Biomedical subjects

E Ohga

Publications and source records attributed to E Ohga.

At least 37 records · Page 2Linked to original sources

PubMed1998

Immunohistochemical localisation of advanced glycation end products in pulmonary fibrosis.

AIM: To investigate the presence and distribution of advanced glycation end products (AGE) in pulmonary fibrosis. METHODS: Lung tissue samples obtained from seven necropsy cases with idiopathic pulmonary fibrosis and seven with normal pulmonary parenchyma were examined immunohistochemically with a monoclonal antibody specific for AGE: 6D12. We also tested three cases with diffuse alveolar damage. RESULTS: All the specimens from cases with pulmonary fibrosis and diffuse alveolar damage showed strong AGE expression on macrophages. Lung specimens from normal parenchyma showed positive AGE immunoreactivity on macrophages from only two of seven cases. CONCLUSIONS: These findings suggest that AGE modified proteins accumulate in alveolar macrophages in patients with diffuse alveolar damage and idiopathic pulmonary fibrosis.

Aged↗

PubMed1998

Inhibitory effect of ambroxol on superoxide anion production and generation by murine lung alveolar macrophages.

We examined the effect of ambroxol on superoxide anion production before and generation after phorbol-myristate acetate (PMA) stimulation of lung alveolar macrophages. Lung free cells including lung alveolar macrophages were obtained from Fischer 344 rats and guinea pigs using bronchoalveolar lavage. The superoxide anion produced by lung alveolar macrophages with or without stimulation of PMA was measured by lucigenin-dependent chemiluminescence method using a photon counter. Ambroxol inhibited the superoxide anion production and generation by lung alveolar macrophages harvested from both F344 rats and guinea pigs in a dose-dependent fashion. Approximately 16 mumol/L of ambroxol inhibited 50% of superoxide production of lung alveolar macrophages in rats and guinea pigs, whereas a slightly greater dose of ambroxol, i.e., 18-26 mumol/L, was necessary to inhibit 50% of PMA-enhanced superoxide generation by lung alveolar macrophages. These results suggest that ambroxol acts as an antioxidant in murine lungs and may be a potential therapeutic option for reactive oxygen species-associated lung disorders including bronchial asthma.

Acridines↗

PubMed1998

[Influence of kyphosis on the age-related decline in pulmonary function].

To examine the influence of kyphosis on pulmonary function in the elderly, 300 consecutive healthy subjects (aged 20-94 years old) were evaluated using pulmonary function tests (TLC, VC, FEV1, RV) and static maximal pressures (PImax and PEmax). Kyphosis of the thoracic bones was measured at Cobb's angle. VC, FEV1. PImax and PEmax showed a significant age-dependent decline. Cobb's angle had a positive relationship with age and was negatively correlated with TLC, VC, FEV1 and PImax. Further, RV/TLC strongly correlated with Cobb's angle and PImax. Stepwise regression analysis revealed that the kyphotic angle was an independent determinant for PImax and RV/TLC. These results indicate that kyphosis significantly affects lung volume and maximal inspiratory pressure in the elderly and those affected should have careful assessment of their pulmonary function and respiratory pressures.

Adult↗

PubMed1998

[An animal model of aspiration and aspiration pneumonia using lacZ gene expression in lungs by adenoviral vectors].

To examine the relationship between disturbed upper airway reflexes and aspiration pneumonia, we administered a total volume of 20 microliters of Ad-CMV-lacZ (Ad vector) or 20 microliters of phosphate buffer solution (PBS) intranasal to C57 black mice. In nostrils, the lacZ gene expression was investigated in each mouse with or without anesthesia. Under anesthesia, the lacZ gene expression was detected by Xgal staining in the lungs of every mouse given the Ad vector. However, no gene expression was measured in the lungs of those given the Ad vector without anesthesia. In mice treated with PBS, there was no lacZ gene expression in the nostrils, trachea, or lungs, irrespective of anesthesia. These results suggest that unconsciousness or disturbed upper airway reflexes caused by anesthesia caused aspiration, resulting in an intranasal bolus that can reached the lower airways. This process can be analyzed in mice tracted with adenovirus vectors carrying the E. coli LacZ gene. Mice given Ad-CMV-lacZ transnasally can be used to study aspiration pneumonia in relation to unconsciousness.

Adenoviridae↗

PubMed1998

[Determinant factors of pulmonary function and respiratory muscle strength on exertional dyspnea in patients with chronic obstructive pulmonary disease (COPD)].

The effects of pulmonary function and respiratory muscle strength on exertional dyspnea in patients with chronic obstructive pulmonary disease (COPD) have not been fully elucidated. We examined the relationships between pulmonary function, static respiratory pressure, and dyspneic sensation during exercise in 48 patients with COPD. Dyspneic sensation during exercise was quantitated by a Borg scale slope (BSS, BS/VO2) and the threshold load of dyspnea (TLD). BSS was negatively correlated with VC, FEV1, V 25, RV/TLC (%). DLCO and PImax, whereas TLD was positively correlated with VC, FEV1, V 25, FRC and RV/TLC. Linear regression analysis revealed that FEV 1 and FRC were independent predictors for TLD, and that RV/TLC (%) was an independent predictor for BSS. These results suggest that an increase of air trapping as indicated by RV/TLC may be a major factor contributing to both decreased TLD and increased BSS, resulting in an increased sensation of dyspnea during exercise in patients with COPD.

Dyspnea↗

PubMed1998

[Effects of thyroid hormone replacement therapy on nocturnal apnea in elderly patients with hypothyroidism].

Because the incidence of sleep apnea is known to increase in both hypothyroidism and with age, elderly hypothyroid patients may experience more sleep apnea than younger hypothyroidism patients. However, the features of nocturnal disturbed breathing in elderly hypothyroid patients have not been fully elucidated. Concise polysomnographic studies including respiratory movement and oxyhemoglobin saturation (SaO2) were done on 18 elderly subjects with hypothyroidism (73.6 +/- 5.9 years old) before and after thyroid hormone replacement therapy. Fourteen of the patients exhibited a significant incidence of nocturnal apnea. Lower incidence of nocturnal apnea and higher nocturnal nadir SaO2 were observed in the patients 3 to 6 months after thyroxine therapy. Although the levels of thyroid hormones returned to normal in the patients, 9 patients had more than 5 bouts of nocturnal apnea per hour after the hormone replacement therapy. Further, no relationship was found between the level of thyroid hormones and the frequency of nocturnal apnea. These results suggest that levels of thyroid hormones are not indicators of the potential severity of nocturnal apnea in elderly hypothyroid patients, and that sleep studies may be necessary to assess the efficacy of thyroid hormone replacement therapy in the treatment of nocturnal apnea.

Aged↗

PubMed1997

Kinetics of adenovirus-mediated gene transfer to human lung fibroblasts.

Many features of Ad-mediated gene transfer to human lung fibroblasts are not well understood. We tested kinetics of transduction efficiency of LacZ gene to human lung fibroblasts by E1-deleted adenovriuses containing two different promoters, i.e. CMV and RSV LTR. A dose-dependent relationship between the vector multiplicity of infection (moi) and the efficiency of LacZ gene transfer to fibroblasts was observed with each vector, and higher moi of vectors achieved 100% of transduction efficiency. Further, Ad-mediated gene transfer was enhanced by a long period of vector exposure to fibroblasts up to 6 hours. There were no differences in transduction efficiency between the two Ad vectors. LacZ gene expression by Ad vectors consistently decreased one day after infection. These results indicate that both Ad vectors are equally effective for gene transfer to human lung fibroblasts, and higher moi of vectors and/or a longer period exposure of fibroblasts to vectors can facilitate more efficient transduction of LacZ reporter gene into human lung fibroblasts.

Adenoviruses, Human↗

PubMed1997

[Two elderly patients with Rhabdomyolysis and respiratory infection with Streptococcus pneumoniae].

Rhabdomyolysis is not common in the elderly. Two elderly patients with rhabdomyolysis and respiratory infection with Streptococcus pneumoniae. The first patient was a 71-year-old woman with bronchiectasis who admitted to our hospital due to pneumonia. The second patient was an 84-year-old man who was admitted because of appetite loss, fever, and a cough producing of yellowish sputum. In both patients, sputum cultures were positive for S. pneumoniae, but blood cultures were not. The serum creatine kinase levels peaked on the day of admission at levels ten to thirty times higher than fold above the upper limit of normal; the serum lactate dehydrogenase levels were 1.5 times higher than the upper limit of normal. The creatine kinase levels returned to normal 5 to 7 days after admission, treated with antibiotics and recovered from pneumonia. The cases of these two patients, along with those described in previous reports of rhabdomyolysis associated with pneumococcal pneumonia indicate that measuring the serum creatine kinase level is important in detecting rhabdomyolysis, especially in elderly patients with respiratory infection caused by S. pneumoniae, and detection may help to prevent renal failure.

Aged↗

PubMed1997

[Duration of effect of pulmonary rehabilitation in elderly patients with chronic obstructive pulmonary disease].

Pulmonary rehabilitation has been reported to be effective in patients with chronic obstructive pulmonary disease (COPD). To investigate the effect of a moderate period of pulmonary rehabilitation combined with inspiratory muscle training (IMT) in elderly patients with COPD, we instituted pulmonary rehabilitation for 60 weeks in five elderly patients (age: 65.4 +/- 3.7 SE years). IMT was performed for 15 min twice daily using a pressure threshold device. The inspiratory threshold was set at 15% of the maximal inspiratory pressure (PImax) of each individual. Maximal peak flow significantly increased from 3.0 +/- 0.6 (L/s) at baseline to 4.1 +/- 0.7 (L/s) after 12 weeks (p < 0.02) and was maintained at that level for 60 weeks. PImax increased significantly from 49.9 +/- 6.4 cmH2O at baseline to 67.3 +/- 3.0 cmH2O after 12 weeks (p < 0.05) and to 72.8 +/- 3.5 cmH2O (p < 0.02) after 60 weeks of rehabilitation. The 10-minute walking distance increased from 666.6 +/- 55.0 to 764.0 +/- 49.9 m (p < 0.05) after 12 weeks and was maintained at the same level. We conclude that pulmonary rehabilitation combined with IMT improves pulmonary function and inspiratory muscle strength in elderly patients with COPD between for 12 weeks after commencement, but occurs that no significant increase on lung function or 10-minute walking distance from 12 to 60 weeks. Respiratory muscle strength may further increase after 60 weeks.

Age Factors↗

PubMed1997

[The effects of pulmonary rehabilitation combined with inspiratory muscle training on pulmonary function and inspiratory muscle strength in elderly patients with chronic obstructive pulmonary disease].

It has been suggested that pulmonary rehabilitation compined with inspiratory muscle training (IMT) might improve pulmonary function and respiratory muscle strength in elderly patients with chronic obstructive pulmonary disease (COPD). To test this hypothesis, inspiratory muscle strength (PImax), expiratory muscle strength (PEmax) and resting pulmonary function were measured in 13 elderly patients with COPD (aged 70.3 +/- 2.7 years). Inspiratory muscle training (IMT) was performed for 15 min twice a day, using a pressure threshold device, for a total of 12 weeks. The inspiratory threshold was set at 15% of maximal inspiratory pressure (PImax) for each individual. Pulmonary rehabilitation was performed for 12-h sessions over a 12-week period. Patients with COPD were assigned randomly to two groups: pulmonary rehabilitation combined with IMT (group A) (n = 7), and conventional pulmonary rehabilitation only (group B) (n = 6). Functional residual capacity (FRC) decreased significantly from 4.3 +/- 0.4 L at baseline to 3.9 +/- 0.4 L after rehabilitation (p < 0.01), Vp significantly increased from 4.6 +/- 0.8 L/sec at baseline to 5.1 +/- 0.7 L/sec after rehabilitation (p < 0.05) and the PImax increased significantly from 51.5 +/- 5.4 cmH2O at baseline to 80.9 +/- 7.0 cmH2O after rehabilitation (p < 0.02) in group A. However, these variables did not change in group B. There was no improvement in the 10-minutes walking distance of group A, but there was a significant increase in that of group B. It can be concluded that pulmonary rehabilitation combined with IMT improves pulmonary function and inspiratory muscle strength in elderly patients with COPD.

Aged↗

PubMed1997

[Transfer of genes to human airway epithelial cells in vitro via DNA virus vectors].

Transfer of genes via DNA virus vectors to human airway epithelial cells is not fully understood. We tested the effects of multiplicities of infection (moi) and incubation time on the efficiency of gene transfer by adenovirus vectors and AAV vectors in cultures of human airway epithelial cells. The cells were exposed to Ad-CMV-lacZ or AAV-CMV-LacZ for 1 to 48 hours at different moi from 0.1 to 100. Efficiency of transduction was assessed as the percentage of cells that expressed LacZ, and was measured by using X-gal staining. A dose-dependent relationship was found between vector moi and the percentage of cells that expressed LacZ. For both vectors, gene expression was greater when incubation time was longer (up to 12 hours), which suggests that the uptake of vectors into the cells is not selective. Efficiency of transduction did not differ between adenovirus and AAV vectors at the same moi. These results suggest that (1) gene transfer via DNA virus vectors increases in a moi-dependent fashion, and that (2) gene expression of the DNA virus vector may be increased by prolonged exposure of the vector to human airway epithelial cells.

Adenoviridae↗

PubMed1997

[The effect of inhaled anticholinergic drug on dyspnea and on the physiologic function of respiratory system in patients with chronic obstructive pulmonary disease].

The mechanism underlying the relief of the sensation of dyspnea during exercise following the inhalation of anticholinergic drug in patients with chronic obstructive pulmonary disease (COPD) has not been fully elucidated. We examined pulmonary function, static respiratory pressure, and dyspneic sensations during exercise before and after the inhalation of oxitropium bromide (OTB) in 14 male patients with COPD. FEV1 and FVC were increased after the inhalation of OTB, whereas RV and the ratio of RV to TLC were decreased after inhalation. Maximum inspiratory pressure (PImax) was significantly increased after the administration of OTB. Dyspneic sensation during exercise, measured as a Borg scale slope (BSS, delta BS/ delta Vo2) were reduced after the inhalation of OTB. There were significant correlations among BSS, PImax and RV/TLC. These results suggest that a reduction in air trapping after the inhalation of OTB may enhance the ability of the to diaphragm generate pressure at a given neural input, resulting in a reduced sensation of dyspnea during exercise in patients with COPD.

Administration, Inhalation↗

PubMed1997

Airway and lung tissue behaviour during endothelin-1 induced constriction in rats: effects of receptor antagonists.

Endothelin (ET) 1, a 21 amino acid constrictor peptide, is one of the most potent agonists of airway smooth muscle and acts on two different receptors, i.e., ETA and ETB receptors. Recently, it has been shown that there are species and organ differences in physiological roles of each ET receptor. In rats, however, the physiological roles of ET receptors remain to be clarified. We questioned whether ET-1 might affect airway and lung tissue via different ET receptor subtypes in rats. To answer this question, we investigated the effects of ET-1 on lung behaviour in anesthetized, open-chested, mechanically ventilated (f = 1 Hz, VT = 9 mL/kg, PEEP = 3 cmH2O (1 cmH2O = 98.1 Pa)) rats in the absence or the presence of ETA and ETB selective antagonists, i.e., BQ-123 and BQ-788, respectively. Using alveolar capsules, we calculated lung elastance (EL), resistance of lung (RL), tissue (Rti), and airway (Raw), and hysteresivity (eta = 2 pifRti/EL) under control conditions and after intravenous administration of ET-1 (10(-8) mol/kg). ET-1 induced significant increases in RL, Rti, Raw, EL, and eta. BQ-123 did not affect ET-1 induced constriction, while BQ-788 significantly reduced delta RL, delta Rti, delta Raw, delta EL during ET-1 induced constriction. The effects of the combination of BQ-123 and BQ-788 were not different compared with BQ-788. Eta was not affected by BQ-123 and BQ-788. These data suggest that ETB, but not ETA, receptors may have significant physiological roles in rat lungs in response to ET-1.

Airway Resistance↗

PubMed1997

[Effect of DNA topoisomerase I inhibitor on the transduction efficiency of an deno-associated virus vector in human airway epithelial cells].

We tested the effects of a DNA topoisomerase inhibitor (camptothecin; CPT) on the transduction efficiency of AAV vectors in cultured human airway epithelial cells. The cells were treated with CPT for 24 hours, then exposed to AAV-CMV-LacZ for 1 hour at different multiplicities of infection (moi). Transduction efficiency of AAV vectors was assessed using X-gal staining as the percentage of LacZ-expressing cells. The transduction efficiency was approximately 1.5 to 10 fold increased by treatment with CPT prior to AAV vector exposure. However, treatment with CPT after AAV vector infection did not enhance the transduction efficiency of the vectors. These results suggest that pre-treatment with CPT increases the transduction efficiency of AAV vectors, probably by nodulating cellular function.

Camptothecin↗

PubMed1996

Effects of activin A on proliferation and differentiation of human lung fibroblasts.

An increase in fibroblasts and associated connective tissue is a feature of pulmonary fibrosis. Activin A belongs to the transforming growth factor-beta (TGF-beta) supergene family and is known to have important roles in the induction of mesoderm and differentiation processes during development in early embryogenesis. It also modifies the growth and differentiation of various target cells. In this study we determined whether activin A could modulate human lung fibroblast (HFL1) activity, particularly with respect to proliferation and its differentiation into myofibroblast. A maximal effect on cell proliferation was observed at a low concentration of activin A (10(-11) M), and the effect of activin A was abolished by follistatin, an activin-binding protein. Activin A stimulated differentiation of HFL1 into myofibroblast in a dose-dependent manner. Thus activin A has potential effects on proliferation of lung fibroblast and its differentiation into myofibroblast, and may contribute to structural remodeling observed in pulmonary fibrosis.

Actins↗

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

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↗