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Biomedical subjects

T Hata

Publications and source records attributed to T Hata.

At least 271 records · Page 15Linked to original sources
PubMed1995

Successful bone marrow transplantation for idiopathic hypereosinophilic syndrome.

A 21-year-old man who had an increased number of eosinophils with morphological abnormalities, bone marrow fibrosis and multiple organ dysfunction failed to respond to methylprednisolone and hydroxyurea. He was diagnosed with hypereosinophilic syndrome (HES) probably due to myeloproliferative disorder, and underwent allogeneic bone marrow transplantation (allo-BMT) from an HLA-identical sibling. The engraftment was confirmed on day 21 after BMT, but the patient developed acute graft-versus-host disease (GVHD) with grade I veno-occlusive disease, and transient increase of eosinophils of the donor type followed by chronic GVHD of the extensive type. These complications were eventually controlled with cyclosporin A. The patient survived free of disease for more than a year after BMT. Allo-BMT seems to be a possible treatment of HES/MPD.

Adult↗
PubMed1995

Chemical synthesis of phosphopeptides using the arylthio group for protection of phosphate: application to identification of cdc2 kinase phosphorylation sites.

Synthesis of two O-phosphorylated dipeptides, N-Boc-O[S,S-bis(p-methoxyphenyl)phosphorodithioyl] -serylproline and N-Boc-O-[S,S-bis(p-methoxyphenyl) phosphorodithioyl]threonylproline, as new O-phosphorylated dipeptide building blocks for the synthesis of O-phosphorylated peptides, is described. Peptides containing phosphoserine or phosphothreonine were prepared by use of these building blocks in the Boc mode of liquid-phase peptide synthesis. Sites phosphorylated by cdc2 kinase were easily identified using these chemically synthesized phosphopeptides.

Amino Acid Sequence↗
PubMed1995

Ophthalmic artery velocimetry in preeclampsia.

Our objective was to compare ophthalmic artery pulsatility index values from normal pregnant women with those from preeclampsia patients. The ophthalmic artery of 20 normotensive pregnant women, 7 mildly preeclamptic and 2 severely preeclamptic patients was studied once with color Doppler flow imaging and pulsed Doppler ultrasonography after 32 weeks gestation. The peak systolic velocity [49.0 +/- 11.8 (SD) cm/s] in mild preeclampsia was significantly higher (p < 0.0001) than that (32.1 +/- 9.5 cm/s) in normotensive pregnant women, as were the end-diastolic velocity (14.1 +/- 7.7 cm/s vs. 3.7 +/- 1.4 cm/s, p < 0.0001) and time-averaged mean peak velocity (24.4 +/- 10.2 cm/s vs. 10.5 +/- 2.9 cm/s, p < 0.0001). The pulsatility index (1.58 +/- 0.47) in mild preeclampsia was significantly lower (p < 0.0001) than that (2.75 +/- 0.66) in normotensive pregnant women. In the 2 cases of severe preeclampsia, pulsatility index values (case 1: 1.86; case 2: 2.44) in the late stage of the disease process were significantly higher than those (case 1: 1.19; case 2: 1.20) in the early stage. We conclude that mild preeclampsia was associated with a significant decrease in ophthalmic artery vascular resistance, whereas ophthalmic artery vascular resistance in severe preeclampsia increased as the disease process advanced. However, in view of the small number of severe preeclamptic patients, these observations must be considered preliminary.

Adult↗
PubMed1995

Effective treatment of drug-induced agranulocytosis using recombinant human granulocyte colony stimulating factor in pregnancy.

Drug-induced immune system mediated agranulocytosis is a rare but potentially life-threatening condition. There have been only a few reports on the drug-induced agranulocytosis during pregnancy. We present a case of agranulocytosis after prolonged intravenous infusion of ritodrine hydrochloride and additional administration of indomethacin suppositories, effectively treated using recombinant human granulocyte colony stimulating factor without any infection in a mother with twin-to-twin transfusion syndrome. Recombinant human granulocyte colony stimulating factor may have a potential use for drug-induced agranulocytosis during pregnancy.

Adult↗
PubMed1995

Hypoplastic left heart syndrome: color Doppler sonographic and magnetic resonance imaging features in utero.

A 26-year-old Japanese woman, gravida 2, para 1, was referred to our ultrasonography clinic at 27 weeks' gestation, because of a suspected fetal heart anomaly. The hemodynamic examination, specific for hypoplastic left heart syndrome and obtained with color Doppler sonography, gave a clue to an accurate diagnosis of this entity. Moreover, the use of magnetic resonance imaging provided information complementary to the sonographic findings. The sophisticated type of fetal cardiac examination with color Doppler sonography and magnetic resonance imaging was very effective to interpret hypoplastic left heart syndrome with total anomalous pulmonary venous return. An accurate prenatal diagnosis of congenital heart anomalies is useful for obstetrical management.

Adult↗
PubMed1995

Longitudinal Doppler ultrasonographic assessment of alterations in regional vascular resistance of arteries in normal and growth-retarded fetuses.

The objective of this longitudinal study was to evaluate alterations in regional vascular resistance of arteries with advancing gestation in normal and growth-retarded fetuses. Color Doppler flow imaging and pulsed Doppler ultrasonographic assessments were performed on 13 normal and 7 growth-retarded fetuses, ranging from 15 to 40 weeks menstrual age. The pulsatility index was calculated for middle cerebral artery, descending aorta, splenic artery, renal artery, femoral artery and umbilical artery, respectively. Optimal models for these pulsatility index values were determined by regression analysis. A normal range of the pulsatility index for each artery generated in the normal fetuses. In the middle cerebral artery, the models showed a parabolic pattern during pregnancy in the two groups and the predicted pulsatility index values in growth-retarded fetuses were always lower than those in the normal fetuses, especially late in pregnancy. In the renal artery, the predicted pulsatility index values in growth-retarded fetuses were higher than those in normal fetuses near term. In other arteries, the predicted pulsatility index values showed their own specific patterns and there were no significant differences in predicted pulsatility index values in the two groups. In conclusion, alterations in regional vascular resistance of arteries with advancing menstrual age occur evidenced in both normal and growth-retarded fetuses.

Adult↗
PubMed1995

Leukemia developing after 131I treatment for thyroid cancer in a patient with Werner's syndrome: molecular and cytogenetic studies.

A 40-year-old female patient with Werner's syndrome (WS) suffering from thyroid cancer and myelodysplastic syndrome (MDS) is reported. She had been diagnosed as having WS complicated with thyroid cancer seven years previously. Total thyroidectomy and radioactive iodine (131I, 100 mCi/year) therapy for seven years had slowed the progression of thyroid cancer. She suffered a sudden onset of MDS at the age of 40 years. After six months she died from overt leukemia. We found an additional chromosome aberration of chromosome 10 in the progression of leukemia from MDS.

Adenocarcinoma, Papillary↗
PubMed1995

Sex-dependent and independent renal excretion of nilvadipine metabolites in rat: evidence for a sex-dependent active secretion in kidney.

1. To clarify the mechanism of sex-dependent and independent kidney secretion of major nilvadipine metabolites (3, 7) in rat, renal clearance corrected for protein binding and glomerular filtration rate (GFR) was measured in both sexes. The effect of probenecid, an inhibitor of organic anion transport, on these measurements was also investigated. 2. Clear sex-dependent active secretion was observed in the renal excretion of 3 (3-carboxylic acid pyridine derivative). In the female rat, 3, clearance was approximately 32-fold greater than GFR and was markedly decreased by probenecid. Conversely, in the male rat, renal clearance of 3 was only a fraction of GFR and was unaffected by probenecid. 3. Sex-independent active secretion was observed in the renal excretion of 7 (5-carboxylic acid pyridine derivative). In both sexes of rat 7 clearance was about 22-fold greater than GFR and was markedly reduced by probenecid. 4. A clear presence of sex-dependent and independent active secretion mechanisms in the kidney has been demonstrated in rat. The female rat is able to eliminate 3 and 7 in urine by an active secretion mechanism that is inhibited by probenecid. In the male rat, a transport mechanism for 7 is present, but either lacks or is apparently inactive for 3.

Animals↗
PubMed1995

Species and sex differences of testosterone and nifedipine oxidation in liver microsomes of rat, dog and monkey.

1. Species and sex differences in testosterone hydroxylation and nifedipine oxidation in liver microsomes from rat, dog and monkey have been investigated. 2. The formation of 2 alpha-, 2 beta-, 6 beta-, and 16 alpha-hydroxytestosterone and androstenedione in the male rat was higher than that in the female rat. Microsomes prepared from the male rat oxidized nifedipine about eight times faster than did those from the female rat. In contrast, marked sex-related differences were not seen in the dog and monkey. 3. Nifedipine oxidase activity in rat, dog and monkey correlated significantly with the activities for both testosterone 2 beta-hydroxylation and 6 beta-hydroxylation, suggesting the involvement of P4503A isozymes in these reactions. The ratios of formation of the 2 beta- to 6 beta-hydroxytestosterone in male rat and monkey were 0.17 and 0.18 respectively, whereas that in dog was 0.46. The corresponding activity ratios catalysed by P450DPB-1, a P4503A isoform purified from dog liver microsomes, was 0.36. 4. The formation of 16 beta-hydroxytestosterone was higher than that of the 16 alpha-hydrolated metabolite in liver microsomes from monkey, whereas 16 alpha-hydroxytestosterone was the predominant metabolite in the rat and dog, indicating species differences in stereoselectivity at the 16-position.

Animals↗
PubMed1995

Species- and gender-related differences in amine, alcohol and phenol sulphoconjugations.

1. Species-, gender- and strain-related differences in amine sulphoconjugations were studied in 105,000 g supernatants of liver samples isolated from mouse, rat, guinea pig, rabbit, dog, monkey and man and were compared with those of alcoholic and phenolic compounds. Substrates examined were desipramine (an alkylamine), piperazine and piperidine derivatives (alicyclic amines), aniline (an arylamine), tiaramide and dehydroepiandrosterone (alcoholic compounds) and 2-naphthol (a phenolic compound). 2. Sulphoconjugating activities of alicyclic and aryl-amines and tiaramide varied depending on the animal species, sex and strain used. In all animal species examined, the activity for desipramine was low or negligible but for 2-naphthol was consistently detected and high. Amine sulphoconjugations were higher in rabbit than in other animal species. Dog hepatic 105,000g supernatants exhibited low or neglible activities for amines and tiaramide. Females showed higher sulphoconjugating activities for all substrates in mouse and for amines and tiaramide in rat; males exhibited higher activities for 2-naphthol in rat and monkey and for amines in rabbit; there were no clear sex-related differences in other sulphoconjugations. 3. Among BALB/c, C57BL/6, DBA/2, and AKR mouse strains, the AKR strain showed higher activities towards amines and tiaramide than others. 4. In human liver 105,000g supernatants, sulphoconjugating activities for alicyclic amines, dehydroepiandrosterone, and 2-naphthol were detected. Among them, higher activities were observed in piperazine and phenol sulphoconjugations. There were no sex-related differences in the activities of all substrates examined. Good correlations were observed in activities between alicyclic amine and dehydroepiandrosterone sulphoconjugations. 5. These results indicate that activities of amine and alcohol sulphoconjugations vary considerably depending on the substrate, species, sex and strain but phenol sulphoconjugation is consistently detected in all species examined.

Adolescent↗
PubMed1995

Osteotropic drug delivery system (ODDS) based on bisphosphonic prodrug. I: synthesis and in vivo characterization of osteotropic carboxyfluorescein.

An osteotropic drug delivery system (ODDS) based on a bisphosphonic prodrug was designed as a novel method for site-specific and controlled delivery of drugs to the bone. Due to the chemical adsorption of bisphosphonic promoiety to the mineral component, hydroxyapatite, a bisphosphonic prodrug is predominantly taken up into the bone. To verify the concept, bisphosphonic promoiety was chemically introduced into 6-carboxyfluorescein (CF) as a model compound and the disposition after intravenous injection was studied in rats. The bisphosphonic prodrug of CF, disodium (fluorescein-6-carbonyloxy) acetoaminomethylene bisphosphonate (CF-BP) was highly taken up to the skeleton (62.1% of dose) and the remainder was excreted into the urine (35.9% of dose). Subsequently, regeneration of CF by hydrolysis of CF-BP in the bone was observed. The microscopic observation showed that CF-BP was buried into the bone with a calcification of the bone. According to the remodeling of the bone, bisphosphonic prodrug buried was supposed to be released in the vicinity of the osteoclast or resorption surface of the bone. Thus, it is suggested that ODDS has a potential to achieve osteoclast-specific or resorption surface-specific targeting of the drugs.

Animals↗
PubMed1995

Further metabolism of FK506 (tacrolimus). Identification and biological activities of the metabolites oxidized at multiple sites of FK506.

To characterize the metabolic pathway of FK506 (tacrolimus), FK506 or its 31-O-desmethyl metabolite was incubated with liver microsomes prepared from dexamethasone-treated rats in the presence of a NADPH-generating system under aerobic conditions. Besides the four oxidized metabolites already reported, four new metabolites were isolated and identified by HPLC, mass spectrometry, and NMR spectroscopy, and their biological activities were examined. The di-demethylated metabolites at the 15- and 31-, 13- and 31-, and 13- and 15-methoxy groups of FK506, were designated respectively as M-V, M-VI, and M-VII. The fourth, M-VIII, was the metabolite produced after O-demethylation at the 31-methoxy group and formation of a fused 10-membered ring structure through the 19- to 22-carbon of the macrolide ring after oxidation of the 19-methyl group, and of the 36- and 37-vinyl group of FK506. The immunosuppressive activity of the isolated metabolites was estimated in a mouse mixed lymphocyte reaction system and the IC50 values for M-V, M-VI, M-VII, M-VIII, and FK506 were > 1000, 8.78, > 1000, 15.27, and 0.11 ng/ml, respectively. Reactivity of the metabolites with mouse anti-FK506 monoclonal antibody was studied and immunocrossreactivity of M-V was 92.3% of FK506, but no reactivity was observed for M-VI, M-VII, and M-VIII. FK506 thus was metabolized at multiple sites by rat hepatic microsomes and the metabolites formed (M-V) - (M-VIII) exhibited weak or negligible immunosuppressive activity.

Animals↗
PubMed1995

[Trial of combined cytosine arabinoside with granulocyte colony-stimulating factor therapy or refractory acute myeloid leukemia].

Thirteen cases, including 10 relapse cases, of refractory acute myeloid leukemia (AML) (aged 17-70, median 46) by cytosine arabinoside (Ara-C) combined with granulocyte colony-stimulating factor (G-CSF) simultaneously to enhance the sensitivity to Ara-C. Low dose Ara-C (10-40 mg/day) combined with G-CSF was administered in most of them. Complete (CR) and partial remission (PR) were achieved in 5 and 4 patients, respectively, and response (CR + PR) rate was 69.2%. We obtained 5 CRs and 3 PRs in 10 patients with relapsed AML. However, CR and PR duration was short in all cases. None of the 3 patients with MO, AML transformed from myelodysplastic syndrome (MDS), and de novo AML with trilineage myelodysplasia (TMDS) had any response. There was no leukemic colony formation in the culture medium containing G-CSF in the nonresponding patients. The combination therapy caused severe myelosuppression, and most patients experienced prolonged neutropenia, and suffered from infections. In some patients enhanced chemosensitivity of leukemic cells induced by G-CSF was indicated but, the effect of this approach must be determined by large scale controlled studies.

Adolescent↗