The important role of mast cells in allergic mediator release and allergy is well established although the possibility that other cell types may also contribute important mediators of their own is not included. Mast cell growth and replication in part under the control of lymphokines providing an important link between cellular immunity and immediate hypersensitivity. Mast cell mediators including histamine, PGE_2 and LTB_4 in turn suppress a number of lymphocyte and phagocytic functions including helper T cell activity suggesting a possible role in controlling immune reactivity. Serotonin may also play a related role by suppressing Ia expression on macrophages. Inhibition of immune reactivity by allergic mediators may be of particular importance in the respiratory tract which is subjected to continual antigenic exposure. A variety of stimuli can release mediators from mast cells including antigen and IgE, complement fragments, Iymphokines and monokines, drugs, hyperosmolar solutions and proteolytic enzymes. In the case of IgE mediated reactions cross-linking of IgE molecules is sufficient to produce release. Sensitization of mast cells and basophils by IgE takes place through glycoprotein receptors. This IgE binding molecule has been purified and attempts are now being made to determine its molecular structure by DNA cloning and sequencing. The receptor also contains a 30000mw component which may be involved in signal transmission into the cell. One of the early events in stimulated cells is accumulation of diacylglycerol, presumably through activation of phospholipase C. Diacylglycerol may contribute to cell activation both by activation of C type kinases and as a source of arachidonic acid. Diacylglycerol may also participate directly in granule lysis, since part of the diacylglycerol produced may be within the granule membrane itself. Leukotriene generation involves the activation of a 5-lipoxygenase leading to LTB_4 and the slow reacting substances, LTC_4, LTD_4 and LTE_4. The mechanism of activation of the enzyme is still not completely clear although Ca^<2+>, protein kinases and proteolytic enzymes may all be involved. The recently acquired information on mediators and mast cell function may provide new approaches to the treatment of allergy.

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The release fluoroimmunoassay (RFIA), a new method of enzyme immunoassay (ELISA), was employed for the determination of specific IgE antibody in patients allergic to Japanese cedar pollen. A polystyrene plate coated with allergen was incubated sequentially with test sera (2 hr), with β-D-galactosidase conjugated anti-IgE (3 hr), and with 4-methylumbelliferyl-β-D-galactoside (17 hr) with intervening washing steps. The probe from hydrolysing (4-methyl-umbelliferone) was measured by MicroFluor reader (USA). 1. Data obtained in this test showed that RFIA clearly discriminated between allergic patients and health subjects. 2. The optimal concentration of the allergen which coated the plate was 2.5μg/100μl of dilleunt/well. 3. RFIA was able to detect the minute IgE antibody in 32 diluted patient's serum. Practically no non-specific reaction was found with undiluted sera of individuals. 4. The coefficient of correlation between RFIA and RAST values was 0.870. The coefficient obtained from RFIA and ELISA using polystyrene beads values was 0.937. These findings show that the RFIA method has an advantage over the other procedures (RAST or ELISA) for the diagnosis of immediate-type allergy.

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The pharmacokinetics of theophylline and respiratory impedance as an indicator of airway obstruction were studied in asthmatic patients. Each received multiple oral doses of a new sustained-release theophylline tablet formulation in amounts of 600 mg as the loading dose and maintenanace dose at a half of the loading dose. The theophylline concentrations in plasma and saliva were measured by substrate-labeled fluorescent immunoassay and respiratory impedance was measured by forced oscillatory technique. The data were analyzed by applying a one-compartment model using the computer program NONLIN. The apparent volume of distribution and plasma theophylline clearance were 0.336±0.054l/kg and 34.17±3.54ml/kg/hr, respectively. The mean apparent oral absorption rate constant was calculated to be 0.227±0.053 hr^<-1> and the apparent elimination rate constant was 0.101±0.015 hr^<-1> with an elimination half-life of 7.63±1.00 hr. The dose schedule in the present study indicated that steady state plasma concentrations in the range of 10-20μg/ml were maintained in four of the six patients. Furthermore, there was significant reduction in respiratory impedance at steady state trough times 84 and 96 hours compared with that obtained from pre-dose. These results showed that when steady state of plasma concentration exceeded 8μg/ml, respiratory impedance was reduced or unchanged. On the other hand, there was a good relationship between steady state trough concentrations in plasma and saliva (n=18, r=0.993, p<0.001). The mean saliva/plasma ratio of plasma theophylline concentration was 0.58±0.01 and the coefficient of variation for the variability was 9.0%. It is likely that once steady state trough plasma and saliva concentrations have been measured, monitoring of theophylline therapy using saliva measurements alone could be possible.

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Occupational allergy induced by experimental mice was investigated in seventy-two individuals who had contact with experimental mice for more than one year. The seventy-two individuals were divided into two groups. Group A included twelve persons who were diagnosed as having type I allergy to mouse dander. They showed allergic symptoms including rhinitis, asthma, itching and strong skin reaction to mouse dander. Nine of the twelve showed positive scores on a radioallergosorbent test (RAST) to mouse dander antigens. Group B induced sixty persons who showed neither allergic symptoms nor skin reaction and who had negative score on RAST. There was no difference in frequency of personal or family history of atopy between the two groups. No significant difference in the frequencies of HLA class I and class II antigens were observed between the two groups. The result indicate that genetic factors may not contribute significantly to occupational mouse allergy. Specific lymphocyte proliferative response (LPR) to mouse dander antigen in vitro was frequently observed in groupe A, whereas none of the subjects in group B showed specific LPR. Specific LPR was regarded as class II antigen dependent T cell reaction, since the reaction was inhibited by monoclonal antibodies specific to class II and human T-cell antigens.

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Food allergy is classified into two types, immediate type and non-immediate type. There is a discrepancy between values of specific IgE antibodies and clinical symptoms. On the other hand, blastogenesis of lymphocytes to antigens or lectins represents cell mediated immunity, especially delayed hypersensitivity. In this study, blastogenesis of lymphocytes to food allergens, ovalbumin (OA) or bovine serum albumin (BSA) were investigated in patients with food allergy. The results disclosed that in cases showing non-immediate type hen egg allergy blastogenesis of lymphocytes to OA was positive in 7 out of 9 cases (78%) and in the cases showing non-immediate type cow milk allergy blastogenesis of lymphocytes to BSA was positive in all 7 cases (100%). However, in the control or the cases showing immediate type hen egg or cow milk allergy, blastogenesis of lymphocytes was negative in all cases. These results suggest that blastogenesis of lymphocytes to food allergens is helpful in detecting food allergens in patients with food allergy.

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The environmental and background factors affecting allergic conjunctivitis were investigated through a questionnaire prepared by the authors. The questionnaire covered patient's living area, onset season, familial history, other allergic disorders and whether the patients underwent breast or cow's milk feeding. The prevalence of younger individuals in the cow's milk feeding group suffering allergic symptoms was markedly higher than that of younger individuals in governmental statistics. In the patient group whose members had no allergic familial history and who were fed with breast milk, the prevalence rate of allergic symptoms was higher among those living near a busy road than among those living distant from that road (p<0.01). Therefore, the onset of allergic conjunctivitis can be said to be related to familial history, absence of breast-feeding and living proximity to a busy road.

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The effects of Atrovent^[○!R] on bronchial hyperresponsiveness and characteristics of pulmonary muscarinic acetylcholine receptors (mAchR) were studied in guinea-pigs. In this study, we examined bronchial hyperresponsiveness by measuring transcutaneous oxygen pressure (tcPo_2) during inhalation of acetylcholine. Furthermore, we assessed the characteristics of pulmonary mAchR by determining the affinity and density of mAchR using ^3[H]-quinuclidinyl benzilate, a potent muscarinic antagonist. The following results were obtained. 1) Low dose administration of Atrovent^[○!R] (0.1mg/kg, 10 days) had no effect on bronchial hyperresponsiveness and did not affect the characteristics of pulmonary mAchR. 2) High dose administration of Atrovent^[○!R] (1.0mg/kg, 10 days and 5 weeks) significantly reduced bronchial hyperresponsiveness (p<0.01). Simultaneously, a significant decrease (p<0.01)in the density of mAchR was observed in these groups. These results suggest that reduced bronchial hyperresponsiveness by Atrovent^[○!R] might be due to decreased density of mAchR.

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The authors examined the effect of culture supernatant from influenza virus-sensitized human mononuclear cell (virus-sup) on a variety of functions of human neutrophils and eosinophils. Functions of neutrophils, i.e. the migration against zymosan-activated serum, the production of superoxide anion in neutrophils stimulated with opsonized zymosan particles, and the release of some lysozomal enzymes, such as peroxidase, arylsulfatase B and beta-glucuronidase, were markedly enhanced after preincubation with the virus-sup. The enhancing effect of the preincubation were suggested to be mediated through an increment of complement receptors on neutrophils. In the case of eosinophils, the functions mentioned above were decreased after treatment with virus-sup. All of the above mentioned effect of virus-sup on neutrophils and eosinophils were abolished by an addition of anti-interferon antibody. The effect of virsus-sup were also mimicked by preincubation with interferon preparations. The quantity of slow-reacting substance of anaphylaxis (SRS-A), which was generated in eosinophils stimulated with human IgG-coupled Sepharose 4B beads, increased after preincubation with leukocyte interferon. The enhancing effect of the preincubation were suggested to be mediated through a decrease of the release of peroxidase from the cells and of expression of Fc-gamma receptors on the cells. From these results, the following possibility is suggested: that interferon enhances the inflammatory process and plays a role in the worsening of the patient's condition in allergic disorders such as bronchial asthma. A possible relation between viral infection and the worsening of allergic reactions is also suggested.

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It is nowaday very controversial whether nasomucosal stimulation (Ns・S) and also nasopharyngeal stimulation (Rp・S) cause bronchoconstriction or dilation in both healthy animals and humans. Neverthless, we recently found that peroral Rp・S evoked concurrent lower esophageal sphincter-relaxation with bronchodilation in child-asthmatics, but that pernasal Rp・S and Ns・S induced bronchconstriction in most of these cases. This suggests the possibility that peroral Rp・S specifically activates the so-called nonadrenergic noncholinergic inhibitory nerve (NANCIN) system. The purpose of this study is to demonstrate the actual brochodilation shown by an increased peak expiratory flow rate (PEFR) after Rp・S in child-asthmatics. 51 asthmatic children with or without attacks were chosen randomly for the study. The Rp・S was performed perorally without anticholinergic drug, Ipratropium bromide (Sch-1000), pretreatment. The subjects were divided into two groups with attack and two groups without attack. One on attack group and one off attack group were composed of 12 cases and 16 cases respectively in which Rp・S followed β_2 receptor stimulation (β_2・S) was performed. The other on attack group and its control group (off attack) were composed of 12 cases and 11 cases respectively in which β_2・S followed by Rp・S was performed. The following conclusions were obtained; 1. Rp・S resolved or alleviated asthmatic attacks in about 15 seconds, 2. The combinations of Rp・S and β_2・S or β_2・S and Rp・S were more effective than either of the two stimulations, 3. 7 out of 51 cases showed a decrease in PEFR after the final stimulation which was probably caused by myogenic activity, 4. These results revealed the existence of a possible NANCIN control of airways in asthmatic children in situ.

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