[A questionnaire survey on the self-assessment to the asthmatic treatment in Saitama Prefecture: results from 2825 cases].

The aim of this study was to survey the self-assessment to the treatment of adult bronchial asthmatics in Saitama prefecture. A questionnaire on daily symptoms and medications was distributed to 2825 adult asthmatic subjects who were treated at 125 hospitals/clinics in Saitama prefecture between September 15th and October 30th 1998. More than half (52.7%) of patients described that their general condition of asthma was poorly controlled. Even among the patients described that their condition was good or fair, 30.2% of them had some asthmatic symptoms such as shortness of breath or nocturnal awakening. Although inhaled corticosteroids were used in 66.2%, the ratio of patients who used spacer and kept drug compliance as prescribed were 59.6% and 45.8%, respectively. According to the physician's reports, cysteinyl leukotriene antagonist was used in 35.7%, which was comparable to the total of another anti-allergic drugs (37.3%). These results suggest that more than half of asthmatic patients in Saitama prefecture were not satisfied with their conditions of the disease control. Furthermore, more thorough education on the technique and compliance of inhaled corticosteroids would be required.

Effect of inhaled cyclosporin A on the allergen-induced late asthmatic response and increased in airway hyperresponsiveness in a guinea pig model of asthma.

Oral administration of cyclosporin (CsA), a potent inhibitor of helper T cell function, prevents the allergen-induced late asthmatic response (LAR) and the increase in airway hyperresponsiveness (AH) seen in actively sensitized guinea pigs. The systemic administration of this agent in humans has been associated with serious side effect, therefore, the effects of inhaled CsA were therefore examined in guinea pigs that were actively sensitized by repeated exposure to nebulized ovalbumin. Respiratory resistance (Rrs) of the animals was measured by an oscillation method and the extent of AH was inferred from the inhaled concentration of histamine required to increase Rrs by 200%. The magnitude of ovalbumin-induced immediate bronchoconstriction after sensitization was similar in CsA-treated and nontreated control animals. However, a LAR was observed in 4/5 control animals but in 0/5 CsA-treated animals. The increase in AH observed 24 hours after antigen exposure in control animals was significantly inhibited by prior CsA inhalation. Significant CsA concentrations were detected by radioimmunoassay in the lungs of CsA-treated animals. Thus, inhaled CsA should be further investigated because it may be useful treating asthma while avoiding side effects.

Sensitization primes platelet-activating factor (PAF)-induced accumulation of eosinophils in mouse skin lesions: contribution of cytokines to the response.

We have examined the hypothesis that cytokines mediate the enhanced responsiveness of eosinophils to PAF in sensitized mouse skin. PAF (10 ng per site) resulted in a considerable degree of eosinophil accumulation in ovalbumin (OA)-sensitized mice but not in non-sensitized mice. Intradermal preadministration of cytokines (IL-5, IL-3 and GM-CSF) also significantly enhanced PAF-induced migration of eosinophils in a dose-dependent manner. The relative potency with which these cytokines primed cell migration was IL-5 greater than IL-3 greater than GM-CSF, however, each cytokine alone showed no direct effect. We conclude that the sensitization or the exogenous application of cytokines is capable of augmenting PAF-induced eosinophil migration in mice in vivo, and the cytokines thus elicited by sensitization may contribute to the extensive recruitment of inflammatory cells in allergic diseases.

[Platelet activating factor (PAF)-induced late asthmatic response in sensitized but not in non-sensitized guinea pigs].

We have recently demonstrated that pretreatment with WEB 2086, a specific PAF antagonist or cyclosporine A (CsA), a potent helper T cell suppressant, resulted in preventing the development of late asthmatic response (LAR) and increase of airway hyperreactivity (AH) in guinea pig experimental models of asthma. We have now examined whether exogenously applied PAF causes LAR in these models in vivo. The respiratory resistance (Rrs) of guinea pigs was measured by an oscillation technique and histological studies of the bronchi were also made. Guinea pigs, actively sensitized by repeated antigen (ovalbumin; OA) inhalation, showed a leftward shift of the inhaled PAF dose response curve of Rrs compared with that in control animals, indicating that the sensitized animals were more sensitive to inhaled, PAF. PC200 PAF, which indicate provocative concentrations of PAF aerosols causing a 200% increase in the baseline Rrs, were 3800 +/- 604.9 micrograms/ml and 780 +/- 94.3 micrograms/ml, in the control and sensitized animals, respectively. The same magnitude of immediate bronchoconstriction after 780 and 3800 micrograms/ml of PAF exposure was observed in the actively sensitized and non-sensitized control animals, respectively. However, LAR developed 4 out of 6 animals only in the sensitized guinea pigs. We conclude that both exogenously applied PAF by inhalation and antigen exposure are capable of inducing LAR in sensitized guinea pigs, and thus the priming effect of immunization and PAF may contribute to the development of LAR observed in asthma.

[Cyclosporine A inhibits allergen-induced late asthmatic response and increase of airway hyperresponsiveness in guinea pigs].

Considerable interest has recently focused on the role of T-cell function in the pathogenesis of asthma. We have previously demonstrated that repeated inhaled antigen (ovalbumin; OA) exposure resulted in an appearance of late phase airway obstruction (LAR) in more than 50% and significant increase of airway hyperresponsiveness (AH) in guinea pig experimental models. We have studied the effect of cyclosporine A (CsA), a potent helper T-cell suppressant, on these models in vivo. Respiratory resistance (Rrs) of sensitized guinea pigs by repeated OA inhalation was measured by the oscillation method and AH estimated as an inhaled concentration of histamine, causing a 200% increase in the baseline Rrs (PC200 Hist). The magnitude of immediate OA (10 mg/ml/min) inhalation-induced bronchoconstriction was not significantly different in CsA-treated (25 mg/kg/day, 7-day oral administration) and non-treated groups. However, the development of LAR was markedly inhibited in CsA treatment groups (n = 5). Antigen-induced increase of AH at 24 hr and 5 days was also significantly inhibited by CsA pretreatment. We conclude that CsA is capable of inhibiting the development of LAR and increase of AH, and thus the regulation of T-cell function may contribute to the treatment of asthma.

[Involvement of platelet activating factor (PAF) in ovalbumin antigen-induced late asthmatic response and increase of airway hyperresponsiveness in a guinea pig experimental model of asthma].

Platelet activating factor, a potent chemical mediator, has been implicated in the pathogenesis of asthma in terms of inflammatory cell recruitment and activation. We have recently demonstrated that repeated antigen (ovalbumin; OA) exposure by inhalation to guinea pigs results in a development of late asthmatic response (LAR) in more than 50% of the animals and significant increase in airway hyperresponsiveness (AH). We have studied the effect of WEB 2086, a specific PAF receptor-antagonist, on this model. Respiratoly resistance (Res) of guinea pigs was measured by a oscillation technique and AH was evaluated by the provocative concentration of aerosols of histamine causing 200% increase of Rrs over the baseline Rrs (PC200 Hist). Four out of 5 actively sensitized and diphenhydramine-pretreated animals developed LAR 3 to 9 hr after allergen (20 mg/ml OA, 10 min inhalation)-induced immediate bronchoconstriction (LAR). Treatment with WEB 2086 (3 mg/kg intravenously) 30 min before and 3 hr after the exposure suppressed LAR clearly without affecting the IAR. Significant increase in AH from 2.80 +/- 0.03 to 2.51 +/- 0.01 and 2.60 +/- 0.08 (p less than 0.05, n = 8) of PC200 Hist (mg/ml, log) was observed 24 hr and 5 day after the OA exposure, respectively. The WEB 2086 treatment also prevented the increase of AH after the OA exposure (PC200 Hist; 2.82 +/- 0.09 before the challenge 2.80 +/- 0.07 and 2.75 +/- 0.09 24 hr and 5 days after, respectively. n = 8). Administration of WEB 2086 did not affect baseline Rrs and PC200 Hist in normal guinea pigs without any antigen challenge. We conclude that WEB 2086 is capable of preventing the development of LAR and increase in AH, and thus PAF may play an important causal role in LAR and increased AH observed in asthma.

Hemoglobin transition in early development stages of the tadpole, Rana catesbeiana.

Five hemoglobin components (a, I, II, III and IV) were isolated from the hemolysates of the tadpole, Rana catesbeiana. Component a was monomeric molecule and the other four were tetrameric molecules. Component I predominating in younger tadpoles was replaced by component II during tadpole development. Electrophoretic and chemical analyses on the constituent globin chains revealed that component a was very similar to the alpha-chains of components I and II, ad that components I and II differed from one another in their beta chains.