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Biomedical subjects

A Hirose

Publications and source records attributed to A Hirose.

At least 55 records · Page 3Linked to original sources
PubMed1991

Autoradiographic localization and pharmacological characterization of [3H]tandospirone binding sites in the rat brain.

The regional distribution and pharmacological properties of [3H]tandospirone binding sites in the rat brain were investigated using quantitative autoradiography. [3H]Tandospirone binding was notably high in the dentate gyrus and CA1 area of the hippocampus, lateral septum, entorhinal cortex, interpeduncular nucleus and dorsal raphe nucleus. The distribution profiles of [3H]tandospirone binding sites significantly correlated with that of serotonin (5-HT)1A receptors identified using [3H]8-OH-DPAT. In competitive binding studies, [3H]tandospirone binding was inhibited by 5-HT, 8-OH-DPAT, pindolol, buspirone and N-(a,a,a-trifluoro-m-tolyl)-piperazine. The potencies of these ligands correlated with their affinities for 5-HT1A receptors. In addition, there was no significant difference in the dissociation constant of [3H]tandospirone binding between the dentate gyrus, CA1 area, dorsal raphe nucleus, lateral septum and entorhinal cortex (about 10 nM) suggesting that [3H]tandospirone binds to 5-HT1A receptors with same affinities in these brain structures. The distribution pattern of binding sites for [3H]tandospirone was also compared with that of benzodiazepine receptors identified using [3H]fludiazepam to find common effector sites for different types of anxiolytics. Some similarities were observed. It is evident in the hippocampal formation that an overlap of intense binding occurred. 5-HT1A receptors in the hippocampus may participate in the anxiolytic effects of tandospirone.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1991

Detection of heat-stable delta 3,delta 2-enoyl-CoA isomerase in rat liver mitochondria and peroxisomes by immunochemical study using specific antibody.

The subcellular distribution of delta 3,delta 2-enoyl-CoA isomerase [EC 5.3.3.8] and the inducing effect of clofibrate, a peroxisomal proliferator, on the enzyme activity were examined in rat liver. From the results of spectrophotometric investigation of the fractions, which were prepared by sucrose discontinuous gradient centrifugation from the light mitochondrial fraction, the isomerase activity was found in the fractions enriched in mitochondria and those enriched in peroxisomes of the control and the clofibrate treated rat livers. The anti-isomerase antibody reacted with both the mitochondrial isomerase and the peroxisomal isomerase, revealing a single band with an apparent molecular weight of 30,000. However, the isomerase was induced by clofibrate administration mainly in the mitochondrial fraction. These results suggest that delta 3,delta 2-enoyl-CoA isomerase is located in the mitochondria and the peroxisomes of the normal rat liver, and that the isomerase in the mitochondria is induced by clofibrate administration.

Animals↗
PubMed1991

[Study on essential metal concentration in the organs of rats (report 2)--lung.liver.kidney.spleen].

The objective of this study was to obtain the normal ranges of essential metals in male and female Slc: Wister rats aged 9 or 11 weeks. Concentration of 10 elements (Ca, Cu, Fe, K, Mg, Mn, Na, P, S and Zn) in the lung, liver, kidney and spleen of rats was determined by inductively coupled argon plasma atomic emission spectrometry (ICP). Each sample was digested with nitric acid and perchloric acid in a sealed double Teflon vessel with polypropylene jacket by heating with a microwave oven. The concentrations of Fe and Mn in the liver were different between males and females. The Fe level in the female was higher than that in the male, and Mn level in male was higher than that in female. The concentration of Fe in the spleen was different by sex and ago. The Fe level in female was 2.3 times higher than that in male, and that in rats of 11 weeks was 1.8 times higher than that of 9 weeks.

Animals↗
PubMed1990

cDNA cloning of rat liver 2,4-dienoyl-CoA reductase.

cDNA clones of 2,4-dienoyl-CoA reductase were isolated from rat liver cDNA libraries constructed in phages lambda gt11 and lambda gt10. Hybrid selected translation analysis revealed that 2,4-dienoyl-CoA reductase was translated as a polypeptide with a molecular weight of about 36,000, which was about 3,000 molecular weight units larger than mature reductase. Sequencing analysis revealed that the open reading frame encoded a polypeptide consisting of 335 amino acid residues (predicted molecular weight = 36,132), which contained an N-terminal extension peptide of 34 amino acid residues (presequence) in addition to the mature enzyme. Thus, 2,4-dienoyl-CoA reductase is synthesized as a larger precursor polypeptide, and the N-terminal extension peptide may be acting as the mitochondrial import signal.

Amino Acid Sequence↗
PubMed1990

Inhibition of hippocampal CA1 neurons by 5-hydroxytryptamine, derived from the dorsal raphe nucleus and the 5-hydroxytryptamine1A agonist SM-3997.

Electrophysiological studies, using chloral hydrate-anesthetized rats, were undertaken to determine whether hippocampal pyramidal neurons, receiving input from the medial septal nucleus, were affected by 5-hydroxytryptamine (5-HT) derived from the dorsal raphe nucleus. The pyramidal neurons in the CA1 region of the hippocampus were classified into short- and long-latency neurons, based on their response to stimulation of the medial septal nucleus. Microiontophoretically applied atropine inhibited the generation of spikes upon stimulation of the medial septal nucleus in short-latency neurons, but had no effect on long-latency neurons. In the short-latency neurons, the stimulation-induced spikes of the medial septal nucleus were inhibited by conditioning stimuli applied to the dorsal raphe nucleus and iontophoretic application of 5-HT and the 5-HT1A agonists, SM-3997 (3 a alpha,4 beta,7 beta,7a alpha-hexahydro-2-(4-(4-(2-pyrimidinyl)-1- piperazinyl)-butyl)-4,7-methano-1H-isoindole-1,3(2H)-dione dihydrogen citrate) and 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin). The conditioning effect of the dorsal raphe nucleus was antagonized by methysergide. However, in the long-latency neurons, the spikes elicited by stimulation of the medial septal nucleus were not affected by the conditioning stimulation of the dorsal raphe nucleus, or iontophoretically applied 5-HT. These results indicate that 5-HT, originating in the dorsal raphe nucleus inhibited hippocampal pyramidal neurons receiving cholinergic input from the medial septal nucleus, but not those receiving non-cholinergic input from the medial septal nucleus. The drug SM-3997 inhibited the activity of hippocampal pyramidal neurons, that receive excitatory cholinergic input from the medial septal nucleus by acting on 5-HT1A receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1990

Autoradiographic evidence for the interaction of SM-3997 with 5-HT1A receptors in the rat brain.

[3H]8-OH-DPAT binding to rat brain sections and inhibition by SM-3997 were investigated. Very high densities of [3H]8-OH-DPAT binding sites were found in the dentate gyrus, entorhinal cortex, dorsal raphe, interpeduncular nucleus and lateral septum. In contrast, their densities were sparse in the substantia nigra, caudate putamen and choroid plexus. In the presence of 1 microM of SM-3997, [3H]8-OH-DPAT binding was strongly inhibited in all the brain structures we examined. These results indicate that SM-3997 binds to 5-HT1A receptors of rat brain sections.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1990

Pharmacological actions of SM-9018, a new neuroleptic drug with both potent 5-hydroxytryptamine2 and dopamine2 antagonistic actions.

Pharmacological studies were undertaken to clarify the profile of cis-2-(4-(4-(1,2-benzisothiazol-3-yl)-1-piperazinyl) butyl) hexahydro-1H-isoindole-1,3-(2H)-dione hydrochloride (SM-9018), a new neuroleptic drug. SM-9018 had very high binding affinities for both 5-hydroxytryptamine2 (5-HT2) and dopamine2 (D2) receptors, unlike many other neuroleptics. SM-9018 also strongly inhibited 5-HT2 receptor-mediated behavior such as tryptamine-induced clonic seizure and D2 receptor-mediated behavior such as methamphetamine-induced hyperactivity, apomorphine-induced stereotypy and climbing behavior. SM-9018 possessed only a weak cataleptogenic activity, which may be clinically related to extrapyramidal side effects, despite its potent D2 antagonistic activity. Moreover, SM-9018 induced weak central depressant effects such as inhibition of spontaneous locomotor activity and motor coordination, as compared with classical neuroleptics (haloperidol and chlorpromazine). These results suggest that SM-9018 is a new neuroleptic drug with both potent 5-HT2 and D2 antagonistic activities and with low cataleptogenic and central depressant activities.

Animals↗
PubMed1990

Binding profile of SM-9018, a novel antipsychotic candidate.

The present study employed various receptor-binding assays to clarify the biochemical characteristics of SM-9018. SM-9018 possessed very high affinity for 5-HT2, D2 and 5-HT1A receptors (Ki = 0.61, 1.4 and 2.9 nM, respectively), and it had moderate affinity for alpha 1 and D1 receptors (Ki = 17 and 41 nM, respectively). However, SM-9018 had only negligible affinity for alpha 2, opiate, glutamate, phencyclidine, benzodiazepine and GABAA receptors. These results suggest that SM-9018 may be a novel antipsychotic agent with binding affinity for 5-HT2 and 5-HT1A receptors.

Animals↗
PubMed1990

[Unilateral absence of pulmonary perfusion by lung scanning with 99mTc-MAA: report of two cases].

Unilateral absence of pulmonary artery perfusion by 99mTc-MAA lung scanning is associated with a variety of congenital, inflammatory, neoplastic, vascular etiologies. We present of two cases of this scan abnormality. One case had isolated agenesis of the right pulmonary artery and the other was the systemic-to-pulmonary artery fistula associated with recurrent pneumonia. Although pulmonary angiography, including IVDSA, is indicated to rule out other possibilities, eg. thromboembolism, radionuclide perfusion scan is a non-invasive method suitable for the screening.

Arterio-Arterial Fistula↗
PubMed1989

Induction of microsomal 1-acylglycerophosphocholine acyltransferase by peroxisome proliferators in rat kidney; co-induction with peroxisomal beta-oxidation.

Induction of microsomal 1-acyl-glycerophosphocholine (GPC) acyltransferase in rat tissues by four peroxisome proliferators, clofibric acid, tiadenol, DEHP and PFOA, was examined. Among the nine tissues examined, kidney, liver and intestinal mucosa responded to the challenges by the peroxisome proliferators to induce the enzyme. The treatment of rats with various dose of clofibric acid, tiadenol, DEHP or PFOA resulted in an induction of kidney microsomal 1-acyl-GPC acyltransferase in a dose-dependent manner. Despite the structural dissimilarity of peroxisome proliferators, the induction of microsomal 1-acyl-GPC acyltransferase was highly correlated with the induction of peroxisomal beta-oxidation. The activity of microsomal 1-acyl-GPC acyltransferase was not affected by changes in hormonal (adrenalectomy, diabetes, hyperthyroidism and hypothyroidism) and nutritional (starvation, starvation-refeeding, fat-free-diet feeding and high-fat-diet feeding) states. The induction of renal microsomal 1-acyl-GPC acyltransferase was seen in mice subsequent to the administration of clofibric acid and tiadenol and in guinea pigs subsequent to the administration of tiadenol. These results may indicate that kidney microsomal 1-acyl-GPC acyltransferase is a highly specific parameter responsive to the challenges by peroxisome proliferators and may suggest that the possibility that the inductions by peroxisome proliferators of microsomal 1-acyl-GPC acyltransferase and peroxisomal beta-oxidation in kidney are co-regulated.

1-Acylglycerophosphocholine O-Acyltransferase↗
PubMed1989

Co-induction by peroxisome proliferators of microsomal 1-acylglycerophosphocholine acyltransferase with peroxisomal beta-oxidation in rat liver.

Administration of clofibric acid, 2,2'-(decamethylenedithio)diethanol, di(2-ethylhexyl)phthalate or perfluorooctanoic acid to male rates increased markedly microsomal 1-acylglycerophosphocholine (a-acyl-GPC) acyltransferase in a dose-dependent manner in liver. Simultaneous administration of actinomycin D or cycloheximide completely abolished the increase in the enzyme activity. The treatment of rats with clofibric acid did not affect the rate of decay of 1-acyl-GPC acyltransferase. Regardless of a great difference in the chemical structures of the peroxisome proliferators, high correlation was observed between the induced activities of microsomal 1-acyl-GPC acyltransferase and peroxisomal beta-oxidation. Stearoyl-CoA desaturase was induced by peroxisome proliferators in a dose-dependent manner; nevertheless, high correlation was not seen between the induced activities of desaturase and peroxisomal beta-oxidation. Hormonal (adrenalectomy, diabetes, hyperthyroidism and hypothyroidism) and nutritional (starvation, starvation-refeeding, fat-free diet feeding and high-fat diet feeding) alterations hardly affected the activity of 1-acyl-GPC acyltransferase. The present results indicate that microsomal 1-acyl-GPC acyltransferase is a useful parameter responsive to the challenges by peroxisome proliferators and suggest that a similar regulatory mechanism operates for the inductions of microsomal 1-acyl-GPC acyltransferase and peroxisomal beta-oxidation.

1-Acylglycerophosphocholine O-Acyltransferase↗
PubMed1989

A case of the pathogenesis of choledochocele in relation to dysfunction of the sphincter of Oddi.

A 47-year-old woman was admitted for evaluation of pain in the right upper quadrant of the abdomen. Seventeen years previously, she had undergone cholecystectomy for cholelithiasis. Endoscopic retrograde cholangiopancreatography (ERCP) showed a cystic dilatation of the terminal portion of the common bile duct (CBD) protruding into the duodenal lumen and delaying the drainage of contrast medium. In this patient the CBD and the pancreatic duct appeared to be unimportant in the formation of the cyst. Repeated changes in the radius of the cyst suggested dysfunction of the ampullary component of the sphincter of Oddi, with maintenance of normal function of the common duct component. The pathogenesis of the choledochocele in this patient is discussed in relation to dysfunction of the sphincter of Oddi. In addition, 2 criteria for the diagnosis of choledochocele by ERCP are proposed: [1] cystic dilatation of the terminal portion of the CBD protruding into the duodenal lumen, and [2] absence of the narrow segment of the CBD.

Ampulla of Vater↗
PubMed1989

Effects of the putative anxiolytic SM-3997 on central monoaminergic systems.

The effects of SM-3997 on central monoaminergic systems were evaluated by ex vivo measurement of monoamines and their metabolite levels in rat brain after intraperitoneal treatment of drugs and by in vitro measurement of monoamine uptake into rat brain slices. The effects of SM-3997 were also compared with those of other new nonbenzodiazepine anxiolytic compounds. SM-3997, buspirone, gepirone and ipsapirone showed no effects on serotonin uptake and dopamine uptake, and a weak inhibition of norepinephrine uptake at the concentration of 100 microM. SM-3997 decreased the serotonin metabolite (5-hydroxyindole-3-acetic acid) level without changing the serotonin level in hippocampus and increased dopamine metabolite (3,4-dihydroxyphenylacetic acid, homovanillic acid) level with no effect on the dopamine level in striatum. SM-3997 also produced an increase in the norepinephrine metabolite (3-methoxy-4-hydroxyphenylglycol) level with a decrease in the norepinephrine levels in hippocampus. Similar effects on serotonin metabolites and norepinephrine metabolites were observed in several other regions. Although the serotonergic effect of SM-3997 was similar to that of buspirone, gepirone and ipsapirone, the dopaminergic effect of SM-3997 was much weaker than that of buspirone.

Animals↗
PubMed1989

[Electroencephalographic study on the central action of a new anxiolytic: 3a alpha, 4 beta, 7 beta, 7a alpha-hexahydro-2-(4-(4-(2-pyrimidinyl)-1- piperazinyl)-butyl)-4, 7-methano-1H-isoindole-1, 3(2H)-dione dihydrogen citrate (SM-3997)].

Electroencephalographic (EEG) studies were performed to examine the effects of SM-3997 on the spontaneous EEG, EEG arousal responses, recruiting responses and hippocampal afterdischarges in rabbits and the spontaneous EEG in chronically electrode-implanted rats. In acute experiments using rabbits, SM-3997 at doses of 1-3 mg/kg, i.v., produced low-voltage fast waves in cortical EEG and slow waves with reduction of the amplitude in hippocampal EEG. The drug at doses of 1-3 mg/kg, i.v., dose-dependently inhibited the threshold stimulus voltages in EEG arousal responses induced by stimulation of the midbrain reticular formation and slightly inhibited the threshold in recruiting responses by stimulation of the centromedian nucleus of the thalamus. However, the cortical and hippocampal afterdischarges induced by hippocampal stimulation remained unaffected by SM-3997 at doses up to 3 mg/kg, i.v., while they were inhibited by diazepam of 1 mg/kg, i.v. In the study using rats in which electrodes were chronically implanted, SM-3997 at doses of 10-30 mg/kg, i.p., also produced low voltage fast waves in cortical EEG and slow waves of reduced amplitude in hippocampal EEG; and it simultaneously caused flat body posture. These results suggest that SM-3997 acts on both the cerebral cortex and hippocampus, inducing much more pronounced inhibition on the midbrain reticular formation-hippocampal system

Animals↗
PubMed1989

Immunocytochemical localization of delta 3, delta 2-enoyl-CoA isomerase in rat liver. The effects of di-(2-ethylhexyl)phthalate, a peroxisome proliferator.

Immunocytochemical localization of delta 3, delta 2-enoyl-CoA isomerase (isomerase) was investigated in rat liver. Livers of di-(2-ethylhexyl)phthalate (DEHP)-treated or untreated rats were perfusion-fixed and embedded in Epon or Lowicryl K4M. By light microscopy, reaction deposits for the enzyme were present in the cytoplasmic granules of hepatocytes and interlobular bile duct epithelium. Weak staining was noted in sinus-lining cells. After administration of DEHP, the granular staining of the hepatocytes was markedly enhanced, whereas the staining reaction of the sinus-lining cells decreased. The isomerase staining pattern was quite similar to that of long-chain acyl-CoA dehydrogenase (a mitochondrial marker), but different from that of catalase (a peroxisomal marker). Under electron microscopy, gold particles for isomerase were seen to be confined mainly to mitochondria of the hepatocytes, the bile duct epithelial cells and sinus-lining cells. Peroxisomes were weakly labeled. After DEHP administration, the peroxisomes were markedly induced, but the mitochondria were not. Quantitative analysis showed that the induction of the peroxisomal isomerase was only 2-fold whereas the mitochondrial isomerase was enhanced about 5-fold, 40 times as high as the peroxisomal enzyme. The results show that the mitochondria are the main intracellular site for isomerase and the peroxisomes a minor site. The mitochondrial isomerase of the rat liver is markedly induced by peroxisome proliferators, DEHP and clofibrate.

Animals↗