Biomedical subjects

M Yoshii

Publications and source records attributed to M Yoshii.

At least 55 records · Page 3Linked to original sources

PubMed1998

[Mitochondrial benzodiazepine receptors (MBR) in association with neurological disorders].

Ro 5-4864, a specific agonist of the peripheral-type benzodiazepine receptor (PBR), elicited convulsions 2.6 times more potently in EL mice (an animal model of epilepsy) than in DDY mice (control animal). A binding assay revealed a 50% higher density of [3H] Ro 5-4864 binding sites in the mitochondrial fraction (i.e., mitochondrial benzodiazepine receptors; MBR) of the brain tissues in EL mice as compared with DDY mice. On an elevated plus-maze, EL mice showed fear responses similar to those increased in DDY mice after PBR stimulation, suggesting a hyperfunction of MBR underlying the abnormal behaviors of EL mice. In fluorometric studies using NG108-15 cells, Ro 5-4864 depolarized mitochondrial membranes and, possibly as a consequence of this, raised intracellular Ca2+. Finally, we propose that MBR could be a major target of therapy for various neurological disorders, so drugs such as "mitochondrial membrane stabilizers" should be developed.

Animals↗

PubMed1998

[Detection of parafoveal scotoma by multifocal electroretinograms].

We investigated the relation between multifocal electroretinograms (M-ERGs) and artificial parafoveal scotoma. M-ERGs were recorded from normal subjects using a circular piece of black paper attached to a monitor. Lower response density around the 10 to 15 degree parafovea region was not observed up to 3 degree scotoma (visual angle), but was detected above 5 degree scotoma in field topography of M-ERGs. The shape of the scotoma in field topography was not circular but somewhat oval. The results from two cases of parafoveal retinal degeneration were in good accordance with this basic study in normal subjects. We proved that detection of parafoveal scotoma by M-ERG is limited in comparison with the results obtained by automated static perimetry.

Electroretinography↗

PubMed1997

Comparative studies on omega-hydroxylation of 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol in the mitochondrial and microsomal fraction of the liver from several vertebrates.

The activity and the stereospecificity of omega-hydroxylation, a hydroxylation at one of the two terminal methyl groups of 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol, which is thought to be the first step in side-chain degradation resulting in the formation of cholic acid, was elucidated in mitochondria and microsomes of the liver from several evolutionarily primitive vertebrates, fish, frogs, turtles, and chickens in addition to such mammals as rats. hamsters, and rabbits. The detection of omega-hydroxylation products (25R)- and (25S)-5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 26-tetrols as well as the separation of their two isomers was facilitated using high-performance liquid chromatography after conversion to 9-anthroyl derivatives. All the mammals examined, except for the rat, exhibited predominant activity in the mitochondrial fraction. Although the hydroxylation activity was somewhat lower in the primitive vertebrates, it was present in the mitochondria more than in the microsomes. Furthermore, the stereospecific formation of a 25R-isomer was detected in the mitochondrial fraction of most animals estimated. However, activity in the carp liver was seven times higher in the microsomes than in the mitochondria, and the hydroxylation product was almost always a 25R-isomer. Omega-Hydroxylation activity could not be detected in rainbow trout, suggesting the existence of another biosynthetic pathway, not via 26-hydroxylation, as in the 25-hydroxylation pathway, for the production of bile acid.

Animals↗

PubMed1997

Cellular mechanisms underlying cognition-enhancing actions of nefiracetam (DM-9384).

We have studied cellular mechanisms underlying cognition-enhancing actions of nefiracetam (DM-9384), a newly developed cognitive enhancer, by biochemical experiments on cholinergic and GABAergic transmissions as well as electrophysiological experiments on neuronal Ca2+ channels. In behavioral experiments in rats, nefiracetam (3 mg/kg) ameliorated amnesia induced by basal forebrain (BF) lesion or treatment of scopolamine. Biochemical experiments revealed that nefiracetam increased uptake and release of transmitters in both cholinergic and GABAergic systems in rat brain. In electrophysiological studies, nefiracetam (1 microM) increased long-lasting (N/L-type) Ca2+ channel currents in NG108-15 cells. The nefiracetam action on Ca2+ channels was blocked by pertussis toxin (PTX). The results suggest that nefiracetam improves impaired memory by facilitating cholinergic and GABAergic transmissions in the brain. It is further suggested that PTX-sensitive G-proteins and Ca2+ channels associated with these G-proteins are responsible for the action of nefiracetam on neurotransmission.

Animals↗

PubMed1997

Bile acid profiles in a peroxisomal D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein deficiency.

Bile acid profiles in serum, urine and bile from an infant with a peroxisomal D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein (D-bifunctional protein) deficiency were analyzed by means of gas-liquid chromatography, gas-liquid chromatography-mass spectrometry, and high-performance liquid chromatography. As in such several peroxisomal disorders as Zellweger syndrome, neonatal adrenoleukodystrophy, and infantile Refsum disease, the accumulation of C27-bile acid intermediates was also demonstrated in the infant with D-bifunctional protein deficiency, accounting for 74% of the total bile acids in serum, 59% in urine, and 35% in bile. In addition, the major constituents of the C27-bile acids were (24R,25R)- and (24R,25S)-3alpha,7alpha,12alpha,24-tetrahydroxy-5be ta-cholestanoic acids along with small amounts of their 24S counterparts. Since immunoreactive acyl-CoA oxidase, L-bifunctional protein, and thiolase were all present in the liver, the impairment of the oxidative side-chain cleavage in bile acid biosynthesis is considered to be due to the defect of D-bifunctional protein.

17-Hydroxysteroid Dehydrogenases↗

PubMed1997

[A case of primary orbital chondrosarcoma].

The case of a twenty-year-old male with orbital chondrosarcoma is reported. He visited National Defense Medical College Hospital because of reduced vision in the right eye since two months previously. His corrected visual acuity was 8/20 in the right eye and 20/20 in the left eye. Fifteen degrees lateral displacement of the right globe and limitation of right ocular movement were recognized. Right fundus examination revealed optic disc edema and protuberant nasal fundus. Orbital computed tomography (CT) demonstrated a high density area between the inner part of the right orbit and the ethmoid sinus. Magnetic resonance imaging (MRI) showed a smoothly outlined and low intensity (T1) space occupying lesion. This lesion was irregularly enhanced by gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA). This orbital tumor was removed by an anterior approach. Histopathological examination revealed well-differentiated chondrosarcoma (grade 1) as determined by small prominent chondromatous cell projection into the collagen fibrous stroma, and existence of binucleate cells in the hypercellular region. After the operation the disc edema disappeared and his corrected right visual acuity improved to 20/20.

Adult↗

PubMed1997

[CT guided percutaneous microwave tumor coagulation therapy for local recurrence of rectal cancer].

PURPOSE: To evaluate the usefulness of the CT guided percutaneous microwave tumor coagulation (PMTC) therapy for local recurrence of rectal cancer. MATERIALS AND METHODS: The CT guided PMTC was performed for two patients with local recurrence of rectal cancer. Maximum axial diameter of the tumor was 30 mm on CT images. With patients in the prone position on the CT table, a 14-gauge needle-electrode was used to penetrate the tumor under epidural and local anesthesia. PMTC was performed with an output of 60 watts for 60 seconds at a time. Effects of the PMTC were evaluated by CT images obtained three months after the therapy. RESULTS: In both cases, there was no evidence of tumor growth on the CT images. Clinical symptoms disappeared soon after the therapy, and no major complication was observed. CONCLUSION: The CT guided PMTC therapy was useful for local recurrence of rectal cancer.

Aged↗

PubMed1997

[An elderly patient with purpura nephritis that appeared after extracorporeal shock wave lithotripsy].

We report a 63-year-old male patient with purpura nephritis, which appeared 7 days after extracorporeal shock wave lithotripsy (ESWL). He was referred to our clinic because of a petechial rash on both lower extremities, pretibial edema and massive proteinuria. Urinalysis showed proteinuria and hematuria and some hyaline casts. A 24-hour urine sample contained 5.0 g of protein. Renal function on admission was decreased: serum creatinine was 1.5 mg/dl and creatinine clearance, 21 ml/min. Immunoserological tests demonstrated an increase in serum IgA (424.3 mg/dl). A skin biopsy revealed leukocytoclastic vasculitis. A renal biopsy showed endocapillary proliferation in a diffuse, but segmental fashion. However, no crescent formation was seen. Immunofluorescence microscopy disclosed mesangial staining for IgA and C3. Electron microscopy demonstrated severe injury to endothelial and epithelial cells: detachment of endothelial and epithelial cells, foot process effacement and macrophage infiltration. Electron-dense deposits were observed in the subendothelial and paramesangial areas. Because renal function was deteriorating rapidly, methylprednisolone pulse therapy and immunosuppressive treatment were implemented. Treatment was effective and the patient's renal function and proteinuria improved remarkably. The electron microscopic findings in this case of purpura nephritis seemed to be more severe than usual, suggesting that ESWL may aggravate glomerular damage.

Drug Administration Schedule↗

PubMed1996

Peripheral-type benzodiazepine receptors in association with epileptic seizures in EL mice.

Peripheral-type benzodiazepine receptors (PBR) in the brain were studied in association with epileptic seizures using EL mice, an animal model of epilepsy, and DDY mice as controls. Ro 5-4864 (i.p.), a specific agonist for PBR, elicited tonic-clonic convulsions in EL mice 2.6-times more potently than in DDY mice with CD50s of 11.9 and 31.2 mg/kg for EL and DDY mice, respectively. In contrast, pentylenetetrazole (i.p.) exerted convulsant actions on EL and DDY mice in a less differential way with CD50s of 29.2 and 48.1 mg/kg for EL and DDY mice, respectively. PK 11195 (i.v.), a specific antagonist for PBR, raised seizure thresholds of EL mice at a dose of 2 mg/kg. Binding assay revealed a 50% higher density of [3H]Ro 5-4864 binding sites in the mitochondrial fraction isolated from the cerebrum of EL mice in comparison with DDY mice. Similarly, a 40% higher density of [3H]flunitrazepam binding was observed in the mitochondrial fraction of EL mice. The results support the hypothesis that PBR, particularly those associated with mitochondria, are involved in the pathogenesis of epileptic seizures in EL mice.

Animals↗

PubMed1996

Dermabrasion using an ultrasonic surgical aspirator.

We used an ultrasonic surgical aspirator on the epidermal surface to perform dermabrasion instead of the conventional motor-driven grinder. It was determined on histologic examination that it is possible to fragment the epidermis with greater selectively using the ultrasonic surgical aspirator. Abrasion also can be performed safely on spotty lesions and intricate, problematic regions with the ultrasonic surgical aspirator. We feel that the ultrasonic surgical aspirator is a promising device for use in dermabrasion.

Adult↗

PubMed1996

Effect of some sulfonate analogues of ursodeoxycholic acid on biliary lipid secretion in the rat.

The effect of the sulfonate analogues of ursodeoxycholic acid, namely sodium 3 alpha,7 beta-dihydroxy-24-nor-5 beta-cholane-23-sulfonate (norUDC-SO3Na) and sodium 3 alpha, 7 beta-dihydroxy-5 beta-cholane-24-sulfonate (UDC-SO3Na), on biliary lipid secretion was studied in bile fistula rats. During intravenous infusion of the two sulfonate analogues, bile flow and biliary lipid secretion were stimulated in a dose-dependent manner. This suggests that the analogues exert an effect on biliary lipid secretion comparable to that of the naturally occurring bile acid, ursodeoxycholyltaurine (UDC-tau). The effects of norUDC-SO3Na and UDC-SO3Na on bile flow were similar but slightly smaller than that of UDC-tau. The output of bile salts was similar with both sulfonates but greater than that with UDC-tau. The infusion of norUDC-SO3Na or UDC-SO3Na induced cholesterol secretion and phospholipid secretion more significantly than UDC-tau infusion. The increase in phospholipid secretion was particularly pronounced during high-dose administration of norUDC-SO3Na. Although norUDC-SO3Na stimulated cholesterol secretion more intensely than the other two bile salts, it also facilitated phospholipid output, perhaps as a compensatory mechanism, and the biliary cholesterol/phospholipid ratio was decreased to a greater extent by the sulfonates than by UDC-tau. Consequently, the administration of norUDC-SO3Na or UDC-SO3Na produces a more "stable" bile than UDC-tau, suggesting that these sulfonates possess potential cholelitholytic activity.

Animals↗

PubMed1996

15 alpha-hydroxylation of a bile acid analogue, sodium 3 alpha,7 alpha-dihydroxy-25,26-bishomo-5 beta-cholane-26-sulfonate in the hamster.

The metabolism of 3 alpha,7 alpha-dihydroxy-25,26-bishomo-5 beta-cholane-26-sulfonate (bishomoCDC-sul), the sulfonate analogue of bishomochenodeoxycholic acid, and its effect on biliary bile acid composition were studied during chronic administration in the hamster. After oral administration of radiolabeled bishomoCDC-sul, more than 80% of the radioactivity was excreted into the feces within 7 days, both as the unchanged sulfonate (38.5%) and two more polar metabolites (50.0% and 11.5%). The half time of the fecal excretion was 1.6 days. In gallbladder bile, the unchanged sulfonate and its major metabolite accounted for 19.1% and 19.8% of total bile acids, respectively. In another experiment, hamsters were fed bishomoCDC-sul with antibiotics to evaluate the site of biotransformation. Even when the number of intestinal microorganisms was greatly reduced, the same three metabolites were found in the feces: bishomoCDC-sul (44.0%) and the two polar metabolites (30.8% and 25.1%). The major metabolite was isolated from feces of the hamsters fed bishomoCDC-sul without antibiotics. Its chemical structure was identified by mass spectrometry and nuclear magnetic resonance spectroscopy as the 15 alpha-hydroxylated derivative, namely sodium 3 alpha,7 alpha,15 alpha-trihydroxy-25,26-bishomo-5 beta-cholane-26-sulfonate. These results indicate that after oral administration, the sulfonate analogue of bishomochenodeoxycholic acid underwent enterohepatic circulation like a natural bile acid and was transformed, in part, into the 15 alpha-hydroxylated derivative and another more polar metabolite in the liver of hamsters. There was no evidence that bishomoCDC-sul was dehydroxylated to a lithocholic acid analogue during enterohepatic cycling.

Animals↗

PubMed1996

Comparison of side chain oxidation of potential C27-bile acid intermediates between mitochondria and peroxisomes of the rat liver: presence of beta-oxidation activity for bile acid biosynthesis in mitochondria.

The oxidation of the side chains of two potential bile acid intermediates, 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid (THCA) and 3 alpha,7 alpha-dihydroxy-5 beta-cholestanoic acid (DHCA), were investigated in rat liver mitochondria and peroxisomes. Both THCA and DHCA were efficiently oxidized to yield cholic acid and chenodeoxycholic acid, along with 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholest-24-enoic acid and 3 alpha,7 alpha-dihydroxy-5 beta-cholest-24-enoic acid, respectively, in both the mitochondria and peroxisomes. However, the spectrum of the metabolites in the mitochondria differed greatly from those in the peroxisomes. The major products from THCA and DHCA in the mitochondria were 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-chol-22-enoic acid and 3 alpha,7 alpha-trihydroxy-5 beta-chol-22-enoic acid, respectively, which were tentatively identified from the mass spectral data. However, the formation of these C24-unsaturated bile acids was not observed in the peroxisomes. These results strongly suggest that the cleavage of the side chain of the C27-intermediates for bile acid biosynthesis also occurs independently in the mitochondria, not due to the contamination of peroxisomes.

Animals↗

PubMed1995

Missense mutation of rhodopsin gene codon 15 found in Japanese autosomal dominant retinitis pigmentosa.

Heterozygous missense mutation in codon 15 of the rhodopsin gene was detected in a patient with autosomal dominant retinitis pigmentosa (ADRP), where a transition of adenine to guanine at the second nucleotide in codon 15 (AAT-->AGT), corresponding to a substitution of serine residue for asparagine residue (Asn-15-Ser) was detected. None of the remaining unrelated 42 ADRP, 24 autosomal recessive RP (ARRP) and 34 normal individuals had this alteration. Her funduscopic findings were sectorial in type similar to that of the patients with the same mutation found in an Australian pedigree (Sullivan et al., 1993). This study shows phenotypic similarities in patients with the same mutation of a different ancestry.

Amino Acid Sequence↗

PubMed1995

Synthesis and metabolism of sodium 3 alpha,7 alpha-dihydroxy-25,26-bishomo-5 beta-cholane-26-sulfonate in the hamster.

This paper reports the chemical synthesis of a new bile acid analogue, namely sodium 3 alpha,7 alpha-dihydroxy-25,26-bishomo-5 beta-cholane-26-sulfonate (bishomoCDC-sul) from chenodeoxycholic acid and describes its metabolism in the hamster. The structure of the new compound was confirmed by proton and carbon-13 nuclear magnetic resonance spectroscopy. After intravenous infusion of [3H]-labeled sulfonate into bile fistula hamsters, it was extracted by the liver and secreted into the bile; more than 65% of the radioactivity was recovered in the bile within 1 h. Following intraduodenal administration of the [3H]sulfonate and [14C]chenodeoxycholyltaurine, both compounds were excreted into the bile more slowly; only 41 and 43% of the radioactivity, respectively, were recovered in the bile during the four-hour experimental period. In contrast, when the labeled compounds were injected into the terminal ileum, both the sulfonate and chenodeoxycholyltaurine were rapidly absorbed and secreted into the bile; 84 and 97%, respectively, of the radioactivity were recovered during a four-hour period. Chromatographic analysis demonstrated that in these short-term experiments most (> 95%) of the sulfonate was secreted into the bile without biotransformation regardless of the route of administration. When infused intravenously at increasing doses, bishomoCDC-sul induced cholestasis at an infusion rate of 1 mumol/min/kg. These results suggest that sodium 3 alpha,7 alpha-dihydroxy-25,26-bishomo-5 beta-cholane-26-sulfonate was absorbed from the terminal ileum by active transport, extracted by the liver, and secreted into the bile in a manner similar to that of the natural bile acids.

Animals↗

PubMed1995

Hypocholesterolemic effect of 5 beta-cholane-3 alpha,7 beta,24-triol-24- sulfate in hamsters.

We studied the effect of 5 beta-cholane-3 alpha,7 beta,24-triol-24-sulfate (UDC-O-sulfate) on ileal active transport of cholyltaurine, on hepatic cholesterol 7 alpha-hydroxylase activity, on serum and liver cholesterol levels, on intestinal absorption of cholesterol, and on bile salt composition of gallbladder bile in hamsters. Experiments using the everted gut sacs show that UDC-O-sulfate inhibits the ileal active transport of cholyltaurine. In experiments feeding the diets with either UDC-O-sulfate, cholesterol, or both to hamsters, the addition of UDC-O-sulfate to the cholesterol-enriched diet reduced the elevation of serum and liver cholesterol levels caused by cholesterol feeding. Supplementation with UDC-O-sulfate to the standard diet was likely to reduce serum and liver cholesterol levels. Cholesterol 7 alpha-hydroxylase activity was higher in the two UDC-O-sulfate supplemented groups than in the two corresponding groups, the standard diet group and the cholesterol enriched diet group, respectively. Addition of UDC-O-sulfate to the standard and cholesterol diets did not change intestinal absorption of cholesterol. The change of the bile salt composition in hamsters fed UDC-O-sulfate may also suggest that the bile alcohol sulfate inhibits the intestinal absorption of endogenous bile salts. Hence the hypocholesterolemic activity of dietary UDC-O-sulfate is thought to be the effect of the partial interruption of the enterohepatic circulation of endogenous bile salts.

Animals↗

PubMed1995

[A case of radiation optic neuropathy after resection of a pituitary adenoma].

A case of optic neuropathy after postoperative radiation therapy is reported. A 69-year-old woman had a partial resection of a pituitary adenoma in 1990 and was treated with 45Gy of irradiation to the postoperative pituitary lesion for one month. Seven months later she had sudden right visual field loss. Goldmann perimetry examination revealed remarked visual field defect in her right eye with visual acuity of 1.0. The right relative afferent pupillary defect was positive. The value of critical flicker fusion for her right eye was reduced and the amplitude of steady-state pattern-reversal visually evoked cortical potential was significantly less for the right monocular stimulation than that for the fellow eye stimulation, but Ganzfeld electroretinograms were normal for both eyes. Magnetic resonance imaging using Gadolinium-diethylene triaminepenta-acetic acid revealed enhancement on the right optic nerve, which had not been recognized immediately after the radiation therapy, without any suggestion of right optic nerve compression by the residual pituitary adenoma.

Adenoma↗

PubMed1994

Enhancement of neuronal calcium channel currents by the nootropic agent, nefiracetam (DM-9384), in NG108-15 cells.

Effects of nootropic agents on neuronal calcium channels were studied in NG108-15 cells using the whole-cell patch-clamp technique. Nefiracetam (DM-9384) at a concentration of 1 microM increased a long-lasting component of calcium channel currents two-fold without affecting a transient component. The dose-response relationship yielded a bell-shaped curve with a peak at 1 microM. Similar, but slightly less potent effects were observed by aniracetam. Dibutyryl cyclic AMP (1 mM) also enhanced the currents, which were not further increased by nefiracetam, or vice versa. The currents enhanced by nefiracetam were markedly reduced by nifedipine (10 microM), an 'L-type' calcium channel blocker. Cells treated with pertussis toxin (PTX; 500 ng/ml, > 20 h) to inactivate inhibitory G-proteins were apparently insensitive to nefiracetam. The results suggest that the nootropic agents may enhance the activity of neuronal L-type calcium channels under the regulation of inhibitory G-proteins and possibly, cyclic AMP-dependent processes.

Animals↗