Biomedical subjects

H Okudaira

Publications and source records attributed to H Okudaira.

At least 19 recordsLinked to original sources

PubMed1992

Prolonged survival of MRL-lpr/lpr mice treated with Tripterygium Wilfordii Hook-F.

MRL-lpr/lpr mice were treated with Tripterygium Wilfordii Hook-F (TWHF), a Chinese herbal medicine successfully used for human rheumatoid arthritis. Dramatic prolongation of survival and the reduction of urinary protein were observed in mice treated with a high dose of TWHF (20 mg/kg, three times a week) compared to the control animals receiving solvent alone. A slight but significant reduction was also seen in the degree of lymphadenopathy and arthritis with the high dose treatment. Surprisingly, no significant difference was present in IgM rheumatoid factor and IgG anti-double-stranded DNA antibody levels or in the histopathology of lupus nephritis. These results indicate the dissociation of histopathological renal disease and the degree of proteinuria or the life span. Although further pharmacological analysis is required, TWHF might be potentially useful for diseases such as systemic lupus erythematosus or nephrotic syndrome.

Animals↗

PubMed1992

Hypersensitivity pneumonitis in athymic nude mice. Additional evidence of T cell dependency.

We previously demonstrated that C57 Black/6 mice develop lung lesions similar to human hypersensitivity pneumonitis (HP) by repeated transnasal administration of Thermoactinomyces vulgaris (Tv) antigen. To elucidate the role of T cells in the development of this disease, Tv antigen (90 micrograms/day) was transnasally administered to athymic nude C57 Black/nu/nu (nu) mice and their littermates (+/nu) three times a week for 3 wk. The nude mice developed minimal lung lesions, whereas their thymus-intact littermates (+/nu) showed changes equivalent to those in C57 Black/6. Changes in local inflammatory cell responses were evaluated by bronchoalveolar lavage, and increases in the numbers of lymphocytes and macrophages were significantly less severe in the nude mice than in the +/nu mice. Interestingly, the increase in polymorphonuclear leukocytes 6 h after the last antigen inoculation was equivalently seen in both groups. When spleen-derived T cells (more than 95% Thy-1.2+) from the sensitized +/nu mice were adoptively transferred to nude mice, the HP-like lesions in the recipients were found after Tv antigen challenge. These results suggest that Thy-1.2+ T cell-mediated immunity was necessary for the development of HP in this murine model.

Alveolitis, Extrinsic Allergic↗

PubMed1992

Specific measurement of a major mite allergen, Der f II, by an enzyme-linked immunosorbent assay system using monoclonal anti-Der f II antibodies.

An enzyme linked immunosorbent assay system using a monoclonal antibody, 15E11, specific for a major allergen Der f II in house dust mite, was developed. This system detected only Der f II in the presence of Der p II and other allergens. The Der f II contents in several house dust samples significantly correlated with the numbers of the mites in the same house dust samples (n = 14, r = 0.88, p < 0.001). These data showed that this system was useful for specific measurement of Der f II in house dusts.

Allergens↗

PubMed1992

[An autopsy case of sarcoidosis associated with renal failure].

A 62-year-old woman presented with uveitis and abnormal chest X-ray (bilateral hilar adenopathy). Skin biopsy in 1983 had revealed non-caseating epithelioid cell granuloma consistent with sarcoidosis. Her serum biochemical investigations and exploratory laparoscopy suggested nodular liver cirrhosis, but biopsy was not performed. Both blood urea nitrogen (BUN) and serum creatinine values were within normal limits. She received prednisolone therapy of 15 mg daily initially, and later a maintenance dose of 5 mg daily. In 1985, she complained of skin itching and her laboratory data revealed severe renal insufficiency (BUN 97 mg/dl, serum creatinine 12.2 mg/dl) and hypercalcemia (corrected serum calcium level: 11.5 mg/dl). Prednisolone treatment (40 mg daily) resulted in a dramatic improvement of renal function as well as other clinical abnormalities due to sarcoidosis, without any significant changes in liver function. She died of cerebral infarction in 1989. Autopsy showed interstitial nephritis with tubular calcinosis and hyalinized glomeruli. It is postulated that hypercalcemia due to sarcoidosis contributed to the renal failure in this patient. This case suggests that renal damage due to sarcoidosis may be reversible with appropriate corticosteroid therapy.

Female↗

PubMed1991

Food-dependent, exercise-induced anaphylaxis: a study on 11 Japanese cases.

Eleven patients with food-dependent, exercise-induced anaphylaxis were studied. Seven patients experienced anaphylactic symptoms only after eating certain foods, such as shellfish, wheat, and grape before exercise. In the remaining four patients, no specific food could be identified, but the act of eating itself predisposed to anaphylaxis. Their anaphylactic symptoms were all clearly distinguished from cholinergic urticaria by history. Patients who developed anaphylactic symptoms before 20 years of age (N = 7) were atopic themselves or had atopic first-degree relatives. Six patients had increased serum IgE levels, and IgE antibodies against the causative food allergens were detected by the skin prick test or RAST in four cases. In contrast, patients who developed the symptoms after 30 years of age (N = 4) appeared to have a less atopic background, and IgE levels were within normal range except in one case. Three of four patients in the latter group developed symptoms after ingesting food made of wheat followed by exercise. All patients were sensitive to wheat as determined by the skin prick test. In six of 11 patients, a considerable rise in plasma histamine concentration was observed after exercise challenge with treadmill alone, and food intake followed by exercise induced a further increase in one patient.

Adolescent↗

PubMed1991

T-cell-dependent accumulation of eosinophils in the lung and its inhibition by monoclonal anti-interleukin-5.

The transnasal administration of an extract of the parasite Ascaris suum to C57BL/6 mice for 3 weeks produced marked eosinophilia in the bronchoalveolar lavage (BAL) fluid. The oral administration of ciclosporin significantly suppressed the pulmonary eosinophilia. Athymic C57BL/6-nu/nu mice failed to develop pulmonary eosinophilia. These data indicate that the pulmonary eosinophilia caused by this parasite extract is T-cell-dependent. Genetically mast-cell-deficient (WB x C57BL/6) F1-W/Wv (W/Wv) mice developed marked eosinophilia in the BAL, which shows that mast cells are not necessary in the formation of lung eosinophilia in this model. Monoclonal antimurine interleukin-5 injected intraperitoneally clearly inhibited the infiltration of eosinophils in the lung, suggesting that T-cell-derived interleukin-5 is essential.

Animals↗

PubMed1991

Interleukin-4 gene expression and IgE responsiveness.

Interleukin-4 (IL-4) gene expression by stimulation with concanavalin A (Con A) in murine spleen cells was examined. The amount of IL-4 mRNA induced by Con A was greatest in spleen cells obtained from IgE high responder strains of mice. A trace amount of IL-4 mRNA was induced in spleen cells from IgE low responder (SJL) mice. The amount of IL-4 mRNA induced in spleen cells from an IgE intermediate responder (C57BL/6) was smaller than that from high responders, but significantly greater than that from low responders. Spleen cells from IgE nonresponders (SJA/9) developed only a negligible amount of IL-4 mRNA. IL-4 mRNA was detected in human peripheral blood mononuclear cells (PBMC) stimulated with Con A. The IL-4 gene expression seemed to be greater in PBMC obtained from highly atopic patients and was decreased in PBMC from individuals showing hypo-IgE immunoglobulinemia (less than 10 IU/ml). The results obtained in the present study may indicate that high and low IgE responder traits are determined depending on their levels of IL-4 mRNA expression.

Animals↗

PubMed1991

Inhibition of allergen-induced bronchoconstriction in sensitized guinea pigs by orally administered allergen.

Crude mite extract (CME) was orally administered to guinea pigs sensitized to CME. It was shown that such treatment reduces the bronchoconstrictive response upon allergen provocation. Isolated tracheae taken from guinea pigs orally administered CME allergen showed less contraction in response to CME as compared to those obtained from sensitized but not orally treated animals. The oral administration of allergens seemed to attenuate the bronchial hyperresponsiveness of sensitized animals to a non-specific chemical stimulus (histamine). IgE antibodies titrated by 8 days passive cutaneous anaphylaxis, and IgG1 and IgG2 antibodies measured by ELISA were comparable in the sera obtained from animals before and after CME treatment.

Administration, Oral↗

PubMed1991

Synthesis of biologically active recombinant Der f II.

A cDNA library corresponding to mite protein was screened employing anti-Der f II antibody. Two possible clones containing plasmids pFL1 and pFL11 were obtained. The two plasmids had insertions of about 500 basepairs. The DNA sequences of the two insertions were determined, from which the amino acid sequences were deduced. The amino acid sequence of the purified native Der f II protein could be determined to 45 residues from the N terminus. As a result of comparison, we concluded that the cDNAs prepared from live Dermatophagoides farinae mite corresponded to the mite allergen Der f II. The recombinant Der f II was biologically active.

Allergens↗

PubMed1991

Interleukin-4 gene expression in human peripheral blood mononuclear cells.

Interleukin-4 (IL-4) mRNA was detected in normal human peripheral blood mononuclear cells (PBMC) stimulated with concanavalin A by Northern blot analysis. The signal was undetectable in PBMC before the stimulation, but became detectable 3 hrs after the stimulation and reached a maximum in 3-6 h and disappeared gradually thereafter. Immunosuppressive drugs such as ciclosporin, hydrocortisone and prednisolone inhibited the IL-4 mRNA expression dose dependently. Interferon-gamma did not show any inhibitory effect on IL-4 gene expression.

Blotting, Northern↗

PubMed1991

Isolation of cysteine protease in the crude mite extract, Dermatophagoides farinae.

In order to study the relationship between cysteine protease and Der f I, which is one of the major allergens in the mite, Dermatophagoides farinae, isolation of cysteine protease was attempted using various column chromatographies. Both the potent cysteine protease activity and the allergenic activity were detected in the same fractions by anion exchange chromatography on a DEAE-Sephacel, gel chromatographies and chelating Sepharose 6B chromatography. In the double immunodiffusion test, the finally isolated fraction and rabbit anti-Der f I sera reacted to give a single precipitation line which fused completely with the precipitation line formed by Der f I and anti-Der f I sera. Sequence analysis for the first 10 N-terminal amino acids from cysteine protease and Der f I were identical. These results strongly suggest that cysteine protease of mites may be Der f I allergen and that measuring cysteine protease activity may possibly become a beneficial method for detecting Der f I allergens.

Allergens↗

PubMed1991

Cloning and expression of cDNA coding for the major house dust mite allergen Der f II in Escherichia coli.

A cDNA library corresponding to mite protein was screened using anti-Der f II, a major allergen from the house dust mite Dermatophagoides farinae, antibody. Three possible clones were obtained that contained cDNA fragments coding for Der f II, and the nucleotide sequences of the fragments were determined. There were minor differences observed affecting the deduced amino acid sequence among the three cDNA fragments. The amino acid sequence of the purified native Der f II protein could be analyzed to 45 residues from the N-terminus. As a result of comparison, all the three cDNA fragments code for a mature protein with a derived molecular weight of about 14,000. The amino acid sequence was not homologous to any known protein sequences and it contained six cysteine residues and no N-glycosylation sites.

Allergens↗

PubMed1991

[Histamine release test of patients allergic to the house dust mite, Dermatophagoides farinae--analysis according to various clinical backgrounds].

Since the histamine release test is more complicated than some of the other tests, there are smaller number of clinical studies employing this method. In this study, we selected 25 males and 20 females, allergic to the house dust mite, to undergo the histamine release test challenged by 7 serial concentrations of the mite allergen diluted from 10 times to 10 million times the original allergen at a concentration of 0.01%. Histamine release was expressed as a percentage of the total histamine concentration contained in the cells. Allergen induced dose response curve of histamine release was drawn for each patient, and in order to characterize each curve, 5 different indices were selected and were averaged according to the clinical backgrounds of the patients. Significant increases in histamine release were observed in males under 25 and females above 26 years of age. Histamine release rate in patients with RAST score of above 3+ was significantly more enhanced than in those with RAST score of below 2+, though this result was significant only for those under 25 years of age. Blood samples taken in June-August, and September-November, showed significant increases in the histamine release, though the indices for enhancement differed in both seasons. When analyzed according to the numbers of years the patient was desensitized, the results showed, contrary to our expectations, a more increased release in the desensitized group than in the non-desensitized group.

Adolescent↗

PubMed1991

[Evaluation of new system for the detection of IgE antibodies (CAP) in atopic diseases].

An evaluation of a newly developed IgE antibody assay system (CAP) was carried out. There was a clear correlation between IgE antibody titers measured by CAP single and RAST (= 0.642 to 0.979). It turned out that CAP single is more sensitive than RAST and non-specific adsorption of IgE immunoglobulin to the solid phase was assumed to be less in CAP than in RAST. Pathogenic allergens diagnosed either clinically or by in vitro assay systems were compared. The sensitivity and specificity of the CAP system were 94.2% and 87.3%, respectively. CAP multi which binds groups of multiple allergens on the solid phase, was examined for the screening of hypersensitivity to categories of allergens. Statistical sensitivities of CAP multi resided between 63.9% to 86.2%, while the specificities were 98% to 100%, indicating that CAP multi is useful for the exploration of causative allergens. Phadiatop, which fixes multiple inhalant allergens, showed a sensitivity of 89.6%. The specificity of phadiatop was 93.9%, when examined for intrinsic bronchial asthma patients, and 91.2% for normal subjects indicating that phadiatop is more useful than total IgE measurement for the screening of atopic trait.

Adolescent↗

PubMed1991

Preparation of specific monoclonal antibodies against Der f II one of the major allergens of Dermatophagoides farinae.

Five monoclonal antibodies (Mabs) against Der f II, one of the major allergens of Dermatophagoides farinae, were obtained from mice immunized with the allergen. Western blotting analysis revealed that only one Mab, named 15E11, was specific for Der f II, whereas the other Mabs crossreacted with Der p II, one of the major allergens of Dermatophagoides pteronyssinus. These results indicate the possibility that the Der f II-specific Mab, 15E11, is a useful reagent for specific determination of Der f II.

Allergens↗

PubMed1990

Bronchial responsiveness to mite allergen in atopic dermatitis without asthma.

Eight patients with atopic dermatitis (AD) without a history of asthmatic episodes and 8 patients with mite-allergic bronchial asthma (BA) were subjected to bronchial inhalation challenge with a nonspecific stimulus (acetylcholine) and an immunologically specific stimulus (house dust mite allergen). AD patients had a significantly greater concentration of IgE (p less than 0.01) and antimite IgE antibody (p less than 0.05) than BA patients. Nonspecific bronchial hyperreactivities of AD patients distributed from normal to asthmatic range. After allergen challenge, all 8 AD patients and all 8 BA patients showed an immediate asthmatic response (IAR). The mite extract concentration to induce an IAR was significantly (p less than 0.01) greater in AD patients than in BA patients. A late asthmatic response was observed in 6 out of 8 BA patients, whereas it was not observed in any AD patient. Our results showed that AD patients are less reactive to a specific mite allergen than BA patients in spite of greater concentrations of antimite IgE antibody. They suggest that this difference in the bronchial reactivity to the allergen concerns the difference in the onset of clinical symptoms and that a certain level of bronchial hyperreactivity to the allergen is a prerequisite for the development of asthmatic symptoms.

Adolescent↗

PubMed1990

Interleukin-4 gene expression in high and low IgE responder mice.

Interleukin-4 (IL-4) gene expression in murine spleen cells was examined by stimulation with concanavalin A (Con A). Spleen cells from a DBA/2 strain of mice, a high IgE responder, expressed IL-4 mRNA within 3 h after incubation with Con A. Maximal IL-4 mRNA expression was observed 6-9 h after stimulation. The amount of IL-4 mRNA induced by Con A was greatest in spleen cells obtained from high IgE responder strains of mice. A trace amount of mRNA was induced in spleen cells from low IgE responder (SJL) mice. The amount of mRNA induced in spleen cells from an intermediate IgE responder (C57BL/6) was smaller than that from high responders, but significantly greater than that from low responders. Spleen cells from IgE nonresponders (SJA/9) developed only a negligible amount of IL-4 mRNA after stimulation with Con A. Time course and optimal concentration of Con A for the expression of IL-4 mRNA were essentially the same in high (DBA/2) and low (SJL) responder strains of mice. The decreased expression of IL-4 mRNA in low IgE responder spleen cells upon stimulation was not due to the decrease in Thy-1-positive cells or L3T4-positive cells in the spleen. The results obtained in the present study may indicate that high and low IgE responder traits are determined depending on their levels of IL-4 mRNA expression.

Animals↗

PubMed1990

Experimental pulmonary eosinophilia in mice by Ascaris suum extract.

The transnasal administration of an extract of the parasite Ascaris suum (Asc) to C57BL/6 mice for 3 wk produced marked eosinophilia in the bronchoalveolar lavage (BAL) fluid. This pulmonary eosinophilia was not accompanied by blood eosinophilia. The oral administration of cyclosporin, 50 mg/kg body weight, every other day significantly suppressed the pulmonary eosinophilia. Athymic C57BL/6-nu/nu mice failed to develop pulmonary eosinophilia. These data indicate that pulmonary eosinophilia caused by this parasite extract is T-cell-dependent. Genetically mast-cell-deficient (WB X C57BL/6)F1-W/WV (W/WV) mice developed marked eosinophilia in the BAL, which shows that mast cells are not necessary in the formation of eosinophilia in BAL in this model. C57BL/6, W/WV, and Balb-C mice that developed eosinophilia in the BAL also showed elevated total IgE levels and IgE titers against Asc in the sera. On the other hand, C57BL/6-nu/nu mice and IgE low-responder SJL mice, which developed little eosinophilia, did not show elevated total IgE levels and IgE titers against Asc in the sera. However, oral administration of cyclosporin, 50 mg/kg, which inhibited eosinophilia in the BAL in C57BL/6 mice, did not significantly inhibit the elevation of total IgE or IgE against Asc in the sera. This indicates that serum IgE production is not required for the formation of eosinophilia.

Animals↗