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Biomedical subjects

T Higuchi

Publications and source records attributed to T Higuchi.

At least 487 records · Page 27Linked to original sources

The osmoreceptor complex in the rat: evidence for interactions between the supraoptic and other diencephalic nuclei.

1. Experiments were undertaken to provide evidence for the existence of a circuit of neuronal interconnections between the supraoptic nucleus (SON), the ventral anteroventral third ventricular region (including the organum vasculosum of the lamina terminalis; ventral AV3V) and the median preoptic nucleus (MnPO), and to determine the importance of these connections in the osmotic control of the neuronal activity of the SON. Extracellular recordings were made in the urethane-anaesthetized male rat from neurones in one of these three sites, while the other two sites were electrically stimulated. 2. During recording from the SON, electrical stimulus pulses applied either to the ventral AV3V or to the MnPO were followed by orthodromic excitation (OD+) or initial short-duration inhibition followed by long-duration excitation (OD- +) of most SON neurones (44/48). The latency of OD+ or OD+ component of OD- + response produced by electrical stimulation of the MnPO was significantly (paired t test, P less than 0.01) shorter than that by the stimulation of the ventral AV3V. None of the neurones we recorded in the SON was activated antidromically by stimulation of either the ventral AV3V or the MnPO. Pressure injection of lidocaine (10%, 50 nl) into the MnPO reversibly depressed the OD+ effect after stimulation of the ventral AV3V in all the SON neurones tested (11/11), while injection of lidocaine into the ventral AV3V did not affect the OD+ effect after stimulation of the MnPO in most neurones (7/9). Both types of observation are consistent with the presence of an excitatory input to SON through the MnPO. 3. Pressure injection of lidocaine into both the ventral AV3V and the MnPO reversibly blocked the activation of SON neurones following an I.P. injection of 1.5 M-NaCl (1 ml) (ventral AV3V 11/11; MnPO, 10/10 cells tested). Injection of lidocaine at both sites, however, did not prevent activation of SON neurones by hypovolaemia (2 ml of blood was withdrawn through a cannula in the right atrium: ventral AV3V, 4/5; MnPO, 4/4 cells tested). The integrity of connections in the ventral AV3V and MnPO thus appeared to be essential for osmotic activation of the SON. 4. Of the 119 ventral AV3V neurones which were tested for their response to electrical stimulation of the SON, forty-nine neurones showed orthodromic excitation (OD+; n = 33) or initial inhibition followed by excitation (OD- +; n = 16). Thirty of the forty-nine OD+ or OD- + neurones also showed antidromic excitation (AD) after electrical stimulation of the MnPO.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Application of chemical P-450 model systems to study drug metabolism. III. Metabolism of 3-isobutyryl-2-isopropylpyrazolo[1,5-alpha]pyridine.

Oxidation of 3-isobutyryl-2-isopropylpyrazolo[1,5-alpha]pyridine (IBPP) was carried out with various chemical model systems for cytochrome P-450 in comparison with the liver microsomal system of rats or humans. Alpha-hydroxylation of side chains and ring hydroxylation at the 6 and 7 positions were the main reactions in both systems. A pattern analysis of products using two dimensional thin layer chromatography was employed to compare the functions of the chemical model systems with those of microsomal systems. The reaction profile of IBPP by the catalyst/Pt-colloid/H2, O2 system was most similar to that of human or rat microsomal system. The utility of these chemical models is discussed from the viewpoint of drug metabolism.

Animals↗

Increasing 5-lipoxygenase inhibitory activities by oxidative conversion of o-methoxyphenols to catechols using a Cu2(+)-ascorbic acid-O2 system.

Several complicated o-methoxyphenols were oxidized with high selectivity to catechols by a Cu2(+)-ascorbic acid-O2 system. In this way, the RBL-1 5-lipoxygenase inhibitory activities of o-methoxyphenols were greatly increased. [6]-Norgingerol (4), a novel compound derived from [6]-gingerol (3), shows promise as a lead compound for new drugs because of its high inhibitory potency (IC50 = 5.0 x 10(-8) M).

Anisoles↗

[Convulsive seizures and heterotopic gray matter; report of two cases].

We reported CT and MRI findings of heterotopic gray matter in two patients with intractable convulsive seizures. CT demonstrated space-occupying but non-expansive lesions isodense with the cortical gray matter adjacent to the body of the lateral ventricle. These lesions were not enhanced with contrast infusion. MRI was performed in one case in which the lesion was isointense with the cortical gray matter.

Brain Neoplasms↗

Determination of dopamine, norepinephrine, and related trace amines by prechromatographic derivatization with naphthalene-2,3-dicarboxaldehyde.

Dopamine, norepinephrine, octopamine, tyramine, and 3,4-dihydroxybenzylamine react readily with naphthalene-2,3-dicarboxaldehyde in the presence of cyanide ion under mild conditions to give highly fluorescent cyanobenz[f]isoindole (CBI) products. The CBI products exhibit good solution chemical stability. The high-fluorescence quantum efficiency of the CBI fluorophore and the ability to excite these adducts in the visible region (420-450 nm) enhance the sensitivity and selectivity of this derivatization detection technique. The CBI products of catecholamines and "trace" amines are readily separated by reverse-phase HPLC giving detection limits in the 20 to 60 fmol range (S/N = 3). A prechromatographic derivatization HPLC assay for the trace analysis of dopamine and norepinephrine in urine is described.

Biogenic Amines↗

12S,19- and 12S,20-dihydroxyeicosanoids: novel 12S-hydroxy-5,8-cis-10-trans-14-cis-eicosatetraenoic acid metabolites formed by hydroxylation and reduction in murine lymphocytes.

Murine spleen cells and purified B lymphocytes oxidized arachidonic acid via the lipoxygenase pathway. The major metabolite of both the whole spleen and enriched B lymphocytes was 12S-hydroxy-5,8-cis-10-trans-14-cis-eicosatetraenoic acid. A novel metabolite was observed that did not have an absorbance from 210 to 400 nm, indicating the absence of a conjugated double bond system. The new metabolite was converted to the methyl ester, reduced by platinum oxide, derivatized to the trimethylsilyl ether, and analyzed by gas chromatography-mass spectrometry. A major and a minor component were observed in the analysis of the new compound. The major component had major diagnostic ions indicating the presence of hydroxyl groups at C-12 and C-19. The minor component had major diagnostic ions indicating the presence of hydroxyl groups at C-12 and C-20. The new metabolites are characterized as a mixture of 12S,19- and 12S,20-dihydroxyeicosanoids presumably formed by hydroxylation and reduction of one or more double bonds of 12S-hydroxy-5,8-cis-10-trans-14-cis-eicosatetraenoic acid. These metabolites were formed predominantly with whole spleen lymphocytes but could be detected at longer incubation times or by using 12S-hydroxy-5,8-cis-10-trans-14-cis-eicosatetraenoic acid as the starting substrate with highly enriched B lymphocytes.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

The role of the anteroventral 3rd ventricle area in the osmotic control of paraventricular neurosecretory cells.

To obtain electrophysiological evidence of an involvement of the anteroventral 3rd ventricle (AV3V) area in the osmotic control of neurohypophysial hormone release, extracellular action potentials of paraventricular (PVN) oxytocinergic and vasopressinergic cells during osmotic stimulation induced by i.p. injection of 1.5 M-NaCl solution were obtained from urethane anesthetized AV3V-lesioned, intact and sham-lesioned lactating rats. In intact and sham-lesioned rats the electrical activities of both oxytocinergic and vasopressinergic cells increased in response to the i.p. injection of hypertonic saline. After electrolytic lesion of the AV3V, the responsiveness of both types of cells to osmotic stimuli was severely impaired, whereas oxytocinergic cells were still capable of responding to suckling stimuli by displaying high frequency discharges of action potentials preceding milk-ejection. These results provide electrophysiological evidence that destruction of the AV3V area selectively impairs osmoregulatory input to PVN neurones and that the area has osmosensitive elements which activate the PVN neurosecretory cells when plasma osmotic pressure rises.

Animals↗

Magnetic resonance imaging of brain contusion.

In this study we investigated the time course of brain contusions using magnetic resonance imaging and compared the findings with those of a computed tomography scan. The lesions, which were demonstrated as homogeneous density areas on the computed tomography scan were demonstrated as different intensity areas in the magnetic resonance image. The intensity of the images varied according to the time at which the images were obtained. The findings indicated changes in the nature of the contusions including hematoma hemoglobin, perifocal edema extension, and so on. In conclusion, magnetic resonance imaging is important in the follow-up of chronological change as well as in original diagnosis of brain contusions.

Adolescent↗

Crystallization and preliminary X-ray characterization of branched-chain amino acid aminotransferase from Escherichia coli.

The branched-chain amino acid aminotransferase of Escherichia coli was crystallized in two crystal systems, monoclinic and tetragonal, from polyethylene glycol and ammonium sulfate solutions, pH 7.0, respectively. The crystals were of good quality, with diffractions extending beyond 2.8 A. The space group and unit cell dimensions of the monoclinic system crystals were determined from precession photographs to be C2, and a = 93.9, b = 143.6, c = 143.9 A and beta = 134.3 degrees. For the tetragonal system crystals, the possible space group P422 or P4122, and cell dimensions of a = b = 101 A and c = 249 A were determined. Three identical subunits exist per an asymmetric unit in both types of crystals.

Crystallization↗

Effect of human interferons on morphological differentiation and suppression of N-myc gene expression in human neuroblastoma cells.

The activity of human interferons (HuIFNs) to induce morphological changes and the suppression of N-myc gene expression on human neuroblastoma cells (GOTO and KP-N-RT) was evaluated. Morphological differentiation, characterized as the extension and bifurcation of neurites, the formation of multinucleated giant cells and the formation of neurite networks, was induced by treatment with recombinant HuIFN-gamma (rHuIFN-gamma) and also with natural HuIFN-gamma on human neuroblastoma cells (GOTO and KP-N-RT). But recombinant HuIFN-alpha A and recombinant HuIFN-beta did not induce any changes. The rHuIFN-beta and rHuIFN-gamma inhibited the growth of GOTO and KP-N-RT cells more strongly than the rHuIFN-alpha A did. The expression of N-myc gene was suppressed in GOTO cells treated with rHuIFN-gamma. The suppressive effect of rHuIFN-gamma was dependent on the duration of the treatment. However, rHuIFN-alpha A and rHuIFN-beta did not suppress N-myc gene expression. Moreover, both morphological differentiation and the suppressive effect on N-myc gene expression by rHuIFN-gamma were inhibited in the presence of cycloheximide. These results suggest that the morphological changes and N-myc gene expression in neuroblastoma cells are closely related. Furthermore, this decreased N-myc gene expression during the morphological differentiation may be related to the proteins induced by HuIFN-gamma.

Cell Differentiation↗

Nonacute subdural hematoma: fundamental interpretation of MR images based on biochemical and in vitro MR analysis.

Few reports have described the nature of the appearance of nonacute subdural hematoma on magnetic resonance (MR) images. The authors analyzed MR images in 39 cases of nonacute subdural hematoma and subdural effusion by measuring in vitro proton relaxation times and the biochemical variables of hematoma fluids. T1 became proportionally shorter than T2 with an increase in hematocrit but the direct cause of the variation in T1 and T2 was the amount of methemoglobin. The free iron content, not the bound iron content, was another main cause for shortened T1 and T2. Paradoxical findings in the correlation between the total protein or albumin concentration and relaxation times were noted. It is possible that as the protein level in the supernatant increased, more free iron was bound to the protein, decreasing the influence of the free iron on the relaxation times.

Adult↗

Variant human neuroblastoma cell lines resistant to the differentiation-inducing effect of interferon-gamma.

Human recombinant interferon, (rIFN)-gamma, induced a human neuroblastoma cell line GOTO to differentiate, but neither rIFN-alpha A nor -beta did. To elucidate the mechanism of this rIFN-gamma-specific differentiation-inducing effect, we established two rIFN-gamma-resistant variant GOTO clones. They were insensitive to the growth-inhibitory and differentiation-inducing effect of 1 X 10(3) IU/ml rIFN-gamma. They were slightly sensitive to the growth-inhibitory effect of rIFN-gamma (2 X 10(4) IU/ml). Parental GOTO cells were very insensitive to the antivesicular stomatitis virus (VSV) effect of all three types of rIFNs and even 2 X 10(4) IU/ml rIFN-gamma could not inhibit the cytopathic effect of 5 TCID50 VSV by 50%. The degree of this insensitivity was the same in the variant GOTO cells as in the parental GOTO cells.

Cell Line↗

Stereoselective reduction of acetohexamide in cytosol of rabbit liver.

The stereoselective reduction of acetohexamide, an oral antidiabetic drug, was studied by using the cytosol of rabbit liver. A major metabolite of acetohexamide was isolated in 41.5% yield from the enzyme reaction mixture, and identified as (-)-hydroxyhexamide by techniques including the melting point, thin-layer chromatography, infrared spectrometry and optical rotation. The enantiomeric purity of (-)-hydroxyhexamide was determined on the basis of the proton nuclear magnetic resonance (400 MHz) spectrum of ester (diasteromer) derived by the reaction of (-)-hydroxyhexamide with (R)-(+)-alpha-methoxy-alpha-trifluoromethylphenylacetyl chloride. The (-)-hydroxyhexamide isolated from the enzyme reaction mixture was almost 100% in that enantiomeric form. The metabolic reduction of acetohexamide in the cytosol of rabbit liver appeared to be catalyzed by some enzymes with the same stereoselectivity.

Acetohexamide↗

Further studies on reductive metabolism of acetohexamide in heart.

Species and sex differences of acetohexamide reductase activity were investigated using the cytosolic fraction of heart homogenate. The activity in the rabbit was considerably higher than that in the other species (guinea pig, hamster, rat and mouse). No sex difference of the activity was observed in any of the species tested. Ketone-containing drugs (daunorubicin, befunolol and levobunolol) other than acetohexamide were little reduced in the cytosol of rabbit heart. Some aldehyde reductase inhibitors (phenobarbital, valproate and chlorothiazide) were found to decrease the acetohexamide reductase activity in the cytosol of rabbit heart.

Acetohexamide↗