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Biomedical subjects

T Higuchi

Publications and source records attributed to T Higuchi.

At least 469 records · Page 26Linked to original sources

Postnatal development of acetohexamide reductase activities in microsomes and cytosol of rat liver.

The postnatal development of acetohexamide reductase activities in liver microsomes and cytosol were examined in male rats. The developmental pattern of acetohexamide reductase activity in liver microsomes was distinguished from that in liver cytosol. Furthermore, acetohexamide reductase activity in liver microsomes was effectively suppressed by castration, but the activity in liver cytosol was not affected by castration. These results clearly indicate that enzymes with physiologically different roles can catalyze the metabolic reduction of acetohexamide in rat liver.

Age Factors↗

[The application of in vivo diffusion weighted magnetic resonance imaging to intracranial disorders].

We have developed a magnetic resonance (MR) spin echo method to obtain diffusion weighted imaging using motion-probing gradient (MPG) pulses in one or three orthogonal directions before and after a 180 degree pulse. Phantom models containing water and acetone, normal volunteers and patients with brain tumors, brain edema and infarction were examined. Experimental models of brain edema including triethyltin intoxication and cold injuries were also examined in Wistar rats. MRI was performed at a 1.0-T clinical machine or a 4.7-T experimental machine using spin echo pulse sequences with or without additional MPGs on one or three orthogonal axes. The one direction method was useful to define diffusion anisotropy of myelinated axonal fibers in white matter. Faster diffusion was detected in the white matter parallel to the direction of MPGs. On the other hand, slower diffusion was detected perpendicular to the direction of MPGs because the myelin sheath restricted water diffusion. The three orthogonal gradients method was useful to demonstrate the difference in the diffusion coefficients in various diseases due to its larger total gradient strength. The clear distinction between the cytotoxic edema, which revealed slower diffusion, and the vasogenic edema, which revealed faster diffusion, was demonstrated in the experimental models using diffusion weighted image. In the clinical cases, faster diffusion was demonstrated in the brain tumor and perifocal vasogenic edema, which was in agreement with the results in the experimental models of rats. Brain tumors such as low grade astrocytoma with microcysts and perifocal vasogenic edema have very wide extracellular space.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Reactivity for prostaglandins and inhibition by nonsteridal anti-inflammatory drugs of rabbit liver befunolol reductase.

Befunolol (BF) reductase with 3 alpha-hydroxysteroid dehydrogenase activity, which was purified from rabbit liver, catalyzed the oxidoreduction of prostaglandins, indicating that this enzyme has broad substrate specificities for endogenous substances. BF reductase was strongly inhibited by a variety of nonsteridal anti-inflammatory drugs and then a significant correlation was observed between the logarithms of IC50 (concentration required to produce 50% inhibition of BF reductase activity) values and the maximal daily human doses for nonsteroidal anti-inflammatory drugs. These results suggest that the pharmacological potency of nonsteroidal anti-inflammatory drugs may be predicted from the degree of inhibition of BF reductase by these drugs.

Alcohol Oxidoreductases↗

Activation of supraoptic neurosecretory cells by osmotic stimulation of the median preoptic nucleus.

In urethane-anesthetized male rats extracellular recordings were obtained from neurosecretory cells in the supraoptic nucleus (SON) while each of electrical stimulation and local osmotic stimulation produced by pressure injection of hypertonic saline was applied to the median preoptic nucleus (MnPO) or to the medial septal nucleus (MS). Electrical stimulation of the MnPO produced orthodromic excitation or initial inhibition followed by strong excitation in most SON cells (59/61), and local osmotic stimulation of the MnPO excited majority of cells (39/51). On the contrary, local osmotic stimulation of the MS did not excite SON cells, although electrical stimulation excited all the cells (5/5). The results suggest that the MnPO is one of the osmosensitive sites controlling electrical activity of SON neurosecretory cells.

Action Potentials↗

A novel enzymatic decarboxylation of oxalic acid by the lignin peroxidase system of white-rot fungus Phanerochaete chrysosporium.

Oxidation of veratryl alcohol by lignin peroxidase (LiP) was potently inhibited by oxalic acid. The inhibition analysis with Lineweaver-Burk plots clearly showed that the type of inhibition is non-competitive. The enzymatic oxidation of veratryl alcohol in the presence of 14C-oxalic acid yielded radioactive carbon dioxide. The results indicate that the apparent inhibition of LiP is caused by reduction of the veratryl alcohol cation radical intermediate back to the substrate level by oxalate, which is concomitantly oxidized to carbon dioxide.

Benzyl Alcohols↗

3-Hydroxycoumarins: first direct preparation from coumarins using a Cu2(+)-ascorbic acid-O2 system, and their potent bioactivities.

First direct 3-hydroxylation of a coumarin ring via a purely chemical system, previously only possible using cytochrome P-450, was successfully conducted by a Cu2(+)-ascorbic acid-O2 system; the two 3-hydroxycoumarins obtained were novel compounds, 3-hydroxyscopoletin and 3-hydroxyisoscopoletin. 5-Lipoxygenase and alpha-D-glucosidase inhibitory activities of coumarins greatly increased through 3-hydroxylation. 3-Hydroxyscopoletin and 3-hydroxyumbelliferone had a high inhibitory potency for 5-lipoxygenase and for alpha-D-glucosidase respectively; they serve as lead compounds for new drugs.

Arachidonate 5-Lipoxygenase↗

Electrophysiological evidence for neural connections between the supraoptic nuclei.

Effects of electrical stimulation of the contralateral supraoptic nucleus (SON) on the activity of neurosecretory neurons in the SON were studied in urethane-anesthetized lactating rats. Thirty-one out of 41 oxytocin neurons were excited and only two neurons were inhibited by contralateral SON stimulation. Eight out of 26 vasopressin neurons were excited and 8 were inhibited. These responses were not affected by suckling stimuli. Neither oxytocin nor vasopressin neurons tested were antidromically activated by contralateral SON stimulation. Thus monosynaptic connections between the bilateral SON neurosecretory neurons seem to be very few, if any. These results suggest that neural connections exist between the bilateral SON and that they are mainly polysynaptic.

Action Potentials↗

Determination of fluorescent cyanobenz[f]isoindole derivatives of dopamine and norepinephrine using high performance liquid chromatography with chemiluminescence detection.

Dopamine (DA), norepinephrine (NE) and 3,4-dihydroxybenzylamine (DHBA) are converted to highly fluorescent cyanobenz[f]isoindole (CBI) derivatives by reacting these amines with naphthalene-2,3-dicarboxaldehyde in the presence of cyanide ion. Femtomole amounts of these CBI derivatives separated by reverse-phase high performance liquid chromatography can be detected by a post-column chemiluminescence system utilizing bis(2,4-dinitrophenyl) oxalate and hydrogen peroxide. Linear detection response was observed between 1 to 600 fmol, giving a signal to noise ratio of approximately 15 at the 1 fmol level. An assay procedure was developed for the determination of DA and NE in 20 microL of urine sample using DHBA as the internal standard.

Animals↗

Effects of atrial natriuretic peptide on brain oedema: the change of water, sodium, and potassium contents in the brain.

We examined the effect of atrial natriuretic peptide (ANP) administration on cerebral oedema in rats. Intravenous ANP infusion with total dose of 120 micrograms/kg and 100 micrograms/kg suppressed the elevation of water and Na contents in left middle cerebral artery (MCA) occluded and cold injured brain tissue, indicating that ANP has a suppressive effect on cerebral oedema. Similar ANP infusion at a low dose of 1 microgram/kg/h for 6 h also resulted in observation of the anti-oedematous effect in both models, with no observable occurrence of the known systemic effects of ANP on systolic blood pressure (SBP), heart rate (HR), hematocrit, or serum electrolyte ion (Na+, K+, Cl-) concentrations. The results thus suggest that the anti-oedematous effect of ANP is attributable to water and Na content control by ANP specific to the damaged tissue, possibly through inhibition of sodium transport. Taken together with a recent study in which it was shown that ANP might inhibit sodium transport in cerebral microvessel, our results suggest that ANP suppresses the development of brain oedema by inhibiting sodium transport and the coupled water influx.

Animals↗

Effects of atrial natriuretic peptide on ischaemic brain oedema evaluated by the proton magnetic resonance method.

The effect of atrial natriuretic peptide (ANP) on cerebral oedema in rats was examined by magnetic resonance (MR). After occlusion of the left middle cerebral artery (MCA) to induce cerebral ischaemia, rats received continuous infusion of ANP for 24 h at a total dose of 120 micrograms/kg or 150 micrograms/kg. Proton relaxation times (T1 and T2) of excised oedematous tissue were measured in vitro and the area of the oedematous region was determined in vivo by the use of magnetic resonance imaging (MRI). The administration of ANP was found to decrease the lengthening of both T1 and T2 in the oedematous tissues and shown by MRI to decrease the area of the oedematous region, compared with group receiving saline. The topographic observations in vivo suggest that ANP suppress the development of the oedematous region.

Animals↗

Asymptomatic primary sclerosing cholangitis treated with ursodeoxycholic acid.

Ursodeoxycholic acid treatment (600 mg/day) was evaluated in a patient with asymptomatic primary sclerosing cholangitis. Serum levels of biliary enzymes decreased to normal ranges within 1 month's treatment and remained normal for 26 months. Serum chenodeoxycholic acid had been replaced by ursodeoxycholic acid, and hepatic copper metabolism, assessed by x-ray probe analysis, improved during the treatment. However, neither biliary tract sclerosis nor portal tract pathology changed with the treatment. These observations suggest that ursodeoxycholic acid protects the liver in primary sclerosing cholangitis by improving the metabolism of bile acid and copper.

Adult↗

Effects of anticonvulsants and gamma-aminobutyric acid (GABA)-mimetic drugs on immunoreactive somatostatin and GABA contents in the rat brain.

Immunoreactive somatostatin (IR-SRIF) and gamma-aminobutyric acid (GABA) contents in the rat brain were investigated to study chronic effects of the treatment with anticonvulsants, carbamazepine (CBZ), valproic acid (VPA) and phenytoin (PHT). Decreased IR-SRIF levels were found in several brain regions after chronic treatment with VPA and CBZ. GABA concentrations were found to be increased significantly in chronic CBZ and VPA treatment in the rat brain, especially in limbic structures. PHT had no effect on both IR-SRIF and GABA contents in the rat brain. Effects of several GABA-mimetic drugs also were studied on IR-SRIF contents in the rat brain. Aminooxyacetic acid an inhibitor of GABA transaminase, induced a decrease in IR-SRIF concentration in the pyriform and entorhinal cortex, whereas ethanolamine-o-sulfate, another GABA-transaminase inhibitor and muscimol, a GABA receptor agonist had no effect on brain IR-SRIF after acute administration. The present results suggest that endogenous somatostatin has an important role for anticonvulsant properties of CBZ and VPA, but not of PHT. The relationship between the changes in IR-SRIF and the GABA transmitter system in the anticonvulsant action of CBZ and VPA remains to be clarified.

Aminooxyacetic Acid↗

Characterization of sulpiride-displaceable 3H-YM-09151-2 binding sites in rat frontal cortex and the effects of subchronic treatment with haloperidol on cortical D-2 dopamine receptors.

We investigated the pharmacological properties of the sulpiride-displaceable binding sites labeled by 3H-YM-09151-2 in rat frontal cortex, compared to those in striatum. The IC50 value of ketanserin was 486 nM, which was apparently different from its affinity for the 5HT-2 receptor. Various dopamine antagonists showed almost the same inhibitory effects for binding site in frontal cortex and striatum. Sulpiride-displaceable 3H-YM-09151-2 binding sites were considered to be D-2 dopamine receptors. After subchronic treatment with haloperidol, the D-2 receptor density of frontal cortex (0.55 fmol/mg tissue) increased to the same extent (about 25%) as striatum without significant change in apparent affinity.

Animals↗

Submandibular sialoadenitis due to a foreign body.

A case of a painful swelling of a submandibular gland in a 62-year-old woman is reported. This eventually proved to be caused by a foreign body (fish bone) in the main intrasalivary duct of the gland.

Female↗

Rapid phosphorylation of cellular proteins during differentiation of neuroblastoma cells induced by recombinant human interferon-gamma.

Cells of two human neuroblastoma lines, GOTO and KP-N-RT-LN, differentiated in response to treatment with 1,000 IU/ml of recombinant human interferon-gamma (rIFN-gamma), but did not respond to rIFN-alpha 2 or IFN-beta. Treatment with rIFN-gamma rapidly increased the phosphorylation of several cell proteins; in particular, there was enhanced phosphorylation of a 61-kD protein within 1 min after treatment. This enhancement was not observed in variant sublines of GOTO cells, which did not differentiate when treated with rIFN-gamma. These findings suggest that when neuroblastoma cells are induced to differentiate by treatment with rIFN-gamma, phosphorylation of the 61-kD protein plays an important role.

Cell Differentiation↗

Three-dimensional structures of aspartate aminotransferase from Escherichia coli and its mutant enzyme at 2.5 A resolution.

The structure of Escherichia coli aspartate aminotransferase complex with the inhibitor 2-methylaspartate, and that of the mutant enzyme in which an arginine was substituted for a lysine residue thereby forming a Schiff base with the coenzyme pyridoxal 5'-phosphate, were determined at 2.5 A resolution, by the molecular replacement method using the known structure of pig cytosolic aspartate aminotransferase. The enzyme catalyzes the reversible transamination between L-aspartate and alpha-ketoglutarate, and forms a dimeric structure of two identical subunits. Each subunit comprises two domains, a small and a large one. Although, in general, the overall and secondary structure of E. coli enzyme are similar to those of higher animals, some differences of enzymatic action between the enzyme from E. coli and those from higher animals could be explained on the basis of the X-ray structures and molecular mechanics calculation based on them.

Amino Acids↗