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N F Adkinson

Publications and source records attributed to N F Adkinson.

203 records · Page 12Linked to original sources

Cross-allergenicity and immunogenicity of aztreonam.

The immunochemistry of aztreonam, the prototype of the new monobactam class of beta-lactam antibiotics, was studied in a series of experimental and clinical investigations. Rabbit antibodies to aztreonam and naturally occurring human antibodies that recognize aztreonam were found to have negligible cross-reactivity with benzylpenicillin, cephalothin, and cefotaxime. Aztreonam likewise displayed negligible cross-reactivity (less than or equal to 0.001%) with antibodies to penicillin (including human IgE antibodies to major and minor penicillin determinants) and to cephalothin. These studies suggest that aztreonam may be well tolerated by penicillin-allergic individuals, and this possibly is now being evaluated in clinical trials. Seven (6.25%) of 112 healthy persons tested had preexisting IgG antibodies to aztreonam in low titer, presumably as a result of exposure to naturally occurring cross-reacting moieties. Only two of seven patients with preexisting IgG antibodies to aztreonam had a rise in titer following aztreonam treatment. No IgE antibody to aztreonam was detected in serum specimens obtained on day 10 during any of the 112 courses of therapy. These clinical observations suggest but do not prove that aztreonam has only weak potential to elicit a drug-specific immunologic response.

Allergens↗

Exacerbation of diabetes mellitus by antibodies to exogenous insulin.

Three nonobese maturity-onset diabetic patients has worsening hyperglycemia and ketonuria unresponsive to marked increases in dose of beef/pork insulin. In each case, significant cross-reactivity with human insulin of anti-insulin antibodies generated by exogenous insulin therapy was demonstrated by competition experiments using solid phase radioimmunoassay. Normal or near normal levels of endogenous insulin secretion as determined by C-peptide radioimmunoassay were measured in the three cases. The sequence of events that we postulate to explain the initial presentation with severe hyperglycemia in each case begins with a slight deficiency in endogenous insulin reserve. Mild hyperglycemia then led to treatment with beef/pork insulin. The beef component elicited an antibody response that not only bound exogenous insulin, reducing its effectiveness, but also inactivated each patient's endogenous human insulin, provoking an exacerbation of underlying mild diabetes.

Adult↗

A comparison study between ragweed-specific IgG4 as measured by RAST and FAST.

A solid phase Sepharose-based RIA (IgG4 RAST) was compared to the IgG4 FAST enzyme immunoassay for measurements of Ragweed-specific IgG4. Although FAST reagents were used, a standard serum of known antibody content along with modifications in the FAST assay were necessary to attempt to develop a quantitative assay. Various assay parameters such as precision, reproducibility, sensitivity and parallelism were examined. Specificity of the monoclonal anti-IgG4 used in the FAST was not evaluated. Conditions and method of assay for the two systems differed substantially, particularly in the short incubation times for the IgG4 determinations.

Allergens↗

Immunoassays for IgG subclasses: quantitative and methodologic considerations.

In summary I have tried to provide my own statement of the status quo in current efforts to develop quantitative and reliable immunoassays for IgG subclass proteins and antibodies. Some of the trends I have commented upon are summarized in Table III. First, monoclonal antibodies have clearly won the day for almost all IgG subclass work. Second, solid phase immunoassays are almost indispensable for most IgG subclass antibody assays in order to circumvent the problem of subclass antibody competitions for soluble antigen. Third, the "captured" antigen or antibody by insolubilized antisera has a number of demonstrated advantages over passive adsorption or covalent linkage, in terms of assay parallelism, sensitivity, and specificity. Fourth, subclass immune responses can only be compared directly if serum dilution curves are parallel. More attention is needed for further technical refinements to achieve this important goal. Finally, the value of absolute quantitation, that is specification of nominal value in terms of weight/volume units, is an important ultimate goal. Among the feasible approaches to this problem are solid phase elution techniques, myeloma protein based quantitation, and by comparison to a single allergen system where nominal values can be established by conventional techniques. We have come a long way since IgG subclasses were first recognized more than 25 years ago. We are not in a phase of rapid expansion of techniques which seek to quantify IgG subclass immune responses. Much work remains to be done, but the tools for ultimate success are, I believe, within our grasp.

Antibodies, Monoclonal↗