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Biomedical subjects

Y Fukuchi

Publications and source records attributed to Y Fukuchi.

At least 19 recordsLinked to original sources
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

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↗
PubMed1995

Expression of immunoreactive and bioactive activin A protein in adult murine lung after bleomycin treatment.

Activin A is a homodimeric protein structurally and functionally related to transforming growth factor beta (TGF-beta), and the expression of activin A is modulated by TGF-beta. Here, we demonstrate the expression of activin A in normal and bleomycin (BLM)-treated murine lungs. ICR mice were treated with BLM intraperitoneally for 10 days, whereas saline vehicle was injected into control mice. Intra-alveolar fibrotic changes were observed in the lung tissue obtained from the mice at day 14 after the final BLM administration. Immunohistochemical studies using a polyclonal antibody to activin A revealed the presence of activin A in the bronchiolar epithelium and smooth muscle cells of veins in both control and BLM-treated mice. In the BLM-treated mice at days 7 and 14, the marked infiltration of immunoreactive alveolar macrophages was observed in the area of fibrotic changes. Bioactivity of activin A measured by erythroid differentiation factor assay in the conditioned medium of alveolar macrophages obtained from BLM-treated mice at day 14 was significantly increased. These findings indicate that alveolar macrophages are a potent source of activin A after BLM treatment. The present study demonstrates for the first time the abundant expression of activin A in murine lung tissues after BLM administration, suggesting that activin A may play a role in the pathogenesis of BLM-induced pulmonary fibrosis.

Activins↗
PubMed1995

Biochemical characteristics of lungs in senescence-accelerated mouse (SAM).

This study examined age-related biochemical changes of the lung in an animal model of senile lung, senescence-accelerated mouse (SAM). Bronchoalveolar lavage (BAL) was performed on two strains of SAM, the senescence-prone strain (SAM P2) and the senescence-resistant strain (SAM R1), as well as on normal ageing C57 black mice (C57BL), aged 1-24 months. Elastase-like and elastase inhibitory activity of BAL fluid (BALF), glutathione (GSH) and oxidized GSH (GSSG) content both of BALF and lung tissue, and oxygen radical generation of free lung cells obtained by BAL were examined in the three strains of mice. Cell populations did not change throughout the life in SAM strains and C57BL. The elastolytic activity in SAM was greater than in C57BL, but there was no change with age. Both a decreased content of GSH and an increased oxidation of the GSH in BALF were markedly observed with ageing in SAM P2. In the lung tissue, the GSSG/GSH ratio in SAM strains was consistently greater than that in C57BL, suggesting that the GSH redox cycle of the lung may be impaired in SAM strains. The oxygen radical generation by free lung cells increased with age in all three strains, but the increase was earlier and more pronounced in SAM P2 than in the other two strains. In conclusion, an impaired GSH redox cycle and an increased formation of oxygen radicals are observed in the lungs of SAM with increasing age.

Aging↗
PubMed1995

Effect of cigarette smoking on pulmonary function in each phenotype M of alpha-1-protease inhibitor.

Human alpha-1-protease inhibitor (alpha-1-Pi) has been known to be a highly polymorphic protein. We hypothesized that antiprotease activity of each phenotype M of alpha 1-protease inhibitor (PiM) might be different among smokers and that a variation of decrease in pulmonary function for a given amount of cigarette smoking might be associated with PiM phenotypes. To test this, we investigated the effect of cigarette smoking on pulmonary function in each PiM phenotype. The serum level of alpha 1-Pi was measured by the turbidimetric immunoassay and the distribution of PiM phenotypes was determined using isoelectric focusing technique in 247 healthy subjects and 20 COPD patients. Serum levels of alpha-1-antitrypsin of healthy and COPD subjects were 205.1 +/- 31.1 and 179.2 +/- 44.4 (+/- SD) mg/dL, respectively (p > 0.01). The frequency of each PiM phenotype in healthy subjects was shown as follows: M1, 0.555; M1M2, 0.328; M2, 0.041; M1M3, 0.057; M2M3, 0.016; M3, 0.004. The difference in the distribution of PiM phenotypes between healthy and COPD subjects was not significant. Single- and multiple-regression analyses showed that the ratio of FEV1 to forced vital capacity (FVC), in which FEV1 is expressed as percentage of FVC, the maximum flow rate at 50% of FVC divided by measured body height (V50/Ht), and the maximum flow rate at 25% of FVC divided by body height (V25/Ht) were closely related to age and that V25/Ht also was related to smoking index. However, PiM phenotype was unrelated to those pulmonary function variables. We conclude that PiM phenotype is not a major determinant of difference in magnitude of pulmonary impairments caused by cigarette smoking in each individual.

Adult↗
PubMed1995

Postgastrectomy aspiration pneumonia.

One hundred eighty-six patients who had undergone total gastrectomy were analyzed in regard to pulmonary aspiration. Sixteen patients (8.6%) with recurrent respiratory tract inflammation (r-RTI) and 45 patients (24.2%) with sporadic RTI (s-RTI) were observed. The r-RTI group frequently showed symptoms related to esophageal reflux among the many factors affecting the onset of disease. They were also characterized by marked inflammatory responses with various and atypical clinical courses. The swallowing provocation test showed swallowing disturbances (prolonged latency) in patients with r-RTI. We concluded that the aspiration of esophageal reflux contents was the most important risk factor of recurrent pulmonary complications in patients with total gastrectomy.

Adult↗
PubMed1995

[Compliance with prescriptions and adverse drug reactions in the elderly].

We performed a survey concerning prescriptions in the elderly to investigate the influence of ageing on compliance and the occurrence of adverse drug reactions. First, we surveyed 222 outpatients attending at our department (average 70.2 y.o.). The physicians in change examined the account of remaining medicines, and we analyzed the relationship between the compliance with prescriptions, age, diseases and medicines. Secondly, we surveyed 282 inpatients (average 68.0 y.o.). We compared the number of prescriptions before hospitalization, at discharge and 6 months after discharge. We also examined the frequency of adverse drug reactions. The number of medicines, which were prescribed for both in- and outpatients, increased according to age. However, no ageing effect on the number of prescriptions per disease was found. The average number of prescriptions per patient at discharge significantly increased compared to that before hospitalization. The average number of prescriptions of the elderly (above 65 y.o.) admitted at emergency case was significantly more than regularly admitted elderly (p < 0.01). The rate of proper medication taking was significantly higher in the elderly than in the young (p < 0.05). The total percentage of adverse drug reactions among inpatients was 18.8%. Among the patients aged above 60 y.o., the frequency of adverse drug reactions increased according to age. Increased number of the prescribed medicines might be involved in the cause of increased adverse drug reactions in the elderly.

Adult↗
PubMed1994

Adenovirus pulmonary infections identified by PCR and in situ hybridisation in bone marrow transplant recipients.

AIMS: To investigate adenovirus pulmonary infections in bone marrow transplant (BMT) recipients. METHODS: Formalin fixed, paraffin wax embedded lung tissue was examined from 13 necropsy cases after BMT using PCR and in situ hybridisation to detect adenovirus DNA. The E1A region of the adenoviral genome was targeted for PCR. In situ hybridisation was performed only in the PCR positive cases. RESULTS: Of the 13 lung specimens analysed, nine cases were negative for adenoviral nucleic acid. Four (30%) PCR and two (15%) in situ hybridisation positive cases were found. In some of the patients there were clinical and pathological indications that some diseases might be associated with adenovirus infection--haemorrhagic cystitis (three cases); necrotising pneumonia (one case). In necrotising pneumonia in which no pathogenic agents had been shown by conventional histological study, the in situ hybridisation technique showed positive staining for adenovirus. In a patient who died of renal failure caused by adenovirus nephritis, both PCR and in situ hybridisation were positive in the lung as well as in the kidney, although no histological change was found. Two PCR positive cases lacked positive sites for adenovirus by in situ hybridisation. CONCLUSIONS: The combination of PCR and in situ hybridisation could be useful for diagnosing adenovirus infection of the lung in BMT recipients. These results provide a basis for exploring further the clinical use of PCR and in situ hybridisation to diagnose adenovirus infection.

Adenovirus Infections, Human↗
PubMed1994

Mechanical interdependence in relation to age: effects of lung volume on airway resistance in rats.

Elastic recoil has been reported to decrease with increasing age in human subjects. In the current study, we hypothesized that aging influences mechanical interdependence, which affects the magnitude of agonist-induced airway constriction. To examine this hypothesis, we compared the effects of changing lung volume on airway resistance (Raw) under baseline conditions and during methacholine-induced constriction in adult (14 mo old, 624 +/- 14 g; n = 11) and aged (29 mo old, 629 +/- 9 g; n = 11) Sprague-Dawley rats. With use of alveolar capsules, Raw was directly measured under baseline conditions at different levels of end-expiratory transpulmonary pressure (PL; 3-11 cmH2O). Then aerosolized methacholine was delivered (125 mg/ml), and measurements were performed at different levels of PL (3 and 11 cmH2O). From measured tracheal flow and tracheal and alveolar pressures in open-chest animals during mechanical ventilation (6 ml/kg tidal volume, 1 Hz frequency), we calculated dynamic lung elastance and resistance of lung, tissue, and airway. In the baseline conditions, we found that increasing lung volume decreased Raw similarly in both groups but that lung elastance was reduced in the aged group at PL > or = 7 cmH2O. The shape constant obtained from the pressure-volume curve in the aged rats was significantly greater than that in the adult rats. During induced constriction, higher lung volume significantly lowered Raw in the adult group, whereas Raw was not significantly reduced by increasing PL in the aged group. These observations suggest that increasing age may affect the mechanical properties of the airway and/or airway-parenchymal interdependence.

Aging↗
PubMed1994

[Influence of age on mouse pulmonary alveolar macrophage clonal growth].

Although monocyte influx has been suggested as the primary source of pulmonary alveolar macrophages (AM), increasing evidence from recent studies has indicated that AM may be sustained through a self-renewal mechanism. We evaluated the age-related changes of the clonal growth (colony formation) of AM in mice (C57BL/6N mice and senescence accelerated mice). The colony forming unit (CFU) of AM of 24 month old C57BL/6N mice was lower than that of AM of 4-month-old mice (p < 0.05). In SAMP6 (senescence accelerated mice), CFU of AM was decreased with aging (p < 0.05). In SAMR1 (controls for SAMP6), CFU of AM was decreased with aging (p < 0.001). In SAMR1, CFU of bone marrow (BM) adherent cells of 12-month-old mice was similar to that of 4-month-old mice. In SAMP6, CFU of BM adherent cells of 12-month-old mice was larger than that of 4-month-old mice (P < 0.005). It was concluded that the CFU of AM declined with aging, but the CFU of the BM adherent cells did not. The decline of the AM CFU may be partly responsible for the defect of the immune response of the alveolar space in the elderly.

Aging↗
PubMed1994

[Improvement of post-operative activities of daily living in an aged patient with vanishing lung].

A 71-year-old male was admitted to our hospital due to progressive dyspnea. The right lung of this patient was replaced by multiple bulous lesions including giant bullae. He had severe deterioration of lung function and gas exchange. He did not complete the pre-operative examinations for thoracic surgery, but improvement in ventilatory function was expected after bullectomy. After multiple bullectomy, this case showed marked improvements in lung function and gas exchange, subsequently his dyspnea improved, as did his activities of daily living. These lung functional improvement may have resulted not only from the mechanical advantage of diaphragmatic motion due to removal of space-occupying lesion of the lung, but also from the reduction of tough fibrous adhesion between the lung and the parietal pleura which had impaired smooth lung movement. Thorough evaluation of operative indications in necessary before surgery in aged patients with lung diseases.

Activities of Daily Living↗