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Biomedical subjects

S Suga

Publications and source records attributed to S Suga.

At least 163 records · Page 9Linked to original sources
PubMed1995

Role of acyl coenzyme A cholesterol acyltransferase in intrahepatic processing of apo B-lipoprotein in suncus.

We have previously shown that fatty liver was easily induced in suncus by starvation and that the plasma level of apolipoprotein B (apoB) was very low. We also previously reported that a defect in the assembling process of apo B-containing lipoprotein (very low density lipoprotein, VLDL) may be one of the reasons for the low level of plasma apo B and for induction of fatty liver by starvation in suncus. We also found that hepatic acyl coenzyme A cholesterol acyltransferase (ACAT) activity is very low in the animals, resulting in decreased cholesteryl ester contents in the liver. A deficiency of cholesteryl ester in suncus liver may be one of the reasons for the defect in the assembling process of VLDL. In this study, we investigated the effect of cholesterol-feeding, which induces an increase in triglyceride and cholesteryl ester of the liver as a consequence of the induction of both intestinal and hepatic ACAT activities, on the secretion of VLDL. Although the basal ACAT activity of intestinal mucosa was high, cholesterol-feeding did not induce either an increase in plasma lipid or an increase in intestinal ACAT activities in suncus. The hepatic secretion rate of VLDL was estimated by treatment with Triton WR1339, which is well known to inhibit the catabolism of VLDL. Cholesterol-feeding caused a slight increase in hepatic triglyceride and cholesteryl ester but no increase either in the secretion rate of VLDL or in hepatic ACAT activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Altered gene expression of natriuretic peptide receptor subtypes in the kidney of stroke-prone spontaneously hypertensive rats.

1. To elucidate the physiological and pathophysiological role of the natriuretic peptide system in the progression of hypertensive renal disease, we examined the gene expression of natriuretic peptide receptor subtypes, guanylate cyclase-A (GC-A), guanylate cyclase-B (GC-B) and clearance receptor (C receptor), in the kidney of stroke-prone spontaneously hypertensive rats (SHRSP) at 8 and 20 weeks of age, and compared them with their gene expression in age-matched Wistar-Kyoto (WKY) rats. 2. Northern blot analyses revealed that messages for three natriuretic peptide receptor subtypes were expressed in the kidney, and their expressions were higher in the glomeruli than in the whole kidney in each strain. 3. In 20 week old rats with established hypertension, the glomerular concentration of GC-A mRNA was significantly higher in SHRSP than in WKY. The concentrations of GC-B and C receptor mRNA in the glomeruli tended to increase and decrease, respectively, but they were not statistically significant in SHRSP. 4. In 8 week old rats, the glomerular concentrations of GC-A, GC-B and C receptor mRNA were not significantly different between SHRSP and WKY. 5. This study demonstrates that in the progression of hypertension, the expression of GC-A, which mediates biological actions of natriuretic peptides, is enhanced in the kidney of SHRSP compared to that of WKY. Together with the augmented secretion of the ligands previously revealed, altered expression of natriuretic peptide receptor subtypes in SHRSP may have a deterrent role in the development of hypertension and its renal complications.

Animals↗
PubMed1995

Preparation of a monoclonal antibody against mouse brain natriuretic peptide (BNP) and tissue distribution of BNP in mice.

1. In order to explore the significance of brain natriuretic peptide (BNP), a cardiac hormone secreted from the ventricle, in mice, we prepared a monoclonal antibody against mouse BNP (mBNP) and established a specific radioimmunoassay (RIA) for mBNP. 2. A monoclonal antibody, KY-mBNP-I, was prepared by the fusion of mouse myeloma cells X63-Ag8.653 with spleen cells of the BALB/c mouse immunized with synthetic mBNP[108-121] conjugated to bovine thyroglobulin. KY-mBNP-I belonged to an IgG2a subclass and showed a high affinity for mBNP (Ka = 1.8 x 10(11) mol/L-1). 3. The RIA established that using KY-mBNP-I was highly sensitive and specific for mBNP, with an IC50 value of 3 fmol/tube and cross-reactivities of less than 0.003% with related natriuretic peptides. mBNP-like immunoreactivity (mBNP-LI) was detected in the mouse atrium (0.35 +/- 0.02 nmol/g), ventricle (20.5 +/- 0.5 pmol/g) and kidney (0.50 +/- 0.05 pmol/g), but not in other tissues including brain. 4. Gel filtration analysis revealed that the major component of tissue mBNP-LI was co-eluted with synthetic mBNP[77-121], a 45-amino acid mature peptide. 5. The monoclonal antibody and RIA for mBNP established here will provide useful tools to investigate the functional significance of BNP in mice, coupled with the genetic engineering approach.

Animals↗
PubMed1995

Augmented expression of the endothelin-A receptor gene in cultured mesangial cells from stroke-prone spontaneously hypertensive rats.

1. To elucidate the role of endothelin (ET) receptor in hypertension, we studied the expression of the ET-A receptor (ET-AR) gene and the ET-B receptor (ET-BR) gene in cultured mesangial cells isolated from stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto (WKY) rats. 2. The mesangial cells from both SHRSP and WKY expressed ET-AR predominantly. The level of the ET-AR mRNA in mesangial cells from SHRSP was 5-fold higher than that in the cells from WKY. The ET-BR mRNA in the mesangial cells from both strains was hardly detectable by northern blot analysis. 3. These results demonstrate that the expression of the ET-AR gene was markedly augmented in mesangial cells from SHRSP.

Animals↗
PubMed1995

Endothelin-induced activation of mitogen-activated protein kinases in glomerular mesangial cells from normotensive and stroke-prone spontaneously hypertensive rats.

1. Kinase assay in myelin basic protein (MBP) containing polyacrylamide gels revealed that endothelin-1 (ET-1) and ET-3 increased MBP kinase activities in glomerular mesangial cells (MC) from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rat (SHRSP). ET-1 stimulated MBP kinase activities more potently than ET-3. 2. Immunoprecipitation with anti-41-kDa MAPK antiserum showed that the MBP kinases activated by ET-1 correspond to 43- and 41-kDa MAPK. 3. Since Phorbol 12-myristate 13-acetate, a direct activator of protein kinase C, also activated MAPK, protein kinase C was suggested to mediate ET-induced activation of MAPK. 4. These results suggest that MAPK may mediate the ET actions in glomerular mesangial cells from normotensive rats as well as spontaneously hypertensive rats. Since ET is produced by vascular endothelial cells of the kidney and glomerular mesangial cells, the ET signalling pathway may have some physiological and pathophysiological significance in vivo glomerulus.

Animals↗
PubMed1995

Lipoproteins regulate C-type natriuretic peptide secretion from cultured vascular endothelial cells.

We have shown that oxidized low-density lipoprotein (Ox-LDL) modulates various endothelial cell (EC) functions. C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family to be discovered, is secreted from peripheral vascular ECs and regulates body fluid homeostasis, vascular tone, and vascular growth. This study was designed to investigate the effects of lipoproteins on CNP secretion from cultured ECs. Treatment of bovine carotid ECs with OX-LDL and its extracted lipids resulted in a concentration-dependent suppression of the spontaneous and transforming growth factor-beta 1-stimulated secretion CNP. Native LDL, its extracted lipids, and acetylated LDL were inactive. OX-LDL depleted of its amphiphilic lipids, which was prepared by incubation with defatted albumin, lost its suppressive effect on CNP secretion. 7-Ketocholesterol, one of the amphiphilic lipids in OX-LDL that is transferable from OX-LDL to defatted albumin, suppressed CNP secretion by ECs, thus mimicking the effect of OX-LDL. Coincubation with high-density lipoprotein (HDL), which alone had no effect on CNP release, significantly prevented OX-LDL-induced inhibition of CNP secretion by ECs. Analysis by thin-layer chromatography demonstrated that oxysterols, including 7-ketocholesterol, in OX-LDL were transferred from OX-LDL to HDL during coincubation of these two lipoproteins. These results indicate that OX-LDL suppresses CNP secretion from ECs by 7-ketocholesterol or other transferable hydrophilic lipids in OX-LDL, and the suppressive effect of OX-LDL is reversed by HDL. Lipoproteins thus may regulate CNP secretion from the endothelium of atherosclerotic arteries.

Animals↗
PubMed1995

Rapid transcriptional activation and early mRNA turnover of brain natriuretic peptide in cardiocyte hypertrophy. Evidence for brain natriuretic peptide as an "emergency" cardiac hormone against ventricular overload.

We previously demonstrated that brain natriuretic peptide (BNP) is a cardiac hormone mainly produced in the ventricle, while the major production site of atrial natriuretic peptide (ANP) is the atrium. To assess the pathophysiological role of BNP in ventricular overload, we have examined the gene expression of BNP, In comparison with that of ANP, in a model of cardiac hypertrophy using cultured neonatal rat ventricular cardiocytes. During cardiocyte hypertrophy evoked by endothelin-1, Phenylephrine, or PMA, the steady state level of BNP mRNA increased as rapidly as the "immediate-early" induction of the c-fos gene expression, and reached a maximal level within 1 h. Actinomycin D, a transcriptional inhibitor, completely diminished the response, while the translational blocked with cycloheximide did not inhibit it. In contrast, ANP mRNA began to increase 3 h after the stimulation, and accumulated during cardiocyte hypertrophy. The BNP secretion from ventricular cardiocytes was also stimulated, more rapidly than the ANP secretion. Furthermore, the turnover of BNP mRNA was significantly faster than that of ANP mRNA, being consistent with the existence of AUUUA motif in the 3'-untranslated region of BNP mRNA. These results demonstrate that the gene expression of BNP is distinctly regulated from that of ANP at transcriptional and posttranscriptional levels, and indicate that the characteristics of the BNP gene expression are suitable for its possible role as an " emergency" cardiac hormone against ventricular overload.

Animals↗
PubMed1995

Identification of fusion regulatory protein (FRP)-1/4F2 related molecules: cytoskeletal proteins are associated with FRP-1 molecules that regulate multinucleated giant cell formation of monocytes and HIV-induced cell fusion.

Fusion regulatory proteins (FRPs) regulate virus-mediated cell fusion and multinucleated giant cell formation of monocytes. Anti-FRP-1 mAbs immunoprecipitated 80 kDa and 38 kDa proteins from HeLa cells. After long exposure other bands were detected, suggesting the presence of molecule(s) associated with FRP-1. To identify the molecule(s), we prepared monoclonal antibodies against immunoaffinity-purified FRP-1 complex derived from membrane fractions of HeLa cells. Immunofluorescence microscopy revealed that these monoclonal antibodies recognized the intracytoplasmic molecules in HeLa cells. Using immunoblotting, the antibodies reacted with 200 kDa, 70 kDa, 55 kDa and 35 kDa molecules, so we designated these molecules as FRP-related molecules (FRMs). Subsequently, we performed gene cloning from a HeLa lambda gt11 cDNA library using anti-FRM mAbs and immunoblotting analysis with either purified cytoskeletal proteins or specific antibodies against various cytoskeletal proteins. Three kinds of positive clone were obtained, which encoded partial sequences of vimentin, tropomyosin, and heat shock cognate protein 70 (hsc70). The 200 kDa molecule was expected to be a myosin heavy chain, judging from the immunoblotting pattern. Immunoblotting confirmed that these purified proteins were readily recognized by anti-FRM mAbs. Furthermore, anti-vimentin and anti-myosin mAbs reacted with the precipitates by anti-FRP-1 mAb, indicating a physical association between FRP-1 molecules and these cytoskeletal proteins. When anti-FRP-1 mAb was added to culture fluids of HeLa cells, the cell-shape and immunofluorescence-pattern stained with anti-FRM mAbs changed. Taken together, the fusion regulatory molecular complex is suggested to consist of at least FRP-1, hsc70, actomyosin and vimentin systems.

Antibodies, Monoclonal↗
PubMed1995

Neutron generator at Hiroshima University for use in radiobiology study.

A neutron generator (HIRRAC) for use in radiobiology study has been constructed at the Research Institute for Radiation Biology and Medicine, Hiroshima University (RIRBM). Monoenergetic neutrons of which energy is less than 1.3 MeV are generated by the 7Li(p,n)7 Be reaction at proton energies up to 3 MeV. The protons are accelerated by a Schenkel-type-accelerator and are bombared onto the 7Li-target. An apparatus for the irradiation of biological material such as mice, cultured cells and so on, was designed and will be manufactured. Neutron and gamma-ray dose rates were measured by paired (TE-TE and C-CO2) ionization chambers. Contamination of the gamma ray was less than about 6% when using 10-microns-thick 7Li as a target. Maximum dose rates for the tissue equivalent materials was 40 cGy/min at a distance of 10 cm from the target. Energy distributions of the obtained neutrons have been measured by a 3He-gas proportional counter. The monoenergetic neutrons within an energy region from 0.1 to 1.3 MeV produced by thin 7Li or 7LiF targets had a small energy spread of about 50 keV (1 sigma width of gaussian). The energy spread of neutrons was about 10% or less at an incident proton energy of 2.3 MeV. We found that HIRRAC produces small energy spread neutrons and at sufficient dose rates for use in radiobiology studies.

Animals↗
PubMed1995

Stimulated Ca2+ entry activates Cl- currents after releasing Ca2+ from the intracellular store in submandibular gland cells of the rat.

In order to examine whether Ca2+ entry is directly involved in controlling exocrine secretion, the Ca(2+)-activated Cl- currents were recorded in single and clusters of rat submandibular gland cells using the whole-cell patch-clamp method. Extracellularly applied acetylcholine (ACh, 10 nM) as well as intracellularly applied GTP gamma S and InsP3 caused repetitive transients of the Cl- currents activated by intracellular Ca2+. These responses occurred also in the absence of external Ca2+, but disappeared after several minutes. Readmission of Ca2+ to the extracellular solution restored the repetitive current transients, while introduction of Sr2+ failed to restore the current signals in spite of the presence of Sr2+ entry detected by microfluorimetry. On the other hand, direct application of Sr2+ to the cell inside caused activation of the Cl- currents although less effectively than Ca2+. When Ca2+ was introduced to the extracellular solution during an interruption of ACh stimulation after the ACh-induced depletion of intracellular Ca2+ store, the Cl- current was not elicited. However, a subsequent challenge with ACh at the same concentration in the absence of extracellular Ca2+ caused repetitive transient Cl- currents. The results suggest that in this cell type the stimulated Ca2+ entry does not by itself activate the Cl- currents but activates them indirectly by triggering Ca2+ release from the intracellular Ca2+ store which may take up Ca2+ soon after the Ca2+ entry.

Acetylcholine↗
PubMed1995

Cardiac accumulation of 125I-labeled monoclonal antibody to atrial natriuretic peptide in a rat model of myocardial infarction.

Atrial natriuretic peptide (ANP) may be an important factor in myocardial infarction and subsequent congestive heart failure. In the failing heart, ANP is expressed in both the atrium and the ventricle. ANP has now been localized with 125I-labeled monoclonal antibodies (MAbs) in vivo in a rat model of myocardial infarction. Myocardial infarction was produced in 3-month-old Wistar rats by ligating the left anterior coronary artery. Two MAbs to rat alpha-ANP accumulated in the infarcted left ventricles of treated rats to a significantly greater extent (p < 0.01) than in the noninfarcted left ventricles of control rats. However, an irrelevant MAb also accumulated to a significantly greater extent in infarcted myocardium than in control myocardium. Thus, the accumulation of the two MAbs to ANP in infarcted tissue seems to be nonspecific and may be due to increased permeability of the injured myocardium.

Animals↗
PubMed1995

[Relationship between insulin secretion and insulin resistance in nondiabetic subjects with myotonic dystrophy--a case control study].

Hyperinsulinemia in myotonic dystrophy (MyD) is generally considered as a result of insulin resistance. However, as a consequence of abnormality in systemic membrane fluidity in this disease, abnormal insulin clearance or intrinsic pancreatic beta-cell dysfunction could also contribute to the hyperinsulinemia. To clarify the cause of hyperinsulinemia in MyD, we examined the insulin resistance, insulin clearance and the capacity of insulin secretion in 6 patients with MyD. They received a euglycemic hyperinsulinemic (insulin 40 mU/m2/min) clamp study for the quantification of insulin resistance by the glucose infusion rate (GIR). We evaluated their capacity of insulin secretion by the ratio of increment of serum insulin level to that of plasma glucose level 30 minutes after a 75 g oral glucose load (insulinogenic index; I.I.) and the ratio of area under the curve of serum insulin levels to that of plasma glucose levels during a 75 g oral glucose load (AUCIRI/AUCPG). The I.I. (1.1 +/- 0.6 vs 0.4 +/- 0.3, p < 0.05) and the AUCIRI/AUCPG (0.5 +/- 0.2 vs 0.2 +/- 0.1, p < 0.01) in MyD were significantly greater than those of GIR, body mass index and sex matched 6 non-diabetic controls respectively. Insulin clearance, estimated by the level of insulin and C-peptide before and during a euglycemic clamp study did not differ between the two groups. These results indicate that the postload hyperinsulinemia observed in MyD is not solely resulted from insulin resistance. Other factors, such as intrinsic beta-cell disorder may be involved.

Adult↗
PubMed1995

Tissue distribution of fusion regulatory protein-1 and fusion regulatory protein-2.

OBJECTIVE: To show which organs (tissues or cells) express fusion regulatory protein-1 and -2. DESIGN: Tissue distribution of fusion regulatory protein-1 and -2 was investigated by indirect immunofluorescence and indirect immunoperoxidase techniques on cryostat tissue sections, using anti-fusion regulatory protein-1 and -2 monoclonal antibodies. RESULTS: Immunohistochemical analysis of human tissue sections revealed the expression of fusion regulatory protein-1 on hair follicle epithelium, skeletal muscle sarcolemma, some bone marrow stem cells, stomach surface and glandular epithelia, pancreatic islets, kidney proximal tubules, testicular seminiferous tubules, follicular epithelium and ova in the ovary, and parathyroid gland. Fusion regulatory protein-2 was expressed on kidney glomerular basement membrane and many glandular epithelia, such as the skin, stomach, thyroid gland, and lung. CONCLUSIONS: The distribution suggested that the expression of fusion regulatory protein-1 might be related to proliferation, peptide or protein secretion, and cell fusion. The distribution of fusion regulatory protein-2 was identical to that of the alpha 3 subunit of integrin.

Antigens, Surface↗
PubMed1995

Clinical features and viral excretion in an infant with primary human herpesvirus 7 infection.

OBJECTIVE: To find clinical features of a virologically-confirmed patient with primary human herpesvirus 7 (HHV-7) infection and a relationship of the excretion of viruses between HHV-7 and human herpes-virus 6 (HHV-6). PATIENT AND METHODS: A 13-month-old boy who had a known prior history of exanthem subitum at 6 months of age developed fever for 3 days and a skin rash appeared as the fever was resolving. The course was accompanying with nonspecific signs and symptoms such as anorexia, irritability, mild diarrhea, palpebral edema, mild inflammation of pharynx, and mild occipital and cervical lymphadenopathy. Heparinized blood samples were used for isolation of HHV-6 and HHV-7 and detection of both virus DNA sequences by a nested polymerase chain reaction (PCR) amplification. Samples from other body sites were also tested for their DNA sequences using the PCR. Both virus antibody activity was measured by an indirect immunofluorescent assay or a neutralization test. RESULTS: Cultured mononuclear cells from the patient at the acute stage of the disease produced morphologic changes, which reacted only with the monoclonal antibody to HHV-7 but not with the antibody to HHV-6. Both viruses were not isolated from blood obtained at the convalescent stage. An antibody response of the patient indicated a seroconversion to HHV-7 but not to other microbial agents including HHV-6 and Mycoplasma pneumoniae. Both virus DNA sequences were detected in peripheral blood mononuclear cells at acute and convalescent stages. HHV-7 DNA was excreted into saliva and transiently into stool at an early convalescent stage followed by HHV-6 excretion into saliva. No HHV-7 and HHV-6 was excreted into urine. CONCLUSIONS: Clinical features of a virologically confirmed patient with primary HHV-7 infection were comparable with those of primary HHV-6 infection and HHV-7 infection may reactivate HHV-6.

Antibodies, Viral↗
PubMed1995

[Combination chemotherapy with FP versus FEP in patients with advanced gastric cancer. Research group of gastric cancer chemotherapy].

Forty-eight patients with unresectable gastric cancer were enrolled for a randomized trial of FP (n = 24) vs FEP (n = 24) combination chemotherapy with respect to their effects on survival period. Of these, excluding 7 patients, 21 in FP group were treated with 400 mg/m2 UFT po daily and 50 mg/m2 CDDP i.v. on days 1 and 8 every 4 weeks, and 20 in FEP group were treated with 400 mg/m2 UFT po daily, 50 mg/m2 etoposide iv and 50 mg/m2 CDDP i.v. on days 1 and 8 every 4 weeks. In FP group, 10 PR in primary lesions were observed with an overall response rate of 52.4%. In FEP group, 5 PR in primary lesions were observed with an overall response rate of 35.0%. Toxicities over Grade 3 were anorexia (35%), vomiting (25%), and leukopenia (12%), which were manageable. The 50% survival time in FP and FEP group was 233 and 176 days, respectively. Because of the high response rate and prolongation of the survival period, combination chemotherapy with FP seemed to be useful for the treatment of patients with advanced gastric cancer.

Adenocarcinoma↗
PubMed1995

Successful bone marrow transplantation in a child with combined IgG subclass deficiency and neutropenia.

An 8-year-old boy with combined IgG1 deficiency and neutropenia underwent allogeneic BMT from his HLA-identical, MLC-negative sister, because immunoglobulin (Ig) infusions and prophylactic antibiotics failed to prevent life-threatening infections. Conditioning was with busulfan and cyclophosphamide, MTX and CYA were given for the prophylaxis of GVHD. For 16 months after BMT no serious infections have occurred and serum IgG1 levels have returned to the normal range without Ig replacement. BMT may be appropriate treatment for patients with IgG subclass deficiency who rarely respond to conservative therapy.

Bone Marrow Transplantation↗