Biomedical subjects

H Wada

Publications and source records attributed to H Wada.

At least 685 records · Page 38Linked to original sources

PubMed1991

Effect of bright light in the morning on diurnal variations of pineal indoles in NZBWF1 mice.

Exposure to bright light (2000 lx) for 2 h at the beginning of a 12 h light period (10 lx) resulted in about 1 h advances in the onset and termination of N-acetylserotonin (NAc5HT) synthesis in the pineal gland of NZBWF1 strain mice compared with those in mice not exposed to bright light. These effects are in contrast with the effect of exposure to bright light throughout the light period, which delayed the onset of pineal NAc5HT synthesis in NZB mice. The possible relationship of these effects with the mechanism of action of phototherapy of human affective disorder is discussed.

Animals↗

PubMed1991

Organization of the histaminergic system in the brain of the teleost, Trachurus trachurus.

To accumulate phylogenetic information on the central histaminergic system, we investigated the histaminergic system in the brain of a teleost, the jack mackerel (Trachurus trachurus), using the indirect immunofluorescent method with antiserum against histamine. A small number of histamine-immunoreactive cell bodies were observed in the posterior hypothalamus around the posterior recess. Histamine-immunoreactive fibers innervated the telencephalon, diencephalon, tegmentum, and rostral part of the medulla oblongata. The immunoreactive fibers were very sparse or absent in the olfactory bulb, optic tectum, cerebellum, caudal part of the medulla oblongata, spinal cord, and hypophysis. Ascending fiber bundles were seen in the basal hypothalamus, supplying fiber collaterals to the telencephalon and diencephalon, whereas descending fibers were observed in the midline of the lower brainstem. These findings suggest that the central histaminergic system of the jack mackerel is homologous to those of mammals, reptiles, and amphibians, although poorly developed compared with them. The histamine-immunoreactive neuronal cell bodies found in the border area between the mesencephalon and rhombencephalon of the river lamprey were not detected in the brain of the jack mackerel.

Animals↗

PubMed1991

Effect of cholecystokinin receptor antagonists, MK-329 and L-365,260, on cholecystokinin-induced acid secretion and histidine decarboxylase activity in the rat.

To elucidate the regulatory mechanism of acid secretion by cholecystokinin (CCK) in vivo, we compared the effects of CCK and gastrin on acid secretion and histidine decarboxylase (HDC) activity. We also examined the effects of MK-329, a specific antagonist for pancreatic-type CCK receptor, and L-365,260, a specific antagonist for gastrin-type CCK receptor, on the action of CCK. Graded doses of CCK or gastrin were intravenously infused into conscious rats with gastric fistula. Gastrin-17 I infusion up to 10 nmol/kg/h resulted in dose-related increases in acid secretion. CCK-8 infusion also caused an increase in acid secretion. However, it reached a peak with 0.3 nmol/kg/h CCK-8 and attenuated with higher concentrations of CCK-8. This attenuating effect of a higher dose of CCK was reversed by MK-329, but not by L-365,260. Both CCK and gastrin were potent in increasing fundic HDC activity, and the effect of CCK on HDC activity was significantly inhibited by L-365,260, but not by MK-329. Taken together, the present study suggests that CCK and gastrin stimulate histamine formation via a gastrin-type CCK receptor, and the attenuating action of CCK with higher concentrations on acid secretion in vivo is mediated by a pancreatic-type CCK receptor.

Animals↗

PubMed1991

Type-2 astrocytes show intracellular Ca2+ elevation in response to various neuroactive substances.

The effects of various neuroactive substances on the intracellular free Ca2+ concentration ([Ca2+]i) in cultured type-2 astrocytes were examined by fura-2-based microfluorometry. Type-2 astrocytes showed [Ca2+]i elevation in response to all the substances examined, i.e. carbachol (10(-4) M), histamine (10(-4) M), noradrenaline (10(-4) M), serotonin (10(-4) M), substance P (10(-6) M), vasopressin (10(-6) M) and glutamate (10(-4) M). Not all type-2 astrocytes, however, responded to these substances at the concentrations tested, and the percentages of astrocytes showing a Ca2+ response differed depending on the substance. These results indicate that type-2 astrocytes are potential targets for widely diverse neuroactive substances and heterogeneous in response to them.

Animals↗

PubMed1991

High-performance liquid chromatographic determination of histamine N-methyltransferase activity.

A method for the determination of histamine N-methyltransferase (HMT) activity by high-performance liquid chromatography based on post-column derivatization with omicron-phthalaldehyde is described. The determination involves the separation of the substrate, histamine, from its product. N tau-methylhistamine, using a weak cation exchanger, followed by on-line derivatization of these imidazoleamines with omicron-phthalaldehyde and their detection and quantitation with a fluorimetric detector. This assay method is suitable for the measurement of HMT activity during enzyme purification.

Animals↗

PubMed1991

Presynaptic localization of histamine H3-receptors in rat brain.

The localization of histamine H3-receptors in subcellular fractions from the rat brain was examined in a [3H] (R) alpha-methylhistamine binding assay and compared with those of histamine H1- and adrenaline alpha 1- and alpha 2-receptors. Major [3H](R) alpha-methylhistamine binding sites with increased specific activities ([3H]ligand binding vs. protein amount) were recovered from the P2 fraction by differential centrifugation. Minor [3H](R)alpha-methylhistamine binding sites with increased specific activities were also detected in the P3 fraction. Further subfractionation of the P2 fraction by discontinuous sucrose density gradient centrifugation showed major recoveries of [3H](R)alpha-methylhistamine binding in myelin (MYE) and synaptic plasma membrane (SPM) fractions. A further increase in specific activity was observed in the MYE fraction, but the SPM fraction showed no significant increase in specific activity. Adrenaline alpha 2-receptors, the pre-synaptic autoreceptors, in a [3H] yohimbine binding assay showed distribution patterns similar to histamine H3-receptors. On the other hand, post-synaptic histamine H1- and adrenaline alpha 1-receptors were closely localized and distributed mainly in the SPM fraction with increased specific activity. Only a negligible amount was recovered in the MYE fraction, unlike the histamine H3- and adrenaline alpha 2-receptors.

Animals↗

PubMed1991

Biochemical characterization of histamine H1 receptors in bovine adrenal medulla.

Bovine adrenal medullary membranes display high affinity and saturable binding to [3H]mepyramine, a selective H1 antagonist, with Kd of 1.5 +/- 0.1 nM and Bmax of 694 +/- 12 fmol/mg protein. [3H]Azidobenzpyramine, an azidobenzamide derivative of mepyramine, was synthesized and used to photolabel the high affinity mepyramine binding sites. Following photolysis, a protein component with an approximate molecular weight of 53-58 kDa was shown to be covalently labeled, as judged by gel filtration and SDS/PAGE; labeling being greatly reduced in the presence of excess unlabeled mepyramine. These results indicate that bovine adrenal medulla expresses a large number of H1 receptors, which are pharmacologically and biochemically indistinguishable from the H1 receptor of many other tissues of various species.

Adrenal Medulla↗

PubMed1991

Histamine-induced inositol phosphate accumulation in type-2 astrocytes.

Histamine elicited dose-dependent accumulation of [3H]inositol phosphates in type-2 astrocytes, but not in type-1 astrocytes. The ED50 was about 2.4 x 10(-6) M and the maximal response was obtained at 10(-4) M. This response was dose-dependently inhibited by H1-antagonists, mepyramine and D- and L-chlorpheniramine. Furthermore, D- and L-chlorpheniramine showed stereoselectivity in the inhibition. On the other hand, an H2-antagonist, famotidine, and an H3-antagonist, thioperamide, did not inhibit the response. These results indicate that histamine stimulates accumulation of inositol phosphates in type-2 astrocytes via H1-receptors.

Animals↗

PubMed1991

Single type-2 astrocytes show multiple independent sites of Ca2+ signaling in response to histamine.

Intracellular Ca2+ plays an important role in signal transduction as a second messenger. In various types of cells, inositol 1,4,5-trisphosphate-induced elevations of intracellular free Ca2+ concentration ([Ca2+]i) have been reported to be uniform in single cells or originate at discrete sites from which they then propagate throughout the cells. These observations so far imply that a single cell functions as a minimal unit for inositol 1,4,5-trisphosphate-induced Ca2+ signaling. In this study, we examined the effects of histamine on [Ca2+]i of type-2 astrocytes using fura-2-based digital imaging fluorescence microscopy and found an unusual type of Ca2+ signaling in these cells. Histamine induced [Ca2+]i elevation in type-2 astrocytes by means of histamine H1 receptors. Submaximal concentrations of histamine (10(-7)-10(-6) M) evoked multiple sites of oscillatory [Ca2+]i elevation in single type-2 astrocytes. These Ca2+ "hot spots" were localized in the processes of the astrocytes but not in the cell bodies. The time courses of [Ca2+]i oscillations in different hot spots were not synchronized, indicating that each of them formed an independent compartment of Ca2+ signaling. When higher concentrations (10(-5)-10(-4) M) of histamine were added, [Ca2+]i in the processes remained elevated at high levels and [Ca2+]i elevations propagated from the processes to the cell bodies. These results suggest that individual processes of type-2 astrocytes can form minimal units for Ca2+ signaling in response to submaximal concentrations of histamine and that single type-2 astrocytes may function as multiple units for Ca2+ signaling.

Animals↗

PubMed1991

A new congenital abnormal fibrinogen Ise characterized by the replacement of B beta glycine-15 by cysteine.

A new case of heterozygous dysfibrinogenemia characterized by the replacement of NH2-terminal amino acid of fibrin beta-chain was found in a 50-year-old man. Despite a prolonged thrombin time, the propositus' fibrinogen had a normal reptilase time with the normal release of fibrinopeptide A. Release of fibrinopeptide B by thrombin was strongly affected, but a very high concentration of thrombin almost completely released fibrinopeptide B with a normal elution pattern on reversed-phase high performance liquid chromatography (HPLC). Lysylendopeptidase-cleavage of purified B beta-chains analyzed on HPLC showed the decrease of one peptide compared with the normal and the appearance of an abnormal peptide peak. These peptides were treated with thrombin and further separated on HPLC. Amino acid sequence analysis of the abnormal peptide demonstrated that B beta glycine-15, NH2-terminus of the fibrin beta-chain, was replaced by cysteine. These findings will be of particular importance because they strongly support the hypothesis that the NH2-terminal portion of the fibrin beta-chain is involved in the polymerization reaction by thrombin. The propositus' daughter and two sisters had the same abnormal fibrinogen. This unique inherited abnormal fibrinogen was designated as fibrinogen Ise. During these studies, we found that a very high concentration of thrombin cleaves not only the A alpha Arg19-Val20 bond but also the COOH-terminal region of alpha-chains, which results in the generation of further degraded alpha-chains with apparent molecular weights of 44,000 or less.

Amino Acid Sequence↗

PubMed1991

Plasma level of IL-1 beta in disseminated intravascular coagulation.

The plasma level of interleukin-1 beta (IL-1 beta) was determined in normal individuals, patients with disseminated intravascular coagulation (DIC), patients in the pre-DIC period (within 7 days before the onset of DIC), and non-DIC patients to examine the relationship between DIC and the plasma IL-1 beta level. The plasma IL-1 beta level was 0-0.085 ng/ml in normal individuals, with little difference being seen according to related age. It was significantly higher in the DIC group (0.19 +/- 0.19 ng/ml) than in the pre-DIC group (0.05 +/- 0.08 ng/ml) or the non-DIC group (0.09 +/- 0.01 ng/ml). The plasma IL-1 beta level was not markedly elevated in leukemia patients, even in the DIC group, but it was significantly increased in the DIC group of solid cancer patients and was generally elevated in patients with sepsis. It was markedly elevated to 0.39 +/- 0.26 ng/ml in patients with organ failure. When mononuclear cells were incubated with lipopolysaccharide, it was found that IL-1 beta, tumor necrosis factor, and tissue factor (TF) were released into the medium, and there was an increase of TF release from endothelial cells incubated with this medium. These results suggest that the increase in IL-1 beta reflected the activation of monocytes and may be an important factor in DIC and its associated organ failure.

Adult↗

PubMed1991

Effects of intracerebroventricular histamine injection on circadian activity phase entrainment during rapid illumination changes.

Histamine is reported to have different effects on shifting the circadian activity phase depending on its circadian administration time (CT). The delay-sensitive period is CT 12-15, and the advance-sensitive period is CT 0-3. The activity phase of rats was entrained by a new light-dark cycle within a week in groups treated with either saline or i.c.v. histamine at CT 12-15. However, on treatment at CT 0-3 the activity phase of the group treated with histamine was entrained by the new light-dark cycle in half the period required for entrainment in the control group.

Activity Cycles↗

PubMed1991

Synaptic and extra-synaptic distribution of histamine H1-receptors in rat and guinea pig brains.

Localization of histamine H1-receptors in subcellular fractions from rat and guinea pig brains was examined in a [3H]mepyramine binding study. Major [3H]mepyramine binding sites with increased specific activities [( 3H]mepyramine binding vs. protein amount) were recovered from P2 fractions from both rat and guinea pig brains by differential centrifugation. Further subfractionation of both rat and guinea pig P2 fractions by a discontinuous sucrose density gradient centrifugation showed the highest recovery of [3H]mepyramine binding with further increased specific activities found in synaptic plasma membrane (SPM) fractions. Minor [3H]mepyramine binding sites with increased specific activities were detected in both rat and guinea pig P3 fractions. [3H]Mepyramine binding sites in SPM and P3 fractions showed identical Kd values in each species. These results indicate that histamine H1-receptors are located not only in synaptic but also in extra-synaptic membranes of both rat and guinea pig brains.

Animals↗

PubMed1991

Establishment and characterization of a human leukemic cell line with megakaryocytic features: dependency on granulocyte-macrophage colony-stimulating factor, interleukin 3, or erythropoietin for growth and survival.

A new human leukemia cell line with megakaryocytic features, designated UT-7, was established from the bone marrow of a patient with acute megakaryoblastic leukemia. Surface marker analysis revealed that the majority of the cells reacted with monoclonal antibodies against platelet glycoprotein Ib (CD42b), glycoprotein IIb/IIIa (CD41a), MY 7 (CD13), MY 9 (CD33), and glycophorin A antigens. Cytogenetic analysis showed a human male near-tetraploid karyotype with a modal chromosome number of 92-96. Flow cytometry-derived DNA histograms demonstrated that the majority of the cells spontaneously contained 4 N DNA ploidy levels. Ultrastructural study showed that platelet peroxidase activity was weakly positive but myeloperoxidase activity was negative. Ferritin and theta-granule, which have been used as ultrastructural markers for the erythroid lineage, could not be detected. In response to phorbol myristate acetate, platelet factor 4 and beta-thromboglobulin, which were specifically synthesized in the process of megakaryocyte maturation, dramatically increased in UT-7 cells. This was accompanied by an increase in cell size, ploidy level, platelet peroxidase activity, and the surface density of glycoprotein IIb/IIIa antigen. These findings suggest that UT-7 is a new leukemic cell line with megakaryocytic features and with the potential to differentiate into cells with more mature megakaryocytic properties in response to phorbol myristate acetate. This cell line showed strict dependency on interleukin 3 (IL-3), granulocyte-macrophage colony-stimulating factor, or erythropoietin. The maximal effective doses of IL-3, granulocyte-macrophage colony-stimulating factor, and erythropoietin for proliferation in liquid culture were 10 units/ml, 1 ng/ml, and 1 unit/ml, respectively. These concentrations were comparable to the doses that maximally stimulate the clonal growth of normal hemopoietic cells. IL-6 could stimulate the proliferation of UT-7 cells but not maintain the line in long-term culture. UT-7 cells may be a useful model for (a) the analysis of gene regulation of megakaryocytic maturation-associated proteins expressed in the process of megakaryocytic differentiation and (b) the study of signal transduction of hemopoietic factors associated with megakaryocytopoiesis.

Antigens, CD↗

PubMed1991

High rate of portal thrombosis after splenectomy in patients with esophageal varices and idiopathic portal hypertension.

Data on 126 consecutive patients who were admitted to our clinics from January 1979 to May 1989 were scrutinized to assess changes in portal hemodynamics following splenectomy. Two groups were classified: (1) a group of 106 patients with cirrhosis of the liver and (2) a group of 20 patients with idiopathic portal hypertension (IPH). Portal thrombosis was present in five (25.0%) of the 20 patients with IPH and in two (1.8%) of the 106 patients with cirrhosis of the liver. As seen on celiac arteriography, the mean (+/- SD) diameter of the trunk of the splenic artery and vein was 8.99 +/- 1.55 and 16.2 +/- 3.6 mm, respectively, in patients with IPH, while it was 7.94 +/- 1.28 and 14.2 +/- 3.1 mm, respectively, in patients with cirrhosis of the liver. Changes in portal venous pressure were 78.4 +/- 59.4 mm H2O in patients with IPH and 43.5 +/- 38.7 mm H2O in patients with cirrhosis of the liver. There were no significant differences in the maximum level of thrombocytes in patients with IPH or in those patients with cirrhosis of the liver. These events suggest that portal thrombosis can occur with a significantly higher incidence in patients with IPH than in those patients with cirrhosis of the liver after splenectomy, and a decrease in blood flow in the portal vein may be closely linked to the formation of portal thrombosis after splenectomy in patients with IPH. Preoperative examination of portal hemodynamics must be thorough.

Esophageal and Gastric Varices↗

PubMed1991

Plasma level of tumor necrosis factor in disseminated intravascular coagulation.

The plasma level of tumor necrosis factor (TNF) was determined in 20 normal individuals, 52 patients with disseminated intravascular coagulation (DIC), 22 pre-DIC patients, and 39 non-DIC patients. TNF was not detected in the normal subjects, and the level was very low in non-DIC patients. However, the TNF level was significantly elevated in DIC patients, and it was moderately increased in pre-DIC patients shortly before the onset of DIC. This increase in circulating TNF may be associated with DIC. TNF was higher in DIC associated with solid cancer than in DIC associated with leukemia or sepsis. The increase in plasma TNF level was mildly correlated with DIC score, and it was significantly increased in patients with poor prognosis. However, the plasma TNF level in DIC patients with organ failure was not significantly different from those without organ failure. We conclude that the increase in circulating TNF reflects the pathogenic factors in DIC rather than being a consequence of organ failure due to DIC.

Disseminated Intravascular Coagulation↗

PubMed1991

Dynamic fluctuations in blood of thrombin/antithrombin III complex (TAT).

The dynamic fluctuation of thrombin-antithrombin III complex (TAT) was studied in blood obtained during the daytime (at 9 AM, noon, 3 PM), during extracorporeal circulation and during the course of disseminated intravascular coagulation (DIC), to certify whether the level of TAT in blood can reflect the generation of thrombin. In 10 healthy male volunteers, the mean values of TAT (micrograms/liter) were 1.74 (+/- 1.36) at 9 AM, 1.22 (+/- 0.47) at noon, and 1.25 (+/- 0.68) at 3 PM. TAT did not show a daytime fluctuation, unlike fibrinolytic factors. The mean values of TAT in 38 hemodialyzed patients were 4.83 (+/- 2.8) before the initiation, 6.59 (+/- 4.39) in the first hour, and 13.42 (+/- 10.96) at the end of a dialysis session. In 20 patients undergoing open heart surgery, the mean value of TAT was increased during cardiopulmonary bypass (CPB) and decreased with time after the end of surgery. The fibrinopeptide A (FPA) value was increased with TAT during CPB but achieved a maximum level immediately after heparin neutralization by protamine. In 20 patients with DIC, the values of TAT varied from 5.8 to 297 micrograms/liter in the blood at the onset of DIC. In seven of eight patients treated with low-molecular-weight heparin (LMW-H), the values of TAT and FPA were lower 24 hr after LMW-H than before the treatment. These results suggest that the level of TAT in blood reflected the formation of thrombin and could serve as a sensitive parameter of activated coagulation in circulating blood.

Adult↗

PubMed1991

Histaminergic neuron system: morphological features and possible functions.

The histaminergic neuron systems in rat brain have been identified by immunocytochemical techniques using antibodies against histidine decarboxylase or histamine itself. Here, the details of the distribution of the histaminergic neuron networks are presented. Judging from the widespread distribution of the nervous system, it is postulated that the histaminergic neuron system is involved in various brain functions. Some functions, including the circadian rhythms, sleep-arousal cycles, drinking, feeding, thermoregulation, and neuroendocrine controls which were elucidated by administration of alpha-fluoromethylhistidine, a suicide substrate for histidine decarboxylase, are discussed here, although the true functions are still under investigations.

Animals↗