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Biomedical subjects

T Sugimoto

Publications and source records attributed to T Sugimoto.

At least 595 records · Page 33Linked to original sources
PubMed1994

Role of ouabainlike compound in rats with reduced renal mass-saline hypertension.

Ouabainlike compound (OLC) has recently been identified as a likely mammalian endogenous digitalis-like factor (EDLF) from human plasma. In this study, plasma levels of OLC were determined to assess the role of OLC in a model known as volume-expanded, reduced renal mass (RRM)-saline (S) hypertension in rats with use of a newly developed radioimmunoassay for ouabain. In the first experiment, at 3 wk after subtotal nephrectomy and drinking 1% saline solution, sysolic blood pressure (SBP) of 18 rats with reduced renal mass (RRM-S rats) was significantly higher than in 17 sham-operated saline-drinking control (C-S) rats [154 +/- 4 (SE) vs. 132 +/- 2 mmHg; P < 0.01]. Plasma OLC levels were 355 +/- 68 pmol/l in RRM-S rats, sevenfold higher than in C-S rats (54 +/- 4 pmol/l; P < 0.01). In the second experiment, we measured plasma OLC levels of 10 RRM-S, 12 sham-operated control (C), and 10 subtotally nephrectomized rats drinking distilled water (RRM rats). Concomitant with a marked increase in blood pressure (203 +/- 5 mmHg), RRM-S rats showed significantly higher plasma OLC levels compared with C and RRM rats (RRM-S 114 +/- 24, C 47 +/- 11, and RRM 52 +/- 9 pmol/l; P < 0.05). In both experiments, plasma OLC levels correlated significantly with SBP (P < 0.05). These findings suggest that plasma OLC shows a similar behavior to that of EDLFs or Na(+)-K(+)-adenosinetriphosphatase inhibitors reported in previous publications and may play a role in hypertensive mechanisms in rats with RRM and excess Na intake.

Animals↗
PubMed1994

Protective role of intracellular superoxide dismutase against extracellular oxidants in cultured rat gastric cells.

We examined the role of intracellular superoxide dismutase (SOD) as an antioxidant by studying the effect of diethyldithiocarbamate (DDC) on extracellular H2O2-induced damage in cultured rat gastric mucosal cells. 51Cr-labeled monolayers from rat stomachs were exposed to glucose oxidase-generated H2O2 or reagent H2O2, which both caused a dose-dependent increase in 51Cr release. DDC dose-dependently enhanced 51Cr release by hydrogen peroxide, corresponding with inhibition of endogenous SOD activity. This inhibition was not associated either with modulation of other antioxidant defenses, or with potentiation of injury by nonoxidant toxic agents. Enhanced hydrogen peroxide damage by DDC was significantly prevented by chelating cellular iron with deferoxamine or phenanthroline. Inhibition of cellular xanthine oxidase (possible source of superoxide production) by oxypurinol neither prevented lysis by hydrogen peroxide nor diminished DDC-induced sensitization to H2O2. We conclude that (a) extracellular H2O2 induces dose dependent damage to cultured gastric mucosal cells; (b) intracellular SOD plays an important role in preventing H2O2 damage; (c) generation of superoxide seems to occur intracellularly after exposure to H2O2, but independent of cellular xanthine oxidase; and (d) cellular iron mediates the damage by catalyzing the production of more reactive species from superoxide and H2O2, the process which causes ultimate cell injury.

Animals↗
PubMed1994

Fulminant hepatitis following exposure to dichlorohydrin--report of two cases.

A 34-year-old man suffered from fulminant hepatitis after cleaning a tank in which there were traces of dichlorohydrin. In spite of daily plasma exchanges, he died 10 days after exposure. A 27-year-old man with much lighter exposure showed only slight liver dysfunction. This is the first report of lethal injury following exposure to dichlorohydrin.

Adult↗
PubMed1994

Carboxyl-terminal parathyroid hormone fragments stimulate osteoclast-like cell formation and osteoclastic activity.

The controversy still exists about the biological activity of carboxyl (C)-terminal PTH fragments. The present study was performed to examine the effect of C-terminal PTH fragments on osteoclast-like cell formation and bone-resorbing activity. In contrast to human (h) PTH-(1-34) or hPTH-(1-84), any C-terminal fragments examined [hPTH-(35-84), hPTH-(53-84), and hPTH-(69-84)] did not affect cellular cAMP production and intracellular calcium in osteoblastic UMR-106 cells. Although hPTH-(1-84) caused an increase in cAMP production and intracellular calcium less effectively than hPTH-(1-34) in UMR-106 cells, the former caused a stimulation of osteoclast-like cell formation in osteoblast-containing mouse bone cell cultures more effectively than the latter. All of the C-terminal fragments significantly stimulated osteoclast-like cell formation, and their effectiveness seemed to depend on the amino acid length of the fragments. The conditioned medium from UMR-106 cells pretreated with C-terminal PTH as well as amino-terminal PTH significantly stimulated osteoclast-like cell formation from mouse hemopoietic blast cells supported by granulocyte-macrophage colony-stimulating factor. Moreover, all of the C-terminal fragments stimulated osteoclast-like cell formation from hemopoietic blast cells even in the absence of osteoblasts, and their effectiveness seemed to depend on the length of fragments. As for bone-resorbing activity by mature osteoclasts, all of the C-terminal fragments stimulated bone resorption in osteoblast-containing mouse bone cell cultures, whereas these fragments did not affect the bone-resorbing activity of isolated rabbit osteoclasts. The present study first indicates that C-terminal PTH fragments stimulate osteoclast-like cell formation as well as bone-resorbing activity by mature osteoclasts in the presence of osteoblasts and accelerate osteoclast-like cell formation from hemopoietic blast cells in the absence of osteoblasts.

Animals↗
PubMed1994

Calcitonin inhibits osteopontin mRNA expression in isolated rabbit osteoclasts.

Recent evidence indicates that osteopontin (Opn), one of the bone matrix proteins, plays an important role in the attachment of osteoclasts to bone matrix. Besides being elaborated by osteoblasts, this protein is also produced by osteoclasts. The present study was performed to examine the effect of calcitonin (CT) on Opn mRNA expression of isolated rabbit osteoclasts and to clarify the second messenger signaling of this effect. Eel CT inhibited Opn mRNA expression as well as bone-resorbing activity of isolated rabbit osteoclasts. Eel CT caused a transient increase in intracellular calcium followed by a sustained increase as well as an increase in cAMP production in these cells. Dibutyryl-cAMP (10(-4) M) and Sp-cAMPS (10(-4) M), an activator of cAMP-dependent protein kinase (PKA), as well as A23187 (10(-7) M), a calcium ionophore, and phorbol myristate acetate (10(-7) M), an activator of protein kinase C (PKC), caused a significant inhibition of Opn mRNA expression, and suppressed bone-resorbing activity of isolated osteoclasts. The present study is the first to demonstrate that CT inhibits Opn mRNA expression in isolated rabbit osteoclasts, presumably through the activation of PKA and calcium/PKC pathways, by which the bone-resorbing activity might be attenuated subsequently.

Animals↗
PubMed1994

The effects of dobutamine, propranolol and nitroglycerin on an experimental canine model of congestive heart failure.

A new experimental model of acute congestive heart failure was established in open-chest dogs, and it was employed to examine the effects of dobutamine, propranolol and nitroglycerin. The model was induced by intracoronary administration of saponin, volume loading and intravenous infusion of methoxamine. Left ventricular end-diastolic pressure (LVEDP) increased from 7.9 +/- 0.6 to 24.2 +/- 1.4 mmHg, and aortic blood flow (AoF) decreased from 0.89 +/- 0.06 to 0.53 +/- 0.04 l/min. Systemic vascular resistance (SVR) increased from 9618 +/- 585 to 16492 +/- 1213 dynes.sec/cm5 and right atrial pressure (RAP) increased from 2.5 +/- 0.2 to 4.2 +/- 0.4 mmHg. Furthermore, Vmax decreased from 71.6 +/- 5.1 to 45.8 +/- 2.9 1/sec, and the time constant of left ventricular pressure decay (T) increased from 40.0 +/- 2.6 to 90.2 +/- 7.9 msec. These hemodynamic changes were stable for up to 80 min. Dobutamine improved cardiac function by increasing Vmax and by decreasing T. Consequently, dobutamine increased AoF and decreased LVEDP, while there was no change in SVR. Nitroglycerin reduced LVEDP, SVR and T; increased AoF; and did not change Vmax. Propranolol produced no improvement in the hemodynamics or cardiac function. These results indicate that the present congestive heart failure model is characterized by global left ventricular dysfunction with lowered cardiac output and increased peripheral vascular tone, and it is beneficial for evaluating the pharmacological properties of drugs for acute congestive heart failure.

Analysis of Variance↗
PubMed1994

Xenotransplantation of canine tumors into severe combined immunodeficient (SCID) mice.

Canine tumors resected at surgery or autopsy were subcutaneously xenotransplanted into SCID mice. Thirty of the seventy-three tumors (41.1%) grew primarily in SCID mice. The primary take rate of mammary tumors and skin and subcutaneous tumors was 55.9% (19/34) and 28.6% (8/28), respectively. One thyroid carcinoma, one oral leiomyosarcoma and one osteosarcoma also underwent successful primary growth. Thirteen of the forty-one benign tumors (31.7%) and 17 of the thirty-two malignant ones (53.1%) were successfully transplantable. The histological features of the primary xenografts and their original tumors were similar to each other in all the cases. Three xenografts of the four malignant tumors with metastasis in the canine patients were shown to grow also in SCID mice and two mammary tumor xenografts out of the three metastasized to the lungs of SCID mice as well. All the 30 primary tumor xenografts grown in the first recipient were successfully transplantable to the second generation of the SCID mice. Xenotransplantation using SCID mice appears to be a valuable tool for investigating the biological characteristics of canine neoplasmas.

Animals↗
PubMed1994

An intracranial epidermal cyst in a Sprague-Dawley rat.

An intracranial epidermal cyst was found incidentally in a 10-week-old female Sprague-Dawley rat. The cyst was located in the leptomeninx of the longitudinal cerebral fissure, ventral to the corpus callosum and dorsal to the third ventricle. It was approximately 0.7 mm in diameter, lined by stratified squamous epithelium and filled with concentric layers of desquamated keratin. The wall consisted of 2-4 layers of cells. Ultrastructurally, the sequence of epidermal differentiation was not normal in that the basal cell layer and was absent in certain areas. The adjacent brain tissues were slightly compressed but not otherwise damaged by the cyst.

Animals↗
PubMed1994

Involvement of protein kinase C in the stimulation of sodium-dependent phosphate transport by parathyroid hormone in osteoblast-like cells.

The rat osteosarcoma cell line UMR-106 has an osteoblast-like phenotype and possesses parathyroid hormone (PTH)-responsive dual signal transduction systems [adenosine 3',5'-cyclic monophosphate-dependent protein kinase (PKA) and calcium-protein kinase C (Ca-PKC)]. These cells transport inorganic phosphate (Pi) by a Na(+)-dependent carrier under stimulation by PTH. The present study aimed to clarify PTH-responsive signal transduction mechanisms in the regulation of Na(+)-dependent Pi transport by PTH in UMR-106 cells. Exposure of these cells to 10(-7) mol/l PTH induced a significant increase in Pi uptake within 30 min of incubation and it became maximal after 2 h. Parathyroid hormone (10(-9)-10(-7) mol/l) stimulated Pi uptake dose dependently. Activation of PKC by 12-O-tetradecanoyl phorbol-13-acetate (TPA) also increased Pi uptake in time- and dose-dependent manners similar to PTH. In contrast, neither PKA activation by 10(-4) mol/l forskolin or by 10(-4) mol/l dibutyryladenosine 3',5'-cyclic monophosphate nor calcium ionophore treatment with 10(-7) mol/l A23187 or with 10(-7) mol/l ionomycin during 3-h incubations affect Pi uptake, except its increase by 10(-4) mol/l forskolin at a 3-h incubation. These agents had no influence on Pi uptake even in combined treatments with TPA. The PTH-induced increase in Pi uptake was abolished almost completely by pretreating cells with PKC inhibitors, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine dihydrochloride (H-7) (50 mumol/l) or staurosporin (10 and 50 nmol/l), and by down-regulating PKC with a prolonged TPA treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

A quantitative estimation of electric current due to myocardial injury.

Myocardial injury causes electric current at the border of injured muscle and the surrounding intact region. In order to determine the magnitude of the injury current, experiments were performed with the isolated canine heart perfused with Tyrode's solution. The anterior descending branch of the left coronary artery was perfused selectively with high potassium (K+) solution and the resulting injury current was reflected in the ST shift of the orthogonal electrocardiogram, derived from the surface of a cubic container in which the heart was placed. After measurement of the ST vector with different K+ concentrations, the heart has fixed with formalin and the injury zone was delineated with serial sections. The boundaries of the selectively perfused region were reconstructed. The algebraic sum of orthogonal components of boundary surfaces determined the average direction normal to the boundary, which was found to be parallel with the ST vector. With increasing K+ concentrations, the ST shift became more marked. However, it was saturated at about 30 mEq/L K+. The maximum injury current, calculated from the saturated value of the ST magnitude, amounted to 0.10 mA.cm per unit area of the boundary surface. Additional experiments were performed with right ventricular papillary muscle preparations. Injuries were caused by a cotton pad containing high K+ solution placed in two directions to make the border along and across the long axis of the papillary muscle. The results indicate that the injury current in an anisotropic structure was essentially directed along the fiber orientation.

Aged↗
PubMed1994

Cardiac tamponade secondary to hemorrhagic pericarditis during continuous hemofiltration for renal failure. The role of the anticoagulant.

Cardiac tamponade secondary to hemorrhagic pericarditis during continuous hemofiltration (CHF) for renal failure is reported. Cardiac tamponade developed while heparin was being used as an anticoagulant and did not recur when nafamostat mesilate was substituted. The role of the anticoagulant in the etiology of hemorrhagic pericarditis in dialysis patients is discussed.

Cardiac Tamponade↗
PubMed1994

Mechanisms of the natriuretic effects of neutral endopeptidase inhibition in Dahl salt-sensitive and salt-resistant rats.

To explore the mechanisms of the renal effects of neutral endopeptidase (NEP) inhibition, the effects of an NEP inhibitor, candoxatril (UK 79,300; UK), in Dahl salt-sensitive (SS) and salt-resistant (SR) rats were examined. UK dose-dependently decreased blood pressure (BP) in SS rats (20 mg/kg: 174 +/- 5 vs. 155 +/- 8 mm Hg, p < 0.01) but not in SR rats. Urinary sodium excretion (UNaV) of both rat strains receiving high-salt diets was increased to a greater extent than that of rats receiving low-salt diets. Basal plasma atrial natriuretic peptide (ANP) level in hypertensive SS rats was higher than in SR rats (192 +/- 18 vs. 118 +/- 24 pg/ml, p < 0.05). UK increased ANP levels in the plasma and urine two- and 11-fold, respectively. UK-induced increases in UNaV, urinary cyclic GMP, and plasma ANP concentrations were significantly augmented by coadministration of a clearance receptor agonist, C-ANF(4-23) or brain natriuretic peptide (BNP). Thus, the effects of NEP inhibition appear to be potentiated by the reduced receptor-mediated metabolism of ANP. This may explain the greater response to the NEP inhibitor in Dahl rats with hypertension or high-salt feeding.

Animals↗
PubMed1994

Hemodynamic and coronary vasodilative properties of a selective and full beta 1-adrenoceptor agonist, T-0509, in comparison with isoproterenol in anesthesized dogs.

Recently, the beta 1-adrenoceptor was shown to mediate direct coronary vasodilation independent of metabolic demand in canine arrested heart preparation. To investigate the beta 1-adrenoceptor-mediated direct vasodilation in a beating heart preparation, we compared coronary blood flow (CBF) and coronary sinus oxygen tension (PO2) in anesthetized open-chest dogs using a beta 1-selective agonist, T-0509. T-0509 (0.005-0.05 microgram/kg intravenously, i.v.) increased the maximal rate of increase in left ventricular pressure (LVdp/dtmax) and heart rate (HR) to an extent similar to that induced by isoproterenol (ISO) without decreasing diastolic blood pressure (DBP). A beta 1-adrenoceptor antagonist, (-)-bisoprolol (10 micrograms/kg), but not a beta 2-adrenoceptor antagonist, ICI 118,551 (30 micrograms/kg), inhibited the T-0509-induced increase in LVdp/dtmax and HR. Thus, T-0509 showed selective beta 1 stimulation at the doses used. T-0509 also caused beta 1-selective relaxation in isolated coronary arteries. ISO increased both CBF and PO2. The early phase of the increase in CBF and the concurrent increases in PO2 were inhibited by ICI 118,551, whereas the late phase of the increase in CBF was inhibited by (-)-bisoprolol. T-0509 increased CBF, and this increase was inhibited by (-)-bisoprolol. A slight but significant increase in PO2 induced by T-0509 was not altered by these doses of the antagonists. Our results indicate that the T-0509-induced increase in CBF is due mainly to an indirect effect on myocardial beta 1-adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-1 Receptor Agonists↗
PubMed1994

Purification of meprin from human kidney and its role in parathyroid hormone degradation.

Meprin (EC 3.4.24.18) is known to occur in the kidneys of mice and rats, but has not previously been found in human kidneys. Here we report the isolation of meprin from human kidney and show that it has a role in the degradation of parathyroid hormone (PTH) in that organ. The purified human meprin had properties almost identical to those of rat meprin including molecular size, substrate specificity and inhibitor sensitivity, and it also cross-reacted well with an antibody raised against rat meprin. Both the purified human meprin and the microvillar membranes of human kidney readily hydrolyzed human parathyroid hormone [hPTH-(1-84)] into several fragments, whose amino acid sequences corresponded well to each other. Thus, meprin appears to play a major role in the PTH-degrading activity in the microvillar membranes of human kidney. Our results indicate that meprin, which so far has mainly been investigated in mice and rats, is found not only in these rodents, but also in the human kidney, and suggest that its physiological role in humans is to degrade PTH in the kidney.

Amino Acid Sequence↗
PubMed1994

Surgical treatment of ventricular septal defect and ruptured sinus of Valsalva associated with infective endocarditis.

Two patients with ventricular septal defect of Kirklin type I and ruptured right coronary sinus of Valsalva associated with infective endocarditis were operated on. Both had bacillus vegetation clinging to the aortic and pulmonary valves and the right ventricular intimal wall around the septal defect. Aortic and pulmonary regurgitation were also found. The surgical approach included vertical incision of the right ventricular outflow tract and pulmonary trunk and transverse aortotomy. The right coronary sinus of Valsalva showed distinct aneurysmal change in one patient. The aortic valve and infected Valsalva sinus were excised in both cases, and the pulmonary valve and right ventricular wall where infection extended thoroughly débrided. The resulting defect, including the ventricular septal defect and excised right Valsalva sinus and aortic annulus, was closed with one patch, and the prosthetic valve inserted in the position of the original aortic valve using this patch as part of the annulus. Both patients had a good postoperative course and are doing well, although slight pulmonary regurgitation persists.

Adult↗
PubMed1994

[Late phase II study with 21-consecutive-day oral administration of etoposide for malignant lymphoma].

We conducted a multi-institutional (33 institutes), late phase II study with a 21-consecutive-day oral administration of etoposide for malignant lymphoma. Patient entry criteria were either those refractory to standard therapies or those for whom no appropriate therapy was available. A once-daily dose of 50 mg/body was administered for 21 consecutive days. Of the evaluable 83 among 88 entry patients, the overall response rate was 53.0% (44/83), including 10 CR; 52.5% (42/80, 9 CR) with non-Hodgkin's lymphoma and 100% (2/2, 1 CR) with Hodgkin's disease. Regarding abnormal laboratory findings, myelosuppression was observed; the incidence rates of leukopenia (23.3% with Grade 3), neutropenia (32.6%), hemoglobin decrease (17.4%) and thrombocytopenia (4.7%) were 70.9%, 65.1%, 54.7% and 19.8%, respectively. Major adverse reactions and their incidence were: anorexia 43.0%, alopecia 37.2%, nausea/vomiting 32.6%, fatigue 18.6%, stomatitis 15.1%, fever 7.0% and diarrhea 5.8%. Therefore, a 21-consecutive-day oral administration of 50 mg/body/day or 75 mg/body/day appears to be effective for the treatment of malignant lymphoma.

Administration, Oral↗