Biomedical subjects

Y Ohno

Publications and source records attributed to Y Ohno.

At least 19 recordsLinked to original sources

PubMed1992

A novel post-translational incorporation of tyrosine into multiple proteins in activated human neutrophils. Correlation with phagocytosis and activation of the NADPH oxidase-mediated respiratory burst.

Activation of human neutrophils by PMA causes a post-translational incorporation of 14C-labeled tyrosine into multiple neutrophil (PMN) proteins, that is distinctly different from the enzymatic tyrosinolation of tubulin in FMLP-stimulated PMN. Post-translational incorporation of other radiolabeled amino acids, including the structurally similar amino acid phenylalanine, does not occur under identical conditions of neutrophil activation, suggesting an involvement of the phenolic hydroxyl group of tyrosine in the PMA-mediated reaction. Similar to the stimulation of PMN tubulin tyrosinolation by FMLP, the PMA-induced incorporation of tyrosine into multiple PMN proteins is closely associated with activation of the NADPH oxidase-mediated respiratory burst in stimulated PMN and can be inhibited by a variety of reducing agents, inhibitors of peroxidase-mediated reactions, and intracellular scavengers of oxygen radicals. Moreover, the PMA-induced post-translational incorporation of tyrosine does not occur in PMN from patients with chronic granulomatous disease and is significantly reduced (50%) in PMN of an individual with myeloperoxidase deficiency. A similar stimulus-induced incorporation of tyrosine into multiple PMN proteins is also observed in PMN exposed to various phagocytic stimuli, and the incorporated radioactivity in cells undergoing phagocytosis is substantially enriched (40- to 50-fold) in isolated PMN phagolysosomes. Consistent with this latter observation, HPLC fractionation of stimulated PMN proteins and analysis of the incorporated radioactivity reveal that the 14C label is primarily associated with PMN membrane proteins. Furthermore, this post-translational incorporation of tyrosine, like that associated with PMA stimulation, is associated with production of oxygen radicals and the generation of protein carbonyl derivatives, which are indicative of oxidative protein modifications via mixed function oxidases. Our findings indicate that tyrosine incorporation into membrane proteins of stimulated PMN is functionally relevant to the physiologic host-defense responses of human neutrophils undergoing phagocytosis.

Blood Proteins↗

PubMed1992

Estimation of the rate constants associated with the inhibitory effect of okadaic acid on type 2A protein phosphatase by time-course analysis.

As is often the case with tightly binding inhibitors, okadaic acid produces its inhibitory effect on type 2A protein phosphatase (PP2A) in a time-dependent manner. We measured the rate constants associated with the binding of okadaic acid to PP2A by analysing the time-course of the reduction of the p-nitrophenyl phosphate (pNPP) phosphatase activity of the enzyme after application of okadaic acid. The rate constants for dissociation of okadaic acid from PP2A were also estimated from the time-course of the recovery of the activity from inhibition by okadaic acid after addition of a mouse IgG1 monoclonal antibody raised against the inhibitor. Our results show that the rate constants for the binding of okadaic acid and PP2A are of the order of 10(7) M-1.s-1, a typical value for reactions involving relatively large molecules, whereas those for their dissociation are in the range 10(-4)-10(-3) s-1. The very low values of the latter seems to be the determining factor for the exceedingly high affinity of okadaic acid for PP2A. The dissociation constants for the interaction of okadaic acid with the free enzyme and the enzyme-substrate complex, estimated as the ratio of the rate constants, are both in the range 30-40 pM, in agreement with the results of previous dose-inhibition analyses.

Animals↗

PubMed1992

Musk xylene is a novel specific inducer of cytochrome P-450IA2.

The effect of musk xylene on contents of both cytochrome P-450IA1 and cytochrome P-450IA2 in rat liver was investigated using Western blotting analysis. Rats were treated i.p. for five consecutive days with either 50, 100 or 200 mg musk xylene/kg body weight. Musk xylene increased both total cytochrome P-450 and cytochrome b5 contents in rat liver microsomes. Musk xylene induced cytochrome P-450IA2 (384 pmol/mg protein) strongly and preferentially and the ratio of cytochrome P450IA2/P-450IA1 was about 12 at the lowest dose tested. Musk xylene also induced the cytochrome P-450IA1 dose-dependently, but these extents were very small (32-174 pmol/mg protein). These results suggest that musk xylene may be a more specific inducer for cytochrome P-450IA2 than any other inducers reported.

Animals↗

PubMed1992

[A case of significant, non-neoplastic, ovarian hypertestosteronism].

A 24-year-old female with significant ovarian hypertestosteronism, who responded well both to gonadotropin releasing hormone (GnRH) agonist and cyclic administration of estrogen and gestagens in terms of suppressing circulating testosterone levels is reported. The patient's menstrual periods had been regular since menarche at the age of 12 until she became amenorrheic at the age of 20. She visited our facility in November 1988 after receiving three cycles of estrogen and gestagen replacement therapy from a previous physician which caused withdrawal bleeding. Clomiphen citrate reportedly failed to induce apparent ovulation. On her first visit with us, she was 160 cm tall weighing 47 kg with apparent hoarseness but not with hirsutism. Pelvic examination revealed significant clitoromegaly but otherwise normal external and internal genitalia. Laparoscopic examination disclosed that her uterus appeared to be normal with bilateral ovaries relatively small (4 x 4 x 3 cm) without tumorous or polycystic appearance. Histological examination of her ovaries obtained at laparoscopy showed several primary follicles with mild infiltration of the stromal cells. No thickened tunica albuginea or cystic formation were observed. These findings did not support either polycystic ovary or hyperthecosis. Serum testosterone (T) levels were extremely high (7.1 ng/ml), while serum androstenedione levels were only slightly above normal range (3.1 ng/ml). Urine 17-KS excretion was slightly increased (6.1 mg/day), while 17-OHCS output was within normal range (4.0 mg/day). Basal serum LH and FSH levels were within normal range and LH pulse frequency was reduced to 1 in 4 hours. Administration of dexamethasone 1 mg/day for 2 days did not suppress circulating T and free T levels but lowered serum cortisol concentration and urine excretion of 17-OHCS. Blood glucose and insulin levels were within normal limits and their responses to oral glucose administration were normal. Abdominal and pelvic ultrasonography and computed tomography as well as adrenal scintigraphy did not reveal any tumorous lesions in bilateral adrenals and ovaries. Administration of GnRH agonist, Buserelin 900 micrograms/day, suppressed circulating T concentrations to 0.7 ng/ml in 8 days, while it had no significant effects on DHEA and DHEA-S levels. After 16 weeks of Buserelin administration, ovulation was successfully induced by hMG administration. Cyclic estrogen and gestagen replacement therapy by Kaufmann's schedule for 2 cycles also suppressed serum T levels to normal, female range. Thus, the present case represents non-neoplastic, non-PCO, ovarian hypertestosteronism which responded well both to GnRH agonist and estrogen and gestagen replacement therapy in terms of lowering circulating T levels.

Adult↗

PubMed1992

Effect of tetrakis-mu-3,5-diisopropylsalicylatodiaquodicopper(II) on the status of reduced glutathione in freshly isolated hepatocytes.

Effects of different concentrations of tetrakis-mu-3,5-diisopropylsalicylatodiaquodicopper(II) (Cu(II)2(3,5-DIPS)4(H2O2)2) on the reduced status of glutathione (GSH), the major nonprotein thiol in tissues, were investigated using freshly isolated hepatocytes. Cu(II)2(3,5-DIPS)4 below 100 microM did not have any significant effects on either the GSH content or viability of the hepatocytes, but at 150-250 microM it decreased both parameters after 1 h of incubation. The decrease in cellular GSH was not followed by an increase in the oxidized form of GSH (GSSG) in the cell suspension. The addition of deferoxamine with Cu(II)2(3,5-DIPS)4 to the hepatocyte suspension prevented depletion in GSH content and loss of cell viability by Cu(II)2(3,5-DIPS)4. Both GSH depletion and loss of cell viability were found to be Cu(II)2(3,5-DIPS)4 dose dependent. From these results, it appears that Cu(II)2(3,5-DIPS)4 penetrated the cell membrane and acted by decreasing the GSH level by forming a copper-glutathione complex.

Animals↗

PubMed1992

N-nitrosodialkylamine dealkylation in reconstituted systems containing cytochrome P-450 purified from phenobarbital- and beta-naphthoflavone-treated rats.

Five cytochrome P-450 forms were purified from livers of rats pretreated with phenobarbital (PB) or beta-naphthoflavone (BNF), and the oxidative dealkylation of N-nitrosodialkylamines by the reconstituted cytochrome P-450 systems was measured. PB-II (P450IIB1) showed very high N-nitrosomethybutylamine (NMBA) debutylase activity, high NMBA demethylase activity and high N-nitrosomethyl-benzylamine (NMBeA) debenzylase activity, suggesting that the increase following PB treatment in hepatic microsomal NMBA debutylation and NMBeA debenzylation was due to the induction of PB-II. BNF-H (P450IA2) showed very high NMBA debutylase and high NMBeA debenzylase activities, and BNF-L (P450IA1) showed NMBA debutylase and high NMBeA debenzylase activities. These results suggested that the increase by BNF pretreatment in hepatic microsomal NMBA debutylation was due mainly to the induction of BNF-H and in some part to that of BNF-L. PB-II also showed very high dealkylation activity of lipophilic N-nitrosodialkylamines with long alkyl moieties. On the other hand, BNF-H dealkylated N-nitrosodipropylamine (NDPA), N-nitrosomethylbutylamine (NMBA) and N-nitrosoethylbutylamine (NEBA) at higher rates than N-nitrosodibutylamine (NDBA). BNF-L dealkylated NEBA at higher rates than NMBeA and NDBA. These results reveal that substrate specificity of each cytochrome P-450 form in N-nitrosodialkylamine metabolism is different from each other and several forms of cytochrome P-450 support each N-nitrosamine dealkylase activity in mammalians.

Animals↗

PubMed1992

Indium inhibits gap junctional communication between rat hepatocytes in primary culture.

The effect of indium on gap junctional communication was investigated in primary cultured rat hepatocytes. Treatment of hepatocytes with indium chloride at concentrations of 100 microM to 1 mM for 2 h resulted in dose-dependent inhibition of gap junctional communication between hepatocytes. The effect of indium on hepatocytes was also evaluated using two indices for cell viability: lactate dehydrogenase (LDH) leakage and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction. Indium did not cause any increase in LDH leakage from hepatocytes at the above concentrations, but inhibition of MTT reduction was observed at concentrations above 500 microM. These results suggest that the gap junctions between hepatocytes may be vulnerable sites to indium toxicity.

Animals↗

PubMed1992

Generation of active oxygen species in vitro by the interaction of potassium bromate with rat kidney cell.

Active oxygen species derived from the interaction of potassium bromate (KBrO3), a rat renal carcinogen, with cells from rat kidney and other organs were examined by electron spin resonance spectrometry using the spin trapping agents 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and 2,2,6,6-tetramethylpiperidine (TEMP). DMPO-OH, an indicator of hydroxyl radical production, was generated from KBrO3 by kidney cells or homogenate, but not by liver preparations and to only a limited extent by heart and brain homogenates, suggesting relative kidney specificity. To assess what chemical components are responsible for production of DMPO-OH, several physiologically related materials were examined. Glucose, saccharose, albumin and methyl linolate were found not to be involved in the KBrO3 reaction, but reduced glutathione and also ferric ions participated to produce DMPO-OH. In addition, DMPO-OH production derived from the reaction of KBrO3 with kidney homogenate was not affected by superoxide dismutase, catalase or hydroxyl radical scavengers such as DMSO or ethanol, but was effectively inhibited by singlet oxygen scavengers such as histidine and NaN3, implying singlet oxygen production. To assess this possibility, TEMP was used as a trapping agent, and TEMPO, derived from singlet oxygen, was found to be produced by the reaction of KBrO3 with homogenates of kidney, but not of liver. Furthermore, singlet oxygen production was confirmed by studies of chemiluminescence using 2-methyl-6-phenyl-3,7-dihydroimidazo[1,2a]pyrazine-3-one. As a control, DMPO-OH was also demonstrated to be produced by a known singlet oxygen source, toluidine blue plus light. The results thus indicate that singlet oxygen is a very probably candidate for the active oxygen species generated in the specific interaction of KBrO3 with rat kidney cells in vitro. This raises the question of its concern with renal carcinogenicity in vivo.

Animals↗

PubMed1992

Malignant lymphomas of the nasal cavity and paranasal sinuses. A clinicopathologic and immunohistochemical study.

The clinicopathologic and immunohistological features of 20 Japanese patients with non-Hodgkin's lymphomas (NHLs) limited to the sinonasal area were studied using a broad panel of T- and B-cell markers on paraffin-embedded and fresh frozen tissue. All cases showed a diffuse growth pattern. Nine cases were B-cell lymphomas (immunoblastic n = 4, centroblastic n = 3, immunocytoma n = 1, centrocytic n = 1), and nine were T-cell lymphomas (pleomorphic medium and large cell n = 8, angioimmunoblastic n = 1). In two cases, the cell lineage could not be determined. No morphologic features of angiocentric/angiodestructive lymphoproliferative lesions or lymphoepithelial lesions in ductal or glandular epithelium were seen in our series. Eight (89%) of the nine T-cell tumors and four (44%) of the nine B-cell neoplasms involved both the nasal cavity and paranasal sinuses. Six of the nine T-cell neoplasms showed a clinical presentation of rhinitis, whereas all of the B-cell neoplasms showed tumor masses in the nasal cavity and/or paranasal sinuses. The two-year survival rate for T-cell lymphomas was poorer than that for B-cell lymphomas. The five-year survival of patients with NHLs involving both the nasal cavity and paranasal sinuses was also poorer than that of patients in whom NHLs were limited to the nasal cavity.

Adult↗

PubMed1992

VDD pacing with a previously implanted single lead system.

Three patients who had undergone implantation of a rate modulated, atrial sensitive RS4 pacemaker, with a single orthogonal lead underwent replacement of a depleted unit with a DDD pulse generator, reusing the original lead with an adapter that allowed conversion of the bipolar atrial electrode into unipolar configuration. The mean atrial electrogram amplitude was 1.8 mV and no significant atrial sensing defects were found during Holter monitoring. As the RS4 pulse generator is no longer available, continued VDD pacing is possible by replacing it with a DDD pulse generator using the previously implanted single lead system.

Aged↗

PubMed1992

Clinical significance of QRS duration during ventricular pacing.

To clarify the clinical significance of an abnormally prolonged paced QRS duration, we studied 114 patients who had undergone pacing for atrioventricular block (AVB). Patients were divided into two groups: group I consisted of 29 patients with at least one paced QRS duration greater than or equal to 180 msec during the follow-up period; group II consisted of 85 patients with paced QRS durations less than 180 msec. The clinical background, QRS complexes before pacing, and the echocardiographic findings were assessed. Males (P less than 0.05), those with H-V block (P less than 0.05) and a wider QRS complex of conducted and escape beats (both P less than 0.01) were dominant in group I. The incidence of underlying heart disease was greater in group I than in group II (83% vs 32%, P less than 0.01). Reduced left ventricular ejection fraction (LVEF) and increased left ventricular end-diastolic dimension (LVDd) were more prominent in group I than in group II (LVEF 0.49 +/- 0.17 vs 0.68 +/- 0.10, P less than 0.01, LVDd 57.1 +/- 7.9 mm vs 48.5 +/- 5.6 mm, P less than 0.01). The paced QRS duration correlated with LVEF (r = -0.61) and LVDd (r = 0.81). A paced QRS duration greater than or equal to 180 msec was sensitive and specific for a LVEF less than 0.5 (83.3% and 85.2%) and LVDd greater than or equal to 60 mm (100% and 81.4%). We conclude that patients with a prolonged paced QRS duration have more serious heart disease, and the paced QRS duration can be a useful indicator of impaired LV function.

Cardiac Pacing, Artificial↗

PubMed1992

Disturbed calcium metabolism in offspring of hypertensive parents.

To assess a possible heritability of a disturbed calcium metabolism in relation to blood pressure regulation, 28 young normotensive offspring of either hypertensive or normotensive parents were studied while administered a defined diet with daily sodium chloride of 6 and 20 g/day for 7 days each. Before the high salt diet was begun, the cytosolic calcium concentration ([Ca2+]i) in platelets was elevated in offspring of hypertensive parents, whereas serum electrolytes, plasma renin activity, plasma catecholamines, and 24-hour urinary excretion of sodium and calcium showed no difference between the two groups. On exposure to a high salt diet, the mean blood pressure increased (from 80 +/- 2 to 85 +/- 2 mm Hg, p less than 0.05) in offspring of hypertensive parents. These changes in mean blood pressure were positively correlated with the basal platelet [Ca2+]i (r = 0.61, p less than 0.01), whereas [Ca2+]i did not demonstrate any significant changes. When the subjects were administered the high salt diet, plasma ionized calcium decreased (from 2.37 to 2.21 meq/l, p less than 0.05) and 1,25-dihydroxyvitamin D3 increased (from 32.7 to 40.8 pg/ml, p less than 0.05) with a transient relative hypercalciuria in offspring of hypertensive parents. This increase of 1,25-dihydroxyvitamin D3 was significantly correlated with the changes in mean blood pressure (r = 0.62, p less than 0.01). Disturbed intraplatelet and systemic calcium metabolism may be of predictive value in the development of hypertension.

Adolescent↗

PubMed1992

Long-term follow-up study of three patients with the long QT syndrome.

We studied three women with the long QT syndrome. They were aged 42, 52 and 25 years and had experienced recurrent syncopal attacks. We followed case 1 for 17, case 2 for 18, and case 3 for over 6 y. The attacks tended to occur during the premenstrual stage in case 1 and case 2; case 3 often experienced attacks after exercise. The QT(U)c intervals on admission were 0.68, 0.62, and 0.50 in case 1, 2, and 3, respectively. Torsade de pointes followed by ventricular fibrillation was documented in case 1 and case 2. Although each was treated with a beta-blocker, none was fully compliant with the regimen. In case 1, estrogen therapy administered to maintain the hormonal balance premenstrually effectively prevented attacks. Despite the inconsistent use of beta-blockers, the attacks in case 1 and case 2 tended to decrease with age. Case 2 experienced no attacks after menopause. Cause 3 took medication consistently and remained free of attacks for over 6 y. Although she discontinued beta-blocker therapy because of pregnancy, she has experienced no attacks to date. These case studies suggest that hormonal status may be important in the development of syncopal attacks in female patients with the long QT syndrome.

Adult↗

PubMed1992

Serum estradiol 17-sulphate and lipid peroxides in late pregnancy.

Estradiol 17-sulphate is readily converted to 2-OH or 4-OH estradiol 17-sulphate. The latter two strongly antagonize lipid peroxidation, which may play certain roles during pregnancy, such as pregnancy-induced hypertension. Serum estradiol 17-sulphate during mid and late pregnancy was measured using a direct radioimmunoassay without hydrolysis, and the level increased as pregnancy progressed. The levels in the sixth (20-23 weeks) and tenth months (36-39 weeks) of gestation were 1.42 +/- 0.04 nmol/l (mean +/- SD) and 3.42 +/- 1.09 nmol/l, respectively. The maternal venous levels before and at delivery and in the umbilical veins and artery were 3.38 +/- 0.83, 3.48 +/- 1.53, 4.11 +/- 1.40 and 4.30 +/- 1.81 nmol/l, respectively. The latter two values were slightly higher than the former two. Estradiol 17-sulphate in maternal venous blood began to decrease around delivery. Serum lipid peroxides were measured using the method of Yagi. Estradiol 17-sulphate and lipid peroxides showed a simple regression slope (r = -0.548, p less than 0.05) during late pregnancy. These results suggest that estradiol 17-sulphate may be converted to 2-OH or 4-OH estradiol 17-sulphate, which act as lipid peroxide scavengers during pregnancy.

Estradiol↗

PubMed1992

The influence of tetrodotoxin on the toxic effects of aconitine in vivo.

Both aconite toxins (aconitine, mesaconitine, and hypaconitine) and a pufferfish toxin (tetrodotoxin, TTX) were detected in the blood of a legal autopsy case. In order to elucidate the in vivo influence of TTX on the toxic effects of aconitine, a mixture of aconitine and TTX was administered to male ICR mice orally or intraperitoneally. The animal experiments revealed that the time of death due to aconitine was significantly delayed in proportion to the dose of TTX compared with the case for aconitine alone, and that the mortality of aconitine was lowered by TTX when the dose ratio of the two toxins was in a particular range. Accordingly, it is thought that the toxic effects of aconitine are attenuated by TTX in vivo.

Aconitine↗

PubMed1992

[Intraarterial COMPA (cis-diammine-dichloroplatinum (II), vincristine, methotrexate, peplomycin, adriamycin) chemotherapy for bladder cancer].

Seventeen patients with bladder cancer were treated with semiselective intraarterial COMPA chemotherapy. One course of COMPA consisted of 20 mg/m2 cis-diammine-dichloroplatinum (CDDP) on days 4 and 5, 0.6 mg/m2 vincristine (VCR) (Oncovin) on days 1 and 2, 5 mg/m2 methotrexate (MTX) on days 2 and 3, 5 mg/body peplomycin (PEP) on days 1, 2 and 3, and 15 mg/m2 adriamycin (ADM) on day 4. These drugs were injected every 2 or 3 weeks through a polyurethane catheter the tip of which was placed just proximal to the aortic bifurcation and during injection both thighs were tied with a pressure of over 250 mmHg. From 2 to 6 courses (mean, 4.4 courses) were administered. Of the 17 patients, 4 achieved complete remission, 10 achieved partial remission and 3 showed no change. After this COMPA chemotherapy eight patients were able to retain their bladders while seven underwent immediate radical cystectomy. The adjuvant COMPA chemotherapy for two patients with pelvic metastasis after radical cystectomy showed good results. Mild degrees of anorexia, nausea, vomiting, hair loss, numbness of fingers and/or toes, leukopenia and intestinal paralysis were observed. Instrumental troubles were seen in two cases; one involved dislocation of the tip of the catheter, the other was infection of the reservoir. Intraarterial COMPA chemotherapy is effective for neoadjuvant therapy of invasive bladder cancer, bladder-preserving treatment and adjuvant therapy of pelvic metastasis.

Aged↗

PubMed1992

The metabolism of 1,6-dinitropyrene in rat hepatocytes.

This paper reports investigations using hepatocytes to study the metabolism and DNA binding of the environmental contaminant, 1,6-dinitropyrene. Since 1,6-dinitropyrene is not believed to be mutagenic per se, metabolites were synthesized and the metabolism of 1,6-dinitropyrene was subsequently studied in rat hepatocytes. The mode of activation of dinitropyrenes is reduction of one of the nitro groups. Nitroreduction has been shown previously to be oxygen sensitive and therefore the effect of oxygen on the metabolic pattern and DNA binding was investigated by comparing results from aerobic and anaerobic conditions. The binding of [14C]1,6-dinitropyrene equivalents to rat hepatocyte DNA was increased by 15% in the presence of oxygen. Although there was little difference in the rate of 1,6-dinitropyrene metabolism, with or without O2, there was a difference in the metabolic pattern. Under anaerobic conditions there was an increase in the level of the terminal reduction product 1-amino-6-nitropyrene.

Animals↗

PubMed1992

[Clinical assessment of 99mTc-HMPAO scintigraphy in thoracic tumors].

99mTc-hexamethylpropylene amineoxime (99mTc-HMPAO) scintigraphy was performed in 15 malignant tumors in 11 patients and a patient with bronchopneumonia. A high 99mTc-HMPAO affinity for the tumors was observed on SPECT, however, the mean tumor/contralateral normal lung ratios of 99mTc-HMPAO activity (1.26) was lower than that of 201Tl-chloride (2.29). 99mTc-HMPAO uptake was seen not only in the tumors but also in the bronchopneumonia, atelectasis, and irradiated lung (containing radiation fibrosis). Moreover, a diffuse uptake in the lung was seen in a patient received repeated chemotherapy. Therefore, it is emphasized that there is a non-specific 99mTc-HMPAO uptake in those various pulmonary conditions.

Adult↗