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Biomedical subjects

S Ohta

Publications and source records attributed to S Ohta.

At least 649 records · Page 36Linked to original sources

Postmortem changes in mitochondrial respiratory enzymes in brain and a preliminary observation in Parkinson's disease.

Postmortem changes in mitochondrial respiratory enzymes (Complex I-IV and NAD(+)-linked dehydrogenases in the TCA cycle) were studied in mouse brains and human frontal lobes. In mouse brains, activities of the enzymes studied were generally stable for as long as 12 h after cervical dislocation, except for the alpha-ketoglutarate dehydrogenase complex and NADP(+)-linked isocitrate dehydrogenase. In human frontal cortices, only NADH-ubiquinone reductase (Complex I) activity showed significant negative correlation with the duration between the patient's death and the freezing of the brain. No correlations between the activities of the enzymes studied and the age of the patients were noted. As most of our patients were 50 years of age or above, absence of the correlation cannot be extended to younger patients. From our observation, it was felt that analyses of these mitochondrial enzymes in human autopsy brains would give meaningful data. Preliminary observation in Parkinson's disease revealed a small but a significant decrease in the activity of Complex III in the striatum as compared with the control. Although, significance of our observation is not yet known, further studies on this line appear to be important to elucidate pathogenesis of Parkinson's disease.

Animals↗

Metabolism and brain accumulation of tetrahydroisoquinoline (TIQ) a possible parkinsonism inducing substance, in an animal model of a poor debrisoquine metabolizer.

4-Hydroxytetrahydroisoquinoline (4OH-TIQ) was detected as a metabolite of a possible parkinsonism-inducing substance, tetrahydroisoquinoline (TIQ), in rat liver microsomes and rat urine. Urinary excretion of 4OH-TIQ was significantly reduced in female DA rat, an animal model of a poor debrisoquine metabolizer. The female DA rat also showed significantly higher brain accumulation of TIQ. These results suggest that the metabolic detoxication process is depressed and TIQ accumulation in the brain is enhanced in a poor debrisoquine metabolizer, which may be one possible explanation for poor debrisoquine metabolizers being susceptible to Parkinson's disease.

Animals↗

Retrobulbar optic neuritis in a two-year-old boy.

We report a 2-year-4-month-old boy with retrobulbar optic neuritis. He had a sudden onset of impaired vision, which progressed to total blindness within a day. The visual evoked potential (VEP) showed no activity, but the electroretinogram was normal. Computed tomography (CT) and magnetic resonance imaging (MRI) showed no abnormal findings in the visual tract. The cerebrospinal fluid (CSF) myelin basic protein (MBP) level was elevated and serum anti-myelin antibody was positive. These findings suggested that optic neuritis in our patient was induced by retrobulbar demyelination, perhaps as a result of an autoimmune process. His visual impairment recovered gradually, but not completely, following oral prednisolone therapy. We have followed him for one year since discharge and have found neither recurrence of optic neuritis nor any other neurological disorders. Optic neuritis in children is rare and, to our knowledge, this patient is one of the youngest to be reported. This case suggests that autoimmune mechanisms may induce optic neuritis even in early childhood. In addition to VEP and MRI studies, the CSF MBP and serum anti-myelin antibody can be useful in the diagnosis and follow-up the patients with optic neuritis.

Child, Preschool↗

Effect of stellate ganglion block on cerebral blood flow in normoxemic and hyperoxemic states.

This study was undertaken to clarify whether stellate ganglion block (SGB) changed cerebral blood flow (CBF) in both atmospheric conditions (rest) and hyperbaric oxygen (HBO, under 2 atm absolute). Unilateral SGB was performed on 16 patients with sudden deafness with the injection of 8 ml of 1% mepivacaine and CBF was measured 20 min thereafter. The mean hemispheric blood flow on the block side (CBFi) and the nonblock side (CBFc) was measured by the intravenous xenon-133 method, being expressed as the initial slope index. In the atmospheric condition, the CBFi of seven patients before and after SGB was 50.4 +/- 8.4 and 49.0 +/- 5.9 (mean +/- SD) ml/100 g/min, respectively, with no significant change between them. There was also no significant change in the regional distribution of CBF, i.e., the blood flow of the frontal, pariental, temporal, and occipital lobes in hemispheres. In the hyperbaric condition, the CBFi of nine patients under HBO(mean PaO2 = 1,141 mm Hg) and HBO with SGB (mean PaO2 = 1,138 mm Hg) was 39.4 +/- 6.2 and 37.7 +/- 7.0 ml/100 g/min, respectively, being significantly less (p <0.05) than 46.5 +/- 8.0 ml/100 g/min at rest (mean PaO2 = 88 mm Hg). However, SGB had no effect on the reduction in CBFi in the hyperoxemic state. There was also no effect of SGB on CBFc, which was almost equal to the corresponding CBFi in the atmospheric and hyperbaric environments. It is concluded that unilateral SGB does not alter CBF and its regional distribution at least in neurologically normal humans, whether in the normoxemic or hyperoxemic state. It is also suggested that blockade of the cervical sympathetic nervous system is not preventive of the CBF reduction in the hyperoxemic state.

Journal Article↗

Flowcytometric analysis of DNA pattern of cells derived from xeroderma pigmentosum A--hypersensitivity to vincristine, etoposide and methotrexate.

Xeroderma pigmentosum complementation group A (XPA) is one of the DNA repair deficient syndromes. The cell biological features of XPA were examined by flowcytometry using Epstein Barr (EB) virus-transformed lymphoblastoid cells. Cellular sensitivity to vincristine (VCR), etoposide (VP-16) and methotrexate (MTX) were assayed by DNA pattern changes by flowcytometry. Recently, ataxia-telangiectasia (AT), one of the same kind of disorder, has been reported to have an increased sensitivity to VCR and VP-16. However, AT showed some resistance to MTX according to other reports. Our results showed that XPA had an increased sensitivity to VCR and also to VP-16. Moreover, different from AT, XPA showed some sensitivity to MTX. Thus there is some cell biological similarity between XPA and AT, as well as some difference of the abnormality in the DNA repair pathway.

Cell Line↗

A novel and neurotoxic tetrahydroisoquinoline derivative in vivo: formation of 1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline, a condensation product of amphetamines, in brains of rats under chronic ethanol treatment.

Repeated amphetamine administration to rats under chronic ethanol intoxication resulted in the formation of 1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline (1,3-DiMeTIQ), a novel metabolite of amphetamines. 1,3-DiMeTIQ was quantified with a sensitive, specific assay using gas chromatography-mass spectrometry. It was not found in the brains of rats given repeated amphetamine administration but no ethanol. The chronic ethanol-intoxicated rats subjected to repeated amphetamine administration exhibited behavioral abnormalities, such as repeated convulsions and curving of the back. 1,3-DiMeTIQ contents were markedly higher in the brain or plasma of rats manifesting abnormal behavior in comparison with those in rats behaving normally. Thus, the 1,3-DiMeTIQ content in the rat brain seems to have some relationship with behavioral abnormalities. This study also confirmed that 1,3-DiMeTIQ can cross the blood-brain barrier in the rat. Intraperitoneal 1,3-DiMeTIQ injections to rats caused behavioral symptoms similar to those observed in rats with chronic ethanol intoxication and repeated amphetamine administration. The effect of toxic doses of 1,3-DiMeTIQ on dopaminergic and serotonergic metabolism in the whole rat brain was also investigated.

Alcoholism↗

Episodic fluctuation in serum intact parathyroid hormone concentration in men.

To evaluate the temporal features of physiological fluctuation in serum PTH concentration, we sampled peripheral blood at 4-min intervals for 24 h from five normal men (32.8 yr; range, 26-40 yr) and measured serum PTH levels using a two-site immunoradiometric assay with the exquisite sensitivity and specificity for human PTH-(1-84) (intact PTH). The resultant 24-h time series of serum intact PTH levels were assessed by contemporary techniques in chronophysiology for rhythmic and episodic peak detection. Cosinor analysis disclosed a significant circadian rhythm in serum intact PTH concentrations in all five men, with the mean circadian amplitude and acrophase of 7.2 +/- 4.4 ng/L and 2305 +/- 401 h, respectively (mean +/- SD; n = 5). No apparent fixed ultradian periodicity was found by autocorrelation and spectral analyses. Evaluation of episodic intact PTH pulsatility by Cluster analysis revealed 23.0 +/- 4.4 discrete PTH pulses/24 h (P less than 0.01 vs. signal-free noise), which occurred at an interpulse interval of 61.6 +/- 11.1 min. The average duration of a serum intact PTH peak was 42.8 +/- 7.3 min, and its mean incremental amplitude was 12.6 +/- 1.3 ng/L, which corresponded to a 31.8 +/- 5.2% increase above the preceding nadir. Discrete PTH peaks were separated by nonpulsatile valleys which lasted for 17.9 +/- 4.4 min. Cross-correlation between the time series of serum intact PTH and whole blood ionized calcium (Ca2+) was at its maximum (-0.5) at concurrent time points in three subjects, while significant positive correlation between serum intact PTH and simultaneous serum inorganic phosphorus concentrations was observed in four of five subjects. There was no apparent correlation between the levels of serum intact PTH and serum magnesium. Our data show that serum levels of intact PTH, the only biologically active form of PTH in the blood, is characterized by a significant circadian periodicity, spontaneous episodic pulsatility with distinct peak properties, and a significant temporal coupling with Ca2+ and inorganic phosphorus concentrations. We conclude that PTH secretion, as judged by the temporal pattern of serum intact PTH levels, is pulsatile in normal men.

Adult↗

Protective effects of various Chinese traditional medicines against experimental cholestasis.

In a previous paper, we reported that methanol extracts obtained from 13 Chinese traditional medicines showed remarkable choleretic effects in normal rats. This paper examines the protective effects against experimental cholestasis induced by carbon tetrachloride (CCl4) or alpha-naphthylisothiocyanate (ANIT) in rats. No medicines, including sodium dehydrocholate and 1-phenylpropanol which are used clinically as choleretic drugs, inhibited the decrease of bile flow induced by CCl4. On the other hand, Intinko-to, Saiko-seikan-to and Bohu-tusyo-san revealed marked improvement of the dysfunction in bile secretion induced by ANIT. These three medicines inhibited the decrease of excretion of bile acid or bilirubin in the bile. They also exerted a protective effect against the alterations of serum components induced by ANIT, i.e., of glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, alkaline phosphatase and the concentration of serum bilirubin. These results indicate that methanol extracts of Intinko-to, Saiko-seikan-to and Bohu-tusyo-san demonstrate not only choleretic effects but also improvement of cholestasis and liver parenchymal injury in rats.

Animals↗

[Studies on chemical protectors against radiation. XXX. Radioprotective substances of cnidii rhizoma].

Radiation protective effects of the methanol extract and its fractions of Cnidii Rhizoma on lethality and skin injury induced by X-irradiation were studied. As a result of these studies, it was observed that significant protective effects exist in both ether and water soluble portions prepared from the above methanol extract, and two of the active principles in the ether and water soluble ones were identified as ferulic acid and adenosine, respectively.

Adenosine↗

[Studies on chemical protectors against radiation. XXXI. Protection effects of Aloe arborescens on skin injury induced by X-irradiation].

Protective effects of Aloe arborescens (AA) on mouse skin injury induced by soft X-irradiation were examined. The mechanisms on radiation protection by measuring scavenge activity of activated oxygen, protective effects of nucleic acid, induction of antioxidative protein and so on were further investigated. Consequently a significant protective effect of skin injury was observed in AA S6-3-b. As the mechanisms of radiation protection in AA, the following matters were found. AA S6-3-b showed scavenge activity of hydroxyl radicals generated by Haber-Weiss reaction. AA S6-3-b suppressed the changes of activity in superoxide dismutase and glutathione peroxidase at 7d after soft X-irradiation. Metallothionein was induced in the skin and liver against normal mice at 24 h after administration of AA S6-3-b.

Aloe↗

[Studies on chemical protectors against radiation. XXXII. Protective effects of methanol extracts of various Taiwan crude drugs on radiation injuries].

This study is to investigate radioprotective effects of 23 Taiwan crude drugs on X-ray induced bone marrow death and skin injury in mice. Each methanol extract of these Taiwan crude drugs was injected intraperitoneally into ICR male mice at 6 weeks of age before irradiation. Mice were whole-body irradiated with a soft X-ray generator. Radiation factors of the two screening tests used were as follows: 70 kVp, 10 mA, 10 mm acrylate filter, 70R/min, 2100R for survival test, and 30 kVp, 10 mA, 190R/min, 1100R for protective test on skin injury. As a result of these studies, the survival effect was recognized in Solani Incani Herba and Orthosiphi Aristati Herba. On the other hand, Mimosae Herba, Canarii Radix, Bombacis Radix, Arecae Fructus, Hedyotidis Diffusae Herba and Cynomorii Caulis were shown to have significant protective potency on skin injury.

Animals↗

[Protective effects of various methanol extracts of crude drugs on experimental hepatic injury induced by carbon tetrachloride in rats].

The protective effects of 67 methanol extracts of crude drugs on rat hepatic injury by carbon tetrachloride (CC14) were examined. In terms of the release of intrahepatic enzymes and bilirubin into the blood, 11 methanol extracts decreased these factors significantly. Among them methanol extracts of Caryophylli Flos, Angelicae Dahuricae Radix, Polygoni Avicularis Herba, Myricae Cortex and Forsythiae Fructus were newly found to have protective effects against acute hepatic injury induced by CCl4. And then these 11 extracts which protected hepatic injury by CCl4 were investigated for their membrane stabilizing and inhibitory effects of lipid peroxidation. The extract of Bupleuri Radix only decreased the hemolysis induced by hypotonic pressure. Nine kinds of extracts without those of Desmodii Herba and Bupleuri Radix suppressed the lipid peroxidation induced by CCl4 in rat hepatic microsomes. In addition, Scutellariae Radix, Caryophylli Flos and Myricae Cortex were shown to have inhibitory effects of non-enzymatic lipid peroxidation in rat hepatic mitochondria. This study reports that the methanol extracts of Caryophylli Flos, Angelicae Dahuricae Radix, Polygoni Avicularis Herba, Myricae Cortex and Forsythiae Fructus protect the hepatic injury by CC14 and these protective effects are connected with the inhibitory effects of the lipid peroxidation in hepatic microsomes.

Animals↗

[Studies on chemical protectors against radiation. XXVIII. Protective effect of nucleic acid constitutional compounds on radiation damages induced by X-irradiation].

The effects of various nucleic acid constitutional compounds, base, nucleoside and nucleotide on lethality and skin injury induced by soft X-irradiation were studied. The survival effect was determined by use of survival days after irradiation of lethal dose of 70 kVp, 2100R and the protective effect on skin injury was determined by use of degrees on skin injury after 30 kVp, 1100R soft X-irradiation. As a result of these studies, the survival effect was observed by single injection of inosine at 120, 60 and 5 min before irradiation and three times injection after irradiation. And the other nucleic acid constitutional compounds had no effect on survival. Protective effect of skin injury was observed by single injection of adenosine, guanosine, inosine, 5'-adenosine monophosphate (5'-AMP), 5'-guanosine monophosphate (5'-GMP) and 5'-inosine monophosphate (5'-IMP) before irradiation. Protective effect of skin injury by three time injection before irradiation were revealed in adenosine, inosine, 5'-AMP and 5'-IMP. For the investigation of superoxide anions and hydroxyl radicals scavenge activities, the relationship between radical scavenge activities and protective effect of radiation by using various nucleosides was not observed.

Adenosine↗

[Studies on chemical protectors against radiation. XXIX. Protective effects of methanol extracts of various Chinese traditional medicines on skin injury induced by X-irradiation].

In order to investigate useful protective medicines for the relief of skin injury induced by irradiation, 60 methanol extracts of Chinese traditional medicines were used in the test of protective potency on skin injury. ICR male mice at 6 weeks of age were whole-body irradiated with 1100R by using a soft X-ray generator (30 kVp, 10 mA, 190 R/min). Each methanol extract of these medicines was injected intraperitoneally into mice before or after irradiation. The degrees of skin injury were determined by a score system of skin reaction within the observation period from 21st to 40th day after irradiation. Protective potency of each medicine on skin injury was calculated from the maximum mean scores of administrated group and un-administrated group. As a result of these studies, the protective potency was detected in Unsei-in, Kumibinro-to, Keisi-syakuyaku-chimo-to, Keigai-rengyo-to, Gosyuyu-to, Koso-san, Saiko-seikan-to, Syo-kankyo-to, Syo-saiko-to, Syoma-kakkon-to, Sen-kan-meimoku-to, Zokumei-to, Sokei-kakketu-to, Bokuryo-in, Mao-to and Rikkunsi-to by intraperitoneal injection before irradiation. Of these effective medicines, only Unsei-in and Mao-to are shown to have a significant protective effect by intraperitoneal injection after irradiation.

Animals↗

[Studies on resistant mechanisms in the resistant bacteria to chlorhexidine. II. Chemical components of the cell membrane and the electron microscopical observation of cell surface structure of chlorhexidine-resistant bacteria].

The mechanisms of resistance of Serratia marcescens and Pseudomonas cepacia to chlorhexidine were studied. Leakage of the cellular component such as protein was observed in a chlorhexidine sensitive strain (S1) of S. marcescens when S1 was treated with chlorhexidine at 40 micrograms/ml concentration, while this phenomenon was not observed in a resistant strain (R1). The following observations were made concerning about cell surface structure in the chlorhexidine sensitive and resistant strains of S. marcescens by chemical analyses of membrane components and electron microscopical studies of the thin sections of the cells. (1) When the S1 strains was treated with chlorhexidine, the outer membrane of the cells formed a wrinkled surface with irregular blebs, and some of which broke out to form various sizes of granules. The R1 strain did not undergo such morphological changes under the same conditions used in the sensitive strain. (2) A prominent protein with apparent molecular weight of 45 K was found exclusively in the R1 strain of S. marcescens as major outer membrane protein, while it was not found in S1 strain. (3) There were no differences in the composition of phospholipids and the amount of 3-hydroxytetradecanoic acid between S1 and R1 strains of S. marcescens. In Pseudomonas cepacia PCJ1 which is resistant to chlorhexidine, 50 K protein was also observed as a major protein of outer membrane of the cells. In contrast to the strain, a mutant of the strain, #102 which was obtained from PCJ1 strain by the treatment with methanesulfonic acid ethylester, did not possess the 50 K protein in its outer membrane. These data suggested that outer membrane components of bacteria were related importantly in resistant mechanism.

Bacterial Proteins↗

[Protective effects of antioxidants on experimental liver injuries].

Protective effects of 14 kinds of antioxidant on liver injury induced by carbon tetrachloride (CCl4) were investigated in terms of serum enzyme activities and bilirubin concentration. Consequently, the significant protective effects were found in sesamol, ellagic acid, cysteamine and cysteine. These antioxidants clearly decreased the lipid peroxide in the liver tissue. The protective effects on CCl4-induced liver injury in vivo were independent of the inhibitory activities on lipid peroxidation in hepatic mitochondria fraction in vitro.

Animals↗

[Acute toxicity study of buspirone hydrochloride in mice, rats and dogs].

Buspirone hydrochloride (abbr. to BH), an anxiolytic drug, was examined for its intravenous, subcutaneous or oral acute toxicity using Crj: CD-1 (ICR) mice, Crj: CD (Sprague-Dawley) rats and beagle dogs of both sexes. The results obtained were summarized as follows: 1. Drug-related toxic signs included decreased activity and convulsions accompanied with salivation and opisthotonus in mice and rats treated with BH regardless of administration routes, and tremors and clonic convulsions accompanied with salivation in dogs treated with BH orally. 2. Pathological examinations revealed distention of the stomach in dead rats treated with BH orally, and hypersecretion of gastric juice and alterations (viz. edema, necrosis and petechia) on the superficial mucous membrane in the gastropyloric region in dead dogs treated with BH orally. 3. The cause of death was considered to be due to respiratory insufficiency in every species of animals examined. 4. LD50 values (mg/kg) were as follows: [table: see text] 5. No sex differences were observed in every species of animals regardless of administration routes on the basis of toxicological parameters examined.

Administration, Oral↗

[Antigenicity study of buspirone hydrochloride in guinea pigs and mice].

Buspirone hydrochloride(buspirone) and buspirone-ovalbumin mixture were examined for their antigenicity in guinea pigs and mice in comparison with ovalbumin (OVA) and 2, 4-dinitrochlorobenzene (DNCB)-OVA conjugate. The results obtained were as follows: 1. When guinea pigs were sensitized with buspirone or buspirone-OVA emulsified with Freund's complete adjuvant (FCA), these animals showed negative reactions in active systemic anaphylaxis (ASA), active cutaneous anaphylaxis (ACA), passive cutaneous anaphylaxis (PCA), passive hemagglutination (PHA) and Schultz-Dale test. 2. When mice were sensitized with buspirone or buspirone-OVA adsorbed to alum, these animals revealed a negative reaction in PCA using rats. 3. As positive controls, guinea pigs were sensitized with OVA or DNCB-OVA emulsified with FCA, and mice with OVA or DNCB-OVA adsorbed to alum. As a result, these animals disclosed positive reactions in ASA, ACA, PCA, PHA and Schultz-Dale test. As shown above, buspirone was considered to possess neither antigenic nor haptenic properties.

Anaphylaxis↗