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Biomedical subjects

K Kanmatsuse

Publications and source records attributed to K Kanmatsuse.

At least 37 records · Page 2Linked to original sources
PubMed2001

Elevated interleukin-18 levels in the urine of nephrotic patients.

BACKGROUND/AIM: The etiology of minimal-change nephritic syndrome (MCNS) is obscure. It has been speculated that T cells play a role in the pathogenesis of MCNS. Interleukin (IL)-18, a novel immunoregulatory cytokine with potent inferon-gamma-inducing activities, may play an important role in T-helper type 1-mediated immune responses. To examine further the possible role of IL-18 in nephrotic syndrome (NS), in the present study we measured IL-18 levels in the urine in different clinical stages of MCNS. The aim of this study was to investigate the involvement of IL-18 in MCNS. METHODS: Urine samples were obtained from 20 MCNS patients. The disease controls included 20 patients with IgA nephropathy. The samples were assayed for IL-18 protein by a sandwich enzyme-linked immunosorbent assay. RESULTS: Compared with normal controls, significantly increased urinary levels of IL-18 were detected in MCNS patients with the NS. The urinary IL-18 (uIL-18) levels correlated with the degree of proteinuria in MCNS patients. Moreover, when individual MCNS patients were followed through their clinical illness, uIL-18 levels were increased during the active phase and decreased as the patients went into remission. CONCLUSIONS: These results indicate that uIL- 18 is detectable in a subgroup of patients with active NS and correlates to their disease activity in patients with MCNS. Our findings support the notion that IL-18 may play a role in the pathophysiology of NS.

Adult↗
PubMed2001

Relationship between insulin resistance and uremic toxins in the gastrointestinal tract.

The relationship between insulin resistance and local uremic toxins was examined using an oral adsorbent. Fourteen rats demonstrating a diabetic state underwent two-thirds, nephrectomy and were divided into two groups. The control group was fed standard rat chow, and the test group was fed standard rat chow containing 5% AST-120. The target level of blood glucose was achieved by controlling the dosage of exogenous insulin. All rats were sacrificed at week 6. Body weight, blood glucose level, and renal function at week 6 were not significantly different between both groups. However, the mean blood glucose level and the mean dose of exogenous insulin in the AST-120-fed group were significantly reduced as compared with the control group. The results of the present study indicate that administration of an oral adsorbent in diabetic nephropathy decreases the doses of exogenous insulin and improves insulin resistance, and that uremic toxins which exist in the gastrointestinal tract play important roles.

Adsorption↗
PubMed2001

Association study between the variants of the human ANP gene and essential hypertension.

Variants of atrial natriuretic peptide (ANP) are reported to be more common in blacks with hypertension than in normotensive controls and constitute an independent risk factor for cerebral infarction. The purpose of the present study was to investigate the role of ANP in the pathogenesis of essential hypertension (EH) in the Japanese. We investigated 2 previously reported ANP gene markers, G1837A and T2238C, for their possible associations with EH. A total of 233 individuals with EH and 213 age-matched normotensive (NT) control subjects were studied. The frequencies of the G and A alleles were 0.09 (42/466) and 0.91 (424/466), respectively, for the NT group and 0.11 (47/426) and 0.89 (379/426), respectively, for the EH group. These frequencies did not differ significantly between the two groups. The frequencies of the T and C alleles were 0.024 (11/466) and 0.97 (455/466), respectively, for the NT group and 0.03 (13/426) and 0.97 (413/426), respectively, for the EH group. These frequencies also did not differ significantly between the two groups. Neither G1837A nor the T2238C polymorphism of the ANP gene was associated with EH. Our findings do not support the hypothesis that the G1837A and T2238C polymorphisms of the ANP gene are markers for EH in the Japanese.

Adult↗
PubMed2001

A novel mutation in Ca2+-sensing receptor gene in familial hypocalciuric hypercalcemia.

Missense mutations in the calcium-sensing receptor (CaSR) gene have previously been identified in patients with familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism. We identified a newborn with hypercalcemia in our hospital by mass screening. The family members were studied, and we found a novel CaSR missense mutation with polymerase chain reaction single-strand conformational polymorphism analysis. The mother, grandmother, and aunt of the baby all had FHH. A heterozygous missense mutation in exon 6 that substitutes a glutamic acid for the glycine at codon 557 (Gly557Glu), which corresponds to the extracellular domain of CaSR, was identified and shown to cosegregate with the disease. Identification of the mutation responsible for the FHH phenotype in this family may facilitate rapid testing of individuals at risk for FHH.

Adult↗
PubMed2001

Regulation of in situ complement activation via the lectin pathway in patients with IgA nephropathy.

The lectin pathway, which is initiated by mannose-binding lectin (MBL) and MBL-associated serine protease (MASP), is one of the possible routes to activate the complement cascade in immunoglobulin A (IgA) nephropathy. The purpose of this study was to elucidate the regulatory mechanism of the pathway. Levels of complement activation products and regulatory proteins were measured in sera from 27 patients with IgA nephropathy, and generation of fluid-phase complement activation products in the presence of pooled normal human serum was quantified to evaluate activation in vitro. Although there were no significant differences in the serum levels and in vitro activation between the MBL-MASP positive (n = 14) and negative (n = 13) groups, there were positive correlations between complement activation products (Bb fragment and C4d fragment) and regulatory proteins (factor H, C4-binding protein, and C1 inhibitor) in the MBL-MASP-positive group. Furthermore, immunohistochemical studies demonstrated glomerular deposition of the regulatory protein (C4-binding protein, alpha2-macroglobulin, and factor H) in all patients in the MBL-MASP-positive group. These findings suggest that the regulatory proteins control in situ complement activation via the lectin pathway immediately, and continuous activation due to inadequate control will lead to the advanced glomerular injury.

Carrier Proteins↗
PubMed2001

Elevated vascular endothelial growth factor levels in the urine of patients with minimal-change nephrotic syndrome.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a selective endothelial mitogen and vascular permeability factor (VPF), that is mainly produced by activated monocytes/macrophages and T cells. To our knowledge, very little is known about the involvement of VEGF in minimal-change nephrotic syndrome (MCNS). The aim here was to define further the involvement of VEGF in MCNS. PATIENTS AND METHODS: Urine samples were obtained from 20 MCNS patients. The disease controls included 20 patients with IgA nephropathy (IgAN). The samples were assayed for VEGF protein by a sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with normal controls, markedly increased urinary levels of VEGF were detected in both MCNS and IgAN patients with the nephrotic syndrome (NS). The urinary VEGF (uVEGF) levels correlated with the degree ofproteinuria in MCNS and IgAN patients. Moreover, when individual MCNS patients were followed through their clinical illness, uVEGF levels were increased during the active phase and decreased as the patients went into remission. Our main concern is to distinguish between two possibilities: Increases in uVEGF excretion might indeed relate to specific glomerular pathology and thus have a pathophysiological role. Alternatively, uVEGF may be derived from the circulation and as such may be nothing more than an assay for proteinuria. In fact, given the strict correlation between uVEGF excretion and the amount of proteinuria, the second possibility appears quite conceivable. CONCLUSION: Therefore, this may be a coincidental finding which has no bearing on the pathophysiology of MCNS.

Adult↗
PubMed2001

[Usefulness of combination post-stress dysfunction and perfusion imaging in technetium-99m-tetrofosmin myocardial scintigraphy].

OBJECTIVES: Myocardial perfusion imaging has lower sensitivity for the diagnosis of coronary artery disease in patients with three-vessel disease. The presence of post-stress dysfunction of the left ventricle, evaluated by electrocardiography(ECG) gated single photon emission computed tomography(SPECT) with a quantitative gated SPECT program, was investigated in patients with coronary artery disease, and also whether combining post-stress dysfunction and myocardial perfusion imaging improved the diagnosis of coronary artery disease. METHODS: ECG gated technetium-99m-tetrofosmin SPECT was performed using a one day, stress and rest, protocol in 139 patients. SPECT and coronary angiography were performed within 1 month. The coronary artery disease group consisted of 89 patients: 43 with one-vessel disease(1VD), 28 with two-vessel disease(2VD), and 18 with three-vessel disease(3VD). The group with zero-vessel disease(0VD) consisted of 50 patients. According to post-stress and rest ejection fraction(EF) and end-systolic volume (ESV), post-stress dysfunction is defined as follows: rest EF--post-stress EF > or = 5% and post-stress ESV--rest ESV > or = 5 ml. RESULTS: In the coronary artery disease group, post-stress ESV was larger than rest ESV(37.8 +/- 26.4, 34.0 +/- 24.2 ml, p < 0.001), and post-stress EF was lower than rest EF (61.5 +/- 11.1%, 64.2 +/- 10.8%, p < 0.001). In the 0VD group, ESV and EF were the same for post-stress and rest (25.7 +/- 20.8, 26.2 +/- 21.6 ml, NS; 70.4 +/- 9.5%, 70.0 +/- 9.6%, NS). Post-stress dysfunction was 6.0% in the 0VD group and 30.3% in the coronary artery disease group(p < 0.001). Furthermore, post-stress dysfunction in the 2VD (35.7%) and 3VD(38.9%) groups was higher than that in the 0VD group(p < 0.01, p < 0.01). Sensitivity of coronary artery disease diagnosis by myocardial perfusion imaging was 75%. The combination of post-stress dysfunction and myocardial perfusion imaging improved sensitivity from 75% to 82%(p < 0.05), but reduced the specificity from 92% to 86%(p = 0.08). CONCLUSIONS: Post-stress dysfunction is a useful parameter for clinical diagnosis of coronary artery disease.

Aged↗
PubMed2000

Ribozyme to human TGF-beta1 mRNA inhibits the proliferation of human vascular smooth muscle cells.

Transforming growth factor-beta (TGF-beta) has been reported to be involved in the pathogenesis of cardiovascular proliferative diseases such as hypertensive vascular disease, atherosclerosis, and arterial restenosis after angioplasty. We designed a 38-base DNA-RNA chimeric hammerhead ribozyme to cleave human TGF-beta1 mRNA as a gene therapy for human arterial proliferative diseases. In the presence of MgCl(2), synthetic ribozyme to human TGF-beta1 mRNA cleaved the synthetic target RNA into two RNA fragments of predicted size. A control mismatch ribozyme, with one different base in the catalytic loop region, was inactive. DNA-RNA chimeric ribozyme (0. 01-1.0 microM) significantly inhibited angiotensin II (Ang II)-stimulated DNA synthesis in a dose-dependent manner in human vascular smooth muscle cells (VSMC). The mismatch ribozyme did not affect Ang II-stimulated DNA synthesis in the cells. DNA-RNA chimeric ribozyme (1.0 microM) inhibited the proliferation of human VSMC in the presence of Ang II. DNA-RNA chimeric ribozyme (1.0 microM) significantly inhibited Ang II-stimulated TGF-beta1 mRNA and protein expression in human VSMC. These results indicate that the designed DNA-RNA chimeric hammerhead ribozyme targeted to human TGF-beta1 mRNA can effectively and potentially inhibit growth of human VSMC by cleaving the TGF-beta1 mRNA. This finding suggests that this ribozyme will be useful in the gene therapy of arterial proliferative diseases.

Base Sequence↗
PubMed2000

Enhanced serotonin-mediated responses in the nucleus tractus solitarius of spontaneously hypertensive rats.

Previous studies have demonstrated that injection of serotonin into the nucleus tractus solitarius (NTS) elicits hypotension and bradycardia in rats. The present study sought to further characterize this response and to examine the role of serotonergic mechanisms in the NTS in cardiovascular regulation in spontaneously hypertensive (SHR) rats. Injections of picomole amounts of serotonin into the NTS of chloralose-anesthetized normotensive Sprague-Dawley (S-D) or Wistar-Kyoto (WKY) rats produced hypotension and bradycardia that were eliminated by prior injection into the NTS of the selective 5HT(2) antagonist sarpogrelate. Bilateral injection of sarpogrelate did not alter blood pressure or reflex changes in heart rate in response to phenylephrine-induced increases in blood pressure or nitroprusside-induced decreases in blood pressure. In SHR rats, the depressor response produced by injection of serotonin into the NTS was markedly larger than in WKY rats, and was larger than depressor responses previously reported for other excitatory substances injected into the NTS. In SHR rats bilateral injection of sarpogrelate produced an increase in blood pressure, although it did not alter baroreceptor-evoked changes in heart rate. These results provide further support for the hypothesis that stimulation of 5HT(2) receptors in the NTS contributes to cardiovascular regulation independent of the baroreceptor reflex. Furthermore, this serotonergic system is altered in SHR rats, apparently acting tonically to reduce blood pressure.

Animals↗
PubMed2000

Functional deletion mutation of the 5'-flanking region of type A human natriuretic peptide receptor gene and its association with essential hypertension and left ventricular hypertrophy in the Japanese.

The natriuretic peptide (NP) family is involved in the regulation of blood pressure and fluid volume. We isolated the 5'-flanking region of the type A human NP receptor gene and identified an insertion/deletion mutation in this region. We then assessed whether there is a genetic association between this mutation and essential hypertension (EH). The deletion allele lacks 8 nucleotides and alters binding sites for the activator protein-2 (AP-2) and Zeste transcriptional factors. We genotyped 200 EH and 200 normotensive (NT) individuals and found 9 subjects with the deletion (8 in the EH group and 1 in the NT group). All 9 individuals were heterozygous. The NT subject with the mutation had left ventricular hypertrophy without hypertension. Transcriptional activity of the deletion allele was <30% that of the wild-type allele. The plasma levels of brain NP in EH patients with the deleted allele were significantly higher than the levels in the EH patients with the wild-type allele, and plasma brain NP levels were significantly higher in subjects with the deleted allele than in subjects with the wild-type allele, despite comparable blood pressures. These findings suggest that in Japanese individuals, this deletion in the human NP receptor gene reduces receptor activity and may confer increased susceptibility to developing EH or left ventricular hypertrophy.

Adult↗
PubMed2000

Effect of methylene methylimino linkage of antisense oligonucleotide to the platelet-derived growth factor A-chain on growth of vascular smooth muscle cells from spontaneously hypertensive rats.

Spontaneously hypertensive rats (SHR)-derived vascular smooth muscle cells show exaggerated growth and increased expression of platelet-derived growth factor (PDGF) A-chain mRNA. We examined the effect of methylene methylimino linkage of antisense oligodeoxynucleotide, a novel modification of antisense oligodeoxynucleotide designed to increase nuclease resistance, to PDGF A-chain on the exaggerated growth of vascular smooth muscle cells from SHR. Methylene methylimino-linked oligodeoxynucleotide provided complete resistance against S1 nuclease. Methylene methylimino linkage of antisense oligodeoxynucleotide to PDGF A-chain resulted in a rapid inhibition of basal DNA synthesis of vascular smooth muscle cells from SHR. This inhibition was much greater than that produced by phosphorothioate linkage of antisense oligodeoxynucleotide to PDGF A-chain. The methylene methylimino linkage of antisense oligodeoxynucleotide to PDGF A-chain may prove useful in the treatment of arterial proliferative diseases including hypertension.

Alkenes↗
PubMed2000

DNA-RNA chimeric hammerhead ribozyme to transforming growth factor-beta(1) mRNA inhibits the exaggerated growth of vascular smooth muscle cells from spontaneously hypertensive rats.

OBJECTIVE: The purpose of this study was to develop DNA-RNA chimeric hammerhead ribozyme against transforming growth factor-beta(1) (TGF-beta(1)) mRNA as a gene therapy agent for arterial proliferative diseases. METHODS: A 38-base hammerhead ribozyme against rat TGF-beta(1) mRNA, to produce cleavage at the GUC sequence at nucleotide 825 according to the secondary structure of rat TGF-beta(1) mRNA was designed. To enhance its stability, we synthesized a DNA-RNA chimeric ribozyme with two phosphorothioate linkages at the 3'-terminal. We also synthesized a mismatch ribozyme with single base change in the catalytic loop region as a control. These ribozymes were delivered into rat vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats by lipofectin-mediated transfection, and their biological effects were investigated. RESULTS: According to in vitro cleavage studies, the synthetic ribozyme can cleave the synthetic substrate RNA into two RNA fragments. Chimeric ribozyme significantly inhibited DNA synthesis in VSMC from SHR but not in cells from WKY rats. Mismatch ribozyme showed only a little effect on growth of VSMC from SHR. Chimeric ribozyme significantly inhibited proliferation of VSMC from SHR; in contrast, the proliferation of VSMC from WKY rats was significantly increased by this chimeric ribozyme. Mismatch ribozyme did not affect proliferation of VSMC from either rat strain. Chimeric hammerhead ribozyme to rat TGF-beta(1) dose-dependently inhibited TGF-beta(1) mRNA expression detected by reverse transcription and polymerase chain reaction analysis in VSMC from both rat strains. Chimeric hammerhead ribozyme to rat TGF-beta(1) also dose-dependently inhibited TGF-beta(1) protein production detected by Western blot analysis. CONCLUSIONS: The present results demonstrated that our designed DNA-RNA chimeric hammerhead ribozyme to TGF-beta(1) mRNA might be a useful gene therapy agent for hypertensive vascular diseases.

Analysis of Variance↗
PubMed2000

Cardiopulmonary cerebral resuscitation using emergency cardiopulmonary bypass, coronary reperfusion therapy and mild hypothermia in patients with cardiac arrest outside the hospital.

OBJECTIVES: The purpose of this study was to evaluate the efficacy of an alternative cardiopulmonary cerebral resuscitation (CPCR) using emergency cardiopulmonary bypass (CPB), coronary reperfusion therapy and mild hypothermia. BACKGROUND: Good recovery of patients with out-of-hospital cardiac arrest is still inadequate. An alternative therapeutic method for patients who do not respond to conventional CPCR is required. METHODS: A prospective preliminary study was performed in 50 patients with out-of-hospital cardiac arrest meeting the inclusion criteria. Patients were treated with standard CPCR and, if there was no response, by emergency CPB plus intra-aortic balloon pumping. Immediate coronary angiography for coronary reperfusion therapy was performed in patients with suspected acute coronary syndrome. Subsequently, in patients with systolic blood pressure above 90 mm Hg and Glasgow coma scale score of 3 to 5, mild hypothermia (34 C for at least two days) was induced by coil cooling. Neurologic outcome was assessed by cerebral performance categories at hospital discharge. RESULTS: Thirty-six of the 50 patients were treated with emergency CPB, and 30 of 39 patients who underwent angiography suffered acute coronary artery occlusion. Return of spontaneous circulation and successful coronary reperfusion were achieved in 92% and 87%, respectively. Mild hypothermia could be induced in 23 patients, and 12 (52%) of them showed good recovery. Factors related to a good recovery were cardiac index in hypothermia and the presence of serious complications with hypothermia or CPB. CONCLUSIONS: The alternative CPCR demonstrated an improvement in the incidence of good recovery. Based upon these findings, randomized studies of this hypothermia are needed.

Adolescent↗
PubMed2000

Angiotensin II regulates the cell cycle of vascular smooth muscle cells from SHR.

We have demonstrated that spontaneously hypertensive rats (SHR)-derived vascular smooth muscle cells (VSMC) show the exaggerated growth and produce angiotensin II (Ang II). In the current study, we investigated the role of endogenous Ang II in the regulation of the cell cycle in VSMC from SHR. Levels of Ang II in conditioned medium from SHR-derived VSMC cultured without serum were significantly higher than levels in conditioned medium from Wistar-Kyoto (WKY) rat-derived VSMC. Basal DNA synthesis was higher in quiescent VSMC from SHR than that in cells from WKY rats. An Ang II type 1 receptor antagonist, CV11974, significantly inhibited the elevation in DNA synthesis in quiescent VSMC from SHR but did not affect it in cells from WKY rats. Cellular DNA content analysis by flow cytometry revealed that the proportion of cells in S phase was higher, whereas the proportion of cells in G1+G0 phase was lower in VSMC from SHR than those in cells from WKY rats. CV11974 significantly decreased the proportion of cells in S phase and correspondingly increased the proportion of cells in G1+G0 phase in VSMC from SHR, but it did not affect the proportion in cells from WKY rats. Cyclin-dependent kinase 2 (CDK2) activity, which is known to induce the progression from G1 to S phase, was higher in VSMC from SHR than in cells from WKY rats. Expression of CDK2 inhibitor p27(kip1) mRNA was markedly higher in VSMC from SHR than in cells from WKY rats. CV11974 decreased expression of p27(kip1) mRNA in VSMC from SHR, whereas CV11974 increased it in cells from WKY rats. These findings indicate that enhanced production of endogenous Ang II regulates the cell cycle especially in the progression from G1 to S phase, and increases CDK2 activity, which is independent of p27(kip1) in VSMC from SHR.

Angiotensin II↗
PubMed2000

Association of 5' upstream promoter region of prostacyclin synthase gene variant with cerebral infarction.

The aim of this study was to investigate whether there is an association between the promoter region of the prostacyclin synthase gene and cerebral infarction (CI). Using the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) method, we found a variable-number tandem repeat polymorphism in the 5'-upstream promoter region of the prostacyclin synthase gene. This region contains transcriptional factors-binding sites of Spl (CCCGCC) and AP-2 (CCGCCAGCCCC). The alleles varied in size from three to seven repeats of nine base pairs (bp). We performed an association study using the polymorphism in 111 patients and 152 control subjects. The transcriptional activity of the abnormal promoter region allele was determined by luciferase assay. The overall distribution of alleles differed significantly between both groups. Logistic linear regression analysis revealed the small number repeat allele to be found more frequently with CI. Transcriptional activity increased with increasing numbers of repeats. This study provides consistent support for the association between CI and the PGIS gene.

Aged↗