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Biomedical subjects

Y Shinohara

Publications and source records attributed to Y Shinohara.

At least 127 records · Page 7Linked to original sources

Fluid attenuation inversion recovery (FLAIR) images of dentatorubropallidoluysian atrophy: case report.

The white matter lesions in a patient with late adult onset dentatorubropallidoluysian atrophy (DRPLA) were studied in detail by MRI using the fluid attenuation inversion recovery (FLAIR) technique. The patient was a 60 year old woman with a family history of DRPLA, in whom the number of CAG repeats in the DRPLA gene on chromosome 12 was expanded to 59 (normal allele 10). In addition to atrophy of the cerebral cortex, cerebellum, and pontomesencephalic tegmentum, the cerebral white matter and a part of the white matter tracts within the brainstem showed prominent high signal intensities on FLAIR images. These MR findings suggest that, in addition to the degeneration of the dentatorubral and pallidoluysian systems, the pathological process extends to the white matter in DRPLA. This could be important for differentiating DRPLA from other clinically similar diseases such as Machado-Joseph disease or Huntington's disease.

Adult↗

Ebselen in acute ischemic stroke: a placebo-controlled, double-blind clinical trial. Ebselen Study Group.

BACKGROUND AND PURPOSE: The effect of ebselen, a seleno-organic compound with antioxidant activity through a glutathione peroxidase-like action, on the outcome of acute ischemic stroke was evaluated in a multicenter, placebo-controlled, double-blind clinical trial. METHODS: Patients diagnosed as having acute ischemic stroke who could receive drug treatment within 48 hours of stroke onset were enrolled. Oral administration of ebselen granules suspended in water (150 mg BID) or placebo was started immediately after admission and was continued for 2 weeks. The major end points were the Glasgow Outcome Scale scores at 1 month and 3 months after the start of treatment. The modified Mathew Scale and modified Barthel Index scores at 1 month and 3 months were also studied as secondary outcome measures. RESULTS: Three hundred two patients were enrolled in the trial. Intent-to-treat analysis of 300 patients (151 given ebselen and 149 given placebo) revealed that ebselen treatment achieved a significantly better outcome than placebo at 1 month (P = .023, Wilcoxon rank sum test) but not at 3 months (P = .056, Wilcoxon rank sum test). The improvement was significant in patients who started ebselen within 24 hours of stroke onset but not in those who started treatment after 24 hours. There was a corresponding improvement in the modified Mathew Scale and modified Barthel Index scores. CONCLUSIONS: Early treatment with ebselen improved the outcome of acute ischemic stroke. Ebselen may be a promising neuroprotective agent.

Acute Disease↗

The brainstem and thalamic lesions in dentatorubral-pallidoluysian atrophy: an MRI study.

We studied the frequency and characteristics of brainstem and thalamic lesions in dentatorubral-pallidoluysian atrophy using MRI. Of 15 subjects diagnosed by DNA analysis, 13 had lesions in the pontine base, nine in the midbrain, and five in the thalamus. Lesions were correlated positively with the patient's age, but not with neurologic features or numbers of CAG repeats. Patients with Machado-Joseph disease or spinocerebellar ataxia 1 did not show these characteristic lesions.

Adult↗

Studies on the stereoselective internal acyl migration of ketoprofen glucuronides using 13C labeling and nuclear magnetic resonance spectroscopy.

Internal acyl migration reactions of drug 1beta-O-acyl glucuronides are of interest because of their possible role in covalent binding to serum proteins and consequent allergic reactions as well as their influence on drug disposition. An approach using 13C labeling and nuclear magnetic resonance (NMR) spectroscopy has been used to investigate in situ the kinetics of acyl migration and hydrolysis of 1beta-O-acyl glucuronides of enantiomeric ketoprofens (KPs) in phosphate buffer solutions at 37 degrees C. Apparent first-order degradation of the 1beta-O-acyl glucuronide labeled in the ester carbonyl carbon and the sequential appearance of 2-, 3-, and 4-O-acyl isomers as both alpha- and beta-anomeric forms were observed for each enantiomer. All of the positional isomers and anomers were characterized using two-dimensional NMR spectroscopy (heteronuclear multiple bond correlation, correlated spectroscopy, totally correlated spectroscopy) of the reaction mixtures. The overall degradation rate constants (hr-1) of (R)- and (S)-KP glucuronides were 1.07 +/- 0.154 and 0.55 +/- 0.034, respectively. To evaluate in detail the stereoselective reactivity, a kinetic model describing the rearrangement reactions was constructed, and the kinetics were simulated using a theoretical approach. Only the acyl migration, 1beta-->2beta, was found to have significant stereoselectivity. The rate constants (hr-1) for 1beta-->2beta migration of (R)- and (S)-KP glucuronides were 1.04 +/- 0.158 and 0. 52 +/- 0.029, respectively. The results may suggest that (R)-KP glucuronide could be more susceptible to covalent binding to proteins via acyl migration than the corresponding antipode. This stereoselective reactivity may be responsible for the stereoselective pharmacokinetics of KP. The direct approach using 13C labeling and NMR spectroscopy could also provide insight into the reactivities of other labile drug acyl glucuronides and their isomeric glucuronides.

Acylation↗

[Complicated form of spastic paraplegia with congenital cataract: a case report].

We report a 33-year-old man who manifested spastic paraplegia with congenital cataract, dementia, deformity of the foot (pes cavus, high arch and hammer toes), ataxia, and peripheral neuropathy. Magnetic resonance imaging showed mild deformity of the trunk of the corpus callosum and atrophy of superior cerebellar vermis. Metabolic diseases were ruled out by the clinical course and special examinations. Other patients, including 2 of ours, with spastic paraplegia and thin corpus callosum have been reported, but the present case is different because of congenital cataract and the form of the corpus callosum. We consider that there may be a variety of complicated forms of spastic paraplegia. To assess the etiology of complicated forms of spastic paraplegia, further case accumulation is very important.

Adult↗

[Long-term gadolinium-enhancement of cauda equina on MRI in a case of spinal cord infarction after epidural anesthesia].

A 49-year-old woman developed paraplegia 26 hours after appendectomy under epidural and general anesthesia. Systolic blood pressure fell to 85 mmHg for 25 minutes after epidural anesthesia, which was performed at the level of the L1/2 intravertebral space. Neurological examination revealed paraplegia and superficial sensory impairment below the level of the L 1 spinal cord. The bladder was atonic by cystometry. MRI showed gadolinium enhancement of the cauda equina extending over a long period (3 months) and spinal cord infarction. The infarction was at the level of 10th thoracic spinal vertebra to conus and was limited to the gray matter of the spinal cord. We consider that the reason for spinal cord infarction was prolonged hypotension of the patient, who was diabetic, hypertensive and hypercoagulopathic. The blood supply to the gray matter is mainly from the central artery which is derived from the anterior spinal artery, and the gray matter is particularly vulnerable to hypotension. Our hypotheses concerning gadolinium enhancement of the cauda equina are the following: 1) enhancement of the cauda equina was seen due to collateral formation after spinal cord infarction, and 2) long-term enhancement of the cauda equina was observed due to an ischemic lesion involving a large area.

Anesthesia, Epidural↗

Dramatic enhancement of the specific expression of the heart-type fatty acid binding protein in rat brown adipose tissue by cold exposure.

To understand the difference in energy metabolisms in brown (BAT) and white (WAT) adipose tissues, we examined the steady-state transcript levels of the heart-type and adipose-type fatty acid binding proteins (H-FABP and A-FABP, respectively) by Northern blot analysis. The transcript of H-FABP in rat BAT was increased about 100-fold by cold exposure, whereas that in WAT was negligible, and was increased only slightly by cold exposure. The transcript of A-FABP was observed in both BAT and WAT, the level being slightly greater in WAT. However, its transcript level was not affected by cold exposure in either adipose tissue. In addition, on treatment with norepinephrine (NE), transcript level of H-FABP was elevated markedly but that of A-FABP was not changed in rat brown adipocytes. Therefore, the stimulatory effect of cold exposure on the transcript of H-FABP in BAT was concluded to be mediated by NE, like that of the uncoupling protein (UCP). Thus, the expressions of H-FABP and UCP may be controlled by the same mechanism.

Adipocytes↗

Structural features of the gene encoding human muscle type carnitine palmitoyltransferase I.

We isolated a human muscle type of carnitine palmitoyltransferase I (CPTI-M) genomic clone and determined its entire nucleotide sequence. By comparison of the nucleotide sequence of the genomic clone with that of cDNA, we determined the intron/exon junctions. For detection of the exon(s) in the 5'-region of the CPTI-M gene, we isolated cDNA clones corresponding to the 5'-region of its transcript by 5'-rapid amplification of cDNA ends (5'-RACE method). Results showed two alternative exons, 1A and 1B, that do not encode amino acids in the 5'-region of the human CPTI-M gene. The gene encoding human CPTI-M was found to consist of two 5'-non-coding exons, 18 coding exons and one 3'-non-coding exon spanning approximately 10 kbp. Furthermore, on analysis of the 5'-flanking region, a putative gene encoding a 'choline kinase homologue' was found to be located only about 300 bp upstream from exon 1A of the human CPTI-M gene. Comparison of the gene structure of human CPTI-M with the reported partial gene structure of human liver type CPTI (CPTI-L) showed that the intron insertion sites were completely conserved in these two genes.

Amino Acid Sequence↗

Source of ATP for hexokinase-catalyzed glucose phosphorylation in tumor cells: dependence on the rate of oxidative phosphorylation relative to that of extramitochondrial ATP generation.

We isolated highly intact and tightly coupled mitochondria from the rat ascites hepatoma cell line AH130 by disruption of the cell membrane by nitrogen cavitation. These isolated mitochondria were found to have essentially the same functional properties as rat liver mitochondria, but unlike the latter, hexokinase (HK) was bound to their membrane. Using the tumor mitochondrial preparation, we examined the source of ATP for phosphorylation of glucose by HK under conditions in which intra- and extramitochondrial ATP-generation systems operated separately or together. Results showed that the membrane-bound HK utilized ATP derived from the most efficiently operating ATP generation system, i.e., oxidative phosphorylation. However, when the rate of extramitochondrial ATP generation was much greater than that of oxidative phosphorylation, HK used ATP from the extramitochondrial ATP-generation system.

Adenosine Diphosphate↗

Determination of [D-Ala2,D-Leu5]enkephalin and the metabolites containing C-terminal D-leucine by high-performance liquid chromatography.

A high-performance liquid chromatographic procedure has been developed for the determination of [D-Ala2,D-Leu5]enkephalin (DADLE) and the fragments containing D-leucine in rat blood. The procedure was applied to the determination of blood levels of [3H-D-Leu5]DADLE and the C-terminal fragments after intravenous administration of [3H-D-Leu5]DADLE to a rat. Unlabelled DADLE and the C-terminal fragments were spiked as carriers to rat blood samples and the blood samples were extracted with 1% trifluoroacetic acid in methanol. The recoveries from rat blood were quantitative for all compounds. DADLE and the C-terminal four fragments were well separated on a reversed-phase column with gradient elution using a mobile phase composed of 0.14% HClO4 and acetonitrile.

Animals↗

Mechanism of reduction of cortical blood flow in striatocapsular infarction: studies using [123I]iomazenil SPECT.

Single photon emission computed tomography (SPECT) using [123I]iomazenil (radioligand of central-type benzodiazepine receptors) was employed to examine two patients with striatocapsular infarction. Patient 1 was a 61-year-old female with motor aphasia and hemiplegia on the right side. Magnetic resonance imaging (MRI) showed a lesion in the anterior limb of internal capsule and putamen on the left side. SPECT using 99mTc-HMPAO revealed a reduction of cerebral blood flow (CBF) in the frontoparietal region on the left side, but the delayed images in SPECT using [123I]iomazenil showed only a mild decrease of accumulation in the frontal lobe. Patient 2 was a 55-year-old male with hemiplegia on the left side. MRI showed a lesion localized in the basal ganglia and posterior limb of the internal capsule on the right side. SPECT using 99mTc-HMPAO revealed a reduction of CBF in the frontoparietal region on the right side and in the cerebellar hemisphere on the left side, but the delayed images in SPECT using [123I]iomazenil showed little decrease of accumulation in parietal lobe. The discrepancy between CBF and receptor images suggested that cortical hypoperfusion on striatocapsular infarction might reflect hypometabolism due to disconnection of the neuronal network between subcortical structure and cortex.

Aphasia↗

Primary malignant lymphoma of the rectum with distant metastasis to the stomach: report of a case.

Primary extranodal malignant lymphoma frequently occurs in the gastrointestinal tract: however, it is rarely encountered in the rectum. We report herein the case of an 85-year-old man who underwent abdominoperineal resection for primary malignant lymphoma of the rectum, and 1 year later, developed hematemesis caused by gastric metastasis. To our knowledge this is the first case report of such distant metastasis developing from malignant lymphoma of the rectum.

Aged↗

Potassium channel opener reduces extracellular glutamate concentration in rat focal cerebral ischemia.

The vasodilatory action of potassium channel openers through a membrane hyperpolarizing action is well known, but little is known about the effect of these drugs on ischemia-induced glutamate release in the brain. We evaluated the effects of a potassium channel opener (Y-26763), given intravenously at 0.03 mg/kg/h from 50 min prior to occlusion until 3 h postocclusion, on cerebral blood flow, extracellular glutamate concentration, and infarct volume in rats with focal ischemia. Y-26763 significantly inhibited the increase in extracellular glutamate concentration at 50 and 60 min of ischemia with a significant reduction of mean arterial blood pressure. However, there was no significant difference in blood flow in the core of infarcted cortex or in infarct volume between Y-26763- and vehicle-treated groups. These results suggest that Y-26763 inhibited presynaptic glutamate release through hyperpolarizing the membrane, but infarct volume was not reduced because of insufficient perfusion owing to its hypotensive effect.

Animals↗