Changes in pulse rate, blood pressure and serum dopamine-β-hydroxylase activity of 10 asthmatic children who could be provoked into an asthmatic attack by master two step test and 8 normal children were compared while pool and sea swimming. The asthmatic group showed significantly higher pulse rates than the controls, especially during pool swimming. Systolic blood pressure of both groups was elevated after each exercise. The control group showed significantly higher values than the asthmatic group during pool swimming. The asthmatic group showed a significantly lower level of serum dopamine-β-hydroxylase activity than the controls after 5 min of the master two step test (p<0.1-0.05). In pool swimming, both groups showed the same pattern of serum dopamine-β-hydroxylase activity changes, i, e, an increase immediately after swimming. Thirty min after swimming, however, the serum dopamine-β-hydroxylase activity decreased more in the asthmatic group than the normal controls, especially after long distance swimming (p<0.05). After sea swimming, the serum dopamine-β-hydroxylase activity increased and was still increased 2 hours later. On the basis of the results, we would suggest that serum dopamine-β-hydroxylase was secreted less or inactivated more quickly in asthmatic patients with EIA. In conclusion, the repeated swimming training is effective on the sympathetic nervous system of asthmatic patients.

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One hundred and seven samples of colostrum were obtained from healthy mothers on the 1st to 5th postpartum days. In addition, paired samples of serum and colostrum were collected from 16 healthy mothers. IgG, IgA, IgM, C3, C4 and C3-activator levels in colostrum were measured by a single radial immunodiffusion technique using immunoelectrophoresis. The IgE level in paired samples of serum and colostrum were measured by the radioimmunosorbebt test (RIST) and paper radio immunosorbent test (Prist). A very high level of IgA and an elevated ratio of IgA to IgG in colostrum were demonstrated. In addition, the IgA level in colostrum was significantly higher than that in the paired serum. C3, C4 and C3-activator were apparently present in colostrum, but their levels were low compared to those in serum. C3 level corresponded to C4 level in cases where both C3 and C4 were detected in high levels. IgD, C5 and C9 were not detected by immunoelectrophoresis. The IgE level obtained by PRIST corresponded to the level obtained by RIST. Some unknown factor in colostrum might be nonspecifically interfering with RIST. The ratio of colostral IgE level to serum IgE level detected by PRIST in paired samples was lower than the corresponding IgG ratio. IgE in colostrum might be the result of diffusion from blood circulation.

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In order to determine whether type(s) of immunologic reaction (mainly Arhtus reaction) other than the immediate type reaction are related to the development of bronchial asthma the following experiment was done. Eighty patients with bronchial asthma received bronchial provocation and skin tests. These were compared to time-related changes in serum CH50, counts of blood and nasal eosinophils, types of asthma, and effectiveness of immunotherapy. The antigens used were house dust, polyvalent vaccine and mixed fungal antigens. It was found that: 1. No apparent correlation was observed between the type of bronchial response and the type of skin reaction. However, most of the patients with type III or III+IV skin reaction showed a late asthmatic response (LAR). 2. Infectionus type asthmatics tended to show a LAR more more than atopic type asthmatics. 3. Serum CH50 in the patients who received inhalation tests remained within the normal range, except for one patient whose CH50 level decreased 6 hours after the inhalation. This patient had a type I+III skin reaction with a LAR. 4. By double immunodiffusion test, precipitating antibody against house dust was found in two cases. One showed a LAR, the other a dual type reaction. By single radial immunodiffusion test, the precipitating antibody against Staph. Aureus was found in three cases. One of these showed a LAR, another a dual type bronchial response and the third, no bronchial response. 5. Counts of blood eosinophils decreased one hour following the inhalation test, in patients who showed an immediate or dual bronchial response. Thereafer eosinophil counts gradually increased, reaching a maximum at 12-24 hours. Nasal eosinophils increased reaching a maximum 1-3 hours after the inhalation test. In cases with a late bronchial response, however, no significant change in eosinophil counts was observed. 6. The relationship between type of bronchial response and effectiveness of immunotherapy was as follows: In patients showing an immediate bronchial response, immunotherapy was 100% effective. In patients with a dual bronchial response, it was 75.0% effective and in LAR patients, it was 72.7% effective. The effectiveness of immunotherapy in these groups with a possitive bronchial response was significantly higher than the effectiveness in the negative bronchial response group. From these results, it is suggested that most patients developed bronchial asthma by the mechanism of the immediate type reaction. However, it should be considered that Arthus and/or delayed type reactions are also involved in the induction of bronchial asthma.

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The changeability of airway narrowing is one of the main feature of human asthma. There have veen, however, no suitable means to directly demonstrate, assess or analyze such a phenomenon in experimental animals. In the present study, guinea pigs were passively sensitized with homocytotropic antibodies to yueld reproducible anaphylactic responses. Guinea pigs injected intravenously with anti-egg albumin antiserum were challenged intravenously with 500 μg of the antigen at 1, 4, 8 or 21 days after sensitixation. Their symptoms were graded according to the arbitrary system proposed by Ambrus. Tracheal sensitivity was assessed in vitro by the minimal concentration of antigen necessary to give a positive anaphylactic reaction. The time course of tracheal anaphylactic response was observed in vitro. The in vitro reactions appear to be representative of at least two aspects of the in vivo occurrences. First, there was a significant correlation between the rating of the in vivo response and the grade of tracheal sensitivity assessed in vitro (p<0.01). Secondly, the spontaneous relaxation demonstrated in vitro corresponded well to the trasient dyspnea observed in vivo. Neither the addition of anti-adrenergic agents or anti-purinergic one into bathing solutions nor the deletion of an anti-cholinergic agent from the solutions changed the half time of the tracheal anaphylactic contraction. Only an increased supply of oxygen lengthened the half time.

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Recent progress in immunology has revealed the important roles that various lymphokines (LK) play in the chronic inflammatory process, for example, as migration inhibitory factors, mitogenic factors and lymphotozins. This research was carried out to search for fibrogenic activity in culture supernatants of peripheral lymphocytes activated by PHA-P. Both active supernatants containing LK and control supernatants were harvested three times, at-hour intervals. Fibrogenic activity in active was tested on a monolarer of cultured L_<929> fibroblasts (L cells). To investigate the fibrogenic effect of active supernatants on collagen synthesis of L_<929> fibroblasts we determined 1) cokkagen contents of L cell layers, 2) the incorporation rate of (^3H) proline into collagen fractions isolated from L cell layers and cultured supernatants of these layers, and 3) the hydroxylation rate of proline to hydroxyproline in collage fractions. In addition, the effects of LK on non-collagenous protein synthesis of L cells were also examined. The following results were obtained: 1) The active supernatants containing LK generated from lymphocyte between 24 and 48 hours after activation by PHA-P, induced a 43% increase in collagen content of L cells and a 51% increase in the incorporation rate of (^3H) proline into the collagen isolated from L cells, when compared with the matched control grop. 2) The active supernatants generated from lymphocytes between 0 and 24 hours and between 48 and 72 hours had no such effects on L cells. 3) Interestingly, the active supernatants which stimulated collagen bilsynthesis had no effects on non-collagenous protein synthesis of L cells. 3) Interestingly, the active supernatants which stimulated collagen biosynthesis had no effects on non-collagenous protein synthesis of L cells. From this data, we concluded that fibrogenic factors were present main in active supernatants contaaining LK generated from lymphocytes between 24 and 48 hours after activation by PHA-P, and these factors stimulated the collagen synthesis of L cells. We suspect that this activity in LK might play an important role in the progression of fibrosis seen in chronic inflammation associated with cellular immunity.

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Experimental allergic angitis induced by two separate intravenous injections of horse serum antigen into rabbits was studied by immunofluorescent procedures. Free specific antibody persisted in the periarterial connective tissue of the heart, liver and speen up to 21 days after primary immunization. Shortly after the booster shot, Ig, C3 and antigen were simultaneously and intensely and intensely present in the intimal layer of small arteries and in the periarterial connective tissue of the heart and liver. This finding indicates that the inducing antigen is trapped by the preexisting specific antibody and local Arthus's reaction follows at this site. From 7 to 10 days after the booster shot, periarterial infiltration of inflammatory cells and panarteritis with fibrinoid degeneration were observed in these organs. It was considered that panarteritis was not observed in the spleen because the splenic structure allows leakage of the injected antigen via a peripheral central artery into the marginal azone. Therefore, antigen-antibody reaction in the periarterial region may not have been conspicous. The author concludes that the deposition of circulating immune complexes in the intimal layer of arteries and the occurrence of local Arthus' reaction in the periarterial connective tissue were responsible for the development of panarteritis observed after the booster shot by inducing injury from both the luminal and periarterial sides.

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