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Biomedical subjects

J E Slater

Publications and source records attributed to J E Slater.

16 recordsLinked to original sources

Latex antigens.

Previous studies have demonstrated that some children with spina bifida have IgE to proteins in natural rubber. In this study we compare different sources of latex antigen and identify possible antigenic peptides by radioimmunoblotting technique. Sera were collected from 26 children with spina bifida, tested by RAST with ammoniated latex extract (AL), and frozen until use. Extracts were prepared from ammoniated and nonammoniated latex, and the proteins were separated by electrophoresis on a 15% sodium dodecyl suflate-polyacrylamide gel and transferred to polyvinylene difluoride (PVDF). Strips of PVDF were then incubated with individual sera and 125I-labeled rabbit antihuman IgE before development by autoradiography; 18/26 sera were AL RAST positive; 0/8 AL RAST-negative patients had any binding to the latex proteins on PVDF. Sera from all patients were tested in a RAST with a nonammoniated latex extract (NAL), and the results were comparable to the AL RAST. Liquid-phase AL and NAL were comparable in their ability to inhibit the binding of patient's IgE to solid-phase AL and NAL. Sera from 14 RAST-positive patients were tested by immunoblotting with separated, reduced, and nonreduced AL and NAL. All 14 sera demonstrated IgE binding to a 14 kd peptide, which was more pronounced in reduced NAL. These results suggest that the 14 kd peptide in NAL is a major antigen in rubber allergy but that AL is an acceptable antigen source for in vitro diagnostic studies.

Antibody Specificity

Allergic reactions to natural rubber.

Immediate hypersensitivity reactions to natural rubber pose a significant risk to patients with spina bifida and urogenital abnormalities, health care workers, and rubber industry workers. Other patients, outside of these high risk groups, have experienced severe allergic reactions to natural rubber as well. Awareness of this life-threatening condition by health care providers is essential if reactions are to be prevented. History alone is inadequate to identify all patients at risk, and reliable testing materials are not yet approved or widely available. Nonrubber medical devices are readily available for most uses; however, the only rubber-free condoms currently on the market do not prevent the transmission of sexually transmitted disease. The identification and detection of rubber antigens, along with mandated labeling for rubber antigen content, will contribute to the care of this growing population of patients. Efforts by the rubber industry to decrease the antigen content of natural rubber products will decrease the risk of reaction among sensitized patients and will, very likely, decrease the rate of sensitization in the future.

Humans

Rubber-specific IgE in children with spina bifida.

We attempted to determine the prevalence and clinical significance of rubber-specific IgE in a prospective case control study of 32 preoperative children with spina bifida, compared with 45 outpatient controls and 35 age-matched preoperative controls without spina bifida. A latex-specific radioallergosorbent test was positive in 11 of the 32 spina bifida patients (34%), compared with 1 (2%) and 4 (11%) of the respective controls (p less than 0.05). Within the spina bifida group 5 of 11 antibody-positive patients had a history of rubber-associated, intraoperative or otherwise idiopathic allergic episodes and 1 of 21 antibody-negative patients gave such a history (p = 0.012). Children with spina bifida have a significantly greater likelihood than controls of having IgE specific for rubber antigens. In addition, the presence of rubber-specific IgE is associated with a higher frequency of rubber-associated, intraoperative or idiopathic allergic reactions.

Adolescent

Type I hypersensitivity to rubber.

Seven patients with type I hypersensitivity reactions to rubber are reported. Radioallergosorbent testing with crude latex antigen was positive in 6/7 patients. Five patients had coexisting spina bifida, and all had undergone surgery before the development of rubber allergy. Rubber allergy is a new phenomenon that should be in the differential diagnosis of idiopathic anaphylaxis and urticaria.

Adolescent

IgE immunotoxins. Effect of an IgE-ricin A chain conjugate on rat skin histamine content.

Immunotoxins--toxins covalently conjugated to specific antibodies--have been studied as possible agents in the treatment of cancer. The avid binding of IgE antibodies to FcR on mast cells and basophils suggested the possible use of an IgE-immunotoxin in the treatment of malignant mastocytosis or as a method to generate mast cell-depleted animals for study. To this end, the effect of a covalent conjugate of rat myeloma IgE and ricin A chain on rat cutaneous mast cells was examined in vivo. IgE-ricin A chain was capable of binding to and sensitizing cutaneous mast cells in vivo as indicated by a bluing response to intracutaneous anti-ricin A chain. IgE-ricin A chain, given either as a single dose or, even more effectively, as two split doses, significantly reduced cutaneous histamine content for 6 to 8 days. Neither a mixture of IgE and ricin A chain that were not conjugated nor the induction of cutaneous mast cell degranulation with anti-IgE affected cutaneous histamine levels. Therefore, IgE-ricin A chain produces a prolonged depletion of cutaneous histamine levels.

Animals

Effects of sex hormones on basophil histamine release in recurrent idiopathic anaphylaxis.

A subset of patients with recurrent anaphylaxis experience ovarian hormone-related exacerbations. Symptoms in several of these women may be provoked by gonadotropins or progesterone (P) and improved by ovarian suppression, with long-term remissions noted in several patients after oophorectomy. Since adverse reactions to P might explain this association, the effects of P and estrogen on basophil histamine release from these patients were studied. Eight patients and 10 control subjects were examined. Neither estrogen nor P caused histamine release from the basophils of patients or control subjects. Moreover, anti-IgE-induced histamine release was not influenced by P or estrogen. Attempts to culture basophils for 24 hours revealed that basophil preparations from eight of 10 normal subjects but only three of eight patients retained the capacity to respond to anti-IgE after 24 hours (p = 0.088). Culture with dexamethasone reduced anti-IgE-induced histamine release in all subjects, and the possibility that P might interfere with the effect of dexamethasone was also studied. P failed to affect dexamethasone-induced reduction of basophil histamine release. Therefore, P and estradiol appear to have no effect on basophils from either patients with hormone-related exacerbations of anaphylaxis or from control subjects.

Adolescent

Recurrent anaphylaxis in menstruating women: treatment with a luteinizing hormone-releasing hormone agonist--a preliminary report.

Recurrent idiopathic anaphylaxis is an illness consisting of recurring anaphylactic or anaphylactoid attacks of unknown cause. A patient has been described whose attacks appeared to be associated with endogenous progesterone secretion and who was treated successfully with an analog of luteinizing hormone-releasing hormone (LHRH). This report summarizes the treatment of four additional women with recurrent anaphylaxis in a randomized, double-blind trial of an LHRH agonist and placebo. Two out of the four women experienced remission of their symptoms with the LHRH analog. The patients who responded to therapy had experienced systemic anaphylactoid reactions after provocation with an LHRH infusion and the intradermal injection of medroxyprogesterone; the nonresponders had no adverse reactions to either challenge. Ovarian suppression with LHRH agonist may benefit a subset of women with recurrent idiopathic anaphylaxis.

Adult

Production of monoclonal cyclic GMP and cyclic AMP antisera.

In order to facilitate the in situ localization of cyclic nucleotides, a large supply of high-titer anti-sera for immunohistologic analyses would be valuable. Therefore, monoclonal antibodies (Mab) directed at 2'-0-succinyl cyclic GMP (s-cGMP) or 2'-0-succinyl cyclic AMP (s-cAMP) were generated. Immunized mice developed polyclonal antibodies of high titer to either cyclic nucleotide as reflected in an enzyme-linked immunosorbent assay (ELISA) employed to monitor these anti-sera. With the use of standard hybridoma technology and ELISA to monitor anti-cyclic nucleotide antibody production from positive clones, several Mab-producing clones were grown to large volume in tissue culture and ascites fluid. The anti-cGMP and anti-cAMP anti-sera, which demonstrated significant ELISA titers at greater than 1:2,000,000 dilutions, are monospecific and can be employed for radioimmunoassays, ELISA, or immunohistologic localization of cyclic nucleotides in situ.

Animals