[Occupational bronchitis, bronchiolitis, and occupational lung disease].
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Bronchiolitis↗
Biomedical subjects
T Nakadate
Publications and source records attributed to T Nakadate.
[Chronic type hypersensitivity pneumonitis].
The clinical features and chest X-ray appearances of chronic type hypersensitivity pneumonitis closely resemble those of idiopathic interstitial pneumonia. Therefore, it is very difficult to make a correct diagnosis without detailed information. Our study showed that bronchoalveolar lavage and lung biopsy are useful examinations for the differential diagnosis of these two diseases. The characteristic finding of bronchoalveolar lavage of chronic type hypersensitivity pneumonitis is still lymphocytosis, as is also seen in the acute type. The pathological findings of chronic type hypersensitivity pneumonitis are alveolitis with marked lymphocyte infiltrations and granuloma formation although the number of granulomas is low. Recently, we experienced five patients with chronic type farmer's lung. The average age of these five patients was significantly older than that of acute type farmer's lung. They had engaged in farming after the onset of their disease, which suggested continuous chronic exposure to mouldy hay. It is concluded that patients with hypersensitivity pneumonitis, especially aged people, should avoid antigen exposure and should be followed up the progress of the disease with intensive care.
Chronic Disease↗
Glycoprotein Ia/IIa-mediated activation-dependent platelet adhesion to collagen.
In the presence of anti-glycoprotein (GP) IIb/IIIa antibody at the concentration which completely inhibit platelet aggregation, ADP (0.5-3 microM) increased platelet adhesion to collagen in a concentration-dependent manner under static conditions when platelet-rich plasma (PRP) was used for the assay instead of washed platelets. This was also supported by the results of scanning electron microscopic analyses. The ADP-induced platelet adhesion to collagen was inhibited by PGI2 or beraprost, a stable analogue of PGI2, in a concentration-dependent manner (1-10 ng/ml). These findings suggested the presence of activation-dependent platelet adhesion to collagen. ADP-induced platelet adhesion to collagen was almost completely inhibited by anti-GPIa/IIa and anti-GPIIa antibodies. In the present study, we provide the first direct evidence that the activation-dependent platelet adhesion to collagen is induced by ADP and that GPIa/IIa also plays an important role in the mechanisms of this adhesion.
Adenosine Diphosphate↗
Four-year follow-up of effects of toluene diisocyanate exposure on the respiratory system in polyurethane foam manufacturing workers. I. Study design and results of the first cross-sectional observation.
A 4-year cohort study was designed to assess the exposure-effect relationship of working in polyurethane foam (PF) manufacturing factories with exposure to toluene diisocyanate (TDI) and its effects on the respiratory system. This paper describes the results of the first cross-sectional observations. The study population included 90 male workers who had been working in PF factories for 0.5-25 years (mean 13.3 years) (PF workers) and 44 reference workers in the same factories. The mean exposure concentration of TDI calculated from 129 personal samples was 3.2 ppb. Peak exposure excursions above 20 ppb occurred in 16 of 129 samples. Pulmonary function and its change during the working day as assessed by examining the forced expiratory flow-volume curve, respiratory impedance, and airway resistance and specific airway conductance were not different in the PF workers from those in the reference workers. Chest X-radiographs did not show any noteworthy radiological changes. Prevalences of "phlegm in winter," "nasal stuffiness or discharge in winter," and "irritation of eye and throat mucous membranes" were significantly higher in the PF workers. The findings indicate that TDI exposure at levels around 3 ppb may not adversely affect the pulmonary function over many years of exposure of those who are not hypersensitive to TDI. The causal chemicals inducing some respiratory and irritative symptoms could not be specifically identified since the PF workers were exposed not only to TDI but also to other irritative agents in the PF manufacturing processes.
Adolescent↗
Four-year follow-up of effects of toluene diisocyanate exposure on the respiratory system in polyurethane foam manufacturing workers. II. Four-year changes in the effects on the respiratory system.
Fifty-seven polyurethane foam manufacturing workers (PF workers) and 24 reference workers were followed for 4 years to clarify the effects on pulmonary function of working in PF factories with exposure to toluene diisocyanate (TDI). No significant differences in the average annual losses (AALs) of pulmonary function for 4 years were observed among the 28PF workers whose TDI exposure levels were very low (mean = 0.1 ppb, group L), the remaining 29 PF workers with mean TDI exposure of 5.7 ppb (group H), and the reference workers. However, 15 PF workers in group H who had experienced peak exposure excursions to 30 ppb or above with a mean concentration of 8.2 ppb showed significantly larger AALs in percentage maximal mid-expiratory flow, forced expiratory volume in 1 s ratio to vital capacity (FVC), and forced expiratory flow at 25% of FVC than expected, and significantly larger AALs in some obstructive pulmonary function indices than those of the 14 remaining PF workers in group H whose peak exposure excursion levels were 3-14 ppb with a mean time-weighted average (TWA) of 1.7 ppb, group L, and the reference workers. These findings suggest that the peak exposure excursion level of TDI might be important in inducing obstructive pulmonary function changes in the PF workers rather than the TWA exposure levels, though further comparative studies of the AAL in those who are exposed to different peak exposure excursion levels but the same mean exposure levels are necessary. From the standpoint of prevention, the proposition that peak exposure excursion levels exceeding 20 ppb should be avoided is reasonable.
Adult↗
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↗
Cytoprotective action of beraprost sodium against peroxide-induced damage in vascular endothelial cells.
Using a peroxide-injured endothelial cell model, beraprost sodium (beraprost) was tested in relation to the action to protect against the damage of vascular endothelial cells employing the viability of the cells and change in lipid peroxides as the indicators. At a concentration of 1-3 mumol/l or higher, beraprost significantly inhibited the decrease in viability of the cells and the increase in lipid peroxides level caused by t-butyl hydroperoxide or 15-hydroperoxy-5,8,11,13-eicosatetraenoic acid. When similar tests were conducted with prostaglandin I2, its inhibiting action was equal to or slightly weaker than that of beraprost unlike PGE1 and PGD2. This action of beraprost in inhibiting cell damage caused by peroxides suggests that beraprost may be useful for protecting cells from damage due to ischemic diseases.
Animals↗
Suppression by high glucose concentration of insulin receptor up-regulation in diaphragm and flexor digitorum brevis muscles from diabetic KK-CAy and streptozotocin-diabetic mice.
The specific binding of insulin to diaphragm and flexor digitorum brevis (FDB) muscles isolated from diabetic KK-CAy and streptozotocin (STZ)-diabetic ddY mice was investigated under high glucose concentration in vitro. For high-affinity insulin receptor under 2.8 mM glucose, amounts of the receptor and values of dissociation constant (Kd) were greater in both diabetic muscles than in the corresponding normal control muscles, respectively. High glucose concentration up to 16.7 mM reduced both the up-regulation of the receptor and the decrease in the affinity by the diabetic state. These studies strongly suggest that high glucose level in the diabetic state in vivo may suppress the up-regulation of high-affinity insulin receptor in both models of diabetic mice.
Animals↗
[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↗
Lung cancer in patients with idiopathic pulmonary fibrosis.
We investigated lung cancer in 99 patients with idiopathic pulmonary fibrosis (IPF). Lung cancer was found in 31 (31.3%) of 99 patients with IPF. Most (87.9%) tumors, including squamous cell carcinoma, were observed in the peripheral region of the lung, whereas the distribution of histologic types of cancers was similar to that seen in ordinary lung cancer. Peripheral tumors were frequently seen in the lower lobe, where fibrotic shadow was prominent. However, the severity of fibrosis was not related with the prevalence or histologic type of lung cancer. Two-thirds of IPF patients having a smoking history of over 40 years developed lung cancer. When compared with nonsmoking IPF control subjects, the relative risk of smoking in IPF patients was 3.5, identical with that reported for smokers in the general population. We suggest that smoking in patients with IPF is an additive risk factor for the development of lung cancer. We also speculate that the high prevalence of peripheral squamous cell carcinoma might be associated with cigarette smoking.
Aged↗
[Cytokine gene expression in interstitial lung diseases].
We studied the role of macrophages in the process of pulmonary fibrosis, focusing on gene expressions of cytokines. TGF-alpha is a factor which stimulates fibroblasts or endothelial cells to proliferate, by combining to receptors of EGF competitively with EGF in vitro. Total RNA was extracted from alveolar macrophages recovered by bronchoalveolar lavage from patients with idiopathic pulmonary fibrosis or normal healthy volunteers, and the expression of TGF-alpha mRNA was evaluated by Northern analysis. There was no detectable TGF-alpha mRNA in alveolar macrophages from normal healthy volunteers; however, in patients with idiopathic pulmonary fibrosis, a considerable level of mRNA of TGF-alpha could be detected. Using an experimental rat model of alveolitis induced by bleomycin, the expression of TNF-alpha mRNA in alveolar macrophages recovered by BAL was evaluated by Northern analysis. Alveolar macrophages from bleomycin-treated rats expressed a significant level of TNF-alpha mRNA. Both TGF-alpha and TNF-alpha have proliferative activity on fibroblasts, and may have an important role in the process of fibrosis of the lung.
Cell Division↗
Enhancement by beraprost sodium, a stable analogue of prostacyclin, in thrombomodulin expression on membrane surface of cultured vascular endothelial cells via increase in cyclic AMP level.
Prostacyclin and beraprost sodium (beraprost), a stable analogue of prostacyclin, increased cyclic AMP (cAMP) levels of cultured human umbilical vein endothelial cells (HUVEC) in a concentration-dependent manner. The elevation of cAMP by beraprost was sustained longer than that by prostacyclin. The expression of thrombomodulin (TM) on membrane surface of HUVEC was enhanced by beraprost and prostacyclin, and the persistence of the increase in TM expression by beraprost was greater than prostacyclin. Dibutyryl cAMP (db-cAMP) mimicked the effects of beraprost and 3-isobutyl-1-methylxanthine enhanced the effects. Beraprost, prostacyclin and db-cAMP also effectively blocked the interleukin-1- and tumor necrosis factor-induced depression of TM expression substantially. These results suggest that TM expression is positively regulated by cAMP in HUVEC, and that beraprost may be potentially effective for reducing thrombotic events through the mechanism which initiates the stimulation of cAMP/TM system in vascular endothelial cells.
1-Methyl-3-isobutylxanthine↗
The potent anti-tumor-promoting agent isoliquiritigenin.
A topical application of a chalcone derivative, 4,2',4'-trihydroxychalcone (isoliquiritigenin) inhibited epidermal ornithine decarboxylase (ODC) induction and ear edema formation, i.e. inflammation, caused by a topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA) in CD-1 mice. In addition, isoliquiritigenin potently inhibited 7,12-dimethylbenz[alpha]anthracene (DMBA)-initiated and TPA-promoted skin papilloma formation. This inhibitory effect of isoliquiritigenin was not due to any damage inflicted on the initiated cells but due to its anti-tumor-promoting action. Isoliquiritigenin also inhibited epidermal ODC induction and skin tumor promotion caused by 7-bromomethylbenz[alpha]anthracene (BrMBA), a non-TPA type of tumor-promoting agent, in DMBA-initiated mice. Isoliquiritigenin inhibits neither 12-lipoxygenase nor cyclooxygenase in epidermal subcellular fractions. This compound, however, inhibited TPA-stimulated prostaglandin E2 (PGE2) production in intact epidermal cells. ODC induction caused by TPA was inhibited by a topical application of cyclooxygenase inhibitor, indomethacin. Inhibition of ODC induction by indomethacin was counteracted by a topical application of PGE2, while inhibition caused by isoliquiritigenin was not overcome by PGE2. The results suggest that a mechanism other than the inhibition of PGE2 production is involved in the anti-tumor-promoting action of isoliquiritigenin. Isoliquiritigenin failed to inhibit phospholipase A2 activity of platelet sonicates, but inhibited platelet 12-lipoxygenase and 5-lipoxygenase in polymorphonuclear leukocytes. Therefore, it might be possible that isoliquiritigenin exerts its anti-tumor-promoting action through the lipoxygenase inhibition by acting on cells other than the target epidermal cells. Our present results, in combination with our previous data, demonstrate that some chalcone derivatives and flavonoids which show a potent lipoxygenase inhibitory action act on a common step in the skin tumor promotion caused by two different types of tumor-promoting agents, i.e. TPA and BrMBA, and suggest that these compounds show promise as drugs to prevent tumor promotion.
9,10-Dimethyl-1,2-benzanthracene↗
Inhibitory regulation of serum factor(s)-caused ornithine decarboxylase induction by the protein kinase C system in A431 human epidermoid carcinoma cells.
Replacement of the culture medium with fresh medium containing 10% fetal calf serum caused ornithine decarboxylase (ODC) induction in A431 human epidermoid carcinoma cells. Two peaks of ODC activity were observed at 5 and 14 hr after the medium replacement. The peak activity observed at 5 hr was more prominent than that at 14 hr. The first peak of ODC induction was suppressed by a potent protein kinase C activator, 12-O-tetradecanoylphorbol-13-acetate (TPA), in a concentration-dependent manner. The second peak, however, was not suppressed by TPA. Other potent protein kinase C activators, such as mezerein and 12-O-retinoylphorbol-13-acetate, also suppressed the first peak of ODC induction. Synthetic diacylglycerols, 1,2-dioctanoyl-sn-glycerol and 1-oleoyl-2-acetylglycerol, did not inhibit the serum factor(s)-caused ODC induction. Phorbol-13-acetate, an inactive phorbol ester, also failed to inhibit the ODC induction. The growth of A431 cells was slightly suppressed by TPA. In protein kinase C down-regulated cells, TPA failed to inhibit the serum factor(s)-caused ODC induction. These results suggest that the serum factor(s)-caused ODC induction in A431 cells is negatively regulated by the protein kinase C system, which may not be activated by exogenous diacylglycerols.
Blood↗
Comparison of longitudinally and cross-sectionally determined age-related decline in spirometric measurements.
In order to compare the longitudinally and cross-sectionally determined annual decline of spirometric measurements, we measured spirograms from 326 male adults four times over five years. Acceptable results were obtained three times or more in 269 subjects aged 30 to 55 at the initial survey. Longitudinal annual changes in the height-squared proportional values of forced vital capacity (CFVC), forced expiratory volume in one second (CFEV1), and maximal expiratory flow at 50% and 25% of FVC (CVmax 50 and CVmax 25), was estimated by the model in which the effect of each individual's level was included as an explanatory variable. The cross-sectional annual change in those indices was determined by including the effect of each survey's level in the model. The longitudinal estimate of annual decline was significantly smaller than the cross-sectional estimate for all indices except CVmax 25. No evidence suggested that systemic error of measurement or a learning effect caused significant bias in the data. The discrepancy in the estimated annual changes seemed to be caused by the cohort effect in our subjects, since the cross-sectional analysis is primarily sensitive to harmful factors operating in the past. We concluded that the longitudinal data for individuals or groups should not be compared with any reference value based on a cross-sectional analysis.
Adult↗
[Longitudinal analysis of a four-year follow up of pulmonary function development in children with a past history of asthma].
In order to longitudinally study the pulmonary function development of children with a history of asthma, we measured the flow-volume curves of 441 fourth-grade children in seven primary schools randomly selected from the Kashima district in Ibaraki prefecture in 1980, and again in 1982 and 1984. Levels and slopes of pulmonary function indices for individual children were calculated in 325 children who performed acceptable forced expiratory maneuvers at all of the three surveys. In FVC and FEV1, no significant difference of levels and slopes was observed between children with asthmatic history and control children. However, the level and slope of V25 of children with asthmatic history were significantly lower than those of control children (0.5 l/sec for the level, 0.08 l/sec for the slope) even when only those who did not suffer from wheezing attack during the follow-up period were concerned. These results suggested that the functional change of peripheral airways in children with asthmatic history did not recover within a couple of years even when they were in remission. Moreover, the functional differences between those two groups of children might become larger in early adolescence.
Asthma↗
[Response to the ATS-DLD Questionnaire translated into Japanese: comparison of telephone interview and self-administration method].
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Adult↗