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Biomedical subjects

N Iwata

Publications and source records attributed to N Iwata.

At least 127 records · Page 7Linked to original sources
PubMed1995

Changes in levels of monoamines and their metabolites in incompletely ischemic brains of spontaneously hypertensive rats.

In order to investigate changes in levels of monoamines and their related substances together with those of other neurotransmitters (acetylcholine and GABA), choline and substances related to energy metabolism (ATP, lactate and glucose) accompanying incomplete cerebral ischemia, a bilateral common carotid artery occlusion model of spontaneously hypertensive rats (SHR) was utilized. Animals were subjected to 1 or 2 h ischemia. Then the concentrations of substances were measured in the cerebral cortex, hippocampus and striatum and compared with control values. Due to the incomplete ischemia, ATP showed a moderate decrease, while lactate and choline increased remarkably, and GABA underwent a moderate increase. With regard to monoamines, both noradrenaline and serotonin levels were reduced in the cerebral cortex and hippocampus, whereas dopamine levels increased in the hippocampus. All monoamine metabolites, i.e. metabolites by monoamine oxidase (MAO), metabolites by catechol-O-methyltransferase (COMT), and metabolites by both MAO and COMT, underwent increases. The 3-methoxytyramine level in particular showed marked increases. Furthermore levels of precursor amino acids as well as 5-hydroxytryptophan rose. Acetylcholine decreased moderately only in the cerebral cortex. Among these changes, sustained increases in all the monoamine metabolites were characteristic of changes in the incompletely ischemic brain, suggesting that both COMT and MAO retain their activities in the incompletely ischemic brain.

Acetylcholine↗
PubMed1995

Cyclic change in 3 alpha-hydroxysteroid dehydrogenase in rat ovary during the estrous cycle.

3 alpha-Hydroxysteroid dehydrogenase (3 alpha-HSD) activity and content in the rat ovary were measured at various stages of the estrous cycle, and the enzyme protein in the ovary was localized by immunohistochemistry. The cyclic change of ovarian 3 alpha-HSD activity towards 5 alpha-dihydrotestosterone (5 alpha-DHT) as a substrate was characterized by two peaks. The first peak occurred at 0800 h on proestrus; then the reductase activity decreased and reached its minimum at 2000 h on proestrus. Thereafter, it gradually increased, reaching the second peak (170% of the value at 2000 h on proestrus) at noon of estrus. Quantitative analysis by immunoblotting revealed that the alteration in 3 alpha-HSD content in the rat ovary during the estrous cycle was essentially similar to that in 5 alpha-DHT reductase activity. Changes in the reductase activities towards 5 alpha-androstane-3,17-dione and 5 alpha-DHT and in the dehydrogenase activity towards androsterone in the ovary were entirely different from those in the 5 alpha-DHT reductase activity and 3 alpha-HSD content; on the other hand, the change in carbonyl reductase activity towards p-nitroacetophenone was similar to changes in 5 alpha-DHT reductase activity and 3 alpha-HSD content. Therefore, p-nitroacetophenone may be a useful substrate, instead of 5 alpha-DHT, for detection of 3 alpha-HSD activity at a high sensitivity, since the p-nitroacetophenone reductase activity was 10-fold higher than the 5 alpha-DHT reductase activity. The enzyme was primarily localized in the granulosa cells and CL cells. At 2000 h on proestrus, however, the overall intensity of immunostaining in the granulosa cells of the Graafian follicles was markedly diminished. In addition, immunoreactivity in the CL cells at 0800 h on estrus was observed only in the cells outlining the CL in some cases.

3-Hydroxysteroid Dehydrogenases↗
PubMed1995

A supplemental measure of stay-times in the light box on step-through passive avoidance.

The avoidance behavior of rats in a typical step-through passive avoidance task was evaluated by using two types of time measurements that differed from traditional step-through latency (STL). The total stay-time in the light box (TL) was calculated as an index of the dark box avoidance throughout the retention trial, counting the time before and after the first step-through. The total stay-time in the far area of the light box (TF) was calculated as an index of the tendency to keep away from the dark box. TL, TF and the STL increased with electrical shock intensity at acquisition trials and gradually decreased through an extinction procedure. The discrepancy between our new measures and the STL was observed when the effects of a new drug, RS-8359, which was reported to ameliorate ischemic brain damage, were examined in ischemic animals. TL, TF and STL decreased in rats receiving brain ischemia, and we found that after treatment with RS-8359, TL and TF increased, but no effect was observed on STL. The discrepancy observed suggests that a short STL does not necessarily imply a loss of avoidance behaviour. Passive avoidance tests can be more revealing about a drug's effects when stay-time measures are used.

Animals↗
PubMed1995

Changes in adrenal carbonyl reductase activity in pregnant rats.

Changes in adrenal carbonyl reductase (CR) activity during pregnancy and postparturition in rats were investigated using two substrates, 13,14-dihydro-15-keto-prostaglandin F2 alpha (15KD-PGF2 alpha) and p-nitroacetophenone (PNAP). 15KD-PGF2 alpha reductase activity showed the lowest level on day 16 of pregnancy and steeply increased on the morning of postpartum day 1. PNAP reductase activity did not change up to day 18 of pregnancy, then was gradually increased and maintained the highest levels between day 19 and the morning of day 21 of pregnancy. Thereafter, the enzyme activity was rapidly decreased after parturition, on the contrary of changes in the 15KD-PGF2 alpha reductase activity. On the other hand, exogenous glucocorticoid treatment increased the 15KD-PGF2 alpha activity and decreased the PNAP reductase activity in adrenal glands of nonpregnant animals. Thus, it is found that the adrenal CRs in the above two classes are regulated by different mechanisms. As maternal corticosterone level is increased rapidly during late pregnancy by maternal transfer of fetal corticosterone, the present results suggest that adrenal CR activity during pregnancy, in particular at periparturition, may be influenced by fetal corticosteroids.

Adrenal Glands↗
PubMed1995

Increase in oxygen tension after intraperitoneal N-methyl-DL-aspartate in rat cerebral cortex.

An oxygen electrode equipped with a thermocouple enabled us to determine the absolute oxygen tension (PO2) in brain regions by taking account of local changes in temperature. Under urethane anesthesia, the PO2 of rat cerebral cortex was significantly increased up to 90 min after N-methyl-DL-aspartate administration (200 mg/kg, i.p.). This suggests that stimulation of NMDA receptors enhances oxygen supply to the cerebrum in vivo.

Animals↗
PubMed1995

[Perihepatitis].

Explore the source record for details and available documents.

Adolescent↗
PubMed1995

Interindividual variation in carboxylesterase levels in human liver microsomes.

Microsomal carboxylesterase activities in 12 human livers were determined using 10 kinds of carboxylesterase substrates (p-nitrophenylacetate, p-nitrophenylpropionate, p-nitrophenylbutyrate, butanilicaine, isocarboxazid, palmitoyl-coenzyme-A, malathion, clofibrate, acetanilide, and phenacetin). There were large individual differences in the 12 humans based on experimental results in the past several years in our laboratory. We found that all human liver microsomes have RH1-immunoreactive carboxylesterase, and the carboxylesterase content in liver also showed large individual differences. The RH1-immunoreactive carboxylesterase concentration correlated well with those of p-nitrophenylesters, clofibrate, butanilicaine, and isocarboxazid, and anti-RH1 immunoglobulin G strongly inhibited human liver hydrolase activity. These findings indicate that one major carboxylesterase isozyme that is immunoreactive with anti-RH1 in human liver microsomes has catalytic activity on major carboxylesterase substrates, and thus hydrolase activity in human liver depends on the expression level of this carboxylesterase isozyme. These observations should be useful in understanding the action of carboxylesterases on drug metabolism in humans.

Adult↗
PubMed1994

Plasma cell leukemia with myelofibrosis.

We describe a case of plasma cell leukemia associated with myelofibrosis. A 60-year-old woman was admitted due to lumbago and monoclonal hypergammaglobulinemia. Peripheral blood showed about 40% of plasma-cell-like cells. A bone marrow aspiration was dry tap. The patient was diagnosed as having plasma cell leukemia with myelofibrosis by bone marrow biopsy. Plasma cell leukemia as well as myelofibrosis improved with combination chemotherapy using vincristine, pirarubicin, and dexamethasone. However, when plasma cell leukemia became resistant to chemotherapies, myelofibrosis also reappeared. This case strongly suggests the pathogenetic relationship between plasma cell leukemia and myelofibrosis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Responses to a self-administered depression scale among younger adolescents in Japan.

Response patterns on the Center for Epidemiologic Studies Depression Scale (CES-D) items among Japanese adolescents were compared with those of their U.S. counterparts. The data were obtained from approximately 1,500 junior high school students, aged 12-15 years. Japanese responses to positively worded items markedly differed from those of American adolescents, whereas responses to negatively worded items were comparable in the two groups. This resulted in poor psychometric properties for the CES-D and spurious higher positive subscale and whole scale scores among the Japanese sample. It is possible that Japanese respondents tend to suppress positive affect expression and, thus, the positively worded questioning is presumably inappropriate for Japanese samples.

Adolescent↗
PubMed1994

Psychometric properties of the 30-item version general health questionnaire in Japanese.

Psychometric properties of the 30-item General Health Questionnaire (GHQ-30) were explored using the Japanese data collected in various settings. A six- or seven-factor structure emerged for the entire sample and each gender and age-group divided into a 10-year interval. The factors were highly identical across the subsamples. The main four factors showed a high agreement with those of UK and Hong Kong studies: approximately 80% of the items were similarly allocated to factors. However, the response endorsement of two "loss of positive attitude" items was much common regardless of the score level. These items counted up approximately one-fourths of the score, so that these items made the score spuriously higher. According, a question arose as to whether these items should be included in the scale for its use in Japanese.

Adult↗
PubMed1994

Effects of RS-8359 on reduced local cerebral glucose utilization in the rat subjected to transient forebrain ischemia.

Changes in local cerebral glucose utilization (LCGU) of the postischemic rat brain were investigated using the rat four-vessel occlusion model. Following 20 or 30 min of ischemia, LCGUs of the cerebral cortices, striatum and hippocampus were decreased at 1 and 3 days postischemia, but were recovered at 7 days postischemia. Effects of repeated administration of RS-8359, (+-)-4-(4-cyanoanilino)-7-hydroxycyclopenta(3,2-e)pyrimidin e, (30 mg/kg x 2/day, p.o., 4 days) were examined at 3 days postischemia following 20 min of ischemia. Compared with the sham-operated group, the LCGUs of 22 out of 34 structures examined in the ischemic-control group were significantly reduced. In the RS-8359-treated group, however, significant reduction was observed in only 9 structures. Compared with the ischemic-control group, RS-8359 significantly ameliorated the reduction of LCGU in 12 structures. These results suggest that RS-8359 has beneficial effects on reduced glucose metabolism in the postischemic brain.

Animals↗
PubMed1994

Functional characterization of two cholecystokinin-B/gastrin receptor isoforms: a preferential splice donor site in the human receptor gene.

The cholecystokinin-B and gastrin receptor is encoded by a single gene composed of five exons and spanning over 10 kilobases on human chromosome 11p 15.5-->15.4. Exon 4 has two possible alternative splicing donor sites that seem to be conserved in other species such as the canine, rat, Mastomys, and mouse. They could generate two receptor isoforms (short- and long-form), which differ in their putative third cytoplasmic domain of the serpentine G-protein-coupled receptors. In the present study, we examined whether an alternative splicing is operated in a tissue-specific manner and whether two receptor isoforms have functional differences. RNase-protection assay and S1 nuclease mapping demonstrated the preferential expression of the short-form in the human brain as well as the digestive organs, stomach and pancreas. The two putative isoforms of the cholecystokinin-B/gastrin receptor expressed in mouse fibroblasts showed the same characteristics in their ligand-bindings, the major signal transduction such as phosphoinositides production, cytoplasmic Ca2+ increase, tyrosine phosphorylation of focal adhesion kinase, activation of mitogen-activated protein kinase, and the induction of early-responsive genes such as c-fos, c-myc, and c-jun. Moreover, the ligand-dependent trophic effect was seen in both receptor isoforms. Taken together with the absence of tissue-specific expression of two receptor isoforms, these results suggest a species-specific dominant splice donor site in exon 4 of the human receptor gene.

3T3 Cells↗
PubMed1993

Induction of cytochrome P450 1A2 by musk analogues and other inducing agents in rat liver.

We characterized the inducing effects of two musk analogues, musk xylene and musk ambrette, on phase I and phase II drug-metabolizing enzymes in rat liver and compared their effects with 3-methylcholanthrene, isosafrole and 2(3)-tertbutylhydroxyanisole (BHA) at 0.1 mmol/kg dose level. Musk xylene and isosafrole increased more efficiently the metabolic activation of 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1) to mutagen than that of benzo(a)pyrene. Musk ambrette increased both the activation of Glu-P-1 and benzo(a)pyrene to the same extent. Western blot analyses revealed that musk xylene, musk ambrette, isosafrole and BHA induced more strongly cytochrome P450 1A2 (CYP1A2) in microsomes than CYP1A1. 3-Methylcholanthrene induced CYP1A1 in preference to CYP1A2. On the other hand, all drugs except for 3-methylcholanthrene did not show remarkable increases in phase II enzyme activities, such as DT-diaphorase, glutathione S-transferase and UDP-glucuronyltransferase, at 0.1 mmol/kg dose level. These results show that musk xylene, musk ambrette, isosafrole and BHA at the dose level used in this study possess the potency to induce CYP1A2 without remarkable induction of CYP1A1 and phase II enzyme activities as observed for 3-methylcholanthrene, although they have been considered to induce both phase I and phase II drug-metabolizing enzymes at higher doses.

Animals↗
PubMed1993

An unusual profile of musk xylene-induced drug-metabolizing enzymes in rat liver.

We have demonstrated previously that musk xylene, a non-mutagenic carcinogen, is a novel and specific inducer of CYP1A2 in rats (Iwata et al., Biochem Biophys Res Commun 184: 149-153, 1992). In the present study, the effects of musk xylene (50, 100 or 200 mg/kg body weight, i.p., for 5 consecutive days) on both Phase I and Phase II metabolizing enzymes in rat liver were investigated further and more completely. Among the mixed-function oxidases monitored, 7-ethoxycoumarin deethylase and 7-pentoxyresorufin depentylase activities were increased at all dose levels from 1.6- to 1.7-fold and 2.6- to 3.1-fold, respectively. Benzo[a]pyrene hydroxylase activity was increased significantly at only the 200 mg/kg dose level of musk xylene (1.5-fold). Regarding Phase II enzymes, activities of both cytosolic DT-diaphorase and glutathione S-transferase (GST) were increased up to 2.0- to 2.4-fold by musk xylene in a dose-dependent manner. Western blot analysis revealed that the changes in these activities were caused by increases in the amounts of DT-diaphorase and GST Ya subunit. Microsomal UDP-glucoronyltransferase (UDPGT) activity assayed with p-nitrophenol as substrate was increased 1.6- to 2.0-fold. These results show that musk xylene induces both Phase I cytochrome P450 mixed-function oxidase (CYP1A2 specific) and Phase II metabolizing enzyme systems (DT-diaphorase, GST Ya subunit and UDPGT) in rat liver.

Animals↗
PubMed1993

Interindividual variability of carbonyl reductase levels in human livers.

Interindividual variability of carbonyl reductase levels in human livers (N = 11) was examined by measuring reductase activity toward various substrates and by western blot analysis using anti-rat ovarian carbonyl reductase CR2 antibody. The carbonyl reductase activity toward p-nitrobenzaldehyde (PNBA) (58.1 +/- 5.4 nmol/mg protein/min, mean +/- SE) was highest among the substrates examined, followed by 4-benzoylpyridine (4BP) (14.4 +/- 2.0 nmol/mg protein/min) and p-nitroacetophenone (PNAP) (2.00 +/- 0.37 nmol/mg protein/min). The reductase activity (6.33 +/- 0.56 pmol/mg protein/min) toward 13,14-dihydro-15-keto-prostaglandin F2 alpha (15KD-PGF2 alpha), which is a diagnostic substrate for rat ovarian carbonyl reductases, was relatively high compared to that in other species. Western blot analysis revealed that each human liver contained several immunoreactive proteins to anti-CR2 antibody. The activities toward 15KD-PGF2 alpha (r = 0.85, P < 0.01) and 4BP (r = 0.84, P < 0.01), but not PNBA (r = 0.53, not significant) or PNAP (r = 0.52, not significant), were closely correlated with the relative amounts of the high molecular weight immunoreactive proteins determined with a densitometer. Thus, the major carbonyl reductases in human liver are similar to those of rat ovarian enzymes.

Acetophenones↗
PubMed1993

Gonadotropin-induced ovarian carbonyl reductase in mice and hamsters: comparison with carbonyl reductase in rats.

We investigated the effects of pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) on ovarian carbonyl reductase activities towards 13,14-dihydro-15-ketoprostaglandin F2 alpha (15KD-PGF2 alpha), p-nitroacetophenone (PNAP) and p-nitrobenzaldehyde (PNBA) in mice and hamsters, and compared with their effects on those we observed previously in rats. The treatment with PMSG and hCG caused a significant increase in ovarian weights and superovulation in both mice and hamsters. Hamster ovary possessed appreciable carbonyl reductase activities towards all three substrates, whereas the activities were lower than those in rat ovary. The reductase activities were not increased by the treatment with gonadotropins, differing from rat ovarian carbonyl reductase. In untreated mice, carbonyl reductase activity towards 15KD-PGF2 alpha was not detected, whereas the activities towards PNAP and PNBA were detected, which activities were lower than those in rats and hamsters. The PNAP and PNBA reductase activities in mouse ovary were significantly increased up to 7.1- and 1.7-fold, respectively, by the treatment with gonadotropins. These results show that there are species differences in ovarian carbonyl reductase and response of the enzyme to gonadotropins.

Alcohol Oxidoreductases↗