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Biomedical subjects

M Kohno

Publications and source records attributed to M Kohno.

At least 217 records · Page 12Linked to original sources
PubMed1996

Plasma brain natriuretic peptide during ergometric exercise in hypertensive patients with left ventricular hypertrophy.

Cardiac ventricle is shown to be an important source of circulating brain natriuretic peptide (BNP) in hypertensive rats with left ventricular hypertrophy (LVH). This study examined the effect of short-term exercise with a bicycle ergometer on plasma BNP concentrations in 21 essential hypertension patients with LVH established by echocardiography. The results were compared with those from 24 age-matched hypertensives without LVH. Blood pressure, heart rate, plasma renin activity (PRA), and plasma norepinephrine level increased during exercise, but the mean increases of these parameters were not different in the two groups. Resting BNP levels were slightly but significantly higher in the LVH group than in the non-LVH group. This peptide increased during exercise in the two groups, but the exercise-induced increase (percent increase) in plasma BNP was significantly greater in the LVH group than in the non-LVH group (207% +/- 50% v 141% +/- 36%, P < .05). The exercise-induced increase in BNP was significantly correlated with the left ventricular (LV) mass index (N = 45, r = .60, P < .01). By contrast, the exercise-induced increase in BNP was not correlated with the exercise-induced increase in heart rate, systolic blood pressure, diastolic blood pressure, mean blood pressure, PRA, or noradrenaline level. These results suggest that short-term exercise induces an accelerated increase of plasma BNP in hypertensive subjects with LVH. The LV mass appeared to be related to the observed increase of plasma BNP concentration, at least in our hypertensive patients with LVH.

Adult↗
PubMed1996

Scavenging effects of dopamine agonists on nitric oxide radicals.

It has recently been considered that free radicals are closely involved in the pathogenesis of Parkinson's disease (PD), and the level of nitric oxide radical (.NO), one of the free radicals, is reported to increase in PD brain. In the present study, we established a direct detection system for .NO in an in vitro .NO-generating system using 3-(2-hydroxy-1-methylethyl-2-nitrosohydrazino)-N-methyl-1-propa namine as an .NO donor and 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (carboxy-PTIO) by electron spin resonance (ESR) spectrometry and examined the quenching effects of the dopamine agonists pergolide and bromocriptine on the amount of.NO generated. .NO appeared to be scavenged by pergolide and, to a lesser extent, by bromocriptine. In the competition assay, the 50% inhibitory concentration values for pergolide and bromocriptine were estimated to be approximately 23 and 200 microM, respectively. It was previously reported that in vivo treatment of pergolide and bromocriptine completely protected against the decrease in levels of striatal dopamine and its metabolites in the 6-hydroxydopamine-injected mouse. Considering these findings, pergolide and probably bromocriptine may also protect against dysfunction of dopaminergic neurons because of its multiple effects; not only does it stimulate the presynaptic autoreceptors, but it also directly scavenges .NO radicals and hence protects against .NO-related cytotoxicity. This ESR spectrometry method using carboxy-PTIO may be useful for screening other drugs that can quench .NO.

Benzoates↗
PubMed1996

Guanidino compounds generate reactive oxygen species.

Methylguanidine, guanidinoacetic acid and guanidinosuccinic acid are endogenous substances in body tissues. Extremely high levels of these substances are known to be related to the pathogenesis of epilepsy and renal failure such as uremia. In this study it was demonstrated that methylguanidine, guanidinoacetic acid and guanidinosuccinic acid, and arginine generate hydroxyl radicals in aqueous solution. These findings suggest that a high level of guanidino compounds accumulating near or within cells such as neurons (in an epileptogenic focus) or nephrons (in uremic patients) may cause free radical damage leading to these clinical disorders. Arginine may have a similar role in the pathogenesis of hyperarginemia.

Electron Spin Resonance Spectroscopy↗
PubMed1996

The crystal structure of lipase II from Rhizopus niveus at 2.2 A resolution.

The crystal and molecular structure of Lipase II from Rhizopus niveus was analyzed using X-ray single crystal diffraction data at a resolution of 2.2 A. The structure was refined to an R-factor of 0.19 for all available data. This lipase was purified and crystallized as Lipase I, which contains two polypeptide chains combined through non-covalent interaction. However, during crystal growth, Lipase I was converted to Lipase II, which consists of a single polypeptide chain of 269 amino acid residues, by limited proteolysis. The structure of Lipase II shows a typical alpha/beta hydrolase fold containing the so-called nucleophilic elbow. The catalytic center of this enzyme is analogous to those of other neutral lipases and serine proteases. This catalytic center is sheltered by an alpha-helix lid, which appears in neutral lipases, opening the active site at the oil-water interface.

Amino Acid Sequence↗
PubMed1996

Adrenomedullin as a novel antiproliferative factor of vascular smooth muscle cells.

OBJECTIVE: The present study was designed to examine whether adrenomedullin affects fetal calf serum (FCS)-stimulated proliferation in cultured rat vascular smooth muscle cells (VSMCs). METHODS: Rat VSMCs were grown from explants of Sprague-Dawley rat aorta and were grown using the standard cell culture method. After incubation for 24 h with various concentrations of adrenomedullin in the presence of 5% FCS, trichloroacetic acid-insoluble tritiated thymidine was measured in a liquid scintillation counter. After incubation for 48 h, cell counts were performed. Cyclic adenosine 3',5'-monophosphate (AMP) levels were determined by radioimmunoassay. RESULTS: Rat adrenomedullin exhibited concentration-dependent inhibition of the FCS-stimulated increase in thymidine incorporation between 10(-7) and 10(-9) mol/l and of cell number at 10(-7) mol/l. However, the calcitonin generelated peptide (CGRP) receptor antagonist human CGRP(8-37) abolished these antiproliferative effects of rat adrenomedullin. Inhibition by adrenomedullin of FCS-stimulated cellular proliferation was paralleled by an increase in the cellular level of cyclic AMP. 8-Bromocyclic AMP, a cyclic AMP analogue, and forskolin, an activator of adenylate cyclase, inhibited the FCS-stimulated increase in thymidine incorporation and cell number. CONCLUSIONS: These results suggest that adrenomedullin inhibits FCS-stimulated proliferation in cultured rat VSMCs, probably through a cyclic AMP-dependent process. Taken together with the finding that adrenomedullin is synthesized in and secreted from vascular endothelial cells, adrenomedullin may play a role as an antiproliferative factor for VSMCs in a paracrine fashion.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1996

Nitric oxide mediates the cardiovascular instability of haemodialysis patients.

Acute hypotension is a major cardiovascular complication of haemodialysis. The cardiac output falls but the total peripheral resistance remains unchanged at the time when hypotension develops. Nitric oxide affects myocardial contraction and noradrenergic response, and regulates vascular tone. This review discusses the mechanisms of acute hypotension occurring during haemodialysis, focusing on the role of nitric oxide in the associated cardiovascular instability.

Animals↗
PubMed1996

Plasma adrenomedullin concentrations in essential hypertension.

We designed the present study to assess any changes in plasma concentrations of the novel vasorelaxant peptide adrenomedullin in patients with essential hypertension. Plasma adrenomedullin concentrations were measured in 45 patients with untreated essential hypertension, 15 patients with borderline hypertension, and 30 normotensive control subjects. After 4 weeks of effective calcium channel blocker-based antihypertensive therapy, adrenomedullin concentrations were measured again. The concentrations were higher in hypertensive patients with increased serum creatinine levels or decreased glomerular filtration rates compared with borderline hypertensive patients and normotensive subjects, although values in normotensive and hypertensive individuals overlapped. Plasma adrenomedullin concentrations were positively correlated with serum creatinine levels and inversely correlated with glomerular filtration rates in the hypertensive patients, whereas adrenomedullin values were not correlated with blood pressure level, left ventricular mass index, or left ventricular ejection fraction. Despite blood pressure control with antihypertensive therapy, plasma adrenomedullin concentrations were not changed. Reversed-phase high-performance liquid chromatographic analysis showed that a major component of immunoreactive adrenomedullin in the plasma of normotensive subjects and hypertensive patients is human adrenomedullin-(1-52). These results indicate that plasma adrenomedullin concentrations are elevated in many hypertensive patients with renal dysfunction and its major component is human adrenomedullin-(1-52).

Adrenomedullin↗
PubMed1996

Interaction of adrenomedullin and platelet-derived growth factor on rat mesangial cell production of endothelin.

Adrenomedullin has recently been isolated from human pheochromocytoma. We designed the present study to examine the effect of adrenomedullin on the production of the vasoconstrictive and growth-promoting peptide endothelin-1 (ET-1) after stimulation with platelet-derived growth factor (PDGF) in cultured rat glomerular mesangial cells. PDGF stimulated ET-1 production in a concentration-dependent manner. Rat adrenomedullin inhibited this stimulated ET-1 production in a concentration-dependent manner between 10(-7) and 10(-8) mol/L. Rat adrenomedullin also increased the cellular level of cAMP in a concentration-dependent manner between 10(-7) and 10(-8) mol/L. Human adrenomedullin was less effective than rat adrenomedullin with respect to inhibiting ET-1 production and increasing cAMP levels. The addition of 8-bromo-cAMP (10(-3) and 10(-4) mol/L) reduced PDGF-induced ET-1 production. Furthermore, forskolin (10(-4) and 10(-5) mol/L), an activator of adenylate cyclase, reduced PDGF-induced ET-1 production. In contrast, the basal production of ET-1 was not significantly altered by rat and human adrenomedullin. These results indicate that adrenomedullin inhibits PDGF-induced ET-1 production in cultured rat mesangial cells, probably through a cAMP-dependent process.

Adrenomedullin↗
PubMed1996

Possible involvement of phospholipase D and protein kinase C in vascular growth induced by elevated glucose concentration.

Hyperglycemia is believed to be a major cause of diabetic vascular complications. To elucidate the effect of hyperglycemia on vascular response, we studied hyperproliferation, hypertrophy, and the natriuretic peptide response of vascular smooth muscle cells under high-glucose conditions. We observed that cells cultured in high glucose (22.2 mmol/L) showed hyper-proliferation and hypertrophy and that natriuretic peptide receptor responses were suppressed compared with cells cultured in normal glucose (5.6 mmol/L). We also examined phospholipase D and protein kinase C activities and found that in high-glucose conditions such activities are higher than in cells cultured in normal glucose. The activation of phospholipase D was not prevented by coincubation with 1 mumol/L protein kinase C(19-36), a specific protein kinase C inhibitor, but the activation of protein kinase C was. Protein kinase C(19-36) also markedly attenuated vascular hyperproliferation and hypertrophy as well as glucose-induced suppression of natriuretic peptide receptor response. These results show that hyperglycemia may be linked to vascular hyperproliferation, hypertrophy, and a suppressed natriuretic peptide receptor response, which are caused by increased phospholipase D and protein kinase C activities.

Animals↗
PubMed1996

Stroke volume generation of the left ventricle and its relation to chamber shape in normal subjects and patients with mitral or aortic regurgitation.

The total stroke volume of the left ventricle (LV) is equal to the sum of the regional cavity shrinkage. Since nonuniformity of regional wall motion in LV has been well documented even in normal subjects, the extent of the contribution of each region to total stroke volume cannot be easily determined. To assess the left ventricular regional contributions to total stroke volume under normal conditions and in compensated chronic mitral or aortic regurgitation, LV cineangiograms were analyzed in 14 normal subjects (N), 8 patients with mitral regurgitation (MR) and 10 patients with aortic regurgitation (AR). We assumed that the LV cavity could be viewed as a stack of 30 half-cylindrical discs, 15 in the anterior and 15 in the inferior wall regions. LV chamber shape was more spherical in MR than in N, but was more conical in AR. Percent regional hemichordal shortening was significantly decreased in the anterobasal and anteroapical walls in AR, but was similar between N and MR. The regional contribution to total stroke volume showed a significant quadratic correlation with the end-diastolic regional shape index (N, r = 0.87; MR, r = 0.79; AR, r = 0.90), which was defined as the regional hemiaxial length divided by the LV long-axis length, but was not correlated with percent regional hemichordal shortening. Therefore, stroke volume is generated mainly in the mid-ventricular portion in N and MR, but in the basal portion in AR due to the characteristic change in cavity shape.

Adult↗
PubMed1996

The effect of nifedipine on ventriculoarterial coupling in old myocardial infarction.

The effect of nifedipine on ventriculoarterial coupling was examined in 8 patients with old myocardial infarction who showed a depressed ejection fraction (37 +/- 7%). Left ventricular (LV) pressure and LV volume were determined simultaneously by micromanometer and conductance catheter, respectively. We measured the slope (Ees) of the end-systolic pressure-volume relation during transient inferior vena caval occlusion, the slope (Ea) of the end-systolic pressure-stroke volume relation, the ratio of Ea to Ees (Ea/Ees), and the work efficiency (the ratio of external work to the systolic pressure-volume area) at baseline and after the sublingual administration of nifedipine (10 mg). Nifedipine slightly increased the heart rate from 71 +/- 14 to 78 +/- 17 beats/min. Although nifedipine had little effect on Ees (2.54 +/- 0.68 vs 2.47 +/- 0.62 mmHg/ml/m2, ns), it significantly decreased Ea from 3.47 +/- 1.16 to 2.37 +/- 0.54 mmHg/ml/m2. Consequently, Ea/Ees decreased from 1.42 +/- 0.47 to 0.97 +/- 0.31 and work efficiency increased from 48 +/- 12 to 59 +/- 13% after nifedipine administration. These data suggest that nifedipine reduces afterload (Ea) and improves left ventriculoarterial coupling without depressing left ventricular contractility in patients with failing hearts due to old myocardial infarction.

Aged↗
PubMed1996

Effect of right ventricular volume overload on left ventricular diastolic function in patients with atrial septal defect.

This study was undertaken to investigate the effect of chronic right ventricular (RV) volume overload on left ventricular (LV) diastolic function. Twelve patients with atrial septal defect and 7 age-matched normal controls were examined. Patients with atrial septal defect were divided into 2 groups based on their Qp/Qs values (ASD1:Qp/Qs < or = 3, n = 7; ASD2:Qp/Qs > 3, n = 5). The LV volume curve and its first derivative were derived by a frame-by-frame analysis of the left ventriculogram. The peak filling rate was defined by the peak positive first derivative of the LV volume curve. We measured the time constant, isovolumetric relaxation time, stiffness constant and compliance at LV end-diastole. The time constant was significantly prolonged in the ASD2 group compared with the controls, and the isovolumetric relaxation time in both atrial septal defect groups was also prolonged compared with the controls. The peak filling rate, which was normalized by end-diastolic volume, was lower in the ASD2 group than in the controls. Although the stiffness constant and the compliance at LV end-diastole in the controls were not significantly different from those in the atrial septal defect group, an upward and leftward displacement of the left ventricular pressure-volume curve was observed in patients with atrial septal defect. Moreover, a significant correlation (r = 0.78, p < 0.01) was observed between the time constant and RV end-diastolic pressure. Thus, these results suggest that chronic RV volume overload affects left ventricular diastolic function.

Adult↗
PubMed1996

Hemagglutination with porcine reproductive and respiratory syndrome virus.

Porcine reproductive and respiratory syndrome (PRRS) virus grown on MARC-145 cell cultures was tested for hemagglutination (HA) with erythrocytes from a variety of species at 4 degrees C, room temperature and 37 degrees C. HA was observed at all temperatures with mouse erythrocytes but not with cattle, sheep, goat, horse, swine, guinea pig, mongolian gerbil, goose and chicken erythrocytes. The HA activity was enhanced by treatment of virus materials with Tween 80 followed by treatment with ether. The HA titer and HA pattern of virus materials treated with Tween 80 and ether (TE) were 4- to 8-fold higher and more clear than those of the virus materials without TE treatment. The optimum conditions consisted in pretreatment of virus material with Tween 80 at a final concentration of 0.06-0.125% (v/ v) for 15-60 min followed by treatment with ether at a concentration of 50% (v/v) for 5-15 min in ice bath with continuous shaking. The curve of active virus production in intra- and extracellular virus samples resembled that of HA production although it rose somewhat earlier in intracellular virus samples. The HA reaction was inhibited by specific antiserum. HI antibody titers of individual pig sera showed a significant positive correlation with their neutralizing antibody titers.

Animals↗
PubMed1996

[Henoch-Schönlein nephritis with nephrotic syndrome during pregnancy].

We report a 33-year-old female with nephrotic syndrome associated with Henoch-Schönlein nephritis (HSN) during pregnancy. She presented purpura in the legs at 20 weeks in her third pregnancy. A biopsy of her purpuric skin lesion showed leukocytoclastic vasculitis. After a month she was admitted to Sapporo City General Hospital because of development of a nephrotic syndrome. She was treated with heparin as anticoagulants therapy and delivered of a healthy girl by Cesarean section at 34 weeks. Renal biopsy, carried out beyond a month after delivery, revealed diffuse proliferative glomerulonephritis with prominent IgA deposits, which made the diagnosis of HSN (grade III of classification of the renal histopathology of HSN from the International Study of Kidney Disease in Childhood). Prednisolone 40 mg, dipyridamole 300 mg per day and pulse doses of steroid were administrated. Two months later proteinuria was not detected. A sister of the patient had also Henoch-Schönlein Purpura in her childhood. They shared HLA DR 4, DQ 4 which are known to be associated with IgA nephropathy. Fifty percent of pregnant women with chronic glomerulonephritis shows increased proteinuria. Pregnancy may have influence on the increased proteinuria in this case.

Adult↗
PubMed1996

A cervical dural arteriovenous fistula in a patient presenting with radiculopathy. Case report.

A 51-year-old man presenting with radiculopathy a rare cervical dural arteriovenous fistula (AVF) is reported. Angiography revealed that the cervical dural AVF was fed mainly by the left C-3 and C-4 radicular arteries and drained into the internal vertebral venous plexus with no communication with intradural structures. The dural AVF was treated surgically after embolization therapy. Although the AVF showed mass effect on computerized tomography (CT) scanning, abnormal vessels, which were suspected to drain the AVF, were observed intraoperatively to compress the left C-4 and C-5 nerve root sleeves. After resection of these abnormal epidural vessels, monoparesis of the left proximal upper extremity was markedly improved. In this patient, dynamic CT scanning was useful in the initial diagnosis, and the preoperative embolization therapy was very effective.

Arteriovenous Fistula↗
PubMed1996

Bone morphogenetic protein-2 is markedly synergistic with tumor necrosis factor in stimulating the production of nerve growth factor in fibroblasts.

A possible interaction between tumor necrosis factor (TNF) and transforming growth factor-beta (TGF-beta) superfamily cytokines in stimulating the production of nerve growth factor (NGF) in Swiss 3T3 cells was studied. Although TGF-beta 1 and Activin A stimulated NGF production in Swiss 3T3 cells, they antagonized the stimulatory effect of TNF on fibroblast NGF production when used in combination. On the contrary, TNF's stimulatory activity on fibroblast NGF production was markedly synergized by bone morphogenetic protein-2 (BMP-2); BMP-2 by itself did not stimulate NGF production in the cells. These findings suggest that BMP-2, in concert with TNF, plays an essential role in regulating the regeneration of peripheral nerves following injury with bone fracture through an indirect mechanism by which it stimulates NGF production in fibroblasts.

3T3 Cells↗
PubMed1996

[Massive ascites as an initial sign, plasmacytoma of the cervical supine, and hyperammonemic consciousness disturbance in a patient with biclonal type multiple myeloma].

A 69-year-old male presented with fever, ascites and leg edema in February, 1994. He had a pathological fracture of cervical supine in October. Pathological findings at operation showed plasmacytoma. Bone marrow aspiration showed 16.2% myeloma cells. So he was diagnosed as multiple myeloma presenting biclonal gammopathy of IgA-L and IgD-K. Ascites was massive and drainage of 2 to 4 liter per week was required. Ascites was supposed to be related to multiple myeloma, because the IL-6 level in the ascites was increased (2,440 pg/ml), although repeated cytologic studies were negative. After the operation, he developed hyperammonemic drowsiness. It was also suggested that hyperammonemia was associated with multiple myeloma. In addition to radiation therapy for the cervical lesion, MP therapy, Interferon-alpha, VAD therapy and intraperitoneal cyclophosphamide infusion were administered. But no improvement of ascites or hyperammonemia were noticed. Here we described a case of multiple myeloma with very notable clinical features.

Aged↗