Biomedical subjects

S Morimoto

Publications and source records attributed to S Morimoto.

At least 289 records · Page 16Linked to original sources

PubMed1994

[Effects of pravastatin administration for 12 months on serum lipid levels in aged patients with hypercholesterolemia].

To evaluate long-term efficacy of pravastatin, we administered this HMG-CoA reductase inhibitor at a mean dose of 9.9 mg/day to 208 aged patients with serum levels of total cholesterol (TC) over 220 mg/dl (mean +/- SD aged of 70 +/- 7 years; 62 males and 146 females) for 12 months. The mean serum value of TC significantly decreased from the basal level of 265 mg/dl to 216 mg/dl in the 3rd month, and this decrease was maintained throughout the observation period. Similar change was observed in the serum level of low density lipoprotein-cholesterol (LDL-C). Although the mean serum level of high density lipoprotein-cholesterol (HLC-C) in all patients did not change significantly, the HDL-C level in 34 patients with a HDL-C level below 40 mg/dl significantly increased from the 3rd month. The mean serum level of triglyceride (TG) in all patients significantly decreased from the 3rd month, and this decrease in the TG was more prominent in 101 aged patients with TG levels higher than 150 mg/dl. In 168 aged patients on 10 mg/day of pravastatin throughout the period, there were significant negative correlations between the ratio of the decrease in TC in basal serum and each of the basal serum TC levels (r = -0.345, p < 0.001) and age of the subjects (r = -0.208, p = 0.007). These results indicate that long-term administration of pravastatin is effective treatment for lipid metabolism even in aged patients.

Aged↗

PubMed1994

[Therapeutic policy for elderly hypertensives in Japan--a questionnaire survey of specialists].

In order to clarify the therapeutic policy for hypertension in the elderly, we mailed a questionnaire to 147 specialists in Japan and received 123 replies. The upper age limit for antihypertensive treatment was considered to be 80-85 years old by about 50% of the specialists, but the other 50% did not consider an upper age limit. The range of the systolic blood pressure (BP) for which drug treatment was indicated in those without cardiovascular complications was considered to be increased with age, being 160 mmHg and higher in those aged 60-69, 160-170 mmHg and higher in those aged 70-79, and 170-180 mmHg and higher in those aged 80-89, while the level of diastolic BP requiring treatment was considered to be 90-95 mmHg and higher in all age ranges. The goal of BP control was considered to be less than 150/90 mmHg in those aged 60-69, and less than 160/90 mmHg in those aged 70-79 by the majority of the specialists, and to be higher in those aged 80-90, i.e. less than 170-180/95-100 mmHg by more than 20% of the specialists. As the initial selection of antihypertensive regimen, calcium antagonists followed by angiotensin I-converting enzyme inhibitors (ACEI) were selected by the majority, while diuretics, beta-blockers and alpha 1 blockers were chosen by the minority.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1994

Isolation and characterization of a new 12-membered macrolide FD-895.

During the course of our screening program for natural product drugs effective against multidrug resistant cells by using adriamycin resistant HL-60 cells, we have discovered a new 12 membered macrolide FD-895 in the fermentation broth of Streptomyces hygroscopicus A-9561 isolated from a soil sample collected at Iriomote Island, Okinawa prefecture, Japan. FD-895 showed stronger cytocidal activities against in vitro tumor cell lines than adriamycin. FD-895 had the same IC50 values against parent and adriamycin resistant HL-60 cells.

Anti-Bacterial Agents↗

PubMed1994

[A case report of interstitial pneumonia caused by granulocyte colony-stimulating factor].

Several clinical trials have demonstrated that granulocyte colony-stimulating factor (G-CSF) accelerates the recovery of neutropenia in chemotherapy-induced bone marrow suppression. In this report, we describe a 46-year-old female with glioblastoma multiforme who developed interstitial pneumonia due to administration of G-CSF during the phase of immunochemoradiotherapy-induced neutropenia. Thirty-three days after starting immunochemoradiotherapy (ACNU, VCR, IFN -beta, radiation), she developed neutropenia (1,000/microliters). Administration of G-CSF at doses of 125-250 micrograms/day led to an increase of peripheral neutrophil counts. Eleven days later, the patient developed sudden severe respiratory failure and cyanosis with worsening of lung shadows. Blood gas levels on room air were PaO2 49.3mmHg, PaCO2 28.0mmHg, and pH 7.46. At this time, her neutrophil count had risen to 26,080/microliters. LDH and alpha - HBD had also increased to 1,439 IU/l and 1,117IU/l respectively. Chest radiograph and CT scan demonstrated interstitial pneumonia. After treatment with methyl prednisolone, her respiratory symptoms were gradually resolved. A number of side-effects have been reported with granulocyte-macrophage colony-stimulating factor (GM-CSF). These include fluid retention with pericardial and pleural effusion, fever, bone pain, fatigue, and rash. This report also suggests that G-CSF might be a cause of interstitial pneumonia during the phase of immunochemoradiotherapy-induced neutropenia.

Brain Neoplasms↗

PubMed1994

Effects of an angiotensin II receptor antagonist, CV-11974, on angiotensin II-induced increases in cytosolic free calcium concentration, hyperplasia, and hypertrophy of cultured vascular smooth muscle cells.

The effects of CV-11974, a potent nonpeptide antagonist of the angiotensin II (AII) type-1 receptor (AT1), on cytosolic free calcium concentration ([Ca2+]i), hyperplasia, and hypertrophy of cultured vascular smooth muscle cells (VSMC) from rat aorta were studied. [Ca2+]i was measured by fura 2, and hyperplasia and hypertrophy were determined by incorporation of [3H]thymidine and [3H]leucine, respectively. CV-11974 had no effect on [Ca2+]i itself, but suppressed 10(-7) M AII-induced increase in [Ca2+]i dose dependently at concentrations from 10(-10) M and completely at 10(-7) M. CV-11974 suppressed both Ca2+ release from intracellular Ca2+ stores and Ca2+ influx from the extracellular space. However, CV-11974 had no effect on the increases in [Ca2+]i induced by prostaglandin F2 alpha (PGF2 alpha), a potent vasoconstrictor, or ionomycin, a Ca2+ ionophore. These results indicate that the suppressive effects of CV-11974 act on the binding of AII and its specific receptors. AII 10(-7) M increased the synthesis of DNA and protein to 1.5 and 1.7 times the control values, respectively. CV-11974 had no effect on synthesis of DNA or protein, but suppressed the AII-stimulated synthesis of DNA and protein dose dependently at concentrations > or = 10(-8) and 10(-10) M, respectively and completely at 10(-6) M. These results indicate that AII increases [Ca2+]i and synthesis of DNA and protein in VSMC through activation of AT1. CV-11974 showed no partial agonistic effects on AII. Thus, CV-11974 may act not only as an antihypertensive agent, but also as an inhibitor of vascular injury stimulated by AII.

Angiotensin II↗

PubMed1994

The effects of NG-nitro-L-arginine, a nitric oxide synthase inhibitor, on norepinephrine overflow and antidiuresis induced by stimulation of renal nerves in anesthetized dogs.

We examined the involvement of endogenous nitric oxide (NO) in noradrenergic neurotransmission and renal function in anesthetized dogs, by using NG-nitro-L-arginine (NOARG), a NO synthase inhibitor. Renal nerve stimulation (RNS) produced the frequency-dependent increase in the rate of norepinephrine secretion. The low frequency RNS (0.5-2.0 Hz) decreased urine flow and urinary excretion of sodium, without affecting renal hemodynamics. High frequency RNS (2.5-5.0 Hz) caused a more potent antidiuresis and renal vasoconstriction that resulted in reductions in renal blood flow and glomerular filtration rate. Intrarenal arterial infusion of NOARG, at a dose (10 micrograms/kg/min) which had no effect on renal hemodynamics, significantly enhanced the RNS-induced reductions of urine formation and renal vasoconstriction and increments in norepinephrine secretion rate. Qualitatively similar results were observed with a higher dose of NOARG (40 micrograms/kg/min), although this dose did decrease basal levels of renal blood flow and urine flow. Enhancement of NOARG on RNS-induced actions was abolished by the simultaneous administration of L-arginine. Endogenous NO probably has a role as inhibitory modulator of renal noradrenergic neurotransmission.

Amino Acid Oxidoreductases↗

PubMed1994

[A case of prostatic cystadenoma].

We report a case of prostatic cystadenoma in a 45-year-old man with the complaint of urinary retention. The large mass was palpated on rectal examination. The tumor was localized in the position of the left lobe of the prostate and was seen as multi-ocular on computerized tomographic (CT) scan. The serum levels of prostatic acid phosphatase (PAP) and prostate specific antigen (PSA) were slightly elevated. The tumor was enucleated retropubically, it weighed 210 g and had an multilocular structure macroscopically. The cyst seen on microscopic examination was lined with cuboidal or columnar epithelial cells and the lining cells were focally multilayered and formed papillary projections. The stroma surrounding the glands was composed of fibrous tissue containing smooth muscle fibers. The epithelial cells were immunoreactive for PAP and PSA.

Cystadenoma↗

PubMed1994

[Fluoroscopic contrast medium percutaneous ethanol injection therapy (FCM-PEIT): newly developed clinical useful method for injecting ethanol into nodules of hepatocellular carcinoma].

We have performed fluoroscopic contrast medium percutaneous ethanol injection therapy (FCM-PEIT) total 266 times to 82 hepatocellular carcinoma (HCC) nodules in 44 HCC cases: FCM-PEIT is the newly developed method that HCC nodules are punctured by a needle and injected with ethanol mixed with water-soluble contrast medium (Iopamidol containing 370 mg/ml iodine) (vol/vol: 7/3) under the fluoroscopic observation as well as ultrasonic diagnostic equipment (US). Autopsy analyses have demonstrated nearly complete tumor necrosis by FCM-PEIT. We analyzed the detectable rate (%) of the contrast medium-mixed ethanol (CME) leakage out of HCC nodules by US-alone, fluoroscope-alone, and US-fluoroscope observation. The detectable rate of the leakage was 63% by US-fluoroscope, while was only 32% by US-alone. Particularly, all leakages into intra hepatic bile duct were missed by US-alone. The maximal CME-amount for injection without any leakage was not uniform and not related to the size of HCC nodules. The present results suggest that FCM-PEIT is clinically more useful method for the treatment of HCC compared to general PEIT that HCC nodules are injected with ethanol under the US-alone observation, since it is easy to confirm whether ethanol can be sufficiently injected into HCC nodules without any leakage.

Carcinoma, Hepatocellular↗

PubMed1994

[Clinical analysis of the fatal cases of adult malignant gliomas after aggressive treatment].

Six patients operated on for supratentorial malignant astrocytomas and seven patients operated on for glioblastoma multiforme were analyzed to evaluate the effect of aggressive surgical resection on the length of survival and causes of death. Early postoperative contrast enhanced CT scan was used to assess the extent of surgical resection. A gross total resection was considered to have been accomplished when there was no evidence of any residual enhanced mass. When 10% or less of the preoperative enhanced mass remained, the resection was classified as a subtotal resection. Subsequent follow-up CT scan showed that a gross total resection was accomplished in nine patients, and a subtotal resection was attained in four patients. The patients' ages ranged from 40 to 78 years (mean, 59 years). The median survival after the first aggressive surgical resection was 18.0 months in patients with malignant astrocytoma and 13.6 months in those with glioblastoma multiforme. The median duration between first operation and recurrence of tumor was 8.8 months in patients with malignant astrocytoma and 11.5 months in those with glioblastoma multiforme. A second aggressive surgical resection for recurrent malignant astrocytoma or glioblastoma multiforme was carried out in four patients (40%) of the evaluated ten patients. The median survival of these patients after reoperation was 8.25 months. Accordingly, aggressive surgical resection of malignant astrocytoma and glioblastoma multiforme is correlated with longer survival and is advocated in the treatment of recurrent tumors. Leptomeningeal dissemination was diagnosed in nine patients (90%) of evaluated ten patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Platelets-induced stimulation of endothelin-1 production and inhibition by phosphoramidon.

The effects of platelets on endothelin-1 (ET-1) production were examined by using cultured bovine pulmonary artery endothelial cells (ECs). Platelets (6 x 10(6) to 2 x 10(9) platelets/ml) prepared from rat peripheral arterial blood markedly stimulated immunoreactive (IR)-ET release from ECs into the culture medium, in a time-and platelet number-dependent manner. High-performance liquid chromatography analysis of the culture supernatant following exposure to platelets revealed one major IR-ET component corresponding to the elution position of synthetic ET-1. Northern blot analysis showed that platelets enhanced prepro ET-1 mRNA expression in the ECs. Increased IR-ET release was observed with the supernatant obtained after incubation of platelets, and this increment was significantly inhibited by transforming growth factor-beta 1 neutralizing antibody. Phosphoramidon, an ET converting enzyme inhibitor, significantly decreased the amount of IR-ET accumulating in the culture medium of ECs, incubated with or without platelets, and the decreasing effect of phosphoramidon in the presence of platelets was greater than that in their absence. A similar effectiveness of phosphoramidon was seen when transforming growth factor-beta 1 was used instead of platelets. Thus, platelets appear to stimulate the endothelial production of ET-1 in vitro, probably through a release of transforming growth factor-beta 1. We also suggest that the inhibition of ET converting enzyme by phosphoramidon is more effective in the augmented condition of ET-1 production than in the basal condition.

Animals↗

PubMed1994

[A case of dural type of histiocytosis X presenting as a mass lesion in the tentorium cerebelli].

Histiocytosis X is a disease of unknown etiology, characterized by a mass of proliferating histiocytes, plasma cells and inflammatory cells foaming a granuloma within the reticuloendothelial elements of any organ in the body. In the central nervous system (CNS), hypothalamic disorder of histiocytosis X is often found, but histiocytosis X in other regions is quite rare. We report a case of a 5-year-old girl with histiocytosis X of the zygoma presenting as a mass lesion in the tentorium cerebelli. A computed tomographic (CT) scan demonstrated a tumor at the left tentorial region, extending along the dura mater of the tentorium cerebelli. Magnetic resonance imaging (MRI) revealed a low signal intensity region on both T1 and T2-weighted images. MRI with Gd-DTPA showed a homogeneous enhanced mass extending to right and inferior sites with a thickened tentorium. As the thickened dura matter continued from the left middle fossa to the mass lesion, the tumor was considered to arise from the left zygoma and extend to the tentorium cerebelli. CNS extension of histiocytosis X is manifested either as (1) the cerebral type or (2) the dural type. Many cases of cerebral type histiocytosis X including hypothalamic disorder have been reported. Only 6 cases of the dural type of histiocytosis X have been described. Although the lesions of the cerebral type of histiocytosis X show prolonged T1 and T2 values on MRI, the MRI findings of the dural type have not been reported. The present case is the first report of the appearance of the lesion on MRI.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebellar Diseases↗

PubMed1994

FS2. a mamba venom toxin, is a specific blocker of the L-type calcium channels.

The peptide FS2 is a mamba venom toxin, consisting of 60 amino acids, three residues of which are different from those of calciseptine (CaS), a natural L-type Ca2+ channel blocker. The biological activities of synthetic FS2 for L-type Ca2+ channels were determined under comparisons to those of CaS and nitrendipine, a 1,4-dihydropyridine derivative. Similar to CaS, FS2 competitively inhibited the binding of [3H]nitrendipine to rat brain synaptosomal membranes on Lineweaver-Bulk plot, with Kd value of 210 nM, which was similar to that of CaS being 290 nM, but did not affect binding of an N-type Ca2+ channel ligand omega-[125I]-conotoxin GVIA to the membranes. Pretreatment of A7r5 cells with either FS2 or CaS at concentrations of 10(-8) M and greater for 5 min significantly and dose-dependently reduced 10(-6) M Bay K8644-induced increase in the cytosolic free Ca2+ concentration ([Ca2+]i) of the cells determined by the fluorescent Ca2+ indicator fura-2, with the half inhibitory concentrations (IC50) of 2.3 x 10(-8) and 2.7 x 10(-8) M, being similar to that of the IC50 value of nitrendipine (4.4 x 10(-8) M). These observations indicate that FS2, similar to CaS, is an active natural L-type Ca2+ blocker sharing the binding site on the channels with the 1,4-dihydropyridines.

Amino Acid Sequence↗

PubMed1993

Endothelium-independent pressor effect of big endothelin-1 and its inhibition by phosphoramidon in rat mesenteric artery.

We asked whether or not the endothelium plays a functional role in the conversion of big endothelin-1 to endothelin-1 in the perfused rat mesenteric artery. In endothelium-denuded preparations, big endothelin-1 produced a much more potent pressor effect than in intact preparations. Phosphoramidon suppressed the big endothelin-1-induced pressor action without affecting the action of endothelin-1, irrespective of the presence or absence of the endothelium. The amounts of immunoreactive-endothelin in the perfusate during perfusion of endothelium-denuded preparations with big endothelin-1 were extremely low compared with those observed in intact preparations and were not significantly suppressed by the metalloproteinase inhibitor, phosphoramidon, in contrast to the case with intact preparations. When synthetic endothelin-1 was perfused in the endothelium-denuded mesentery, the peptide disappeared from the perfusate more rapidly than with intact preparations, suggesting that endothelin-1 generated from big endothelin-1 is effectively trapped by vascular smooth muscle cells in the endothelium-denuded preparation. Our results suggest that the endothelium is not essential for the conversion of big endothelin-1 to endothelin-1, in rat mesenteric artery.

Animals↗

PubMed1993

Calciseptine binding to a 1,4-dihydropyridine recognition site of the L-type calcium channel of rat synaptosomal membranes.

Calciseptine (CaS) is a natural peptidic L-type Ca2+ channel blocker consisting of 60 amino acids with four disulfide bonds. The effects of synthetic CaS on the binding of various ligands to Ca2+ channels of rat brain synaptosomal membranes were studied. The membranes possessed specific binding sites for L-type Ca2+ channel ligands [3H]nitrendipine, [3H]diltiazem and [3H]verapamil, derivatives of 1,4-dihydropyridine, benzothiazepine and papaverine, respectively, and also for N-type Ca2+ channel ligand omega-[125I]-conotoxin GVIA (omega-[125I]CTX). Lineweaver-Bulk plot analysis disclosed that CaS competitively inhibited the binding of [3H]nitrendipine, with maximal binding capacity of 0.19 pmol/mg protein and dissociation constant (Kd) of 290 nM, being about 10(3) times the Kd value of [3H]nitrendipine. Similar to nitrendipine, CaS noncompetitively enhanced the binding of [3H]diltiazem, but did not affect the binding of [3']verapamil. CaS at up to 10.0 microM did not affect the binding of omega-[125I]CTX. These observations indicate that CaS shares the properties of 1,4-dihydropyridine derivatives, and allosterically modulates the binding of other L-type Ca2+ channel ligands.

Animals↗

PubMed1993

Nitric oxide mediates interleukin-1-induced prostaglandin E2 production by vascular smooth muscle cells.

We examined the possible participation of nitric oxide (NO) in the activation of cyclooxygenase, a heme-containing enzyme, induced by interleukin-1 (IL-1) in vascular smooth muscle cells (VSMC). IL-1 induced a delayed and prolonged release of both NO and prostaglandin E2 (PGE2) from VSMC. NG-monomethyl-L-arginine (L-NMMA), an inhibitor of NO synthesis, partially but significantly inhibited the PGE2 release induced by IL-1, whereas it completely inhibited the IL-1-induced NO production. The inhibitory effects of L-NMMA on IL-1-induced production of both NO and PGE2 were partially reversed by a 10-fold excess of L-arginine. In addition, coincubation with superoxide dismutase enhanced the IL-1-induced PGE2 release from VSMC. In contrast, 8-bromo-cyclic GMP did not stimulate PGE2 release. Furthermore, 0.2 mM sodium nitroprusside directly stimulated PGE2 release from VSMC. These findings suggest that NO at least in part mediates the IL-1-induced PGE2 production, and that NO may be one of the important signals for the activation of cyclooxygenase to produce PGE2 in VSMC.

Animals↗

PubMed1993

[Aldosterone response to various stimuli in hyperthyroidism: in vivo and in vitro studies].

Responses of plasma aldosterone (PA) to alpha-ACTH-(1-24) (250 micrograms, im) injection and graded angiotensin II (AII) infusions (2, 4 and 8ng/kg/min for 30 min at each dose) on a constant sodium intake (170mEq daily) were assessed in 17 patients with Basedow's disease and 13 age-matched normal subjects. Aldosterone production in response to ACTH, AII and potassium in adrenal zona glomerulosa cells from L-thyroxine-induced hyperthyroid rats (H-rats) were also examined. Basal levels of plasma renin activity (PRA) and urinary aldosterone excretion were significantly higher (p < 0.01 and p < 0.05, respectively) in the patients with Basedow's disease than in the normal subjects, whereas basal PA level was similar in the two groups. The ACTH injection induced similar increases in plasma cortisol, plasma 18-hydroxycorticosterone (18-OHB) and PA in the two groups. The graded AII infusions also produced increases in plasma 18-OHB and PA in the two groups. Responses of these two corticosteroids to AII were, however, significantly lower (p < 0.05) in the patients with Basedow's disease than in the normal subjects. In the experimental animal study, basal PRA levels and the adrenal glomerulosa cell count/adrenal were significantly higher (p < 0.05) in the H-rats than in the control rats, whereas basal PA levels were similar in the two groups. Aldosterone production in response to AII, ACTH, and potassium increased in a dose-dependent manner in the two groups. Responses of aldosterone production to AII were, however, significantly lower (p < 0.05) in the H-rats than in the control rats. These results suggest that the impaired responsiveness of adrenal zona glomerulosa cells to AII, as well as an increased metabolic clearance rate of aldosterone, may be involved in the abnormal aldosterone metabolism in hyperthyroidism.

18-Hydroxycorticosterone↗

PubMed1993

Big endothelin-3-induced hypertension and its inhibition by phosphoramidon in anaesthetized rats.

Intravenous injection of big endothelin-3 (big ET-3, 1-41 amide) at 3 nmol/kg to ganglion-blocked anaesthetized rats produced a long-lasting hypertensive action, but the action was less potent than that seen with the same dose of ET-3-(1-21). The pressor effect induced by big ET-3 was markedly attenuated by pretreatment with phosphoramidon, 5 mg/kg i.v., a dose which had no effect on the hypertensive action induced by ET-3. These results strongly suggest that big ET-3 is converted to mature ET-3 by a phosphoramidon-sensitive metalloproteinase in vivo, in a manner similar to the conversion of big ET-1 to ET-1.

Anesthesia↗

PubMed1993

Effect of trimebutine maleate on emptying of stomach and gallbladder and release of gut peptide following a solid meal in man.

We investigated the effect of orally administered trimebutine maleate on gastric and gallbladder emptying and on the release of gut peptide, pancreatic polypeptide (PP), and gastrin in humans for 120 min after ingestion of a solid meal. Gastric emptying was measured by a radionuclide technique. Gallbladder emptying was estimated by real-time ultrasonography. The oral administration of 200 mg of trimebutine maleate significantly shortened the lag time in starting gastric emptying (P < 0.05). Considering gallbladder emptying, trimebutine significantly inhibited the fasting emptying induced by neural reflex. Postprandially, there was a tendency toward an accelerated gallbladder emptying in the early phase. Neither the maximal percentage of gallbladder emptying nor the time of peak gallbladder emptying were affected. Trimebutine significantly blunted the post-prandial PP response in the cephalic and gastric phases, reflecting a vagal-cholinergic activity (P < 0.05). The PP response in the intestinal phase was also blunted. Gastrin release was significantly augmented only during the period of fasting after drug administration (P < 0.05). The major effect of trimebutine maleate appears to be a shortening of the lag time at the start of gastric emptying probably via its anticholinergic activity.

Administration, Oral↗