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Biomedical subjects

Y Fukuchi

Publications and source records attributed to Y Fukuchi.

At least 163 records · Page 9Linked to original sources
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↗
PubMed1995

[A case of pulmonary infiltration with eosinophilia (PIE) syndrome associated with syndrome of inappropriate secretion of ADH (SIADH) in the elderly patient].

A 76-year-old woman was admitted to our hospital because of productive cough, fever and anorexia in January 1995. She had suffered from bronchial asthma for 25 years. From 1983, exacerbation of PIE was recorded three times, on which occasions prednisolone and antibiotics were quite effective. On admission, marked leukocytosis (28,000/microliters) and eosinophilia (18,000/microliters) were found. However, plasma IgE level was normal, and specific antigen for eosinophilia was not detected by RAST or the skin allergic reaction test. Chest X-ray film and CT scan revealed extensive bilateral pulmonary infiltration. Increase in eosinophils (33%) was demonstrated in bronchoalveolar lavage. Furthermore, biopsy specimen of the affected lung revealed diffuse infiltration of eosinophils into alveolar septa. On the basis of these findings, the patient was diagnosed as chronic eosinophilic pneumonia (PIE syndrome). Hyponatremia (117 mEq/l) was persistent after the hydration with normal saline. Plasma ADH was not suppressed (2.29 pg/ml) in spite of hypoosmolality of plasma. Laboratory examination showed that renal, adrenal and thyroid function as well as plasma renin activity were normal. Taking these findings together, she was diagnosed as having SIADH. Treatment with prednisolone improved not only the PIE syndrome but also SIADH.

Aged↗
PubMed1994

Age-related changes in the antioxidant screen of the distal lung in mice.

We studied the influence of age on glutathione (GSH) content in the distal lung and the lung tissue of mice. From 1 to 28 months of age, the quantity of GSH and glutathione disulfide (GSSG) in bronchoalveolar lavage (BAL) fluid and in the lung tissue were determined. The GSH content in BAL fluid, which reflects the antioxidant screen of the distal lung, decreased with advancing age. The ratio of GSSG to GSH increased in later life, suggesting increase of oxidation of the epithelial lining fluid in old mice. The GSH content in the lung tissue also decreased with aging. Therefore the lower respiratory tract may be less able to defend against external attack, including attack by oxygen-derived active molecules, in senescent mice. The decrease of the antioxidant screen of the distal lung may be associated with impaired lung defense in relation to oxidant-antioxidant balance in aged mice.

Aging↗
PubMed1994

The effect of food on the interaction of ofloxacin with sucralfate in healthy volunteers.

We have studied the effect of food on the interaction of ofloxacin with sucralfate. Six healthy men took a single oral dose of ofloxacin (200 mg) on 4 occasions: alone after overnight fasting or after breakfast (non-fasting), and with sucralfate fasting or non-fasting. There were no significant differences in the plasma concentration-time profiles of ofloxacin after ofloxacin alone between fasting and non-fasting conditions. On the other hand, the peak plasma concentration and AUC of ofloxacin after co-administration with sucralfate while fasting fell by 70 and 61% compared with ofloxacin alone; the changes non-fasting were 39 and 31% respectively. The interaction of ofloxacin with sucralfate was markedly reduced by food, but still could not be disregarded.

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

Immunohistochemical and in situ hybridisation detection of adenovirus early region 1A (E1A) gene in the microglia of human brain tissue.

To investigate whether brain tissue is infected latently by adenovirus via a monocyte/microglia-mediated entry mechanism, brain tissue resected at necropsy from seven senile subjects (five with senile dementia of Alzheimer type (SDAT) and two subjects without pathological changes) was examined for adenovirus early region 1A (E1A) gene and its expression using in situ hybridisation and immunohistochemical staining. HLA-DR positive, reactive microglial cells in both SDAT and normal brain tissue showed positive hybridisation and immunoreactive expression of adenovirus E1A. Thus there may be monocyte/microglia-mediated entry of adenovirus in the central nervous system which would be a novel and presumably common interaction between brain tissue and adenovirus.

Adenoviridae↗
PubMed1994

Residual neurobehavioural effects associated with chronic exposure to mercury vapour.

To find the residual effects of long term exposure to mercury vapour, neurobehavioural tests were given to ex-mercury miners about 18 years after the end of mercury exposure. Seventy six male ex-mercury miners who had been exposed to high concentrations of mercury vapour (over 1.0 mg/m3) and with a history of mercury intoxication were compared with controls matched for age (within 3 years), sex, and education. Although the extent of the workers' symptoms caused by mercury poisoning, termed erethismus merculialis, decreased considerably after the end of exposure, matched paired comparison showed that performances of motor coordination, simple reaction time, and short term memory had deteriorated significantly in the exposed group. Multiple linear regression analysis of exposure variables with neurological examination measures showed positive correlations between poorer neurological performance and variables related to mercury exposure. Thus the duration of exposure correlated with poorer performance of hand-eye coordination, tapping, and a colour card reading test. Job categories classified by exposure to mercury also had a significant negative correlation with these performances. The period of years after the end of exposure had a significant correlation with better performance of reaction time and digit span. On the other hand, the history of intoxication itself had no significant correlation with any of the current neurobehavioural performances. These results suggest that there are slight but persistent effects on neurobehavioural function, especially on motor coordination, among mercury miners even more than 10 years after the end of exposure.

Aged↗
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

Effect of chronic tobacco smoke exposure on the function of alveolar macrophages in mice.

We evaluated the effect of chronic tobacco smoke exposure on the function of the alveolar macrophage (AM) in mice. Tumor necrosis factor-alpha production of the AM triggered by lipopolysaccharides was smaller in smoke-exposed mice as compared to control mice but did not reach statistical significance (27.3 +/- 4.0 vs. 34.8 +/- 4.9 U/ml). The percentage of AM which did not phagocytize latex particles in the smoke-exposed mice was significantly larger than that in control mice (33.9 +/- 2.3 vs. 20.8 +/- 2.1%; p < 0.05). Ia antigen expression of the AM was significantly larger in smoke-exposed mice (cytotoxicity index: 0.180 +/- 0.033 vs. 0.038 +/- 0.0118; p < 0.01). The asialo-GM1 antigen expression was similar in both groups (0.949 +/- 0.007 vs. 0.961 +/- 0.011). Although the precise mechanisms of these functional changes of the AM by tobacco smoke exposure are not clear, they may have some immunological effects on the alveolar space.

Animals↗
PubMed1994

A novel model of senile lung: senescence-accelerated mouse (SAM).

Senescence-accelerated mouse (SAM) has been characterized as a unique animal model to investigate spontaneous aging as well as age-related disorders. However, little is known about the properties of the lung. We examined age-related morphologic and functional changes of the lung in SAM P2, as the senescence-prone strain, and in SAM R1, as the senescence-resistant strain. On morphologic examination, the earlier (starting at 6 mo) and more severe change in airspace size (mean linear intercept: MLI) was observed in SAM P2 (MLI [micron]; 3 mo: 72.1 +/- 2.4; 6 mo: 80.8 +/- 2.9; 12 mo: 91.1 +/- 3.1; 18 mo: 143.4 +/- 6.6), compared with SAM R1 (MLI [micron]; 3 mo: 68.9 +/- 1.8; 6 mo: 70.8 +/- 2.6; 12 mo: 76.1 +/- 2.8; 18 mo: 101.2 +/- 4.7). The destructive index was not remarkably changed through life in both strains, suggesting that the alveolar wall was relatively intact in SAM. On functional examination, the left-sided shift of the pressure-volume (P-V) curves observed in SAM P2 at an early stage of aging (starting at 9 mo) compared with SAM R1. The shape constant (K) obtained from the P-V curve was increased with aging in SAM P2 (K; 3 mo: 0.124 +/- 0.004; 9 mo: 0.142 +/- 0.003; 18 mo: 0.183 +/- 0.008), and also increased at a late stage of aging in SAM R1 (K; 3 mo: 0.123 +/- 0.005; 9 mo: 0.135 +/- 0.004; 18 mo: 0.148 +/- 0.007). This study demonstrates that SAM P2 manifested most of the characteristic changes in senile lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1994

[Diffuse aspiration bronchiolitis (DAB) produced in animals by repeated HCl microaspiration].

We recently reported that diffuse aspiration bronchiolitis (DAB) was detected in 1% of autopsied lungs of aged cases of pneumonia. We hypothesized whether repeated HCl micro-aspiration (RHMA) is involved in DAB and established an animal model by administering HCl intratracheally to rats every two days for 2 weeks. Saline was given to control animals in the same fashion. Then, we performed bronchio-alveolar lavage (BAL) or excised lungs for histologic examination. There was no difference in BAL cell counts, TNF alpha-production, elastase-like activity or albumin levels between the HCl and control groups. Histologically, DAB-like findings were observed in the HCl-treated animals. These data suggest that RHMA might be involved in DAB, while neither TNF alpha-production nor elastase-like activity may play a significant role in inducing DAB.

Animals↗
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↗