Biomedical subjects

S Morimoto

Publications and source records attributed to S Morimoto.

At least 199 records · Page 11Linked to original sources

PubMed1996

2-aminopropionitrile polymer. I. The hydrolyzate of the basic fraction.

The basic fraction of a 2-aminopropionitrile polymer was subjected to acid hydrolysis and was analyzed by means of GC-MS, after trimethylsilylation. The fundamental polymer structural units were alanine, 2,2'-iminodipropionic acid, N-(1-cyanoethyl)alanine, N-ethylalanine, glycine, cyanoglycine, and 5-amino-4-carboxyimidazole residues. The last three units may be derived from hydrogen cyanide. Oligomeric combinations of these units were also detected in the hydrolyzate, due to partial hydrolysis of the polymer.

Acetaldehyde↗

PubMed1996

ETA receptor-mediated role of endothelin in the kidney of DOCA-salt hypertensive rats.

Renal effects of FR139317, an endothelin ETA receptor antagonist, were examined using anesthetized normotensive and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. The intravenous bolus injection of FR139317 (10 mg/kg) produced a slight decrease in mean blood pressure (MAP; -13%) in the control rats and this hypotension was accompanied by a moderate renal vasodilation (renal vascular resistance: RVR; -12%). In the DOCA-salt hypertensive rat, FR139317 had a more pronounced hypotensive effect (MAP; -26%) accompanied by a potent renal vasodilation (RVR; -33%). FR139317 significantly increased renal blood flow only in the DOCA-salt rats. In contrast, FR139317 produced a significant decrease in urine flow and urinary sodium excretion only in control rats. Northern blot analysis revealed that the renal prepro endothelin-1 (ET-1) mRNA level was significantly increased in DOCA-salt hypertensive rats. Thus, it seems likely that endogenous ET-1 is responsible for the maintenance of DOCA-salt-induced hypertension. We also suggest that at least in part, ET-1 and ETA receptors are involved in renal hemodynamic abnormalities in DOCA-salt-induced hypertension. The augmentation of renal ET-1 production may possibly have a function in the development and maintenance of DOCA-salt-induced hypertension.

Animals↗

PubMed1996

Plasmin stimulates expression of endothelin-1 mRNA and endothelin-1 release in vascular endothelial cells.

Incubation of cultured porcine aortic endothelial cells (ECs) with plasmin resulted in a significant and concentration-dependent increase in endothelin-1 (ET-1) release from the cells. This increasing effect was completely inhibited by aprotinin but not by tranexamic acid, thereby suggesting that the plasmin-induced stimulation of ET-1 release requires the catalytic site but not the lysine binding site, in plasmin molecule. Plasmin stimulated the expression of prepro ET-1 mRNA in ECs. Actinomycin D chase experiments suggested that enhanced stability of ET-T mRNA could not account for the above plasmin-induced stimulation. It is likely that plasmin potentiates the endothelial ET-1 production, probably by the stimulation of ET-1 gene transcription. It remains to be seen whether the endothelial ET-1 production is enhanced after the thrombolytic therapy.

Animals↗

PubMed1996

Endothelin-1 secretion from cultured vascular endothelial cells of DOCA-salt hypertensive rats.

The profile of endothelin-1 (ET-1) release from cultured vascular endothelial cells (ECs) obtained from deoxycorticosterone acetate (DOCA)-salt hypertensive rats, was examined and compared with that from normotensive sham rats. ET-1 release from ECs was increased in a time-dependent manner, and the level of DOCA-salt hypertensive rats was higher than that of sham rats. Incubation of ECs with transforming growth factor (TGF)-beta 1 or thrombin resulted in a significant increase in the ET-1 release, while FK409, a novel nitric oxide donor, produced a dose-dependent decrease in the release. In the case of ECs from DOCA-salt hypertensive rats, the potencies of TGF-beta 1- or thrombin-induced action was much less than that seen with sham rats, while the difference of reactivity to FK409 was not observed between ECs of DOCA-salt rats and sham rats. Thus, ET-1 production in ECs appears to be up-regulated in DOCA-salt hypertensive rats. In addition, there seems to be an abnormalities in the signaling pathway via TGF-beta 1- or thrombin-induced enhancement of ET-1 production in ECs of DOCA-salt hypertensive rats.

Animals↗

PubMed1996

EM523L, a nonpeptide motilin agonist, stimulates gastric emptying and pancreatic polypeptide secretion.

We investigated the efficacy and the mechanism of action of EM523L, a nonpeptide motilin agonist (motilide), on the stimulation of gastric emptying and on the release of gut peptides after ingestion of a solid meat in normal controls (n = 8) and in diabetic patients (n = 8) with signs of neuropathy. A dose of 2 mg EM523L was administered IV over 15 min just after ingestion of a solid meal (200 kcal Gastric emptying was measured by a radionuclide technique. EM523L accelerated gastric emptying and markedly augmented postprandial pancreatic polypeptide (PP) response in both normal control and diabetic patients. This may suggest the mediation of the Vagal-cholinergic pathway to accelerate gastric emptying. The present study offers a promising therapeutic potential of the motilide in gastrointestinal motility disorders like those observed in diabetics mellitus.

Adult↗

PubMed1996

Effect of sodium nitroprusside on norepinephrine overflow and antidiuresis induced by stimulation of renal nerves in anesthetized dogs.

To investigate the role of nitric oxide (NO) in the regulation of renal sympathetic nerve activity and renal function, we examined the effect of sodium nitroprusside (SNP), a NO donor, on renal actions induced by renal nerve stimulation (RNS) in anesthetized dogs, with or without blockade of an endogenous NO generation by NG-nitro-L-arginine (NOARG), a NO synthase inhibitor. Low-frequency RNS (0.5-2.0 Hz) enhanced the rate of norepinephrine secretion rate (NESR) from the kidney and decreased urine flow (UF), urinary excretion of sodium (U(Na)V), and fractional excretion of sodium (FENa, without affecting systemic and renal hemodynamics. The intrarenal arterial infusion of SNP, in a dose (1 mu g/kg/min) that does not affect renal hemodynamics and urine formation at the basal level, significantly attenuated the RNS-induced decreases in UF, UNa V and FENa. The intrarenal administration of NOARG (40 mu g/kg/min) elicited renal vasoconstriction and reduced urine formation. RNS during NOARG administration reduced renal blood flow (RBF) and glomerular filtration rate (GFR) and augmented RNS-induced reduction in urine formation. Simultaneously, NESR was markedly enhanced. The renal actions observed with NOARG administration during control and RNS periods were almost completely abolished by treatment with SNP. Therefore, we suggest that NO plays an important role in the regulation of renal function. Endogenous NO probably functions as an inhibitory modulator of renal noradrenergic neurotransmission at the prejunctional level.

Adrenergic Fibers↗

PubMed1996

Inhibitory effects of endothelin-3 on antidiuresis and norepinephrine overflow induced by stimulation of renal nerves in anesthetized dogs.

The effects of endothelin-3 (ET-3) on changes in renal hemodynamics, urine formation, and norepinephrine (NE) overflow induced by renal nerve stimulation (RNS) were examined in anesthetized dogs. RNS at a low frequency (0.5-2.0 Hz) produced significant decreases in urine flow (UF), urinary excretion of sodium (UNaV), and fractional excretion of sodium (FENa), and increased the NE secretion rate (NESR) without affecting systemic or renal hemodynamics. RNS at a high frequency (2.5-5.0 Hz), which diminishes renal hemodynamics by causing renal vasoconstriction, affected urine formation and NESR more potently than did low-frequency RNS. When ET-3 (2.0 ng/kg/min) was infused into the renal artery, there was a slight and transient increase in renal blood flow (RBF); this response was followed by a gradual reduction. ET-3 infusion tended to increase the basal levels of UF without affecting UNaV, indicating the excretion of hypotonic urine with administration of this peptide. During ET-3 infusion, low-frequency RNS-induced antidiuretic action was significantly attenuated. Simultaneously, increase in NESR elicited by low-frequency RNS was markedly suppressed. Qualitatively similar results were observed in the case of high-frequency RNS. In addition, high-frequency RNS-induced decreases in the glomerular filtration rate (GFR) and the filtration fraction (FF) were suppressed by ET-3 infusion. These findings suggest that ET-3 suppresses renal responses to stimulated renal noradrenergic neurotransmission by inhibiting the release of NE. These findings, together with our previous findings, suggest that ET-3 (and/or ET-1) functions as an inhibitory modulator of the renal noradrenergic nervous system through the prejunctional ETB-receptor mechanism.

Anesthesia, Intravenous↗

PubMed1996

Painless thyroiditis occurring during long-term treatment with interferon alfa in a patient with chronic active hepatitis C.

We describe here painless thyroiditis during interferon (IFN) therapy in a 65-year-old man with chronic active hepatitis C. The patient had hypothyroidism in the late stage of a 24-week course of treatment with IFN-alpha. After cessation of the treatment a small, firm goiter was noticed, and chronic focal thyroiditis was diagnosed histologically. Analyses of the stock serum samples drawn before, during, and after IFN-alpha therapy revealed transient hyperthyroidism followed by transient hypothyroid states with aggravation of antithyroid hormone antibody titers. These findings suggest that long-term IFN-alpha therapy caused painless thyroiditis with aggravation of autoimmunity in our patient with preexisting chronic thyroiditis.

Aged↗

PubMed1996

Alteration of intercellular communication in a human urothelial carcinoma cell-line by tumor-promoting agents.

BACKGROUND: Most of the findings that support a good association between inhibition of intercellular communication and tumor promotion have been demonstrated by studies of animal cells, while it has been accepted that most tumor-promoting agents are specific to species and organs. Therefore, the influence of tumor-promoting agents on intercellular communication was investigated using a human urothelial cell-line. METHODS: The effects of six tumor-promoting agents, including dichlorodiphenyltrichloroethane (DDT), butylated hydroxyanisole (BHA), saccharin, cyclamic acid, phenobarbital, and DL-tryptophan, on intercellular communication in a human urothelial cell-line (JTC-30) were investigated by using a dye-transfer assay after 48- and 96-hour exposure to each agent. Cytotoxicity was determined using the colony-forming method after 48-hour and 7-day exposure to each agent. RESULTS: DDT, BHA, saccharin, and cyclamic acid inhibited intercellular communication after either 48- or 96-hour exposure at concentrations that were nontoxic to the cells after 7-day exposure. Phenobarbital and DL-tryptophan inhibited intercellular communication only at toxic concentrations. CONCLUSIONS: Since the former four agents are known to be direct tumor promoters, and the metabolites of the later two agents have been regarded as tumor promoters, the results suggest that current methodology using the JTC-30 cell-line may be applicable to the screening to detect direct tumor promoters of human urothelium.

Adult↗

PubMed1996

Hypertension and unilateral renal ischemia (Page kidney) due to compression of a retroperitoneal paraganglioma.

We describe a 17-year-old hypertensive man with a left abdominal mass on the computed tomographic scan. Radiologic studies revealed a large tumor near the left renal hilus, resulting in renal compression and displacement toward the posterolateral abdominal cavity. Aortography excluded stenosis of the renal arterial vessels. Plasma and urinary catecholamines were normal and plasma renin activity (PRA) was high. The left renal vein renin was 2.1-fold higher than the right one. After resecting the tumor including the left kidney and adrenal, high blood pressure and elevated PRA returned to normal. Histologically, the tumor was a paraganglioma, and the affected kidney showed hyperplasia of the juxtaglomerular apparatus. Thus, the hypertension in our patient was probably due to renal ischemia extrinsically compressed by a non-functioning retroperitoneal paraganglioma (Page kidney).

Adolescent↗

PubMed1996

A case of renovascular hypertension with marked polyuria after percutaneous transluminal renal angioplasty.

A 43-year-old female patient with hypertension was diagnosed as having one-kidney renovascular hypertension with dysfunction of the contralateral kidney, and percutaneous transluminal renal angioplasty was carried out. Marked polyuria was observed during the 2- to 72-hour postoperative period. During the 12- to 18-hour period of polyuria, the urine volume was 8.9 liters/6 h, which was 62% of the glomerular filtration, and was accompanied by high fractional excretion of sodium and of potassium and a high urine beta 2-microglobulin level. The mechanism of polyuria in this case is discussed.

Adult↗

PubMed1996

Parathyroid hormone-related protein inhibits indothelin-1 production.

The effect of human parathyroid hormone-related protein, a powerful vasodilator, on endothelin-1 production in cultured bovine pulmonary arterial endothelial cells was studied. Treatment with parathyroid hormone-related protein(1-34) at concentrations of 10(-9) to 10(-6) mol/L for 24 hours caused dose-dependent suppression of the secretion of endothelin-1, with maximal suppression at 10(-7) mol/L to 74% of the control value. This inhibitory effect was completely abolished by coincubation with 100 ng/mL pertussis toxin, an inhibitor of GTP binding protein. Furthermore, addition of Ng-monomethyl-L-arginine, an inhibitor of nitric oxide synthase, at 10(-3) mol/L significantly blocked the suppressive effect of parathyroid hormone-related protein (1-34) on endothelin-1 secretion, and further addition of 5x10(-3) mol/L L-arginine significantly attenuated the blocking effect of N(G)-monomethyl-L-arginine. Parathyroid hormone-related protein (1-34) at 10(-7) mol/L resulted in an approximately fivefold increase in intracellular cGMP level. Northern blot analysis revealed that parathyroid hormone-related protein (1-34) inhibited both basal and thrombin-induced endothelin-1 gene expression. These findings suggest that the vasodilating property of parathyroid hormone-related protein may be mediated in part through its inhibitory effect on endothelin-1 production, which is probably mediated through nitric oxide and cGMP in endothelial cells. Thus, a feedback regulatory mechanism may exist between parathyroid hormone-related protein and endothelin-1 in the vascular wall.

Animals↗

PubMed1996

Nitric oxide induces upregulation of Fas and apoptosis in vascular smooth muscle.

Interleukin-1 induced a time-dependent release of high levels of nitric oxide from rat vascular smooth muscle cells up to 96 hours. A time-dependent release of lactate dehydrogenase was also induced by Interleukin-1 from 72 to 96 hours after its stimulation. In situ nick end-labeling assay revealed that incubation for 48 hours with interleukin-1 induced a positive staining of fragmented nuclei. However, NG-monomethyl-L-arginine, an inhibitor of nitric oxide synthase, inhibited both lactate dehydrogenase release and DNA fragmentation induced by interleukin-1. Furthermore, sodium nitroprusside, a nitric oxide donor, also induced lactate dehydrogenase release and DNA fragmentation. Fluorescent staining of DNA revealed patches of irregularly dispersed, brightly staining, and condensed chromatin in rat vascular smooth muscle cells treated with sodium nitroprusside. Flow cytometric analysis with monoclonal antibody against human Fas revealed that expression of Fas was upregulated by sodium nitroprusside in human vascular smooth muscle cells. Methylene blue, an inhibitor of soluble guanylate cyclase, did not affect sodium nitroprusside-induced upregulation of Fas. Furthermore, 8-bromo-guanosine 3':5'-cyclic monophosphate, an analogue of cGMP, did not upregulate Fas expression. These findings indicate that nitric oxide released from vascular smooth muscle cells may induce apoptosis in vascular smooth muscle cells themselves and also induced upregulation of Fas via a cGMP-independent mechanism. Thus, nitric oxide could trigger the remodeling of atherosclerotic plaques.

Animals↗

PubMed1996

Buerger's disease in a middle-aged woman with diabetes mellitus. A case report.

Buerger's disease or thromboangiitis obliterans with involvement of small arteries of the upper and lower extremities usually afflicts young male smokers, but this report presents a middle-age female nonsmoker with diabetes mellitus who satisfied clinical, angiographic and histologic criteria for the diagnosis of Buerger's disease.

Adult↗

PubMed1996

Role of endogenous angiotensin II in renal hemodynamic and excretory responses to L-arginine infusion.

The purpose of this study was to investigate whether endogenous angiotensin II has a functional role in renal hemodynamic and excretory changes induced by L-arginine, a substrate for nitric oxide (NO), in anesthetized rats. During the intravenous infusion of L-arginine (50, 100, 200 mumol/kg.min), there was no significant change in systemic or renal hemodynamics, but urine flow and urinary sodium excretion markedly increased in a dose-dependent manner. Simultaneously, L-arginine infusion produced an increase in urinary excretion of NO metabolites, NO2- and NO3-. Treatment with L-158809 ¿5,7-dimethyl-2-ethyl-3-[[2'-(1H-tetrazol-5-yl) [1,1']-biphenyl-4-yl]methyl]-3H-imidazo[4,5-b]pyridine¿ (0.3 mg/kg), a selective angiotensin II type I receptor antagonist, caused a reduction in mean arterial pressure, and a rise in renal blood flow and glomerular filtration rate, with no changes in excretory responses. In the presence of L-158809, L-arginine-induced diuretic and natriuretic actions were observed to the same extent as seen in the absence of L-158809. These data suggest that the infusion of L-arginine causes diuresis and natriuresis, possibly via the formation of nitric oxide in the kidney, and that endogenous angiotensin II is not involved in the L-arginine-induced renal actions.

Anesthesia↗

PubMed1996

Effects of the endothelin ETA-receptor antagonist FR139317 on development of hypertension and cardiovascular hypertrophy in deoxycorticosterone acetate-salt hypertensive rats.

We investigated the role of endothelin-1 (ET-1) in the development of hypertension and cardiovascular hypertrophy in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Two weeks after the start of DOCA-salt treatment, the rats were divided into two groups and were given FR139317 [(R)2-[(R)-2-[(S)-2-[[1-(hexahydro-1H-azepinyl)]- carbonyl]amino-4-methyl-pentanoyl]amino-3-[3-(1-methyl-1H-indolyl)] propionyl]amino-3-(2-pyridyl) propionic acid], a specific ETA-receptor antagonist, or its vehicle for 2 weeks. Uninephrectomized rats without DOCA-salt treatment served as controls. Vehicle-treated DOCA-salt rats developed marked hypertension after 4 weeks. FR139317 significantly suppressed the increase in systolic blood pressure with values averaging 163 +/- 8 mmHg (P < 0.05 vs DOCA-salt rats receiving vehicle, 195 +/- 9 mmHg). Morphological studies in the rats given the vehicle showed vascular medial hypertrophy, with a significant increase in the wall area and wall-to-lumen ratio. A marked decrease in vascular wall hypertrophy was observed in the FR139317-treated DOCA-salt rats. The cardiac hypertrophy in DOCA-salt hypertensive rats was also significantly reduced by FR139317. Therefore, these results suggest that ET-1 plays an important role in the development of DOCA-salt hypertension presumably by stimulating the ETA receptor. In addition, we found that an ETA-receptor antagonist effectively reduced cardiovascular hypertrophy in the rats, so the cardiovascular hypertrophy noted in DOCA-salt hypertensive rats may be related to ET-1.

Analysis of Variance↗

PubMed1996

Cerebral venous sinus thrombosis associated with systemic multiple hemangiomas manifesting as chronic subdural hematoma--case report.

A 35-year-old male was admitted with headache, nausea, and vomiting persisting for 2 days. Computed tomography (CT) revealed a left chronic subdural hematoma. Cerebral angiography demonstrated cerebral venous sinus thrombosis (CVST). He had presented with a subcutaneous mass involving the neck at age 2 years, which was shown to be a cavernous angioma, and thereafter shown signs of consumptive coagulopathy with systemic multiple hemangiomas. Burr hole aspiration of the hematoma was performed. Seventy-two-hours later, he developed clouding of consciousness and right hemiparesis. CT revealed a fresh hematoma in the operated subdural cavity and hemorrhagic diathesis manifested. A frontotemporoparietal large craniotomy was performed to remove the hematoma. Extensive electrocauterization was required. He had a satisfactory postoperative course. Collateral venous pathways, resulting from the CVST due to systemic multiple hemangiomas, may have caused hemodynamic stress in the bridging veins which subsequently induced chronic subdural hematoma.

Adult↗

PubMed1996

A case of myocarditis associated with IDDM.

We report a case of diabetic ketoacidosis (DKA) complicated by acute myocarditis, which was confirmed by cardiac biopsy. A 26-year-old man was hospitalized with severe DKA. On admission, nonspecific ST-T change was noted on the electrocardiogram (ECG). The patient's levels of creatine phosphokinase (CPK) and glutamic oxaloacetic transaminase were slightly elevated, but he did not complain of chest discomfort or symptoms of heart disease. On the first day after admission, ST-T elevation was noted on ECG during treatment of DKA. By cardiac angiography and cardiac biopsy, coronary heart disease was ruled out and postmyocarditic change was histologically confirmed. An episode of upper respiratory viral infection before the onset of acute diabetes suggested that the patient suffered from viral-induced myocarditis and consequent development of IDDM. This possibility was confirmed by the clinical course of ECG change, with elevated CPK and lactate dehydrogenase and a slightly elevated antibody titer for echovirus.

Adult↗