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Biomedical subjects

T Hata

Publications and source records attributed to T Hata.

At least 451 records · Page 25Linked to original sources

Modulation of Na+-Ca2+ exchange in cardiac sarcolemmal vesicles by Ca2+ antagonists.

The purpose of this study was to examine the effect of three classes of Ca2+ antagonists, diltiazem, verapamil and nifedipine on Na+-Ca2+ exchange mechanism in the sarcolemmal vesicles isolated from canine heart. Na+-Ca2+ exchange and Ca2+ pump (ATP-dependent Ca2+ uptake) activities were assessed using the Millipore filtration technique. Sarcolemmal vesicles used in this study are estimated to consist of several subpopulations wherein 23% are inside-out and 55% are right side-out sealed vesicles in orientation. The affect of each Ca2+ antagonist on the Na+ dependent Ca2+ uptake was studied in the total population of sarcolemmal vesicles, in which none of the agents depressed the initial rate of Ca2+ uptake until concentrations of 10 microM were incubated in the incubation medium. However, when sarcolemmal vesicles were preloaded with Ca2+ via ATP-dependent Ca2+ uptake, cellular Ca2+ influx was depressed only by verapamil (28%) at 1 microM in the efflux medium with 8 mM Na+. Furthermore, inhibition of Ca2+ efflux by verapamil was more pronounced in the presence of 16 mM Na+ in the efflux medium. The order of inhibition was verapamil greater than diltiazem greater than nifedipine. These results indicate that same forms of Ca2+-antagonist drugs may affect the Na+-Ca2+ exchange mechanism in the cardiac sarcolemmal vesicles and therefore we suggest this site of action may contribute to their effects on the myocardium.

Adenosine Triphosphate↗

Imaging local cerebral blood flow by Xenon-enhanced computed tomography--technical optimization procedures.

Methods are described for non-invasive, computer-assisted serial scanning throughout the human brain during eight minutes of inhalation of 27%-30% Xenon gas in order to measure local cerebral blood flow (LCBF). Optimized Xenon-enhanced computed tomography (XeCT) was achieved by 5-second scanning at one-minute intervals utilizing a state-of-the-art CT scanner and rapid delivery of Xenon gas via a face mask. Values for local brain-blood partition coefficients (L lambda) measured in vivo were utilized to calculate LCBF values. Previous methods assumed L lambda values to be normal, introducing the risk of systematic errors, because L lambda values differ throughout normal brain and may be altered by disease. Color-coded maps of L lambda and LCBF values were formatted directly onto CT images for exact correlation of function with anatomic and pathologic observations (spatial resolution: 26.5 cubic mm). Results were compared among eight normal volunteers, aged between 50 and 88 years. Mean cortical gray matter blood flow was 46.3 +/- 7.7, for subcortical gray matter was 50.3 +/- 13.2 and for white matter was 18.8 +/- 3.2. Modern CT scanners provide stability, improved signal to noise ratio and minimal radiation scatter. Combining these advantages with rapid Xenon saturation of the blood provides correlations of L lambda and LCBF with images of normal and abnormal brain in a safe, useful and non-invasive manner.

Aged↗

Ultrasonographic identification and measurement of the human fetal pancreas in utero.

One hundred seventy ultrasonographic examinations, done to identify and measure the fetal pancreas in utero, were performed on 78 women with regular menstrual cycle, at 20-41 weeks of gestation. The pancreas, which could be identified after 20 weeks of gestation was measured in 38.4% at 36-39 weeks and 80.0% at 20-23 weeks gestation. The length of the fetal pancreas from the head to tail (FP-L) correlated well with the gestational age (r = 0.90, P less than 0.001). The normal sonographic characteristics of the fetal pancreas are discussed.

Female↗

Angiotensin-converting enzyme inhibitors. 2. Perhydroazepin-2-one derivatives.

alpha-[(3S)-3-[[(S)-1-(Ethoxycarbonyl)-3-phenylpropyl]amino]-2-oxo-6 or 7-phenylperhydroazepin-1-yl]acetic acids (monoester monoacids) and their dicarboxylic acids were synthesized, and their angiotensin-converting enzyme (ACE) inhibitory activities were evaluated. The dicarboxylic acids having phenyl substituents at the 6R, 6S, and 7S positions on the azepinone ring showed potent inhibition in vitro. The corresponding monoester monoacids, when administered orally, suppressed the pressor response to angiotensin I administered intravenously. The monoester monoacids having the phenyl substituent at the 6-position showed a longer duration of action than one having the substituent at the 7-position. The structure-activity relationship was studied on the basis of the conformational energy calculation.

Angiotensin-Converting Enzyme Inhibitors↗

X-ray study of baker's yeast lipoamide dehydrogenase at 4.5 A resolution by molecular replacement method.

The molecular structure of lipoamide dehydrogenase from baker's yeast has been determined at 4.5 A resolution by molecular replacement techniques using the known structure of human erythrocyte glutathione reductase as a starting model. The enzyme crystallizes in the space group P2(1)2(1)2(1) with a = 98.6(2), b = 162.0(2), c = 69.4(2) A. There is one molecule per asymmetric unit. The enzyme is a dimeric protein of identical subunits related by a local two-fold symmetry. Comparison of the tertiary structures between glutathione reductase and the present enzyme shows that the folding is almost the same except for the N and C termini, although some slight shortening or shifting of alpha-helices was found in the electron density map. FAD molecules are found at similar positions to those of glutathione reductase. Since the amino acid residues around FAD and NAD binding sites and at the reaction centers of the two enzymes are strongly conserved, the lipoamide dehydrogenase may catalyze the opposite reaction through a similar mechanism to that proposed for glutathione reductase. The newly found C terminus is located near the edge of a deep cave at the interface between the two subunits. These additional 18 residues form a narrow entrance to the cave, in which the long chain of the dihydrolipoyl moiety of lipoate acetyltransferase will be bound.

Crystallization↗

The relationship of hyperalgesia in SART (repeated cold)-stressed animals to the autonomic nervous system.

1. The mechanism of hyperalgesia observed in SART (repeated cold)-stressed animals (mice and rats) was studied in relation to the autonomic nervous system. 2. SART stress reduced the nociceptive threshold previously increased in vagotomized mice, but failed to change the threshold previously decreased in sympathectomized mice. 3. The nociceptive threshold previously decreased in SART-stressed mice was elevated by vagotomy, but decreased still more by sympathectomy. 4. Lesion of ventromedial (VMH), anterior (AH) or posterior hypothalamus (PH) prevented decrease in the nociceptive threshold of rats by SART stress, but lesion of the lateral hypothalamus (LH) had no such effect. 5. The nociceptive threshold previously decreased in stressed rats did not change by VMH, AH or PH lesion, but increased by LH lesion. 6. The above findings indicate that hyperalgesia in SART-stressed animals apparently bears little relation to the parasympathetic nervous system, but is associated relatively more with reduced tone in the sympathetic nervous system.

Animals↗

Ultrasonographic evaluation of adrenal involution during antenatal and neonatal periods.

Using real-time ultrasonography, 25 adrenal glands from prenatal to neonatal periods were prospectively examined to assess the process of shrinkage. A similar sonographic structure was seen in both prenatal and neonatal adrenal glands. The area of adrenal gland (AGA) and the rate of decrease were calculated during antenatal and early neonatal periods. The values of AGA were 350 +/- 19 mm2 within a week of delivery, 304 +/- 17 mm2 (87 +/- 2%) just after delivery, 273 +/- 25 mm2 (77 +/- 5%) on the 1st day, 246 +/- 24 mm2 (70 +/- 5%) on the 2nd day, 215 +/- 23 mm2 (61 +/- 5%) on the 3rd day, 196 +/- 22 mm2 (56 +/- 5%) on the 4th day, 173 +/- 18 mm2 (50 +/- 4%) on the 5th day, 154 +/- 14 (44 +/- 4%) on the 6th day, 140 +/- 12 mm2 (40 +/- 2%) on the 7th day, respectively. In conclusion, the postnatal involution of the adrenals was documented by ultrasound.

Adrenal Glands↗

Antenatal diagnosis of congenital heart disease and fetal arrhythmia by ultrasound: prospective study.

Fetal echocardiographic and Doppler ultrasonographic prospective studies were performed in utero on 299 babies delivered at Hirata Municipal Hospital, Shimane, Japan, from May 1984 to June 1986. Two or three ultrasonographic examinations were performed on each fetus from 20 weeks of gestation to term. Three congenital heart anomalies and 12 fetal arrhythmias were diagnosed antenatally, but 3 heart anomalies (2 small ventricular septal defects and 1 moderate pulmonary stenosis) were not detected in utero. Routine echocardiographic screening appears to be a useful diagnostic tool to detect congenital heart anomalies and fetal arrhythmia antenatally.

Arrhythmias, Cardiac↗

Ultrasonographic evidence of ileus.

Twenty-seven patients with ileus were assessed using ultrasound and the related variables suggestive of ileus are presented. If special attention is directed to these variables when a patient complains of nausea, vomiting, colicky abdominal pain and so forth, this entity can be diagnosed early and accurately. Since the distended, air-filled loops of bowel are not so readily recognized, the combined use of X-ray and ultrasound will aid in a follow-up study during treatment as well as in the diagnosis.

Adult↗

Ultrasonographic identification and measurement of the human fetal adrenal gland in utero: clinical application.

The size of the fetal adrenal gland was determined using ultrasonography in 346 fetuses with no complications at 28-40 weeks of gestation and in 12 fetuses of abnormal pregnancies (8 intrauterine growth retardations, 2 anencephalies, 1 intrauterine fetal death and 1 fetus of a mother who had been on steroids for treatment of systemic lupus erythematosus). The fetal adrenal gland area (FAGA), circumference (FAGC) and length (FAGL) were calculated. In 12 abnormal fetuses, FAGA values always fell below the mean +/- 2 SD. Deviations from the normal values were seen in 9 out of 12 cases (75%) in FAGC and in 4 out of 12 cases (33.3%) in FAGL. Of these pregnancies, 4 (33.3%) resulted in intrauterine fetal or neonatal death, and 2 neonates (16.6%) had to be admitted to the neonatal intensive care unit. Measurement of the fetal adrenal gland, especially of the FAGA, should be a pertinent diagnostic tool for perinatologists to manage and control high-risk pregnancies.

Adrenal Glands↗

Succenturiate placenta diagnosed by ultrasound.

The succenturiate placenta is a morphological abnormality, the antenatal recognition of which is important as vessels connecting the main placenta with the succenturiate placenta may rupture during labor and fetal death may ensue. In addition, retention of the placental material may lead to postpartum hemorrhage. We treated 5 patients with a succenturiate placenta and the antenatal ultrasonograms and related discussions are presented herein.

Adult↗

[Effects of neurotropin and other drugs on EEG alterations in SART-stressed (repeated cold-stressed) rats].

SART-stressed (repeated cold-stressed) rats, experimental model animals for vagotonic-type dysautonomia, have been reported to show EEG with lower-amplitude fast waves during resting-arousal and higher-amplitude slow waves during slow-wave sleep compared to normal rats. In this report, the effects of certain drugs on EEG alterations were investigated using the power spectral analysis. EEG was measured 60 min after a single dose of drugs and on the day following the final dose of 6 administrations. Neurotropin, a sedative analgesic, slightly increased faster waves on resting-arousal EEG and slower waves on slow-wave sleep EEG in normal rats, and it prevented SART stress-induced EEG alterations during both resting-arousal and slow-wave sleep. Alprazolam, a minor tranquilizer, and GABOB, a GABA related compound, were also effective on SART stress-induced EEG alterations. Alprazolam produced remarkable but transient high-amplitude fast waves in the resting-arousal EEG of normal rats, and GABOB produced lasting low-amplitude fast waves in the slow-wave sleep EEG of normal rats. From the above results, it appears that Neurotropin may have an effect on EEG alterations caused by SART stress and that its action is likely due to mechanisms different from those of alprazolam and GABOB.

Alprazolam↗

Changes in platelet count and related parameters in SART-stressed mice and the action of administered neurotropin.

In order to hematologically characterize SART-stressed (repeated cold-stressed) animals, which are regarded as model animals of clinical dysautonomia, general hematological analyses were performed in mice subjected to various types of stress. SART-stressed mice showed significant increases in erythrocyte count, hemoglobin, hematocrit and specific gravity of whole blood, no change in leukocyte count and a marked decrease in platelet count. Among the above changes, the decreased platelet count was particularly characteristic of SART-stressed mice. Splenectomy failed to inhibit the SART stress-induced thrombocytopenia. Bone marrow megakaryocyte counts increased following the stress. The bleeding time of SART-stressed mice was more than double that of normal mice. Consecutive administrations of Neurotropin, a sedative analgesic, completely blocked the alterations in platelet count, megakaryocyte count and bleeding time in SART-stressed mice without producing any effect in unstressed mice. From the present results, it is suggested that SART-stressed mice may be characterized by thrombocytopenia, which is not attributable to enhanced function of the spleen or suppressed platelet production in the bone marrow. Moreover, Neurotropin appears to be effective for moderating SART stress.

Alprazolam↗

Mechanism of the analgesic effect of neurotropin.

Neurotropin, an extract from the inflamed skin of vaccinia virus-inoculated rabbits, has been observed clinically to be effective for treating pain in patients with lumbago, SMON and other neuropathies. In the present study, we examined the mechanism of the antinociceptive effect of neurotropin in mice in relation to administration routes, opioids, and noradrenergic or GABAergic drugs, by the tail pressure method. The antinociceptive effects of neurotropin were large when administered by the i.p. and intracisternal (i.cist.) routes, but comparatively small in the case of the intrathecal (i.th.) route. Neurotropin may thus act at the supraspinal level rather than on the spinal cord. The antinociceptive effect of neurotropin was not blocked by naloxone, and no cross-tolerance developed between neurotropin and morphine. The effect of neurotropin was blocked by phentolamine and reserpine, but not by atropine. Its effect was enhanced by GABA, muscimol, aminooxyacetic acid and diaminobutyric acid, but not by baclofen, and blocked by bicuculline methiodide. From these results, the antinociceptive action of neurotropin appears to be non-opioid in nature, and may possible be mediated by the noradrenergic and GABAergic systems, but unrelated to the cholinergic system.

Analgesics↗

Effects of synthetic omega-conotoxin on the contractile responses of segments of rat ileum, stomach fundus and uterus and guinea pig taenia coli.

The effect of synthetic omega-conotoxin (omega-CgTX) on the contractile responses of segments of rat ileum, stomach fundus and uterus and guinea pig taenia coli were investigated. Omega-CgTX (10(-9)-5 x 10(-6) M) did not inhibit the contractile responses of all smooth muscle segments to high KCl and/or ACh. However, unexpectedly, omega-CgTX (3 x 10(-7)-10(-5) M) alone caused dose-dependent contraction of segments of the stomach fundus and uterus. These contractile responses to omega-CgTX alone depended upon the presence and/or the influx of extracellular Ca2+; and they were inhibited by calcium antagonists such as diltiazem, nitrendipine and verapamil, with the exception that the segments of stomach fundus was not inhibited by verapamil. With the segments of uterus, but not those of other tissues, omega-CgTX (10(-7)-5 x 10(-6) M) significantly enhanced the contractile responses to various concentrations of ACh and high KCl. With rat ileum and guinea pig taenia coli segments, omega-CgTX (10(-9)-5 x 10(-6) M) did not induce a contractile response or have an enhancing effect. These findings suggest that omega-CgTX may have a calcium agonist-like effect on smooth muscles such as the stomach fundus and uterus of rats.

Acetylcholine↗

The abnormal open-field behavior of SART-stressed rats and effects of some drugs on it.

As part of an investigation on the behavioral characteristics of SART-stressed animals, an animal model of autonomic imbalance, the open-field behavior of SART-stressed (repeated cold-stressed) rats was studied and compared with that of rats exposed to other types of stress. In addition, the effects of several drugs on it were also studied. As compared with normal rats, SART-stressed rats exhibited increased locomotor activity, rearing and center-field penetration, together with decreased grooming and increased defecation, whereas they showed no significant changes in spontaneous movements in the daytime as measured by an Animex activity meter. These behavioral abnormalities were remarkably different from those due to 1-hr cold, 48-hr cold and repeated restraint stresses. These abnormal forms of open-field behavior due to SART stress were considerably inhibited by chlorpromazine, imipramine and neurotropin at doses having no corresponding influence on normal rats; and they were partially inhibited by alprazolam, diazepam and carpipramine at doses exerting considerable influence on normal rats. The above results show that SART-stressed rats exhibit open-field behavioral abnormalities that are different from those of rats exposed to other types of stress. Such abnormalities include excessive activity, which is considered to be caused by excessive emotionality.

Alprazolam↗