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Biomedical subjects

N F Adkinson

Publications and source records attributed to N F Adkinson.

At least 199 records · Page 11Linked to original sources

Environmental influences on the immune system and allergic reactions.

Environmental interactions with the immune system may result in two types of adverse outcomes: immunodeficiency and immunopathology. Serious immunodeficiency most commonly results from ionizing radiation or as a recognized side effect of iatrogenic drug therapy, usually cancer chemotherapy. At present there is little basis for believing that biologically significant suppression of immune competence in man results from more subtle interactions with environmental agents. On the other hand, environmentally triggered immunopathology is a source of considerable morbidity and mortality. Additional research is needed in the following areas: (a) basic mechanisms of immunopathological reactions; (b) development of methods for accurately implicating or excluding immunological mechanisms in the etiology of hypersensitivity states; (c) development of methods for assessing in advance the potential immunogenicity of new industrial chemicals and occupational allergens; (d) identification of the risk factors which predispose to immunopathological outcomes when individuals are exposed to sensitizing chemicals or other "natural" allergens.

Allergens↗

Measurement of IgE on human basophils: relation to serum IgE and anti-IgE-induced histamine release.

The number of IgE molecules bound to human basophils was calculated from direct measurements of the IgE dissociated after exposing leukocytes to pH 3.7 acetate buffer in the cold. In 18 donors studied, cell-bound IgE ranged from 4000 to 500,000 molecules/basophil and correlated with the serum IgE concentration (r = 0.89, p less than 0.001) which ranged from 5 to 3,000 ng/ml. Sensitivity of these cells to anti-IgE was tested to explore the relationship between cell-bound IgE and the concentration of anti-IgE required for histamine release. Cells from some nonatopic donors (4000 to 100,000 IgE molecules/basophil) were as sensitive as cells from allergic donors (100,00 to 500,000 IgE molecules/basophil). Moreover, cells from donors having approximately the same cell-bound IgE concentration varied widely in their sensitivity to anti-IgE. We conclude that an intrinsic property of human basophils ("releasability") is an important parameter in determing mediator release.

Acetates↗

Allergy to insect stings. II. Phospholipase A: the major allergen in honeybee venom.

In order to determine the proteins of major allergenic importance in honeybee venom (Apis mellifera) it was chromatographed on G-50 Sephadex. The four major protein peaks eluted were identified as hyaluronidase, phospholipase, melittin, and apamin. Testing these preparations on the leukocytes of 6 honeybee-sensitive patients, with the in vitro method of histamine release, revealed that all individuals were most sensitive to phospholipase A. IgE antibodies against phospholipase A (RAST) were found in the sera of honeybee-sensitive patients and IgG antibodies to this venom component were found in the sera from beekeepers and venom-treated patients. Melittin appeared to be allergenic in several patients, but the results were variable and were possibly due to contamination with phospholipase. All patients were insensitive to the hyaluronidase and apamin preparations. We conclude that phospholipase A is the major allergen of honeybee venom and, since this protein is readily available, it should be useful for diagnostic and therapeutic studies as well as for the standardization of materials used in the management of honeybee-sensitive patients.

Allergens↗

Penicillin hypersensitivity in systemic lupus erythematosus.

The prevalence of positive immediate-type skin tests to penicillin antigens among patients with systemic lupus erythematosus (SLE) was compared with hospitalized controls without SLE and found not to differ significantly. On the other hand, we confirmed previous reports that the prevalence of histories of prior penicillin reaction was significantly higher in SLE patients than among controls. This is felt to be related to the primary disease process, and we conclude that patients with SLE do not have an increased risk of IgE-mediated allergic reactions to penicillin.

Antigens, Fungal↗

Measurement of absolute amounts of antigen-specific human IgE by a radioallergosorbent test (RAST) elution technique.

A technique for the absolute quantification of antigen-specific human IgE is described. It employs elution of a calculable amount of antigen-specific IgE from an allergosorbent-antibody complex by means of alkaline pH treatment, followed by measurement of the IgE content of the eluate with a modified radioimmunosorbent test (RIST). With this method IgE antibody directed against the benzylpenicilloyl determinant of penicillin (BPO) was measured quantitatively in sera from seven penicillin allergic patients. IgE specific for ragweed antigen E was measured in sera from 33 ragweed allergic patients. Values obtained for IgE anti-BPO ranged from 19 to 1806 ng/ml and comprised from 1.3 to 27.5% of total serum IgE. Values of IgE anti-antigen E ranged from 9 to 1807 ng/ml, comprising from 3 to 84% of total serum IgE. Excellent correlation (r = 0.99; p less than 0.001) was obtained for both antigen systems between values determined by the RAST elution technique and by simple RAST assay with interpolation from a reference serum of known specific IgE content as determined by the elution technique may be needed only for primary standardization of reference sera.

Allergens↗

Lymphocytes in patients with variable immunodeficiency and panhypogammaglobulinemia. Evaluation of B and T cell surface markers and a proposed classification.

Peripheral blood lymphocytes from 15 patients with variable immunodeficiency and severe panhypogammaglobulinemia were evaluated for B and T cell surface markers. B cells were enumerated by immunofluorescent detection of both surface immunoglobulin (Ig) and the ability to bind aggregated Ig complexes. T cells were identified by their ability to form nonimmune rosettes with sheep red blood cells. Four distinct patterns were observed which were designated types I-IV. Type I: six patients had normal percentages (8.5-19.0%) of Ig-bearing B lymphocytes. Type II: four patients were observed to have B lymphocytes (4.5-15.0%) which lacked fluorescence-detectable surface Ig. Type III: the peripheral blood of these four patients contained a subpopulation (11.3-20.0%) of lymphocytes which apparently lacked both B and T cell markers ("null" cells). Type IV: one patient's blood was characterized by a subpopulation (18.0-22.0%) of lymphocytes which bore both B and T cell markers. Patients of each type had some clinical features in common. It is concluded that evaluation of lymphocyte surface markers provides a means of separating patients with variable immunodeficiency and panhypogammaglobulinemia into distinct groups which appear to differ in the nature of their fundamental defect.

Adolescent↗

Allergy to protamine.

Recent advances in medicine, such as cardiac catheterization, phoresis, dialysis, and cardiopulmonary bypass technology, have increased the need for heparin anticoagulation. To antagonize heparin's effect and prevent hemorrhagic complications after the procedure, protamine has likewise been used more frequently. With its increased use have come increased reports of adverse protamine reactions consisting of rash, urticaria, elevation of pulmonary artery pressure, systemic hypotension, and, at times, death. The elevation of pulmonary artery pressure, which appears to be a rather common occurrence in animals, may be an isolated finding without clinical consequences in humans. However, this pulmonary vasoconstriction may, when severe, lead to acute right-sided heart failure and systemic hypotension. Other protamine reactions involve a decrease in systemic vascular resistance and systemic hypotension without changes in pulmonary artery pressure. Causes of acute protamine reactions may involve the generation of anaphyatoxins and prostanoids either from protamine-heparin complexes or complement-fixing antiprotamine IgG antibodies, from inhibition of plasma Carboxypeptidase N, from crosslinking of cell-surface antiprotamine IgE on mast cells and basophils with subsequent mediator release, or from potentiation of IgE-mediated release of histamine through a polycationin-recognition site. Although we have come a long way in understanding the mechanisms by which protamine can cause its ill effects in humans, more work is clearly needed to define, in prospective studies, the incidence of and risk factors for protamine reactions in various patient groups, and to delineate more clearly which mechanisms are involved in each clinical type of acute protamine reaction. Hopefully, this will lead to strategies and protamine alternatives that will prevent or diminish, in frequency or severity, adverse protamine reactions. Alternatively, a clearer picture of the risk factors important for protamine reactions and the predictive value of diagnostic tests (e.g., protamine IgE antibody) can also minimize the clinical impact of this increasingly common adverse event.

Acute Disease↗

Evaluation of the immunologic cross-reactivity of aztreonam in patients with cystic fibrosis who are allergic to penicillin and/or cephalosporin antibiotics.

The immunogenicity, allergenicity, and cross-reactivity of aztreonam were investigated in 19 patients with cystic fibrosis (CF) who are allergic to beta-lactam antibiotics. Skin tests with benzyl-penicilloyl polylysine (BPO), minor determinant mixture, and the drug responsible for the previous allergic reaction were positive for 26%, 53%, and 79% of the patients, respectively. Serum IgG, but not IgE, antibodies to BPO were detected in nine of 14 patients. Eighteen patients whose skin tests with aztreonam were negative were treated. One developed bronchospasm. The others tolerated aztreonam, with an improvement in clinical score greater than or equal to 1 month after treatment (P less than .001). One patient without previous exposure had positive aztreonam skin tests and was later treated uneventfully after iv desensitization. Treatment with aztreonam did not result in IgG or IgE antibody responses in vitro. However, two patients had anaphylactic reactions on reexposure. In patients with CF, allergy to beta-lactam antibiotics is primarily drug-specific. But despite reduced immunogenicity and cross-reactivity, aztreonam should be administered cautiously to patients with CF who are allergic to other beta-lactam antibiotics because it is potentially allergenic with repeated use.

Adolescent↗