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Biomedical subjects

N Iwata

Publications and source records attributed to N Iwata.

At least 145 records · Page 8Linked to original sources

Involvement of opioid receptors in shaking behaviour induced by paraquat in rats.

Paraquat (30-70 mg/kg intraperitoneally) caused typical shaking behaviour in rats in a dose-dependent manner. Myoclonus also appeared after the shaking behaviour in several rats treated with the highest dose of paraquat. Morphine (5 mg/kg intraperitoneally, 30 min. before paraquat) significantly reduced the frequency of shaking behaviour. The alleviation by morphine disappeared when naloxone (1.5 mg/kg intraperitoneally 15 min. after morphine) was coadministered. Although there was no histological change in brain slices of paraquat-treated rats (70 mg/kg intraperitoneally), the fluorescein uptake into brain was increased by the treatment. Morphine prevented the increase of fluorescein uptake, but naloxone failed to antagonize this effect. On the other hand, intracerebroventricularly administered paraquat (25.7 micrograms/rat) caused tremor in all rats, but not shaking behaviour nor myoclonus. These findings suggest that paraquat administered systemically as well as centrally may be toxic to the brain. Although the actions of paraquat on the brain seem to be complicated, opioid receptors may play a role in the actions.

Animals↗

moaR, a gene that encodes a positive regulator of the monoamine regulon in Klebsiella aerogenes.

We cloned and sequenced a Klebsiella aerogenes gene (moaR) for activation of arylsulfatase synthesis by tyramine. This gene was cloned by complementation of a K. aerogenes mutant in which tyramine fails to relieve the arylsulfatase repression caused by sulfur compounds. The moaR gene also activated induction of the synthesis of both tyramine oxidase and the 30-kDa protein that is specifically induced by high concentrations of tyramine or catecholamines. The moaR gene on the chromosome of the wild-type strain of K. aerogenes was disrupted by homologous recombination with a plasmid containing the inactivated moaR. The resultant mutant showed the same phenotype as previously isolated atsT mutant strains that are negative for the derepressed synthesis of arylsulfatase. In this mutant strain, tyramine also failed to induce the synthesis of tyramine oxidase or the production of a 30-kDa protein. The moaR gene is capable of encoding a protein of 26,238 Da. The putative MoaR protein has a helix-turn-helix motif in its C terminus. Thus, it seems likely that the MoaR protein regulates the operons by binding to the regulatory region of the monoamine regulon. The MoaR protein is subject to autogenous control, which was shown by use of a moaR'-lacZ transcriptional fusion.

Amino Acid Sequence↗

Changes in glucose utilization in the rat brain after transient forebrain ischemia.

BACKGROUND AND PURPOSE: Although several local cerebral glucose utilization (LCGU) studies using rat forebrain ischemia models have been performed to date, none that investigate long-term postischemic changes in LCGU throughout the brain have been reported. We investigated postischemic changes throughout the brain over 14 days using a rat forebrain ischemia model. METHODS: Cerebral ischemia was produced using the rat four-vessel occlusion model. After 30 minutes of ischemia cerebral blood flow was restored, and LCGU in 34 structures in the brain was evaluated at 1, 3, 5, 7, and 14 days after ischemia. RESULTS: LCGU changes were characterized and could be divided into two major patterns, type 1 and type 2. In type 1, LCGU was reduced remarkably at 1 and 3 days, and it returned to near the control level at 5 days. In type 2, LCGU was reduced mildly at 1 day and returned to near the control level at 3 days. Included in type 1 were the severely ischemic structures such as the cerebral cortices and striatum. Included in type 2 were the less severely ischemic structures such as the midbrain, cerebellum, and pons and medulla oblongata. Drastic changes in LCGU took place not only in gray matter but also in white matter, and the patterns of LCGU changes were similar in both regions. Atypical changes in LCGU were observed in the hippocampal CA1 and substantia nigra pars reticulata. In both structures, LCGU was remarkably increased around 7 days after ischemia. CONCLUSIONS: There are two major patterns of LCGU changes after transient forebrain ischemia. LCGU changes in the hippocampal CA1 and substantia nigra pars reticulata are atypical.

Analysis of Variance↗

Local cerebral glucose utilization in rats with decerebrate rigidity and effects of centrally acting muscle relaxants, diazepam and tizanidine.

Local cerebral glucose utilization (LCGU) was investigated in rats with decerebrate rigidity using the [14C]2-deoxyglucose (2DG) method in order to identify the site responsible for the rigidity. LCGU was increased in the medial vestibular nucleus, the fastigial nucleus, the interpositus nucleus and the dentate nucleus during decerebrate rigidity. Diazepam and tizanidine, centrally acting muscle relaxants, reduced the increase of LCGU in the vestibular and cerebellar nuclei. These results suggest that the vestibular and cerebellar nuclei are the possible sites responsible for the development of decerebrate rigidity and the action of some centrally acting muscle relaxants.

Animals↗

Sites of action of CS-722, a newly synthesized centrally acting muscle relaxant.

Sites of the muscle relaxant action of CS-722 were investigated in rats. Doses injected intra-4th ventricularly (i.c.v.) or intrathecally (i.t.) were determined according to measurements of CS-722 concentration in the brain stem and the spinal cord after systemic administration. When administered i.c.v. (50 and 100 micrograms) or i.t. (200 and 400 micrograms), CS-722 reduced the radio frequency decerebrate rigidity, although the effect after i.c.v. injection was transient. These results indicate that CS-722 exerts its muscle relaxant action by affecting both the supraspinal structure and the spinal cord. Spinal reflexes were not affected by CS-722 injected i.c.v. It seems that muscle relaxation is not always accompanied by impairment of the spinal reflex.

Animals↗

Housing factors and perceived health status among Japanese women living in aggregated dwelling units.

An epidemiologic survey was conducted of the 818 households in a community consisting of aggregated dwelling units in Tokyo, Japan, in order to assess the relationship between housing environment and psychological or physical health status of the female residents. Psychological health status was assessed by the 28-item General Health Questionnaire in Japanese translation. Main housing factors such as internal density (person-to-room ratio) and floor level (vertical location) of the dwelling unit did not have significant effects on the psychological health status of the sample of Japanese women, but the internal density generally did not exceed 1.5 persons per room. However, physical health status might be associated with floor level: women living at the highest levels complained of more symptoms than did those at lower floor levels, when the type of dwelling unit (i.e., high-rise, low or medium height building) was not taken into account. Poor psychological health status was found among women who were dissatisfied with the plan of their house or with the room arrangement, were anxious about earthquake or other accidents, perceived the house as inadequate for the children, were annoyed by indoor noise, and complained of outdoor noise.

Adolescent↗

Musk xylene is a novel specific inducer of cytochrome P-450IA2.

The effect of musk xylene on contents of both cytochrome P-450IA1 and cytochrome P-450IA2 in rat liver was investigated using Western blotting analysis. Rats were treated i.p. for five consecutive days with either 50, 100 or 200 mg musk xylene/kg body weight. Musk xylene increased both total cytochrome P-450 and cytochrome b5 contents in rat liver microsomes. Musk xylene induced cytochrome P-450IA2 (384 pmol/mg protein) strongly and preferentially and the ratio of cytochrome P450IA2/P-450IA1 was about 12 at the lowest dose tested. Musk xylene also induced the cytochrome P-450IA1 dose-dependently, but these extents were very small (32-174 pmol/mg protein). These results suggest that musk xylene may be a more specific inducer for cytochrome P-450IA2 than any other inducers reported.

Animals↗

Structure of the mouse tyrosine hydroxylase gene.

The mouse tyrosine hydroxylase (TH) gene was isolated from a genomic library by cross-hybridization with human TH cDNA probe. Nucleotide sequence analysis of two overlapping genomic clones showed that this gene is split into 13 exons distributed about 7.5 kb in length. The transcription initiation site was determined by primer extension analysis with mouse adrenal gland poly(A)+RNA. The structure of the mouse TH gene was similar to that of the human TH gene, but it contained neither the alternative splice donor site around the 3'-end of the first exon nor an independent exon corresponding to the second exon of the human TH gene. There were the canonical TATA and GC boxes, cyclic AMP responsive element (CRE), and AP1 binding site in the 5'-flanking region of the mouse TH gene.

Amino Acid Sequence↗

The factor structure of the 28-item General Health Questionnaire when used in Japanese early adolescents and adult employees: age- and cross-cultural comparisons.

The principal-component analysis (PCA) with varimax rotation on the 28-item General Health Questionnaire (GHQ-28) in Japanese translation was performed separately for two samples of the Japanese population: early adolescents (junior high school students) and adult employees. The initial PCA yielded different number of components across sub-samples. The later PCA, however, with restriction of the number of components four generally produced a similar structure across sub-samples by means of visual inspection and the coefficient of factor similarity between the components calculated by using the loadings matrices, while a slight different structure emerged for the employees aged 40-49 years. Then, based on these two ways of comparison, the factor structure of GHQ-28 was compared between the present Japanese samples and the European and Turkish school-aged adolescent populations with three ethnic backgrounds. The results showed that its structure was highly stable across age (generation) and several cultural backgrounds, at least among these nations. The internal consistency reliability of the GHQ-28 was at a high level among the present sample of Japanese.

Adolescent↗

Reduction properties of nitrated naphthalenes: relationship between electrochemical reduction potential and the enzymatic reduction by microsomes or cytosol from rat liver.

The nitroreductase activities of rat liver microsomes and cytosol towards various nitrated naphthalenes (1-, 2-mononitro-, 1,3-, 1,5-, 1,7-, 1,8-dinitro-1,3,5- and 1,3,8-trinitronaphthalenes) were characterized as follows. (1) The rates of reduction of nitrated naphthalenes in either microsomal or cytosolic incubation were found to increase in the order of trinitro- > dinitro- > mono-nitronaphthalene, although, in the case of microsomal nitroreduction, trinitronaphthalenes were reduced more rapidly than in cytosol. (2) The effective cofactors, electron donors, in the nitroreduction of nitrated naphthalenes in cytosol were NADH and hypoxanthine, but not NADPH. (3) The nitrated naphthalenes with a nitro group at a beta-position appear to be more easily reduced among the various isomers. The cytosolic nitroreductase activities towards the nitrated naphthalenes were closely related to the single-electron reduction potentials measured by cyclic voltammetry and hence, there was a good relationship between the logarithm of nitroreductase activities and the electrochemical reduction potentials. In microsomes, nitroreductase activities were rather less well related to electrochemical reduction potentials.

Animals↗

The pharmacological properties of CS-722, a newly synthesized centrally acting muscle relaxant.

The pharmacological properties of (R)-4-chloro-2-(2-hydroxy-3-morpholinopropyl)-5-phenyl-4-isoxaz olin-3-one hydrochloride (CS-722), a newly synthesized, centrally acting muscle relaxant, were studied in rats. The drug CS-722 reduced the radio frequency decerebrate rigidity in a dose-dependent manner (25-100 mg/kg, p.o.); it inhibited the increase in discharges from Ia afferent fibers, gamma-motor activity, which was induced by stimulation of the reticular formation. The compound, however, showed no effect on the basal discharge of Ia afferent fibers. The polysynaptic reflex was depressed by CS-722, with less influence on the monosynaptic reflex in intact and spinal preparations and CS-722 did not prolong thiopental-induced sleeping time. In rats anesthetized with halothane, CS-722 did not affect the electroencephalogram (EEG) arousal response, which was elicited by stimulation of the reticular formation. The results of this study suggest that CS-722 can exert a muscle relaxant action, at a dose range at which depression of the ascending reticular activating system was negligible. The results also suggest that depressions of the gamma-motor system and the polysynaptic reflex may contribute to the muscle relaxant action of CS-722.

Animals↗

Mechanisms of spinal reflex depressant effects of CS-722, a newly synthesized centrally acting muscle relaxant, in spinal rats.

The mechanisms of the depressant action of (R)-4-chloro-2-(2-hydroxy-3-morpholinopropyl)-5-phenyl-4-isoxaz olin-3-one hydrochloride (CS-722), a newly synthesized centrally acting muscle relaxant, on spinal reflexes were investigated in spinal rats. The drug CS-722 (50 mg/kg, i.v.) depressed the polysynaptic reflex but was less effective on the monosynaptic reflex. Eperisone-HCl (10 mg/kg, i.v.) and baclofen (2 mg/kg, i.v.) markedly decreased the monosynaptic and polysynaptic reflexes, with longer durations than CS-722; CS-722, eperisone and baclofen depressed the dorsal root reflex. The excitability of the motoneurone was reduced by CS-722 and eperisone. Excitability of the primary afferent fibres was reduced by CS-722, while eperisone and baclofen had no effect. Both CS-722 and eperisone did not have a depressant influence on the focal synaptic potential. These results suggest that CS-722 and eperisone but not baclofen, have a common motoneurone-membrane-stabilizing action and that this action may contribute, in part, to the spinal reflex depressant effects of CS-722 and eperisone.

Animals↗

Glycoprotein receptors for a heat-stable enterotoxin (STh) produced by enterotoxigenic Escherichia coli.

Glycoprotein receptors for heat-stable enterotoxin STh of enterotoxigenic Escherichia coli in the rat intestinal cell membrane were identified and characterized. Incubation of rat intestinal cell membranes with radioiodinated N-5-azidonitrobenzoyl-STh[5-19] (125I-ANB-STh[5-19]) followed by photolysis resulted in specific radiolabeling of two distinct proteins with M(r)s of 200,000 (designated STR-200A and STR-200B). STR-200A was found to be composed of two molecules of a protein with an M(r) of 70,000 (70-kDa protein), whereas STR-200B was composed of two different protein molecules with M(r)s of 53,000 (53-kDa protein) and 77,000 (77-kDa protein). These proteins showed no guanylate cyclase activity. The 70-kDa protein was labeled most with 125I-ANB-STh[5-19], suggesting that STR-200A is the main receptor protein in the rat intestinal cell membrane. The carbohydrate moieties of STR-200A and STR-200B were examined by enzymatic deglycosylation. The 70-kDa protein of STR-200A was found to contain N-linked high-mannose-type and/or hybrid-type oligosaccharides, and results suggested that it possesses at least three N glycosylation sites. The 53-kDa protein of STR-200B was found to have an N-linked complex-type oligosaccharide side chain. The deglycosylated 70-kDa protein retained activity for binding to STh, suggesting that the carbohydrate moieties of these receptor proteins are not important for binding with STh.

Animals↗

Consecutive treatment of disulfiram inhibits ovarian carbonyl reductase activity in rats.

We investigated the effects of disulfiram (DS) on ovarian carbonyl reductase activity in rats to determine the influence of DS on female reproductive function. Three consecutive treatments with DS significantly inhibited ovarian carbonyl reductase activity as well as ovulation, dose-dependently. Single treatment with DS had no effect on ovarian carbonyl reductase activity. Our observations indicate that consecutive treatment with DS has an inhibitory action on female reproductive function, although DS is well-known to inhibit aldehyde dehydrogenase and dopamine beta-hydroxylase.

Alcohol Oxidoreductases↗

Purification and primary structure of proteinous alpha-amylase inhibitor from Streptomyces chartreusis.

A new polypeptide inhibitor, AI-409, that inhibits human salivary alpha-amylase, was purified from a fermentation broth of Streptomyces chartreusis strain No. 409. This protein consists of a single-chain polypeptide of 78 amino acid residues, and includes two disulfide bridges. The primary structure of AI-409 and the locations of the disulfide bridges were identified by enzymatic digestion and the automatic Edman technique. Enzymatic digestion was done with trypsin, carboxypeptidase Y, and chymotrypsin. One of the disulfide bridges was between Cys(10) and Cys(26), and the other between Cys(44) and Cys(71).

Amino Acid Sequence↗

[Primary myelofibrosis successfully treated with allogeneic bone marrow transplantation].

A 31-year-old man with primary myelofibrosis initially received low dose Ara C. Splenomegaly decreased but pancytopenia continued. Allogeneic bone marrow transplantation from his sister was then performed. Busulfan and cyclophosphamide were used as a preconditioning regimen, which included neither irradiation nor splenectomy. As the bone marrow was hypoplastic after transplantation, G-CSF was given. It was useful for systemic infection. After transplantation, leukoerythroblastosis and tear drop poikilocytosis disappeared in peripheral blood. Finally, bone marrow fibrosis disappeared and hemopoiesis to normal limits recovered 17 months later. These results demonstrate that bone marrow transplantation is effective for primary myelofibrosis for which there is no otherwise curative therapy.

Adult↗

[Involuntary smoking in a workplace situation--discomfort of nonsmokers and interpersonal awareness of smokers].

A questionnaire survey was conducted to examine the socio-behavioral interaction between smokers and nonsmokers in a workplace situation. A socio-behavioral interaction is hypothesized to be centered around the subjective discomfort such as 'bothered feelings' towards involuntary smoking among nonsmokers. Study subjects were 1,134 nonsmokers and 1,457 smokers working in 21 small-scale production companies in Japan. Among nonsmokers, a combined 93.3% reported 'perceived exposure to smoking', 'always', 'often', or 'sometimes' compared to 6.6% reporting 'never'. Similarly, 74.6% experienced 'bothered feelings' 'sometimes', 'always', or 'often' compared to 25.3% reporting 'never'. A combined total of 39.4% expressed their discomfort to smokers 'sometimes', 'often', and 'always' compared to 60.6% who 'never' did. In contrast, 59.1% of smokers responded that they smoked with consideration of nonsmokers' presence (interpersonal awareness) 'sometimes', 'often', and 'always' compared to 41.0% for 'never'. 'Bothered feelings' among nonsmokers was significantly lower among those with past smoking history and correlated positively with 'perceived exposure to smoking' (rs = 0.22, p less than 0.001) and with 'expression of discomfort among both male (rs = 0.32, p less than 0.001) and female nonsmokers (rs = 0.34, p less than 0.001). Among male smokers 'interpersonal awareness' was significantly higher for those with less cigarette consumption and with past history of smoking cessation. A regression analysis was performed using mean scores calculated for smokers and nonsmokers of each workplace. Lower 'bothered feelings' of nonsmokers significantly correlated with higher 'interpersonal awareness' of smokers (r = -0.59, p less than 0.005). These finding imply the presence of socio-behavioral interactions between smokers and nonsmokers and thus suggest the significance of workplace education on involuntary smoking.

Adult↗

Antioxidant effect of calmodulin antagonists in rat brain homogenate.

Several calmodulin antagonists, W-7, amitriptyline, trifluoperazine, chlorpromazine, dibucaine, prenylamine, calmidazolium, and compound 48/80, inhibited lipid peroxidation induced non-enzymatically in rat brain homogenate by ascorbate and Fe2+. Suggestions of involvement of calmodulin in various oxidative cellular responses, based on experiments using calmodulin antagonists, may need to be re-evaluated.

Animals↗