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Biomedical subjects

N F Adkinson

Publications and source records attributed to N F Adkinson.

At least 181 records · Page 10Linked to original sources
PubMed1981

IgE responses in human filariasis. I. Quantitation of filaria-specific IgE.

We have developed a noncompetitive solid phase radioimmunoassay to quantitate human IgE antibodies against soluble adult antigens of Brugia malayi (B.m.), a filarial parasite, in sera of patients with various forms of clinical filariasis in Madras, India. A single reference serum was shown to contain 23 micrograms/ml of B.m.-specific IgE by depletion analysis and was used as a standard serum throughout the study. The levels of specific IgE ranged in the patients sera from 2 to 23,000 ng/ml. When these individuals were divided into clinical groups, the individuals with tropical pulmonary eosinophilia had the highest levels (mean = 8630 ng/ml) and were significantly higher than all the other groups (p less than 0.001). The lowest levels were seen in patients with circulating microfilariae (mean = 30.5 ng/ml). Patients exhibiting lymphatic obstruction (i.e., chronic pathology group) had levels slightly higher than microfilaremics (mean = 68 ng/ml) but were not significantly different (p less than 0.1). Surprisingly, individuals living in endemic areas but who had no clinical signs of filariasis also showed appreciable levels of B.m.-specific IgE (mean = 55 ng/ml). The B.m.-specific IgE represented 0.1 to 48% of the total IgE. High percentages of specific IgE may be responsible for evoking allergic symptomatology in patients with tropical pulmonary eosinophilia.

Adolescent↗
PubMed1980

Treatment of ragweed hay fever with urea-denatured antigen E.

Urea-denatured antigen E (UDE) has lost the major determinants of antigen E (AgE), eliciting neither IgE nor IgG antibodies to native AgE in mice. UDE, however, stimulates T cells so that repeated injections result in specific but partial suppression of ongoing IgE responses to native AgE. An attempt was made to apply this property to the treatment of 10 ragweed-allergic human volunteers by repeated subcutaneous injections of UDE over about 18 mo. Local and systemic allergic reactions limited the dose to 4 to 75 microgram UDE per injection. Little or no antibody response to AgE was induced. Five patients had increased basophil sensitivity to UDE after 4 mo of injections. Five of eight patients who completed the study had evidence of suppression of IgE responses by exhibiting a 20% or less increase of IgE antibodies to ragweed on natural seasonal exposure. Three patients still exhibited this evidence at the next season of exposure 10 mo after the last injection. The two patients who received the lowest doses had greater than usual seasonal rises of IgE antibodies. There was no clinical evidence of improvement of hay fever symptoms. The results indicate that the immunologic properties of UDE in humans are similar to those in mice. The clinical applicability of these properties remains doubtful.

Antigens↗
PubMed1980

A controlled study of the effectiveness of the Rinkel method of immunotherapy for ragweed pollen hay fever.

In a double-blind study, we compared the effects of the Rinkel method of immunotherapy with ragweed pollen extract and placebo on symptoms of ragweed hay fever and immunologic parameters in 24 ragweed-sensitive patients. Each had a skin-test end point by Rinkel serial dilution titration to ragweed pollen extract at 1:312,500 w/v or greater dilution, a 2 + skin test to ragweed AgE at 0.1 microgram /ml or greater dilution, and in vitro leukocyte histamine release by ragweed pollen extract. None had had immunotherapy for at least 7 yr. Patients matched on the basis of leukocyte histamine release by ragweed were assigned to two treatment groups (12 patients in each group). One group received ragweed pollen extract, and the other, placebo, both administered by the Rinkel method between June and October, 1978. Treatment doses were derived from skin-test end points. The median maintenance ("optimal dose") for patients receiving ragweed pollen extract was 0.53 ml of 1:312,500 w/v and the mean cumulative dose of ragweed pollen extract given during the study contained 0.094 micrograms of ragweed AgE. Symptom-medication scores of all patients rose and fell with ragweed pollen counts. No significant differences were observed in mean daily symptom-medication scores, antiragweed IgG or IgE levels, leukocyte histamine release by ragweed, total IgE levels, or skin-test end-point dilutions with ragweed pollen extract between the group receiving ragweed pollen extract and the group receiving placebo. Despite the absence of specific effect on symptom-medication scores and measured immunologic variates, 10 3f the 12 ragweed-treated patients and 10 of the 12 placebo-treated patients were of the opinion that their hay fever symptoms during the ragweed pollen season were less severe in 1978 than in 1977 and that they had been helped by Rinkel method immunotherapy. Under the conditions of the study, Rinkel method immunotherapy with ragweed pollen extract was no more effective than placebo given in an imitation of the Rinkel method.

Adolescent↗
PubMed1979

Assessment of the influence of irrelevant IgE on allergic sensitivity to two independent allergens.

Serum samples from 31 patients sensitive to both ragweed and rye grass were quantitated for IgE specific for ragweed antigen E (AgE) and rye grass group I (rye I) antigens employing the previously described radioallergosorbent test (RAST) elution technique. IgE anti-AgE ranged from 0.4 to 320 ng/ml and comprised 0.4% to 14.2% of total serum IgE. The same sera contained IgE anti-rye I ranging from 7.9 to 1,168 ng/ml, comprising 1.6% to 29.6% of total serum IgE. A new theoretical parameter (RF), representing the percent of total IgE-Fc receptors of target cells occupied by allergen-specific IgE, was calculated for each IgE specificity by using the determinations of allergen-specific IgE antibody, total serum IgE, and assuming an equilibrium constant for binding of IgE molecules to basophils of 10(9)M-1. This "% occupancy" parameter correlated with skin test titration, basophil cell sensitivity, and hay fever symptom scores as well as, but not better than, the absolute values of allergen-specific IgE. This finding suggests that in most atopic patients, the quantity of irrelevant IgE plays a relatively minor role in determining allergic sensitivity to a given allergen. The implications of this finding are discussed.

Allergens↗
PubMed1979

Passive sensitization of human basophils: evidence for heterogeneity in the IgE molecule.

Possible functional heterogeneity of human IgE antibody was studied by passively sensitizing human basophils for antigen-induced histamine release. Six sera of known IgE anti-ragweed antigen E and total IgE content were diluted to contain 10 ng of antibody but differed with respect to the ratio of specific/total IgE. The relative ability of the sera to passively sensitize generally reflected the specific/total IgE ratio but one serum was 2.5 times more active than the remainder. This ability did not reflect the IgG antibody level nor was it due to a dialyzable or heat-stable factor. These data indicate functional IgE heterogeneity, probably due to the interaction of the Fc portion of IgE with the basophil receptor.

Basophils↗
PubMed1979

Solid phase radioimmunoassay for quantitation of antigen-specific IgG in human sera with 125I-protein A from Staphylococcus aureus.

Radiolabeled protein A from Staphylococcus aureus (Staph A) has been used to develop a solid phase, noncompetitive radioimmunoassay for quantitation of specific IgG antibody. The assay involves two incubations: First, agarose-insolubilized antigen is mixed with serum samples for 1 to 4 hr during which specific antibody is bound; second, after a washing procedure, the solid phase immune complexes are incubated for 4 to 18 hr with 125I-Staph A, during which the radiolabeled detection protein binds to the insolubilized specific IgG antibody. In a comparative study of the IgG antiphospholipase A antibody content of 23 human sera drawn from honeybee venom-sensitive patients, resulted of the Staph A assay correlated highly (r = 0.981, p less than 0.001, N = 23) with those obtained from a liquid phase, competitive radioimmunoprecipitation (double antibody) assay. The two assays demonstrated comparable precision, sensitivity, and reproducibility. In contrast, the use of 125I-Staph A in the solid phase radioimmunoassay was superior to 125I rabbit anti-human IgG because of lower negative serum (blank) values, shorter time required to reach equilibrium binding, and greater precision and reproducibility. In principle, the 125I Staph A assay may be applied ot IgG quantitation for crude allergen extracts as well as purified antigens. Furthermore, the sera of a number of mammalian species may be studied without further modification.

Animals↗
PubMed1978

IgE receptors on human basophils. Relationship to serum IgE concentration.

As reported previously, and confirmed here in 26 donors, the serum IgE level (2.6-5,500 ng/ml) correlates well (rs = 0.95, P less than 0.001) with the in vivo number of IgE molecules/basophil (6,000-600,000). The total number of IgE receptors/basophil was monitored by incubating them with an IgE-rich serum (15 microgram/ml), quantitatively stripping IgE from the cells at pH 3.7, and measuring eluted IgE by a direct radioimmunosorbent test. Saturation of receptors for each donor was achieved with 15 nM IgE (3 microgram/ml). The proportion of receptors occupied in vivo correlated with the serum IgE (rs = 0.84, P less than 0.001) whereas the average association constant of the receptors was independent of serum IgE and ranged from 7.1 X 10(8)/M to 2.8 X 10(10)/M, averaging 7.7 X 10(9)/M. Unexpectedly, the total number of IgE receptors/basophil was closely related to the serum IgE level. (rs = 0.92, P less than 0.001). Thus, either there is genetic association between serum IgE and the number of basophil IgE receptors, or, more likely, the receptor number is modulated by the serum IgE concentration.

Basophils↗
PubMed1978

Asthma improved by nonsteroidal anti-inflammatory drugs.

A patient who claimed benefit from aspirin for her reversible bronchospasm was challenged orally in a placebo-controlled study with aspirin and other aspirin-like drugs. Specific airways conductance and spirometry were monitored for up to 150 minutes after oral challenge. Aspirin, mefenamic acid, and ibuprofen administration resulted in marked (45% to 80%) improvement in forced expiratory volume in 1 second (FEV1) compared to lactose placebo. Indomethacin, sodium salicylate, and tartrazine resulted in modest (15% to 25%) FEV1 improvement, while phenylbutazone produced a 25% decrease. These results are discussed here in terms of the ability of these drugs to inhibit the prostaglandin synthetase enzyme system. This case suggests that aspirin and other nonsteroidal anti-inflammatory drugs may be beneficial rather than harmful in some asthmatic patients.

Airway Resistance↗
PubMed1978

Allergy to insect stings. IV. Diagnosis by radioallergosorbent test (R.A.S.T.).

Radioallergosorbent tests (RAST(s)) have been developed and assessed for the diagnosis of insect hypersensitivity by using a purified allergen from honeybee venom, phospholipase A, and crude yellow jacket venom. Sera from 193 patients positive both by history and skin test to one of these insects were compared with various groups of control sera. Eighty percent of sera from skin test-positive patients were RAST positive; positive RAST were found in 16% of sera tested from skin test-negative patients. A highly positive RAST correlates well with a positive skin test and clinical sensitivity, but serum IgE is not measurable in many patients with mast cell or basophil bound antibody. Since biologically important reactions of antigen with IgE require that the antibody be cell bound, skin testing would be preferred to RAST if one were limited to a single test for the diagnosis of insect allergy.

Animals↗