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Y Washio

Publications and source records attributed to Y Washio.

34 records · Page 2Linked to original sources

Risk factors for adverse systemic reactions occurring during immunotherapy with standardized Dermatophagoides farinae extracts.

The most serious problem in practical immunotherapy is the risk of occasional, potentially life-threatening adverse systemic reactions. Elucidation of the incidence of, and possible risk factors for, systemic reactions would have a profound effect on the decision about how to manage allergic rhinitis. The aim of this retrospective study was to document the incidence and risk factors of adverse systemic reactions during immunotherapy using standardized Dermatophagoides farinae (D. farinae) extracts for perennial allergic rhinitis. This study included 386 patients (22,722 injections) with perennial allergic rhinitis who had received immunotherapy with standardized D. farinae extracts in our clinics for the past 5 years. The incidence of systemic reactions was 6.22% per patient and 0.12% per injection. The time of onset of systemic reactions ranged from 3 to 30 min (mean 11.3 min) after injections. Our study has demonstrated that asthma, atopic dermatitis and a high level of IgE in serum, but not a high level of specific IgE in serum, are important high risk factors that may induce severe adverse systemic reactions in patients who receive immunotherapy for perennial allergic rhinitis. The incidence of systemic reactions in those who had a high level of IgE (higher than 1000 U/ml) and asthma and/or atopic dermatitis was 66.67% (12/18) per patient. Conversely, the incidence of systemic reactions in those who had none of the risk factors was 1.64% per patient. Thus, the rate of systemic reactions is thought to be reduced by 75% if patients with high risk factors are strictly excluded from immunotherapy for allergic rhinitis.

Allergens↗

The herbal medicine shoseiryu-to inhibits allergen-induced synthesis of tumour necrosis factor alpha by peripheral blood mononuclear cells in patients with perennial allergic rhinitis.

The herbal medicine shoseiryu-to is an effective agent in the treatment of allergic rhinitis. However, the mechanism by which it exerts its action in improving patient symptoms remains unclear. It might affect the allergen-induced TH1 and/or TH2 responses. This study investigated whether the herbal medicine could affect cytokine synthesis by peripheral blood mononuclear cells (PBMCs) in response to the major Dermatophagoides farinae (D. farinae) allergen, Der f 1. PBMCs were obtained from 15 patients with perennial allergic rhinitis due to D. farinae, and were stimulated for 96 h with 10 micrograms/ml Der f 1 in the presence or absence of 45 mg/ml shoseiryu-to. The culture supernatants were harvested to determine the synthesis of IgE, interleukin 5 (IL-5), IL-6, IL-10, interferon-gamma (IFN-gamma) and tumour necrosis factor alpha (TNF-alpha). The agent did not affect the allergen-induced synthesis of IL-5, IL-6 and IFN-gamma, but somewhat decreased the synthesis of IgE and IL-10. This study highlighted an interesting pharmacological action of shoseiryu-to to substantially inhibit the allergen-induced synthesis of TNF-alpha. Our study suggests that the shoseiryu-to may alleviate nasal symptoms in allergic rhinitis through control of the allergen-induced inflammatory process.

Allergens↗

Suplatast tosilate affects the initial increase in specific IgE and interleukin-4 during immunotherapy for perennial allergic rhinitis.

Suplatast tosilate can inhibit IL-4 production and suppress IgE synthesis in vitro. However, the theory that the agent causes changes in production of IL-4 and IgE in vivo has little experimental support. Immunotherapy could decrease the specific IgE response, but such a favourable effect is only possible with prolonged therapy after an initial increase in specific IgE. The use of suplatast tosilate together with immunotherapy may blunt the initial rise in specific IgE and decrease serum levels of specific IgE more quickly. Eighty-three adult patients with perennial allergic rhinitis due to Dermatophagoides farinae (D. farinae) were treated for 6 months with one of 3 treatments. Seventeen patients were treated with oral administration of 300 mg/day suplatast tosilate alone. Forty-six patients were treated with immunotherapy using standardized D. farinae alone. Twenty patients were treated with immunotherapy together with concurrent oral administration of 300 mg/day suplatast tosilate. Serum samples were collected 3 times from each patient, at enrollment, at 3 months and at 6 months after enrollment. Oral administration of suplatast tosilate for 3 and 6 months significantly decreased serum levels of IL-4 and specific IgE, and the rate of decrease in specific IgE correlated significantly with the rate of decrease in IL-4. The rates of decrease in IL-4 and specific IgE at 3 and 6 months were significantly greater in the patients treated with suplatast tosilate and immunotherapy than in those treated with immunotherapy alone. In conclusion, suplatast tosilate is able significantly to decrease serum levels of IL-4 and specific IgE, and the use of the drug together with immunotherapy can blunt the initial increase in specific IgE during the first 6 months of immunotherapy.

Adult↗

Cry j 1-induced synthesis of interleukin-5 and interferon-gamma by peripheral blood mononuclear cells of patients with seasonal allergic rhinitis due to Japanese cedar pollens.

This study comprised 130 adult patients with Japanese cedar pollen-specific IgE in the serum and 15 non-atopic individuals. Eighteen patients had no seasonal aggravation of nasal symptoms during the pollen season in 1998 (asymptomatic group). Forty-two patients had not been treated previously with immunotherapy and were treated with antihistamine tablets during the pollen season in 1998 (medication group). Sixty-one patients had undergone variable periods of immunotherapy using pollen extracts, and they were further divided into a good-IT group who responded markedly to immunotherapy and a poor-IT group who responded poorly to immunotherapy. The remaining nine patients had been treated with immunotherapy for more than 12 years and all of them had stopped immunotherapy by the end of May 1997 because they had no nasal symptoms for the last three pollen seasons and were considered to be cured of seasonal allergic rhinitis (cure group). Peripheral blood mononuclear cells (PBMCs) were collected from each subject during the cedar pollen season in 1998 and were stimulated for 96 h with 10 micrograms/ml Cry j 1. The concentrations of interleukin-5 (IL-5) and interferon-gamma (IFN-gamma) in the culture supernatant were determined using an enzyme-linked immunosorbent assay. The levels of IFN-gamma did not differ significantly among the non-atopic group, the asymptomatic group, the medication group, the poor-IT group and the good-IT group. The level of IL-5 in the asymptomatic group was not different from that in the non-atopic group. The levels of IL-5 in the medication group, the good-IT group and the poor-IT group were significantly higher than in the non-atopic group. The level of IL-5 in the good-IT group, but not in the poor-IT group, was significantly lower than in the medication group. The level of IL-5 in the cure group was not significantly different from in the non-atopic group, and the level of IFN-gamma in the cure group was significantly lower than in the non-atopic group. In conclusion, immunotherapy can decrease the pollen allergen-induced synthesis of IL-5, but not of IFN-gamma, and this immunological modulation is involved in the working mechanism of immunotherapy related to its clinical efficacy. A tolerance or anergy of both TH1 and TH2 cells under allergen stimulation may be an immunological indication of cure after the treatment of seasonal allergic rhinitis. Thus, the suppression of synthesis of IL-5 and IFN-gamma by allergen-stimulated PBMCs is likely to be a reliable criterion for a possible cure of seasonal allergic rhinitis after immunotherapy.

Adult↗

Seasonal increase in specific IgE in serum induced by natural Japanese cedar pollen exposure in asymptomatic and symptomatic sensitized individuals.

The aim of this study was to determine whether there is a difference in the specific IgE response to pollen exposure between asymptomatic and symptomatic subjects who were already sensitized to Japanese cedar pollen. Sixty-four subjects with detectable serum levels of cedar pollen-specific IgE, which were apparent even before the pollen season in 1997, were enrolled in the study. Thirty-five had typical symptoms of seasonal allergic rhinitis during the pollen season in 1997 (symptomatic group) and the remainder had no seasonal aggravation during the pollen season in 1997 (asymptomatic group). Serum samples were collected twice from each subject, before and during the pollen season in 1997, to determine specific IgE by the lumiward immunoassay system. In both groups, the serum levels of specific IgE during the pollen season were significantly higher than those before the pollen season, and the rates of seasonal increase in specific IgE did not differ significantly between the groups. In conclusion, the specific IgE response during the pollen season is not a hallmark of clinical allergy and does not discriminate between symptomatic and asymptomatic individuals sensitive to the pollen.

Allergens↗

Clinical evaluation of lumiward immunoassay system for detection of specific IgE associated with allergic rhinitis.

The detection of specific IgE is a critical prerequisite for both the definitive diagnosis and the therapeutic strategy of allergic rhinitis and other allergic disorders. The aim of the present study was thus to evaluate the clinical significance of the solid phase capture system (CAP) and the lumiward immunoassay system (LMD) in the diagnosis of allergic rhinitis due to Dermatophagoides farinae (D. farinae) and Japanese cedar (Cryptomeria japonica) pollens. The specificity of both the CAP and the LMD in the detection of D. farinae-specific IgE and Japanese cedar pollen-specific IgE was 100%. The sensitivity to detect D. farinae-specific IgE was 95.76% in the skin test, 86.53% in the CAP and 88.53% in the LMD, respectively. The combination of the nasal provocation test and the CAP substituted for the skin test resulted in correct diagnoses for 98.25% of the patients, and the combination of the nasal provocation test and the LMD substituted for the skin test resulted in correct diagnoses for 98.00% of the patients. Therefore, the diagnostic significance of the LMD for perennial allergic rhinitis is likely to be equal to that of the CAP. The sensitivity to detect Japanese cedar pollen-specific IgE was 94.50% in the skin test, 84.47% in the CAP, and 96.76% in the LMD, respectively. The sensitivity of the CAP in the detection of Japanese cedar pollen-specific IgE was inferior to that of the skin test, but the sensitivity of the LMD in the detection of pollen-specific IgE was somewhat superior to that of the skin test. In addition, the combination of the nasal provocation test and the CAP substituted for the skin test resulted in correct diagnoses for 98.38% of the patients, whereas the combination of the nasal provocation test and the LMD substituted for the skin test resulted in correct diagnoses for 100% of the patients. Therefore, the diagnostic significance of the LMD for seasonal allergic rhinitis due to Japanese cedar pollens is probably larger than that of the CAP. In conclusion, the LMD may be a better "gold standard" for the detection of Japanese cedar pollen-specific IgE than the skin test, and the combination of the nasal provocation test and the LMD is a better diagnostic tool for the detection of Japanese cedar pollen-induced seasonal allergic rhinitis than the combination of the nasal provocation test and the skin test or the CAP.

Allergens↗

Nitrogen dioxide compromises defence functions of the airway epithelium.

The effect of nitrogen dioxide (NO2) exposure on airway epithelial defence functions, such as ciliary activity, mucociliary transport velocity and junctional barrier function, remains to be elucidated. Our study investigates the effect of 24-h exposure to 3.0 ppm of NO2 on the airway epithelial defence functions in the healthy rabbit. Fifty-two healthy rabbits were exposed to 3.0 ppm of NO2 (NO2 group) or pure air (control group) for 24 successive hours in exposure chambers. After completion of the exposure sequence, the ciliary activity in the trachea was examined by a photoelectric method, the mucociliary transport velocity in the trachea by an endoscopic method and epithelial permeability of the trachea to fluorescein isothiocyanate-dextrans (FD-70s; molecular weight: 70,000 daltons) by an in vitro tracheal sac method. In the NO2 group, all epithelial defence functions, including ciliary activity, mucociliary transport velocity and epithelial permeability were significantly inferior to those in the control group. Although there was considerable overlap in the parameters examined between the two groups, approximately two-thirds of the animals were susceptible to 24-h exposure to 3 ppm of NO2. Dysfunction of both the junctional barrier and the mucociliary system could allow easier entry of allergen molecules to the airway parenchyma, where immunocomponent cells exist. NO2 might be involved to some extent in the clinical manifestation of airway allergic disorders through epithelial dysfunction.

Air Pollutants↗

Chemical microdetermination of heparin in plasma.

A new, simple, and highly sensitive method for the determination of heparin has been established. Heparin was first converted into unsaturated disaccharides through the action of heparin lyases I, II, and III. A major trisulfated unsaturated disaccharide product results, consistent with structural analysis of a number of pharmaceutical heparins using one- and two-dimensional 1H NMR spectroscopy. This disaccharide was analyzed by HPLC using fluorometric postcolumn derivatization. The correlation between the amount of this trisulfated unsaturated disaccharide and anticoagulant activity of heparin as measured by anti-IIa was determined. The analysis of these pharmaceutical heparins showed a linear correlation between both HPLC and bioassay. This HPLC method was then applied to a pharmacokinetic study of heparin intravenously administered to rabbits.

Animals↗

Serum levels of specific IgE, soluble interleukin-2 receptor, and soluble intercellular adhesion molecule-1 in seasonal allergic rhinitis.

BACKGROUND: There is increasing evidence that soluble interleukin-2 receptor (sIL-2R) might reflect T cell activation in vivo and soluble intercellular adhesion molecule-1 (sICAM-1) might reflect the ongoing inflammatory response in the inflamed site. OBJECTIVE: The aim of this study was to determine the effect of antihistamine tablets and allergen-specific immunotherapy on the seasonal changes in specific IgE, sIL-2R, and sICAM-1 in the serum of patients with seasonal allergic rhinitis. METHODS: This prospective study included 99 patients with seasonal allergic rhinitis due to Japanese cedar pollens and 27 nonatopic healthy volunteers. The patients were divided into an antihistamine-treated group and an immunotherapy group. Serum samples were collected before and during the pollen season from each patient to determine specific IgE, sIL-2R, and sICAM-1. RESULTS: Levels of sIL-2R before the pollen season did not differ significantly among the nonatopic group, the antihistamine-treated group, and the immunotherapy group. The levels of sICAM-1 before the pollen season were significantly higher in the antihistamine-treated group and in the immunotherapy group than in the nonatopic group. Seasonal increase in specific IgE was significant in the antihistamine-treated group regardless of their clinical outcomes. In contrast, significant increase in specific IgE was observed during the pollen season in poor responders but not in good responders to immunotherapy. Serum levels of sIL-2R and sICAM-1 were significantly increased during the pollen season in poor responders of the antihistamine-treated group and the immunotherapy group. On the other hand, neither seasonal increase in sIL-2R nor sICAM-1 was significant in good responders of the antihistamine-treated group and the immunotherapy group. CONCLUSIONS: Serum levels of sICAM-1 are higher in patients with seasonal allergic rhinitis, even outside of the pollen season when the allergen does not naturally exist. Seasonal changes in serum sICAM-1 as well as sIL-2R and specific IgE are probably objective markers to indicate the clinical efficacy of antihistamines and immunotherapy on seasonal allergic rhinitis.

Adult↗

Immunotherapy affects the seasonal increase in specific IgE and interleukin-4 in serum of patients with seasonal allergic rhinitis.

This study was designed to determine seasonal changes in cytokines, soluble CD23 and specific IgE in the serum of patients with seasonal allergic rhinitis, and the effect of immunotherapy on these seasonal changes. Fifty-four patients with seasonal allergic rhinitis caused by Japanese ceder pollens were divided into a medication group and an immunotherapy group. The patients of the medication group were treated with non-sedating antihistamines alone during the pollen season. The patients of the immunotherapy group had been treated for variable periods (mean, 5.0 +/- 3.2 years) with immunotherapy using japanese cedar pollen antigens. Serum samples were collected before and during the pollen season from each patient, to determine specific IgE, interleukin-4 (IL-4), interferon-gamma (IFN-gamma) and soluble CD23 levels in serum. A significant increase in specific IgE and IL-4 and a significant decrease in IFN-gamma were observed during the pollen season in the medication group. In contrast, in the immunotherapy group, none of specific IgE, IL-4 and IFN-gamma was significantly changed following natural exposure to pollens. However, these effects were not significant in patients undergoing immunotherapy for 3 or fewer years. Seasonal rates of increase in specific IgE and IL-4 differed significantly between good responders and poor responders to immunotherapy, but seasonal rates of decrease in IFN-gamma did not. A seasonal rate of increase in soluble CD23 was significantly correlated with a seasonal rate of increase in specific IgE, in both the medication and the immunotherapy groups. The seasonal rate of increase in soluble CD23 was significantly smaller in the good responders than in the poor responders to immunotherapy. In conclusion, pollen immunotherapy reduces the seasonal increase in specific IgE, IL-4 and soluble CD23 in serum, and in addition switches the seasonal preferential activation of Th-2 cells to reciprocal activation of Th-1 cells with treatment over several years. It is likely that the mechanisms responsible for the clinically beneficial effects of immunotherapy principally involve the modulation of Th-2 rather than Th-1 cytokines.

Adult↗

Soluble intercellular adhesion molecule-1 level in sera is elevated in perennial allergic rhinitis.

Soluble intercellular adhesion molecule-1 (sICAM-1) in sera was measured in some allergic disorders, but serum sICAM-1 levels in perennial allergic rhinitis remain to be determined. Our study was aimed at elucidating whether the serum sICAM-1 levels in patients with perennial allergic rhinitis are different from those in nonatopic healthy volunteers and whether immunotherapy can modulate sICAM-1 levels. Serum sICAM-1 was determined in 20 nonallergic volunteers and 137 patients with perennial allergic rhinitis by a sandwich enzyme-linked immunosorbent assay. Our study demonstrated that the level of sICAM-1 in untreated patients is significantly elevated, as compared with nonatopic subjects. Immunotherapy could decrease sICAM-1 in perennial allergic rhinitis, but this suppressive effect became apparent only after many years of immunotherapy. In patients on immunotherapy, a close correlation was observed between sICAM-1 and nasal symptom scores. To take these lines of evidence together, a decrease in sICAM-1 might be related to the working mechanism of immunotherapy, and serum sICAM-1 could be used to monitor the effect of immunotherapy.

Adult↗

Effect of immunotherapy on seasonal changes in serum-specific IgE and IgG4 in patients with pollen allergic rhinitis.

Serum specific IgE and IgG4 in 70 patients with seasonal rhinitis caused by Japanese cedar pollens were determined before and during the pollen season. Seasonal increase rate in specific IgE was significantly smaller in the immunotherapy patients than the pharmacotherapy patients, and seasonal increase in specific IgG4 was significant in the immunotherapy patients only. Seasonal increase rate in specific IgE was not significantly different between the patients who responded markedly to short-term immunotherapy and those who did not. On the other hand, seasonal increase rate in specific IgG4 was significantly different between them. In contrast, seasonal increase rate in specific IgE was significantly smaller in the patients who showed marked response to the long-term immunotherapy than those who did not show marked response to the long-term immunotherapy, but seasonal increase rate in specific IgG4 was not significantly different between them. In conclusion, our results suggest that modulation of specific IgG4 response and specific IgE response might be involved in the early and late symptom relief during immunotherapy, respectively. However, further studies might be necessary to definitively establish the clinical roles of specific IgE and specific IgG4 in immunotherapy.

Adolescent↗

Simultaneous determination of dermatan sulfate and oversulfated dermatan sulfate in plasma by high-performance liquid chromatography with postcolumn fluorescence derivatization.

A chemical method for the determination of dermatan sulfate (DS) and oversulfated dermatan sulfate has been developed and applied to the pharmacokinetic study of these polysaccharides in experimental animals. The analytical procedure includes a simple preparation step of administered DS and oversulfated DS from blood plasma, HPLC for the separation and detection of DS and oversulfated DS using an Asahipak NH2P-50 column, fluorometric reaction of the polysaccharides with guanidine in a strong alkaline medium. DS and oversulfated DS were extracted from plasma by treating it with proteinase to remove plasma proteins and recovered with endogenous plasma glycosaminoglycans by ethanol precipitation. Finally, DS and oversulfated DS were analyzed by fluorometric HPLC. The detection limits of DS and oversulfated DS were 10 and 20 ng, respectively. Furthermore, we demonstrated that artificial oversulfation of DS increased its biological half-life after intravenous administration to rats.

Animals↗

Serum level of interleukin-4 in patients with perennial allergic rhinitis during allergen-specific immunotherapy.

Interleukin-4 (IL-4) may play a central role in the IgE synthesis system, the development of Th-2-like cells, and co-ordination as well as the persistence of airway inflammatory process in allergic disorders. Therefore, IL-4 plays a key role in airway allergic disorders. This study aimed at investigating the serum concentrations of IL-4 in patients with perennial allergic rhinitis, with special reference to the possible changes and the clinical relevance following long-term immunotherapy. The study has demonstrated that the serum level of IL-4 in allergic rhinitis patients before immunotherapy is significantly higher than that in non-atopic individuals. However, the serum IL-4 level in allergic rhinitis patients did not decrease following anti-allergic medications but significantly decreased following immunotherapy. The percentage decrease in IL-4 was correlated significantly with the percentage decrease in specific IgE antibodies following long-term immunotherapy. Immunotherapy also significantly decreased specific IgE anti-bodies, but this reduction in specific IgE antibodies was not significantly correlated with the clinical improvement. In contrast, the percentage decrease in serum IL-4 was significantly correlated with the percentage decrease in symptomatic scores. The authors interpret these data to mean that immunotherapy alters T-cell cytokine profiles in the long-term, and a decline of IL-4 following immunotherapy could modulate not only production of specific IgE antibodies but also inflammatory cellular events, leading to symptomatic relief in allergic rhinitis.

Adolescent↗