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Biomedical subjects

S Ohta

Publications and source records attributed to S Ohta.

At least 199 records · Page 11Linked to original sources
PubMed1999

Strain differences of the ability to hydroxylate methotrexate in rats.

Converting activity of methotrexate (MTX) to 7-hydroxymethotrexate (7-OH-MTX) was examined using eight strains of rats. Marked variability of the activity was found in liver cytosols from the rats. The highest activity was observed with Sea:SD rats, followed by LEW/Sea and Jcl:Wistar rats. The lowest activity was observed with WKA/Sea rats. The difference in the activity between Sea:SD and WKA/Sea strains was 104-fold. The variation was correlated to the strain difference of benzaldehyde oxidase activity in the rats. The cytosolic 7-hydroxylase activities in other tissues of Sea:SD rats were much higher than those of WKA/Sea, similarly to the case in liver. The liver microsomes of Sea:SD rats exhibited no 7-hydroxylase activity toward MTX even in the presence of NADPH. The cytosolic 7-hydroxylating activity of the livers of Sea:SD rats was inhibited by menadione, beta-estradiol, chlorpromazine and disulfiram, inhibitors of aldehyde oxidase, but not oxypurinol, an inhibitor of xanthine oxidase. The purified aldehyde oxidase from the livers of Sea:SD rats exhibited a significant 7-hydroxylating activity toward MTX. However, xanthine oxidase had no ability to hydroxylate MTX. These facts suggest that MTX hydroxylating activity in rats is predominantly due to aldehyde oxidase, and the strain differences are due to the variations of the flavoenzyme level.

Aldehyde Oxidase↗
PubMed1999

Sequential scrotal scintigraphy for the study of varicocele.

Scrotal scintigraphy is a non-invasive procedure for evaluating spermatic vein reflux. This technique was used in 43 infertile patients with varicocele. None of them had infections, traumatic, or chromosomal abnormalities that could be associated with their infertility. Twelve patients showed type 1 time activity curve, including 3 with grade II, and 9 with grade III varicocele. A total of 12 patients showed a type 2 pattern and consisted of 2 patients with grade I, 6 with grade II, and 4 with grade III varicocele. Nineteen showed type 3 pattern consisting of 6 with grade I, 6 with grade II, and 7 with grade III. The patients with grade III varicocele showed type 1 pattern more frequently than those with grade I or II (p<0.05). Preoperative sperm concentration in patients with grade I varicocele was significantly lower than that in patients with grade II or III disease (p<0.05, each). Sperm motility of patients with grade I varicocele was also significantly lower than that of those with grade II or III varicocele (p<0.01, each). Patients with grade II or III varicocele showed an increase in sperm concentration postoperatively, and those with grade I varicocele showed a postoperative increase in sperm motility, but the differences between pre- and postoperative values were not significant. While seminal findings in patients with type 2 or 3 pattern did not change after surgery, patients with type 1 pattern showed significant improvement in sperm concentration postoperatively (p<0.05). It is concluded that preoperative sequential scrotal scintigraphy can be a more useful technique for assessing the prognosis for postoperative improvement of seminal findings than the grade decision of varicocele.

Adult↗
PubMed1999

Relationship between zinc concentrations in seminal plasma and various sperm parameters.

The zinc concentration in seminal plasma from 98 infertile male patients and 8 fertile males was measured. The zinc concentration of the seminal plasma in azoospermic and oligoasthenozoospermic patients was significantly lower than that in the other groups (each, p<0.05 ). The seminal plasma zinc concentration in asthenozoospermic males was significantly higher than that in any other group (p<0.05). There was a positive correlation of zinc concentration with sperm concentration (r=0.33, p<0.05) and with sperm motility (r=0.22, p<0.05), while there was no correlation with sperm morphology. A correlation between zinc concentration and plasma testosterone concentration was observed (r=0.24, p<0.05). It is concluded that excessively high zinc concentration is apparently related to defective motility in asthenozoospermic patients, even though adequate seminal plasma content of the element is required for normal sperm function.

Adult↗
PubMed1999

Internal tandem duplication of the FLT3 gene and clinical evaluation in childhood acute myeloid leukemia. The Children's Cancer and Leukemia Study Group, Japan.

We analyzed tandem duplication in the juxtamembrane (JM) domain of the FLT3 (FMS-like tyrosine kinase 3/FLK2, CD135) gene in 94 children with acute myeloid leukemia (AML) and evaluated its correlation with clinical features. Longer polymerase chain reaction (PCR) products were observed in five patients; 1/3 of M0, 119 of M1, 1/39 of M2, 1/9 of M3 and 1/12 of M5. The sequence analyses of abnormal PCR products showed that all the abnormal products were derived from tandem duplications involving the JM domain and that all the lengthened sequences were in-frame as we previously reported. Statistical analyses revealed a significantly lower incidence of the tandem duplication in childhood AML patients than in adult patients (P < 0.05), and significantly shorter disease-free survival in patients with mutant FLT3 than in patients with wild-type FLT3 (P < 0.05). Our results suggest that the tandem duplication in the JM domain of the FLT3 gene is not a frequent phenomenon but might be a factor of poor prognosis in childhood patients with AML.

Acute Disease↗
PubMed1999

Endogenous adenosine protects CA1 neurons from kainic acid-induced neuronal cell loss in the rat hippocampus.

CA3 pyramidal neurons in the rat hippocampus show selective vulnerability to the intracerebroventricular injection of kainic acid (KA). However, the mechanism of this selective neuronal vulnerability remains unclear. In this study, we examined the contribution of endogenous adenosine, a potent inhibitory neuromodulator, to the differences in the neuronal vulnerability of the hippocampus, using microtubule-associated protein (MAP)-2, phosphorylated c-Jun, and major histocompatibility complex (MHC) class II immunoreactivities as markers for neuronal cell loss, neuronal apoptosis and glial activation, respectively. Pretreatment with 8-cyclopenthyltheophylline (CPT), an A1 adenosine receptor antagonist, significantly exacerbated KA-induced neuronal cell loss in both the CA1 and CA3. Although c-Jun phosphorylation, a critical step in neuronal apoptosis, was not detected in the vehicle-injected rat hippocampus, c-Jun phosphorylation was induced in the CA3 by the injection of KA alone. Pretreatment with CPT induced c-Jun phosphorylation in both the CA1 and CA3. MHC class II antigen was also detected in the regions of c-Jun phosphorylation. Coadministration of N6-cyclopenthyladenosine (CHA), an A1 adenosine receptor agonist, attenuated the neuronal cell loss in the CA1 and CA3 with or without pretreatment with CPT. These results strongly suggest that endogenous adenosine has neuroprotective effects against excitotoxin-induced neurodegeneration in the CA1 through its A1 receptors.

Adenosine↗
PubMed1999

Primary intraorbital ectopic meningioma.

We report a case of intraorbital meningioma. Operative findings and histopathological examination revealed the tumoc to be meningothelial meningloma and to be located entirely outside the optic dura. This case demonstrates the occurrence of primary intraorbital ectopic meningioma, and the tumor was removed through a modified Dolenc approach. The primary intraorbital ectopic meningioma is discussed and the surgical approach to the orbital apex region is reviewed.

Case Reports↗
PubMed1999

Intraoperative evoked facial muscle responses and recovery process of the facial nerve in acoustic neuroma surgery.

The prognostic value of intraoperative evoked facial muscle responses (EFMR) was studied and correlated with the recovery process of the facial nerve during a follow-up period of 18 months. The patients were classified into four groups according to EFMR amplitudes, group A (150 microV or greater, 190.8, SD28.9 microV, n = 24), group B (100-149 microV, 125.7, SD14.3 microV, n = 14), group C (50-99 microV, 79.0, SD17.0 microV, n = 13) and group D (less than 50 microV, 22.1, SD13.3 microV, n = 15). Significant improved facial function appeared at 3 months after the operation in group A, at 6 months in group B, at 9 months in group C and at 12 months in group D. The early postoperative facial function and facial outcome of groups A and B were significantly better than those of groups C and D. Our data revealed that the intraoperative EFMR amplitudes have more prognostic value in predicting the recovery process of the nerve than functional outcome.

Analysis of Variance↗
PubMed1999

Eighteen-year survival of a patient with malignant pleomorphic xanthoastrocytoma associated with von Recklinghausen neurofibromatosis.

The authors report the first adult case of pleomorphic xanthoastrocytoma associated with neurofibromatosis-1. A 40-year-old man with history of neurofibromatosis-1 underwent total removal of a right temporo-parietal superficial glioma followed by radiation therapy. Eighteen years after surgery, the patient remained well with no tumour recurrence, which prompted review of the surgical material. The diagnosis of pleomorphic xanthoastrocytoma was then made though the tumour exhibited malignant features histologically, with marked necrosis. This extremely good clinical outcome suggest that some astrocytoma tumours in patients with neurofibromatosis might be associated with a favourable prognosis.

Adenoma, Pleomorphic↗
PubMed1999

Properties of endothelium and smooth muscle cells in canine femoral arteries after lumbar sympathectomy.

OBJECTIVE: To find out whether the lumbar sympathectomy modulated the endothelial function (as measured by nitric oxide (NO) and prostacyclin (PGI2), and blood flow in the canine femoral artery. DESIGN: Laboratory experiments. SETTING: Teaching hospital, Japan. ANIMALS: 16 mongrel dogs. INTERVENTION: Unilateral sympathectomy from L3 to L6. MAIN OUTCOME MEASURES: Five weeks later, the changes in blood flow, the endothelium-dependent responses and the PGI2 production in the canine femoral arteries were measured. RESULTS: The median (range) blood flow of left (denervated) and right (innervated) femoral arteries was 162 ml/min (122-330) and 65 ml/min (40-92), respectively. There was a significant difference between the two groups (p < 0.01). The endothelium-dependent relaxations to acetylcholine, adenosine diphosphate (ADP) and A23187 were comparable. The amounts of PGI2 produced in the two groups were similar. Direct relaxation in response to sodium nitroprusside was also similar in the two groups. CONCLUSIONS: Lumbar sympathectomy did not alter the endothelial function, although the median blood flow in the denervated femoral arteries was significantly higher than in the innervated ones. The continuous vasodilatation after sympathectomy may be a more potent factor in the regulation of vascular tonus than the physiological regulation of NO and PGI2.

Animals↗
PubMed1999

Microsomal carbonyl reductase responsible for reduction of 4-phenyl-3-buten-2-one in rats.

trans-4-Phenyl-3-buten-2-one (PBO), a flavoring additive, was transformed to the carbonyl-reduced product, trans-4-phenyl-3-buten-2-ol (PBOL) by rat liver microsomes, but not by liver cytosol, in the presence of NADH or NADPH. PBOL formed was identified by comparison with an authentic sample. The reductase activity was not inhibited by quercitrin, an inhibitor of cytosolic carbonyl reductase. The carbonyl reduction product of PBO by liver microsomes was identified as the R-enantiomer of PBOL by HPLC analysis. Rat blood also exhibited the carbonyl reductase activity in the presence of NADH or NADPH, but to a lesser extent.

Alcohol Oxidoreductases↗
PubMed1999

Variation of hepatic methotrexate 7-hydroxylase activity in animals and humans.

This study deals with individual and species variations in the converting activity of methotrexate (MTX) to 7-hydroxymethotrexate in animals and humans. When MTX 7-hydroxylase was assayed in six human liver cytosols, a 48-fold range of intersubject variation of the activity was observed. The variations were correlated to the concentrations of aldehyde oxidase activity in human subjects assayed with benzaldehyde as a substrate. Species differences of liver MTX 7-hydroxylase activity were also observed. The activity was highest in rabbits, followed by rats, hamsters, and monkeys but was undetectable in dogs. Strain differences of MTX 7-hydroxylase activity based on aldehyde oxidase activity were also observed in rats and mice. The results suggest that aldehyde oxidase functions as MTX 7-hydroxylase in livers of animals and humans, and the observed differences of MTX 7-hydroxylase activity are due to variations in the amount of aldehyde oxidase present.

Adult↗
PubMed1999

Pseudoenzymatic reduction of N-hydroxy-2-acetylaminofluorene to 2-acetylaminofluorene mediated by cytochrome P450.

N-hydroxy-2-acetylaminofluorene (N-OH-AAF) was reduced to 2-acetylaminofluorene by rat liver microsomes in the presence of both NAD(P)H and FAD under anaerobic conditions. The microsomal reduction proceeds as if it were an enzymatic reaction. However, when the microsomes were boiled, the activity was not abolished, but was enhanced. The activity was also observed with cytochrome P450 2B1 alone, without NADPH-cytochrome P450 reductase, in the presence of these cofactors. Hematin also exhibited a significant reducing activity in the presence of both a reduced pyridine nucleotide and FAD. The activities of microsomes, cytochrome P450 2B1 and hematin were also observed upon the addition of photochemically reduced FAD instead of both NAD(P)H and FAD. The microsomal reduction of N-OH-AAF appears to be a non-enzymatic reaction by the reduced flavin, catalyzed by the heme group of cytochrome P450.

2-Acetylaminofluorene↗
PubMed1999

The effect of intravenous or subarachnoid lidocaine on glutamate accumulation during transient forebrain ischemia in rats.

UNLABELLED: We studied whether IV or subarachnoid (SA) lidocaine would influence the increase in extracellular glutamate concentration in the hippocampal CA1 and the cerebral cortex during transient forebrain ischemia in rats by using the dialysis electrode method. Fifty-four Sprague-Dawley rats were assigned to one of six treatment groups: IV lidocaine 5 mg/kg, IV lidocaine 10 mg/kg, IV 0.9% saline 0.5 mL/kg, SA lidocaine 5 mg/kg, SA lidocaine 10 mg/kg, and SA 0.9% saline 0.5 mL/kg (n = 9 in each group). Transient forebrain ischemia was induced by hemorrhagic hypotension and carotid artery occlusion, 15 min after administration of lidocaine or saline. The maximal values of glutamate concentration and the areas under glutamate concentration curves in the CA1 were significantly less in the IV lidocaine 10 mg/kg group than the IV saline group, whereas those in the CA1 and the cortex were significantly less in the SA lidocaine 5 and 10 mg/kg groups than the SA saline group. The accumulation of glutamate in the CA1 or the cortex during transient forebrain ischemia was attenuated by IV or SA lidocaine. We conclude that the neuroprotective effect of lidocaine against transient cerebral ischemia involves the suppression of the increase in extracellular glutamate concentration. IMPLICATIONS: IV or subarachnoid lidocaine was demonstrated to suppress glutamate accumulation in the hippocampus and the cortex during transient forebrain ischemia in rats by using the dialysis electrode method. Lidocaine can have a neuroprotective effect through the suppression of the increase in extracellular glutamate concentration.

Anesthetics, Local↗
PubMed1999

Outcome in acute stroke with successful intra-arterial thrombolysis and predictive value of initial single-photon emission-computed tomography.

This study investigates retrospectively, in selected patients, the ischemic outcome (reversible ischemia, infarction, and hemorrhage) and neurologic outcome of acute stroke treated with intra-arterial thrombolysis and the predictive value of pretreatment single-photon emission-computed tomography (SPECT). Thirty patients with complete recanalization within 12 hours were analyzed. The extent of ischemia was outlined on SPECT, and two CBF parameters were calculated: the ratio of ischemic regional activity to CBF in the cerebellum and the asymmetry index. Reversible ischemia, infarction, and hemorrhage were identified by comparing SPECT and follow-up computed tomography. Nine patients (30%) had no or small infarction, 14 (47%) had medium or large infarction, and seven (23%) had hemorrhage. Forty-two lesions were identified (22 reversible ischemia, 13 infarction, and 7 hemorrhage). Duration of ischemia, urokinase dose, disease type, and occlusion site were nonsignificant factors, whereas neurologic outcome and CBF parameters were significant among the three patient groups and three types of ischemic lesions. Ischemic tissue with CBF greater than 55% of cerebellar flow still may be salvageable, even with treatment initiated 6 hours after onset of symptoms. Ischemic tissue with CBF greater than 35% of cerebellar flow still may be salvageable with early treatment (less than 5 hours). Ischemic tissue with with CBF less than 35% of cerebellar flow may be at risk for hemorrhage within the critical time window. Pretreatment SPECT can provide useful parameters to increase the efficacy of thrombolysis by reducing hemorrhagic complications and improving neurologic outcome.

Adult↗
PubMed1999

Brief vibrotactile stimulation does not increase cortical oxygen consumption when measured by single inhalation of positron emitting oxygen.

Vibrotactile stimulation of the hand elicits no increase in oxygen consumption commensurate with the increase in blood flow measured in human sensory cortex. To test the hypothesis that previous failures to detect a proportionate increase in oxygen consumption could be an artefact of the sequential bolus, or three-step, method used to measure this parameter in the human brain in vivo, the authors compared the measurements with the results of a novel single bolus, or one-step, method of measuring oxygen consumption. The time of completion of the three-step method was 40 to 50 minutes, whereas the one-step method lasted only 3 minutes. The baseline whole-brain oxygen consumption averaged 185 +/- 32 micromol hg(-1) min(-1) by the three-step method and 153 +/- 15 micromol hg(-1) min(-1) by the one-step method. Vibrotactile stimulation did not elicit a significant increase in oxygen consumption measured by either method. This finding rejects the hypothesis that failure to detect an increase of oxygen consumption could be an artefact caused by limitations of the method used previously. Conversely, it also rejects the hypothesis that observations of an increase of oxygen consumption by the new method are artefacts caused by limitations of the one-step method.

Blood Flow Velocity↗
PubMed1999

Visual evoked oscillatory responses of the human optic tract.

Optic tract oscillatory responses directly recorded during posteroventral pallidotomy were investigated to reveal their features with respect to extracranially recorded visual oscillations and to clarify their contributions to scalp-recorded or far-field visual evoked potentials. Oscillatory responses of the optic tract consisting of early and subsequent late oscillations were recorded in all patients. Early oscillations consist of five negative and positive peaks, and late oscillations consist of two to four negative and positive peaks. The frequency of the first peak of early oscillations (103.0+/-9.2 Hz, n = 14) was significantly lower than that of others (t test, P<0.006), but there were no significant differences among other peaks (t test, P>0.4). This difference was not observed among peaks of late oscillations (t test, P>0.3). As a whole, the frequency of early oscillations (123.9+/-16.7 Hz, n = 70) was significantly higher than that of late oscillations (66.3+/-13.7 Hz, n = 41) (t test, P = 0.0001). Intracerebral recording of the optic responses with the same band filter of scalp-recorded visual evoked potentials (10 Hz to 1 KHz) showed prominent negative (No) and positive (Po) waves, whereas responses obtained over the scalp at Oz and Cz consisted of negative (NI), positive (PI), negative (NII), and positive (PII) waves. Comparisons between No and PI and Po and NII showed overall phase reversal relations between them, but there were significantly different peak latencies between them (t test, P<0.001) except that between Po (116.7+/-11.7 msec, n = 5) and NII of Cz recording (118.4+/-9.4 msec, n = 5) (t test, P<0.3). Our study in conjunction with other studies on visual oscillations revealed that a relatively constant frequency of oscillations is traveling in the subcortical visual system and is probably playing an important role in generating stationary or fixed peaks of the far-field potentials of visual evoked potentials.

Evoked Potentials, Visual↗