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Biomedical subjects

J Kagawa

Publications and source records attributed to J Kagawa.

At least 37 records · Page 2Linked to original sources
PubMed1999

Acute biological effects of intratracheally instilled titanium dioxide whiskers compared with nonfibrous titanium dioxide and amosite in rats.

The dimensions of man-made mineral fiber whiskers are similar to those of some kinds of asbestos. Thus these mineral fibers raise the concern for potential health hazard for workers exposed in the occupational environments. This study was designed to define acute biological effects of intratracheally administered titanium dioxide whiskers (TO1) compared with nonfibrous titanium dioxide (TOP) and UICC amosite (Ams), and their relations to acute lung inflammation in rats. The observed geometric mean length (microm) and width (microm) and geometric standard deviation are: TO1(2.1[2.0], 0.14[1. 53]); Ams (4.3[3.3], 0.31[1.9]); and TOP (50 nm, 1-2 microm aggregates). Ten-week-old Wistar-Jcl male rats received a single tracheal injection of test materials at doses between 0.05 and 1.0 mg/rat. Control animals were injected with the same volume of saline. Lung tissue and bronchoalveolar lavage (BAL) fluid were collected from rats on days 1, 3, and 7 after administration. In the group injected with TO1, total protein, cytokine-induced neutrophil chemoattractant (CINC)/growth-regulated gene product (GRO), interleukin (IL) 1beta, and tumor necrosis factor (TNF) alpha increased on day 1. Subsequently, total elastolytic activity and fucose levels in BAL increased by day 3. All parameters, except for fucose in BAL, recovered to the normal levels. Animals in the Ams group showed increased total protein and CINC/GRO and decreased total elastolytic activity in a dose-dependent manner on day 1. The fucose level increased on day 3 in the Ams group. All parameters returned to their control levels on day 7. Animals in the TOP group did not show significant changes any of parameters during the experimental period. Gene expression of TNF-alpha and monocyte chemoattractant protein (MCP) 3 in the lung increased dose-dependently in the animals treated with the three materials. The mRNAs for eotaxin and MIP-1alpha were overexpressed in the lung of animals treated with Ams and TO1, while RANTES mRNA was overexpressed dose-dependently in the lung of animals treated with Ams on day 1. Onset of inflammatory response was more rapid in the Ams group than the TO1 group. Recovery of the fucose level in BAL was slower in the TO1 group than in the Ams group, though we observed similar histopathological changes in the lung of animals with TO1 or Ams. We conclude that whisker-induced acute biological effects in the lung may be related to the shape of the whiskers and not to their chemical composition or surface crystal structure, showing biological effects similar to those of UICC amosite.

Administration, Inhalation↗
PubMed1999

A new model rat with acute bronchiolitis and its application to research on the toxicology of inhaled particulate matter.

The aim of the present study was to establish a useful animal model that simulates humans sensitive to inhaled particulate matter (PM). We have developed a new rat model of acute bronchiolitis (Br) by exposing animals to NiCl2 (Ni) aerosols for five days. Three days following the Ni exposure, the animals developed signs of tachypnea, mucous hypersecretion, and bronchiolar inflammation which seemed to progress quickly during the fourth to fifth day. They recovered from lesions after four weeks in clean air. To assess the sensitivity of the Br rats to inhaled particles, two kinds of PM of respirable size were tested with doses similar to or a little higher to the recommended threshold limit values (TLVs) for the working environment in Japan. Titanium dioxide (TiO2 = Ti) was chosen as an inert and insoluble particles and vanadium pentoxide (V2O5 = V), as a representative soluble and toxic airborne material. The Br rats exposed to either Ti or V were compared the pathological changes in the lungs and the clearance of particles to those in normal control or Br rats kept in clean air. The following significant differences were observed in Br rats: 1. delayed recovery from pre-existing lesions or exacerbated inflammation, 2. reductions in deposition and clearance rate of inhaled particles with the progress of lesions. The present results suggest that Br rats are more susceptible to inhaled particles than control rats. Therefore, concentrations of particulate matter lower than the TLVs for Japan, which have no harmful effects on normal lungs, may not always be safe in the case of pre-existing lung inflammation.

Acute Disease↗
PubMed1997

Effects of cigarette smoking on the serum concentration of lung surfactant protein A (SP-A).

We have tested the hypothesis that serum surfactant protein A (SP-A) production may be affected by cigarette smoke exposure, and that alterations in serum levels may reflect smoking habits. A total of 52 subjects were divided into the following two groups: active smokers (Group A; n = 23); and nonsmokers (Group B; n = 29). The assessment of smoking habit was determined by self-report, carbon monoxide concentration in expired air, and cotinine concentration in urine. Serum SP-A was compared in both groups and was found to be higher in Group A (active smokers) (p < 0.002). We conclude that surfactant protein A levels are increased in the serum of smokers. However, it was found that this is not a sensitive discriminating factor to separate smokers from nonsmokers.

Adult↗
PubMed1997

Elevated serum levels of pantropic p53 proteins in chromium workers.

OBJECTIVES: This study investigated the possibility of applying serum pantropic p53 proteins in molecular epidemiologic studies, as a biomarker of environmental carcinogenesis. The serum levels of pantropic p53 proteins were determined in workers with past exposure to hexavalent chromium compounds. METHODS: Thirty-one male workers occupationally exposed to hexavalent chromium compounds in the production of chromium compounds for 0 to 23 years served as the exposed group. The referents were 10 volunteers without work-related exposure to chemicals. In the determination of pantropic p53 proteins, commercially available kits for enzyme-linked immunosorbent assay were used which quantitatively detected both mutant and wild-type human p53 proteins. RESULTS: The serum level of pantropic p53 proteins was in the range of 116.4 to 1122.6 pg/ml for the exposed workers and of 117.4 to 305.8 pg/ml for the referents. Nineteen percent of the exposed workers had a high p53 protein level (6 out of 31) when compared with the referents. All but 1 of the 6 workers had been occupationally exposed to chromium compounds for more than 11 years. Two of the 3 workers with a past history of lung cancer also showed high levels. CONCLUSIONS: Our findings confirm that the application of p53 proteins as a biomarker of environmental carcinogenesis merits further exploration.

Adult↗
PubMed1996

Alveolar destruction in guinea pigs chronically exposed to diesel engine exhaust. A light- and electron-microscopic morphometry study.

Guinea pigs were exposed 16 h a day, 6 d a week, for 6, 12, 18, or 24 mo to filtered air or diesel-exhaust at low (NO2 = 0.22 +/- 0.03 ppm; SO2 = 0.60 +/- 0.19 ppm; particles = 0.21 +/- 0.07 mg/m3), medium (NO2 = 1.07 +/- 0.09; SO2 = 2.83 +/- 0.73; particles = 1.14 +/- 0.26) or high (NO2 = 2.88 +/- 0.29; SO2 = 6.49 +/- 1.75; particles = 2.94 +/- 0.69) concentrations, or at a medium concentration without particles (NO2 = 1.01 +/- 0.09; SO2 = 2.66 +/- 0.64; particles = 0.01 +/- 0.01). We quantitated the holes in the alveolar wall and alveolar size by using scanning electron microscopy (SEM). After 12 mo of exposure, the ratio of the area of alveolar holes to that of the alveolar wall, and the number of holes per alveolus, rose as the concentration and duration of exposure increased. There were no differences in alveolar size between the study groups. Animals exposed to the medium concentration of diesel exhaust without particles showed less of an increase in the development of holes than animals exposed to the same concentration of diesel exhaust with particles. These findings suggest that diesel exhaust causes alveolar destruction (alveolar holes) without an enlargement in alveolar size in a concentration- and duration-dependent manner. Particulate matter in diesel exhaust may play some role in the development of these lesions.

Animals↗
PubMed1995

Oxidative DNA damage induced by silica in vivo.

Occupational exposure to silica has often been associated with the development of pulmonary fibrosis and, occasionally, lung cancer. Their development may be mediated by oxidant-induced cellular injury. The short- and long-term effects of a single intratracheal instillation of silica in rats (10 mg/200 microliters/saline per rat) was assessed by measuring 8-hydroxy-2'-deoxyguanosine (oh8dG) levels in lung tissue and peripheral blood leukocytes. Cell differentials, reduced glutathione (GSH), and superoxide dismutase (SOD), lipid peroxide, and total phospholipids in peripheral blood and/or bronchoalveolar lavage fluid (BALF) were also measured. The pulmonary oh8dG levels increased approximately 2.24- 2.86-fold from 1 to 5 days after exposure to silica. It was still elevated 1 and 4 weeks after installation, but the difference was no longer statistically significant. The oh8dG levels in peripheral blood leukocytes were never significantly different, but they were generally higher than in the controls. The low SOD levels in the BALF of exposed rats in the early stage and the higher GSH levels in the late stage may represent protective reactions against the generation of oxygen species. A significant increase in oh8dG levels in lung tissue suggested the possible carcinogenicity of silica.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1995

[Chemiluminescence assays for cytokines in serum: influence of age, smoking, and race in healthy subjects].

Evidence is accumulating that cytokines are important intermediates in the pathogenesis of many diseases such as asthma and pulmonary fibrosis. However, a major limitation to clinical studies of cytokines has been the inability to measure these important biomarkers in serum from normal, healthy controls. Without this capability, interpretation of apparently elevated levels in problematic, and evaluation of diseased level is impossible. We have recently developed chemiluminescence ELISA (CL-ELISA), resulting in a 100-fold increase in sensitivity. To assess the influence of age, smoking, and race on serum cytokine levels in healthy population, we measured IL-4, 5, 6, 10, IFN-gamma, and GM-CSF in serum of healthy Japanese (n = 38), and Americans (n = 10) using CL-ELISA. In this small population with narrow age range, no difference between smokers and nonsmokers was found for any cytokine. No correlations between age and cytokines was demonstrated. However, Japanese samples had lower levels of IL-4, 5, and 10 than American samples. Further evaluation using more controlled study design and larger populations will be necessary to determine whether this difference is due to inherent racial differences in Th2 cell function.

Adult↗
PubMed1994

Atmospheric pollution due to mobile sources and effects on human health in Japan.

Following the rapid economic growth after World War II, diseases associated with environmental pollution frequently occurred due to delayed implementation of countermeasures against environmental pollution. These diseases are exemplified by Minamata disease, Itai-itai disease, chronic arsenic poisoning, and Yokkaichi asthma. After multiple episodes of these pollution-related diseases were experienced, the government and the private sector made joint efforts to reduce environmental pollution. As a result of these efforts and because of changes in the industrial structure, pollution-related diseases have declined. Instead, however, air pollution from automobile exhaust and the health effects of automobile exhaust on people living along roads with heavy traffic began to attract the public's attention after an increase in the use of automobiles. The epidemiological surveys carried out by the Environmental Agency and the Tokyo Metropolitan Government also have suggested unfavorable effects of automobile-caused air pollution on people living in large cities or along major roads. To solve this problem, it seems imperative to promote the reasonable use of automobiles and to work toward more efficient transportation of goods based on analyses of city structure, the life-styles of city dwellers, and the socioeconomic composition of cities. In addition, the discharge of pollutants from automobiles could be controlled.

Adult↗
PubMed1994

Effect of lifetime cigarette consumption on time domain spirogram indices.

A cross-sectional analysis on the dose-related change in time domain spirogram indices induced by lifetime cigarette consumption was conducted to examine the ability of those indices to detect early changes in the lung periphery in comparison with conventional spirometric indices. The subjects were asymptomatic healthy male workers from three occupational cohorts including asbestos workers and welders. They were asked to perform the forced expiration maneuver at least three times to obtain reliable results. A total of 893 subjects were enrolled in the study, and 484 of them who were aged 30 years or more and were free from chronic respiratory symptoms and abnormalities in chest radiography and spirometry, were analyzed. Although conventional indices, such as forced expiratory volume in one second and maximal midexpiratory flow, were not significantly different between smokers and nonsmokers, the standard deviation of transit times and of time constant distribution in smokers were significantly elevated compared with nonsmokers. Furthermore a dose-related change according to lifetime cigarette consumption was observed in those indices. We conclude that time domain spirogram indices, especially the standard deviation of time constant distribution, would be more useful than conventional indices in detecting early changes in the lung periphery.

Adult↗
PubMed1994

Longitudinal changes in time domain spirogram indices and their variability.

The purpose of this study was to describe longitudinal changes in time domain spirogram indices and their variability. We therefore measured forced expiratory spirograms of 326 middle-aged male employees in two asbestos-using factories four times over 5 yrs. From the original sample of 326, 225 healthy subjects, who provided reliable results for three or more surveys, were selected for analysis. The mean and standard deviation of transit time and their log-transformed values (MTT, STT, ln(MTT), and ln(STT), respectively), as well as two indices of the estimated time constant distribution (Mu and Sigma, respectively) were analysed using a longitudinal model. The longitudinally estimated annual increase of MTT, STT, ln(MTT), and ln(STT) was about three times larger than the cross-sectional estimate, whilst they were comparable in Mu and Sigma. A highly significant contribution of between-subject variability was found in all indices. This was particularly remarkable in the mean components. The between-subject variability was about eight times larger than the error variance in Mu, and three times in MTT and ln(MTT). We conclude that the longitudinal data of transit time indices should not be compared with cross-sectional reference values, and that the magnitude of error variance of these indices in longitudinal repeated measurements will be rather less than the cross-sectional counterpart reported previously.

Adult↗
PubMed1993

Moebius syndrome associated with pituitary dwarfism and hypoplastic optic disc.

A 17 year old male patient with Moebius syndrome with pituitary dwarfism and unilateral hypoplastic optic disc is presented. Although there have been several reports of an association of Moebius syndrome and pituitary dysfunction, growth hormone deficiency has not been reported previously. These associations may give some insight into the pathogenesis of Moebius syndrome.

Adolescent↗
PubMed1993

[Long-term follow up studies of asthma in children. Prognosis of asthmatic school children of the 20 years from the first investigation].

OBJECTIVE: For the prognoses of asthmatic children, reports tend to be in severe cases because most investigations are performed in specialized facilities. We presumed that the prognoses of overall asthmatic cases including mild and moderate case might be better than that reported, we therefore reviewed cases of bronchial asthma in school children in the past 20 years to investigate the prognoses. METHOD: Cases of bronchial asthma in school children detected in an asthma survey conducted in Niigate Prefecture in 1969 were followed up in 1974 and 1982. Recently, the prognoses were studied again in 1989, 20 years after the initial survey. The subjects comprised 164 patients (125 males and 39 females). RESULTS: The most recent survey revealed that 68.7% of the subjects were without attacks, 30.4% were suffered for attacks currently and 0.7% had already died. Asthmatic attacks were mild in 83.7% of the subjects with asthma. The largest percentage of subjects (59.4% of males and 30.4% of females) became negative for attacks after they reached 11 to 14 years of age. In all four surveys, 6.3% of males and 17.5% of females were constantly positive for attacks, while 10.9% of males and 30.3% of females became negative for attacks once but subsequently experienced recurrence of the attacks. The prognoses were worse in females than in males. The subjects who continued to have attacks after they reached adolescence were observed to have attacks frequently even after they became adults. One third of subjects with attacks had remittance lasting for two years or more. Remittance was seen in the period between the age of 15 and 25 years in most cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Effects of alpha 1-proteinase inhibitor on chemotaxis and chemokinesis of polymorphonuclear leukocytes: its possible role in regulating polymorphonuclear leukocyte recruitment in human subjects.

A variety of biologic products derived from bacteria, inflammatory cells, and active degraded proteins have been identified as having chemotactic activity essential for polymorphonuclear leukocyte (PMN) recruitment to the site of inflammation. Little is known, however, concerning factors responsible for regulating the intensity and duration of PMN recruitment. Evidence is growing that proteinase inhibitors modify the migrating ability of PMNs, although the physiologic implications of this have eluded clarification. In an attempt to hypothesize a role of alpha 1-proteinase inhibitor (alpha 1-Pi) in PMN recruitment to inflammatory sites, we examined the effects of alpha 1-Pi in different physiologic concentrations on PMN migration with a microchemotaxis chamber technique. Alpha 1-proteinase inhibitor had both stimulatory and inhibitory effects on cell migration, depending on its concentration. The inhibitor was active in inducing both directed locomotion (chemotaxis) and nondirected locomotion (chemokinesis) in concentrations of 0.02, 0.2, and 2 mg/ml, with maximum potency in both cases at 0.2 mg/ml (corresponding to the normal alveolar surface fluid level in the lung). Alpha 1-proteinase inhibitor impaired chemotactic responsiveness to known chemoattractants at 2 and 10 mg/ml (corresponding to normal and inflammatory blood levels, respectively) in order of potency. These results suggest that alpha 1-Pi may play a role in regulating inflammatory processes, especially in the lung, through its stimulatory and inhibitory effects, depending on its concentration.

Chemotaxis, Leukocyte↗
PubMed1992

Pulmonary function development in children with past history of asthma.

STUDY OBJECTIVE: The aim was to examine whether or not the children with a past history of asthma but free from asthmatic attacks for several years show a different growth pattern in pulmonary function from control children. DESIGN: A community based cohort was surveyed three times during a four year follow up period. SETTING: Kashima district in Ibaraki prefecture, Japan. PARTICIPANTS: In 1980, 441 primary school children between 113 and 124 months of age were enrolled as an initial cohort; 325 of these provided reliable results in each of the three surveys. MAIN RESULTS: A level and a slope of FVC, FEV1, Vmax50, and Vmax25 were calculated for each child, based on a general linear model analysis. Past histories of each child were determined from a standardised questionnaire. The children with a history of doctor diagnosed asthma showed a lower Vmax50 level (p < 0.005) and a lower level and slope of Vmax25 (p < 0.005, p < 0.01) than control children, even when only those who did not suffer from wheezing attacks during the follow up period were considered. CONCLUSIONS: Indices of peripheral airways function in children with an asthmatic history were reduced even if they had been in remission for several years. The difference in pulmonary function in comparison to control children might become greater at the time of the adolescent growth spurt.

Age Factors↗
PubMed1992

Administration of alpha 1-proteinase inhibitor ameliorates bleomycin-induced pulmonary fibrosis in hamsters.

The effect of alpha 1-proteinase inhibitor (alpha 1Pi) administration on the acute lung injury and subsequent fibrosis induced by bleomycin (BLM) was examined in hamsters. Pulmonary lesions were quantitatively reduced in alpha 1Pi-administered BLM-treated (BLM-alpha 1Pi) animals compared with animals treated by BLM alone (BLM-control) at both 7 days (acute stage) and 30 days (fibrotic stage) after BLM treatment. Analysis of intraalveolar cells from bronchoalveolar lavage (BAL) fluid revealed that neutrophils and lymphocytes were significantly decreased in the BLM-alpha 1Pi animals at 7 days after BLM treatment and that 30 days after BLM treatment macrophages as well as neutrophils and lymphocytes were remarkably decreased in the BLM-alpha 1Pi animals. The elastase activity in supernatants of BAL fluid during 7 days following BLM treatment was detected, but there was no difference between the two groups. In vitro studies on neutrophil responsiveness to stimulation of BAL fluid at 3 days after BLM treatment revealed noticeable chemotaxis and generation of superoxide anion of isolated neutrophils, but alpha 1Pi did not show any inhibitory effects on neutrophil responsiveness. We suggest that alpha 1Pi administration ameliorates pulmonary fibrosis preceded by acute lung injury induced by BLM treatment in hamsters and that the inhibitory effects of alpha 1Pi on lung injury may not be brought about by altered elastase activity, chemotaxis, or superoxide generation in neutrophils. Alternative mechanisms are discussed.

Animals↗
PubMed1992

[Between- and within-subject variability of pulmonary function. Four year follow-up of adult males].

Maximal forced expiration of 326 adult males 30 to 55 yr of age was measured four times during a follow-up of 4 yr. Acceptable results were obtained in 270 subjects three times or more. Forced vital capacity (FVC), forced expiratory volume in one second, maximal expiratory flows at 50% and 25% FVC divided by squared height (CFVC, CFEV1, CVmax50, and CVmax25, respectively) were analyzed. Between- and within-subject variance were estimated by a linear model, including the effects of individual and age as explanatory variables. The goodness of fit of the model was satisfactory, since the coefficients of determination of the model were more than 0.96 for CFVC and CFEV1 and around 0.91 for CVmax50 and CVmax25. Estimated between-subject variance was far larger than within-subject variance, being more than ten times for CFVC and CFEV1, about eight times for CVmax50, and five times for CVmax25. At the same time, annual decline of pulmonary function determined cross-sectionally was significantly larger than that determined longitudinally. These results indicated the superiority of longitudinal analysis to cross-sectional analysis in evaluating relatively small effects on pulmonary function especially in the case of chronic exposure of toxic substances in low doses.

Adult↗