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Biomedical subjects

H Wada

Publications and source records attributed to H Wada.

At least 811 records · Page 45Linked to original sources

Application of laser Doppler velocimetry to lung transplantation.

The relationship between healing of a bronchial anastomosis and regional blood flow was studied in adult mongrel dogs after allotransplantation of the left lung. Animals were divided into the following three groups according to the immunosuppressive regimen. Group A: no immunosuppressive treatment (n = 7); Group B: azathioprine (5 mg/kg/day) and prednisolone (2 mg/kg/day) (n = 4); Group C: cyclosporine (20 mg/kg/day) (n = 4). The mucosal blood flow was examined serially after transplantation with laser Doppler velocimetry (LDV) at the tracheal bifurcation of the recipient (1st LDV) and at the bifurcation of the upper lobe bronchus of the transplanted lung (2nd LDV). The LDV values were expressed as a ratio to the preoperative values at the same site. Healing of the bronchial anastomosis was also assessed macroscopically with a fiberoptic bronchoscope and microscopically. The 2nd LDV value of the animals in group A at 13 days after transplantation remained low (32.9 +/- 27.6%). The 2nd LDV value in group B, although not significantly different from group A, had recovered to the preoperative level by that time (93.7 +/- 23.4%). By contrast, the 2nd LDV value in group C remained significantly higher than that in group A (119.9 +/- 23.0%, P less than 0.05). The 1st and 2nd LDV values were reduced in animals having infection at the bronchial anastomosis, even those in groups B and C. Bronchial mucosal blood flow appeared to be affected by infection and rejection of the transplanted lung, and to correlate closely with the healing of the bronchial anastomosis. This LDV method is useful to evaluate bronchial mucosal blood flow in experimental, and possibly in clinical, fields.

Animals↗

Two human myeloma cell lines, amylase-producing KMS-12-PE and amylase-non-producing KMS-12-BM, were established from a patient, having the same chromosome marker, t(11;14)(q13;q32).

Two human myeloma cell lines, KMS-12-PE and KMS-12-BM, were established from a 64-year-old woman with a non-producing type of multiple myeloma. The KMS-12-PE line originated from the pleural effusion and the KMS-12-BM from the bone marrow. These two lines showed the same chromosome marker, t(11:14)(q13:q32). However, their phenotypes of surface markers differed from each other. KMS-12-BM cells were positive to CD20, CD38 and PCA-1. showing the plasmacytoid (immature plasma cell) stage of B-cell differentiation, while KMS-12-PE cells were positive to CD38 and PCA-1, but not to CD20, indicating the terminal differentiated stage of B-cells. As seen in the pleural effusion of the patient. KMS-12-PE cells ectopically produced a salivary type of amylase, but KMS-12-BM cells did not. Interestingly, the chromosome abnormality of del(1)(p22----pter) near the region of 1p21, where the amylase gene was assigned, was noticed in as many as 76% of KMS-12-PE cells.

Amylases↗

Neuronal histamine modulates feeding behavior through H1-receptor in rat hypothalamus.

To clarify the physiological role of hypothalamic neuronal histamine in control of food intake, ingestive behavior and neuronal activity were investigated under blockade or diurnal fluctuation of hypothalamic neuronal histamine. Histamine H1- but not H2-receptor antagonist potently induced feeding in a dose-related manner after infusion into rat third cerebroventricle at 1100 h. Elicitation was attenuated after infusion at 1940 h when histamine content in the hypothalamus was low and was abolished after intraperitoneal pretreatment with 0.11 mmol alpha-fluoromethylhistidine (alpha-FMH), a specific suicide inhibitor of histidine decarboxylase. Electrophoretic application of a histamine H1-receptor antagonist to ventromedial hypothalamic neurons specifically suppressed activities of glucose-responding neurons that are related to food intake. The suppressive effect was also attenuated by intraperitoneal pretreatment with alpha-FMH. These results suggest that feeding induced by histamine H1-receptor antagonists is due to blockade of neuronal histamine at the site of histamine H1-receptors, at least in part, in the ventromedial hypothalamus and that diurnal fluctuation of feeding behavior may reflect circadian variation of neuronal histamine level.

Animals↗

Further physiological observations on the ventralis intermedius neurons in the human thalamus.

1. During the course of stereotaxic thalamotomy for 56 cases with tremor mainly due to Parkinson's disease and essential tremor, extracellular recordings were made from the thalamic ventralis intermedius (Vim) nucleus under local anesthesia. These procedures have been justified as an essential technique to achieve the best therapeutic results by a selective coagulation. These physiological observations provide important information about the functional organization of the ventrolateral thalamic mass in humans. 2. Using Leksell's stereotaxic apparatus, a pair of semimicroelectrodes was introduced simultaneously to the thalamic ventral lateral region from the prefrontal area. The Vim nucleus was identified tentatively by characteristic high background activity which contrasted to that found in its rostral part and by superimposed large amplitude spontaneously active units. 3. In this high activity zone, 135 units (approximately 1/5 of the recorded units) responded to natural stimulation applied to contralateral body parts. Among them, approximately 90% responded to a passive or active movement of a joint. Several lines of evidence suggested that probably muscle receptors were responsible. 4. The rest of units (approximately 10%) responded to light touch applied to contralateral skin surface. Convergent responses between kinesthetic and tactile units were never encountered. Also, kinesthetic and tactile neurons were geographically separated. The latter were found always at the end of our oblique trajectory, following the kinesthetic neurons. 5. Neurons with sensory responses were clustered mostly within the confines of the Vim nucleus, probably extending caudally to the ventrocaudalis externus anterior of Hassler. Evidence for a somatotopic representation in the Vim nucleus was obtained. 6. Electrical stimulation of the appropriate peripheral nerve produced responses of the same thalamic unit(s) that responded to natural stimulation. The latency to upper limb nerve stimulation was between approximately 10 and 20 ms. It was almost fixed in a given case. 7. It is concluded that the Vim nucleus receives kinesthetic afferent input from the contralateral body parts (mainly from the muscle receptor) and may be concerned with muscle sense. This may explain why a small, selective coagulation of the physiologically identified Vim has such a constant effect on several different kinds of tremor.

Action Potentials↗

Effect of histamine depletion on circadian variations of corticotropin and corticosterone in rats.

The effects of cerebral histamine depletion induced by alpha-fluoromethylhistidine (FMH) on corticotropin (ACTH) and corticosterone secretions were examined. Neither acute nor chronic FMH treatment altered the corticoadrenal responses to three types of stress: transposition, immobilization and water immersion. And exposure to stress did not affect the hypothalamic content of histamine. However, chronic intracerebral treatment with FMH had a significant effect on the circadian rhythm of the plasma corticosterone (CS) level in rats. Namely, it caused a marked attenuation of the amplitude of the peaks of the CS level resulting in an almost arrhythmic state. The maximum differences between FMH treated and untreated groups were seen at 8.00 and 20.00 h, the times when the illumination condition changed (light onset 8.00 h). This treatment with FMH also had a similar effect on the plasma ACTH concentration; namely the plasma ACTH level in the saline treated group was lower than that of the FMH-treated group at light onset and higher than the latter at dark onset, but was similar to the latter at other sampling points. These results indicate the histaminergic modulation of the circadian rhythm of hormonal secretion of the adrenal cortex and show that this phenomenon is mediated through the central nervous system by an influence on the rhythm of hypophyseal ACTH secretion possibly through alteration in the concentration of corticotropin-releasing factor.

Adrenocorticotropic Hormone↗

Differential vasodilator effect of nitroglycerin on systemic capacitance and resistance vessels in anesthetized dogs, and the mechanism of its action--a study by measuring mean circulatory pressure and total peripheral resistance.

The aim of our studies was to examine if the baroreceptor reflex induced by intravenous injection of nitroglycerin (NG) nearly nullifies the vasodilator action of NG on the systemic capacitance vessels in dogs anesthetized with pentobarbital. We performed total spinal anesthesia (TSA) in open-chest dogs to eliminate the baroreceptor reflex. Dogs in which mean blood pressure (MBP) was maintained at about 100 mmHg by continuous intravenous infusion of epinephrine formed the TSA 100 group, and those in which MBP was maintained at about 70 mmHg formed the TSA 70 group. Dose-response curves relating 5-6 different doses (0.8 to 200 micrograms/kg) of intravenous NG, to changes in mean circulatory pressure (% delta MCP) and to changes in total peripheral resistance (% delta TPR), were constructed. These data were compared with those from untreated dogs. In addition, we also studied plasma catecholamine (CA) concentrations before and after the intravenous injection of NG. (1) There was no significant difference in the dose-response curves of NG for % delta TPR between the 3 groups. (2) There was no significant difference in the dose-response curves for % delta MCP between the 2 TSA groups. However, there was significant difference in the dose-response curves for % delta MCP between the TSA groups and the untreated dogs. The dose-response curves for % delta MCP in the TSA groups shifted upwards as compared with that of the untreated dogs. (3) In the TSA 100 group, there was no significant increase in the plasma CA concentrations with 100 micrograms/kg of NG. In the untreated group, intravenous injection of 12.5 micrograms/kg and 100 micrograms/kg of NG caused a dose-related fall in MBP and a dose-related rise in the plasma norepinephrine and epinephrine concentrations. Our results suggest that the vasodilator action of NG on the systemic capacitance vessels in the untreated dogs was counterbalanced partly by the vasoconstriction produced by the baroreceptor reflex, with its direct vasodilator effect masked when the hypotensive doses of NG were given acutely.

Anesthesia, Spinal↗

Divalent cations increase the binding capacity of the [3H]mepyramine binding site, a possible histamine H1 receptor, in rat liver membranes.

The [3H]mepyramine binding to rat liver membranes was about 2-fold higher in the presence of 2 mM CaCl2 than in the absence. However, the [3H]mepyramine binding to rat brain membranes was not affected by the presence of 2 mM CaCl2. Scatchard analysis showed that 2 mM CaCl2 did not change the affinity (KD) of liver membranes to [3H]mepyramine, but increased the binding capacity (Bmax). CaCl2 had a half maximal effect (ED50) at 3 microM and a maximal effect at concentrations of more than 10 microM. Other divalent cations, Mg++, Mn++, Sr++ and Ba++, also increased the [3H]mepyramine binding, whereas monovalent cations, Na+, K+, Li+ and Rb+, had no effect.

Aminopyridines↗

Dependency of histamine induced phasic and tonic contractions on intracellular and extracellular calcium in guinea pig tracheal smooth muscle.

Dependency of histamine induced phasic and tonic contractions on intracellular and extracellular calcium in guinea pig tracheal smooth muscle was investigated. In Ca++-free Krebs-Ringer solution, the phasic contraction caused by 10(-5)M histamine was not affected, but the tonic contraction declined much faster than that in normal Krebs-Ringer solution (KR). The phasic contraction in KR containing 3 x 10(-4) M dantrolene was depressed, but reached a level similar to that in normal KR, and the tonic contraction was maintained similarly with or without dantrolene. In KR containing organic calcium channel blockers, 10(-5) M nilvadipine (FR34235), 10(-5) M verapamil or 10(-5) M diltiazem, neither phasic contraction nor tonic contraction was affected. No contraction was observed in Ca++-free KR containing 3 x 10(-4) M dantrolene. These results suggested that the phasic contraction by histamine depended on the intracellular calcium and the tonic one, on the extracellular calcium, and the organic calcium channel blockers had no effect on both phasic and tonic contractions caused by histamine.

Animals↗

Effect of atrial natriuretic peptide on catecholamine release from human pheochromocytoma.

The effect of synthetic alpha human atrial natriuretic peptide on catecholamine release from human pheochromocytomas was studied both in vivo and in vitro. Iv infusion of atrial natriuretic peptide at a rate of 0.1 microgram.kg-1.min-1 for 60 min into two normotensive patients with pheochromocytoma caused a small decrease in the mean blood pressure, increase in the heart rate, and marked increase in the plasma level of norepinephrine (2.08 to 6.83 nmol/l, and 1.15 to 2.83 nmol/l, respectively) compared with 0.60 +/- 0.10 to 1.19 +/- 0.20 nmol/l in normal subjects. Treatment with atrial natriuretic peptide also increased the plasma epinephrine level from 0.34 to 1.27 nmol/l, and from 0.67 to 0.79 nmol/l in the patients with pheochromocytoma, but not in the normal subjects (0.05 +/- 0.01 to 0.05 +/- 0.01 nmol/l). After removal of the tumour, the responses of the plasma norepinephrine and epinephrine to atrial natriuretic peptide infusion were normalized. There was no significant effect of 10(-8) to 10(-5) mol/l atrial natriuretic peptide on the basal release of catecholamines from isolated superfused pheochromocytoma tissue. Atrial natriuretic peptide (10(-7) mol/l) did not affect the increase in catecholamine release induced by glucagon (10(-5) mol/l). These results suggest that the exaggerated responses of plasma catecholamines to atrial natriuretic peptide in patients with pheochromocytoma may be due to a washout effect resulting from change in blood flow in the vessels feeding the tumour rather than increased sympathetic nerve activity induced by hypotension and hypovolemia. The results also suggest that atrial natriuretic peptide dose not have any direct action on pheochromocytoma tissue causing catecholamine release.

Adrenal Gland Neoplasms↗

Estrogen stimulates gonadotropin-releasing hormone release from rat hypothalamus independently through catecholamine and histamine in vitro.

Estradiol is known to stimulate gonadotropin-releasing hormone release from the rat medio-basal hypothalamus. Studies were made in an in vitro perifusion system on whether catecholamine and/or histamine was involved in estradiol-induced GnRH release. Normal cycling female rats were decapitated in diestrus II and their medio-basal hypothalami were combined and, perifused with Earl's balanced salt solution containing 0.01% bovine serum albumin bubbled with 95% O2 and 5% CO2. The levels of norepinephrine, dopamine, and histamine and of GnRH in the effluent were measured by HPLC and radioimmunoassay, respectively. Administration of 10(-6) mol/l estradiol resulted in releases of norepinephrine, dopamine, histamine and GnRH at levels of 98, 70, 91 and 288%, respectively, of initial values. Administration of 10(-6) mol/l norepinephrine or dopamine resulted in no increase in histamine release, and administration of 10(-6) mol/l histamine did not increase release of norepinephrine or dopamine. These data suggest that estradiol stimulates the releases of GnRH, catecholamine and histamine from the rat medio-basal hypothalamus, and that it increases GnRH release independently through catecholamine and histamine. As we found previously that norepinephrine or histamine stimulates GnRH release from the medio-basal hypothalamus, we conclude that estradiol stimulates releases of norepinephrine and histamine, resulting in GnRH release from the medio-basal hypothalamus.

Animals↗

Dynamic behavior of the middle ear based on sweep frequency tympanometry.

A measuring apparatus was developed; its probe tip, which exhibits flat frequency characteristics, enables this apparatus to measure the absolute sound pressure and absolute phase variations versus both sweeping frequency and external auditory canal pressure. Although it is difficult to diagnose ossicular chain separation and fixation from the commonly used tympanograms with a low probe tone frequency (e.g.f = 220 Hz), the results obtained with this apparatus enable one to clearly distinguish patients with ossicular chain disorders from normal subjects. Therefore, it seems to be highly useful in the clinical diagnosis of ossicular chain disorders.

Acoustic Impedance Tests↗

Natural course of unoperated intracranial arteriovenous malformations: study of 50 cases.

The clinical course of 50 patients with conservatively treated intracranial arteriovenous malformations (AVM's) was followed, most of them for more than 5 years. The average follow-up period was 13.4 years. The initial symptom was intracranial bleeding in 29 patients (58%) and seizure in 15 patients (30%). Small and deep-seated AVM's were associated with a high incidence of bleeding; however, repeated hemorrhages were not necessarily indicative of a poor prognosis. Children younger than 15 years had a better prognosis than adults. There was no correlation between pregnancy and bleeding. In the hemorrhage group, the incidence of rebleeding was 6.9% in the 1st year after initial rupture, 1.91% per year after 5 years, and 0.92% per year after 15 years. The overall incidence of rebleeding was 34.5% in the hemorrhage group. Of the 50 patients, 37 (74%) had a good clinical outcome, four (8%) had a fair outcome, and four (8%) had a poor outcome; five patients died.

Adolescent↗

[Middle ear dynamic characteristics of patients obtained by a newly developed measuring apparatus].

A tympanometer is well known to be a valuable apparatus for the diagnosis of secretory otitis media (SOM). However, it is insufficient for the diagnosis of ossicular chain disorders. Therefore, an attempt was made to develop a new measuring apparatus, which had a function of sweeping both frequency and pressure and was measurable the absolute sound pressure variations at the external auditory canal, owing to the carefully designed probe. In the previous papers, the middle ear dynamical characteristics of normal subjects were measured by this apparatus, and the measurement results were compared with the theoretical analysis. In this paper, the middle ear dynamical characteristics of patients were measured, and the effects of various kinds of middle ear diseases upon its dynamical characteristics were examined. The measurement results of the patients with ossicular chain separation, ossicular chain fixation, SOM and tympanic membrane perforation had their own distinctive patterns, and were also clearly different from those of normal subjects. Therefore, this apparatus seems to have a high degree of the clinical applicability to the diagnosis of these diseases.

Adolescent↗

[Blood concentration of granulocytic elastase, surgical invasion and postoperative complications--with special reference to surgical resection of liver cirrhosis].

The blood concentrations of granulocytic elastase (PMN-E), alpha 1-antitrypsin and alpha 2-macroglobulin were examined to evaluate their clinical significance in patients who underwent hepatectomy due to liver cancer with liver cirrhosis (n = 31, Group A), due to liver cancer with chronic hepatitis (n = 5, Group B) and without hepatic complications (n = 6, Group C) and other major surgeries (n = 10, Group D). In all groups, on the first postoperative day, blood PMN-E increased rapidly more than three times of the preoperative levels. Despite a decreasing tendency from postoperative Day 3, the value in Group A reincreased on Day 5. The peak PMN-E values within 24 postoperative hours showed significant positive correlations (p less than 0.01) with the amounts of hemorrhage and blood transfusion during operation in all groups. Even in 18 cases without blood transfusion, peak PMN-E was positively correlated (p less than 0.05) with the operative time and the amount of blood loss during operation. In Group A, patients in whom blood PMN-E increased after postoperative Day 3 developed infection and adult respiratory distress syndrome. After temporary reduction after operation except for Group C, blood alpha 1-antitrypsin increased from postoperative Day 3. However, alpha 1-antitrypsin in Group A was significantly low (p less than 0.01), compared to the increased levels in Group C and D. Blood alpha 2-macroglobulin showed no tendency of postoperative increase in all groups.

Granulocytes↗

[Histological observations of immunosuppressive effects of FK-506 in canine lung allotransplantation].

The Immunosuppressive effects of FK-506 were studied histologically in allotransplanted canine lungs. FK-506 was administered daily in a dose of 0.15 mg/kg after left lung allotransplantation. Nine dogs underwent open lung biopsy on the 7th postoperative day (p.o.d.). Mild mononuclear cell infiltrations around small vessels (MNC cuffings), which suggested an early phase of rejection, were observed in 2 dogs. Two dogs were sacrificed on the 14th and 2 on the 21st p.o.d. MNC cuffings were observed in the lung of one dog and in the bronchial submucosa of 2 dogs. Six dogs were sacrificed on the 28th p.o.d. MNC cuffings were observed in the lungs of 3 dogs and in the bronchial submucosa of 5 dogs. The MNC cuffings were of nearly the same extent in the lung and in the bronchial submucosa of most of the dogs. Alveolar structures were well in all the dogs and the bronchial epithelium in all except 2 of the dogs sacrificed on the 28th p.o.d. preserved. Arterial blood gas was examined before and 20 min. after right hilar ligation in 3 dogs on the 28th p.o.d. The PaO2 (228 mmHg, 312 mmHg, 217 mmHg at FiO2: 0.5, tidal volume: 20 ml/kg, respiratory rate: 20/min) and PaCO2 after rt, hilar ligation indicated that the transplanted lung was functioning well in these dogs. The present study suggests that FK-506 could be a potent immunosuppressive agent in lung transplantation. As 4 of the 14 dogs used in this experiment died from severe diarrhea caused by FK-506, further studies are needed to determine the suitable dose and route of administration of FK-506.

Animals↗

[Inhibitory effect of amlexanox (AA-673) on the immunological and non-immunological release of histamine or leukotrienes].

The effect of amlexanox on the non-immunological or immunological release of histamine or leukotrienes (LTs) from passively sensitized human lung fragments and atopic human leukocytes was investigated and compared with those of AA-861, tranilast, azelastine and disodium cromoglycate. 1) Amlexanox at concentrations of 10(-7)-10(-4) M showed an inhibition of histamine, LTB4, LTC4, LTD4 and LTE4 release from passively sensitized human lung fragments in a concentration-dependent fashion. A selective and competitive inhibitor of the 5-lipoxygenase activity, AA-861 modestly affected the histamine release and potently suppressed the any LT release at 10(-7) and 10(-6) M. Antiallergic drugs, tranilast and disodium cromoglycate also suppressed these chemical mediator release, but the inhibition potency was somewhat weaker than that of amlexanox. 2) Ca ionophore A23187-induced release of LTB4 and LTC4 from atopic human leukocytes was slightly enhanced up to 10(-6) M of amlexanox. However, 10(-4) M of the drug strongly diminished both of LT release. From these results, it is suggested that amlexanox is a clinically effective drug for atopic diseases, especially allergic asthma and rhinitis.

Aminopyridines↗