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Biomedical subjects

Y Fukuchi

Publications and source records attributed to Y Fukuchi.

At least 145 records · Page 8Linked to original sources
PubMed1996

Intercellular adhesion molecule-1 mediates acid aspiration-induced lung injury.

Acid-aspiration-induced injury is one of the leading causes of adult respiratory distress syndrome. Intercellular adhesion molecule-1 (ICAM-1) is a ligand for lymphocyte-function-associated antigen-1 alpha (LFA-1 alpha), and it has been shown to be required for leukocyte migration into inflamed areas. The purpose of this report was to investigate the role of the ICAM-1/LFA-1 alpha pathway in a rat model of acid-aspiration-induced injury. Animals received 3.0 ml/kg HCI (0.1N; pH, 1.0) intratracheally pretreated with control monoclonal antibodies (mAbs) (HCI group) or anti-ICAM-1 and LFA-1 alpha mAbs (Test group). In the HCI group, increases in lung resistance (RL) (229 +/- 23% baseline), lung wet-to-dry weight ratio (W/D) (11.9 +/- 0.4), protein concentration (TP) (0.447 +/- 0.054 mg/ml), and the number of neutrophils (PMN) (159.0 +/- 19.4 x 10(4)) of bronchoalveolar lavage fluid were observed. In the Test group, HCI-induced injury was significantly reduced (RL, 122 +/- 7% baseline; W/D, 7.2 +/- 0.1; TP, 0.277 +/- 0.016 mg/ml; PMN, 8.8 +/- 0.8 x 10(4)). The administration of mAbs to ICAM-1 and LFA-1 alpha after HCI instillation partially attenuated HCI-induced responses. These observations suggest that the ICAM-1/LFA-1 alpha pathway might be involved in the pathogenesis of adult respiratory distress syndrome caused by acid aspiration.

Animals↗
PubMed1996

Roles of calcitonin gene-related peptide (CGRP) in hyperpnea-induced constriction in guinea pigs.

It has been reported that hyperpnea-induced bronchoconstriction in guinea pigs is a potential model for exercise-induced asthma in humans. We hypothesized that calcitonin gene-related peptide (CGRP) could modulate leukotriene D4 (LTD4)-induced responses and be involved in the pathophysiology in this asthma model. We measured tracheal (Ptr) and alveolar pressure (PA) using alveolar capsules in open-chested, mechanically ventilated (f = 1 Hz, VT = 9 ml/kg, PEEP = 4 cm H2O) guinea pigs. Animals were intravenously pretreated with saline (SAL), CGRP(8-37) (CGRP receptor antagonist), CGRP, MK-571 (LTD4 receptor antagonist), MK-886 (5-lipoxygenase inhibitor), or CGRP(8-37) + MK-571, and then underwent dry gas hyperpnea challenge (HC, 95% 02-5% CO2, 150 breaths/min, 7 min). We calculated resistance of lung (RL), tissue (Rti), and airway (Raw). HC increased RL, Rti, and Raw in SAL controls (322 +/- 27, 430 +/- 59, 299 +/- 23% baseline, respectively). MK-571, MK-886, and CGRP significantly reduced the responses to HC, while CGRP(8-37) enhanced HC-induced responses. Pretreatment with CGRP(8-37) and MK-571 in combination attenuated HC-induced constriction. In addition, pretreatment with CGRP reduced responses induced by intravenous administration of LTD4. These observations suggest that CGRP might be involved in the pathophysiology of hyperpnea-induced constriction in guinea pigs via modulation of LTD4-elicited responses.

Animals↗
PubMed1996

Apolipoprotein B inhibits the hemolytic activity of asp-hemolysin from Aspergillus fumigatus.

We investigated the effect of human blood plasma lipoproteins on the hemolytic activity of Asp-hemolysin. Apolipoprotein B (apoB)-containing lipoproteins, such as low density lipoprotein (LDL) and very low density lipoprotein (VLDL), inhibit the activity of this hemolytic toxin. When Asp-hemolysin (15 mu g) was incubated with 100 mu g LDL (as protein), the hemolytic activity was inhibited by 90%. When 20 mu g apoB was added, the hemolytic activity was almost completely inhibited. Furthermore, similar inhibition was obtained in the filtrates which were separated from the incubation mixture of Asp-hemolysin with LDL or apoB following ultrafiltration through a membrane with a molecular cutoff = 100000. The current findings suggest that the inhibition by LDL is due to apoB binding to Asp-hemolysin.

Apolipoproteins B↗
PubMed1996

Importance of diffuse aspiration bronchiolitis caused by chronic occult aspiration in the elderly.

Diffuse aspiration bronchiolitis (DAB) is a new term that we proposed to define a clinical entity that is characterized by a chronic inflammation of bronchioles caused by recurrent aspiration of foreign particles. In the present study, a total of 4,880 consecutive autopsies were reviewed and we found 31 patients with DAB (0.64%). To investigate the clinicopathologic features of DAB, the 23 patients with DAB (age, 81.2 +/- 6.2 years [mean +/- SD]), from whom clinical information was available, had their features compared to those of 40 randomly selected patients with aspiration pneumonia (age, 81.9 +/- 8.3 years [mean +/- SD]). Oropharyngeal dysphagia was observed in half of the patients with DAB, and two thirds of patients with DAB were bedridden. The onset of DAB was more insidious than aspiration pneumonia, and in half of the patients with DAB episodes of aspiration were unrecognized. Neurologic disorders (52.2%) and dementia (47.8%) were common associated diseases. Most patients with DAB showed signs of bronchorrhea, bronchospasm, and dyspnea. The macroscopic appearance of the cut surface of DAB lung showed diffusely scattered miliary yellowish nodules that resembled those of diffuse panbronchiolitis (DPB). Histologic findings of DAB were characterized by localization of chronic mural inflammation with foreign body reaction in bronchioles. Recurrence of small amounts of aspiration might play a role in the pathogenesis of DAB. In view of possible therapeutic intervention, we emphasized the importance of recognizing this entity and differentiating DAB from pulmonary diseases associated with bronchospasm in the elderly, in particular, late-onset asthma and DPB.

Aged↗
PubMed1996

Long-term effects of inhaled anticholinergic drug on lung function, dyspnea, and exercise capacity in patients with chronic obstructive pulmonary disease.

To investigate the long-term effects of the inhaled anticholinergic bronchodilator, oxitropium bromide (OTB), on lung function, exercise capacity, and dyspnea in patients with chronic obstructive pulmonary disease (COPD), spirometry and symptom-limited exercise testing before and 1, 6, and 12 months after the regular use of OTB (600 micrograms/day) were performed in 12 patients with the use of OTB (mean age 69.9 +/- 3.1 years; FEV1/FVC 53.3 +/- 1.6%) as well as in 12 control patients who were not treated with OTB (Mean age 68.8 +/- 2.8 years; FEV1/FVC 52.6 +/- 1.9%). The dyspnea was evaluated by the slope of the regression line between Borg scale and oxygen uptake (Vo2) during exercise (Borg scale slope: BSS). At 1, 6, and 12 months after the start of OTB, the forced expiratory volume in one second (FEV1) and the exercise capacity (maximal Vo2) were greater than the pretreatment values and the dyspnea index (BSS) was significantly improved compared with the pretreatment value, while these parameters slightly worsened in the control patients over one year. In conclusion, the chronic use of an inhaled anticholinergic bronchodilator may provide beneficial improvements in expiratory flow rate, exercise performance, and dyspnea in mild to moderate COPD patients over one year.

Administration, Inhalation↗
PubMed1996

Increased spontaneous production and generation of superoxide anion by blood neutrophils in patients with asthma.

Spontaneous production and PMA- and opsonized zymosan- stimulated generation of superoxide anion by blood cells in asthmatic patients were compared with those in normal volunteers and chronic obstructive pulmonary disease (COPD) patients using a lucigenin-dependent chemiluminescence method. Superoxide anion generation by 100 microl of blood in patients with asthma and/or COPD was significantly greater than that in normal subjects [asthma: 5684 +/- 253 chemiluminescence (CL); COPD: 4994 +/- 240 CL; normal: 2543 +/- 213CL]. This is consistent with the increased superoxide generation per leukocyte (PMN) in these patients (Asthma: 1.56 +/- 0.08 CL/PMN; COPD: 1.31 +/- 0.08 CL/PMN; normal: 0.83 +/- 0.07 CL/PMN. However, spontaneous production of superoxide by individual PMNs was increased only in asthmatic patients, compared with that in normal subjects (Asthma: 0.14 +/- 0.02 CL/PMN; COPD: 0.07 +/- 0.01 CL/PMN; normal: 0.07 +/- 0.01 CL/PMN. These results indicate that the respiratory burst is enhanced in both asthmatic patients and COPD patients, and that superoxide production by resting neutrophils is also increased in asthmatic patients, but not in COPD patients, compared with normal subjects.

Adult↗
PubMed1996

[Undergraduate teaching of geriatric medicine in western countries--literature review].

To help plan for the future of undergraduate education in geriatric medicine in Japan, we reviewed the literature concerning undergraduate teaching of geriatric medicine in western countries. Undergraduate teaching in geriatric medicine in the UK is well developed: 22 of 25 universities have a full department of geriatric medicine. Training in geriatric medicine is mandatory in almost all universities. In contrast, geriatric medicine is an elective in most universities in the US. There is a shortage of geriatric medicine faculty in the US, which is similar to the situation in Japan. Clinical and basic research in geriatric medicine and gerontology should be encouraged to attract persons into this field.

Education, Medical, Undergraduate↗
PubMed1996

Expression of immunoreactive activin A protein in remodeling lesions associated with interstitial pulmonary fibrosis.

The expression of activin A, one of the transforming growth factor-beta supergene family, was studied in various pulmonary conditions associated with interstitial pulmonary fibrosis (3 cases with diffuse alveolar damage, 6 cases with idiopathic pulmonary fibrosis, and 1 case with pulmonary fibrosis associated with rheumatoid arthritis) using immunohistochemical techniques on paraffin-embedded sections. Controls consisted of 10 cases with normal pulmonary parenchyma, and 2 cases with primary pulmonary hypertension and 1 case with secondary pulmonary hypertension were also studied. The lung specimens from normal parenchyma weakly expressed immunoreactive activin A on the bronchiolar epithelium. In marked contrast, all of the specimens from cases with diffuse alveolar damage and interstitial pulmonary fibrosis demonstrated strong expression of activin A on metaplastic epithelium, hyperplastic smooth muscle cells, desquamated cells, and alveolar macrophages. Pulmonary arteries from patients with primary or secondary pulmonary hypertension showed abundant immunoreactive activin A on smooth muscle cells. These findings suggest a potential role for this growth factor, activin A, in the pathogenesis of pulmonary tissue remodeling associated with interstitial pulmonary fibrosis.

Activins↗
PubMed1995

Superoxide anion formation and glutathione metabolism of blood in patients with idiopathic pulmonary fibrosis.

The oxidant-antioxidant imbalance in the lower respiratory tract plays a major role in the pathogenesis in idiopathic pulmonary fibrosis (IPF). However, the systemic oxidant-antioxidant balance in the patients with IPF has not been extensively evaluated. In this study, the metabolism of glutathione (GSH) and superoxide anion production of whole blood were tested in 14 IPF patients and 12 normal subjects. While the total amount of GSH in the blood of IPF patients was not different from that of normal subjects (IPF; 22.9 +/- 4.9 micrograms/ml, control; 26.1 +/- 3.7 micrograms/ml), the amount of oxidized GSH (GSSG) and the ratio of GSSG to the total GSH in blood significantly increased in patients with IPF (IPF; 14.4 +/- 3.5%, control; 7.0 +/- 1.7%, P < 0.01), indicating that the glutathione redox cycle may be impaired in IPF. The production and generation of superoxide anions by blood were significantly greater in IPF than in normal subjects. The level of superoxide anion production was correlated with the GSSG/GSH ratio. These results indicate that IPF patients exhibit an impaired GSH metabolism with an increased oxidant formation of blood.

Adult↗
PubMed1995

An index to predict outcome of surgery for reflux esophagitis based on the AFP classification.

Fifteen patients with reflux esophagitis were treated surgically from July 1990 to April 1994. We evaluated these patients using the anatomic-functional-pathologic (AFP) classification both prior to and following the operation. An objective index for surgical outcome was devised. By using the grades Ai, Fj, and Pk, the i2 + j2 + k2 score was determined. The scores ranged from 3 to 22 (mean 9.1 +/- 5.4) prior to the operation. Postoperatively, 12 (80%) of 15 patients showed a complete recovery with a numerical score of 0, and their symptoms also disappeared. The scores of these 12 patients prior to the operation ranged between 3 and 11. However, the other 3 patients did not exhibit a complete recovery. Their scores prior to the operation ranged between 17 and 22, and the symptoms in 2 of these 3 patients persisted following the operation. These results suggest that surgical treatment for reflux esophagitis can be expected to be successful if the preoperative AFP score is less than 11.

Adult↗
PubMed1995

Improvements in exercise capacity and dyspnoea by inhaled anticholinergic drug in elderly patients with chronic obstructive pulmonary disease.

To test the effects of the inhaled anticholinergic drug, oxitropium bromide (OTB), on exercise capacity and dyspnoea in elderly patients (more than 75 years old) with chronic obstructive pulmonary disease (COPD), we performed cycle exercise testing on 12 elderly patients with COPD [mean age 78.7 (SD 1.1) years; FEV1% 41.3 (2.0)%] as well as 12 middle-aged COPD patients [mean age 60.1 (1.0) years; FEV1% 38.9 (2.4)%] before and after inhalation of OTB or placebo in a double-blind and placebo-controlled design. Spirometry was repeated immediately before and 30 min after OTB or placebo inhalation. Dyspnoea was quantitatively evaluated using the slope of the regression line between Borg scale and oxygen uptake (VO2) during exercise (Borg scale slope: BSS). After OTB inhalation, spirometric indices, exercise capacity as indexed by maximal VO2, and dyspnoea index (BSS) were improved compared with pre-inhalation value in both the elderly and middle-aged patients. The magnitude of improvements in these indices in the elderly patients was not different from that in the middle-aged. We conclude that the inhaled anticholinergic drug produces useful improvements in dyspnoea and exercise capacity in both elderly and middle-aged COPD patients.

Administration, Inhalation↗
PubMed1995

A comparison of ventilation components in young and elderly men during exercise.

To elucidate the influence of age on ventilation components during exercise, we investigated the change in fractional contribution of abdomen or thorax during exercise in 12 elderly (71.9 +/- 5.3, mean +/- SD years) and 12 young (25.0 +/- 4.9 years) normal male subjects using respiratory-inductive plethysmography. At rest, abdominal/thoracic contribution was not different between elderly and young. During exercise, abdominal contribution to total ventilation was decreased in the young compared to that at rest (rest: 53.6 +/- 2.9% vs exercise: 50.4 +/- 1.9-48.9 +/- 1.8%; p < .01), but significantly increased in the elderly (rest: 53.9 +/- 1.8% vs exercise: 57.3 +/- 1.7-59.8 +/- 2.0%; p < .01). Only in the elderly, respiratory frequency was increased during exercise compared to that at rest (rest: 20.1 +/- 0.8 [/min] vs exercise; 25.6 +/- 1.5-27.8 +/- 1.6 [/min]; p < .05). The breathing pattern in the elderly during exercise was partly simulated in the young by reducing thoracic compliance using chest strapping. This study demonstrates the greater participation of diaphragmatic motion together with rapid shallow breathing during lower graded exercise in the elderly as compared with the young. This ventilatory pattern during exercise may result from a stiffening of the thorax with advancing age.

Abdomen↗
PubMed1995

In vivo effects of endothelin A- and B-receptor antagonists in guinea pigs.

Endothelin (ET)-1, a novel 21-amino acid constrictor peptide, has been recently reported to have a potential pathophysiological role in asthma. We hypothesized that ET-1 might affect guinea pig lung via different ET receptor subtypes, i.e., ETA and ETB, in vivo. To test this hypothesis, we investigated the effects of ET-1 on airways in anesthetized, open-chest, mechanically ventilated [frequency (f) = 1 Hz; tidal volume (VT) = 9 ml/kg; positive end-expiratory pressure (PEEP) = 4 cmH2O] guinea pigs in the absence or the presence of ETA and ETB selective antagonists, i.e., BQ-123 and BQ-788, respectively. We affixed alveolar capsules to the lungs to measure alveolar pressure and calculated the elastance of lung (EL) and the resistance of lung (RL), tissue (Rti), and airway (R(aw)) under control conditions and after intravenous administration of ET-1 (10(-8) mol/kg). ET-1 induced a concentration-dependent increase in RL, Rti, R(aw), and EL.BQ-123 (2 mg/kg) partially blocks delta RL and delta R(aw) during ET-1 induced constriction, while delta Rti and delta EL were not significantly affected. BQ-788 (2 mg/kg) significantly inhibited delta RL, delta Rti, delta R(aw), and delta EL during ET-1-induced constriction. The combination of BQ-123 and BQ-788 completely ablated the response to ET-1. These data suggest that both ET receptor subtypes, i.e., ETA and ETB, may have physiological roles in guinea pig airways in response to ET-1, a potential mediator of asthma.

Airway Resistance↗
PubMed1995

In vitro airway and tissue response to antigen in sensitized rats. Role of serotonin and leukotriene D4.

We have recently demonstrated that tissue resistance increases during the early response (ER) to antigen challenge in sensitized Brown-Norway rats. The purpose of the present study was to investigate the in vitro airway and tissue responses to antigen and the involvement of the potential mediators serotonin (5-HT) and leukotriene D4 (LTD4). We sensitized Brown-Norway rats with ovalbumin (OA) and subsequently challenged bronchial rings and subpleural parenchymal strips with OA in the organ bath. In selected experiments tissues were incubated with methysergide (a 5-HT receptor antagonist), ketanserin (a 5-HT2 receptor antagonist), MK-571 (a LTD4 receptor antagonist), or MK-886 (5-lipoxygenase inhibitor) prior to challenge. Both bronchial rings and parenchymal strips constricted in response to OA. Methysergide and ketanserin completely inhibited OA-induced constriction of bronchial rings. The effect of MK-571 was not significant, whereas MK-886 partially blocked OA-induced bronchial constriction, suggesting a potential role for LTC4 in antigen-induced airway constriction. In parenchymal strips, methysergide, ketanserin, MK-571, and MK-886 all partially inhibited the OA response, whereas the combinations of methysergide and MK-571 or ketanserin and MK-886 completely ablated the response. These data suggest that both bronchial rings and parenchymal strips constrict after OA challenge but that the relative contributions of 5-HT and LTD4 to the allergic response in central airways and parenchymal tissues differ.

Airway Resistance↗
PubMed1995

Antagonism of ICAM-1 attenuates airway and tissue responses to antigen in sensitized rats.

Airway inflammation is involved in the pathogenesis of bronchial asthma. Intercellular adhesion molecule-1 (ICAM-1) is a ligand for lymphocyte function-associated antigen-1 alpha (LFA-1 alpha) and has been shown to be required for leukocyte migration into inflamed area. The purpose of this report was to investigate the role of ICAM-1/LFA-1 alpha pathway in a rat model of extrinsic asthma using monoclonal antibodies (mAbs). We chose to study ovalbumin (OA)-sensitized Brown-Norway rats, an animal model in which there is a high prevalence of both early (ER) and late responses (LR) after antigen challenge. We measured tracheal and alveolar pressure using alveolar capsules in open-chested, mechanically ventilated animals to calculate resistance of lung (RL), tissue (Rti), and airway (Raw). In the OA group, both ER (RL, Rti, Raw = 263 +/- 16, 235 +/- 10, 309 +/- 38% baseline) and LR (RL, Rti, Raw = 265 +/- 26, 238 +/- 13, 316 +/- 55% baseline) were observed. The administration of mAbs to ICAM-1 and LFA-1 alpha significantly attenuated the ER (RL, Rti, Raw = 146 +/- 9, 141 +/- 11, 156 +/- 8% baseline) and LR (RL, Rti, Raw = 128 +/- 8, 124 +/- 5, 137 +/- 1% baseline), indicating that both airway and lung tissues were involved in this mechanism. The current observations suggest that ICAM-1/LFA-1 alpha pathway is involved in both the early and late responses in a rat model of allergic asthma. The antagonism of ICAM-1 and LFA-1 alpha may provide a potential therapeutic approach to the early and late responses of bronchial asthma.

Airway Resistance↗