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Biomedical subjects

T Hata

Publications and source records attributed to T Hata.

At least 109 records · Page 6Linked to original sources
PubMed1999

Chronic antisense therapy for angiotensinogen on cardiac hypertrophy in spontaneously hypertensive rats.

OBJECTIVE: We examined the effect of the suppression of plasma angiotensinogen (AGT) by the intravenous injection of antisense oligodeoxynucleotides (ODNs) against AGT targeted to the liver on cardiac remodeling in spontaneously hypertensive rats (SHR). The ODNs against rat AGT were coupled to asialoglycoprotein (ASOR) carrier molecules, which serve as an important method for regulating liver gene expression. METHODS: Male SHR (n = 18), and age-matched male Wistar-Kyoto rats (WKY, n = 6) were used for this study. At 10 weeks of age, the SHR were divided into three groups (each group n = 6), and the systolic blood pressure (SBP) did not significantly change among them. The control SHR and WKY groups received saline, the sense SHR group was injected with the sense ODNs complex and the antisense SHR group was injected with the antisense ODNs complex, from 10 to 20 weeks of age. ASOR-poly(L)lysine-ODNs complex was injected via the tail veins twice a week. RESULTS: At the end of the treatment, a reduction of hepatic AGT mRNA, cardiac angiotensin II type 1 receptor mRNA and the plasma AGT concentration was only observed in the antisense-injected SHR but not in the other groups of SHR and WKY. This antisense therapy did not significantly change the mRNA expression for angiotensin converting enzyme, angiotensin II type 2 receptor and AGT in the left ventricle (LV) among all three groups. Although the plasma angiotensin II (Ang II) concentration significantly decreased to the level of WKY after the antisense therapy, the SBP, LV to body weight ratio and % collagen volume fraction also showed a reduction, however, these findings were still larger than in the WKY than in either the sense-injected SHR or control SHR. CONCLUSION: The plasma AGT is considered to play a role in the development of cardiac hypertrophy in SHR, but it has not a complete effects on cardiac remodeling even if the plasma Ang II levels are inhibited because of an insufficient suppression of hypertension.

Analysis of Variance↗
PubMed1999

Comparison of late-second-trimester nonstress test characteristics between small for gestational age and appropriate for gestational age infants.

OBJECTIVE: To compare electronic fetal heart rate (FHR) monitoring characteristics between appropriate for gestational age (AGA) fetuses and small for gestational age (SGA) fetuses and to determine whether SGA fetuses have specific abnormalities at second-trimester electronic fetal monitoring (EFM), using nonstress test. METHODS: Among 953 children born from 1993-1996, we identified 500 singleton infants born after 36 weeks' gestation of uncomplicated pregnancies in whom second-trimester (24-27 weeks' gestation) EFM records were obtained. Individual components of FHR patterns (baseline rate, baseline FHR variability, presence of acceleration [at least 10 beats per minute for at least 10 seconds], and periodic or episodic deceleration [at least 25 beats per minute for at least 15 seconds]) and birth characteristics were compared between AGA and SGA infants, or between pregnancies with or without second-trimester decelerations. RESULTS: Among 500 infants, 443 were AGA and 57 SGA; 105 had and 395 did not have second-trimester decelerations. Baseline FHR variability (12.9+/-3.2 beats per minute) in SGA fetuses was significantly higher than variability (10.3+/-3.4 beats per minute) in AGA fetuses (P<.001). Small for gestational age fetuses were significantly more likely to have second-trimester decelerations than AGA fetuses (33.3% vs. 19.4%, P<.05). There were no significant differences in baseline rate and accelerations between AGA and SGA infants. Small for gestational age infants were more frequent in pregnancies with second-trimester decelerations, compared with those without second-trimester decelerations (18.1% vs. 9.6%, P<.05). Baseline FHR variability in pregnancies with second-trimester decelerations was significantly higher than in pregnancies without second-trimester decelerations (12.2+/-3.7 vs. 10.0+/-3.1 beats per minute, P<.001). CONCLUSION: Periodic or episodic decelerations and increased FHR variability during late second-trimester EFM were associated with an increased risk of SGA birth weight.

Cardiotocography↗
PubMed1999

High rate of chromosomal abnormalities in HTLV-I-infected T-cell colonies derived from prodromal phase of adult T-cell leukemia: a study of IL-2-stimulated colony formation in methylcellulose.

To detect chromosomal abnormalities in prodromal phase of adult T-cell leukemia (ATL), we established a clonal culture method for human T-lymphotropic virus type I (HTLV-I) infected T-cells in methylcellulose containing recombinant human interleukin 2 (rhIL-2). We tried to analyze chromosomes of 187 colonies (4, 23, 69, 74, and 17, from HTLV-I-uninfected normal T-cells, HTLV-I-Infected normal T-cells, HTLV-I carriers, smoldering ATL, and chronic ATL, respectively), using chromosomal banding methods. In the prodromal group, 53% of colonies (84/160) (36/69, 37/74, 11/17 in HTLV-I carriers, smoldering ATLs, and chronic ATL, respectively) had chromosomal abnormal clones. In HTLV-I carriers, multiple clones with simple chromosomal abnormalities were observed. In more progressed chronic ATL, more complex chromosomal abnormalities were detected, and specific colonies were selected. Thus, colonies in the prodromal phase of ATL are characterized by cytogenetical clonal evolution and clonal changes.

Adult↗
PubMed1999

Leptomeningeal melanomatosis with multiple cutaneous pigmented nevi: tumor cell proliferation and malignant transformation in an autopsy case.

We experienced a rare case of leptomeningeal melanomatosis. The proliferative activity and nuclear accumulation of p53 in this tumor were examined, since the relationship between this tumor type and growth has not yet been elucidated. A 33-year-old Japanese man was shown to have leptomeningeal melanomatosis with multiple cutaneous pigmented nevi. The autopsy findings showed the presence not only of benign diffuse melanosis of the leptomeninges but also of leptomeningeal melanomatosis in the subarachnoid space and brain parenchyma. In the brain parenchyma, the direct invasion of tumor cells from the subarachnoid space and Virchow-Robin spaces filled with melanoma cells were observed. Multiple hemorrhagic areas invaded by melanoma cells were also present. Immunohistochemical staining with a monoclonal antibody to melanoma cells showed positivity in the tumor cells. Proliferation analysis using the MIB-1 antibody demonstrated that the labeling index of tumor cells invading brain parenchyma (2.54%) was higher than that in other lesions of the inner (0.89%) and outer layer (0.76%) of the subarachnoid space. Nuclear accumulation of p53 protein was rarely seen in the tumor cells. We reported a case of leptomeningeal melanomatosis. Higher proliferative activity was found in invading cells of the brain parenchyma. Malignant transformation of the tumor did not appear to be associated with p53 gene mutation.

Adult↗
PubMed1999

Multi-clonal expansion of unique human T-lymphotropic virus type-I-infected T cells with high growth potential in response to interleukin-2 in prodromal phase of adult T cell leukemia.

We established a simple IL-2-dependent colony-forming assay for T cells infected with human T-lymphotropic virus type-I (HTLV-I). IL-2-dependent cell lines were subsequently established by expanding individual colonies in liquid cultures. Lymphocyte-rich fractions were prepared from 31 HTLV-I carriers, 12 patients with smoldering ATL, 11 chronic ATL, 12 crisis ATL and 10 acute ATL. Primary colonies of CD4+ p19+ T cells were formed in all cases of carriers, smoldering and chronic ATL, and in 10 of 12 crisis cases. In contrast, no colony was formed from cells of patients with acute ATL. The rate of establishment of cell lines in HTLV-I carriers was significantly lower than that in patients of prodromal phase ATL. Cell lines established from cells of three prodromal cases were clonally identical to the parent ATL cells, while others had clonally distinct cell lines. Our results indicated the presence of four components of HTLV-I-infected T cells: (1) normal carrier T cells capable of forming colonies but not cell lines; (2) pre-malignant T cells capable of forming colonies as well as cell lines; (3) malignant T cells capable of forming colonies as well as cell lines; (4) fully malignant T cells unresponsive to IL-2. Our results suggest the presence of a multiclonal expansion of unique T cells in the prodromal phase of ATL, which have a high growth potential in response to IL-2. The coexistence of multiclonality with a dominant ATL clone may be closely related to the underlying pathology in HTLV-I leukemogenesis.

Case-Control Studies↗
PubMed1999

N-sulphoconjugation of amines by human cytosolic hydroxysteroid sulphotransferase.

1. N- and O-sulphoconjugation of various substrates were studied with human liver cytosol and purified cytosolic sulphotransferase in the presence of 3-phosphoadenosine 5-phosphosulphate. 2. Human liver cytosol catalysed N-sulphoconjugation of alicyclic and aryl-amines, and O-sulphoconjugation of hydroxysteroid and phenol. Activities of amine sulphoconjugation in the cytosol correlated well with those of hydroxysteroid but not with phenol. 3. Alicyclic amine sulphotransferase in human liver cytosol was purified to homogeneity by anion exchange, affinity and hydroxyapatite chromatography. Sulphoconjugating activities of alicyclic amine co-purified with those for hydroxysteroid conjugation. Subunit molecular weight of the purified sulphotransferase was 34 kDa. Contents of the purified enzyme correlated with the sulphoconjugating activities of hydroxysteroid and alicyclic amine. From these results, we concluded that the alicyclic amine sulphotransferase purified in this study was identical to hydroxysteroid sulphotransferse in human liver cytosol. 4. The results of this study indicate that hydroxysteroid sulphotransferase in human liver cytosol catalyses N-sulphoconjugation of alicyclic and aryl-amines. Hydroxysteroid sulphotransferase in the cytosol is reported to catalyse O-sulphoconjugations of various compounds including hydroxysteroids, bile acids, cholesterol, and aliphatic and benzylic alcohols. The present and previously reported results indicate that hydroxysteroid sulphotransferase in the cytosol catalyses both N- and O-sulphoconjugations of several substrates.

Amines↗
PubMed1999

Identification of cytochrome P450 enzymes involved in the metabolism of zotepine, an antipsychotic drug, in human liver microsomes.

1. Studies using human liver microsomes and recombinant human cytochrome P450 (P450) enzymes and flavin-containing monooxygenase (FMO) were performed to identify the enzymes responsible for the formation of zotepine metabolites in man. 2. Human liver microsomes produced four metabolites and a tentative order of importance was: norzotepine, 3-hydroxyzotepine, zotepine S-oxide and 2-hydroxyzotepine. Zotepine N-oxide was also detected, but it could not be quantified. 3. The rates of formation of the major metabolite, norzotepine, and zotepine S-oxide (at a substrate concentration of 20 microM) were significantly correlated with the testosterone 6beta-hydroxylase activities and CYP3A4 contents of the 12 different human liver microsomal samples. Inhibition studies with P450 enzyme selective inhibitors and anti-rat CYP3A2 antibodies also indicated a predominant role of CYP3A4 in the formation of norzotepine and zotepine S-oxide. Furafylline and sulphaphenazole inhibited the N-demethylation of zotepine by up to approximately 30%. 4. Correlation and inhibition data for the 2- and 3-hydroxylation of zotepine were consistent with the predominant role of CYP1A2 and 2D6 in the formation of these metabolites, respectively. 5. Recombinant CYP1A1, 1A2, 2B6, 2C19, 3A4 and 3A5 efficiently catalysed N-demethylation of zotepine. CYP1A1, 1A2, 2B6 and 3A4 were also active for S-oxidation. CYP1A2 and 2D6*1-Val374 efficiently produced 2-hydroxyzotepine and 3-hydroxyzotepine, respectively. Recombinant human FMO3 did not catalyse zotepine S-oxidation. 6. These results suggest that both the N-demethylation and S-oxidation of zotepine are mediated mainly by CYP3A4, and that CYP1A2 and 2D6 play an important role in the 2- and 3-hydroxylation of zotepine, respectively.

Antipsychotic Agents↗
PubMed1999

Saline infusion contrast intrauterine sonographic assessment of the endometrium with high-frequency, real-time miniature transducer in normal menstrual cycle: a preliminary report.

Normal endometrial texture was visualized using saline infusion contrast intrauterine sonography with a specially developed 20 MHz flexible catheter-based high-resolution, real-time miniature (2.4 mm outer diameter) ultrasound transducer in primary infertile women (n = 15) with a normal menstrual cycle. All the women had <2 years infertility duration and were studied in proliferative, and early or mid-secretory phases. Before intrauterine sonography, transvaginal sonographic assessment of the endometrium was conducted. The overall image clarity was subjectively compared between intrauterine and transvaginal sonography. Most endometrial textures in both proliferative and secretory phases were viewed more easily with intrauterine rather than transvaginal sonography, and this was especially true with an intrauterine saline infusion technique. Moreover, it was possible to obtain finer image quality of very small endometrial interfacial and internal textures with intrauterine sonography. However, the depth of penetration of the ultrasound beam is only approximately 2 cm, therefore examination of larger pathological endometrial lesions is markedly limited because of the shallow scanning range of the high-frequency transducer. Intrauterine sonography may be a valuable tool in imaging endometrial texture in normal menstrual cycle, and possibly in infertility practice, complementing and not replacing transvaginal sonography.

Computer Systems↗
PubMed1999

Hepatocyte growth factor concentration in the early second-trimester amniotic fluid does not predict fetal growth at birth.

The purpose of this study was to evaluate whether hepatocyte growth factor (HGF) concentrations in the early second-trimester amniotic fluid predict fetal growth at birth. HGF and insulin-like growth factor-I (IGF-I) concentrations in the early second-trimester amniotic fluid were measured in 12 pregnancies with small for gestational age (SGA) infants, 84 pregnancies with appropriate for gestational age (AGA) infants, and eight pregnancies with large for gestational age (LGA) infants. HGF concentrations were measured from the early second-trimester amniotic fluid samples using an enzyme-linked immunosorbent assay. IGF-I concentrations were measured from the early second-trimester amniotic fluid samples using an immunoradiometric assay. Maternal age in AGA group (34.2 +/- 5.5 years) was significantly lower than in SGA (37.9 +/- 3.0 years) and LGA (37.6 +/- 3.3 years) groups (P < 0.05). There were no significant differences for parity or gestational age at amniocentesis among the groups. There were significant differences for birth age, birth weight, neonatal height, and placental weight among the groups (P < 0.05). HGF concentrations in SGA, AGA and LGA groups were 16.9 +/- 6.6, 16.7 +/- 9.0 and 20.2 +/- 14.8 ng/ml respectively (not significant). There was no correlation between amniotic fluid HGF concentrations and birth weight, height or placental weight. There were also no significant differences for amniotic fluid IGF-I concentrations among the three groups. These results suggest that differences in HGF concentrations in the early second-trimester amniotic fluid do not predict fetal growth at birth. Further study is needed to clarify the role of high HGF concentrations in early second-trimester amniotic fluid during pregnancy.

Adult↗
PubMed1999

Comparison of alterations in fetal regional arterial vascular resistance in appropriate-for-gestational-age singleton, twin and triplet pregnancies.

The objective of this longitudinal study was to evaluate alterations in fetal vascular resistance of fetal peripheral arteries with advancing gestation in singleton appropriate-for-gestational-age (S-AGA), twin appropriate-for-gestational-age (Tw-AGA) and triplet appropriate-for-gestational-age (Tri-AGA) infants. Colour Doppler flow imaging and pulsed Doppler ultrasonographic examinations were performed on 35 S-AGA, 52 Tw-AGA and 12 Tri-AGA fetuses. The pulsatility index for middle cerebral artery (MCAPI), umbilical artery (UAPI), descending aorta (DAPI), splenic artery (SAPI), renal artery (RAPI) and femoral artery (FAPI) was measured as vascular resistance every 2 weeks after 15 weeks of menstrual age until delivery. Optimal models and normal ranges for pulsatility index for each artery in each group were generated. The alterations in various fetal regional arterial pulsatility indices with advancing gestational age showed no significant differences in S-AGA, Tw-AGA and Tri-AGA infants, respectively. These results suggest that there is no significant difference for regional arterial vascular resistance in AGA fetuses among singleton, twin, and triplet pregnancies, whereas there was a slight difference in fetal growth pattern among singleton, twin, and triplet pregnancies described in our previous investigation.

Adult↗
PubMed1999

Laparoscopy-assisted intrapelvic sonography with a high-frequency, real-time miniature transducer for assessment of the Fallopian tube: a preliminary report.

Our purpose was to visualize normal and abnormal Fallopian tubes using laparoscopy-assisted intrapelvic sonography with a specially developed 20 MHz flexible catheter-based high-resolution, real-time miniature (2.4 mm outer diameter) ultrasound transducer in infertile women. A total of 21 women (20 infertile, one with unilateral hydrosalpinx, and one tubal pregnancy) were studied with pelvic saline effusion under laparoscopy. Fimbriae were clearly depicted with a cockscomb-like form in 95% of patients. All ampullae were visualized, and mucosal layers were clearly distinguished from muscle layers in 70% of patients. Scanty intratubal effusion was noted in 50% of patients, and tubal spastic findings were found in 10% of patients. In all, 60% of isthmuses were detected, and mucosal layers were distinguished from muscle layers in 30%. In the subject with hydrosalpinx, the tubal wall was thinner, and it was not possible to distinguish between muscle and mucosal layers. In the subject with a tubal pregnancy, the amniotic membrane and decidua were depicted more clearly than by transvaginal sonography. In conclusion, laparoscopy-assisted intrapelvic sonography with a high-frequency, real-time miniature transducer may be useful in the assessment of tubal texture and function in tubal disorders, possibly in infertility practice.

Fallopian Tube Diseases↗
PubMed1999

Three-dimensional ultrasonographic evaluation of ovarian tumours: a preliminary study.

Our objective was to determine the accuracy of three dimensional (3D) ultrasonography in the differentiation of ovarian tumours. Women (n = 20) with ovarian tumours (13 benign and seven malignant) were first examined using two-dimensional (2D) ultrasonography and were then evaluated with three-dimensional (3D) ultrasonography. All patients underwent surgery within 7 days of 2D and 3D ultrasonographic evaluations, and a histopathological diagnosis was made. A 2D ultrasonographic diagnosis of malignancy was done using an established scoring system. Diagnostic criteria for ovarian malignancy by 3D ultrasonography were: irregular thick septa, irregular papillary projection, mostly solid tumour, high echogenicity, and irregular inner wall. Compared with 2D ultrasound, 3D ultrasound had a significantly higher specificity (P < 0.005) and accuracy (P < 0.01), and a significantly lower false positive rate (P < 0.005). Our results suggest that 3D ultrasonography might be a better means of differentiating between malignant and benign ovarian tumours. However, in view of the small number of ovarian tumours, these observations must be considered preliminary.

Adult↗
PubMed1999

Comparison of fetal growth in singleton, twin, and triplet pregnancies.

The objective of this longitudinal retrospective study was to evaluate differences of the fetal growth and fetal organ growth among singleton small for gestational age (S-SGA), singleton appropriate for gestational age (S-AGA), twin (Tw-AGA), and triplet (Tri-AGA) infants. Ultrasonographic examinations were performed on 35 S-AGA, 18 S-SGA, 52 Tw-AGA and 12 Tri-AGA fetuses. Circumferences of head (HC), abdomen (AC), spleen (SC) and adrenal gland (AGC) and lengths of femur diaphysis (FDL), liver (LL), estimated weight (EWT) were measured every 2 weeks after 15 weeks of menstrual age until delivery. There was no significant difference in predicted HC values in S-AGA, Tw-AGA and Tri-AGA fetuses; these values were lowest in S-SGA fetuses. As the number of fetuses in the uterus increased with advancing menstrual age, the slope of the growth curve for predicted AC value became lower, but there was no significant difference between Tri-AGA and S-SGA fetuses. There was no significant difference in predicted FDL values among Tw-AGA, Tri-AGA and S-SGA fetuses; those values were significantly lower than that in S-AGA fetuses. There was no significant difference in predicted EWT value between Tw-AGA and Tri-AGA fetuses, which were intermediate between those for S-AGA and S-SGA fetuses. There were no significant differences in predicted SC and AGC values between S-AGA and Tw-AGA fetuses, respectively. However, in S-SGA fetuses, the slopes of the growth curve for SC and AGC were lower than those in the other two groups with advancing menstrual age. There were slight differences in predicted LL values between S-AGA, S-SGA and Tw-AGA fetuses. These results suggest that in AGA fetuses, there was a slight difference in growth pattern among singleton, twin, and triplet pregnancies.

Adult↗
PubMed1999

Nitric oxide synthesis is increased after dehydroepiandrosterone sulphate administration in term human pregnancy.

The purpose of this study was to evaluate the role of nitric oxide in the vasodilative effect of dehydroepiandrosterone sulphate (DHEA-S) in term pregnant women. Circulating nitrite, nitrate and oestradiol concentrations were measured on 10 normal full-term pregnant women before (-30 min) and after (10, 30, 60, 90 and 120 min) administration of a 200 mg i.v. dose of DHEA-S dissolved in 20 ml of 5% dextrose (DHEA-S group). Ten normal full-term pregnant women received 20 ml of 5% dextrose as controls (control group). Maternal blood pressure and heart rate were also recorded. The median oestradiol concentration increased significantly after the infusion in DHEA-S group (P < 0.001), whereas there was no significant change in plasma oestradiol in the control group. In the DHEA-S group, plasma circulating nitrate and nitrite increased significantly at 10 and 30 min after DHEA-S administration respectively (P < 0.05). In the control group, there was no change in plasma nitric oxide (NO) metabolites. No change was found in heart rate or mean arterial blood pressure in the control or DHEA-S groups. These results suggest there may be a link between increased NO and increased oestrogen after DHEA-S injection but their peak values did not coincide. Both may be associated with vasodilation in term pregnant women.

Blood Pressure↗
PubMed1999

Crystallization and preliminary X-ray diffraction analysis of cytochrome P450sca-2 from Streptomyces carbophilus involved in production of pravastatin sodium, a tissue-selective inhibitor of HMG-CoA reductase.

Cytochrome P450sca-2 from Streptomyces carbophilus catalyzes the hydroxylation of ML-236B sodium salt to pravastatin sodium, a tissue-selective inhibitor of 3-hydroxy-3-methylglutaryl-coenzymeA (HMG-CoA) reductase. HMG-CoA reductase is a key enzyme in cholesterol biosynthesis. Crystals of the protein were obtained by the vapour-diffusion method, using ammonium sulfate as a precipitant. The crystals belong to the trigonal space group P3121 (or its enantiomorph, P3221) with unit-cell dimensions a = 103.5, c = 79.8 A. Assuming the presence of one molecule in the asymmetric unit, the calculated value of Vm is 2.68 A3 Da-1. A native data set was collected to a resolution of 2.2 A.

Crystallization↗
PubMed1999

Diversity of leukaemic cell morphology in ATL correlates with prognostic factors, aberrant immunophenotype and defective HTLV-1 genotype.

To investigate the diversity of morphology in adult T-cell leukaemia/lymphoma (ATL) and its possible association with the pathophysiology of ATL, we selected 36 acute cases and 14 chronic cases phenotypically confirmed to have >90% ATL cells in peripheral blood mononuclear cells. Prototype ATL cells were observed in all cases, although the percentage of all lymphoid cells varied considerably (48.9 +/- 23.8 in acute type, 29.6 +/- 18.9 in chronic type; P = 0.015). Chronic lymphocytic leukaemia (CLL)-like morphology with round nuclei was more frequent in chronic type than in acute type (52.0 +/- 24.9% v 16.6 +/- 13.1%; P < 0.0001). Unusual morphology (UM; lymphoblastic, vacuolated, granular pleomorphic or large cells) was more frequent in acute type than in chronic type (20.1 +/- 18.7% v 2.7 +/- 3.2%; P < 0.0001). Furthermore, there were significant negative and positive correlations of % CLL-like cells and % UM cells respectively, with serum LDH level, hypercalcaemia, performance status, and total number of involved lesions. Cases with aberrant immunophenotype (n = 6) or defective HTLV-1 integration (n = 22) showed lower % CLL-like cells and higher % UM cells than other cases, respectively. Cases with >50% CLL-like cells (n = 7; all chronic type) were younger (53.1 +/- 12.2 v 66.9 +/- 10.6 years; P = 0.038) and showed longer acute-crisis free survival (mean: 16.7 v 3. 0 years; P = 0.012) than chronic cases with <50% CLL-like cells. These results suggest that diversity in genotype, phenotype, morphology and behaviour of ATL are closely associated, and that CLL-like morphology is a good prognostic factor for chronic type.

Adult↗