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Biomedical subjects

Y Fukuchi

Publications and source records attributed to Y Fukuchi.

At least 109 records · Page 6Linked to original sources

[Survey of noise exposure level of national forestry workers].

Eighty-one national forestry workers who were using chain saws, log cutters, log cutting machines, bush cleaners, timber-collecting cable machines and forklifts were examined for their level of noise exposure in a working day by using a portable sound meter. And their noise exposure levels Leq (8 h) for a year were estimated based on the measured noise levels and on the number of noise exposure days and hours in a year recorded in their work documents. The survey was made from July to December, 1988. The maximum noise levels with all the machines except a case of the forklift were above 100 dB, and with most chain saws they were above 110 dB. The amount of time that workers were exposed to the noise of logging and lumbering with chain saws, cutting by bush cleaners and timber-collecting cable machines without a cabin was longer than the allowable time for 90 dB and 95 dB. The number of noise exposure days in a year is fewer than reported in the past. The estimated Leq (8 h) for 32 out of 34 lumbermen surveyed was more than 85 dB, and for 5 lumbermen the Leq (8 h) was more than 90 dB. From these results, it can be concluded that there is a danger of noise induced hearing loss in national forestry workers using chain saws, log cutters, log cutting machines and timber-collecting cable machines without a cabin in 1987.

Forestry↗

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↗

[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↗

[Summer-type hypersensitivity pneumonitis with remarkable obstructive impairment of pulmonary function].

A 57-year-old-man was admitted because of persistent cough and progressive dyspnea over a period of 2 months. Examination revealed wheezing in both lungs, severe hypoxemia, and marked obstructive impairment of pulmonary function. A chest CT scan showed diffuse small nodular lesions with patchy air space opacifications. The patient was initially given a diagnosis of bronchiolitis of unknown cause. He showed marked improvement after treatment with oral prednisolone, but developed fever and dyspnea after returning home. This episode indicated hypersensitivity pneumonitis, a diagnosis supported by findings of increased CD 8 positive T-lymphocytes in bronchoalveolar lavage fluid, and a high titer of serum anti-Trichosporon antibody. Lung biopsy samples obtained under video-assisted thoracoscopy disclosed noncaseating granulomas in terminal and respiratory bronchioles, which resulted in marked narrowing of the lumen. The pathologic changes seemed to be consistent with obstructive impairment of pulmonary function in this patient.

Alveolitis, Extrinsic Allergic↗

[E 4021, a cGMP phosphodiesterase inhibitor, is a selective pulmonary vasodilator in chronically hypoxic pulmonary hypertensive rats].

To test whether a potent cGMP-specific phosphodiesterase inhibitor, E 4021, is a selective pulmonary vasodilator in pulmonary hypertension, we studied its acute hemodynamic effects in conscious, chronically hypoxic pulmonary hypertensive rats. Chronically hypoxic pulmonary hypertension was induced by keeping adult Sprague-Dawley rats in a hypobaric chamber for 3 weeks. Two days after catheterization. E 4021 was injected intravenously at doses of 3, 10, 30, 100, 300, and 1,000 micrograms/kg at 10-min intervals. E 4021 caused significant decreases in mean pulmonary arterial pressure of 11 +/- 5, 12 +/- 6, and 18 +/- 5% at doses of 100, 300, and 1,000 micrograms/kg, respectively. In contrast to its depressor effect on mean pulmonary arterial pressure, E 4021 decreased mean systemic arterial pressure significantly (by 9 +/- 2%) at a dose of 1,000 micrograms/kg only. Heart rate and cardiac output were unchanged after the administration of E 4021. Tissue cGMP-specific phosphodiesterase activity was markedly higher in lung than in aorta. These results indicate that E 4021 is a relatively selective pulmonary vasodilator in chronically hypoxic pulmonary hypertensive rats. We conclude E 4021 may be useful for the treatment of pulmonary hypertension.

3',5'-Cyclic-GMP Phosphodiesterases↗

[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↗

[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↗

Dissemination in Japanese hospitals of strains of Staphylococcus aureus heterogeneously resistant to vancomycin.

BACKGROUND: Since the discovery of the vancomycin-resistant Staphylococcus aureus (VRSA) strain Mu50 (minimum inhibitory concentration [MIC] 8 mg/L), there has been concern about the potential spread of such strains throughout Japanese hospitals. Two important questions need to be answered: (1) what is the prevalence of VRSA, and (2) by what mechanism does vancomycin resistance occur. METHODS: The vancomycin susceptibilities of three methicillin-resistant S aureus (MRSA) strains (Mu50, Mu3, and H1) and the methicillin-susceptible S aureus type strain FDA209P were compared by MIC determinations and population analysis. Mu3 (MIC 3 mg/L) was isolated from the sputum of a patient with pneumonia after surgery who had failed vancomycin therapy. H1 (MIC 2 mg/L), which is a representative vancomycin-susceptible MRSA strain, was isolated from a patient with pneumonia who responded favourably to vancomycin therapy. Subclones of Mu3 with increased resistance against vancomycin were selected with serial concentrations of vancomycin and their MICs were determined. The prevalence of VRSA and Mu3-like strains in Japanese hospitals was estimated by population analysis from 1149 clinical MRSA isolates obtained from 203 hospitals throughout Japan. The genetic traits of the Mu3 and Mu50 strains were compared with clonotypes of MRSA from around the world. FINDINGS: Mu3 and Mu50 had an identical pulsed-field gel electrophoresis banding pattern. When grown in a drug-free medium, Mu3 produced subpopulation of cells with varying degrees of vancomycin resistance, thus demonstrating natural heterogeneity, or variability, in susceptibility to vancomycin. In the presence of vancomycin, Mu3 produced subclones with resistance roughly proportional to the concentrations of vancomycin used. Selection of Mu3 with 8 mg/L or more of vancomycin gave rise to subclones with vancomycin resistance equal to that of Mu50 (MIC 8 mg/L) at a frequency of 1/1,000,000. During screening of Japanese MRSA strains, no strain of VRSA additional to Mu50 was found. The prevalence of MRSA isolates heterogeneously resistant to vancomycin was 20% in Juntendo University Hospital, 9.3% in the other seven university hospitals, and 1.3% in non-university hospitals or clinics. INTERPRETATION: Heterogeneously resistant VRSA is a preliminary stage that allows development into VRSA upon exposure to vancomycin. Heterogeneously resistant VRSA was found in hospitals throughout Japan. This finding could explain, at least partly, the frequent therapeutic failure of MRSA infection with vancomycin in Japan.

Aged↗

Effects of enprostil on gastric endocrine secretion during chronic administration of lansoprazole.

We investigated changes in the secretory kinetics of gastric endocrine cells related to the administration of lansoprazole, and the effects of enprostil on these altered kinetics. Male Wistar-derived 8-week-old rats were allotted to a control group, a lansoprazole administration group, an enprostil administration group, and a lansoprazole + enprostil administration group. Lansoprazole (30 mg/kg once a day for 4 weeks) and enprostil (10 micrograms/kg twice a day for 4 weeks) were administered into the gastric lumen with a gastric tube. At this time, blood was collected and immunohistological staining of gastric endocrine cells was conducted to investigate the secretory kinetics. Lansoprazole administration induced hypergastrinemia, increase of gastrin cells, and increase of enterochromaffin-like cells. Enprostil administration induced increase of somatostatin cells. The group administered lansoprazole + enprostil exhibited significant decreases in serum gastrin level, total gastrin cell count, and total enterochromaffin-like cell count, compared with the group administered lansoprazole alone. These findings suggest that enprostil may ameliorate the alteration in gastric endocrine secretion produced by the chronic administration of lansoprazole.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Effects of chronic cigarette smoke inhalation on the development of senile lung in senescence-accelerated mouse.

The senescence-accelerated mouse (SAM) manifests most of the features of function and morphology in the senile lung with aging. However, little is known about the effects of age and cigarette smoke on alterations of the lung in SAM. In the present study, we examined the effects of chronic cigarette smoke inhalation and age on the function and morphology of lungs in two strains of SAM, SAMP2 (senescence-prone strain) and SAMR1 (senescence-resistant strain), from 6 months of age (young) and 18 months of age (aged). After 4 weeks of cigarette smoke inhalation, a small but significant airspace along with a leftward shift of the pressure-volume (P-V) curve was observed in young SAMP2, but not in SAMR1. However, the airspace size of young SAMP2 with cigarette inhalation was smaller than that in aged SAM with air inhalation, suggesting that the effect of age may be greater than that of the small burder of tobacco smoke on the lung alterations in SAMP2. In the aged SAM, there were no differences in function and structure between tobacco-exposed and air-exposed mice. Because the changes in the lungs of young SAMP2 exposed to cigarette smoke were partly simulated with age-related alterations in human lung, and because age-dependent changes of lungs were clearly investigated in SAMP2, this strain may be an interesting animal model for investigating the effects of age and/or cigarette smoke on alterations in lung structure and function.

Aging↗

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↗

Progressive interstitial pneumonia associated with myelodysplastic syndrome: implication of superoxide hyperproduction by neutrophils.

Interstitial pneumonia and aseptic neutrophilic infiltration in the lung are rare pulmonary manifestations of myelodysplastic syndrome (MDS). We report a patient with progressive interstitial pneumonia associated with MDS. Histological examination of the lung revealed infiltration of atypical haematopoietic cells associated with MDS and diffuse alveolitis with honeycombing. Neutrophils obtained from the patient showed superoxide hyperproduction after stimulation with phagocytosis and phorbol myristate acetate, which might be attributed to the pathogenesis of interstitial pneumonia.

Bronchoalveolar Lavage↗

ET-1-induced bronchoconstriction is mediated via ETB receptor in mice.

Endothelin (ET)-1 is one of the most potent agonists of airway smooth muscle and can act via two different ET receptor subtypes, i.e., ETA and ETB. To determine the effects of ET-1 on in vivo pulmonary function and which ET receptors are involved in murine lungs, we investigated 1) the effects of ET and sarafotoxin S6c (S6c), a selective ETB agonist, on pulmonary function and 2) the effects of BQ-123 and BQ-788, specific ETA- and ETB-receptor antagonists, on ET-1-induced bronchoconstriction. ICR mice were anesthetized and mechanically ventilated (frequency = 2.5 Hz, tidal volume = 8 ml/kg, positive end-expiratory pressure = 3 cmH2O). Intravenous ET-1, ET-2, and ET-3 increased lung resistance similarly and equipotently, whereas S6c elicited a greater degree of bronchoconstriction. Mice were then pretreated with saline (Sal), BQ-123 (0.2, 1, and 5 mg/kg), or BQ-788 (0.2, 1, and 5 mg/kg) before administration of ET-1 (10(-7) mol/kg iv). No dose of BQ-123 blocked ET-1-induced constriction, whereas pretreatment with each dose of BQ-788 significantly inhibited ET-1-induced responses. There were significant differences in morphometrically assessed airway constriction between Sal and BQ-788 and between BQ-123 and BQ-788, whereas no significant difference was observed between Sal and BQ-123. There were no significant morphometric differences in the airway wall area among the three groups. These observations suggest that the ETB- but not ETA-receptor subtype may mediate the changes in murine pulmonary function in response to ET-1. In addition, the ETB-receptor antagonist reduces ET-1-induced airway narrowing by affecting airway smooth muscle contraction in mice.

Animals↗

Airway responsiveness in transgenic mice overexpressing platelet-activating factor receptor. Roles of thromboxanes and leukotrienes.

Platelet-activating factor (PAF) is a potent proinflammatory compound potentially involved in the pathogenesis of inflammatory disorders, including bronchial asthma. To elucidate the pathophysiologic roles of PAF in bronchial asthma, we studied airway responsiveness in transgenic mice overexpressing PAF receptor. In the transgenic mice, PAF-induced airway smooth muscle contraction was demonstrated by physiologic and morphometric analyses, whereas there was no significant response in the littermate control group. The PAF-elicited bronchoconstriction in the transgenic mice was significantly reduced not only by a PAF receptor antagonist (WEB-2086) but also by a thromboxane synthesis inhibitor (indomethacin or ozagrel), an inhibitor of 5-lipoxygenase-activating protein (MK-886), or a cysteinyl leukotriene (LT) antagonist (pranlukast). LTB4 receptor antagonist (ONO-4057), however, had no effect on the PAF-induced responses. The transgenic mice showed a bronchial hyperreactivity to methacholine challenge, which was also inhibited by pretreatment with either thromboxane synthesis inhibitor or cysteinyl LT antagonist. These observations suggest that both thromboxane A2 and cysteinyl LTs (LTC4, LTD4, and LTE4) are involved in the bronchial responses to PAF or cholinergic stimulus in mice. The transgenic mice overexpressing PAF receptor may provide an appropriate model to study various PAF-related lung diseases, including bronchial asthma.

Animals↗

Assessment of autonomic nervous function in elderly subjects with or without postprandial hypotension.

To examine the role of autonomic nervous dysfunction in postprandial hypotension (PPH) in elderly persons, we non-invasively assessed autonomic nervous function in 50 elderly subjects with or without PPH, defined as a reduction of more than 20 mmHg in systolic blood pressure (SBP) after a meal. The heart rate response to the reduction of SBP during head-up tilt was less and the coefficient of variation of R-R intervals was smaller in subjects with PPH than in those without PPH. The responses to cold pressor test, hyperventilation test, and mental arithmetic test were normal in all subjects. The magnitude of deltaSBP after meal ingestion closely correlated with deltaSBP during tilt-table examination, but did not correlate with the results of the cold pressor test, hyperventilation test, or mental arithmetic test. Stepwise multiple regression analysis revealed that the magnitude of the BP reduction and heart rate increase during the tilt-table test were independent predictors of the magnitude of deltaSBP after meal ingestion. The results indicate that impaired afferent pathways of baroreflexes, including baroreceptors, may play an important role in the pathogenesis of postprandial hypotension in the elderly and that the magnitude of the fall in SBP during tilt-table testing may be related to the degree of the postprandial reduction in BP in elderly persons.

Aged↗