Search for Leptonic Decays of Dark Photons at NA62.

The NA62 experiment at CERN, configured in beam-dump mode, has searched for dark photon decays in flight to electron-positron pairs using a sample of 1.4×10^{17} protons on dump collected in 2021. No evidence for a dark photon signal is observed. The combined result for dark photon searches in lepton-antilepton final states is presented and a region of the parameter space is excluded at 90% confidence level, improving on previous experimental limits for dark photon mass values between 50 and 600 MeV/c^{2} and coupling values in the range 10^{-6} to 4×10^{-5}. An interpretation of the e^{+}e^{-} search result in terms of the emission and decay of an axionlike particle is also presented.

Improved Measurement of the π→eν Branching Ratio.

A new measurement of the branching ratio R_{e/µ}=Γ(π^{+}→e^{+}ν+π^{+}→e^{+}νγ)/Γ(π^{+}→µ^{+}ν+π^{+}→µ^{+}νγ) resulted in R_{e/µ}^{exp}=[1.2344±0.0023(stat)±0.0019(syst)]×10^{-4}. This is in agreement with the standard model prediction and improves the test of electron-muon universality to the level of 0.1%.

Deficiency of platelet-activating factor acetylhydrolase is a severity factor for asthma.

Asthma, a family of airway disorders characterized by airway inflammation, has an increasing incidence worldwide. Platelet-activating factor (PAF) may play a role in the pathophysiology of asthma. Its proinflammatory actions are antagonized by PAF acetylhydrolase. A missense mutation (V279F) in the PAF acetylhydrolase gene results in the complete loss of activity, which occurs in 4% of the Japanese population. We asked if PAF acetylhydrolase deficiency correlates with the incidence and severity of asthma in Japan. We found that the prevalence of PAF acetylhydrolase deficiency is higher in Japanese asthmatics than healthy subjects and that the severity of this syndrome is highest in homozygous-deficient subjects. We conclude that the PAF acetylhydrolase gene is a modulating locus for the severity of asthma.

Effects of pituitary adenylate cyclase activating polypeptide (PACAP) on the cardiovascular system.

The effects of pituitary adenylate cyclase activating polypeptide (PACAP) on the cardiovascular system were examined. When PACAP-38 (270 or 420 pmol/kg body weight) was administered intravenously to the anesthetized dogs, both mean arterial pressure and left ventricular systolic pressure increased within 2 min after a temporal depression. Pulmonary arterial systolic pressure increased promptly. These hemodynamic values and heart rates (HR) 5 min after injection were significantly higher than the corresponding values in physiological saline injected dogs, and some effects were still sustained over 15 min. Cardiac output and stroke volume also increased and the values at 5 min were significantly higher than those in controls. The high dose of PACAP-38 (420 pmol/kg) evoked greater responses than those induced by the low dose (270 pmol/kg). Plasma adrenaline, but neither noradrenaline nor dopamine concentration significantly increased 15 min after injection of 420 pmol/kg PACAP-38. Moreover, PACAP-38 clearly stimulated cyclic AMP production in rat cardiac myocytes with EC50 of 1.5 x 10(-9) M and plasma cAMP levels significantly and dose-dependently increased in dogs 5 min after administration. These results first demonstrated that PACAP has inotropic and chronotropic actions on the heart possibly by a direct stimulation of adenylate cyclase in cardiac myocytes and also that the cardiovascular functions may be possibly modified by an evoked adrenaline secretion in vivo.

[Effects of cefoperazone on respiratory infections of patients of advanced age and/or with underlying respiratory diseases].

Respiratory infections of 19 subjects of advanced age and/or with underlying respiratory disease were treated with cefoperazone (CPZ) and its clinical effects were studied. Sixteen subjects suffered from respiratory tract infection and 3 subjects had pneumonia. The age of the subjects ranged from 39 to 77 years with the mean of 63.8, 7 of them being more than 70 years of age. The underlying respiratory diseases included chronic pulmonary emphysema in 6 subjects, diffuse panbronchiolitis in 3, bronchiectasis in 3, silicosis in 2 and one each of chronic bronchitis, pulmonary fibrosis, lung cancer and old pulmonary tuberculosis. One case, 75 years of age, had renal insufficiency. The daily dose of CPZ was 4 grams in 18 of the 19 subjects and the duration of administration ranged 5 to 22 days. The remaining 1 subject received 2 g of CPZ daily for 6 days. Clinical effects were judged from the changes in fever, cough, amount of sputum, dyspnea, rales, cyanosis, chest X-ray, white blood cell counts, CRP, erythrocyte sedimentation rates and results of sputum culture. Clinical effects were good in 16 subjects, fair in 1, and poor in 2. Bacteriological follow-up was carried out in 13 subjects. Infecting bacteria were eliminated from 5 subjects, reduced in 2 and, in 4 subjects, they were replaced by other bacteria. In 1 subject, P. aeruginosa was isolated from sputum even after the treatment with CPZ, and in another subject H. influenzae relapsed immediately after the cessation of the CPZ treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

[Inhibition of antigen-induced late asthmatic response and bronchial hyperresponsiveness by cyclosporin A].

We have previously demonstrated that Cyclosporin A (CyA), a T lymphocyte-selective immunosuppressive agent, reduced the delayed-phase bronchial eosinophil infiltration after antigen challenge in a guinea pig model of asthma. In the present study, we studied the effects of CyA on antigen-induced late asthmatic response (LAR) and bronchial hyperresponsiveness following LAR. Guinea pigs immunized by repeated exposure to aerosolized ovalbumin (OA) were intravenously given metopirone, a cortisol synthesis inhibitor, 24 hours before and 30 minutes before antigen challenge, and to prevent death from immediate severe bronchoconstriction, chlorpheniramine maleate was also injected. After antigen challenge with high dose of OA, LAR occurred in twelve of fifteen animals (80%) and the bronchial responsiveness to acetylcholine was significantly increased. However, when guinea pigs were treated with CyA from the beginning of immunization period, the development of LAR was completely inhibited, although similar magnitude of immediate bronchoconstriction was observed, and a subsequent increase in bronchial responsiveness was partially but significantly blocked. Since CyA has been shown to suppress activation of guinea pig T lymphocytes and their production of lymphokines, these results suggest that T cell factor(s) may be important for the elicitation of LAR and the antigen-induced bronchial hyperresponsiveness.

[Inhibitory effect of FK-506 on the development of late asthmatic response and on the increased bronchial responsiveness].

We examined the effects of FK-506, a potent immunosuppressive agent, on the development of late asthmatic response (LAR) and on the increased bronchial responsiveness to acetylcholine following LAR in guinea pig model of asthma. Guinea pigs sensitized by repeated inhalation of ovalbumin (OA) were intravenously given metopiron 24 hours before and 30 minutes before antigen challenge and to prevent death from immediate severe bronchoconstriction, chlorpheniramine maleate was also injected. When we defined LAR as the responses with a two-fold increase in respiratory resistance during the late phase of antigen challenge, twelve out of fifteen control animals demonstrated apparent LAR. However, when guinea pigs were treated with FK-506 from the beginning of immunization period, the development of LAR was completely inhibited, although similar magnitude of immediate bronchoconstriction was observed, and a subsequent increase in bronchial responsiveness was significantly blocked. We also measured bronchial responsiveness to acetylcholine before, 24 and 72 hours after antigen challenge. FK-506-treated animals inhibited an increase in bronchial responsiveness to acetylcholine. These results suggest that the involvement of cell-mediated immunity may be important in the development of LAR and an increase in bronchial responsiveness.

Tumor necrosis factor alpha induces migration of human eosinophils.

In order to evaluate the role of tumor necrosis factor alpha (TNF alpha) in the recruitment of eosinophils and neutrophils into the tissues, we studied the effect of TNF alpha on the migration of those cells in vitro, employing a modified Boyden's chamber technique. TNF alpha induced a significant migration of human eosinophils in a dose-dependent manner, and the preincubation of eosinophils with TNF alpha enhanced platelet activating factor (PAF)-induced eosinophil migration. Checkerboard analysis revealed that the eosinophil migration induced by TNF alpha was mainly due to chemokinesis. On the other hand, TNF alpha induced neither neutrophil migration nor enhancement of PAF-induced neutrophil migration. These results indicate that TNF alpha possesses a chemokinetic effect on human eosinophils and that TNF alpha augments the migration of eosinophils by PAF.

[Antigen-induced biphasic eosinophil infiltration in the airways of actively sensitized guinea pigs and its inhibition by PAF antagonist and cyclosporin A].

Bronchial eosinophilia is a characteristic of asthma. To elucidate the mechanisms of eosinophil accumulation in the airways, the time course of eosinophil infiltration in the airway mucosa after antigen inhalation was examined in actively sensitized and passively sensitized guinea pig models of asthma. The lungs and tracheae were removed at intervals after antigen challenge, fixed and stained. The eosinophil infiltration was quantitated in the tracheal walls by counting the number of cells per square millimeter. Guinea pigs sensitized by intraperitoneal injection of ovalbumin (OA) responded to a single exposure to aerosolized OA with biphasic infiltration of eosinophils in the tracheal walls; a striking early-phase which peaked at 6 hr and a delayed-phase which peaked at 24 hr and persisted for as long as 5 days. These kinetics were different from those observed with passively sensitized animals which showed only early-phase infiltration. Administration of CV-6209, a specific PAF antagonist, before and 12 hrs after antigen challenge significantly (p less than 0.01) inhibited the early-phase but not the delayed-phase eosinophil infiltration in actively sensitized animals. In contrast, when guinea pigs were treated with Cyclosporin A, a T lymphocyte-selective immunosuppressive agent, throughout the immunization period, the delayed-phase but not the early-phase infiltration was significantly (p less than 0.01) inhibited. These results suggest that PAF may contribute to early-phase and T cell factor(s) may contribute to delayed-phase eosinophil infiltration of the airways.

[Eosinophil cationic protein in patients with bronchial asthma].

To evaluate the role of eosinophils in the pathogenesis of bronchial asthma, we measured eosinophil cationic protein (ECP), one of the eosinophil granule proteins. Serum ECP levels were measured by radioimmunoassay in asthmatic (n = 59) and non-asthmatic (n = 47) patients. Preliminary study showed that ECP levels were time-dependently increased in the blood samples until 3 hr. Based on the findings, we determined to measure serum ECP levels at 30 min after blood sampling. Serum ECP levels and blood eosinophil counts in asthmatic patients were significantly higher than those in non-asthmatic patients (p less than 0.01). There was also a positive correlation between serum ECP levels and blood eosinophil counts in patients with asthma (r = 0.46, p less than 0.001). No significant difference was observed in either serum ECP levels or blood eosinophil counts in asthmatic patients classified by clinical type and severity. Blood eosinophil counts in patients with asthma attacks were significantly greater than in those in remission (p less than 0.05), but no significant difference was observed in serum ECP levels between these groups, suggesting an enhanced elimination of ECP during attack. Serum alpha-2 macroglobulins, which bind to ECP and may function as scavengers for ECP, were not significantly different in these group. These results suggest that serum ECP levels may not be a direct indicator of eosinophil activation or degranulation in the pathogenesis of asthma.

[Japanese guideline for the diagnosis and management of bronchial asthma (1998)--its results and reversion].

Japanese guideline for the diagnosis and management of bronchial asthma was initially reported in 1998 and revised in 2000. This guideline was based on two former guidelines which were made by Japanese Allergology Society in 1993 and NIH.NHLBI in 1995 (GINA). New version of this guideline in 2000 pointed that the efficacy and adverse reaction of leukotriene receptor antagonists, the effectiveness of new inhaled corticosteroid (fluticasone propionate), and transdermal administration of beta-2 stimulant (tulobuterol hydrochloride). The precise evaluation of this guideline in terms of propriety, reliability, applicability and so on was not performed.

[Advance in eosinophil chemotaxis assay method--automatic count of migrated cells by the image analyzing system in the Boyden method].

Eosinophils, which are prominent inflammatory cells in the asthmatic airway, are attracted to the airway by several chemoattractants. At present, eosinophil chemotaxis is studied employing the Boyden Millipore chamber system in vitro. In the Boyden method, the number of migrated cells are evaluated by direct microscopic observation of individual cells. This microscopic procedure usually requires much time and it is difficult to obtain objective results. Therefore, we have developed a new fractional measurement technique, using the image analyzing system connected with a color video camera and a computer for counting the eosinophils which have migrated into a filter. Using this system with the Boyden method, migrated cells were observed more objectively and quickly. Therefore, this image analyzing system with the Boyden method, may be a useful technique for the fractional measurement of migrated eosinophils in a sample mixture of eosinophils and neutrophils.