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Biomedical subjects

T Takishima

Publications and source records attributed to T Takishima.

At least 361 records · Page 20Linked to original sources

Effect of substance P on mucus secretion of isolated submucosal gland from feline trachea.

To elucidate how substance P (SP) produces submucosal gland secretion, we examined the effects of SP on the glandular contractile response and 3H-labeled glycoconjugate release in isolated submucosal glands from feline tracheae. SP (10(-12) to 10(-4) M) produced dose-dependent increases in the contractile response, and the maximal tension induced by SP was approximately 70% of the response to methacholine. SP-induced contraction is blocked completely by atropine and augmented by neostigmine. Pretreatment with hemicholinium 3, an acetylcholine synthesis inhibitor, inhibited the contractile response to SP. Pretreatment with tetrodotoxin did not inhibit the contractile response to SP. Capsaicin induced tension of a magnitude similar to that of SP. SP (10(-7) M) produced a significant increase (74% above control) in radiolabeled glycoconjugate release from isolated glands, whereas SP had no significant effects on glycoconjugate release from tracheal explants, probably because of epithelial suppression. Atropine abolished SP-evoked glycoconjugate release in isolated glands. Our findings indicate that 1) SP induces glandular contraction, which is related to the squeezing of mucus in the ducts and secretory tubules, 2) SP stimulates radiolabeled glycoconjugate release in isolated submucosal gland, probably involving mucus synthesis and/or cellular secretion, and 3) these two actions are mediated by a peripheral cholinergic mechanism.

Animals↗

Possible sensory receptor of nonadrenergic inhibitory nervous system.

To determine the sensory receptor of the nonadrenergic inhibitory nervous system (NAIS), 22 cats were anesthetized and serotonin was continuously administered (50-250 micrograms.kg-1.min-1 iv) to increase pulmonary resistance (RL) to 377 +/- 57% (SE) of the control value. We then 1) mechanically irritated the trachea, 2) intravenously administered capsaicin (5 micrograms/kg), or 3) induced hypoxia (arterial PO2 30-40 Torr) to stimulate irritant and bronchial C-fiber receptors, pulmonary C-fiber receptors, or the carotid body (chemoreceptors), respectively. After treatment with atropine (3 mg/kg iv) and propranolol (2 mg/kg iv), the serotonin-induced change in RL was reduced by 58.6 +/- 14.3% by mechanical irritation and 63.3 +/- 12.1% by intravenous capsaicin. However, hypoxia produced no dilatation of the airways. In further experiments, we employed capsaicin inhalation to stimulate bronchial C-fiber receptors. Inhaled capsaicin (0.1%, for 5 breaths) also reduced RL by 79.2 +/- 9.2% of the elevated value, after atropine and propranolol. Treatment with a ganglionic blocking agent, hexamethonium (2 mg/kg iv), abolished bronchodilator responses, implying that a reflex pathway through vagal nerves is involved in this phenomenon. These results suggest that pulmonary and bronchial C-fiber receptors may be involved as sensory receptors in NAIS reflex bronchodilatation.

Airway Resistance↗

Effect of a previous voluntary deep breath on laryngeal resistance in normal and asthmatic subjects.

We studied changes in both laryngeal resistance (Rla) and respiratory resistance (Rrs) after a voluntary deep breath in 7 normal and 20 asthmatic subjects. Rla was measured using a low-frequency sound method (Sekizawa et al. J. Appl. Physiol. 55: 591-597, 1983) and Rrs by forced oscillation at 3 Hz. In normal subjects, both Rla and Rrs significantly decreased after a voluntary deep breath (0.05 less than P less than 0.01). During methacholine provocation in the normal subjects, a voluntary deep breath significantly decreased Rrs (0.05 less than P less than 0.01, but Rla was significantly increased (0.05 less than P less than 0.01). In 10 asthmatic subjects in remission, a voluntary deep breath significantly increased Rrs (0.05 less than P less than 0.01) but significantly decreased Rla (0.05 less than P less than 0.01). In another 10 asthmatic subjects during spontaneous mild attacks, a voluntary deep breath significantly increased both Rrs and Rla (0.05 less than P less than 0.01). The present study showed that without obvious bronchoconstriction, Rla decreased after a voluntary deep breath in both normal and asthmatic subjects but, with bronchoconstriction, Rla increased in both groups. Subtraction of the change in Rla from Rrs gives the change in Rrs below the larynx (Rlow). Rlow changed little or decreased in normal subjects and increased in asthmatic subjects, irrespective of base-line bronchomotor tone. These results suggest that airway response below the larynx after a voluntary deep breath differentiates patients with bronchial asthma from normal subjects.

Adult↗

Effects of the pericardium on the diastolic left coronary pressure-flow relationship in the isolated dog heart.

We studied the effects of the pericardium on diastolic left coronary pressure-flow relationships in heart-blocked and isolated canine preparations. In these preparations, the left and right coronary arteries were dilated with adenosine and perfused by means of a pressurized arterial reservoir. The diastolic left heart pressure (LHP) was controlled by the height of a reservoir connected to the left atrium and left ventricle. The right atrial and ventricular pressure i.e., coronary outflow pressure, was kept constant at 0 mm Hg. Before and after pericardiectomy, diastolic coronary pressure-flow relationships were obtained at three values of LHP (0, 15, and 30 mm Hg) with driving pressure decreasing (2 mm Hg/sec or less) from approximately 60 mm Hg to the actual zero-flow pressure (Pf = 0) during a single long diastole induced by cessation of ventricular pacing. The slopes of the coronary pressure-flow relationships were approximated by a linear regression analysis in which the correlation coefficients were greater than .98 in all cases. Before pericardiectomy, with LHP increasing from 0 to 15 and 30 mm Hg, the value of Pf = 0 significantly increased from 7 +/- 1 to 16 +/- 1 (p less than .01) and 28 +/- 2 mm Hg (p less than .01), respectively. After pericardiectomy, it increased from 7 +/- 1 to 14 +/- 1 (p less than .01) and 17 +/- 2 mm Hg (p less than .01), respectively. When LHP was at 0 and 15 mm Hg, the pericardiectomy had no effect on the value of Pf = 0.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Bronchoalveolar lavage and histologic characterization of late asthmatic response in guinea pigs.

To elucidate the mechanisms of late asthmatic response (LAR) observed in asthmatic subjects, we have developed an animal model of LAR using guinea pigs. Fifty guinea pigs were immunized with a mixture of Ascaris suum extract and aluminum hydroxide and then challenged with an inhalation of Ascaris suum extract without anesthesia. Twenty of the 50 guinea pigs showed a dual asthmatic response in which the LAR occurred 3 to 6 h after immediate asthmatic response (IAR). Histologic studies by rapid freezing with liquid nitrogen or bronchoalveolar lavage (BAL) were performed in 14 of these 20 guinea pigs with LAR and compared with those in 10 of 18 guinea pigs with only IAR, 10 control guinea pigs, and 10 nonimmunized but challenged guinea pigs. Both the percentage and the absolute number of neutrophils in the BAL fluid of the guinea pigs with LAR were significantly greater than those of the control guinea pigs (p less than 0.02) and than those of the nonimmunized but challenged guinea pigs (p less than 0.02). However, that of guinea pigs with LAR was not significantly different from that of guinea pigs with only IAR. On the other hand, histologic examination showed that eosinophil infiltration within the airway walls of the guinea pigs with LAR was more prominent than that of the guinea pigs with only IAR, and showed that there was no significant difference in neutrophil infiltration within the airway walls between the guinea pigs with LAR and the animals with only IAR. Contraction of airway (bronchus, bronchiole) smooth muscle, submucosal edema, and mucus in airway lumen were also observed in LAR.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Inhalation of road dust by human subjects.

We measured pneumomagnetic field strength (PMFS) in 42 healthy control subjects living in districts of Northern Japan with low levels of road dust pollution and in 39 healthy subjects living in areas with high levels of road dust pollution. Suspended road dust produced by studded tires increases from 30 micrograms/m3 during the summer season to levels as high as 400 micrograms/m3 during the snow season in the downtown areas of Sendai, Japan. Road dust retained in the lungs, containing 3% iron, was magnetized from the surface of the chest wall, and PMFS was measured. Three to 5 sequential PMFS measurements were made in each subject in March and October of 1984 and 1985, and in March 1986. The PMFS in control subjects in March 1984 was 37 +/- 14 pico-Tesla (mean +/- SD) and did not significantly differ from the PMFS in October 1984 or that in March 1985. In March 1984, the PMFS of the subjects in highly polluted areas was 95 +/- 100 pico-Tesla (mean +/- SD) and was significantly higher than that of control subjects (p less than 0.01) and subsequently decreased in March 1985 and in March 1986, corresponding to a decrease in suspended road dust brought about by a campaign to eliminate the use of studded tires. Our findings suggest that some road dust caused by studded tires is retained in the lungs.

Adult↗

Late asthmatic response to Ascaris antigen challenge in dogs treated with metyrapone.

We developed an experimental dog preparation that shows a biphasic bronchoconstriction after allergen exposure. After anesthetization, the dogs were intubated with endotracheal tubes and manually ventilated. Respiratory resistance (Rrs) was measured by the forced oscillation method at 3 Hz. Ascaris suum, diluted from 10(-5) to 10(-2) of the extract, was inhaled during tidal breathing for 5 min. One hour before antigen challenge, 10 dogs received 70 mg/kg of metyrapone (cortisol synthesis inhibitor), and 2 h after antigen challenge 35 mg/kg of metyrapone were injected intravenously. In another 10 dogs, metyrapone was not administered. After the maximal increase in Rrs had been assessed (immediate asthmatic response), Rrs increased again 4 to 6 h after antigen challenge in 8 of the 10 dogs treated with metyrapone (late asthmatic response, 443 +/- 282% mean +/- SD of initial Rrs), which was significantly higher than Rrs 6 h after antigen challenge (124 +/- 41%) in dogs without metyrapone (p less than 0.01). In another 5 dogs, ragweed challenge with metyrapone caused no change in Rrs. Bronchoalveolar lavage at the time of the late response revealed a significant correlation between late asthmatic response and neutrophil accumulation (p less than 0.01) in all dogs. We conclude that cortisol depletion augments the occurrence of the late response. The present dog model may be a useful tool for study of the late response in bronchial asthma.

Airway Resistance↗

Morphological characterization of basophilic cells in bronchoalveolar lavage fluids from patients with bronchial asthma and idiopathic pulmonary fibrosis.

A marked increase in the number of basophilic cells (BCs) was found in the bronchoalveolar lavage (BAL) fluids from the patients with bronchial asthma and idiopathic pulmonary fibrosis (IPF). Histochemical analysis revealed that basophils were the major components of BCs in asthmatic patients, while formalin-insensitive BCs, which are presumed to be connective tissue mast cells, were observed in BAL fluids from IPF patients. In control subjects, almost all of BCs were mucosal mast cells.

Asthma↗

[Canine orthotopic liver transplantation].

For the purpose of increasing long-term survival in canine orthotopic hepatic allotransplantation, immunosuppression by mizoribine and/or cyclosporin was instituted with the following results: 1) The survival of control dogs without treatment (n = 5) was 10.0 +/- 2.9 days (Mean +/- S.E.), and the survival of dogs treated with mizoribine (n = 15) was 44.6 +/- 31.8 days. There was no statistical difference between the two groups. On the other hand, the mean survival of dogs that were initially treated with cyclosporin and were then switched to mizoribine at one to three months after transplantation reached 145.4 +/- 70.8 days. The survival rate of dogs in the cyclosporin-mizoribine group was significantly greater than that of control group (p less than 0.02); and the survival rate of the former group proved also significantly better than that of the mizoribine group at 20 days after transplantation (X2, p less than 0.05); 2) in cases of acute rejection of the allograft, a gradual increase of the serum bilirubin level with a concomitant rise of S-GPT and alkaline phosphatase was generally observed. For an accurate diagnosis, however, an assessment of the biopsy findings of the allograft is important; 3) in chronic rejection, one animal developed the selective disappearance of interlobular bile ducts, often referred to as the "vanishing bile duct syndrome"; and 4) for differential diagnosis of vascular and/or biliary tract complications, specific morphological diagnostic procedures such as vascular and/or biliary tract angiographies are needed.

Animals↗