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Y Oda

Publications and source records attributed to Y Oda.

At least 415 records · Page 23Linked to original sources

Specificity and sensitivity of Salmonella typhimurium YG1041 and YG1042 strains possessing elevated levels of both nitroreductase and acetyltransferase activity.

Acetyltransferase and nitroreductase are enzymes involved in the intracellular metabolic activation of nitroarenes and/or aromatic amines in Salmonella typhimurium. The plasmid carrying both the acetyltransferase and nitroreductase genes was introduced into S. typhimurium TA98 and TA100. The resulting strains, YG1041 and YG1042, respectively, showed high levels of both enzyme activities and were more sensitive to the mutagenic action of some nitro-aromatic compounds such as 2-nitrofluorene, 1-nitropyrene and p-nitrophenetole than did the sensitive strains previously established in this laboratory or the conventional strains. These results indicate that the new strains permit the very efficient detection of the mutagenicity of nitroarenes in the environment.

Acetyltransferases↗

Roles of different forms of cytochrome P450 in the activation of the promutagen 6-aminochrysene to genotoxic metabolites in human liver microsomes.

We reported previously that the potent mutagen 6-aminochrysene is catalyzed principally by rat liver microsomal P4501A and P4502B enzymes to reactive metabolites that induce umu gene expression in O-acetyltransferase-over-expressing strain Salmonella typhimurium NM2009; the proposal was made that there are different mechanisms in the formation of reactive N-hydroxylated and diolepoxide metabolites by P450 enzymes (Yamazaki, H. and Shimada, T., Biochem. Pharmacol., 44, 913-920, 1992). Here we further examined the roles of human liver P450 enzymes and the mechanism of activation of 6-aminochrysene by rat and human P450 enzymes in the Salmonella tester strains. Liver microsomes from 18 different human samples catalyzed activation of 6-aminochrysene more efficiently in S. typhimurium NM2009 than in the original strain of S. typhimurium TA1535/pSK1002. The rates of 6-aminochrysene activation in 18 human liver samples showed good correlation to the contents of P4502B6 as well as contents of P4503A4 and the respective mono-oxygenase activities catalyzed by P4503A4. Among purified P450 enzymes examined, P4501A2 as well as P4503A4 were highly active in transforming 6-amino-chrysene to reactive metabolites, suggesting the involvement of different human P450 enzymes in the reaction. Four human samples that contained relatively high levels of particular P450 enzymes in their microsomes were selected and used for further characterization. Liver microsomes from human samples HL-13 and HL-4 that contained the highest levels of P4502B6 and P4503A4 respectively, were sensitive to the respective antibodies raised against monkey P4502B and human P4503A4; the activity in sample HL-16 having the highest level of P4501A2 was inhibited by anti-P4501A2 IgG. alpha-Naphthoflavone enhanced the activation of 6-aminochrysene very significantly in human liver microsomes enriched in P4503A4 and P4502B6 enzymes. Pentachlorophenol, an inhibitor of acetyltransferase activity, suppressed the activation of 6-aminochrysene in liver microsomes from phenobarbital-treated rats and from human samples HL-4, HL-13 and HL-18 but not HL-16. In contrast, 1,1,1-trichloropropane-2,3-oxide, an inhibitor of epoxide hydrolase activity, enhanced the activation of 6-aminochrysene catalyzed by liver microsomes from beta-naphthoflavone-treated rats and from human samples HL-16 but not HL-4, HL-13 and HL-18. Inclusion of purified rat epoxide hydrolase to the reconstituted system containing rat and human P4501A enzymes caused a decrease in the rates of 6-aminochrysene activation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Structure-function studies on selectin carbohydrate ligands. Modifications to fucose, sialic acid and sulphate as a sialic acid replacement.

The selectins are a family of carbohydrate-binding proteins that have been implicated in the initial interaction between leukocytes and the vascular endothelium. The three members of this family will bind to the sialyl-Lewisx epitope [Sia alpha 2-3 Gal beta 1-4 (Fuc alpha 1-3) GlcNAc] and related oligosaccharides. In this report, we examine the molecular details of that recognition using synthesized carbohydrates with specific modifications on the sialyl-Lewisx epitope. E- and L-Selectin require hydroxyl groups at the 2, 3 and 4 positions of the fucose residue. P-Selectin, however, requires only the 3-position hydroxyl group, while tolerating removal of the oxygen at positions 2 or 4 of fucose residue. Modifications of the glycerol side chain or the N-acetyl group of the sialic acid have little effect on the binding of any of the selectins. All three selectins bind efficiently to an oligosaccharide with a sulphate replacement for the sialic acid [sulpho-Lewisx, or SO4-3Gal beta 1-4 (Fuc alpha 1-3) Glc-ceramide]. For E-Selectin, binding to sulpho-Lewisx appears to be equivalent to binding to sialyl-Lewisx, while for L- and P-Selectin binding to the sulphated structure shows characteristics distinct from sialyl-Lewisx recognition. Taken together, these data indicate that, while all three selectins can recognize sialyl-Lewisx, E-, L- and P-Selectin each display distinct carbohydrate ligand preferences.

Carbohydrate Metabolism↗

Effect of barbiturate therapy on phenytoin pharmacokinetics.

OBJECTIVE: To evaluate the effect of high-dose pentobarbital therapy on phenytoin pharmacokinetics. DESIGN: A prospective, clinical study. SETTING: The intensive care unit of a university hospital. PATIENTS: Ten adult patients with cerebral lesions requiring anticonvulsants and control of intracranial pressure. INTERVENTIONS: Each patient received phenytoin sufficient to maintain a plasma concentration at 15 micrograms/mL (60 mumol/L) both before and after barbiturate therapy. Plasma concentrations of total phenytoin, unbound phenytoin, and the major metabolite of phenytoin, 5-(p-hydroxyphenyl)-5-phenylhydantoin, were measured, and pharmacokinetic variables obtained before and after barbiturate therapy were compared. MEASUREMENTS AND MAIN RESULTS: Plasma concentrations of total phenytoin remained within the therapeutic range during the 12-hr period preceding barbiturate therapy. After barbiturate therapy, plasma concentrations of both total and unbound phenytoin were significantly less than those concentrations before barbiturate therapy. For total phenytoin, maximum metabolic velocity was increased by 62% (1.09 +/- 0.62 to 1.77 +/- 0.52 mg/L/hr, 1.20 +/- 0.68 to 1.95 +/- 0.57 nmol/L/sec, p < .05), and area under the plasma concentration-time curve (0 to infinity) and mean residence time were each decreased by 73% (32.5 +/- 20.0 to 8.7 +/- 3.1 min.mg/mL, 2.14 +/- 1.25 to 0.57 +/- 0.19 sec.mmol/L, p < .01, and 135,000 +/- 69,000 to 37,000 +/- 11,000 secs, p < .005, respectively) after barbiturate therapy. The plasma concentration of the principal metabolite of phenytoin, 5-(p-hydroxyphenyl)-5-phenylhydantoin, was significantly increased after barbiturate therapy. CONCLUSIONS: Phenytoin metabolism is increased by barbiturate therapy, and supplemental doses of phenytoin and frequent drug monitoring may be required after barbiturate therapy.

Adult↗

Herniation of calcified cervical intervertebral disc causes dissociated motor loss in a child.

Herniation of the calcified nucleus pulposus is a rare complication of intervertebral disc calcification in children. Surgical intervention is rarely indicated in the majority of such cases. This paper reports a 12-year-old boy with a calcified nucleus pulposus at C7-T1 which had ruptured into the spinal canal, causing dissociated motor loss. Anterior discectomy and fusion were performed and the patient's muscle weakness markedly improved after surgery.

Cervical Vertebrae↗

Stroke and meningitis in a case of SLE with anti-phospholipid antibodies.

Anti-phospholipid antibodies (aPL) are concerned with many central nervous system diseases in systemic lupus erythematosus (SLE). However, no report has described the relationship between aseptic meningitis and aPL in SLE. We report a case of SLE with aPL, presenting cerebral infarction and aseptic meningitis. A 14 year old female with SLE with aPL experienced cerebral infarction and recurrent aseptic meningitis. Combination therapy with steroids and aspirin improved the condition and prevented relapses. The aPL are associated with cerebral infarction, even in young patients with SLE. In addition, aPL may induce aseptic meningitis in SLE.

Adolescent↗

Glucose consumption in recurrent gliomas.

In order to investigate the clinical significance of glucose consumption (GC) in recurrent gliomas, positron emission tomography with 18F-labeled fluorodeoxyglucose was measured in 18 cases of histologically verified recurrent gliomas. The GC of the tumors were categorized into four groups. Five tumors were in Group IV, the highest GC, four were in Group III, eight were in Group II, and one was in Group I. Masses in Groups III and IV were clearly defined as a hot spot higher than or similar to the GC of the contralateral cortex. Half of the recurrent gliomas showed the lower GC of Group I or II, but two thirds of these were histologically high-grade gliomas. Although GC in the recurrent gliomas did not always increase as expected, a focal increase of GC, even mild and small, in the area of previous surgery is diagnostically important. Tumors with high GC showed high histological malignancy, irrespective of tissue damage. Patients with tumors of low GC had longer survival rates than those with high GC, although statistical significance was not obtained. Thus, positron emission tomography with 18F-labeled fluorodeoxyglucose was useful for detecting the recurrence of gliomas and suggesting their histological malignancy and prognosis. Care should be taken because viable tumor cells could be present in areas of low GC and small recurrent masses could be missed because of the poor spatial resolution of positron emission tomography.

Adult↗

New lectins from bulbs of Croccus sativum.

Four isolectins were isolated from bulbs of Croccus sativum (saffron), using affinity chromatography on mannan-Sepharose 4B, gel filtration and ion-exchange column chromatography in the presence of 8 M urea. The relative molecular masses of these lectins were determined by gel filtration to be approximately 48 kDa. On polyacrylamide gel electrophoresis, relative molecular masses of 8 kDa were obtained, suggesting that the lectins are hexamers. No carbohydrates were detected in the lectins. The lectins agglutinated the yeasts of Saccharomyces cerevisiae at a minimum concentration of 30 micrograms/ml, however, they did not agglutinate animal erythrocytes (human, sheep, rabbit and mouse) even at a concentration of 1000 micrograms/ml. In inhibitory experiments, mannan from Saccharomyces cerevisiae was the most potent inhibitor of C. sativum lectins. While D-mannose showed no inhibition, manno-oligosaccharides with either (alpha 1-2, 1-3) or (alpha 1-6) linkages were potent inhibitors, suggesting that C. sativum lectins recognized manno-oligosaccharide units larger than mannobiose. Ovomucoid also exhibited potent inhibition, however, the other carbohydrates examined did not.

Agglutination↗

Purification and characterization of alpha-glucosidase from Torulaspora pretoriensis YK-1.

alpha-Glucosidase was partially purified 103-fold from a cell-free extract of Torulaspora pretoriensis YK-1 by column chromatography on Toyopearl HW55F, DEAE-Toyopearl 650M, hydroxylapatite and phenyl-Toyopearl 650M. Further purification by preparative polyacrylamide gel electrophoresis (PAGE) gave the homogenous protein, but the specific activity was reduced. The molecular weight of the enzyme was estimated to be 69,000 by SDS-PAGE and 60,000 by gel filtration. Optimum pH and temperature were 6.8 and 35 degrees C, respectively. The enzyme was inhibited strongly by AgNO3, HgCl2, sodium dodecyl sulfate, and N-ethylmaleimide. The Km (mM) for p-nitrophenyl alpha-D-glucopyranoside, maltose, maltotriose, isomaltose, methyl alpha-glucoside, and sucrose were 0.15, 150, 45, 17, 18, and 29, and Vmax (mumol/min/mg protein) for those substrates were 87, 0.23, 2.4, 9.0, 12, and 7.4, respectively. The N-terminal amino acid sequence of the enzyme was PEVKNHPETQPKWWKEATVY. The properties of alpha-glucosidase from T. pretoriensis YK-1 were similar to those from Saccharomyces cerevisiae.

Amino Acid Sequence↗

The inhibitory effect of noradrenaline on thyrotrophin-stimulated 3,5,3'-tri-iodothyronine and thyroxine release is mediated through a Ca(2+)-dependent process in the thyroid gland of the mouse.

We examined the effect of noradrenaline on the release of 3,5,3'-tri-iodothyronine (T3) and thyroxine (T4) from perifused mouse thyroid. Noradrenaline suppressed the thyrotrophin (TSH)-stimulated release of T3 and T4. The addition of prazosin, which is a specific alpha 1 antagonist, or the depletion of Ca2+ from the perifusion buffer completely abolished the inhibitory effect of noradrenaline on TSH-stimulated T3 and T4 release. Noradrenaline did not inhibit TSH-stimulated cyclic adenosine 3',5'-monophosphate (cAMP) release in the presence of 3-isobutyl-1-methylxanthine (IBMX), which inhibits both cAMP-specific and calmodulin-sensitive phosphodiesterases. Noradrenaline significantly suppressed the TSH-stimulated release of T3 and T4 in the presence of IBMX. These results suggest that the inhibitory effect of noradrenaline on TSH-stimulated T3 and T4 release is not mediated through a cAMP-dependent process or the activation of a calmodulin-sensitive phosphodiesterase, and that this inhibition is mediated through a Ca(2+)-dependent process regulated by the alpha 1-adrenergic system in the mouse thyroid.

1-Methyl-3-isobutylxanthine↗

Clinical experience with expanded polytetrafluoroethylene sheet used as an artificial dura mater.

Dural repair using chemically treated cadaveric dura mater often results in atrophic and fragile change of the substitute as well as adhesion between the dura mater and brain surface at reoperation. Creutz-feldt-Jakob disease has occurred after repair using cadaveric dura mater. Expanded polytetrafluoroethylene (EPTFE) surgical sheet was used for dural repair in 34 patients. Suturing of EPTFE was easy and the incidence of cerebrospinal fluid accumulation in the epidural space was the same as when cadaveric dura mater was used. Six patients underwent reoperation, 1-15 months after the first operation. At reoperation the EPTFE sheet showed no change except for becoming transparent, and the strength was well preserved. A very thin layer of granulation tissue was formed between the EPTFE sheet and brain surface, but the EPTFE sheet was easily detached from the brain surface without adhesion even 15 months after the first operation. Our results suggest that the EPTFE sheet can be used safely and effectively as an artificial dura mater.

Brain Diseases↗

[Morphological changes in the supporting cells of the utricular macula due to streptomycin intoxication].

Morphological changes in cultured utricular supporting cells following streptomycin sulfate (SM) intoxication were investigated using an organ culture system. Utricles of guinea pig were exposed to 30 and 3mg/ml of SM for 1-3 days in culture. The number of lysosomes in the supporting cells increased daily, and mitochondria, myeloid bodies, granules and vesicles were observed within the lysosomes. As these components accumulated in the lysosomes, the number of granules and vesicles in the cytoplasma decreased. Acid phosphatase (AcPase) activity also decreased. After 1-3 days culture with SM, the culture medium was changed to a medium without SM. After removal of SM, the Golgi apparati appeared more developed and AcPase activity was higher. At the same time, lysosomes were markedly decreased in number and the endoplasmic reticulum showed a gradual reproduction. These findings suggest close relationships among the Golgi apparatus, lysosomes, secretory granules and the endplasmic reticulum.

Acid Phosphatase↗

Small cell carcinoma of the esophagus with an esophago-mediastinal fistula successfully treated by chemoradiation therapy and intubation: a case report.

A case of esophageal small cell carcinoma with cervical node metastases and an esophago-mediastinal fistula was treated successfully by chemoradiotherapy. The fistula, after irradiation, was handled successfully by esophageal intubation, followed by infusional 5-fluorouracil and cisplatinum chemotherapy, resulting in the closure of the fistula. Two courses of concurrent chemoradiotherapy, followed by additional cisplatinum and etoposide chemotherapy, were administered. The tumor, including the cervical lymph node metastases, disappeared completely after the treatment.

Antineoplastic Combined Chemotherapy Protocols↗

[Effects of interferon-gamma on cytotoxicity of murine activated macrophages against murine glioma cells].

We studied the effects of mouse IFN-gamma on the cytotoxic activity of murine activated macrophages (M phi) against mouse VM-Glioma cells (H-2b). Activated M phi were obtained from peritoneal exudate cells of mice from four strains, C57BL/6 (H-2b), C3H/He(H-2k), DBA/2 (H-2d), and BALB/c (H-2d), following intraperitoneal injection of (1) LPS 200 micrograms, (2) BCG 200 micrograms, (3) C. parvum 200 micrograms, or (4) MDP 350 micrograms 7 days prior to 20-hr 51Cr release-assay. Of the various combination of mouse strains and activating agents tested, that of activated M phi of the C3H/He mouse with induction by LPS had the most tumoricidal effect against the glioma cells, which was not MHC restricted. Although LPS-activated M phi underwent marked loss of cytotoxicity following initiation of in vitro culture, this 24 hr pretreatment with IFN-gamma inhibited this reduction in tumoricidal effects in a dose-dependent fashion. On the other hand, 24 hr pretreatment of target cells with IFN-gamma did not increase their susceptibility to lysis by activated M phi. These findings suggest that IFN-gamma augments the in vitro tumoricidal activation of M phi; This effect appears to be unrelated to any influence of IFN-gamma on target sensitivity to lysis by macrophages.

Animals↗

[Two-chambered right ventricle--a comparison of the methods of releasing stenosis in the right ventricle].

Twenty-four patients who underwent radical correction for two-chambered right ventricle from 1973 to 1990 were classified into 3 groups according to the method used for releasing the stenosis in the right ventricle; Group A (n = 7): resection of thickened fibrous tissue; Group B (n = 13): resection of the fibrous tissue and abnormal muscular bundles; and Group C (n = 4): resection of the fibrous tissue and abnormal muscular bundles with patch-enlargement of the right ventricular outflow tract. Postoperative cardiac catheterization was performed in the 22 patients. The pressure gradient between the right ventricle and pulmonary artery (RV-PA) at rest was 10 mmHg or less in 5 out of 7 cases in Group A, 7 out of 11 cases in Group B and all 4 cases in Group C. Isoproterenol stress test was performed in patients in whom the RV-PA pressure gradient at rest was low; the right ventricular inflow pressure increased above 50 mmHg in 3 out of 3 cases in Group A and 3 out of 4 in Group B, although it remained below 30 mmHg in 4 out of 4 cases in Group C. In conclusion, patch enlargement of the right ventricular outflow tract is the method of choice for releasing stenosis in the two-chambered right ventricle.

Cardiac Surgical Procedures↗

Survival in synovial sarcoma. A multivariate study of prognostic factors with special emphasis on the comparison between early death and long-term survival.

A retrospective study of 56 patients with synovial sarcoma was done to search for possible prognostic factors affecting survival. In a univariate analysis, age (> or = 20 years), site (proximal), large tumor size (> or = 5 cm), mitotic rate of more than 15 per 10 per high-power fields (hpf), high nuclear grade, tumor necrosis of more than 50%, the presence of rhabdoid cells, a small number of mast cells (< 20/10 hpf), and a high stage according to the criteria of the American Joint Committee (AJC) staging of soft tissue sarcoma, significantly decreased survival (log-rank test; p < 0.05). Moreover, when comparing the 10-year survival (11 patients) and the deaths within 1 year (12 patients), size, high nuclear grade, presence of rhabdoid cells, tumor necrosis, and stage were all considered to be significant prognostic factors (two-sided chi-square test; p < 0.01). In a multivariate analysis (Cox's model), stage was the only strong predictor of a poor prognosis (p = 0.011). We therefore concluded that large tumor size, high nuclear grade, the presence of rhabdoid cells, extensive tumor necrosis, and a high AJC stage were adverse prognostic factors in synovial sarcoma.

Adolescent↗

Enhanced acetylcholine secretion in neuroblastoma x glioma hybrid NG108-15 cells transfected with rat choline acetyltransferase cDNA.

Neuroblastoma x glioma hybrid NG108-15 cells and mouse neuroblastoma N18TG-2 and N1E-115 cells were transiently transfected with the sense cDNA coding for rat choline acetyltransferase (ChAT). All transfected cell lines showed a high level of ChAT activity. ACh secretion was monitored by recording miniature end-plate potentials (MEPPs) in striated muscle cells that had been co-cultured with transfected cells. The number of muscle cells with synaptic responses and the MEPP frequency were higher in co-culture with transfected NG108-15 cells than with control or mock cells. No synaptic response was detected in muscle cells co-cultured with transfected N18TG-2 or N1E-115 cells. The results show that ACh secretion into the synaptic cleft was enhanced due to ChAT overexpression in NG108-15 hybrid cells but not in neuroblastoma cells.

Acetylcholine↗