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Biomedical subjects

T Hata

Publications and source records attributed to T Hata.

At least 163 records · Page 9Linked to original sources

Decreased maternal circulating hepatocyte growth factor (HGF) concentrations in pregnancies with small for gestational age infants.

Our purpose was to evaluate whether maternal and fetal hepatocyte growth factor (HGF) concentrations in pregnancies with small for gestational age (SGA) infants are different from those in pregnancies with appropriate for gestational age (AGA) infants. Maternal and fetal circulating HGF concentrations were compared between 55 pregnancies with AGA infants and 16 pregnancies with SGA infants at birth. HGF concentrations were measured from maternal and cord venous blood samples using an enzyme-linked immunosorbent assay. Umbilical artery blood pH and oxidative pressure (PO2) were also measured. Maternal circulating HGF concentrations (0.60+/-0.35 ng/ml) in pregnancies with SGA infants were significantly lower than those (0.91+/-0.44 ng/ml) in pregnancies with AGA infants (P = 0.012). There were no significant differences in fetal circulating HGF concentrations between both groups. No significant differences in umbilical artery blood pH and PO2 were found between both groups. These results suggest that the maternal serum circulating HGF concentration has a significant role in fetal growth during pregnancy.

Adult↗

Three-dimensional intrauterine sonography in the early first-trimester of human pregnancy: preliminary study.

Our purpose was to visualize normal embryonal surface anatomic structures using three-dimensional (3D) intrauterine sonography with a 20 MHz flexible catheter-based high-resolution real-time miniature transducer in the early first trimester of pregnancy. A total of 15 women about to undergo therapeutic abortion at 7-9.9 weeks gestational age were studied by means of 3D intrauterine sonography with a specially developed catheter-based high-resolution real-time miniature (2.4 mm in outer diameter) ultrasound transducer (20 MHz). This imaging system can provide conventional 2D intrauterine sonographic images and can also generate within seconds high-quality 3D images in the surface and transparent mode. At week 8, prominent forehead was evident, and upper and lower limbs and midgut herniation were clearly depicted. At week 9, fingers and toes were depicted as small digital rays, and the sacral tail protruded caudally. The midline cranial ectodermal cleft was also identified. At week 10, embryonic face and fingers were clearly shown. 3D intrauterine sonography provides a novel means for visualizing of surface anatomic structures of the human embryo in utero. These results suggest that 3D intrauterine sonography can become an important modality in future embryological research and in detection of embryonic developmental disorders in the early first-trimester pregnancy.

Embryo, Mammalian↗

Maternal and fetal nitric oxide synthesis is decreased in pregnancies with small for gestational age infants.

Our purpose was to evaluate whether maternal and fetal nitric oxide synthesis in pregnancies with small for gestational age (SGA) infants are different from those in pregnancies with appropriate for gestational age (AGA) infants. Maternal and fetal circulating nitrate and nitrite concentrations were compared between 30 pregnancies with AGA and 10 pregnancies with SGA at birth. End-products of nitric oxide synthesis were measured in maternal and cord venous blood samples using a fluorometric assay. Umbilical artery blood pH and PO2 were also measured. Maternal circulating nitrite and nitrate concentrations (6.91 +/- 1.27 microM) in pregnancies with SGA were significantly lower than those (11.69 +/- 1.33 microM) in pregnancies with AGA (P = 0.015). Fetal circulating nitrite and nitrate concentrations (7.54 +/- 1.09 microM) in pregnancies with SGA were also significantly lower than those (11.24 +/- 1.08 microM) in pregnancies with AGA (P = 0.024). There were no significant differences in umbilical artery blood pH and PO2 between the two groups. These results suggest that maternal and fetal nitric oxide synthesis are decreased in pregnancies with SGA infants.

Adult↗

Molecular cloning and expression of an amine sulfotransferase cDNA: a new gene family of cytosolic sulfotransferases in mammals.

A cDNA of amine sulfotransferase-RB1 (AST-RB1), which efficiently catalyzes 4-phenyl-1,2,3,6-tetrahydropyridine (PTHP) sulfation, has been isolated by immunoscreening of a rabbit liver cDNA library. The cDNA consisted of 1,117 base pairs and encoded a protein of 301 amino acids with a molecular weight of 35,876. The deduced amino acid sequence matched at six positions those of peptide fragments obtained from purified AST-RB1 protein. The sequence had less than 38% identity at the amino acid level with cytosolic sulfotransferases in mammals, although high degrees of similarity were observed with regions conserved throughout mammalian sulfotransferases. These results indicate that AST-RB1, arbitrarily named sulfotransferase 3A1 (ST3A1), constitutes a new and third gene family of cytosolic sulfotransferases in mammals. ST3A1 expressed in Escherichia coli as a fused protein catalyzed sulfation of amines such as PTHP, aniline, 4-chloroaniline, 2-naphthylamine, and desipramine, but barely O-sulfation of typical aryl and hydroxysteroid sulfotransferase substrates. These data unequivocally demonstrate the existence of a cytosolic sulfotransferase showing a high selectivity for amine substrates, and indicate that multiple forms of sulfotransferase mediate sulfation of xenobiotics in mammalian livers.

Amino Acid Sequence↗

Molecular cloning, expression, and enzymatic characterization of rabbit hydroxysteroid sulfotransferase AST-RB2.

Cytosolic sulfotransferases, which consist of at least three gene families, play a major role in activation and detoxification of both endogenous and exogenous chemicals. We recently purified a rabbit sulfotransferase, AST-RB2, showing high activities to both hydroxysteroids and amines. To characterize this enzyme, a rabbit cDNA library was screened using anti-AST-RB2 antibodies. The isolated cDNA was judged to encode AST-RB2 (ST2A8) based on the amino acid sequences of peptide fragments obtained from purified AST-RB2. The cDNA showed high similarity to other mammalian hydroxysteroid sulfotransferases (ST2) at the amino acid level (58-68%), but low similarity to aryl sulfotransferases (ST1) (less than 37%). The protein expressed in Escherichia coli catalyzed sulfation of typical ST2 substrates. Therefore, ST2A8 was judged to belong to the ST2 family from both its primary structure and substrate specificity. The ST2A8 protein expressed in E. coli clearly differed from rat ST2A1 and ST2A2 on its localization (cytosol/insoluble fraction ratio). ST2A8 had no activity to lithocholate, but showed the highest catalysis on dehydroepiandrosterone and testosterone among the four forms (ST2A1, ST2A2, ST2A3, and ST2A8), indicating a clear difference between ST2A forms in substrate specificity to endogenous chemicals.

Amino Acid Sequence↗

Power Doppler enhancement of the placenta by dehydroepiandrosterone sulphate in term pregnancy.

We studied the effect of dehydroepiandrosterone sulphate (DHAS) on placental blood flow in 11 women with an uncomplicated pregnancy between 37 and 39 weeks of gestation. Power Doppler enhancement of the placenta was performed before and 60 minutes after the administration of a 200 mg intravenous dose of DHAS dissolved in 20 mL of 5% dextrose. Increased power Doppler enhancements of the placenta after DHAS injection were evident in each case studied. The power Doppler enhancement returned to the baseline imaging within 60 minutes. This DHAS loading test, assessed by means of power Doppler imaging, may be a useful technique when attempting to assess fetoplacental function in normal and high risk pregnancies.

Acetone↗

Three-dimensional ultrasonographic assessment of the umbilical cord during the 2nd and 3rd trimesters of pregnancy.

OBJECTIVE: To evaluate the umbilical cord and its abnormalities by use of three-dimensional ultrasonography with a specially developed abdominal three-dimensional transducer. PATIENTS AND METHODS: Ninety-five pregnancies (92 normal, 2 with hydrops fetalis, and 1 with omphalocele) from 14 to 40 weeks of gestation were studied with a specially developed abdominal three-dimensional transducer (3.5 MHz). This system can provide conventional two-dimensional ultrasonography images and can also generate within seconds high-quality three-dimensional images in the surface and transparent mode with no need for an external workstation. A proportion of the umbilical cords (coiled or noncoiled free loop, abdominal insertion, and placental insertion) visualized at each gestational age interval is presented. RESULTS: The proportion of the umbilical cords visualized during pregnancy except for between 24 and 27 weeks of gestation was about 70% (range 64-83%). Optimal visualization of the umbilical cord was achieved between 24 and 27 weeks of gestation. During this period it was possible to adequately depict the umbilical cord in 93% of the cases. The proportions of the noncoiled umbilical cord depicted during pregnancy ranged from 8 to 45%. The detection rate of abdominal insertion of the umbilical cord visualized at 14-19 weeks was 44%; the detection rate decreased thereafter. Placental insertion of the umbilical cord could not be identified after 28 weeks of gestation. In 2 cases with hydrops fetalis, edematous umbilical cord was evident. In 1 fetus, omphalocele was clearly depicted. CONCLUSIONS: The new three-dimensional ultrasound technology generates within seconds high-quality three-dimensional images of the umbilical cord, although limitation of viewing direction exists. These results suggest that the new three-dimensional ultrasonography has the potential to be a supplement to two-dimensional ultrasonography and might be useful in identifying abnormal umbilical cords in utero.

Edema↗

Three-dimensional ultrasonographic visualization of multiple pregnancy.

Our purpose was to describe interrelationships and contacts between twins in utero by use of three-dimensional ultrasonography with a specially developed abdominal three-dimensional transducer. Thirteen twin pregnancies (3 monochorionic and 10 dichorionic pairs) and one triplet pregnancy (trichorionic triplet) from 9 to 36 weeks of gestation were studied with a specially developed abdominal three-dimensional transducer (3.5 MHz). This imaging system can provide conventional two-dimensional ultrasonography images and can also generate within seconds high-quality three-dimensional images in the surface and transparent mode with no need for an external workstation. Interrelationships and contacts between twins or triplets are described. Various types of contacts (head/body/arm/leg) and interrelationships were clearly visualized. Crowding of in utero twin fetuses increased with advancing gestation. Sometimes two placentas and dividing membrane were beautifully depicted. In one triplet pregnancy, the interrelationships among 3 fetuses and dividing membranes were easily recognized. Three-dimensional ultrasonography provides a novel means of visualizing multiple pregnancies in utero. These results suggest that three-dimensional ultrasonography has the potential to be a supplement to two-dimensional ultrasonography and would be useful in evaluating the interhuman contacts and crowdings of twin and triplet fetuses in utero.

Female↗

Interaction of mRNAs for angiotensin II type 1 and type 2 receptors to vascular remodeling in spontaneously hypertensive rats.

We administered angiotensin II (Ang II) receptor type 1 (AT1) blockade (losartan, 40 mg x kg-1 x d-1), type II receptor (AT2) blockade (PD123319, 100 mg x kg-1 x d-1), or angiotensin-converting enzyme (ACE) inhibitor (enalapril, 30 mg x kg-1 x d-1) to spontaneously hypertensive rats (SHR) from 10 to 20 weeks of age. Control SHR and Wister-Kyoto rats (WKY) received a placebo for the same period. At the end of treatment, losartan and enalapril were both found to have significantly reduced the arterial systolic blood pressure and the collagen concentration to the level of WKY, whereas PD123319 had no effect. Enalapril and PD123319 significantly reduced the media cross-sectional area of the aorta in comparison to that of untreated SHR, which was still larger than that of the WKY; however, losartan did not change it. Using reverse transcription-polymerase chain reaction, we next examined the mRNA expressions for ACE, AT1 receptor, and AT2 receptor in experimental animals. We observed significantly enhanced mRNA expression for AT1 and AT2 receptors and ACE in untreated SHR compared with WKY. The AT1 mRNA level was also significantly decreased in the SHR treated with either losartan or enalapril, whereas the AT2 mRNA level was significantly decreased in the SHR treated with either PD123319 or enalapril in comparison to untreated SHR. The level of ACE mRNA was significantly decreased only in the SHR treated with enalapril. These results indicate that AT1 receptor, but not AT2 receptor, plays a crucial role in the remodeling of matrix tissue, while AT2 receptor may play a role in the development of hypertrophy of smooth muscle in aorta in SHR, and that the reduction of hypertrophy of smooth muscle does not fully account for the suppression of hypertension.

Angiotensin Receptor Antagonists↗

Three-dimensional sonographic visualization of the fetal face.

OBJECTIVE: This study was done to show the potential of using three dimensional (3D) sonography to reveal fetal facial anomalies. SUBJECTS AND METHODS: Ninety-four healthy fetuses from 15 to 40 weeks' gestation were studied with a specially developed 3.5-MHz abdominal 3D transducer. This imaging system provided conventional two-dimensional (2D) sonographic images and also generated within seconds high-quality 3D images in the surface and transparent modes with no need for an external workstation. RESULTS: Using this imaging system, we obtained 2D and 3D images of fetal faces (forehead, eyes, nose, lips, and chin) at six gestational ages. At less than 24 weeks' gestation, 65% of facial structures were visualized. The image quality was slightly degraded because of the small fetal size. At or after 24 weeks' gestation, 84% of facial structures were revealed. We found no significant difference in image quality of the fetal face between 2D and 3D sonography. CONCLUSION: The new 3D sonographic technology can generate within seconds high-quality 3D images of the fetal face. The 3D technology seems to perform at least as well as conventional 2D sonography. Our results suggest that 3D sonography has the potential to supplement 2D sonography and might be useful in identifying malformations of the fetal face and chromosomal abnormalities in utero.

Face↗

Osteotropic drug delivery system (ODDS) based on bisphosphonic prodrug. I.v. effects of osteotropic estradiol on bone mineral density and uterine weight in ovariectomized rats.

An osteotropic drug delivery system (ODDS) based on the bisphosphonic prodrug was designed for 17beta-estradiol (E2) in order to improve patient compliance in estrogen replacement therapy of postmenopausal osteoporosis. The bisphosphonic prodrug of E2, disodium [17beta-(3 '-hydroxy- 1',3',5'-estratrienyloxy) carbonylpropyl carboxamidomethylene] bisphosphonate (E2-BP) was synthesized and its effects on bone mineral density and uterine weight were investigated in ovariectomized (OVX) rats. E2-BP was injected intravenously once a week (4 injections/experiment), and E2 was administrated orally 5 times a week (20 administrations/experiment). Once a week treatment with 0.1 mg/kg E2-BP significantly restored bone mineral reduction by 61.8% without significantly increasing uterine weight. Similarly, once in 4 weeks treatment with 1.0 mg/kg E2-BP (1 injection/experiment) showed almost the same therapeutic effects. On the other hand, 5 times a week oral treatment with 1.0 mg/kg E2 significantly improved bone mineral density by 90.5%, but increased uterine weight up to 98.2% of that of the sham group. In vitro bone resorption analysis revealed that E2-BP exhibits antiresorptive activity not as a bisphosphonate but as a prodrug of E2. These results demonstrated that E2-BP has the potential to improve patient compliance in estrogen therapy by its minimal adverse effects and less frequent medication.

Animals↗

[Effects of fimbria-fornix lesion on the temporal discrimination revealed by peak interval procedure in rats].

When temporal discrimination is examined by a peak interval (PI) procedure in rats, a shortening of peak time is induced by the fimbria-fornix (FF) lesion. The aim of this research is to investigate the extent of peak time shortening induced by FF lesion and the acquisition process of temporal discrimination. In FF lesioned rats, the peak time was very short (about 13 sec) in earlier phase, then became longer as the training progressed and reached a steady level, which was approximately 20% shorter than control rats. These results suggest that the "non-timing process" is involved in addition to the "timing process" in FF lesioned rats.

Animals↗

Effect of regular aerobic exercise on cerebrovascular tone in young women.

Our objective was to evaluate the effect of regular aerobic exercise on cerebrovascular tone in young women. Color and pulsed Doppler ultrasonography were used to determine the pulsatility index in the ophthalmic artery in 20 normotensive, nonpregnant young women (aged 19 to 26 years) with a regular menstrual cycle on cycle day 5. Blood pressure and heart rate were recorded at each examination. Blood samples were collected from all the subjects to measure serum estradiol levels and serum lipid profiles. Ten of the 20 women (exercise group) have maintained aerobic exercise for 50 min, 3 to 5 days a week, for at least a year. The other 10 women (nonexercise group) never did regular exercise. There were no significant differences between the two groups regarding age, body mass index, mean blood pressure, and heart rate and serum estradiol, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglyceride levels. The pulsatility index value (mean, 1.89; standard deviation, 0.33) of the ophthalmic artery in the exercise group was significantly lower than that (mean, 2.53; standard deviation, 0.26) in the nonexercise group. Regular aerobic exercise in young women significantly decreases the peripheral cerebrovascular tone, and this might be a favorable adaptation for early prevention of cerebrovascular disease, which is common in older women.

Adaptation, Physiological↗

Pharmacokinetic and pharmacodynamic study of a new nonsteroidal 5 alpha-reductase inhibitor, 4-[3-[3-[Bis(4-isobutylphenyl)methylamino]benzoyl]-1H-indol-1-yl]-butyr ic acid, in rats.

The pharmacokinetic and pharmacodynamic behaviors of 4-[3-[3-[Bis(4-isobutylphenyl) methylamino] benzoyl]-1H-indol-1-yl]-butyric acid (FK143), a new nonsteroidal steroid 5 alpha-reductase inhibitor, in the ventral prostate were investigated after i.v. administration to rats. The relationship between blood concentrations at 24 hr and doses was linear in the range of 0.1 to 20 mg/kg. However, the levels of FK143 in the prostate were saturated over the dose of over 5 mg/kg. The dissociation constant (Kd) and maximum amount of binding substances (Bmax), calculated according to nonlinear kinetic analysis including a specific binding pool, was 0.0553 +/- 0.0117 microgram/ml (92 nM, estimated value +/- S.D.) and 0.908 +/- 0.092 microgram/g tissue, respectively. A combined pharmacokinetic/pharmacodynamic (PK/PD) model was constructed using change in dihydrotestosterone (DHT) levels in the prostate after i.v. administration of FK143 as an index for its pharmacological effect and blood concentration as an input function. The apparent reaction rate constant of drug and enzyme (K) was 39.7 +/- 25.1 g tissue/microgram/hr (estimated value +/- S.D.), the apparent turn-over rate constant of enzyme (k) was 0.140 +/- 0.107 hr-1, the elimination rate constant of DHT (kel, DHT) was 1.13 +/- 0.94 hr-1 and the fraction of FK143-insensitive DHT synthesis (F) was 0.461 +/- 0.037. The PK/PD analysis suggested that the duration of the effect of FK143 was related to its accumulation in the binding pool of the prostate. After i.v. administration of FK143 in the range of 0.1 to 20 mg/kg, the DHT levels in the prostate decreased to about 40% of control value, after which despite the rapid decline of blood FK143 concentration, slowly recovered according to the elimination rate of FK143 in the prostate. Moreover, the PK/PD profiles of FK143 after repeated i.v. administration were predictable by using the PK/PD parameters obtained after single administration of FK143.

5-alpha Reductase Inhibitors↗

[Complicated form of spastic paraplegia with congenital cataract: a case report].

We report a 33-year-old man who manifested spastic paraplegia with congenital cataract, dementia, deformity of the foot (pes cavus, high arch and hammer toes), ataxia, and peripheral neuropathy. Magnetic resonance imaging showed mild deformity of the trunk of the corpus callosum and atrophy of superior cerebellar vermis. Metabolic diseases were ruled out by the clinical course and special examinations. Other patients, including 2 of ours, with spastic paraplegia and thin corpus callosum have been reported, but the present case is different because of congenital cataract and the form of the corpus callosum. We consider that there may be a variety of complicated forms of spastic paraplegia. To assess the etiology of complicated forms of spastic paraplegia, further case accumulation is very important.

Adult↗

Changes in plasma and urinary norepinephrine following transdermal clonidine in spontaneously hypertensive rats.

To support a long-lasting antihypertensive effect of transdermal clonidine (CAS 4205-90-7), changes in plasma norepinephrine (NE) levels and urinary NE excretion as indices of the sympathetic nervous activities were investigated following transdermal and oral clonidine in conscious spontaneously hypertensive rats. Plasma NE levels were significantly reduced for 24 h during transdermal application of clonidine patch at 1.5 and 4.5 mg/kg on the back of each rat. Oral clonidine at 100 microgram/kg also lowered plasma NE levels. However, significant falls in the levels lasted only for 4 h after oral dosing. Urinary NE excretion was significantly decreased during both 4-8 and 8-24 h periods, and during an 8-24 h period following transdermal clonidine at 1.5 and 4.5 mg/kg, respectively. Significant decrease in urinary NE excretion was also produced during a 4-8 h period following oral clonidine at 100 micrograms/kg. Total urinary NE excretion during a 0-24 h period was dose-dependently reduced following transdermal clonidine, but was not altered following oral dosing. These findings suggest that the sympathoinhibitory effect of transdermal clonidine is more persistent than that of oral clonidine. Therefore, long-lasting antihypertensive effect of transdermal clonidine is closely associated with the sustained suppression of the sympathetic nervous activity.

Administration, Cutaneous↗