Biomedical subjects

M Nishiura

Publications and source records attributed to M Nishiura.

At least 19 recordsLinked to original sources

PubMed2001

Pause and rotation of F(1)-ATPase during catalysis.

F(1)-ATPase is a rotary motor enzyme in which a single ATP molecule drives a 120 degrees rotation of the central gamma subunit relative to the surrounding alpha(3)beta(3) ring. Here, we show that the rotation of F(1)-ATPase spontaneously lapses into long (approximately 30 s) pauses during steady-state catalysis. The effects of ADP-Mg and mutation on the pauses, as well as kinetic comparison with bulk-phase catalysis, strongly indicate that the paused enzyme corresponds to the inactive state of F(1)-ATPase previously known as the ADP-Mg inhibited form in which F(1)-ATPase fails to release ADP-Mg from catalytic sites. The pausing position of the gamma subunit deviates from the ATP-waiting position and is most likely the recently found intermediate 90 degrees position.

Adenosine Diphosphate↗

PubMed2001

Plasma perturbation induced by laser photodetachment.

The plasma dynamics arising from laser photodetachment is discussed herein theoretically and experimentally. The hybrid fluid-kinetic model, where the positive ions and electrons are treated by the fluid theory and the negative ions are treated within the ballistic approximation, is extended and applied to the analysis of densities perturbed by laser photodetachment. The agreement between the theory and measured data confirms the validity of the considered plasma dynamics model. This model, including the positive ion perturbation, shows a good agreement with the time evolution and the spatial distribution of perturbed electron densities which are measured by a Langmuir probe inside and outside the laser beam. From the overshoot in the time evolution of perturbed electron current in the center of the laser beam, the positive ion temperature was found to be in the range 0.1-0.25 eV, while the electron temperature changes from 0.3 to 3.2 eV.

Journal Article↗

PubMed2000

A novel alpha-helix-liked metallohelicate series and their structural adjustments for the isomorphous substitution.

A novel metallohelical motif is well designed and synthesized by mimicking the alpha-helical fold structure of protein. The 1D helical structures of [Cd(CH2(COO)2)(SC(NH2)2)2]n (I) and [Zn(CH2(COO)2) (SC(NH2)2)2]n (II) are primarily induced and stabilized by the multiple long-range intrahelix hydrogen bonds. Malonate dianion acts as a bidentate ligand coordinated with metal ions to form the backbone of the helix, and thiourea molecules that bend into the helical turn are involved in the intrahelix hydrogen-bond system. The metal ion occupations in the helix of I and II can be freely substituted by simply controlling the initial ratio of those two metal ions. Single crystals of three mixed metal ion complexes of [Cd0.77Zn0.23(CH2(COO)2)(SC(NH2)2)2]n (III), [Cd0.50Zn0.50(CH2(COO)2)(SC(NH2)2)2]n (IV), and [Cd0.21Zn0.79(CH2(COO)2)(SC(NH2)2)2]n (V) were synthesized from systems with an initial Cd/Zn mole ratio of 1:1 for III, 1:2 for IV, and 1:8 for V. They are isomorphous as confirmed by X-ray characterization. When the metal ion is substituted, the multiple intrahelix hydrogen interaction motifs of the coordination polymer structure are self-adjusted to sustain their 1D helical motifs.

Journal Article↗

PubMed1999

Presence of phospholipid-neutral lipid complex structures in atherosclerotic lesions as detected by a novel monoclonal antibody.

A novel monoclonal antibody (ASH1a/256C) that recognizes atherosclerotic lesions in human and Watanabe heritable hyperlipidemic (WHHL) rabbit aortae is described. When (123)I-labeled ASH1a/256C antibody is injected intravenously into WHHL rabbits, it associates specifically with fatty streaks on the aorta. The antigen recognized by the antibody is lipid, based on extraction with chloroform and methanol from WHHL rabbit tissues. The antigen, purified by high performance liquid chromatography, was shown to be phosphatidylcholine (PC), which contains unsaturated fatty acyl groups based on analyses utilizing (1)H and (13)C nuclear magnetic resonance, Fourier transfer-infrared spectrum, and mass spectrometry. The antibody did not react with other classes of phospholipids or neutral lipids when tested using an enzyme-linked immunosorbent assay. When PC was mixed with either cholesterol, cholesteryl ester, or triacylglycerol, however, the reactivity of the antibody to PC increased up to 8-fold. Homogenates of aorta tissue obtained from normal and WHHL rabbits were fractionated using sucrose density gradient ultracentrifugation in which neutral lipid droplets, cellular membranes, and proteins are separated. The phospholipid content in cellular membrane fractions from WHHL rabbits was twice as high as that of normal rabbits, and there was an enormous difference in the antigenic activity in these fractions. The content of cholesterol in the cellular membrane fraction of WHHL rabbits was approximately 50 times higher than that of normal rabbits. Addition of neutral lipids to the cellular membrane fraction of normal rabbit markedly increased the antigenic activity. Atheromatous lesions in thickened WHHL rabbit aortic intima that were rich in lipid droplets were stained positively with ASH1a/256C immunohistochemically. These results strongly suggest that PC-neutral lipid complex domains are formed in atherosclerotic lesions.

Animals↗

PubMed1999

[Measurement of left ventricular filling by automated contour tracking method in echocardiography: comparison with radionuclide ventriculography].

Recent development of an automated contour tracking (ACT) method using the energy minimization principle provides automated edge detection and tracking of the endocardial boundary of the left ventricle, without tracing a region of interest. This study determined whether left ventricular filling indexes obtained from the ACT method provide a reliable estimate of left ventricular diastolic filling. Fourteen patients were examined by the ACT method and equilibrium radionuclide ventriculography. The volume-time wave form for ACT measurements was obtained from the 4-chamber views. Peak filling rate and time to peak filling rate measured by the ACT method were compared with those determined by radionuclide ventriculography. Peak filling rate and time to peak filling rate by the ACT method were closely correlated with those determined by radionuclide ventriculography (peak filling rate: r = 0.88, y = 0.71x + 0.36, SEE = 0.54 ml/end-diastolic volume/sec, time to peak filling rate: r = 0.89, y = 0.72x + 30.0, SEE = 0.02 msec, respectively) The ACT method is useful for the assessment of left ventricular diastolic filling.

Aged↗

PubMed1998

Enhancement of in vivo binding of [123I]beta-CIT by MK-801 in rat brain.

The effects of MK-801, a noncompetitive NMDA receptor antagonist, on in vivo and in vitro binding of radioactive iodine ([123I] or [125I]) labeled beta-CIT [RTI-55, 3beta-(4-iodophenyl)tropane-2beta-carboxylic acid methyl ester] were investigated in rat brain. In the in vitro binding study, 10 pM of [125I]beta-CIT was incubated with either 0.03 microM or 3 microM of MK-801 at 24 degrees C for 60 min. In vitro, no alterations in [125I]beta-CIT binding in any region of rat brain slices were detected after addition of MK-801. In the in vivo binding study, [123I]beta-CIT was intravenously injected into rats 30 min after intraperitoneal injection of 0.03-1 mg/kg of MK-801. The in vivo [123I]beta-CIT binding in the striatum, frontal cortex, occipital cortex, hypothalamus, and thalamus was significantly increased by pretreatment with 1 mg/kg of MK-801. Kinetic analysis using the cerebellum as a reference region revealed that the increases in in vivo [123I]beta-CIT binding induced by MK-801 were mainly due to increases in both input rate constant k3 and output rate constant k4. The results of this study indicate that the glutamatergic system, including NMDA receptor, plays an important role in regulating neurotransmission in the dopaminergic or serotonergic systems in intact brain.

Animals↗

PubMed1998

Protective effect of FK409, a spontaneous nitric oxide releaser, on ischemic acute renal failure in rats.

The contribution of nitric oxide (NO) to ischemic acute renal failure (ARF) is controversial. In the present study, we investigated the effect of FK409 ((+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexanamide ), a spontaneous NO donor, on ischemic ARF in rats. Ischemic ARF was induced by occlusion of the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. Renal functional parameters such as blood urea nitrogen, plasma creatinine, creatinine clearance, urine flow, urinary osmolality and fractional excretion of sodium were measured to test the effectiveness of the drug. Renal function in untreated ARF rats markedly decreased at 24 hr after reperfusion and thereafter tended to recover gradually. Intravenous bolus injection of FK409 at a dose of 1 mg/kg before the occlusion markedly attenuated the ischemic ARF-induced decreases in renal function, to the same extent as verapamil (1 mg/kg i.v.). The protective effect of FK409, at a dose of 3 mg/kg, was much more potent than that of the lower dose. Histopathological examination of the kidney of untreated ARF rats revealed severe renal damages, such as tubular necrosis, proteinaceous casts in tubuli and medullary congestion. These renal damages were significantly attenuated by treatment with FK409, at each dose given and this attenuation exceeded that seen with verapamil treatment. FK 409 administration led to a dose-dependent increase in NO metabolites concentration in renal venous blood immediately after the reperfusion. These findings suggest that NO has a crucial role in the pathogenesis of ischemic ARF. Spontaneous NO donors may be clinically effective in cases of ischemic ARF.

Acute Kidney Injury↗

PubMed1997

Renal hemodynamic and excretory responses in anesthetized rats to FK409, a novel nitric oxide donor.

Renal hemodynamic and excretory responses to (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (FK409), a novel nitric oxide (NO) donor, were examined using anesthetized rats. When FK409 was infused into the renal artery of normal rats at 10 micrograms/kg per min, a moderate renal vasodilating effect was observed with a decrease in mean arterial blood pressure. Urine flow, urinary excretion of sodium and fractional excretion of sodium significantly increased by about 85%, 110% and 75%, respectively, compared with each control value. Simultaneously, urinary excretion of NO metabolites (UNOxV) was markedly increased with the administration of FK409. In hypertensive rats treated with NG-nitro-L-arginine (NOARG), the NO synthase inhibitor, FK409 produced a potent renal vasodilation, although the hypotensive effect of the agent was comparable to that seen in normal rats. In addition, glomerular filtration rate was significantly elevated by the agent. There were marked increases in the excretory responses, i.e., levels of urine flow, urinary excretion of sodium and fractional excretion of sodium were increased to about 3-, 6- and 5-fold of each control value, respectively. The extent of increment of UNOxV was similar to that seen in normal rats. These results clearly indicate that FK409 causes renal vasodilation and diuresis, via NO formation. Renal hemodynamic and excretory responses to the agent are sensitive in NO-depleted conditions. FK409 and related compounds may be useful for the treatment of renal diseases, in cases where the basal NO formation is impaired.

Anesthesia↗

PubMed1997

Enhancement of [123I]beta-CIT binding in the striatum with clomipramine: is there a serotonin-dopamine interaction?

Many reports support the concept of serotonergic-dopaminergic interaction in the brain. However, at present, there are few methods to study this relationship in vivo. The purpose of this study was to investigate the effect of serotonin (5-HT) uptake inhibitor, clomipramine, on a dopamine (DA) transporter ligand, [123I]beta-CIT (RTI-55), in rat brain. Dose-dependent changes in [123I]beta-CIT specific binding induced by clomipramine were studied in the striatum (rich in DA transporter) and the hypothalamus (rich in 5-HT transporter). The changes in the time-activity curves of [123I]beta-CIT specific binding after clomipramine injection were also examined in these two regions. Using the cerebellum as the reference region, k3 and k4 values with and without clomipramine administration were estimated by a two-compartment kinetic analysis. Clomipramine inhibited [123I]beta-CIT specific binding in the hypothalamus, but enhanced its specific binding in the striatum in a dose-dependent manner. Kinetic analysis showed that k3 in the striatum was increased by 55%. In conclusion, enhancement of [123I]beta-CIT binding in the striatum after clomipramine administration indicated the possibility of 5-HT-DA interaction.

Animals↗

PubMed1997

Echocardiographic estimation of left ventricular cavity area with a newly developed automated contour tracking method.

Development of an automated contour tracking method provides detection and tracking of the endocardial boundary using the energy minimization method without tracing a region of interest. The purpose of this study was to compare the automated contour tracking method and manually drawn methods for the measurement of left ventricular cavity areas and fractional area change. Apical four-chamber view was visualized and recorded for off-line analysis in 11 patients by means of two-dimensional echocardiography. The automated contour tracking method automatically traces the endocardial border from the recorded images and calculates left ventricular cavity areas (end-diastole and end-systole) and fractional area change. In the same images selected as end-diastole and end-systole in the automated contour tracking method, left ventricular endocardial border was manually traced to calculate left ventricular cavity areas and fractional area change. Both methods were compared by linear regression analysis for the measurement of cavity areas and fractional area change. Left ventricular areas measured by the automated contour tracking method showed an excellent correlation with those by the manual method (end-diastole: r = 0.99, y = 0.83x + 2.6; standard error of the estimate = 1.5 cm2; end-systole: r = 0.99, y = 0.96x -0.8, standard error of the estimate = 1.2 cm2). The mean differences between the automated contour tracking and manual methods were -3.1 +/- 5.1 cm2 and -1.6 +/- 2.4 cm2 at end-diastole and end-systole, respectively. Fractional area change determined by the automated contour tracking method correlated well with that by the manual method (r = 0.95, y = 1.17x -6.5, standard error of the estimate = 3.4%). The mean difference between the automated contour tracking and manual methods was -0.8% +/- 7.1%. In conclusion, a newly developed automated contour tracking method correlates highly with the manual method for the estimation of left ventricular cavity areas and fractional area change in high-quality images. This suggests that this new technique may be useful in the automated quantitation of left ventricular function in patients with high-quality images with no dropout and no intercavity artifact or structure.

Echocardiography↗

PubMed1997

[Evaluation of left ventricular ejection fraction using an automated contour tracking method: comparison with equilibrium radionuclide angiography].

A recently developed contour tracking method provides automated edge detection of left ventricular endocardium without a region of interest. The accuracy of this automated contour tracking (ACT) method in the evaluation of left ventricular ejection fraction was assessed in 20 patients (16 males and 4 females, mean age 58 years) using both the ACT method and equilibrium radionuclide angiography. Ejection fractions measured by the ACT method correlated well with those measured by equilibrium radionuclide angiography (y = 0.8x + 11.9, r = 0.91, SEE = 4.0%, p < 0.01). The ACT method provides an accurate estimate of left ventricular ejection fraction.

Echocardiography↗

PubMed1996

Differential kinetics of [123I]beta-CIT binding to dopamine and serotonin transporters.

Iodine-123-labelled 3beta-(4-iodophenyl)tropane-2beta-carboxylic acid ([123I]beta-CIT) labels both the dopamine transporter (DAT) and the serotonin transporter (5-HTT) and this ligand is able to clarify pathological changes in both dopaminergic and serotonergic systems. However, the differential kinetics of beta-CIT binding to DAT and 5-HTT has not been clarified fully. In this study we examined time-activity curves of [123I]beta-CIT in individual regions in the rat brain. Using cerebellum as the reference region, k3 and k4 values were estimated by a two-compartment kinetic analysis. In the striatum, the kinetics was slowest among all brain areas. In this area specific binding reached its peak 4 h after the injection. In the hypothalamus, specific binding reached its peak 1 h after the injection and its amount did not change until 4 h after the injection. In the occipital cortex, the binding and washout of the ligand were fastest among all brain regions. Estimated k3 values were 0.040+/-0.003 in the striatum, 0.019+/-0.002 in the hypothalamus and 0.082+/-0.011 in the occipital cortex (min-1, mean +/-SD). Estimated k4 values were 0.0034+/-0.0005 in the striatum, 0.0071+/-0.0009 in the hypothalamus and 0.083+/-0.013 in the occipital cortex (min-1, mean +/-SD). Therefore binding kinetics of [123i]beta-cit in the region rich in dat is apparently different from that in the region rich in 5-HTT. These results will provide fundamental data to image both DAT and 5-HTT in one series of examinations with [123I]beta-CIT.

Animals↗

PubMed1996

Role of endogenous angiotensin II in renal hemodynamic and excretory responses to L-arginine infusion.

The purpose of this study was to investigate whether endogenous angiotensin II has a functional role in renal hemodynamic and excretory changes induced by L-arginine, a substrate for nitric oxide (NO), in anesthetized rats. During the intravenous infusion of L-arginine (50, 100, 200 mumol/kg.min), there was no significant change in systemic or renal hemodynamics, but urine flow and urinary sodium excretion markedly increased in a dose-dependent manner. Simultaneously, L-arginine infusion produced an increase in urinary excretion of NO metabolites, NO2- and NO3-. Treatment with L-158809 ¿5,7-dimethyl-2-ethyl-3-[[2'-(1H-tetrazol-5-yl) [1,1']-biphenyl-4-yl]methyl]-3H-imidazo[4,5-b]pyridine¿ (0.3 mg/kg), a selective angiotensin II type I receptor antagonist, caused a reduction in mean arterial pressure, and a rise in renal blood flow and glomerular filtration rate, with no changes in excretory responses. In the presence of L-158809, L-arginine-induced diuretic and natriuretic actions were observed to the same extent as seen in the absence of L-158809. These data suggest that the infusion of L-arginine causes diuresis and natriuresis, possibly via the formation of nitric oxide in the kidney, and that endogenous angiotensin II is not involved in the L-arginine-induced renal actions.

Anesthesia↗

PubMed1994

Induction of ischaemic tolerance in gerbil hippocampus by pretreatment with focal ischaemia.

We investigated the induction of ischaemic tolerance in the hippocampal CA1 neurones to transient forebrain ischaemia following pretreatment with unilateral middle cerebral artery occlusion (MCAO) in gerbils. Histological evaluation was carried out after 5 min bilateral carotid artery occlusion (5BCO) in the gerbils with no MCAO pretreatment, MCAO pretreatment 3 days prior to 5BCO (MCAO-3d-5BCO), MCAO pretreatment 7 days prior to 5BCO and sham MCAO pretreatment 3 days prior to 5BCO. CA1 neurones were preserved at > 40% of normal controls only in the left hippocampus in the MCAO-3d-5BCO gerbils. CA1 neurones in the right side of MCAO-3d-5BCO gerbils as well as in both sides of animals in the other pretreatment groups almost completely disappeared after 5BCO. While the exact mechanism remains to be resolved, pretreatment with focal ischaemia seems to induce ischaemic tolerance in neurones outside of the primary ischaemic lesion.

Adaptation, Physiological↗

PubMed1992

Prorenin-renin axis in synovial fluid in patients with rheumatoid arthritis and osteoarthritis.

This study was undertaken 1) to determine whether or not renin is present in synovial fluid in patients with rheumatoid arthritis and osteoarthritis, and, if present, 2) to investigate whether it is synthesized in synovial fluid, or it is only transported from the circulation into the synovial cavity. The active renin concentration (indirect) was measured with angiotensin I radioimmunoassay kits. Inactive renin was converted into active renin with Sepharose-bound trypsin. Both active and inactive forms of renin were found in synovial fluid. They were significantly higher in patients with rheumatoid arthritis (n = 9) than in those with osteoarthritis (n = 16). In plasma, the concentration of inactive renin was significantly higher (P less than 0.001) in the former. Albumin, transferrin, alpha 2-macroglobulin, ceruloplasmin and immunoglobulins G and M were also found in synovial fluid. In each disease, a plot of the log ratio of synovial fluid to the serum concentration against the log molecular weight of each protein gave an approximately straight line curve, suggesting that these proteins are derived from the circulation and are transported into the synovial cavity. In contrast, the ratio of synovial fluid to plasma concentrations of active renin was significantly higher than that predicted on the basis of the above-mentioned interrelationships in both diseases, whereas the ratio of inactive renin was significantly lower. These findings suggest that 1) inactive and active renin are filtered into the synovial fluid from the circulation, and that 2) inactive renin is converted into the active form in the fluid.

Aged↗

PubMed1991

Characterization of a radioimmunoassay to determine plasma total renin.

The determination of plasma total renin is useful not only as a tool to investigate the physiology of hypertension but also as a marker for Wilms' tumor. A radioimmunoassay (RIA) system to determine plasma total renin was newly developed using monoclonal antibodies specific for both inactive and active renin (inactive + active = total); in this study, an effort was made to confirm that this RIA system truly determines plasma total renin concentrations. First, it was found that this monoclonal antibody stains only the juxtaglomerular apparatus of the kidney. Second, the data determined by the RIA were compared with those obtained by the conventional enzymatic method: samples were activated, and renin activity was assayed by measuring angiotensin I. The coefficient of the data obtained by this RIA system and by the conventional method was 0.921 (p less than 0.01) based on all 89 samples, and 0.809 (p less than 0.01) based on 86 of the 89 samples whose values were less than 600 pg/ml by RIA. As a result of these studies, it was concluded that the newly developed RIA system does determine total renin levels in patients' plasma.

Antibodies, Monoclonal↗

PubMed1990

Determination of plasma total renin level by RIA with a monoclonal antibody: value as a marker for nephroblastoma.

Plasma total renin is a new, useful marker for nephroblastoma, but the conventional method for determining its level is sophisticated and requires large blood samples. To develop a simpler technique, a monoclonal antibody specific for both inactive and active renin (inactive + active = total) was raised, and a radioimmunoassay (RIA) system was established. This monoclonal antibody stains only the juxtaglomerular apparatus; values determined by this RIA did not change before and after activation. So far, the RIA system has been applied to 136 samples from 92 patients. Plasma total renin levels were also determined with the conventional method: samples were activated, then renin activity was assayed by measuring angiotensin I. The coefficient of the data obtained by these two different techniques was 0.921 (P less than .01). Plasma total renin levels in patients with nephroblastoma were significantly increased (546.5 +/- 297.8 pg/mL) over those in patients with neuroblastoma (218.6 +/- 46.5 pg/mL) and in controls (165.8 +/- 67.5 pg/mL, P less than .01). After removal of Wilms' tumors, the levels decreased to normal when sampled every 2 weeks. It was concluded that a newly developed RIA system is more useful in determining plasma total renin levels in patients with nephroblastoma.

Antibodies, Monoclonal↗

PubMed1990

Circadian variations of total renin, active renin, plasma renin activity and plasma aldosterone in clinically healthy young subjects.

The direct assay of total renin (TRC) and active renin concentration (ARC) is a reality due to the availability of monoclonal antibodies against human renin. Because of this, a study has been performed in order to assess the circadian rhythmicity of TRC and ARC. The study was extended to plasma renin activity (PRA) and plasma aldosterone concentration (PAC) for a more complete assessment of the renin-angiotensin-aldosterone system (RAAS). Twelve clinically healthy subjects (6 males and 6 females, age from 20 to 25 years) volunteered for this study. Time-qualified data series were analysed by means of chronobiological procedures in order to validate the circadian rhythm and to correlate the sinusoidal profiles. The circadian rhythm was validated at a high significance for TRC, ARC, PRA and at a borderline significance for PAC. The periodic oscillations were significantly correlated, demonstrating that TRC, ARC, PRA and PAC cycles oscillate in synchronism during the 24-hour span.

Adult↗