were measured by using the ultrasound and impedance cardiography. Serum concentrations of growth hormone (GH), vascular endothelial growth factor (VEGF), noradrenaline (NE), insulin-like growth factor (IGF)-1, ghrelin, and lactate were also measured. Under the conditions with Kaatsu, the arterial flow was reduced to about 30% of the control. STLIRE with Kaatsu significantly increased GH (0.11+/-0.03 to 8.6+/-1.1 ng/ml, P < 0.01), IGF-1 (210+/-40 to 236+/-56 ng/ml, P < 0.01), and VEGF (41+/-13 to 103+/-38 pg/ml, P < 0.05). The increase in GH was related to neither NE nor lactate, but the increase in VEGF was related to that in lactate (r = 0.57, P < 0.05). Ghrelin did not change during the exercise. The maximal heart rate (HR) and blood pressure (BP) in STLIRE with Kaatsu were higher than that without Kaatsu. Stroke volume (SV) was lower due to the decrease of the venous return by Kaatsu, but, total peripheral resistance (TPR) did not change significantly. These results suggest that STLIRE with Kaatsu significantly stimulates the exercise-induced GH, IGF, and VEGF responses with the reduction of cardiac preload during exercise, which may become a unique method for rehabilitation in patients with cardiovascular diseases.

Adaptation, Physiological↗
PubMed2005

Comparison of various bone marrow fractions in the ability to participate in vascular remodeling after mechanical injury.

In contrast to conventional assumption, recent reports propose the possibility that hematopoietic stem cells (HSCs) may have broader potential to differentiate into various cell types. Here, we tested the pluripotency of HSCs by comparing vascular lesions induced by mechanical injury after bone marrow reconstitution with total bone marrow (TBM) cells, c-Kit+ Sca-1+ Lin- (KSL) cells, or a single HSC cell (Tip-SP CD34-KSL cell, CD34- c-Kit+ Sca-1+ Lin- cell with the strongest dye-efflux activity) harboring green fluorescent protein (GFP). The lesions contained a significant number of GFP-positive cells in the TBM and KSL groups, whereas GFP-positive cells were rarely detected in the HSC group. These results suggest that transdifferentiation of a highly purified HSC seems to be a rare event, if it occurs at all, whereas bone marrow cells including the KSL fraction can give rise to vascular cells that substantially contribute to repair or lesion formation after mechanical injury.

Animals↗
PubMed2005

Highly sensitive near-infrared fluorescent probes for nitric oxide and their application to isolated organs.

Novel near-infrared (NIR) fluorescent probes for nitric oxide (NO) have been designed, synthesized, and evaluated. Their NIR fluorescence was increased in an NO concentration-dependent manner under physiological conditions, and their reaction efficiency with NO was at least 53 times higher than that of a widely used NO probe, DAF-2. They were confirmed to function in isolated intact rat kidneys. Because NIR light can penetrate deeply into tissues, these probes may have potential for in vivo NO imaging.

Animals↗
PubMed2005

Blockade of endogenous cytokines mitigates neointimal formation in obese Zucker rats.

BACKGROUND: It is well known that diabetes mellitus is a major risk factor for vascular diseases such as atherosclerosis and restenosis after angioplasty. It has become clear that advanced glycation end products (AGE) and their receptor (RAGE) are implicated in vascular diseases, especially in diabetes mellitus. Nevertheless, the mechanisms by which diabetes mellitus is often associated with vascular diseases remain unclear. METHODS AND RESULTS: To study the role of endogenous cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 in the development of vascular diseases and in the expression of RAGE, we used semapimod, a pharmacological inhibitor of cytokine production, and examined its effect on neointimal formation in the femoral artery of obese Zucker (OZ) rats. We also used an adenovirus construct expressing a dominant negative mutant of the receptor for TNF-alpha (AdTNFRDeltaC) to block the action of endogenous TNF-alpha. Semapimod significantly suppressed neointimal formation and RAGE expression in OZ rats compared with untreated OZ rats. This inhibitory effect of semapimod on neointimal formation was overcome by infection of an adenovirus expressing RAGE into the femoral artery of OZ rats. Furthermore, AdTNFRDeltaC infection significantly suppressed neointimal formation and RAGE expression in the femoral artery of OZ rats. CONCLUSIONS: These results suggest that endogenous cytokines, especially TNF-alpha, were implicated in neointimal formation in OZ rats and that RAGE was a mediator of the effect of these cytokines on neointimal formation.

Adenoviridae↗