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Biomedical subjects

M Murakami

Publications and source records attributed to M Murakami.

At least 721 records · Page 40Linked to original sources
PubMed1994

Does the anabolic metabolism of L-[2-18F]fluorophenylalanine and L-[2,6-3H]phenylalanine differ in the cerebrum and the cerebellum?

The anabolism of isotopically labeled amino acids was compared between the cerebrum and the cerebellum in conscious rat at three feeding conditions. After L-[2-18F]fluorophenylalanine and L-[2,6-3H]phenylalanine injections, the incorporation rate of both radioactivity into protein fraction showed no difference between the cerebrum and the cerebellum at normal condition, but the lipid fraction in the cerebellum was higher than that in the cerebrum in any conditions. These results show the usefulness of L-[2-18F]fluorophenylalanine as a positron emission tomography tracer and different anabolic rate of the amino acids to lipid between the cerebrum and cerebellum.

Animals↗
PubMed1994

Stability of acyl derivatives of insulin in the small intestine: relative importance of insulin association characteristics in aqueous solution.

The stability of insulin and its acyl derivatives in the small intestine was examined in vitro. When these compounds were incubated in small intestinal fluid at 37 degrees C, proteolysis of monoacyl insulins was reduced by increasing the carbon number of the fatty acid attached to Phe-B1 of the insulin molecule. In contrast, Phe-B1 and Lys-B29 diacylated insulins were more susceptible to hydrolysis than native insulin. Similar results were obtained using homogenates of the small intestinal mucosa, although the extent of the contribution of acylation to insulin degradation differed. The mechanism of the accelerated insulin proteolysis by diacylation was studied by circular dichroism (CD). The negative maxima at 270 nm in the CD spectra were attenuated for the diacyl derivatives, indicating that insulin association was inhibited by diacylation. Therefore, the increased proportion of monomers available for insulin proteolysis represents a main factor that makes diacyl derivatives unstable.

Acylation↗
PubMed1994

Effects of various protease inhibitors on the intestinal absorption and degradation of insulin in rats.

The effects of protease inhibitors on the intestinal absorption of insulin were investigated in situ in closed small and large intestinal loops in rats, and the stability of insulin was examined in homogenates of the small and large intestine. The intestinal absorption of insulin was evaluated by its hypoglycemic effect. When insulin alone was administered into small or large intestinal loops, no marked hypoglycemic response was observed in either region. Of the coadministered protease inhibitors, soybean trypsin inhibitor (1.5, 10 mg/ml) marginally promoted insulin absorption from the large intestine, whereas aprotinin (10 mg/ml) did to a moderate degree. However, a significant hypoglycemic effect was obtained following large intestinal administration of insulin with 20 mM of Na-glycocholate, camostat mesilate and bacitracin, when compared with the controls. In contrast, we found little hypoglycemic effect following small intestinal coadministration of insulin with these protease inhibitors. In the stability experiment, bacitracin, camostat mesilate and Na-glycocholate were effective in reducing insulin degradation in both small and large intestinal homogenates. It was found that the reduction in the proteolytic rate of insulin was related to the decrease in plasma glucose concentration by these protease inhibitors in the large intestine. These findings suggest that coadministration of protease inhibitors would be useful for improving the large intestinal absorption of insulin.

Animals↗
PubMed1994

Developmental change in activity of red cell porphobilinogen deaminase and its electrophoretic variant in the Japanese population.

The activity of porphobilinogen deaminase (PBGD), an enzyme whose partial deficiency is associated with acute intermittent porphyria (AIP), changes during development. Little is known about the postnatal change of PBGD activity and the prevalence of its electrophoretic variant in the Japanese population. The activity of PBGD was measured fluorometrically in 194 infants aged 0-12 months, while isoelectric focusing of PBGD was performed in 400 healthy Japanese adults aged 20-45 years and 30 children with various hematological disorders aged 1-15 years. The PBGD level was 1.9 times higher in the neonates than in the adults, decreased abruptly during the first month of life, and reached the adult level at the age of 9 months. None of the 400 healthy Japanese adults and the 30 children with hematological disorders showed any electrophoretic variant. These results suggest that there is no need to consider any polymorphism in the gene dose study of PBGD and that the biochemical screening of AIP is applicable to since the late infancy.

Adult↗
PubMed1994

Analysis of AP-1 function in cellular transformation pathways.

To understand the role of endogenous AP-1 activity in cellular transformation induced by oncogenes, we have made use of a fos mutant (supfos-1) and a jun mutant (supjun-1), either of which can function as a transdominant inhibitor of AP-1-mediated transcriptional regulation. Chicken embryo fibroblasts (CEF) infected with a series of transforming retroviruses were doubly infected with retrovirus carrying supfos-1 or supjun-1, and suppression of cellular transformation was monitored in terms of reversion to normal cellular morphology or acquisition of anchorage-dependent growth. Cellular transformation induced by several exogenously expressed transforming genes of the fos or jun family was efficiently suppressed, as expected. CEF transformed by v-src, v-yes, v-fps, c-Ha-ras, and N-terminally truncated c-raf were also induced to revert to the normal phenotype by these transdominant mutants, suggesting that functional transcription factor AP-1 activity is essential for the cellular transformation induced by these oncogenes. The suppression is not attributable to nonspecific inhibition of cellular proliferation, because CEF transformed by v-ros or v-myc were not induced to revert to the normal phenotype. We next analyzed changes in all known components of chicken AP-1 induced by v-src, c-Ha-ras, or activated c-raf transformation. The levels of both Fra-2 and c-Jun expression were elevated two- to fourfold, and hyperphosphorylation of Fra-2 was also observed. We further showed that Fra-2-c-Jun heterodimer is mainly responsible for the elevated AP-1 DNA-binding activity in these transformed cells, and we propose that this heterodimer play a crucial role in the transformation induced by these oncogenes.

Animals↗
PubMed1994

Methionine PET for follow-up of radiation therapy of primary lymphoma of the brain.

Positron emission tomography (PET) with carbon-11 methionine, computed tomography (CT), and magnetic resonance (MR) imaging were performed in 10 patients with histologically verified central nervous system (CNS) lymphoma before and after radiation therapy to compare the radiologic findings and to evaluate the usefulness of PET in monitoring tumor response to radiation therapy. Methionine PET clearly depicted CNS lymphoma before radiation therapy as an increased accumulation of C-11 methionine. The extent of increased accumulation of the radiotracer in tumor tissue markedly decreased after radiation therapy. The area of increased uptake was larger than the enhancing lesions on CT or MR images in most cases. One patient was confirmed to have tumor recurrence at the region of residual increased accumulation on methionine PET images. Methionine PET is useful for the delineation of CNS lymphoma and for monitoring the therapeutic effect of irradiation.

Aged↗
PubMed1994

Effects of oral AVP receptor antagonists OPC-21268 and OPC-31260 on congestive heart failure in conscious dogs.

Rapid right ventricular pacing could induce congestive heart failure in conscious dogs with significant increase in plasma concentration of arginine vasopressin (AVP) (from 1.2 +/- 0.2 to 3.4 +/- 0.6 pg/ml). In this experimental model of heart failure, oral administration of the selective AVP V1 receptor antagonist OPC-21268 significantly increased cardiac output and improved renal function without significant changes in serum electrolytes and hormones. Oral administration of the selective AVP V2 receptor antagonist OPC-31260 induced marked water diuresis, which resulted in significant increases in serum sodium concentration, plasma renin activity, and plasma concentration of AVP, although it did not produce hemodynamic improvement. Combined administration of OPC-21268 and OPC-31260 showed supra-additive hemodynamic responses as well as additive renal and metabolic responses, i.e., it showed prolonged decrease in mean arterial pressure and profound increase in cardiac output. These results suggest that AVP plays a significant role in elevation of vascular tone through V1 receptors and plays a major role in retaining free water through V2 receptors in this model of heart failure. Furthermore, combined administration of V1 and V2 receptor antagonists could induce not only metabolic and hormonal responses but also more beneficial hemodynamic responses than those observed following treatment with V1 receptor antagonist alone.

Animals↗
PubMed1994

Glucocorticoid increases angiotensin II type 1 receptor and its gene expression.

Recently, we demonstrated that glucocorticoid potentiates inositol triphosphate production evoked by angiotensin II in vascular smooth muscle cells. To clarify this mechanism, we investigated the effects of dexamethasone on the modulation of angiotensin II type 1 receptor and on postreceptor mechanisms in vascular smooth muscle cells. The number of angiotensin II type 1 receptors began to increase after 12 hours' incubation with dexamethasone. After 48 hours, the Bmax value reached 27 +/- 3 fmol/mg protein in dexamethasone-treated cells and 15 +/- 3 fmol/mg protein in control cells. However, binding affinity did not change. A glucocorticoid antagonist, RU 38486, completely blocked these effects of dexamethasone. Also, to elucidate the effects of dexamethasone on postreceptor mechanisms, GTP analogue-induced inositol trisphosphate production in permeabilized cells was examined. Pretreatment with 1 mumol/L dexamethasone for 48 hours did not affect these inositol trisphosphate productions. Moreover, dexamethasone had no effect on the level of Gq alpha protein. Furthermore, steady-state levels of angiotensin II type 1 receptor messenger RNA were increased 2.2 +/- 0.3-fold after 30 minutes' exposure to 1 mumol/L dexamethasone and 7.8 +/- 0.4-fold after 24 hours. We conclude that glucocorticoid induced expression of the angiotensin II type 1 receptor gene and resulted in an increase in the number of angiotensin II type 1 receptors through the glucocorticoid-specific receptor, without significant effect on postreceptor systems in vascular smooth muscle cells.

Angiotensin II↗
PubMed1994

Nitric oxide increases renal blood flow by interacting with the sympathetic nervous system.

To investigate whether changes in renal blood flow induced by nondepressor doses of L-arginine, the precursor of nitric oxide, are mediated by a sympathetic neural mechanism, we examined the following in conscious rabbits: (1) the effects of intravenous infusion of L- or D-arginine (15 to 200 mumol/kg per minute) on renal blood flow and renal sympathetic nerve activity with or without intravenous infusion of a nonpressor dose of NG-monomethyl-L-arginine (L-NMMA), a nitric oxide synthase inhibitor, and (2) the effects of L-arginine on renal blood flow after renal denervation with or without L-NMMA pretreatment. In renal innervated rabbits, L-arginine (100 and 200 mumol/kg per minute) increased renal blood flow by 9 +/- 2 and 16 +/- 3 mL/min (P < .05, respectively) and decreased renal sympathetic nerve activity by 12 +/- 4% and 19 +/- 3% of control (P < .05, respectively). In contrast, no changes occurred in any variable during D-arginine infusion. L-NMMA attenuated the renal blood flow and renal sympathetic nerve activity responses to L-arginine (P < .05). In renal denervated rabbits, L-NMMA also attenuated the renal blood flow responses to L-arginine (P < .05) and abolished them (P < .05) compared with those in renal innervated rabbits. All renal blood flow responses to L-arginine were accompanied by parallel changes in plasma L-citrulline concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Auditory event-related potentials in benign childhood epilepsy with centrotemporal spike: the effects of carbamazepine.

To clarify the relationship between cognitive function and CBZ therapy, auditory event-related potentials (P300) were examined in 23 patients with Benign Childhood Epilepsy with Centrotemporal Spike (BCECT) compared with 54 normal controls. The results were 1) the mean P300 latency in BCECT (368 +/- 29 msec) was significantly prolonged compared with that in normal controls (349 +/- 30 msec), but most individual patients showed normal values. 2) The prolongation of P300 latency was greatest during the course of therapy. 3) On repeated examination of P300, P300 latency was found to gradually become shorter with age in spite of continuous CBZ therapy. At initiation of CBZ therapy, the P300 latency became shorter; on the other hand, P300 latency became shorter with the discontinuation of CBZ. 4) The age-corrected P300 latency showed a significant positive correlation with the serum concentration of CBZ. Our results suggest that CBZ therapy has both an undesirable effect (chronic impairment) and a desirable effect (improvement of underlying dysfunction caused by epileptogenesis) on cognitive function.

Acoustic Stimulation↗
PubMed1994

Changes in EEG foci with age in childhood partial epilepsies.

The age changes of epileptic foci on EEG were evaluated in 208 patients with childhood partial epilepsies, who were followed for more than 3 years. 1) The incidence of EEG foci in each region apparently differed with age. Frontal and central foci were frequent before school age and after adolescence. Temporal foci showed a peak around adolescence, and occipital foci a peak from 3 to 7 years, respectively. Parietal foci were rare at all ages. 2) The migration of EEG foci was recognized 171 times in 81 of the 208 patients (38.9%) during the clinical course. The migration was frequently seen at early school age and preadolescence, and the direction of migration was predominantly anterior to posterior at early school age, and posterior to anterior at preadolescence. These results suggest that EEG foci show characteristic changes with age during the clinical course, which may be related to maturation of the central nervous system.

Adolescent↗
PubMed1994

Intestinal absorption of azetirelin, a new thyrotropin-releasing hormone (TRH) analogue. I. Possible factors for the low oral bioavailability in rats.

Absorption of azetirelin, a new thyrotropin-releasing hormone (TRH) analogue, from the gastrointestinal (GI) tract was evaluated. The bioavailability of this compound after oral administration was considerably poor in rats. Studies were undertaken to elucidate the mechanisms for this low oral bioavailability of azetirelin. The plasma azetirelin levels following intravenous and hepatoportal vein injection were virtually identical over the dose range of 0.02-0.1 mg/kg, indicating a minor contribution of the hepatic first-pass metabolism of this drug. Azetirelin was stable against peptide hydrolases both in luminal fluid and intestinal mucosal homogenates, whereas its degradation occurred when incubated with cecal contents under an anaerobic condition. In addition, complete degradation of azetirelin during the GI transit was disclosed by analyzing the fecal sample collected after oral administration of [14C]azetirelin. These results suggested that gut bacteria may be responsible for the hydrolysis of azetirelin in the GI tract. The low intestinal permeability of azetirelin was revealed by a modified everted gut experiment in various segments of the rat intestine. The poor membrane transport characteristics of azetirelin may be due to its high hydrophilicity. From these results, it was suggested that the insufficient oral bioavailability of azetirelin may be mainly attributed to its low intestinal permeability due to a lack of lipophilicity, and also to the degradation of the peptide by intestinal microflora.

Administration, Oral↗
PubMed1994

Characterization of cytosolic phospholipase A2 in rat mastocytoma RBL-2H3.

We previously reported that cultured mast cells expressed three discrete phospholipases A2 (PLA2S), one of which showed a remarkable preference for phospholipids bearing an arachidonoyl residue at the sn-2 position [M. Murakami, et al., J. Biochem., 111, 175 (1992)]. In the present study, we have purified and characterized this enzyme using rat mastocytoma RBL-2H3 as an enzyme source. The elution profiles of the arachidonoyl-preferential PLA2 activity of rat mastocytoma RBL-2H3 cells on several column chromatographies were indistinguishable from those of 85-kDa cytosolic PLA2 (cPLA2) characterized so far. The molecular mass of the partially purified PLA2 was estimated to be about 90 kDa by gel filtration and it hydrolyzed arachidonate-containing phospholipids preferentially in the presence of submicromolar Ca2+ concentrations. Furthermore, it was immunoprecipitated with an anti-rabbit cPLA2 antibody almost completely. From these observations, we have concluded that the arachidonoyl-preferential PLA2 in mast cells belongs to the "cPLA2" family.

Animals↗
PubMed1994

Observation of sleep-related breathing disorders in patients with coronary artery disease by ambulatory electrocardiogram-respiration monitoring system.

Eighty-five coronary artery patients examined using an ambulatory electrocardiogram-respiration monitoring system (AERMS) in which a respiratory sensor was strapped to the right upper abdominal wall. Apnea was defined as a cessation of abdominal wall movement lasting at least 10 sec. Sleep-related breathing disorder (SRBD) was diagnosed if at least 30 apneic episodes were observed during sleep. The cardiac events evaluated during follow-up included occurrence of sudden death, myocardial infarction and ventricular tachycardia. SRBD was detected in 9 of 85 patients (11%). There were more patients with low EF (EF < 50%) in the SRBD group than in the non-SRBD group (p < 0.01). During follow-up for a mean period of 18.4 +/- 7.6 months after ambulatory recording, four of nine (44%) patients in the SRBD group had cardiac events, compared with only four of 79 (6%) patients in the non-SRBD group (p < 0.001). Thus, coronary artery patients who were complicated with SRBD showed poor cardiac function and had a high incidence of cardiac events.

Aged↗
PubMed1994

[Hypotensive action of human renin inhibitor KRI-1314 in the common marmoset].

The possibility of using KRI-1314, a new cyclohexylnorstatine derivative, as an antihypertensive drug was examined using common marmosets. KRI-1314 strongly inhibited plasma renin activity (PRA) in both humans and marmosets, with a 50% inhibitory concentration of 4.7 x 10(-9) and 6.9 x 10(-9) M, respectively. In anesthetized marmosets, the increase in both blood pressure and PRA induced by bolus intravenous injection of RH-renin (0.15 microgram/kg) was suppressed by constant intravenous infusion of KRI-1314 (0.01 and 0.1 mg/kg/min) in a dose-dependent manner. In the sustained hypertension induced by continuous intravenous infusion of RH-renin (0.1 microgram/kg/min), a dose-dependent hypotensive response was produced by bolus intravenous injection of KRI-1314 (0.03-3 mg/kg). In the sodium-depleted model, whose PRA was increased by a two-week low-sodium diet coupled with furosemide loading, both intravenous injection (0.1-3 mg/kg) and oral administration (10 and 30 mg/kg) of KRI-1314 to anesthetized and conscious animals, respectively, lowered blood pressure dose-dependently with PRA suppression. The hypotensive activity of orally administered KRI-1314 (30 mg/kg) was almost equal to that of orally administered captopril (1 mg/kg). KRI-1314 did not affect heart rate in any of the experiments. These results indicate that the potent human renin inhibitor KRI-1314 may become an orally effective drug for treating renin-dependent hypertension.

Administration, Oral↗
PubMed1994

Effects of glibenclamide on negative cardiac responses to cholinergic and purinergic stimuli and cromakalim in the isolated dog heart.

We investigated the effects of an ATP-sensitive K+ channel blocker, glibenclamide, on the negative chronotropic and inotropic responses to intracardiac parasympathetic nerve stimulation, acetylcholine (ACh, a muscarinic receptor agonist), ATP (a P2-purinergic receptor agonist), adenosine (a P1-purinergic receptor agonist) and cromakalim (a potassium channel opener) in the isolated, blood-perfused canine right atrium of left ventricle. A high dose of glibenclamide (3 mumol) did not affect the negative chronotropic and inotropic responses to parasympathetic stimulation (frequencies of 1-30 Hz), although it slightly but significantly attenuated the negative cardiac responses to exogenous ACh (0.3-10 nmol). Furthermore, adenosine (0.03-0.3 mumol)-induced negative chronotropic and inotropic responses were significantly inhibited by glibenclamide (3 mumol), but ATP (0.01-1 mumol)-induced negative cardiac responses were not affected. A cumulative administration of cromakalim (0.01-1 mumol) dose-dependently caused much greater decreases in the contractile force of atrial and ventricular muscles than in sinus rate. Glibenclamide (0.3-3 mumol) similarly blocked the negative chronotropic and inotropic responses to cromakalim in a dose-dependent manner. These results suggest that glibenclamide modifies the negative cardiac responses to parasympathetic activation both in pre- and postjunctional sites and the responses to adenosine but not to ATP at K+ channels in the dog heart, although the modifications are minor under physiological conditions.

Acetylcholine↗