Search PubMed⌕ Search

Biomedical subjects

S Suga

Publications and source records attributed to S Suga.

At least 145 records · Page 8Linked to original sources
PubMed1996

Insulin suppresses endothelial secretion of C-type natriuretic peptide, a novel endothelium-derived relaxing peptide.

We have previously reported that C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, is produced in vascular endothelial cells (ECs) and acts as an endothelium-derived relaxing peptide. We further demonstrated the detection of the gene transcripts of CNP and atrial natriuretic peptide (ANP) B receptor, a specific receptor for CNP, in human blood vessels. We thus propose the existence of a vascular natriuretic peptide system (NPS). CNP secretion was also demonstrated to be stimulated by various growth factors and cytokines. To clarify the significance of vascular NPS in proliferative vascular complications associated with diabetes, hypertension, or atherosclerosis, in the present study we examined the effect of insulin on CNP secretion from cultured ECs. Insulin at a concentration in the physiological range (10(-10)-10(-7) mol/l) potently suppressed CNP secretion, whereas insulin at the same concentration did not suppress endothelin (ET) secretion from EC. IGF-I had no significant effect on CNP secretion. Insulin, therefore, can be a potent inhibitor of CNP secretion through the activation of insulin receptor. Since CNP has been shown to be a potent inhibitor of vascular smooth muscle cell proliferation, the present study suggests the possibility that attenuated activity of vascular NPS is associated with hyperinsulinemia, which might result in proliferative vascular lesions.

Animals↗
PubMed1996

Intracellular localization of antigens recognized by anti-vimentin monoclonal antibodies (mAbs): cross-reactivities of anti-vimentin mAbs with other cellular components.

Monoclonal antibodies were raised against immunoaffinity-purified fusion regulatory protein (FRP)-1 complex from membrane fraction of HeLa cells. Immunoblotting and immunoprecipitation studies showed all ten antibodies reacted with a 55 kDa band of cell lysate and purified vimentin. Interestingly, one of the antibodies (mAb57) cross-reacted with purified tropomyosin and myosin. Further analyses using vimentin chemically cleaved by 2-nitro-5-thio-cyanobenzoic acid, and lambda gt 11 cDNA which encoded a partial sequence of vimentin indicated that six mAbs recognized epitopes between amino acids 1 and 313 and the other four mAbs recognized epitopes in the area between residues 314 and 326. Indirect immunofluorescence microscopy using 3% formalin-fixed, 0.1% Triton X-100 treated HeLa cells revealed that seven antibodies stained various intracellular components other than vimentin, while three antibodies stained vimentin filaments alone. Furthermore, flow cytometric analysis showed one of the antibodies (mAb25) clearly stained the surface of unfixed HeLa cells. All immunofluorescent findings were the same when HeLa, baby hamster kidney (BHK) and murine L229 cells were examined. These results indicate that we could obtain unique anti-vimentin mAbs which show cross-reactivities with previously undescribed cell surface and intracellular molecules including tropomyosin and myosin. Taken together, there are two possibilities that explain our findings: (1) The unknown molecules may have structural similarity to vimentin. (2) Our anti-vimentin mAbs can react specifically with structurally distinct epitopes present on both unknown molecules and vimentin. In either case, our cross-reactive mAbs, which recognized undescribed epitopes on vimentin, maybe provide useful tools for studying intermediate filaments and related cellular components.

Animals↗
PubMed1996

C-type natriuretic peptide in chronic renal failure and its action in humans.

We have previously reported that C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, is produced in vascular endothelial cells and acts as an endothelium-derived relaxing peptide. To clarify the clinical significance of CNP in renal disorders, we examined the plasma level of CNP in patients with various cardiovascular diseases, including chronic renal failure (CRF) patients who were under hemodialysis therapy. We also investigated biological effects of intravenously-administered CNP (0.43 nmol/kg) by bolus injection from the peripheral vein in healthy volunteers and measured systemic hemodynamic variables, plasma levels of CNP, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), cGMP, aldosterone and also urine volume, urinary excretions of sodium, potassium, chloride and cGMP. The plasma CNP levels in healthy humans (N = 13) was 1.4 +/- 0.6 fmol/ml. In CRF patients, the plasma CNP significantly increased up to 3.0 +/- 1.1 fmol/ml. The administration of CNP elicited significant increase of plasma cGMP level (from 4.77 +/- 1.25 to 8.33 +/- 1.59 pmol/ml 15 min after the administration) and of urinary cGMP excretion (from 30.7 +/- 4.3 to 74.9 +/- 13.4 nmol/30 min). Intravenously-administered CNP exerted significant diuretic (% increase: +117 +/- 85.0), natriuretic, kalliuretic and chloriuretic actions with the increase of endogenous creatinine clearance. CNP also elicited significant hypotensive actions (delta BPs/delta BPd: -4.3 +/- 1.3/-4.1 +/- 1.0 mm Hg) with the concomitant increase of heart rate (+7.6 +/- 2.6 bpm). Plasma aldosterone concentration significantly decreased from 45.4 +/- 2.3 to 35.4 +/- 4.9 pg/ml 30 minutes after the administration. Taken together, these results suggest a role for CNP in human renal function.

Adult↗
PubMed1996

Rhabdomyolysis following administration of cyclophosphamide: a case report in a BMT recipient.

Massive rhabdomyolysis followed by myocardial necrosis was observed in a 14-year-old patient undergoing allogeneic bone marrow transplantation for severe aplastic anemia. Rhabdomyolysis was preceded by the administration of cyclophosphamide as part of a preparative regimen for transplantation Although the specific etiology of this rhabdomyolysis is still unknown, an association with high-dose cyclophosphamide should be noted.

Bone Marrow Transplantation↗
PubMed1996

[Optimum dose study of cefozopran in the pediatric field].

Cefozopran (SCE-2787, CZOP) was administered to patients with pediatric infections three to four times daily by intravenous injection or 30-minute intravenous drip infusion, and investigations were made in individual cases, on relationships among doses, pharmacokinetics, effects on pathogenic bacteria and MIC against them, and clinical effects. The following results on optimal doses of CZOP were obtained. 1. Clinical cases in which CZOP was administered at a dose of 10 mg (potency)/kg The subjects were 7 patients including 4 patients with pneumonia. Severities of the diseases were severe in one of the patients with pneumonia, and moderate in the other patients. The MIC against pathogenic bacteria (4 strains) isolated from these cases ranged from 0.2 to 1.56 micrograms/ml. The serum concentrations were in a range between 1.4 and 7.6 micrograms/ml at 4 hours after administration. In some cases, the serum concentrations were lower than the MICs, though slightly. In the clinical evaluation, CZOP was excellent in 3 cases, good in 2 cases and fair in 1 case. The evaluation was impossible in 1 case. The efficacy rate was 83.3% (5/6). In bacteriological evaluation, 3 out of the 4 strains disappeared. Adverse reactions and abnormal laboratory test values were not observed. 2. Cases in which CZOP was administered at a dose of 20 mg (potency)/kg The subjects were 5 patients including 2 with pneumonia, and severities were severe in one of the patients with pneumonia, and moderate in the other patients. The MICs against the pathogenic bacteria (3 strains) isolated from these cases ranged from 0.1 to 1.56 micrograms/ml. While, serum concentrations at 4 hours after administration were in a range between 3.0 and 7.7 micrograms/ml sufficiently exceeding the MICs. In the clinical evaluation, CZOP was excellent in 1 case and good in four cases, with an efficacy rate of 100% (5/5). In the bacteriological evaluation, all the 3 strains disappeared. No adverse reactions were observed, but an abnormal laboratory test value showing eosinophilia was noted in one case. 3. Cases in which CZOP was administered at a dose of 40 mg (potency)/kg The subjects were 5 patients including 3 with pneumonia. The severity was moderate in 2 of the pneumonia patients, and severe in the other three cases. The MICs against the pathogenic bacteria (4 strains) isolated from these cases were in a range between 0.1 and 0.78 micrograms/ml. The serum concentrations at 4 hours after administration ranged from 6.5 to 21.9 micrograms/ml, sufficiently exceeding the MICs. In the clinical evaluation, CZOP was excellent in 4 cases and good in 1 case, with an efficacy rate of 100% (5/5). The efficacy rate in the bacteriological evaluation was also 100%. As adverse reaction, red urine was observed in one case. Eosinophlia was noted in one case in the laboratory tests. When CZOP was administered to patients with pediatric infections at a dose of 10 mg (potency)/kg, the clinical effect of the drug was insufficient in a case in which serum concentration of CZOP at 4 hours after administration was lower than the MICs against the pathogenic bacteria. When CZOP was administered at a dose of 20 mg (potency)/kg, sufficient concentrations were obtained, and the drug efficacies were found to be excellent or good in all cases. Therefore, the effective dose normally used is considered to be 20 mg (potency)/kg. When CZOP was administered at a dose of 40 mg (potency)/kg, the drug was found to be excellent or good in all of the cases although the severities were high in more than half of the cases tested. In addition, the rate of excellent efficacies was 80% (4/5). Furthermore, no severe adverse reactions were observed. It was, therefore, confirmed that CZOP should be administered at a dose of 40 mg (potency)/kg in severe or intractable cases.

Bacterial Infections↗
PubMed1995

Molecular characterization of fusion regulatory protein-1 (FRP-1) that induces multinucleated giant cell formation of monocytes and HIV gp160-mediated cell fusion. FRP-1 and 4F2/CD98 are identical molecules.

Fusion regulatory protein (FRP)-1 regulates virus-mediated cell fusion and fusion of monocytes. Eleven of fifteen N-terminal amino acids of FRP-1 were the same as the amino acid sequence of 4F2/CD98 heavy chain. FRP-1 molecules were detected in Con A- or IL-2-stimulated lymphocytes, while FRP-1 was rare on resting lymphocytes. These properties of FRP-1 are similar to those of 4F2/CD98. Treatment of monocytes with anti-4F2/CD98 mAbs resulted in cell fusion, and other mAbs directed against 4F2/CD98 induced formation of multinucleated giant cells of Cd+U2ME-7 cells, a CD4+U937 cell line transfected with the HIV gp160 gene. Both anti-4F2/CD98 and anti-FRP-1 mAbs reacted with murine L929 cells expressing human 4F2/CD98 transiently or constitutively. When Newcastle disease virus (NDV)-infected L929 cells expressing human FRP-1/CD98 were incubated with mAb 4-5-1, an anti-FRP-1 mAb, multinucleated giant cells were induced; thus, FRP-1/CD98 molecules expressed in L929 cells are functional for fusion regulatory activity.

Amino Acid Sequence↗
PubMed1995

Rapid ventricular induction of brain natriuretic peptide gene expression in experimental acute myocardial infarction.

BACKGROUND: We have demonstrated that brain natriuretic peptide (BNP) is a cardiac hormone predominantly synthesized in and secreted from the ventricle. We have also reported that, compared with atrial natriuretic peptide (ANP), the plasma concentration of BNP is increased to a greater degree in patients with congestive heart failure and more rapidly in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: To investigate ventricular gene expression of BNP in AMI, we analyzed plasma and ventricular BNP concentrations along with ventricular BNP mRNA in rats with AMI produced by coronary artery ligation. The BNP concentration in the left ventricle increased about 2-fold as early as 12 hours postinfarction and 5-fold 1 day postinfarction compared with sham-operated rats, whereas left ventricular ANP concentration remained unchanged within 1 day. The tissue concentration of BNP increased in the noninfarcted region as well as in the infarcted region. The surviving myocytes in and around the necrotic tissues in the infarcted region were intensely stained with the anti-BNP antiserum, indicating augmented production in the remaining myocytes in the infarcts. The BNP concentration in the right ventricle also increased about 10-fold 12 hours postinfarction, whereas the ANP concentration remained unchanged within 12 hours. Northern blot analysis revealed that BNP mRNA expression was augmented 3-fold in the left ventricle as early as 4 hours postinfarction. In contrast, ANP mRNA expression was unchanged. Reflecting the rapid induction of ventricular BNP production, the plasma BNP concentration rose to about 100 pg/mL 12 hours postinfarction (sham-operated rats, < 70 pg/mL). CONCLUSIONS: These results demonstrate the rapid induction of ventricular BNP gene expression in rats with AMI compared with ANP and suggest that BNP gene expression in the ventricle is regulated distinctively from ANP gene expression against acute ventricular overload. They also suggest that the BNP gene can be one of the acutely responsive cardiac genes for the ventricular overload and suggest a possible pathophysiological role of BNP distinct from ANP in AMI.

Animals↗
PubMed1995

Detection of human herpesvirus 6 DNAs in samples from several body sites of patients with exanthem subitum and their mothers by polymerase chain reaction assay.

Polymerase chain reaction amplification was used to detect human herpesvirus 6 (HHV-6) DNAs in peripheral blood mononuclear cells (MNCs), plasma, saliva, stool, and urine from three patients with exanthem subitum and in peripheral blood MNCs, plasma, and saliva from their mothers. HHV-6 DNAs were detected in MNCs during and after the disease and were found in plasma only in the acute phase. The virus DNAs were also detected in saliva after recovery from the illness and were found persistently or intermittently in stool but not in urine samples after the onset of the disease. In contrast, one of the three mothers excreted HHV-6 DNAs persistently in saliva. None of the mothers had the virus DNAs in peripheral blood MNCs and plasma nor a significant increase in antibody titers to HHV-6 after possible exposure from their children. These findings suggest systemic replication of HHV-6 during the acute phase in patients with exanthem subitum and persistent infection of the virus in several organs after recovery from the disease.

Adult↗
PubMed1995

Umbilical venous guanosine 3',5'-cyclic phosphate (cGMP) concentration increases in asphyxiated newborns.

Guanosine 3',5'-cyclic phosphate (cGMP) is known to be the second messenger of natriuretic peptides and nitric oxide (NO). To investigate the involvement of natriuretic peptides in the regulation of the feto-placental circulation, specific radioimmunoassays were used to measure the concentrations of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and cGMP in the umbilical venous plasma of normal and asphyxiated newborns. The plasma concentrations of ANP, BNP and cGMP in asphyxiated newborns were 48.3 +/- 12.9 pm, 24.5 +/- 9.4 pm and 4.4 +/- 1.6 nM (mean +/- s.e.m., n = 10), respectively. These values were significantly higher than those in the normal newborns (17.4 +/- 1.9 pm, 4.7 +/- 1.0 pm, and 0.78 +/- 0.14 nM, respectively). Moreover, the expression of both ANP-A and ANP-B receptor, biologically active receptors for natriuretic peptides, was detected in term human placenta by Northern bolt analysis. The expression of natriuretic peptide receptors was further confirmed by binding assay using [125I]-labelled ANP and solubilized crude membrane preparations of placental tissue. These findings suggest that cGMP is produced in the placenta, at least partly, by the action of ANP and BNP secreted from fetal heart, in pathophysiological conditions such as fetal hypoxia.

Asphyxia Neonatorum↗