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H Wada

Publications and source records attributed to H Wada.

At least 703 records · Page 39Linked to original sources
PubMed1991

Histamine H1-receptors on astrocytes in primary cultures: a possible target for histaminergic neurones.

The characteristics of histamine H1-receptors expressed on astrocytes from the cerebral cortex of new born rats were analysed by the [3H]-mepyramine binding assay. The apparent dissociation constant (Kd) was 10.4 nM and the binding capacity (Bmax) of 262 fmol/mg protein. H1-antagonists inhibited the [3H]mepyramine bindings and the isomers of chlorpheniramine showed a stereoselectivity for the inhibition of the bindings. Two distinct populations of cultured astrocytes, type-1 and type-2 astrocytes, were enriched and histamine-induced accumulations of inositol phosphates (IP) and cyclic AMP and histamine-evoked Ca++ signals were examined. Histamine stimulated the accumulation of IP in type-2 astrocytes, but not in type-1 astrocytes. The accumulation of cyclic AMP induced by histamine was observed in type-1 astrocytes, although not in type-2 astrocytes. Histamine-induced Ca++ signals were observed in 17.2% of type-1 astrocytes and in 72.9% of type-2 astrocytes. Histamine-induced Ca++ signals in type-2 astrocytes were antagonized by H1-antagonists, but not by H2- antagonists. Histamine-induced Ca++ signals were classified into 4 patterns, ie. transient, oscillatory, sustained and biphasic. When extracellular Ca++ was omitted or La was added to the extracellular medium, sustained phase of Ca++ signal disappeared and transient and oscillatory patterns were only observed. Phorbol ester inhibited histamine-induced Ca++ signals but pertussis toxin (IAP) and organic voltage dependent Ca++ channel blockers had no effect. Histamine-induced Ca++ elevation appeared initially in processes and then Ca++ wave propagated to the cell soma. Ca++ elevation was observed only in the processes in some cells.

Animals↗
PubMed1991

In vivo release of neuronal histamine in the hypothalamus of rats measured by microdialysis.

Using an in vivo intracerebral microdialysis method coupled with an HPLC-fluorometric method, we investigated the extracellular level of endogenous histamine in the anterior hypothalamic area of urethane-anaesthetized rats. The basal rate of release of endogenous histamine in the anterior hypothalamic area measured by this method was 0.09 +/- 0.01 pmol/20 min. When the anterior hypothalamic area was depolarized by infusion of 100 mM K+ through the dialysis membrane or electrical stimulation at 200 mu A was applied through an electrode implanted into the ipsilateral tuberomammillary nucleus, histamine release increased to 175% and 188%, respectively, of the basal level. These increases were completely suppressed by removal of extracellular Ca2+. The basal release of histamine was also suppressed after infusion of 10(-6) M tetrodotoxin or i.p. administration of 100 mg/kg of alpha-fluoromethylhistidine. On the other hand, 3-fold increase in the basal release was observed after i.p. administration of 5 mg/kg thioperamide. These results clearly indicate that both the basal and evoked release of histamine measured by our method are of neuronal origin.

Animals↗
PubMed1991

Marked increase in gastric histidine decarboxylase activity in patients with hypergastrinemia.

Histidine decarboxylase (HDC) activity and histamine content were measured in endoscopic gastric biopsy specimens of 19 control subjects with normogastrinemia and 6 patients with hypergastrinemia. In controls, the HDC activity was 3 fold higher in fundic mucosa (120 +/- 13 fmol/min/mg protein, mean +/- S.E.) than in antral mucosa (39 +/- 5 fmol/min/mg protein). In patients with hypergastrinemia, an extremely high HDC activity (713 +/- 181 fmol/min/mg protein) was observed in fundic mucosa, although the HDC activity in antral mucosa was not significantly different from that of controls. The histamine content in fundic mucosa was also significantly higher in patients with hypergastrinemia than in controls but no significant difference was seen in histamine content in antral mucosa between the two groups. These results are compatible with the hypothesis that in man, as well as in rat, histamine synthesis in fundic mucosa is enhanced by gastrin.

Adult↗
PubMed1991

Effect of histamine depletion on the circadian amplitude of the sleep-wakefulness cycle.

Behavioral states of rats were automatically classified with a newly developed computer program into three sleep stages (awake, slow-wave sleep and REM sleep) from continuous long-term EEG and EMG recordings for several circadian cycles under entrained circumstances (L:D = 12:12). Histamine was depleted by 100 mg/kg intraperitoneal administration of a specific inhibitor of its synthesis, alpha-fluoromethylhistidine, in the mid-light period. This treatment had no effect on the amount of each sleep stage in the total 24-h period or in the light period, but caused significant increases in slow-wave sleep and REM sleep in the dark period. Equivalent decrease in the awake stage during the dark period was also observed. As a result, histamine depletion decreased the light:dark ratio of slow-wave sleep. These findings suggest that decrease of the histamine content of the brain attenuated the circadian amplitude of sleep-wakefulness by suppressing the surge of wakefulness during the dark period. From these results, histamine is suggested to modulate the circadian amplitude of the sleep-wakefulness cycle.

Animals↗
PubMed1991

High efficacy of monomethoxypolyethylene glycol-conjugated L-asparaginase (PEG2-ASP) in two patients with hematological malignancies.

Two patients with hematological malignancies were successfully treated with monomethoxypolyethylene glycol-conjugated Escherichia coli L-asparaginase (PEG2-ASP), which reportedly lacks both antigenicity and immunogenicity but retains catalytic activity as well as slow clearance in an experimental animal model. A 20-year-old male patient with leukemic lymphoma was refractory to conventional chemotherapy but responsive to L-asparaginase (L-ASP) followed, however, by severe adverse effects. On relapse, an intravenous infusion of 100-200 IU/day dose of PEG2-ASP alone led to a complete remission 2 months later without hypersensitivity or other significant adverse reactions. Surprisingly, he remained in a complete remission for over one year with a regular weekly infusion of PEG2-ASP, combined with a weekly small dose of Ara-C. During this period, blood asparagine was not detectable. The other patient, a 64-year-old woman with chronic myelogenous leukemia in blast crisis achieved, within 6 weeks, a complete remission with twice-weekly infusions of PEG2-ASP. Thus, PEG2-ASP is a highly effective antitumor agent overcoming the limitations in therapeutic use of L-ASP.

Adult↗
PubMed1991

Is the histaminergic neuron system a regulatory center for whole-brain activity?

Recent immunocytochemical studies have demonstrated the existence of histaminergic neurons in the brain, which are concentrated in the tuberomammillary nucleus of the posterior hypothalamus, and which project efferent fibers to almost all parts of the brain. Three subtypes of histamine receptors are widely distributed in the brain, not only on neurons but also on astrocytes and blood vessels. Consistent with its wide-ranging output, the histaminergic neuron system regulates various activities of the brain, such as the arousal state, brain energy metabolism, locomotor activity, neuroendocrine, autonomic and vestibular functions, feeding, drinking, sexual behavior, and analgesia--this regulation is possibly achieved by the histaminergic system as a whole.

Animals↗
PubMed1991

Spontaneous otoacoustic emissions in the guinea pig.

Measurement of spontaneous otoacoustic emission (SOAE) in a large number of animals was conducted in the guinea pig. A remarkably high incidence of SOAE (51 ears out of 248 ears; 20.6%) was observed in the animals that were raised under unexceptional conditions. The frequencies of SOAE were distributed between 0.7 kHz and 2.3 kHz (average: 1.16 kHz). The emission signals disappeared with hypoxia and with furosemide injection, and recovered after certain periods with some frequency fluctuations. Their electrical correlates that behaved in exactly the same manner as SOAE were clearly distinguished by FFT analysis of the AC potential from the cochlear surface. The signals could be divided into 4 types: (1) emission with pure and stable frequency spectrum and steady level, (2) emission with stable frequency and fluctuating level, (3) emission alternating between two closely situated frequency points, (4) emission having an irregular, wide spectrum band. Light microscopy revealed no abnormalities in the organ of Corti that have been widely accepted to be SOAE-related, i.e., patchy lesions of the organ of Corti and/or irregularities in hair cell arrangement. This suggests that the spontaneous oscillation within the guinea pig cochlea can be generated by some minor, functional, and probably reversible disturbances of the active cochlear transduction mechanism, without major structural derangement of the organ of Corti.

Acoustics↗
PubMed1991

Bronchial circulation after experimental lung transplantation: the effect of direct revascularization of a bronchial artery.

Direct revascularization of a bronchial artery has been proposed as a measure to alleviate the problem of bronchial ischemia after lung transplantation. To assess the effect of restoration of arterial blood flow to the transplanted bronchus, bronchial mucosal blood flow was measured in a model of modified unilateral lung transplantation in pigs. Laser Doppler velocimetry (LDV) and radioisotope studies using radio-labeled erythrocytes (RI) were used to measure blood flow at the donor main carina (DC) and upper lobe carina (DUC) after 3 h of reperfusion. The recipient carina was used as a reference point; values obtained by LDV and RI were expressed as percentage of blood flow at the recipient carina. Two groups of animals were studied. In group 1 (n = 6) standard unilateral transplantation was performed; in group 2 (n = 6) a left bronchial artery was reimplanted into the descending thoracic aorta of the recipient. No differences were observed between the two groups with respect to preoperative or postoperative gas exchange or hemodynamics. In group 1, bronchial blood flow at the DC was 37.6 +/- 2.2% (LDV) and 44.1 +/- 14.8% (RI) of reference blood flow. At the DUC, blood flow was 54.9 +/- 7.7% (LDV) and 61.6 +/- 25.7% (RI) of normal flow. In group 2, blood flow was increased at the DC as measured by LDV (55.3 +/- 17.1%; p less than 0.05) and by RI (60.8 +/- 25.3%; p less than 0.2). A similar increase was found at the DUC (LDV: 81.8 +/- 19.3%; p less than 0.05; RI: 88.6 +/- 31.0%; p less than 0.2). It is concluded that there is a significant gradient of blood flow from intra- to extrapulmonary airways after lung transplantation. Reimplantation of a bronchial artery results in significant improvement of graft bronchial blood flow. Restoration of bronchial perfusion to normal levels, however, cannot be achieved, suggesting a possible defect in the microcirculation of the donor airways.

Animals↗
PubMed1991

A new method for carinal reconstruction: an experimental study.

We developed a new procedure for carinal reconstruction which can be used for lesions of the carina invading the left main bronchus. Twelve mongrel dogs were used. A Y-shaped bronchial graft was autotransplanted from the bifurcation of the right upper bronchus to form a new carina with or without an omentopexy. Six animals survived 10 days to 11 months. In these animals healing of the bronchial anastomotic sites was excellent, and the integrity of the grafts was well preserved. Although the results of this preliminary report were not satisfactory in all cases, intensive perioperative care will improve the outcome of this new procedure.

Animals↗
PubMed1991

Histopathological changes in invasive thymoma in patients with recurrence.

In the last 20 years, we treated 123 cases of thymoma. In 2 patients histopathological features of the tumors changed during the long-term follow up. In one patient the tumor was resected along with the invaded tissues. Eleven years later, recurring tumor and the invaded organs were extirpated. Hepatic metastasis was detected by abdominal CT scanning 16 years after the first operation. Two years later she died in an accident. Histopathologically, the primary thymoma was lymphoepithelial type and the recurrent tumor was epithelial type. In the other patient, four years after the surgical treatment for thymoma with disseminated lesions, recurrent disseminations were removed. Eight years later, both the disseminated and a metastatic lesion were resected. This patient is currently well without tumor 14 years after initial detection of the disease. Both the primary and recurrent thymoma were lymphoepithelial type and the third tumor was epithelial type. Thus, slow-growing thymomas in patients with long-term survival possibly undergo histological change.

Adult↗
PubMed1991

Adenosine induces System A amino acid transport in cultured rat hepatocytes.

Adenosine caused a 2.5-fold increase in the sodium-dependent uptake of 2-aminoisobutyric acid in rat hepatocytes in primary culture following incubation for 3 h. The range of stimulating concentrations of adenosine corresponded to that of cAMP formation. Adenosine increased the Vmax of the transport without altering the Km for 2-aminoisobutyric acid. These effects of adenosine were abolished by actinomycin D. N6-L-Phenylisopropyladenosine also caused twofold increase in the amino acid transport. These findings suggest that adenosine induces System A amino acid transport in a transcription-dependent manner, and the P1-purinergic receptors are mainly involved in this action of the nucleoside.

Adenosine↗
PubMed1991

Nicardipine inhibits the endothelin-1-induced constriction of systemic capacitance and resistance vessels.

We estimated the effects of intravenous injection of endothelin-1 (ET-1; 400 pmol/kg) on the systemic capacitance and resistance vessels in anesthetized mongrel dogs by measuring changes in the mean circulatory pressure (MCP) and total peripheral resistance (TPR), respectively. In addition, the present study investigated the inhibiting action of nicardipine (NIC; 10 micrograms/kg bolus injection followed by 1.0-2.0 micrograms/kg/min continuous infusion) against the vasoconstrictor action of ET-1. We examined the effects of ET-1 (30 to 1,000 pmol/0.1 ml) on the femoral arterial system by measuring the percent changes in the perfusion pressure (% delta PP) of the femoral artery perfused with a constant flow, and investigated the effect of NIC on the vasoconstrictor action of ET-1 in this preparation. We obtained the following results: (a) Intravenous injection of ET-1 raised both TPR and MCP. However, in the presence of NIC, ET-1 raised TPR without influencing MCP. (b) Intra-arterial injection of ET-1 caused a dose-dependent increase in % delta PP. NIC shifted the dose-response curve of ET-1 for % delta PP to the right in a parallel fashion.

Animals↗
PubMed1991

Disruption of binocularly correlated signals alters the postnatal development of spatial properties in cat striate cortical neurons.

1. Extracellular single-cell recording techniques were employed to investigate the effects of ocular misalignment on the postnatal development of the spatial response properties of striate cortical neurons. The primary objective of the study was to gain insight into the neural basis of strabismic amblyopia. 2. Two basic rearing strategies were used to study specific aspects of experimental strabismus in developing kittens. In one group, strabismus was optically induced by fitting kittens with goggles that held a 15-diopter base-in prism in front of one eye (MP) or both eyes (BP) between the ages of 4 wk and 4 mo. In the second group, a unilateral esotropia was surgically induced at 3 wks of age either by the simple resection of the lateral rectus muscle tendon (tenotomy) or by a more drastic procedure that involved removing sections of the lateral rectus and superior oblique muscles (myectomy). In addition, the eyelids of the nondeviating eyes of these kittens were sutured closed (ESO/MD). The first rearing paradigm isolated the effects of conflicting visual inputs on neural development, whereas the second procedure isolated the effects of anomalous ocular motility by producing a misalignment without putting the deviated eye at a competitive disadvantage. 3. The recording experiments were conducted when the animals were greater than or equal to 9 mo of age. A total of 445 striate cortical neurons were isolated and quantitatively studied in 17 cats (3 MPs, 3 BPs, 5 ESO/MDs, 3 goggle-reared controls, and 3 normals). In addition, we analyzed the distribution of preferred stimulus orientations of 1,205 single units that had been studied qualitatively in our previous investigation of 42 kittens reared with optically induced strabismus. 4. As expected, the proportion of binocularly driven units was reduced in both MP and BP cats. The great majority of units in ESO/MD animals were exclusively driven or highly dominated by the open deviating eye. 5. Prism-reared animals showed physiological deficits in spatial resolution, contrast sensitivity, contrast gain, and peak firing rate. These effects were manifest in both eyes, although there was always an interocular asymmetry in the deficits observed in the two eyes. In MP animals, the units dominated by the treated eye, which was contralateral to the recording hemisphere, were on the average more severely affected. The interocular asymmetry was smaller in BP cats; however, two of the three BP animals also showed a greater deficit in those units dominated by the contralateral eye.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Platelet aggregability and prostacyclin/thromboxane A2 ratio after endoscopic injection sclerotherapy with different sclerosants.

Platelet aggregability and coagulative and fibrinolytic systems were analyzed with regard to positive effects and for side effects of 5% ethanolamine oleate (EO) versus 5% sodium morrhuate (SM) used for endoscopic injection sclerotherapy (EIS). Twelve patients each were treated with each sclerosant. There was a temporary activation of coagulative and fibrinolytic systems within 1 h in both groups. Platelet aggregability was significantly suppressed to 78.6 +/- 8.9% of that before EIS in the EO group, but was activated to 110.0 +/- 10.5% in the SM group at 1 h after EIS. The ratio of concentrations of prostacyclin (PGI2) to thromboxane A2 (TXA2) increased in the EO group and decreased in the SM group after EIS. The clinical effect in the SM group after the initial session was weaker than that in the EO group with regard to endoscopic findings at the second session. As change in platelet aggregability after EIS is apparently induced by alterations in the ratio of PGI2/TXA2, there would be related effects concerning the sclerosants.

Adult↗
PubMed1991

Role of the kinin-kallikrein system in the vasodilator action of an angiotensin converting enzyme inhibitor (captopril) on the systemic resistance and capacitance vessels of dogs.

We investigated the vasodilator effects of captopril (CAP) on the systemic capacitance and resistance vessels by measuring changes in the mean circulatory pressure (MCP) and total peripheral resistance (TPR) that occurred in response to the intravenous injection of CAP (1 mg/kg) in open-chest dogs. The following five groups of dogs received CAP: (1) Group of untreated dogs, (2) TSA Group in which the dogs were subjected to total spinal anesthesia (TSA), (3) Ang II Group in which the dogs received a continuous intravenous infusion of angiotensin II (Ang II), (4) APR + Ang II Group in which the dogs received a continuous intravenous infusion of Ang II after pretreatment with aprotinin (APR, 25,000 K.I.E.), a kallikrein inhibitor, and (5) IND + APR + Ang II Group in which the dogs received a continuous intravenous infusion of Ang II after pretreatment with indomethacin (IND, 5 mg/kg), a prostaglandin synthesis inhibitor, and APR. 1) CAP significantly decreased TPR and MCP in the untreated Group. 2) CAP significantly decreased TPR and MCP in the TSA Group. There were no significant differences in percentage change of TPR (% delta TPR) and percentage change of MCP (% delta MCP) between the untreated and TSA Groups. 3) In the Ang II Group, CAP decreased the elevated TPR significantly, but hardly affected the elevated MCP. 4) CAP significantly decreased TPR without significant change in MCP in the APR + Ang II Group. The % delta TPR was significantly smaller in this Group than in the Ang II Group. 5) CAP significantly decreased TPR without significant change in MCP in the IND + APR + Ang II Group.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1991

Functional expression of H1-histaminergic receptors in Xenopus laevis oocytes injected with bovine adrenal medullary mRNA.

We prepared poly (A)+ mRNA from bovine adrenal medulla and electrophysiologically examined the expression of H1-histaminergic receptors in Xenopus laevis oocytes. Histamine dose-dependently induced inward currents in oocytes injected with the mRNA, but not in those injected with water or the non-injected oocytes. This response was also induced by H1-agonists and antagonized by H1-antagonists, while both an H2-agonist and an antagonist had no effect. These results clearly demonstrate that H1-histaminergic receptors are functionally expressed in oocytes injected with exogenous mRNA.

Adrenal Medulla↗
PubMed1991

Microtubule subunits of guinea pig vestibular epithelial cells.

Guinea pig cochlear supporting cells have microtubules which are composed of 15, instead of the ordinary 13, protofilaments. The microtubules form a large and stiff bundle involving abundant actin filaments to provide effective rigidity to the cell specialized for transduction of extremely high-frequent mechanical stimuli. We examined microtubules in guinea pig vestibular end organs with the transmission electron microscopy after treatment with tannic acid. Solitary microtubules occurred abundantly in the supranuclear region of type I hair cells, but sparsely in type II hair cells. Individual microtubules consisted of an ordinary set of 13 protofilaments in these hair cells as well as in the supporting cells. Supporting cells were characterized by cytoskeletal bundles of 2 to 30 microtubules which were found to be connected with actin filaments via cross-linking units. Results from the present investigation indicate that such less-organized microtubules of 13 protofilaments are sufficient for vestibular supporting cells which are specialized for detection of lower-frequency vibration together with fellow sensory cells.

Actins↗