Biomedical subjects

K Kanmatsuse

Publications and source records attributed to K Kanmatsuse.

At least 91 records · Page 5Linked to original sources

PubMed1999

[Conservative management in patients with acute coronary syndrome].

Plaque rupture has been thought to cause acute coronary syndrome. To manage the patients with unstable angina, it is necessary to understand the patients' pathophysiology. Based on the classification of unstable angina, initial medical treatment including aspirin and oral isosorbide dinitrate should be started immediately after admission. Ca antagonist and beta-blocking agent should be added according to the symptoms. If ischemic symptoms continue after administration of those oral medical treatments, intravenous nitroglycerin and heparin should be started. K channel opener (nicorandil) may be effective to stabilize the symptom. However, high-risk patients should immediately receive coronary angiography to decide further medical or interventional therapy.

Angina, Unstable↗

PubMed1999

[The role of nitric oxide in deoxycorticosterone acetate-salt hypertensive rats].

The relationship between nitric oxide (NO) and blood pressure (BP) in deoxycorticosterone acetate-salt hypertensive rats (DOC) was investigated. Although urinary NO2- + NO3- (NOx) excretion (UNOxV) increased 2 weeks after surgery (2W-DOC), UNOxV decreased 4 weeks after surgery (4W-DOC) compared with that of the control. BP and UNOxV did not change in DOC after treatment with L-arginine (Arg-DOC). Aorta from 4W-DOC and Arg-DOC had significantly decreased relaxation responses to acetylcholine. Deendothelialized aorta from 4W-DOC and Arg-DOC had significantly decreased relaxation responses to lipopolysaccharide. These data suggest that: 1) transient increase of NO synthesis is accompanied by elevation of BP, but long-term elevation of BP decreases NO synthesis in endothelium and smooth muscle cells; 2) L-arginine supplement has no effect on the development of hypertension nor on NO production by endothelium and smooth muscle cells in DOC.

Acetylcholine↗

PubMed1999

[Effect of lipoprotein metabolism abnormality for intimal thickening].

Recent advances of lipoprotein metabolism abnormality were reviewed. Recombinant apolipoprotein and transgenic mice expressing high levels of apolipoproteins or apolipoprotein deficient mice produced by gene targetting technique are providing important information on effect of lipoprotein metabolism. We made novel mouse cuff injury model for transgenic mice and knock-out mice. This injury model will also provide important information on intimal thickening using transgenic mice and knock-out mouse.

Animals↗

PubMed1999

[Three cases of pregnancy in primary glomerulonephritis with successful outcomes in spite of severe histological findings].

When women with kidney disease wish to have children, concerns are raised about the adverse effect on their renal function. Although the situation is less clear in regard to the effects, there is general agreement that a moderately severe decrease in renal function, especially in the presence of significant hypertension, reduces the chance of conception, and a successful outcome of gestation. On the other hand, several reports maintain that in most patients, pregnancy does not change the natural history of glomerular disease. Accordingly, we reported successful cases in whom renal function remained preserved. The three cases suffered from different types of glomerulonephritis (GN) and percutaneous renal biopsies were conducted before pregnancy. All biopsy specimens were examined by light and immunofluorescence microscopy, and were diagnosed as IgA nephropathy, sclerosing GN and membranoproliferative GN, respectively. Since severe histological findings were found and their data worsened (serum creatinine > 1.3 mg/dl, 24-hr creatinine clearance < 70 ml/min), their chance of having children appeared low. However, as we did not observe deterioration of clinical findings and hypertension over the ten-year follow-up, we allowed conception resulting in the birth of normal children. Thus we should mention the relatively favourable courses of nephropathy in some patients with GN, particularly in patients with stable renal disease and normal blood pressure, it should not be considered an indication for termination. It is important to observe the status of glomerular disease for as long as possible.

Adult↗

PubMed1999

Interleukin-15 and interleukin-12 have an additive effect on the release of vascular permeability factor by peripheral blood mononuclear cells in normals and in patients with nephrotic syndrome.

BACKGROUND: The vascular permeability factor (VPF) is a lymphokine that has been shown to play a role in minimal-change nephrotic syndrome (MCNS). A better understanding of the mechanisms that upregulate VPF release is of basic importance to control the immune system in nephrotic syndrome (NS). Interleukin (IL)-15 is a key inducer of differentiation of uncommitted T helper cells, which regulates cellular immunity. The cytokine IL-15 appears to mimic the stimulatory activity of IL-2 on T cells. PATIENTS AND METHODS: In the present report, we studied the ability of IL-15, alone or in combination with IL-12, to influence the release of VPF by peripheral blood mononuclear cells (PBMC) from nephrotic patients. We have analyzed the release of VPF by concanavalin-A- (Con A) stimulated PBMC in normals, 16 patients with MCNS and 16 patients with IgA nephropathy (IgAN). RESULTS: In both patient groups 50% had a proteinuria below 0.8 g/day. We demonstrate that nephrotic, but not non-nephrotic patients (both MCNS and IgAN), exhibit a high VPF release, which can be stimulated further by IL-15 + IL-12. To determine the specificity of the stimulatory effect, neutralizing anti-IL-15 and anti-IL-12 antibodies were preincubated with IL- 15 and IL-12 prior to the addition of responder cells, respectively. The antibodies completely inhibited the effects of IL-15 and IL-12. CONCLUSION: These results indicate that IL-15 plus IL-12 acted additively to augment VPF release. These biological interactions between IL-15 and IL-12 may be important in the pathophysiology of VPF in vitro.

Adolescent↗

PubMed1999

[Role of endothelium-derived hyperpolarizing factor in insulin-induced vasodilation in rat mesenteric artery].

Endothelium-derived hyperpolarizing factor (EDHF) as a factor in blood pressure regulation has received attention recently. However, its role in insulin-induced vasodilation is not clear. We investigated the mechanism of vasodilation induced by insulin in vitro using mesenteric arteries isolated from normotensive rats. The 2nd branch of the mesenteric artery was isolated from male Sprague-Dawley rats (12-14 weeks old), mounted on microcannules in a chamber and perfused with Krebs solution. The diameter of this segment was measured continuously with a video system under the following conditions: intraluminal insulin administration (10 and 100 mU/ml) with and without pretreatment by denudation, N omega-methyl-L-arginine methyl ester (L-NAME), indomethacin, tetrabuthylammonium (TBA, non-specific Ca2+ activated K channel blocker), charybdotoxin (ChTx, large-conductance Ca2+ activated K channel blocker), apaminn (small-conductance Ca2+ activated K channel blocker) or Na+/k(+)-ATPase blocker (ouabain). Insulin treatment induced dose-dependent vasodilation. The effects of insulin were significantly suppressed by denudation, TBA, apamin, and ChTx. L-NAME, indomethacin and ouabain did not influence the insulin-induced vasodilation. Results suggested that insulin dilates small arteries by activating the Ca2+ activated K channel.

Animals↗

PubMed1999

[Effects of angiotensin II receptor antagonist on insulin sensitivity and sympathetic activity in spontaneously hypertensive rats].

Although angiotensin AT1 receptor antagonist(AT1 A) improves insulin sensitivity in insulin resistant models, its effect on spontaneously hypertensive rats(SHR) has not been elucidated. We investigated the effects of AT1 A, candesartan on insulin sensitivity in SHR/Izm and the role of sympathetic activity in its mechanism. In 9-week-old SHR/Izm, candesartan(10 mg/kg/day) was given orally for 5 days. A control group received vehicle. On the 6th day, mean arterial pressure (MAP), heart rate(HR), plasma norepinephrine (PNE), plasma epinephrine(PE) and plasma dopaminc(PDA) were measured in both groups (n = 11 in each group). In the separate groups of rats, fasting blood glucose (FBG), serum sodium, serum potassium and insulin sensitivity by steady state blood glucose (SSBG) were assessed (n = 16 in the Candesartan group and n = 8 in the Control group). MAP and SSBG were significantly lower in the Candesartan group (117 +/- 2 mmHg and 138 +/- 5 mg/dl) than those in the Control group(155 +/- 6 mmHg and 164 +/- 10 mg/dl). Body weight, HR, FBG, PNE, PE, PDA, sodium and potassium were the same between the groups. In conclusion, since AT1 A, candesartal lowers blood pressure and improves insulin sensitivity irrespective of sympathetic activity in SHR/Izm, it is useful in treating hypertension associated with insulin resistance.

Angiotensin Receptor Antagonists↗

PubMed1999

[Evaluation of coronary flow velocity and coronary flow reserve before and after coronary angioplasty using transthoracic Doppler echocardiography and Doppler guide wire].

Evaluation of left anterior descending coronary (LAD) blood flow before and after coronary angioplasty was carried out non-invasively by ultrasonic Doppler echocardiography with a newly developed digital, high-frequency, high-resolution transthoracic ultrasonic Doppler flowmeter and a 7.5 MHz probe. The results were compared with those obtained using an intracoronary Doppler guide wire. Sixteen patients, 12 males and 4 females (mean age 57 +/- 14 years) with old myocardial infarction (8 patients) and angina pectoris (8 patients) were studied. Coronary flow reserve was compared following intravenous administration of adenosine triphosphate in 12 patients. The LAD blood flow was detected in 15 of 16 patients. There was a significant increase in the diastolic peak velocity from 22.2 +/- 10.6 to 29.4 +/- 14.6 cm/sec (mean +/- SD) and the coronary flow reserve from 1.8 +/- 0.3 to 2.8 +/- 0.6 (mean +/- SD). There was a good correlation between the data obtained using transthoracic flow measurement and intracoronary flow measurement (r = 0.61, p < 0.05). LAD blood flow can be easily detected parasternally using a digital, high frequency, high-resolution ultrasonic Doppler flowmeter. This method may be applicable for judging the efficacy of coronary angioplasty by measuring coronary flow reserve and for observing the clinical course of the patient non-invasively.

Adenosine Triphosphate↗

PubMed1998

Organization of the human natriuretic peptide receptor A gene.

We have determined the structural organization of the human natriuretic peptide receptor A (hNPRA) gene without screening the genomic library. Based on the information for the cDNA of hNPRA, we amplified some fragments of the long polymerase chain reaction (PCR) products covering all genomic sequences of the gene and directly sequenced the products after extraction and purification. The hNPRA gene spans approximately 16 kb and contains 22 exons and 21 introns. All of the exon-intron junction sequences coincide with the GT/AG consensus sequence. The sequence encoding the transmembrane domain, one part of the hNPRA topological structure, exists in exon 7. The results of this first study, determination of the hNPRA gene structure, will facilitate further genetic analysis of the hNPRA gene and its related diseases.

Asian People↗

PubMed1998

Influence of FK506 on experimental atherosclerosis in cholesterol-fed rabbits.

To investigate the role of activated T lymphocytes in the formation of atherosclerotic lesions, we studied the influence of FK506, an immunosuppressant, on the development of atherosclerosis in cholesterol-fed rabbits. New Zealand White rabbits fed on a 1.5% cholesterol diet were administered FK506 at 0.05 mg/kg (n = 12), 0.1 mg/kg (n = 12) or isotonic saline (as the control, n = 12) intramuscularly three times a week for 12 weeks. Although FK506 treatment did not affect plasma lipid levels, it caused an increase in the development of atherosclerotic lesions in a dose-dependent manner. Immunohistochemical analysis of the aorta after 8 weeks on the diet revealed that the ratio of T lymphocytes to the total number of cells in the plaques decreased significantly in the FK506 treated rabbits compared to the control rabbits. In culture, FK506 did not affect smooth muscle cell proliferation and cholesteryl ester formation in the macrophages. In contrast, culture medium from lymphocytes stimulated by concanavalin A decreased the accumulation of cholesteryl ester in the macrophages. This effect was inhibited by the culture medium in the presence of FK506. These findings suggest that activated T lymphocytes may inhibit intracellular cholesterol accumulation in atherosclerotic plaque.

Animals↗

PubMed1998

Variations in insulin sensitivity in spontaneously hypertensive rats from different sources.

We investigated the possibility of variations in the genetic transmission of insulin sensitivity in the offspring of spontaneously hypertensive rats (SHRs) and Wistar Kyoto rats (WKYs) obtained from different sources (Charles River, Tokyo, Japan [NCrj]; and Funabashi Farm, Chiba, Japan [Izm]) with the insulin suppression test (IST) using a somatostatin analog, glucose, and insulin. The steady-state blood glucose (SSBG) in the IST and the glucose infusion required (GIR) in the euglycemic-hyperinsulinemic clamp differ significantly between obese and lean Zucker rats, indicating that both methods are useful for identifying insulin resistance. The fasting blood glucose and SSBG of the IST were significantly higher in SHR/Izm than in WKY/Izm. We did not observe a significant difference between SHR/NCrj and WKY/NCrj. These results indicate that the genetic transmission of hypertension and impaired insulin sensitivity may be variable and that insulin resistance does not play an important role in the pathogenesis of hypertension in the SHR.

Animals↗

PubMed1998

Association of a variable number of tandem repeats in the endothelial constitutive nitric oxide synthase gene with essential hypertension in Japanese.

An impaired synthesis of nitric oxide (NO) by the vascular endothelium has been implicated in the pathogenesis of essential hypertension (EH). The possible association between a variable number of tandem repeats (VNTR) polymorphism in intron 4 of the endothelial constitutive NO synthase (ecNOS) gene and EH in Japanese subjects was investigated. A total of 123 individuals with EH and 120 normotensive control subjects were studied. The VNTR region of the ecNOS gene was amplified by the polymerase chain reaction to determine the number of repeats, and the allele frequencies were compared between the hypertensive and normotensive groups. Two alleles, containing four and five repeats, were identified. The overall distributions of allele frequencies differed significantly between the two groups, with the four-repeat allele more frequent in the EH group than in the normotensive group (P = .00027, odds ratio = 4.0). The four-repeat allele of the ecNOS gene was thus associated with EH and may be a genetic marker of this disease in Japanese subjects.

Alleles↗

PubMed1998

Left ventricular geometric patterns and QT dispersion in borderline and mild hypertension: their evolution and regression.

To investigate whether QT dispersion increases in borderline and mild hypertension during a longitudinal observation of > 3 years and whether it is improved with medications, left ventricular geometric patterns and QT dispersion were studied with special regard to their longitudinal changes in 85 male borderline and mild hypertensive subjects with left ventricular mass index < 125 g/m2. These subjects were followed for > 3 years without medication. Thirty-two patients with a left ventricular mass index > 125 g/m2 at the end of follow-up period were further observed using antihypertensive drugs for an additional 3 years. Echocardiograms and electrocardiograms were obtained at the beginning and end of the follow-up period. At the end of the follow-up period, subjects were classified into four groups based on ventricular geometric patterns determined by left ventricular mass index and relative wall thickness in diastole. The QT dispersion was greater in patients with concentric hypertrophy (56+/-18 msec) than in patients with normal geometry (41+/-17 msec) (P < .05) and increased significantly in the former group during the follow-up period. After medication, the left ventricular mass index regressed and the QT dispersion decreased (from 55+/-21 to 50+/-26 msec, P < .01) in these patients. Thus, these findings suggest that changes in the QT dispersion reflect both concentric evolution and regression of left ventricular hypertrophy.

Adult↗

PubMed1998

A T1083C polymorphism in the human adenosine A2a receptor gene is not associated with essential hypertension.

The adenosine A2a receptor (A2aAR) gene is thought to be involved in essential hypertension because adenosine elicits vasodilation and decreases arterial blood pressure via this receptor, and because disruption of the A2aAR gene increases blood pressure in mice. Therefore, using a restriction fragment length polymorphism (RFLP) of the A2aAR gene, we performed an association study in patients with essential hypertension. One hundred forty-two patients with essential hypertension and 142 age-matched subjects with normal blood pressure were studied. Polymerase chain reaction (PCR) was applied to amplify the T1083C polymorphic site in the A2aAR gene, and restriction analysis of the PCR product was employed to score the T and C alleles. Overall distributions of allele frequencies in the two groups were not significantly different. Thus, the alleles detected by this RFLP polymorphism in the A2aAR gene are not associated with essential hypertension.

Adult↗

PubMed1998

Adrenal renin-angiotensin-aldosterone system in streptozotocin-diabetic rats.

Previous studies have indicated that the local renin-angiotensin system (RAS) plays an important role in the regulation of aldosterone release. We focused this study on examining the dissociating changes in circulating RAS and adrenal RAS, and we produced a low plasma renin status in streptozotocin (STZ)-induced diabetic rats. Four and six weeks after treatment with STZ, the rats showed hyperglycemia, hyporeninemia, decrease in plasma angiotensin II (AII), and a slight, but non-significant increase in plasma aldosterone in the rats. The adrenal renin activity and aldosterone concentration were significantly increased in the group of rats six weeks after induction of diabetes compared to those in control rats. The group of rats four weeks after induction of diabetes showed an increase in adrenal aldosterone concentration and a slight, but non-significant increase in adrenal renin activity. Plasma ACTH, serum sodium, and potassium were unchanged in both treatment groups compared to the control. The present results indicate that hyperactivity or residual activity of adrenal RAS under hyporeninemia is associated with severe diabetes mellitus.

Adrenal Glands↗

PubMed1998

Bunazosin hydrochloride inhibits exaggerated growth of vascular smooth muscle cells from spontaneously hypertensive rats by suppressing the response to growth factors.

Selective alpha1-adrenoreceptor blockers were recently reported to have an in vivo antiproliferative effect on hypertensive cardiovascular organs. Cultured vascular smooth-muscle cells (VSMCs) from spontaneously hypertensive rats (SHRs) show exaggerated growth compared with cells from Wistar-Kyoto (WKY) rats. We investigated the effects of an alpha1-adrenoreceptor blocker, bunazosin hydrochloride (HCl), on the growth of VSMCs from SHRs. In the absence of serum, bunazosin HCl significantly inhibited basal DNA synthesis by VSMCs from SHRs, but not by cells from WKY rats. In the presence of serum, bunazosin HCl significantly inhibited DNA synthesis by VSMCs from both rat strains. Angiotensin (Ang) II, platelet-derived growth factor (PDGF)-AA, and epidermal growth factor (EGF) dose-dependently increased DNA synthesis by VSMCs from SHRs, but not by VSMCs from WKY rats. Bunazosin HCl significantly suppressed the response of DNA synthesis to PDGF-AA and EGF, but not to Ang II, in VSMCs from SHRs. Expression of basic fibroblast growth factor (bFGF), transforming growth factor-beta1 (TGFbeta1), and PDGF messenger RNA (mRNA) was markedly greater in VSMCs from SHRs than in cells from WKY rats. Bunazosin HCl significantly inhibited the expression of bFGF and TGFbeta1 mRNA in VSMCs from SHRs, but not in cells from WKY rats. These findings suggest that the inhibition of growth factor hyperresponsiveness and inhibition of the expression of growth factors in VSMCs from SHRs are associated with the antiproliferative effect of bunazosin.

Adrenergic alpha-Antagonists↗

PubMed1998

Production of eicosanoids and angiotensin II in resistance vessels in spontaneously hypertensive rats.

1. Angiotensin II (AngII) and eicosanoids may be important in vascular remodelling and the pressor response via autocrine and paracrine mechanisms. We evaluated the influences of ageing and beta-adrenoceptor stimulation on the production of vascular AngII and eicosanoids in male spontaneously hypertensive rats (SHR), aged 5, 17 and 30 weeks, and age-matched Wistar-Kyoto (WKY) rats. 2. All rats were weighed and their systolic blood pressure (SBP) was measured by the tail-cuff method. Mesenteric arteries were isolated and perfused with Krebs'-Henseleit solution. The outflows of prostaglandin E2 (PGE2), 6-keto-PGF1 alpha, thromboxane B2 (TxB2) and AngII were measured by specific radioimmunoassays. 3. The SBP was higher in SHR than in WKY rats in the 17- and 30-week-old groups and increased with age. Basal levels of PGE2 were significantly lower in SHR than in WKY rats. The ratios of 6-keto-PGF1 alpha to TxB2 and PGE2 to TxB2 were significantly lower in 17-week-old SHR compared with age-matched WKY rats. Basal AngII release did not differ between SHR and WKY rats and decreased with age. Isoproterenol stimulated the release of AngII; the magnitude of the increment was greater in WKY rats than in age-matched SHR. These results show that there is an imbalance in the production of vasodilator and vasoconstrictor eicosanoids in the resistance vessels of SHR at ages at which hypertension developed. 4. This imbalance may contribute to the increased vasoconstrictor response and vascular remodelling in SHR. Our findings suggest that vascular AngII plays a role in the ageing process and that beta-adrenoceptor-stimulated release of vascular AngII is impaired in SHR.

6-Ketoprostaglandin F1 alpha↗

PubMed1998

Genetic and serological evidence for multiple instances of unrecognized transmission of hepatitis C virus in hemodialysis units.

We investigated the unrecognized patient-to-patient transmission of hepatitis C virus (HCV) in hemodialysis units by performing phylogenetic and serological analyses of hypervariable region 1 (HVR1) of HCV. Of the 62 patients in one center, 11 were positive for HCV RNA. A total of 24 HVR1 sequences, including the minor population of sequences of HCV isolates, from each patient were closely related and classified into five clusters by phylogenetic analysis. Of the 11 patients, 5 were infected with multiple clusters of HCV. Two patients were infected with HCV during an 18-month interval between examinations, and these HVR1 sequences fell into one of the five clusters. In another hemodialysis center, 5 of the 20 patients were HCV RNA positive, and two HVR1 sequences were found to be closely related and phylogenetically derived from the same cluster. The antibody responses of these patients to the HVR1 peptides representative of the genetic clusters revealed exactly the same clustering as that shown by phylogenetic analysis. These findings suggest that phylogenetic and serological analyses of HVR1 sensitively detect unrecognized and multiple transmission of HCV occurring within the same room in hemodialysis centers. Fingerprinting analyses using hypervariable regions of infectious agents are useful in identifying the precise route of transmission of infection.

Amino Acid Sequence↗