Biomedical subjects

C Okada

Publications and source records attributed to C Okada.

At least 37 records · Page 2Linked to original sources

PubMed1995

[Clinical study of bronchial asthma in adult, intractable asthmatics after introduction of guideline therapy].

Introduction of Guideline for asthma treatment proposed by the committee of Japanese allergology have a tremendous impact on patients with bronchial asthma. Intractable asthmatics who have had to take some oral steroid to overcome disease severity, may have also some merit by this treatment, so that some of them might be no longer considered as intractable asthmatics. To clarify this, multicenter study was conducted. In this study, a case who have had more than 5 mg of prednisolone and/or 800 mu g of beclomethasone dipropionate throughout the year, was diagnosed as intractable asthmatics. In 845 case, 14.7%, 123 cases were diagnosed as intractable. These cases were significantly to be non-atopic and adult onset. Also, they have a significant tendency to be deteriorated by infection and careless drug administrations. Using the multiquantification method to examine the most powerful factor on intractable asthmatics, type of asthmatics was the most important and the past history of severe attack was the second. When intractable asthmatics diagnosed mainly by their BDP usage (BDP-intractable) were compared with intractable diagnosed by oral PSL (PSL-intractables), BDP-intractables were significantly atopic compared to PSL-intractables.

Asthma↗

PubMed1994

Effect of cetirizine on human eosinophil superoxide generation, eosinophil chemotaxis and eosinophil peroxidase in vitro.

Cetirizine, a potent H1-antagonist, has been reported to inhibit eosinophil migration into human skin. We, therefore, further evaluated the effect of cetirizine on eosinophil function, including superoxide anion generation, chemotaxis, and eosinophil peroxidase (EP) release. In allergic subjects, superoxide anion generation 60 min after platelet-activating factor (PAF) activation was inhibited by concentrations of cetirizine ranging from 0.01 to 1 microgram/ml (2.612 x 10(-8) to 2.612 x 10(-6) M). No significant inhibition was observed in normal subjects. PAF (10(-6) M)-induced eosinophil chemotaxis was also inhibited by cetirizine. In allergic subjects, percent inhibitions were 47.5 +/- 6.1% at 0.01 microgram/ml, 50.8 +/- 5.1% at 0.1 microgram/ml and 58.9 +/- 6.4% at 1 microgram/ml of cetirizine. In allergic subjects, N-formyl-methionyl-lencyl-phenylalanine induced eosinophil chemotaxis was inhibited by cetirizine, although EP release was not. These results suggest cetirizine has effects on eosinophils which can not be explained by H1-blockade alone.

Adult↗

PubMed1994

[Therapeutic potential of sparfloxacin for preventing mycobacterial infections].

We studied the therapeutic potential of utilizing sparfloxacin (SPFX), a newly developed quinolone, to prevent various mycobacterial infections. The in vitro activity of SPFX as a preventive agent for various mycobacteria was determined using the actual count method on Ogawa egg medium. The minimal inhibitory concentrations (MICs) of SPFX were as follows: ofloxacin-sensitive M. tuberculosis, 0.16-0.32 microgram/ml; ofloxacin-resistant M. tuberculosis, 0.63-2.5 micrograms/ml; M. avium; 0.63-10 micrograms/ml (MICs were equal or less than 1.25 micrograms/ml in seven out of 11 strains); M. intracellulare, 2.5-10 micrograms/ml (MICs were equal or more than 10 micrograms/ml in 17 out of 23 strains); M. kansasii, < or = 0.08-0.16 microgram/ml; M. fortuitum, < or = 0.08 microgram/ml; M. chelonae subsp. abscessus, > 10 micrograms/ml; M. chelonae subsp. chelonae, 0.63 microgram/ml; M. scrofulaceum, < or = 0.08 microgram/ml; M. nonchromogenicum, 1.25 micrograms/ml; M. xenopi, < or = 0.08 microgram/ml; M. gordonae, < or = 0.08 microgram/ml. The average serum concentrations of SPFX during the period of multiple oral administration (200 mg once a day) were 0.35 +/- 0.16 microgram/ml before administration, 0.67 +/- 0.32 microgram/ml after one hour, 1.13 +/- 0.21 microgram/ml after two hours, 1.27 +/- 0.32 microgram/ml after four hours and 1.31 +/- 0.34 micrograms/ml after six hours. These results indicate that SPFX has a strong therapeutic potential to prevent infections due to M. tuberculosis, M. kansasii, M. fortuitum, M. chelonae subsp. chelonae, M. scrofulaceum, M. xenopi and M. gordonae. Moreover, it may be expected to be a promising agent against infections due to ofloxacin-resistant M. tuberculosis, M. avium and M. nonchromogenicum.

Anti-Infective Agents↗

PubMed1994

[Henoch-Schönlein purpura associated with pulmonary tuberculosis].

A 34-year-old man was admitted to our hospital because of cough and fever. Chest radiograph showed multiple cavities mainly on the right lung. His sputum was positive for acid-fast bacilli on smear, and he was treated with daily isoniazide, rifampicin and streptomycin. Antituberculous treatment was successfully performed, so acid-fast bacilli of his sputa disappeared on smear and culture. Five months later, he developed a purpuric lesions over both legs accompanied by low grade fever and arthralgia, but proteinuria and abdominal pain could not be observed. Laboratory findings showed a normal platelet count and a normal bleeding time. High levels of serum IgG, IgA, C3 and C4 were evident. ASLO and ASK titer were elevated and they markedly increased within two weeks. A direct invasion of the vessel wall by tubercle bacilli is deniable because antituberculous treatment was successfully continued. Henoch-Schönlein purpura was diagnosed judging from these findings. High levels of ASLO and ASK suggest a preceding streptococcal infection for developing purpura but a possible infectious focus could not be identified. He was treated with 15 mg of prednisolone daily for two weeks and the lesion was subsided. The effect of prednisolone suggests that a subsequent antigen-antibody interaction caused by a streptococcal infection may participate in the formation of the purpura.

Adult↗

PubMed1993

Inhibitory effects of formoterol on platelet-activating factor induced eosinophil chemotaxis and degranulation.

A new long-acting beta 2-agonist, formoterol, has been reported to have a greater efficacy and duration of action in asthmatic patients as compared to conventional beta 2-agonists. We recently demonstrated that formoterol inhibited antigen-induced late asthmatic response (LAR) and accompanying airway eosinophilia in guinea pigs. In this study, we investigated the direct effect of formoterol in vitro on human eosinophil function, focusing on platelet-activating factor (PAF)-induced eosinophil chemotaxis and eosinophil cationic protein (ECP) release. Purified normodense eosinophils were separated by discontinuous gradient from 12 mild asthmatic patients. Formoterol in concentrations of 1-100 microM significantly inhibited PAF-induced eosinophil chemotaxis in a dose-dependent manner with a concentration of drug required to produce 50% inhibition (IC50) of 10.16 microM; % inhibition: 22.9 +/- 13.0% (1 microM), 51.6 +/- 12.7% (10 microM), 75.0 +/- 11.3% (100 microM). When formyl-methionyl-leucyl-phenylamine (FMLP) was used as a chemoattractant, a similar inhibition of eosinophil chemotaxis by formoterol was observed; % inhibition: 13.1 +/- 5.0% (1 microM). 47.7 +/- 7.6% (10 microM), 65.5 +/- 16.5% (100 microM). A conventional beta 2-agonist, salbutamol, at doses to 100 microM did not show any inhibitory effects on PAF-induced eosinophil chemotaxis. Formoterol in concentrations of 1-100 microM also significantly inhibited PAF-induced ECP release from eosinophils; % inhibition: 21.7 +/- 9.0% (1 microM), 39.3 +/- 7.4% (10 microM), 39.6 +/- 8.4% (100 microM). In the presence of phosphodiesterase inhibitors, theophylline or isobutylmethyl xanthine (IBMX), the inhibition by formoterol on PAF-induced ECP release was enhanced.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Effect of formoterol on superoxide anion generation from bronchoalveolar lavage cells after antigen challenge in guinea pigs.

It is well known that antigen challenge of sensitized subjects can induce an immediate and late asthmatic response, airway eosinophilia, and hyperreactivity. Using our modified guinea pig asthma model, we investigated the superoxide anion generation from eosinophils and macrophages recovered from bronchoalveolar lavage (BAL) 24 h after antigen (ovalbumin) challenge. We also investigated the effect of formoterol, a new long-acting selective beta 2-agonist, on these functions. Antigen challenge increased the total cell counts and the ratio of eosinophils in BAL. Eosinophils and macrophages were collected using discontinuous density centrifugation. Antigen challenge enhanced superoxide anion generation from eosinophils, from 5.39 +/- 1.08 to 13.19 +/- 1.95 nmol 60 min after phorbol myristate acetate (PMA) (1 ng/ml) activation, and 0.22 +/- 0.49 to 3.34 +/- 1.67 nmol 40 min after platelet-activating factor (PAF) (10(-6) M) activation. Formoterol treatment before antigen challenge prevented these enhancements. Superoxide anion generation from macrophages was also enhanced by antigen challenge, from 6.57 +/- 0.76 to 10.66 +/- 0.88 nmol 60 min after PMA activation, and 4.20 +/- 1.17 to 6.63 +/- 0.64 nmol 60 min after PAF activation. Formoterol, however, failed to inhibit enhancement of superoxide anion generation from macrophages. These results show antigen challenge of sensitized guinea pigs induces an increase of eosinophils and macrophages in BAL and enhances the functional characteristics of both cells. Formoterol had inhibitory effects on the enhancement of superoxide anion generation from eosinophils but did not have this effect on macrophages.

Analysis of Variance↗

PubMed1993

[Predicting the clinical efficacy of house dust mite immunotherapy in bronchial asthmatics by multiple quantification analysis type II].

To predict the clinical efficacy of house dust mite immunotherapy (IT) for bronchial asthma, clinical factors before IT were analyzed in relation to clinical efficacy. The factors analyzed were severity, skin test threshold, age at which IT was started, duration of asthma, onset of asthma, FEV1.0%, serum IgE levels before IT, the presence of allergens other than HD, family history of atopic disease, complications with other allergic diseases, sex, seasonality of attacks and the maintenance dose. The clinical efficacy ranging from good response to no benefit was well discriminated by this analysis. The rate of discrimination was about 90%, indicating clinical usefulness of the method. In this study, skin test threshold seemed to be the most important factor, followed by FEV1.0%. While severity and age have been reported to be important, those who show good FEV1.0% and low skin test threshold, regardless of their severity or age, may be good candidates for IT.

Adolescent↗

PubMed1993

Density change of neutrophils from allergic subjects by granulocyte-macrophage colony stimulating factor.

We investigated neutrophil density change by platelet activating factor or granulocyte-macrophage colony-stimulating factor (GM-CSF). Although PAF significantly converted neutrophil density, there was no significant difference in density change between allergic subjects and normal subjects by platelet activating factor. Neutrophils from allergic subjects, however, were significantly converted by GM-CSF when compared with neutrophils from normals (P < .05). We conclude that neutrophils from allergic subjects are more sensitive to density change by GM-CSF than neutrophils from normal subjects. This might be due to preactivation or priming by biologic agents.

Adult↗

PubMed1993

[Flow cytometry study on purification of human eosinophils and cell function].

The eosinophil is a well-known leukocyte acting as an effector cell in the allergic reaction mechanism. The application of appropriate materials has led to more exact results from allergic examinations. In an effort to further improve analysis, we established a novel purification method for eosinophils using the flow cytometry (PCM) of peripheral blood and bronchoalveolar lavage fluid (BALF) leucocytes from healthy and allergic subjects. We examined the function of these cells in chemotaxis by platelet activating factor (PAF) and recombinant human (rh) IL-5. We obtained following results. First, we were able to separate human eosinophils containing autofluorescence substance, which was detectable by FCM employing a 450 nm argon ion laser. Second, the purity and recovery rate of the eosinophils were 90.1 +/- 4.2% and 32.1 +/- 7.6% in the healthy subjects who had no peripheral eosinophilia (< 6%) and 93.7 +/- 4.4% and 37.2 +/- 7.5% in the allergic subjects who had eosinophila (> 6%). A relationship was readily apparent between the peripheral and purified eosinophil counts in the healthy subjects (r = 0.62). Autofluorescence of the eosinophil fraction on PCM was further found to be decreased in patients with marked eosinophilia because of an increase in hypodense eosinophils. Third, highly purified eosinophils (76%) were also obtained from the 6.5% eosinophils present in the bronchoalveolar lavage fluid of one bronchial asthma patient. Fourth, the maximal chemotaxis of these eosinophils was shown at 10(-6) M of platelet activating factor (PAF) and at 1 micrograms/ml of IL-5 in a dose-dependent manner. This activity in allergic patients was accelerated compared with that in healthy subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

[The measurement of superoxide generation and eosinophil peroxidase (EPO) from eosinophils].

Eosinophils play an important role in the field of allergy, and release several kinds of granule proteins, leukotrien and superoxide. The most popular method to measure superoxide is utilizing SOD-inhibitable reduction of ferricytochrome c. And recently, the microplate reader enables us to measure superoxide generation from eosinophils more easily using this method. To measure superoxide, we must pay attention to obtain a high purity of eosinophils and not to damage cells. It is also possible to measure eosinophil peroxidase (EPO) using the microplate reader. We are measuring EPO with colorimetric assay using OPD (o-phenylenediamine). OPD is specific to EPO and has no cross reaction to myeloperoxidase. We, now have numerous methods to evaluate eosinophil function, so a selection must be made to select the most correct method.

Cells, Cultured↗

PubMed1992

The effect of WEB 2086 on PAF-induced eosinophil chemotaxis and LTC4 production from eosinophils.

We investigated the effect of WEB 2086, a selective platelet-activating factor (PAF) receptor antagonist, on PAF-induced eosinophil chemotaxis and LTC4 production. WEB 2086 inhibited PAF-induced eosinophil chemotaxis in normals and asthmatics. To further determine if WEB 2086 is a selective PAF receptor antagonist, we examined the effect of WEB 2086 against formyl-methionyl-leucyl-phenylalanine (fMLP)-induced or eosinophil chemotactic factor of anaphylaxis (ECF-A)-induced eosinophil chemotaxis. WEB 2086 did not have a significant inhibition against fMLP or ECF-A-induced eosinophil chemotaxis. These results suggest that WEB 2086 is a selective and potent inhibitor of PAF-induced eosinophil chemotaxis and LTC4 production from eosinophils, due to its antagonism of PAF-receptors.

Adult↗

PubMed1992

The effect of a selective alpha 2-adrenergic receptor antagonist (midaglizole) on the cyclic 3',5'-adenosine monophosphate production in human mononuclear cells.

A selective alpha 2-adrenergic antagonist, midaglizole, has been recently reported to have efficacy in patients with asthma. To understand the mechanisms, we investigated the effect of midaglizole on the cyclic 3', 5'-adenosine monophosphate (cAMP) production in human mononuclear cells (MNCs). MNCs were separated by a histopaque gradient from 10 normal subjects and 10 subjects with asthma. cAMP was measured by RIA kits. Midaglizole (10 mumol/L) significantly enhanced isoproterenol-induced cAMP production in both groups, although midaglizole (from 1 to 100 mumol/L) did not increase the cAMP production by itself. The percent increase in cAMP was more in subjects with asthma (183.8%) than in normal subjects (140.4%); however, the absolute increase was not different. Platelet-activating factor has been demonstrated to inhibit beta-agonist-induced cAMP production in several mammalian tissues, including human MNCs. Midaglizole also prevented platelet-activating factor-induced desensitization of the cAMP response to isoproterenol in MNCs. These findings suggest that midaglizole may be a useful additional agent for the therapy of bronchial asthma through an enhancement of the cAMP production.

Adrenergic alpha-Antagonists↗

PubMed1992

The effect of formoterol on the late asthmatic phenomena in guinea pigs.

We investigated the effects of formoterol, a new, long-acting, selective beta 2-adrenoceptor agonist, on the antigen-induced late asthmatic response (LAR) and airway inflammation in guinea pigs. Animals were sensitized by exposure to aerosolized ovalbumin (2% in saline). After antigen challenge, preceded by administration of an H1-receptor antagonist, specific airway conductance was measured with a two-chambered whole-body plethysmograph. An aerosolized solution of formoterol, isoproterenol, or saline was inhaled 15 minutes before challenge. Bronchoalveolar lavage (BAL) was performed 24 hours after challenge. The provocative concentrations of histamine required to decrease specific airway conductance by 50% were obtained before challenge, at 24 hours, and at 72 hours after challenge. The LAR (52.7% +/- 7.7% of the baseline; p less than 0.02) was observed 6 to 8 hours after antigen challenge. An increased cellular influx in BAL (mainly eosinophils and macrophages) and an increased bronchial responsiveness to histamine occurred 24 hours after antigen challenge. Formoterol completely inhibited the LAR and the cellular increase in BAL; however, isoproterenol failed to prevent either the cellular infiltration or the LAR. Formoterol also decreased the antigen-induced increase in bronchial reactivity. These findings suggest that formoterol has inhibitory effects on the underlying inflammatory processes in antigen-induced asthma in addition to prolonged bronchodilation.

Administration, Inhalation↗

PubMed1992

Effect of terfenadine on neutrophil and eosinophil chemotactic activities after inhalation of platelet-activating factor in vivo and on neutrophil chemotaxis in vitro.

In this double-blind crossover study we evaluated the effect of terfenadine on the rise in neutrophil chemotactic activity (NCA) and eosinophil chemotactic activity (ECA) in serum induced by platelet-activating factor (PAF) inhalation in 8 asthmatics. Additionally, we examined the direct effect of terfenadine on neutrophil chemotaxis in vitro in 7 allergic subjects. NCA and ECA in serum after PAF inhalation and neutrophil chemotaxis were measured using a modified Boyden chamber method. An initial elevation of NCA after PAF inhalation was inhibited by terfenadine, but the effect was diminished after subsequent PAF inhalations. Terfenadine showed no effect on ECA. In vitro PAF- and fMLP-induced neutrophil chemotaxis were significantly inhibited by terfenadine. These results suggest that terfenadine may have antiallergic properties in addition to its H1 receptor blockade.

Administration, Inhalation↗

PubMed1992

Use of cetirizine to investigate non-H1 effects of second-generation antihistamines.

In addition to their increased potency as H1 blockers and their nonsedating effects, the second-generation antihistamines have other unusual and potentially beneficial properties. Evidence is accumulating from several laboratories that at least one of these agents under investigation, cetirizine, may be effective in inhibiting the late reaction. The Johns Hopkins group showed that during the cutaneous late phase response (LPR), histamine release was not altered by cetirizine, 20 mg, pretreatment. The most dramatic effect of cetirizine was attenuation of inflammatory cell migration into the chamber. Eosinophils, neutrophils, and basophils were reduced by about 75% during hours 6 to 8. It can be concluded that cetirizine influences the LPR by causing a reduction in the inflammatory cell infiltrate. Cetirizine, 10 mg, orally once a day also induced a significant decrease in the wheal and flare skin reactions caused by pollen, histamine, and compound 48/80. Cetirizine inhibited eosinophil recruitment and platelet-activating factor (PAF) in skin chambers 24 hours after pollen challenge. We and others have studied the mechanisms of this effect. The release of eosinophil peroxidase induced by PAF and formyl-methionyleucyl/phenylalanine was not attenuated by cetirizine. At therapeutic concentrations, however, cetirizine has a potent inhibitory action in vitro on eosinophil chemotaxis induced either by formyl-methionyleucyl/phenylalanine or PAF and also on IgE-dependent stimulation of platelets. In a separate study in patients with chronic urticaria, cetirizine markedly reduced both the immediate wheal and flare induced by PAF and the delayed reaction at six hours. These results suggest that cetirizine acts on eosinophil migration to inhibit the late reaction.

Cetirizine↗

PubMed1991

Role of lymphocytes in collagen induced arthritis.

We investigated the time related changes of lymphocyte subsets in the blood, regional lymph node and thymus during the development of collagen induced arthritis in mice. Flow cytometric analysis showed that Lyt2+ T, but not L3T4+ T cells in the blood or regional lymph node, was significantly reduced throughout the observation. The number of Lyt2+ T cells was decreased in lymph nodes of collagen immunized vs adjuvant controls while B cells were increased and L3T4+ T cells were not different. These might act as a potential factor for the onset of collagen induced arthritis. The reduction of Lyt2+ cells was not influenced by thymic T cell maturation; it is conceivable that the main immune organ is the regional lymph node.

Animals↗

PubMed1991

Variations in chemotaxis and chemokinesis of neutrophils of different densities from patients with allergic rhinitis.

We investigated chemotaxis and chemokinesis of neutrophils of different densities from normals and subjects with allergic rhinitis (AR). The chemotaxis of neutrophils with lower density was significantly increased compared with neutrophils with higher density in AR using fMLP (P less than .01) or PAF (P less than .05). In normal subjects, however, there was no significant difference in neutrophil chemotaxis of the two fractions. No significant difference was found in neutrophil chemokinesis of the two fractions from AR or normals. These results indicate that neutrophils with lower density from AR possess greater affinity to fMLP or PAF as compared with neutrophils with higher density and this may be relevant to the pathophysiology of AR.

Cell Movement↗

PubMed1990

Heterogeneity in chemotaxis of neutrophils with different densities.

We investigated N-formyl-Methionyl-Leucyl-Phenylalanine (fMLP)-induced chemotaxis of neutrophils with different densities. FMLP-induced (10(-8)M) chemotaxis of neutrophils with lower density were significantly reduced when compared to neutrophils with higher density (p less than 0.05). These findings imply a relationship between the neutrophil density and chemotaxis.

Adult↗