Biomedical subjects

M Kohno

Publications and source records attributed to M Kohno.

At least 253 records · Page 14Linked to original sources

PubMed1995

Brain natriuretic peptide as a marker for hypertensive left ventricular hypertrophy: changes during 1-year antihypertensive therapy with angiotensin-converting enzyme inhibitor.

PURPOSE: Secretion of brain natriuretic peptide (BNP), a cardiac hormone, is accelerated via hypertrophied ventricles in experimental hypertension. The present study examined whether regression of left ventricular (LV) hypertrophy by long-term treatment with an angiotensin-converting enzyme inhibitor (ACEI) affects plasma BNP concentration in patients with essential hypertension. PATIENTS AND METHODS: Thirty-one hypertensive patients with LV hypertrophy were treated with ACEI (16 with enalapril; 15 with lisinopril) for 1 year. Serial changes were recorded in LV mass index, LV systolic function, and plasma concentrations of BNP and atrial natriuretic peptide (ANP). RESULTS: ACEI therapy significantly reduced LV mass index at 6 months, and more so at 1 year. Septal and posterior wall thicknesses were also reduced. Plasma BNP and ANP were markedly elevated at study entry, but only BNP levels correlated with LV mass index. Both peptide levels declined after 6 months, and this decline was enhanced at 1 year. There was a close relation between BNP decline and LV mass index reduction overall and with enalapril and lisinopril separately. Changes in ANP and in LV mass index were not related. CONCLUSION: Long-term ACEI therapy can reduce elevated plasma BNP. In this study, changes in BNP reflected the magnitude of regression of LVH. Plasma BNP may be a useful marker for LVH during antihypertensive therapy in patients with essential hypertension and LVH.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1995

Elevated glucose concentration and natriuretic peptides receptor response on vascular smooth muscle of spontaneously hypertensive rats.

1. Hyperglycaemia is believed to be a major cause of diabetic vascular complications such as accelerated atherosclerosis. In order to elucidate the effect of hyperglycaemia on vascular response in spontaneously hypertensive rats (SHR), the natriuretic peptides receptor responses to vascular smooth muscle cells (VSMC) which are thought to suppress atherosclerosis were studied under high glucose (HG:22.2 mmol/L) conditions. 2. The total number of cells in SHR is higher and natriuretic peptides receptor response is smaller than that of cells in the Wistar-Kyoto (WKY) rat. Membrane bound protein kinase C (PKC) activity in HG or SHR is higher compared to that of cells in normal glucose (NG:5.6 mmol/L) or WKY. Cells cultured in HG for at least 2 passages had higher total cell number and receptor mediated cGMP formation were suppressed compared to cells cultured in NG both in SHR and WKY. Specific PKC inhibitor PKC (19-36) 1 mu mol/L prevented HG induced suppression of natriuretic peptides response. 3. These results show that hyperglycaemia may be linked to suppressed natriuretic peptides receptor response which is caused by increased PKC activity both in WKY and SHR. This suppressed response may cause the accelerated atherosclerosis by hyperglycaemia.

Animals↗

PubMed1995

Enhanced phosphoinositide turnover signalling stimulated by endothelin B-type receptor in endothelial cells from spontaneously hypertensive rats.

1. Endothelin (ET) B-type (ETB) receptor-mediated signal transduction was examined after stimulation with ET-3 in cultured aortic endothelial cells (EC) from spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats (8 weeks old). 2. The EC from both rat strains expressed only ETB receptor mRNA. The receptor densities and affinities, which were non-selective for ET-1, -2, -3 and Sarafotoxin S6c, and mRNA expression were similar in WKY and SHR. 3. The cytosolic Ca2+ level in the absence of extracellular Ca2+, inositol 1,4,5-trisphosphate levels, protein kinase C and phospholipase C activities in response to ET-3 were greater in SHR EC than in WKY EC. 4. The 45Ca uptake in response to ET-3, which was blocked by Ni2+, was smaller in SHR EC than in WKY EC. 5. The 6-keto-PGF1alpha production was augmented in SHR, though nitric oxide formation after stimulation with ET-3 was similar. 6. These results suggest that ETB receptor-mediated phosphoinositide turnover signalling is augmented in SHR EC through postreceptor mechanism.

6-Ketoprostaglandin F1 alpha↗

PubMed1995

Effect of thrombin and PDGF on endothelin production in cultured mesangial cells derived from spontaneously hypertensive rats.

1. Basal endothelin-1 (ET-1) production in mesangial cells of spontaneously hypertensive rats (SHR) was not different from that of Wistar-Kyoto (WKY) rats, although a trend toward increased ET-1 production was observed in these cells of SHR. 2. Thrombin and platelet-derived growth factor (PDGF) stimulated ET-1 production in a concentration-dependent manner in these cells of both rat strains, but thrombin- and PDGF-induced stimulation of ET-1 production were clearly greater in cells of SHR than WKY rats. 3. The protein kinase C (PKC)-activating phorbol ester, phorbol myristate acetate, stimulated ET-1 production in cells of both rat strains, but this stimulation was significantly greater in cells of SHR than in cells of WKY rats. 4. An inactive enantiomer of phorbol ester, 4alpha-PDD, had no effect on the ET-1 production in these cells of both rat strains. 5. Neither thrombin nor PDGF stimulated ET-1 production in PKC-depleted cells of both rat strains.

Animals↗

PubMed1995

Proliferation and differentiation of myelodysplastic CD34+ cells in serum-free medium: II. Response to combined colony-stimulating factors.

To investigate the role of colony stimulating factors (CSFs) in the proliferation and differentiation of progenitor cells from myelodysplastic syndromes (MDS), marrow progenitor cells from 18 MDS patients were highly purified using CD34 monoclonal antibody and immunomagnetic microspheres (MDS CD34+ cells). These cells were cultured in serum-free medium with various combinations of five colony stimulating factors (CSFs): recombinant human interleukin-3 (rIL-3), granulocyte/macrophage-CSF (rGM-CSF), granulocyte-CSF (rG-CSF), macrophage-CSF (rM-CSF), and erythropoietin (rEP). Among the tested CSFs, such as rM-CSF, rG-CSF, rGM-CSF and rIL-3, a combination of the first three CSFs was the most effective stimulus for the proliferation of non-erythroid MDS progenitor cells. An increase of undifferentiated "blast" cell colonies in 5/18 MDS patients occurred and these 5 patients belonged to the high-risk group. In the presence of these three CSFs, rIL-3 had no effect on the proliferation and differentiation of MDS CD34+ cells; however, IL-3 was efficient for the proliferation of MDS CD34+ cells to the erythroid lineage. rGM-CSF or rIL-3 alone did not efficiently support proliferation and differentiation of CD34+ cells. M-CSF is present in normal human serum at a concentration of 550 +/- 110 U/ml, a concentration exceeding that used in this study (100 U/ml). Therefore, in vivo administration of G-CSF combined with GM-CSF to MDS patients may be one of the most effective CSF combinations for proliferation of MDS progenitor cells to the non-erythroid lineage. However, the effect on the capacity for differentiation was minimal, especially in patients belonging to the high-risk group.

Adult↗

PubMed1995

Aldose reductase inhibitor prevents hyperproliferation and hypertrophy of cultured rat vascular smooth muscle cells induced by high glucose.

Vascular remodeling is a key process in the pathophysiology of atherosclerosis. Recent evidence suggests that high glucose levels may function as a vascular smooth muscle growth and proliferation-promoting substance. To explore the role of the polyol pathway in this process, we examined the effect of an aldose reductase inhibitor (ARI), epalrestat, on the growth characteristics of cultured rat vascular smooth muscle cells (VSMCs). Epalrestat (10 nmol/L, 1 mumol/L) significantly suppressed the high glucose-induced proliferative effect as measured by [3H]thymidine incorporation by 67% and 82% in cell number, suggesting ARI as an antimitogenic factor. In VSMCs, epalrestat (10 nmol/L, 1 mumol/L) significantly suppressed the high glucose-induced incorporation of [3H]leucine by 45% and 58% with the concomitant reduction of the cell size estimated by flowcytometry. Epalrestat (1 mumol/L) also suppressed high glucose-induced intracellular NADH/NAD+ increase and membrane-bound protein kinase C activation. These results indicate that this ARI possesses an antiproliferative and antihypertrophic action on VSMCs induced by high glucose possibly through protein kinase C suppression.

Aldehyde Reductase↗

PubMed1995

Inhibition of endothelin production by adrenomedullin in vascular smooth muscle cells.

Adrenomedullin recently has been found to potently stimulate cAMP formation in cultured rat vascular smooth muscle cells (VSMCs). In the present study, we examined the effect of adrenomedullin on the production of a vasoconstrictive and growth-promoting peptide, endothelin-1, after stimulation with a clotting enzyme, thrombin, and a potent mitogen, platelet-derived growth factor (PDGF), in cultured rat VSMCs. Thrombin and PDGF stimulated endothelin-1 production in a dose-dependent manner. Rat adrenomedullin significantly inhibited thrombin- and PDGF-stimulated endothelin-1 production in a dose-dependent manner between 10(-7) and 10(-9) mol/L. Inhibition by rat adrenomedullin of thrombin- and PDGF-stimulated endothelin-1 production was paralleled by an increase in the cellular level of cAMP. Human adrenomedullin also inhibited thrombin- and PDGF-stimulated endothelin-1 production and increased cAMP levels. The addition of 8-bromo-cAMP, a cAMP analogue, reduced thrombin- and PDGF-induced endothelin-1 production. Furthermore, forskolin, a potent activator of adenylate cyclase, reduced thrombin- and PDGF-induced endothelin-1 production. In contrast, basal production of endothelin-1 was not altered by rat or human adrenomedullin. These results indicate that adrenomedullin inhibits not basal but thrombin- and PDGF-induced ET-1 production in cultured VSMCs probably through a cAMP-dependent process. Taken together with the finding that adrenomedullin is synthesized in and secreted from vascular endothelial cells, adrenomedullin may modulate vascular tone as a paracrine regulator partially through the inhibition of VSMC endothelin-1 production in some pathophysiological states.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1995

Endothelin production in cultured mesangial cells of spontaneously hypertensive rats.

Cultured glomerular mesangial cells are shown to produce a potent vasoconstrictive peptide, endothelin-1 (ET-1). We examined whether basal or stimulated ET-1 production by angiotensin II (Ang II) and arginine vasopressin (AVP) is enhanced in cultured mesangial cells of spontaneously hypertensive rats (SHR) compared with Wistar-Kyoto rats (WKY). In addition, we examined which receptor subtypes of Ang II and AVP mediate ET-1 production in these cells. Basal ET-1 production in SHR mesangial cells was not different from that in WKY cells, although a trend toward increased ET-1 production was observed in the SHR cells. Ang II and AVP stimulated ET-1 production in a concentration-dependent manner in mesangial cells of both rat strains, but Ang II- and AVP-induced stimulation of ET-1 production was clearly greater in SHR than WKY cells. The protein kinase C (PKC)-activating phorbol ester phorbol myristate acetate stimulated ET-1 production in a concentration-dependent manner in cells of both rat strains, but this stimulation was significantly greater in SHR than WKY cells. Neither Ang II nor AVP stimulated ET-1 production in PKC-depleted cells of both strains. Ang II- and AVP-induced stimulation was completely abolished by selective angiotensin subtype 1 (AT1) and vasopressin subtype 1 (V1) receptor antagonists, respectively, in cells of both rat strains. These results suggest that AT1 and V1-receptor-mediated mesangial cell production of ET-1 is clearly enhanced in SHR compared with WKYs. Increased response of ET-1 production to PKC activation appears to contribute in part to the observed enhancement of ET-1 production in SHR mesangial cells.

Angiotensin II↗

PubMed1995

Inhibition by cardiac natriuretic peptides of rat vascular endothelial cell migration.

Vascular endothelial cell migration is proposed to be an important process in the initiation and progression of atherosclerosis. We designed the present study to examine the effects of atrial and brain natriuretic peptides on fetal calf serum-stimulated migration of cultured rat aortic endothelial cells using Boyden's chamber method. Fetal calf serum clearly stimulated migration in a concentration- and time-dependent manner. Rat atrial natriuretic peptide-(1-28) and rat brain natriuretic peptide-45, which are the major circulating forms of atrial and brain natriuretic peptides in rats, inhibited fetal calf serum-stimulated migration in a concentration-dependent manner between 10(-10) and 10(-6) mol/L. Such inhibition by these natriuretic peptides was paralleled by an increase in the cellular level of cGMP. The addition of a cGMP analogue 8-bromo-cGMP, significantly inhibited fetal calf serum-stimulated migration in a concentration-dependent manner between 10(-7) and 10(-3) mol/L. Rat atrial natriuretic peptide-(5-25) was much less effective than atrial natriuretic peptide-(1-28) or rat brain natriuretic peptide-45 with respect to inhibiting migration and increasing cGMP levels. These results indicate that atrial and brain natriuretic peptides inhibit fetal calf serum-stimulated vascular endothelial cell migration, probably through a cGMP-dependent process.

Animals↗

PubMed1995

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

The present study investigated the effect of adrenomedullin, a novel vasorelaxant peptide, on the migration of cultured rat vascular smooth muscle cells (SMCs) by using the Boyden-chamber method. Fetal calf serum (FCS) and platelet-derived growth factor (PDGF)-BB strongly stimulated SMC migration. Adrenomedullin clearly inhibited SMC migration stimulated with 5% and 10% FCS in a concentration-dependent manner. The migration induced by 10 and 25 ng/mL PDGF-BB was also inhibited by adrenomedullin in a concentration-dependent manner. Inhibition by adrenomedullin of FCS- and PDGF-induced SMC migration was paralleled by an increase in the cellular level of cAMP. In fact, the percent increase in cAMP level was strongly correlated with the percent decrease in migration activity of SMCs after treatment with adrenomedullin. 8-Bromo cAMP, a cAMP analogue, reproduced the inhibition by adrenomedullin of FCS- and PDGF-induced SMC migration. An activator of adenylate cyclase, forskolin, also reduced FCS- and PDGF-induced SMC migration. These data indicate that adrenomedullin inhibits the migration of SMCs stimulated with FCS and PDGF, probably through a cAMP-dependent process. On the basis of these results and the finding that adrenomedullin is synthesized in and secreted from vascular endothelial cells, adrenomedullin may play a role as a local antimigration factor in some pathophysiological states.

Adrenomedullin↗

PubMed1995

Brain natriuretic peptide in hypertension.

Brain natriuretic peptide (BNP) was first identified in the porcine brain and later isolated from porcine, rat, and human hearts. In humans, plasma BNP concentrations are progressively elevated with increasing severity of hypertension, particularly when left ventricular hypertrophy (LVH) is present. This presumably reflects increases in ventricular mass associated with increased synthesis and constitutive secretion of BNP from ventricular tissue. In this report, plasma BNP may be a marker for hypertensive LVH. Acute administration of BNP induces significant natriuresis and suppresses plasma aldosterone in hypertensive subjects. However, further studies are necessary to clarify the pathophysiological significance of BNP in essential hypertension.

Animals↗

PubMed1995

Vascular dopamine-I receptors.

The modulation of dopamine DA1 receptors of cultured rat renal arterial smooth muscle cells by phorbol ester, glucocorticoid and sodium chloride was studied. The extent of [3H]Sch-23390 binding to phorbol ester-treated cell was increased without any change in the dissociation constant (Kd). At a concentration of 10 nmol/l, the synthetic glucocorticoid dexamethasone increased maximum receptor binding (Bmax) but had no effect on the Kd. 100 mmol/l sodium chloride did not change Bmax, but increased the Kd for DA1 receptor. The production of cAMP in response to DA1 receptor stimulation was enhanced without any change of the adenylate cyclase activity. The glucocorticoid effect on DA1 of arterial smooth muscle cells became apparent after hours of incubation in the presence of the steroid and was significantly inhibited by cycloheximide (10 micrograms/ml) and by the glucocorticoid receptor antagonist RU-38486, indicating that the effect required protein synthesis through glucocorticoid receptors. Treatment of cells with 1 mumol/l dexamethasone for 24 h increased basal and DA1-stimulated adenylate cyclase activity. Basal adenylate cyclase was decreased by sodium chloride in a dose-dependent manner. These results suggest differential control of DA1 receptors on vascular smooth muscle cells by protein kinase C, glucocorticoid or sodium chloride.

Adenylyl Cyclases↗

PubMed1995

Instrumentational posterior fusion for atlanto-axial subluxation in a young child with Down's syndrome--case report.

A 3-year-old girl with Down's syndrome and myelopathy caused by atlanto-axial subluxation (AAS) was treated by C-1 to C-2 posterior fusion with a one-piece cervical device (OPCD). Instrumentation was required because the posterior arch of C-1 was too tiny and fragile to tolerate wiring. Postoperative immobilization was another major problem in this mentally retarded young child, but a hard plastic cervical corset effectively restrained the neck. She had been confined to bed by severe quadriparesis, but became able to walk without assistance 8 months after surgery. We recommend OPCD instrumentation and postoperative immobilization using a hard plastic corset for the treatment of AAS associated with Down's syndrome in young children.

Atlanto-Axial Joint↗

PubMed1995

Efficacy of delayed granulocyte colony-stimulating factor after full dose CHOP therapy in non-Hodgkin's lymphoma: a pilot study for a leukocyte count oriented regimen.

Bone marrow toxicity is a great challenge for physicians treating patients with non-Hodgkin's lymphoma (NHL) and prescribed chemotherapy. Granulocyte colony-stimulating factor (G-CSF) prevents myelotoxicity, but the optimal timing and scheduling of G-CSF administration has not been ascertained. We investigated leukocyte count oriented G-CSF administration schedules, as related to full dose administration of cyclophosphamide, adriamycin, vincristine, and prednisolone (CHOP) chemotherapy, with shortened intervals. Thirty-eight Japanese patients with NHL were included in this study. The standard CHOP combination was administered in six cycles. Patients were given G-CSF in a dose of 2 micrograms/kg/day, subcutaneously starting the day when total leukocytes were < 3,000/microliters. When leukocyte count remained at > 3,000/microliters, G-CSF was started 10 days following CHOP. Treatment with G-CSF was discontinued after the leucocyte count reached > 10,000/microliters, and CHOP was started the next day (CHOP-G treatment; CHOP-G). Doses were not modified in any patient. Patients over 70 years of age received 2/3 of the standard dosage. In the first cycle of CHOP, the day of initiation of G-CSF was 9.6 days following CHOP in the first cycle and 7.7 to 8.5 days during 2 to 6 cycles. The mean duration of G-CSF injection was 7.4 days with a range from 6.8 to 8.0 days, in each CHOP cycle. The mean intervals of CHOP-G was 14.7 days during six consecutive courses, and there was no prolongation of the intervals, even in later cycles. In 23 patients who received all six cycles of CHOP-G, the overall response rate was 91.3% (73.9% complete remission; CR and 17.4% partial remission; PR). In 32 patients with intermediate grade NHL, the overall response rate was 84.4% (65.5% CR and 18.8% PR). Thus, the full dose CHOP with G-CSF, based on the leukocyte count oriented schedule, can be achieved with shortened intervals, an approach which will increase the quality of life (QOL) for the patients by reducing the days of treatment as well as the cost of G-CSF.

Adolescent↗

PubMed1995

Synthesis and evaluation of DMPO-type spin traps.

The spin traps substituted with some groups at the 4-position of dimethyl-1-pyrroline N-oxide(DMPO) were compared with DMPO itself regarding their abilities as spin traps and their physical properties. 4,5,5-Trimethyl-1-pyrolline N-oxide (4MDMPO) and 5,5-dimethyl-4-phenyl-1-pyrolline N-oxide (4PDMPO) were synthesized by the Bonnett method, and 5,5-dimethyl-4-hydroxymethyl-1-pyrolline N-oxide (4HMDMPO) was made by a unique method from 2(5H)-furanone. The melting points of 4MDMPO, 4PDMPO and 4HMDMPO were higher than that of DMPO. The magnitude of hydrophilicity was in the order of 4HMDMPO, DMPO, 4MDMPO, and 4PDMPO based on the partition coefficient experiments in a 1-octanol--water system. Several radicals, O2-., HO., .CH3, .CH2OH, .CH(CH3)OH, (CH3)3CO. and H. radicals, were trapped with these DMPO derivatives for comparison with the trapping by DMPO itself. Spin adducts of O2-. with the three DMPO derivatives showed ESR spectra similar to that of DMPO. In spite of the formation of diastereomers arising from spin trapping, the line-width enlargement was very small. The intensities and the decay rates of the spectra of 4MDMPO-O2-, 4PDMPO-O2-, 4HMDMPO-O2- and DMPO-O2- were almost equal. In the trapping of the .OH radical by 4MDMPO, 4PDMPO and 4HMDMPO, the eight-line ESR spectra observed were different from the well-known four-line spectrum of DMPO-OH.

Cyclic N-Oxides↗

PubMed1995

[Diagnostic and therapeutic problems in vestibular neuronitis: clinical implications for sudden vertigo].

We defined sudden vertigo as a sudden, unilateral peripheral vestibular dysfunction. The criterion for its diagnosis is a single episode of vertigo without cochlear and central symptoms. Among 20 patients with sudden vertigo there was no difference in clinical aspects between those with CP (canal paresis) (CP% > or = 25%) and those without CP (CP% < 25%). This suggests that sudden vertigo with CP is due to sudden vestibular dysfunction with predominant involvement of the lateral semicircular canal. Basically, vestibular neuronitis is considered to be due to acute unilateral neuropathy of the vestibular nerve. However, since we have no routine examination for evaluating vestibular nerve function, sudden vertigo with CP should be diagnosed as vestibular neuronitis. We then assessed the prognosis of sudden vertigo with CP (vestibular neuronitis). About two years after the onset of CP 4 of 10 patients had recovered. However, patients with persistent CP had a handicap in their everyday life because of the dizziness induced by head movements. The possibility of recovery of vestibular function in response to steroid therapy may improve the prognosis in vestibular neuronitis.

Adult↗

PubMed1995

[Surgical outcome of cervical flexion myelopathy in young adults].

We encountered five young male patients with cervical flexion myelopathy, and treated them all surgically. Symptoms were first noted at 15 to 18 years of age (mean: 16.6 years), and their ages at the time of admission to our hospital, ranged from 19 to 25 years old (mean: 20.8 years). Anterior decompression and fusion of the cervical spine with long bone graft following resection of two vertebrae was performed in three cases. The other two patients were treated by posterior fusion of five laminas (C3-C7) using Rogers' method. In selecting the surgical approach, we favored anterior fusion because it allows removal of anterior structures (vertebral bodies, intervertebral discs or osteophytes) compressing the cervical spinal cord in flexed neck position. Posterior fusion was performed in patients whose anterior structures compressing the cervical spinal cord extended over a wide area. Postoperative improvement of muscle weakness was observed in four patients, and sensory disturbance was alleviated in the remaining patient. However, the abnormal deep tendon reflexes and muscle atrophy in the upper extremities observed in all of the patients preoperatively improved in only two of them. Thus, all of the patients showed some neurological improvement, and surgical fusion of the cervical spine appeared to be an effective means of treating cervical flexion myelopathy in young adults. Both the anterior and the posterior approach were useful in treating cervical flexion myelopathy, but it was impossible to conclude which approach is more effective based on this small number of cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

[Hemophagocytic syndrome with syndrome of inappropriate secretion of antidiuretic hormone (SIADH)].

A 69-year-old female was admitted to the hospital because of fever, hyponatremia and anemia. Laboratory data showed hemoglobin 8.6 g/dl, indirect bilirubin 1.9 mg/dl and Na 122 mEq/l. Urine osmolality was elevated and urinary excretion of sodium was increased. Furthermore, antidiuretic hormone (ADH) level was elevated. Renal function and hormonal data were within normal limit. Therefore, she was diagnosed as having syndrome of inappropriate secretion of antidiuretic hormone (SIADH). On the other hand, bone marrow aspiration showed hemophagocytosis and the diagnosis of hemophagocytic syndrome (HPS) was also made. High dose prednisolone and pulse therapy of cyclophosphamide were administered, nevertheless high grade fever persisted. Fever alleviation was acquired by Etoposide. But she died of pneumonia. An autopsy revealed hemophagocytosis in bone marrow, lymphnodes and spleen, but malignant tumor was not detected. And hypophysis was intact. The pathogenesis of SIADH in this case was not clarified. This report is seemed to be the first case of HPS associated with SIADH.

Aged↗