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Biomedical subjects

A Hara

Publications and source records attributed to A Hara.

At least 289 records · Page 16Linked to original sources
PubMed1995

Neurologic features of chronic minamata disease (organic mercury poisoning) and incidence of complications with aging.

To elucidate the neurologic features of chronic Minamata disease, and the incidence of complications with aging, we studied 80 patients with documented Minamata disease (organic mercury poisoning) from 1986 to 1994 (mean age: 63 years). Of the cardinal neurologic findings, sensory impairment was seen with highest frequency in 98.8% of patients limited to the extremities in 86.3%. Impairment of lower extremity coordination was observed in 60%, constriction of the visual field in 51.9%, and retrocochlear hearing loss in 41%. To assess age-related complications, patients were separated into three groups by age: Group I (10 to 39 years); Group II (40 to 69 years); Group III (> or = 70 years). The incidences of hypertension and cerebrovascular diseases, organic ophthalmologic disorders (including cataracts), presbyacusis, and cervical spondylosis deformans increased significantly with age. Compared with a preceding survey (1981 to 1985, 171 patients, mean age: 63.5 years), the incidences of complicated hypertension and cataracts had decreased, whereas those of cerebrovascular disease and retinitis pigmentosa remained unchanged. The incidences of abnormal brain computed tomography (CT), presbyacusis, cervical spondylosis deformans, and positive tests for urine sugar also increased. The incidences of these complications other than retinitis pigmentosa were similar to those in the general population. These results accurately reflect the recent epidemiological disease tendencies in Japan toward a decreased incidence of hypertension and an increased incidence of diabetes.

Adolescent↗
PubMed1995

Chemoprevention of urinary bladder carcinogenesis by the natural phenolic compound protocatechuic acid in rats.

The modifying effect of dietary administration of protocatechuic acid (PCA) during the initiation and postinitiation phases on N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced bladder carcinogenesis was investigated in male F344 rats. Animals were divided into nine groups and groups 1-7 were given 0.05% BBN in drinking water for 6 weeks to induce bladder neoplasms. Rats in groups 2, 3 and 4 were fed diets containing 500, 1000 and 2000 p.p.m. PCA respectively for 8 weeks, starting 1 week before BBN exposure. Groups 5, 6 and 7 were fed the PCA-containing diets at three dose levels for 33 weeks. Group 8 was fed the diet containing 2000 p.p.m. PCA alone throughout the study. Group 9 was given tap water without BBN and the basal diet without PCA and served as an untreated control. At 41 weeks after the start, all animals were killed. The incidence of bladder tumors and preneoplastic lesions, and cell proliferation activity estimated by the numbers of silver-stained nucleolar organizer regions proteins (AgNORs) and proliferating cell nuclear antigen (PCNA)-immunoreactive cells were compared among the groups. PCA administration at 1000 and 2000 p.p.m. during the initiation and postinitiation phases significantly decreased the carcinoma incidence in a dose-dependent manner. Also, PCA at all doses given during either initiation or postinitiation phases reduced the development of the preneoplastic lesions. PCA feeding significantly reduced the numbers of AgNORs and PCNA-positive cells in the non-lesional transitional epithelium, preneoplasms, and neoplasms in the urinary bladder of rats treated with BBN. These results indicate that dietary administration of PCA is quite effective in preventing BBN-induced bladder carcinogenesis.

Animals↗
PubMed1995

Suppression of azoxymethane-induced rat colon carcinogenesis by dietary administration of naturally occurring xanthophylls astaxanthin and canthaxanthin during the postinitiation phase.

The modulating effects of dietary feeding of two xanthophylls, astaxanthin (AX) and canthaxanthin (CX) during the postinitiation phase on colon carcinogenesis initiated with azoxymethane (AOM) were investigated in male F344 rats. Animals were initiated with AOM by weekly s.c. injections of 15 mg/kg body wt for 3 weeks and then they were fed the diets containing AX or CX at concentrations of 100 and 500 p.p.m. for 34 weeks. The others contained the groups of rats treated with AX or CX alone and untreated. At the end of the study (week 37), the incidence and multiplicity of neoplasms (adenoma and adenocarcinoma) in the large intestine of rats initiated with AOM and followed by AX or CX containing diet at a high dose (500 p.p.m.) were significantly smaller than those of rats given AOM alone (P < 0.001). In addition, AX or CX feeding significantly inhibited the development of aberrant crypt foci induced by AOM. Dietary exposure to AX or CX also decreased cell proliferation activity as revealed by measuring 5'-bromodeoxyuridine-labeling index as crypt cells, colonic mucosal ornithine decarboxylase activity and blood polyamine levels. These results indicate that AX and CX are possible chemopreventers for carcinogenesis of colon in addition to urinary bladder and oral cavity and such effects may be partly due to suppression of cell proliferation.

Animals↗
PubMed1995

Inhibition of oral carcinogenesis by the arotinoid mofarotene (Ro 40-8757) in male F344 rats.

The chemopreventive effect of dietary administration of a new arotinoid, mofarotene (Ro 40-8757), which contains a morpholine structure in the polar end group, during the initiation phase of 4-nitroquinoline 1-oxide (4-NQO)-induced oral carcinogenesis was investigated in male F344 rats. Also, modulatory effects of this compound on polyamine levels (biomarkers of proliferation), the 5-bromodeoxyuridine-labeling index and the number of silver stained nucleolar organizer region proteins (AgNORs)/nucleus were assessed in the target epithelium. Rats were fed Ro 40-8757 at concentrations of 250 and 500 p.p.m. for 10 weeks. One week after the commencement of the diets, 4-NQO (20 p.p.m.) was administered in the drinking water for 8 weeks. Feeding of Ro 40-8757 at both doses caused a 78% reduction in the incidence of tongue neoplasms (squamous cell papilloma and carcinoma) by 32 weeks when compared with rats treated with 4-NQO alone (P < 0.05). Similarly, in rats treated with 4-NQO together with Ro 40-8757 the incidence of preneoplastic lesions (hyperplasia and dysplasia) was significantly less than the 4-NQO alone group (P < 0.05). Expression of three biomarkers was also decreased significantly by dietary treatment with Ro 40-8757. Thus a new arotinoid, Ro 40-8757, inhibited the oral carcinogenesis induced by 4-NQO when it was administered concurrently with the carcinogen. These results might suggest the possible application of Ro 40-8757 for cancer chemoprevention in the oral cavity, in addition to the breast.

Animals↗
PubMed1995

Inhibition of 4-nitroquinoline-1-oxide-induced rat oral carcinogenesis by dietary exposure of a new retinoidal butenolide, KYN-54, during the initiation and post-initiation phases.

The modifying effect of dietary exposure of a newly synthesized retinoidal butenolide, 5-hydroxy-4-(2-phenyl-(E)-ethenyl)-2(5H)-furanone (KYN-54) during the initiation and post-initiation phases of oral carcinogenesis initiated with 4-nitroquinoline-1-oxide (4-NQO) was investigated in male F344 rats. At 6 weeks of age, rats were divided into experimental and control groups. At 7 weeks of age, all animals except those treated with KYN-54 alone and those in a control group were given 4-NQO (20 p.p.m.) in the drinking water for 8 weeks to induce oral neoplasms. Seven days after stopping 4-NQO exposure, groups of animals fed the diets containing 100 and 200 p.p.m. KYN-54 for 10 weeks starting 1 week before 4-NQO exposure were switched to the basal diet and kept on this diet until the end of the experiment. Starting 1 week after the cessation of 4-NQO administration, the groups given 4-NQO and the basal diet were switched to the diets containing 100 or 200 p.p.m. KYN-54 and maintained on these diets for 22 weeks. The other group consisted of rats given 200 p.p.m. KYN-54 alone or untreated rats. All animals were necropsied at the termination of the study (week 32). The incidences of tongue neoplasms and preneoplastic lesions, polyamine levels in the tongue tissue, and cell proliferation activity estimated by bromodeoxyuridine (BrdU)-labeling index and by morphometric analysis of silver-stained nucleolar organizer regions protein (AgNORs) were compared among the groups. Feeding of KYN-54 during either initiation or post-initiation phase caused a significant reduction in the frequency of tongue carcinoma (48-71% reduction, P < 0.05) and such chemopreventive efficacy was dose-related. The incidences of preneoplastic lesion in rats fed the diets mixed with KYN-54 at both doses were also decreased (P < 0.05). Dietary administration of KYN-54 also significantly decreased the labeling index of BrdUrd and the number of AgNORs per cell nucleus of the tongue squamous epithelium (P < 0.05). In addition, polyamine levels in the oral mucosa were lowered in rats given 4-NQO and test compound when compared to those given 4-NQO alone, but no significant difference was obtained. These results indicate that the novel synthesized retinoidal butenolide KYN-54 inhibits oral carcinogenesis initiated with 4-NQO and such inhibition may be related to suppression of cell proliferation.

4-Butyrolactone↗
PubMed1995

Crystallization of mouse lung carbonyl reductase complexed with NADPH and analysis of symmetry of its tetrameric molecule.

Mouse lung carbonyl reductase (MLCR), which belongs to the short-chain dehydrogenase/reductase family, is an oxidoreductase involved in the metabolism of biogenic and xenobiotic carbonyl compounds. The crystals of MLCR complexed with its cofactor NADPH belong to a monoclinic space group P2(1) with dimensions a = 79.73 A, b = 105.5 A, c = 60.87 A, and beta = 91.43 degrees. X-ray diffraction data were collected up to 1.8 A resolution using a macromolecule-oriented Weissenberg camera at the Photon Factory synchrotron radiation source. Studies using a self-rotation function revealed the presence of a twofold rotational symmetry relating the subunits. This suggests that the tetrameric MLCR molecule has the 222 point group symmetry.

Alcohol Oxidoreductases↗
PubMed1995

Expression and kinetic properties of a recombinant 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase isoenzyme of human liver.

Human liver cytosol contains multiple forms of 3 alpha-hydroxysteroid dehydrogenase and dihydrodiol dehydrogenase with hydroxysteroid dehydrogenase activity, and multiple cDNAs for the enzymes have been cloned from human liver cDNA libraries. To understand the relationship of the multiple enzyme froms to the genes, a cDNA, which has been reported to code for an isoenzyme of human liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase, was expressed in Escherichia coli. The recombinant enzyme showed structural and functional properties almost identical to those of the isoenzyme purified from human liver. In addition, the recombinant isoenzyme efficiently reduced 5 alpha-dihydrotestosterone and 5 beta-dihydrocortisone, the known substrates of human liver 3 alpha-hydroxysteroid dehydrogenase and chlordecone reductase previously purified, which suggests that these human liver enzymes are identical. Furthermore, the steady-state kinetic data for NADP(+)-linked (S)-1-indanol oxidation by the recombinant isoenzyme were consistent with a sequential ordered mechanism in which NADP+ binds first. Phenolphthalein inhibited this isoenzyme much more potently than it did the other human liver dihydrodiol dehydrogenases, and was a competitive inhibitor (Ki = 20 nM) that bound to the enzyme-NADP+ complex.

3-Hydroxysteroid Dehydrogenases↗
PubMed1995

Congenital ossification of the stapedius tendon: diagnosis with CT.

PURPOSE: To describe the features of congenital ossification of the stapedius tendon at thin-section computed tomography (CT). MATERIALS AND METHODS: Thin-section CT scans, clinical records, and surgical findings were retrospectively evaluated in nine ears of five patients with surgically proved congenital ossification of the stapedius tendon. Thin-section CT scans of 50 control ears were also reviewed. RESULTS: On thin-section CT scans, a linear area of soft-tissue attenuation was demonstrated between the monopod stapes and the pyramidal eminence (nine ears), as well as thickening of the stapes footplate (two ears). In the 50 control ears, the normal stapes tendon was not clearly seen on thin-section CT scans. CONCLUSION: At CT, a linear area of soft-tissue attenuation that extends from the pyramidal eminence to the monopod stapes is suggestive of congenital ossification of the stapedius tendon or a bony bar adjacent to it.

Adolescent↗
PubMed1995

Protective effect of hypoxia on mechanical and metabolic changes induced by hydrogen peroxide in rat hearts.

The effect of hypoxia (20% O2 for 5 min) on the hydrogen peroxide (H2O2)-induced myocardial change was studied in the Langendorff rat heart, which was perfused at a constant flow rate and driven electrically. H2O2 decreased the left ventricular developed pressure, increased the left ventricular end-diastolic pressure, and decreased the myocardial ATP level. These mechanical and metabolic alterations induced by H2O2 were less prominent in the hypoxia-reoxygenated heart than in the normoxic heart (i.e., hypoxia had a protective effect on the H2O2-induced change). Both 8-phenyltheophylline (8-PT), a nonselective adenosine-receptor antagonist, and glyburide (Gly), an inhibitor of the ATP-sensitive potassium (KATP) channel, significantly reduced the protective effect of hypoxia. The adenosine A1-receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DP-CPX) reduced the protective effect of hypoxia incompletely. Gly, 8-PT, and DPCPX did not affect the mechanical function and energy metabolism of the hypoxia-reoxygenated heart without H2O2. These results suggest that brief and mild hypoxia attenuates the H2O2-induced mechanical and metabolic changes and that the protective effect of hypoxia is probably mediated by activation of the adenosine receptors, which open the KATP channel.

Animals↗
PubMed1995

Over-expression of pig lung carbonyl reductase in Escherichia coli.

Tetrameric carbonyl reductase of pig lung has been shown by cDNA cloning to be a member of the short-chain dehydrogenase family of enzymes. Construction of the carbonyl reductase cDNA in an expression vector yielded an abundant, enzymatically active enzyme in Escherichia coli. The recombinant enzyme was purified to homogeneity and shown to be structurally, immunologically and functionally similar to lung carbonyl reductase.

Alcohol Oxidoreductases↗
PubMed1995

3-Deoxyglucosone reductase in dog adrenal glands. Identification as aldose reductase.

3-Deoxyglucosone is one of the major cytotoxic intermediates in the Maillard reaction. Adrenal glands showed the highest NADPH-linked 3-deoxyglucosone reductase activity of dog tissues. The enzyme was purified to homogeneity from the adrenal glands, and demonstrated to be structurally, functionally and immunologically identical with aldose reductase, which comprises about 6% of the soluble adrenal proteins.

Adrenal Glands↗
PubMed1995

Suppressive effect of molybdenum on hepatotoxicity of N-nitrosodiethylamine in rats.

In order to elucidate the mechanism by which molybdenum prevents the carcinogenesis of N-nitroso compounds, the effects of Na2MoO4-pretreatment on N-nitrosodiethylamine (NDEA)-induced DNA strand breaks, fluctuation in cation contents and lipid peroxidation levels in rat liver were examined. Male Wistar rats weighing 170-190 g were pretreated with Na2MoO4 (1.24 mmol/kg body weight, i.p., once a day) for 3 d and on day 4, they were exposed to NDEA (50 mg/kg body weight, once, i.p.). Three days after exposure to NDEA, the nitroso compound caused DNA strand breaks and disrupted potassium (K) and calcium (Ca) metabolism in the liver but did not affect lipid peroxidation levels. Na2MoO4-pretreatment prevented both NDEA-induced DNA damage and disruption of the metabolism of those cations but rather enhanced lipid peroxidation. These results suggest that Mo prevented NDEA-induced DNA damage by preventing disruption of intracellular Ca metabolism while stimulating the metabolism of the nitroso compound via a nontoxic pathway.

Animals↗
PubMed1995

Kinetic studies of the inhibition of a human liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase isozyme by bile acids and anti-inflammatory drugs.

We have investigated the steady-state kinetics for a cytosolic 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase isozyme of human liver and its inhibition by several bile acids and anti-inflammatory drugs such as indomethacin, flufemanic acid and naproxen. Initial velocity and product inhibition studies performed in the NADP(+)-linked (S)-1-indanol oxidation at pH 7.4 were consistent with a sequential ordered mechanism in which NADP+ binds first and leaves last. The bile acids and drugs, competitive inhibitors with respect to the alcohol substrate, exhibited uncompetitive inhibition with respect to the coenzyme, with Ki values less than 1 microM, whereas indomethacin exhibited noncompetitive inhibition (Ki < 24 microM). The kinetics of the inhibition by a mixture of the two inhibitors suggests that bile acids and drugs, except indomethacin, bind to overlapping sites at the active center of the enzyme-coenzyme binary complex.

3-Hydroxysteroid Dehydrogenases↗
PubMed1995

Branch retinal vein occlusion decreases the potential of the inner retinal layer.

To identify the affected retinal layer in cases of branch retinal vein occlusion (BRVO), we analyzed the scotopic electroretinogram (ERG) and electrooculogram (EOG) obtained on the same day in 30 patients with unilateral BRVO. Patients with eye diseases other than unilateral BRVO were excluded. A dome-shaped Ganzfeld illuminator was used for scotopic ERG stimulation and EOG illumination under conventional recording conditions. There was no significant difference in the mean values of scotopic ERG variables between the eyes with BRVO and the normal eyes, but the EOG light peak and L/D ratio were significantly lower in the eyes with BRVO (p < 0.05). However, there was no significant difference between eyes with BRVO and normal eyes regarding the dark through value. Since the light rise potential is induced by background illumination, the low values for light peak and L/D ratio in the eyes with BRVO represent a decrease in the light rise potential compared with that of normal eyes. In addition, since the b wave amplitude of the ERG was normal in the eyes with BRVO, the scotopic ERG and EOG tests suggest that generalized mild hypoxia affects the inner retinal layer of the eyes with BRVO.

Aged↗
PubMed1995

Effect of acoustic overstimulation on the hydropic ear.

The effect of acoustic overstimulation (2 kHz pure tone) on the compound action potential (CAP) threshold was investigated at frequencies ranging from 2 to 16 kHz using albino guinea pigs, both normal and with experimentally induced endolymphatic hydrops. The hydropic ears were less susceptible to acoustic overstimulation than the normal ears. As the CAP threshold was raised, the frequency exhibiting the greatest CAP threshold shift increased in both animal groups. The tendency was more noticeable in the hydropic ears than in the normal ears. These results are discussed from the aspect of cochlear hydrodynamics.

Action Potentials↗
PubMed1995

Analysis of glycosaminoglycans of subretinal fluid in rhegmatogenous retinal detachment--preliminary report.

To determine the correlation between the types of glycosaminoglycans (GAGs) and the features of rhegmatogenous retinal detachment, we analyzed the types of GAGs in the subretinal fluid of 20 eyes with rhegmatogenous retinal detachment. The GAGs were analyzed by cellulose acetate two-dimensional electrophoresis. Hyaluronic acid alone (HA type) was found in 10 of the 20 eyes. A combination of chondroitin sulfate (chSA) and HA was present (chSA type) in 3 of the 20 eyes. A combination of dermatan sulfate (DS) and HA (DS type) was present in 7 of the 20 eyes. No correlation was found between the type of GAGs and the extent, the duration of detachment, location, size or type of break in the 20 eyes. Some correlation was found between the type of GAGs and the grade of vitreous haze, proliferative vitreoretinopathy (PVR) and the number of surgeries. Retinal detachment with a demarcation line resulted in subretinal strand formation in the DS type eyes, while no such formation was seen in the subretinal space of the eyes of the chSA type. Vitreous haze of grade ( ) was seen in one eye of the DS type, but not seen in the other types. All 3 eyes with PVR of grade C were the DS type. The 2 eyes with reoperated surgeries were the DS type. The presence of DS may indicate an advanced condition of retinal detachment.

Adult↗
PubMed1995

The acute toxicity of Riedeliella graciflora in laboratory animals.

Riedeliella graciflora is a plant mainly found in southeast South America and related to bovine mortality in Sao Paulo State, Brazil. Our laboratory showed that cattle intoxicated with 10 g R graciflora leaves/kg had organ congestion, edema and hemorrhage. The aim of this study was to determine which laboratory animal species would present the same lesions found in cattle. We also studied the effects of administering parts of the fruits or leaves po, sc, ip or im. All the laboratory species developed organ congestion, edema and hemorrhage and severe nephrosis regardless which plant part was given or the route of administration used. The effects were more intense in animals dosed with R graciflora fruits ip.

Animals↗