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Biomedical subjects

H Yasui

Publications and source records attributed to H Yasui.

At least 73 records · Page 4Linked to original sources

Successful implantation of a bipolar epicardial lead and an autocapture pacemaker in a low-body-weight infant with congenital atrioventricular block: report of a case.

A permanent pacemaker system was successfully implanted into a low-body-weight infant with congenital atrioventricular (AV) block, using a bipolar epicardial CapSure Epi lead and an autocaptured Pacesetter Solus-micro VVIR pacemaker. The calculated life span of the pacemaker generator is 5 years with a heart rate of 120/min and an output of 1.2 V (0.31 ms), and fortunately, its threshold was autocaptured. Thus, we can conclude that the combination of a steroid-eluted bipolar epicardial lead and the smallest possible autocaptured pacemaker generator is most suitable for a neonate or young infant.

Cardiac Pacing, Artificial↗

Coronary artery bypass grafting on the beating heart evaluated with integrated backscatter.

BACKGROUND: In beating heart coronary artery bypass grafting (CABG) the effect of ischemic insult during coronary occlusion could not be evaluated immediately. Using transesophageal echocardiography, myocardial performance can be evaluated with analysis of integrated backscatter. METHODS: In 15 beating heart CABGs, cyclic variation (CV) of integrated backscatter of the anterior wall before, during, and after the left internal thoracic artery to left anterior descending (LAD) branch anastomosis was measured with transesophageal echocardiography. The patients were divided into two groups according to collateral vessels status (good collateral group n = 6, poor collateral group n = 9). RESULTS: In all patients, CV increased significantly after revascularization (8.56+/-2.50 to 11.47+/-3.32 dB, p < 0.0001). During LAD occlusion, significant decrease in CV was found in patients who had poor collateral arteries. At 15 minutes of LAD occlusion, CV decreased from the preocclusion value of 7.51+/-2.21 to 3.23+/-4.03 dB (p < 0.01). CONCLUSIONS: Measurement of CV can detect the ischemic insult during coronary occlusion and the effect of revascularization in beating heart CABG.

Aged↗

Metallokinetic analysis of disposition of vanadyl complexes as insulin-mimetics in rats using BCM-ESR method.

Among vanadium's wide variety of biological functions, its insulin-mimetic effect is the most interesting and important. Recently, the vanadyl ion (+4 oxidation state of vanadium) and its complexes have been shown to normalize the blood glucose levels of streptozotocin-induced diabetic rats (STZ-rats). During our investigations to find more effective and less toxic vanadyl complexes, the vanadyl-methylpicolinate complex (VO-MPA) was found to exhibit higher insulin-mimetic activity and less toxicity than other complexes, as evaluated by both in vitro and in vivo experiments. Electron spin resonance (ESR) is capable of measuring the paramagnetic species in biological samples. We have developed the in vivo blood circulation monitoring-electron spin resonance (BCM-ESR) method to analyze the ESR signals due to stable organic radicals in real time. In the present investigation, we have applied this method to elucidate the relationship between the blood glucose normalizing effect of VO-MPA and the global disposition of paramagnetic vanadyl species. This paper describes the results of vanadyl species in the circulating blood of rats following intravenous administration of vanadyl compounds. ESR spectra due to the presence of vanadyl species were obtained in the circulating blood, and their pharmacokinetic parameters were estimated using compartment models. The results indicate that vanadyl species are distributed considerably to the peripheral tissues, as estimated by BCM-ESR, and eliminated from the body through the urine, as estimated by ESR at 77 K. The exposure of vanadyl species in the blood was found to be enhanced by VO-MPA treatment. Given these results, we concluded that the pharmacokinetic character of vanadyl species is closely related with the structure and antidiabetic activity of the vanadyl compounds.

Animals↗

Effects of static magnetic field on dissolved oxygen levels in aqueous solutions containing copper(II), iron(II), and heme iron(III) complexes.

Trace metal ions like copper and iron play important roles such as binding, transport, and storage of molecular dioxygen in a wide variety of living systems. The effects of static magnetic fields on the dissolved oxygen (DO) levels in aqueous solutions containing copper(II), iron(II), and their bioligand complexes were investigated. The DO levels in aqueous solutions containing the stable copper(II) complexes such as Cu(II)-Arg, His, GGH and BSA systems increased when the applied magnetic field increased. However, the magnetic field-dependent changes of DO levels were not observed by the unstable Cu(II) complexes such as Cu(II)-Lys, Gly, Gly-His and Hb systems. Especially, DO levels in aqueous solutions containing Cu(II)-His or BSA complexes increased 1.1-fold to those of the control levels at 200 mT of the applied magnetic field. In contrast, DO levels in aqueous solutions containing iron(II) decreased significantly when the magnetic field increased, which in turn promoted the Fe(II)-induced lipidperoxidation in liposomes. DO levels in aqueous solutions containing Fe(II)-His complex decreased 0.9-fold to those of the control levels at 200 mT of the magnetic field for 30 min. While, the magnetic field-dependent changes of DO levels increased significantly in aqueous solutions containing heme iron(III)-complexes, suggesting that heme iron(III) is reduced to heme iron(II) under exposure of the magnetic field and thus the incorporation of molecular dioxygen in aqueous solutions is enhanced. These results indicate that the effect of the magnetic fields on DO levels in aqueous solutions must be discussed in terms of a concept: formation of intermediate complexes consisting of molecular dioxygen-copper or iron and bioligands under physiological conditions and the following enhancement of incorporation of molecular dioxygen by the complexes, that in turn activate the molecular dioxygen.

Journal Article↗

Distribution of Tsc1 protein detected by immunohistochemistry in various normal rat tissues and the renal carcinomas of Eker rat: detection of limited colocalization with Tsc1 and Tsc2 gene products in vivo.

We and others previously demonstrated that hereditary mutation and a subsequent second hit in the rat homolog of tuberous sclerosis gene (Tsc2) are responsible for Eker renal carcinomas (RC). In humans, alteration in the TSC2 gene is known to cause the tuberous sclerosis complex (TSC) that results in hamartomatous lesions in multiple organs, but the function of TSC2 is not fully understood. In recent years, a second gene (TSC1) responsible for human TSC has been cloned, and binding between TSC1 and TSC2 proteins was reported. In this study, to clarify associations between Tsc proteins in vivo, the expression of Tsc1 protein was detected by immunohistochemistry, and compared with Tsc2 expression. Tsc1 protein was expressed in the nervous system and in many endocrine tissues, including pancreatic islets, the parathyroids, testis, and ovary. Tsc1 was also detected in the many epithelial tissues of organs, such as kidney, uterus, small and large intestine, and liver. Our results indicate overlapping, but not identical, organ distributions of Tsc1 and Tsc2 proteins. At the intracellular distribution, double fluorescent immunolabeling allowed the determination that only a partial portion of Tsc1 signals overlapped with Tsc2 in some organs. These results suggest the existence of co-localizing and independent forms of Tsc proteins in endogenous expressions. Additionally, relatively high expression of Tsc1 protein was detected in RC in the Tsc2 mutant (Eker) rat.

Animals↗

Galpha(12) and galpha(13) inhibit Ca(2+)-dependent exocytosis through Rho/Rho-associated kinase-dependent pathway.

The release of neurotransmitters is known to be regulated by activation of heterotrimeric G protein-coupled receptors, although precise mechanisms have not yet been elucidated. To assess the role of the G(12) family of heterotrimeric G proteins in the regulation of neurotransmitter release, we established PC12 cell lines that expressed constitutively active Galpha(12) or Galpha(13) using an isopropyl-beta-D-thiogalactoside-inducible expression system. In the cells, expression of constitutively active Galpha(12) or Galpha(13) inhibited the high K(+)-evoked [(3)H]dopamine release without any effect on the high K(+)-induced increase in intracellular Ca(2+) concentration. A Ca(2+) ionophore ionomycin-induced [(3)H]dopamine release was also inhibited by the expression of active Galpha(12) or Galpha(13). These inhibitory effects of Galpha(12) and Galpha(13) on [(3)H]dopamine release were mimicked by the expression of constitutively active RhoA. In addition, Y-27632, and inhibitor of Rho-associated kinase, a downstream Rho effector, completely abolished the inhibition of [(3)H]dopamine release by Galpha(12), Galpha(13), and RhoA. These results indicate that Ca(2+)-dependent exocytosis is regulated by Galpha(12) and Galpha(13) through a Rho/Rho-associated kinase-dependent pathway.

Animals↗

CT scores of emphysema and oxygen desaturation during low-grade exercise in patients with emphysema.

PURPOSE: We evaluated the usefulness of CT for assessing oxygen desaturation during walking in patients with emphysema. MATERIAL AND METHODS: The study comprised 32 patients with emphysema (mean age 67+/-6 years). Serial CT images of 5 mm were obtained from the apex to the basal regions of the lung during deep inspiration. The severity of emphysema was scored by four physicians according to a visual method. A six-minute walking test and oxygen desaturation (pSO2) measurements were performed. RESULTS AND CONCLUSION: The mean CT score of the four observers was significantly correlated with the nadir pSO2 and deltapSO2, but did not correlate with the total distance walked. These results suggest that CT may be used for the assessment of oxygen desaturation during low-grade exercise in patients with emphysema.

Aged↗

Small GTPase RhoG is a key regulator for neurite outgrowth in PC12 cells.

The Rho family of small GTPases has been implicated in cytoskeletal reorganization and subsequent morphological changes in various cell types. Among them, Rac and Cdc42 have been shown to be involved in neurite outgrowth in neuronal cells. In this study, we examined the role of RhoG, another member of Rho family GTPases, in nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells. Expression of wild-type RhoG in PC12 cells induced neurite outgrowth in the absence of NGF, and the morphology of wild-type RhoG-expressing cells was similar to that of NGF-differentiated cells. Constitutively active RhoG-transfected cells extended short neurites but developed large lamellipodial or filopodial structures at the tips of neurites. RhoG-induced neurite outgrowth was inhibited by coexpression with dominant-negative Rac1 or Cdc42. In addition, expression of constitutively active RhoG elevated endogenous Rac1 and Cdc42 activities. We also found that the NGF-induced neurite outgrowth was enhanced by expression of wild-type RhoG whereas expression of dominant-negative RhoG suppressed the neurite outgrowth. Furthermore, constitutively active Ras-induced neurite outgrowth was also suppressed by dominant-negative RhoG. Taken together, these results suggest that RhoG is a key regulator in NGF-induced neurite outgrowth, acting downstream of Ras and upstream of Rac1 and Cdc42 in PC12 cells.

Animals↗

Pulsatile flow enhances endothelium-derived nitric oxide release in the peripheral vasculature.

The effects of pulsatility in blood flow on endothelium-derived nitric oxide (EDNO) release in the peripheral vasculature were investigated. The basal and flow-stimulated EDNO release were compared between pulsatile and nonpulsatile systemic flows before and after the administration of NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA). Peripheral vascular resistance (PVR) was significantly lower in pulsatile flow than in nonpulsatile flow, but this difference disappeared after L-NMMA. The percent increase in PVR by L-NMMA was significantly larger in pulsatile flow. In reactive hyperemia in the hindlimb, the peak flow did not differ; however, both the repayment flow and the duration were significantly larger in pulsatile flow. Percent changes of these parameters by L-NMMA were significantly larger in pulsatile flow. These data indicated that pulsatility significantly enhances the basal and flow-stimulated EDNO release in the peripheral vasculature under in vivo conditions. We also studied the involvement of the Ca(2+)-dependent and Ca(2+)-independent pathways in flow-induced vasodilation using calmodulin inhibitor calmidazolium and tyrosine kinase inhibitor erbstatin A. PVR was significantly elevated by erbstatin A but not by calmidazolium, suggesting that flow-induced vasodilation was largely caused by tyrosine kinase inhibitor-sensitive activation of NO synthase.

Angiotensin II↗

Effects of nonpulsatile left heart bypass on renal sympathetic nerve activity in rabbits.

To determine the effects of nonpulsatile left heart bypass (LHB) on sympathetic nerve activity the renal sympathetic nerve activity (RSNA) was directly measured in rabbits. In anaesthetized rabbits (n=6), LHB was instituted with a centrifugal pump. Before and during LHB, heart rate (HR), arterial pressure (AP), central venous pressure (CVP), left atrial pressure (LAP) and spike counts of RSNA were measured. After bilateral vagotomy (section of the afferent inputs of the cardiac reflex arc) the same parameters were measured before and during LHB. Data were obtained at the same level of mean AP before and during LHB. Mean AP and CVP were not changed by LHB before and after vagotomy. LAP was significantly decreased by LHB before and after vagotomy. RSNA and HR were not significantly changed by LHB before and after vagotomy. Our results clarify the complex baroreflex control during nonpulsatile LHB and indicate that RSNA is not altered by LHB.

Action Potentials↗

Decreased protein C activation is associated with abnormal collagen turnover in the intraalveolar space of patients with interstitial lung disease.

Activation of the coagulation system in the alveolar space plays an important role in the pathogenesis of interstitial lung disease (ILD) and pulmonary fibrosis. The protein C (PC) pathway is the main modulator of coagulation activation. This study evaluated whether dysfunction of the PC pathway is associated with increased collagen synthesis in the intraalveolar space of patients with ILD. This study comprised 22 patients with ILD; of these, five had idiopathic pulmonary fibrosis (IPF), nine had sarcoidosis-associated ILD, and eight had collagen vascular disease-associated ILD (CVD-ILD). Thrombin-antithrombin complex (TAT) was measured as a marker of coagulation activation. As markers of the PC pathway activity, the concentration of activated PC-PC inhibitor (APC-PCI) complex and the APC-PCI/PC ratio were measured and, as a marker of collagen synthesis, the concentration of aminoterminal propeptide of type III procollagen (PIIINP) was measured in bronchoalveolar lavage fluid (BALF) of ILD patients. TAT was significantly increased in BALF from ILD patients as compared to control subjects. The concentrations of PIIINP were significantly elevated in patients with ILD as compared to healthy subjects. In contrast, the concentration of APC-PCI and the values of APC-PCI/PC ratio were significantly decreased in BALF from patients with ILD. BALF concentration of PIIINP was significantly and inversely correlated with the concentration of APC-PCI and with the APC-PCI/PC ratio. These findings suggest that dysfunction of the protein C pathway may have important physiopathologic implications in the development of pulmonary fibrosis in ILD.

Biomarkers↗

Role of nitric oxide in airway remodelling.

Airway remodelling, which is manifested by thickening of bronchial wall, is an important causative factor of bronchial hyper-responsiveness in asthma. The pathophysiological mechanism of airway remodelling is not clear. In the present study we evaluated the relationship between nitric oxide (NO) generation and airway wall thickening in patients with chronic asthma. As a marker of NO production, the levels of nitrite/nitrate were measured in induced sputum, and bronchial wall thickening was measured by high-resolution computed tomography. Sputum concentrations of nitrite/nitrate were significantly increased in asthmatic patients compared with controls. The ratio of airway wall thickness to lumen diameter was significantly correlated with the sputum concentration of nitrite/nitrate. Although statistical correlation does not prove causation, this finding suggests that NO may play a key role in the pathogenesis of airway remodelling.

Asthma↗

Hyperreactivity of pseudoxanthoma elasticum-affected dermis to vitamin D3.

A 68-year-old woman with pseudoxanthoma elasticum (PXE) was treated with oral vitamin D(3). After 2 weeks, new papules developed on the pre-existing plaques. Biopsy specimens of a fresh papule showed more abundant calcium deposition than before therapy. Electron microscopy revealed electron-lucent areas, which suggested unusual mineralization. From these findings, we propose that in patients with PXE, certain cutaneous tissues are highly sensitive to vitamin D(3), resulting in microdeposition of calcium salts.

Aged↗

[Aortic valve replacement with stentless bioprosthesis: operative methods and pitfalls].

Operative methods and pitfalls of aortic valve replacement using either Toronto SPV and Freestyle prosthesis were described. Precise transverse aortotomy, straight inflow-suture line, and outflow suture not obstructing coronary orifices are the points for the standard procedure. For bicuspid aortic valves, care should be taken for the anomaly of coronary orifices. Our experience with 24 consecutive cases indicated that oversizing of the prosthesis was possible in stentless bioprosthesis.

Aortic Valve↗

Effects of intra-aortic ballon pumping on renal sympathetic nerve activity and renal circulation in dogs.

BACKGROUND: Little is known on how intra-aortic balloon pumping (IABP) affects neural circulatory regulation, even though many studies have been done to clarify the effects of IABP on hemodynamics. Although IABP is used clinically in patients with severe heart failure, whose sympathetic nerve activity is increased, there are no previous reports that demonstrate the effects of IABP on neural regulation in heart failure. The aim of this study is to determine the effects of IABP on neural regulation of renal circulation with both normal and failing heart condition in dogs. METHODS: We directly measured renal sympathetic nerve activity and hemodynamic parameters (heart rate, central venous pressure, distal aortic pressure, proximal aortic pressure, left ventricular pressure, renal sympathetic nerve activity, ascending aortic flow, and renal arterial flow) before and during IABP driving in both normal and failing heart condition in dogs (n=7). Acute heart failure models were made by coronary ligation. RESULTS: IABP driving inhibits renal sympathetic nerve activity and improves renal circulation in failing heart condition, while these phenomena do not occur in normal heart condition. CONCLUSIONS: These findings suggest that IABP may show its full effect on renal circulation via neural regulation especially in failing heart condition.

Animals↗

Roles of CD4+ and CD8+ T cells in discordant skin xenograft rejection.

An essential role of murine CD4+ T cells in immune reactivity and skin graft rejection in discordant xenogeneic combinations have been reported. Our study was conducted to further clarify the roles of CD4+ and CD8+ T cells in discordant skin xenograft rejection, by using CD4 and CD8 knockout [C57BL/6 Cr Slc (B6; H-2b) background] mice. When human skins were grafted on CD8 knockout mice or B6 mice, both hosts rejected human skin grafts within 12 days after grafting. By contrast, survival of human skin grafts was significantly prolonged in CD4 knockout mice (mean survival times=19.3+/-(SD) 1.6 days; median 19 days). Fully allogeneic C3H/He Slc (H-2k) skin grafts were rejected within 14 days in CD4 knockout mice, suggesting that non-CD4+ T cells in CD4 knockout mice were immunocompetent for allograft rejection. In spleens of these recipient mice, CD8+ T cells seemed to be activated 10 days after human skin grafting. Immunohistological analysis revealed the infiltration of CD8+ T cells at the site of transplanted human skin on CD4 knockout mice. To further examine the role of CD8+ T cells in CD4 knockout mice, human skin grafting was performed on day 0 followed by administration of anti-CD8 monoclonal antibody on days 0, 5, and 14. The administration of anti-CD8 monoclonal antibodies caused the significant prolongation of human skin graft survival. These results indicate the following two conclusions: (1) CD4+ T cells have an essential role in rejecting discordant human skin xenografts rapidly and (2) however, CD8+ T cells also are capable of rejecting discordant human skin xenografts.

Animals↗

Involvement of singlet oxygen in cytochrome P450-dependent substrate oxidations.

Cytochrome P450 (P450)-dependent p-hydroxylation of aniline and o-deethylation of 7-ethoxycoumarin were examined in rat liver microsomes in the presence of radical scavengers. The addition of beta-carotene, a quencher of singlet oxygen species ((1)O(2)), suppressed the aniline hydroxylation, while the addition of sodium azide (NaN(3)) ((1)O(2) quencher) enhanced the reaction. No other reactive oxygen scavengers or chelating agents such as superoxide dismutase, catalase, dimethylsulfoxide, or deferoxamine altered the reaction. In contrast, the microsomal o-deethylation of 7-ethoxycoumarin was suppressed by the addition of NaN(3). (1)O(2) was detectable during the reaction of microsomes and NADPH by ESR spin-trapping when 2,2,6,6-tetramethyl-4-piperidone (TMPD) was used as a spin trap, and the (1)O(2) was quenched by the additions of beta-carotene, NaN(3), aniline, and 7-ethoxycoumarin. The enhancement effect of NaN(3) in the hydroxylation of aniline appeared to be due to the conformational change of P450 protein, which in turn enhances the binding of aniline to P450 in terms of the spectral dissociation constant (K(s)). In contrast, (1)O(2) appeared to be active in the o-deethylation of 7-ethoxycoumarin. On the basis of the results, the involvement of (1)O(2) in P450-dependent substrate oxygenations is proposed.

7-Alkoxycoumarin O-Dealkylase↗

Enzymatic activation of oleuropein: a protein crosslinker used as a chemical defense in the privet tree.

Leaves of the privet tree, Ligustrum obtusifolium, contain a large amount of oleuropein, a phenolic secoiridoid glycoside, which is stably kept in a compartment separate from activating enzymes. When the leaf tissue is destroyed by herbivores, enzymes localized in organelles start to activate oleuropein into a very strong protein denaturant that has protein-crosslinking and lysine-decreasing activities. These activities are stronger than ever reported from plant systems and have adverse effects against herbivores by decreasing the nutritive value of dietary protein completely. We report here that strong oleuropein-specific beta-glucosidase in organelles activates oleuropein by converting the secoiridoid glucoside moiety of oleuropein into a glutaraldehyde-like structure, which is also an alpha,beta-unsaturated aldehyde. Oleuropein activated by beta-glucosidase had very strong protein-denaturing, protein-crosslinking, and lysine-alkylating activities that are very similar to, but stronger than, those of glutaraldehyde. Aucubin, another iridoid glycoside, had similar activities after beta-glucosidase treatment. We also detected polyphenol oxidase activity in organelles that activate the dihydroxyphenolic moiety to have protein-crosslinking activities. These data suggest that the privet tree has developed an effective defense mechanism with oleuropein, a unique multivalent alkylator ideal as a protein-crosslinker. Our results that iridoid glycosides are precursors of alkylators may elucidate the chemical bases that underlie various bioactivities and ecological roles of iridoid glycosides.

Journal Article↗