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Biomedical subjects

H Numata

Publications and source records attributed to H Numata.

16 recordsLinked to original sources
PubMed1992

Preventive effects of interleukin 1 beta for ACNU-induced myelosuppression in malignant brain tumors: the experimental and preliminary clinical studies.

The effect of recombinant human interleukin 1 beta (rHuIL-1 beta) on myelosuppression induced by 3-[(4-amino-2-methyl-5-pyrimidynyl)methyl]-1-(2-chloroethyl)-1-nit rosourea hydrochloride (ACNU) was studied. In in vivo study using BALB/c mice, pretreatment with 1 microgram/mouse of rHuIL-1 beta as a single intraperitoneal (i.p.) injection had a significant preventive effect on thrombocytopenia as well as granulocytopenia induced by ACNU at an intravenous dose of 60 mg/kg. Facilitated recovery by rHuIL-1 beta administered seven days after injection of high-dose ACNU was also observed. Experimental combination immunochemotherapy with high-dose ACNU and rHuIL-1 beta was performed in nude mice inoculated with human glioblastoma subcutaneously. The elongation of the survival time of the tumor bearing nude mice was also observed in combined use of high dose ACNU with rHuIL-1 beta. Seven patients with malignant brain tumors received intravenous 2.5-3 mg/kg ACNU. All patients were subcutaneously injected with 2 x 10(4)-U or more rHuIL-1 beta twice a week or daily. The mean nadir of leukocyte, granulocyte, and thrombocyte counts of the 7 patients received 2.5-3 mg/kg ACNU were significantly higher than in matched historical controls. In combination with rHuIL-1 beta, it may be possible to use chemotherapeutic agents at a relatively high dose.

Aged↗
PubMed1992

Toxicity to rats of methanol-fueled engine exhaust inhaled continuously for 28 days.

Fischer 344 rats were exposed to three concentrations of exhaust generated by an M85 methanol-fueled engine (methanol with 15% gasoline) without catalyst for 8 h/d, 7 d/wk for 7, 14, 21, or 28 d. Concentration- and time-dependent yellowing of the fur was prominent in all treated groups. Concentration-dependent increases in the erythrocyte count, hematocrit, hemoglobin concentration, formaldehyde in plasma, and carboxyhemoglobin in the erythrocytes, and decrease in serum alkaline phosphatase activity were seen after all exposure periods. Histopathologically, lesions were found in the nasal cavity and lungs after 7 d of exposure. Squamous metaplasia of the respiratory epithelium of level 1 (level of the posterior edge of the upper incisor teeth) lining of the nasoturbinate and/or maxilloturbinate and infiltration of neutrophils into the submucosa, and decreases of Clara cells in the terminal bronchiolus and of cilia in the bronchiolar epithelium, were observed in the high-concentration group (carbon monoxide, 94 ppm; formaldehyde, 6.9 ppm; methanol, 17.9 ppm; nitrogen oxides, 52.7 ppm; nitrogen dioxide, 10.6 ppm). The histopathological extents of several lesions increased slightly with the exposure time. Slight squamous metaplasia and hyperplasia of the respiratory epithelium at level 1 were also observed in the medium-concentration group (one in three of the high-concentration group). No histopathological changes were found in the olfactory epithelium of the nasal cavity. In the low-concentration group (one in nine of the high-concentration group), no marked histopathological changes in these organs were observed. These results may suggest that the lesions observed in the nasal cavity of rats exposed to methanol-fueled engine exhaust were mainly caused by formaldehyde, although other components in the exhaust also may have affected nasal cavity and/or lungs to less extent.

Alkaline Phosphatase↗
PubMed1992

[A case of microsurgically removed cavernous angioma in the midbrain].

The authors presented a case of microsurgically removed large cavernous angioma in the midbrain. A 46-year old woman was admitted to our service with bilateral nuclear oculomotor pareses and mild tetraparesis. MRI revealed a large round well-circumscribed high signal-intensity lesion on both T1 and T2 weighted image with low signal rim in the midbrain. This lesion was diagnosed preoperatively as a cavernous angioma. The operation was performed in three steps with intermittent hemorrhages by interhemispheric transcallosal-hippocampal commissure--velum interpositum-third ventricular approach and subsequent two infratentorial supracerebellar approaches and finally complete removal was performed. Histological examination of the surgical specimen revealed as a cavernous angioma having abnormal vessels with honeycomb appearance. The patient survived, although remains moderately disabled 6 months after the last operation.

Brain Neoplasms↗
PubMed1992

Effect of thyroid hormone on in vivo contractility of the canine diaphragm.

This study was designed to examine the effects of long-term (4 wk) administration of thyroid hormone on the in vivo contractility of the canine diaphragm. We implanted a pair of piezoelectric crystals chronically in the left crural and costal parts of the diaphragm by a midline laparotomy. Contractility was assessed by changes in the shortening of muscle fibers after twitch stimulation of both the crural and the costal parts of the diaphragm and in the transdiaphragmatic pressure (Pdi) after tetanic stimulation (10 to 100 Hz). As a reference, we also studied the response of the quadriceps femoris. Pretreatment measurements were taken 2 wk after surgery. Then, dogs assigned to the hyperthyroid group were given thyroid powder, 0.6 g/kg/day, orally for 4 wk. The control group was fed a diet without thyroid powder for 4 wk. Serum free-T4 level (RIA) in the hyperthyroid group (n = 9) increased from 0.68 +/- 0.07 to 5.72 +/- 0.95 ng/dl (mean +/- SE) (p less than 0.01). Pdi decreased 30 to 40% at all frequencies (p less than 0.05) except 10 Hz. Twitch shortening of the crural and costal parts, compared with pretreatment state, decreased significantly by 47.7 +/- 13.1 and 48.1 +/- 15.0%, respectively (p less than 0.05). The maximal rate of relaxation became significantly faster, by 63.5% (p less than 0.05), in the crural part, whereas that of the costal part tended to become faster but not to a significant extent. In the quadriceps femoris, although twitch force showed no change, both the maximal rate of contraction and maximal rate of relaxation became faster, and tetanic force decreased. Histologic examination of hyperthyroid dogs showed vacuolization and loss of fiber area of the diaphragm. These observations suggest that thyroid hormone impairs contractility of both the crural and costal parts of the diaphragm similarly, and that the decrease in contractility may be due to a loss of muscle mass and summation impairment of twitch contraction, which differs from that in other skeletal muscles.

Animals↗
PubMed1991

[CO diffusing capacity during continuous negative extra-thoracic pressure].

Eight healthy males were studied to compare CO diffusing capacity (DLCO) during spontaneous breathing with that during continuous negative extra-thoracic pressure (CNETP). Mean DLCO was 33.0 +/- 5.1 ml.min-1.mmHg-1 during spontaneous breathing and 33.5 +/- 4.5 ml.min-1.mmHg-1 during CNETP with an end-expiratory negative extra-thoracic pressure (EENETP) of -20 cmH2O, and there was no significant difference between them (P less than 0.05). Pulmonary capillary blood volume, which was measured only in a male, was 76.7 ml during spontaneous breathing and 80.5 ml during CNETP. This change dose not seem to be significant. The results suggest that the effect of pulmonary diffusing capacity changes during EENETP on improvement of oxygenation may not be significant.

Adult↗
PubMed1990

Effect of alveolar pressure on single-breath CO diffusing capacity at mid-lung volume.

The present study examines whether changes in the alveolar pressure (PA) affect the single breath diffusing capacity for carbon monoxide (DLCO) more strongly at mid-lung volume than at total lung capacity (TLC) in normal subjects. DLCO was measured at 60%, 80% and 100% of TLC, while PA was kept at +30, 0, or -30 cm H2O by the subject's effort during the measurement of DLCO at each lung volume. The capillary blood volume (Vc) and the membrane diffusing capacity (Dm) were also determined. DLCO at zero PA was found to be higher at 100% TLC than at lower lung volumes. At PA = +30 cm H2O, DLCO at 100%, 80%, and 60% TLC decreased by 8%, 13%, and 13%, respectively, and the decreases in Vc were 2%, 10%, and 21%, respectively. However, negative PA did not cause any significant changes in DLCO or Vc at any lung volume. Also, Dm did not change at any PA. We conclude that DLCO is more affected by a positive PA at mid-lung volume than at a high lung volume, probably due to a greater decrease in Vc.

Adult↗
PubMed1988

Lack of effect from a single cigarette challenge on bronchial responsiveness in healthy non-smoking subjects.

The effect of smoking a cigarette on bronchial responsiveness was studied in healthy non-smokers. Twenty two subjects performed a methacholine inhalation test before and after smoking a single cigarette. Ten of the subjects took part in a further study in which propranolol was inhaled before the smoking challenge to diminish the baseline beta adrenergic tone of the airway. After they had smoked a single filtered or non-filtered cigarette the indices of bronchial responsiveness (the cumulative dose of methacholine starting a decrease in the reciprocal of resistance, Grs (Dmin), and the cumulative dose causing a 35% drop in the Grs (PD35Grs)) did not change significantly. With the inhalation of propranolol mean (SD) log Dmin decreased from 1.37 (0.44) units to 0.74 (0.57) (p less than 0.01) and log PD35Grs from 1.93 (0.38) to 1.51 (0.38) (p less than 0.01). Smoking a single cigarette after the inhalation of propranolol did not, however, cause any further change in bronchial responsiveness. This study suggests that smoking a single filtered or non-filtered cigarette does not change bronchial responsiveness in non-smokers, and that changes in beta adrenergic tone of the airway do not modify the effect of smoking a single cigarette on bronchial responsiveness.

Adult↗
PubMed1988

Effects and mechanism of fenoterol on fatigued canine diaphragm.

We have studied the effects and mechanism of fenoterol (a beta 2-agonist) on contractility of the fatigued canine diaphragm. Transdiaphragmatic pressure (Pdi) was measured by a pair of balloons, and diaphragmatic contractility was assessed from changes in tetanic contraction, produced by supramaximal electrical stimulation of the phrenic nerves. Diaphragmatic fatigue was developed by applying an inspiratory resistive load to a spontaneously breathing dog for approximately 30 min. Fenoterol improved the Pdi of the fatigued canine diaphragm at all stimulation frequencies, and the increases in Pdi at low frequencies were greater. The potentiation of Pdi by fenoterol occurred in a dose-dependent manner with doses of 2.5 to 10 micrograms/kg and was equal to that of aminophylline. Dibutyryl cyclic AMP did not have significant effect on the Pdi at all stimulation frequencies. The augmentation of Pdi in the fatigued diaphragm by fenoterol was abolished by administration of a calcium antagonist, verapamil, and fenoterol did not change the diaphragmatic contractility in nonfatigued dogs. We thus have concluded that fenoterol improves contractility in the fatigued canine diaphragm and the effect might be brought about by an increased influx of calcium to the muscle cell.

Aminophylline↗
PubMed1988

Inactivation of dynorphin-(1-8) in isolated preparations by three peptidases.

Inactivation of dynorphin-(1-8) in three in vitro isolated preparations, guinea-pig ileum, mouse vas deferens and rabbit vas deferens, was estimated by employing the relatively specific inhibitors of enkephalin-hydrolyzing enzymes. All three enzyme inhibitors, amastatin, captopril and phosphoramidon, significantly enhanced the inhibitory potency of dynorphin-(1-8) in the three isolated preparations. The magnitude of the enhancement of the dynorphin potency by captopril was significantly higher than that by either amastatin or phosphoramidon in guinea-pig ileum; that by amastatin was significantly higher than that by either captopril or phosphoramidon in rabbit vas deferens; and that by amastatin was similar to that by captopril, but significantly higher than that by phosphoramidon in mouse vas deferens. The Ke values of three antagonists, naloxone, Mr 2266 and ICI 154129, against dynorphin-(1-8) in the presence of the three peptidase inhibitors indicated that dynorphin-(1-8) acted on kappa receptors in guinea-pig ileum and on both kappa and delta receptors in mouse vas deferens. Since amastatin, captopril and phosphoramidon produced the naloxone-reversible inhibition of contractions of guinea-pig ileum in the presence of dynorphin-(1-8), all three dynorphin-inactivating enzymes were indicated to be located very close to kappa receptors.

Aminopeptidases↗
PubMed1988

[Clinical studies of cefpodoxime proxetil in respiratory tract infections].

Twelve patients with respiratory tract infections were treated with cefpodoxime proxetil (CS-807, CPDX-PR), a new cephem antibiotic. It was given orally at a dose of 200 mg 2 times a day for 4 approximately 15 days. Its clinical effects were evaluated as excellent in 1 case, good in 9 cases and poor in 2 cases. The efficacy rate was 83.3%. Its bacteriological effects were evaluated as eradication in 5 strains and decrement in 1 strain. The eradication rate was 83.3%. No adverse reactions and disorder of laboratory findings due to CPDX-PR were observed.

Administration, Oral↗
PubMed1988

[Clinical study of S 6472 granule preparation (sustained-release cefaclor) in chronic respiratory airway infections].

S 6472 granule preparation, a sustained-release preparation of cefaclor, was administered to 21 patients with chronic respiratory airway infections for its clinical study; a daily dosage between 750 and 1,500 mg was orally given in 2 divided doses after breakfast and dinner for a duration of 3 to 14 days. Clinical effects were good in 15 cases, fair in 1 case, poor in 4 cases and unknown in 1 case. No side effects were observed except for a case of impaired appetite. There appeared to be no abnormal laboratory test valued due to the drug.

Administration, Oral↗
PubMed1986

Species differences in vacuolation of the choroid plexus induced by the piperidine-ring drug disobutamide in the rat, dog, and monkey.

A subchronic oral toxicity study of disobutamide, a piperidine ring compound with antiarrhythmic activity, was conducted at doses of 30, 100, and 250 mg/kg in rats, 45 mg/kg in dogs, and 90 mg/kg in monkeys. Numerous vacuoles were observed in various organs such as the liver, kidneys, heart, lungs, spleen, thymus, stomach, and choroid plexus in these animals. The epithelium of the choroid plexus (CP), however, showed severe vacuolation in rats and monkeys but not in dogs. The vacuoles corresponded to enlarged and myelin-figured lysosomes observed by electron microscopy, revealing morphological characteristics which have been reported as drug-induced phospholipidosis. In a further study, the drug penetration to cerebrospinal fluid (CSF) and the drug concentration in CP were examined in these animals. Daily po doses of 250, 45, and 90 mg/kg were, respectively, administered to rats, dogs, and monkeys to maintain approximate equivalency in peak blood concentrations across species, over a course of 35 days. The concentration of the drug in the CP was higher in rats and monkeys than in dogs, and the CSF/serum ratio of the drug concentration was extremely high in rats. The uptake of the drug by the CP in vitro was high in rats, monkeys, and dogs, in this order. In dogs, both direct contact of the drug with the CP during incubation and intraventricular administration induced vacuolation in the epithelium. From these results it was concluded that differences of the drug's penetration into the CSF and its uptake by the choroid plexus epithelium are responsible for the species differences of CP vacuolation in the animals.

Animals↗
PubMed1986

Agonist and antagonist actions of buprenorphine on three types of opioid receptor in isolated preparations.

Both agonist and antagonist actions of buprenorphine on isolated preparations were studied. The Ke (equilibrium dissociation constant) values of both naloxone and Mr 2266 [(-)-2-(3-furylmethyl)-5, 9-diethyl-2'-hydroxy-6,7-benzomorphan] against buprenorphine and the ratio of IC50 (concentration of the drug to produce 50% inhibition of the twitch) value of buprenorphine after to before exposure of mouse vas deferens to beta-FNA (beta-fumarate methyl ester derivatives of naltrexone), an irreversible mu antagonist, suggest that buprenorphine acts as both a mu and kappa agonist on mouse vas deferens. The agonist effect of buprenorphine at relatively high doses on guinea-pig ileum and mouse vas deferens and the negative agonist effect on both rat and rabbit vas deferens indicate that buprenorphine acts as a partial agonist on isolated preparations. The Ke values of buprenorphine show that buprenorphine has about equal antagonist effectiveness against a mu and kappa agonist with approximately five-fold lower effectiveness against a delta agonist. The possible mechanisms for the several characteristic actions of buprenorphine on guinea-pig ileum such as the slow onset of action, the increased magnitude of inhibition after washing the tissue, the negative elimination of the inhibition by either washing the tissue or the naloxone administration, and the negative elimination of the antagonist action by washing the tissue were discussed.

Animals↗
PubMed1985

Difference of lectin binding sites of secretory granules between normal pituitary and adenoma cells.

Electron-immunocytochemical staining with lectin (concanavalin A: Con A) binding sites analysis was applied to study secretory granules of human pituitary adenomas and surrounding normal pituitary tissue using post-embedded serial ultrathin sections. Twelve cases of human pituitary adenoma and three specimens of normal pituitary tissue surrounding adenomas were studied: the cases were operated on between 1982 and 1984. The tumors consisted of four prolactin (PRL)-, six growth hormone (GH)-, and two adrenocorticotropic hormone (ACTH)-producing adenomas. In parallel with the detection of Con A binding sites of secretory granules, their secreting hormones were characterized electron-microscopically with the immunocytochemical horseradish peroxidase (HRP) labeling using the avidin-biotin technique. The two cases of ACTH-producing adenomas showed either weak or negative reactions with Con A on secretory granules, while normal ACTH-producing pituitary cells showed strong reactions with Con A on every secretory granule observed. Large secretory granules of PRL- or GH-producing cells showed negative reactions with Con A both in the pituitary adenoma and normal pituitary, while some small granulated or sparsely granulated adenoma cells also showed strong reactions with Con A. The complexity of human pituitary adenomas is illustrated as well as the difference in biochemical structure of normal pituitary cells and pituitary adenoma cells secreting the same specific hormone.

Adenoma↗