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J A Galloway

Publications and source records attributed to J A Galloway.

At least 37 records · Page 2Linked to original sources

Immunogenicity of recombinant DNA human insulin.

We postulated that human insulin of recombinant DNA origin would be a poor immunogen and might prove to be less immunogenic than purified pork insulin. Results are reported for 100 diabetic subjects not previously treated with insulin. Individuals completed the first 12 months of a clinical trial of human insulin of recombinant DNA origin. These patients are contrasted with 121 similar individuals who are taking part in a trial of purified pork insulin. Prior to therapy, species-specific binding of 125I human insulin and pork insulins and insulin bound to antibody were undetectable in all individuals. In patients treated with human insulin of recombinant DNA origin, binding of 125I human insulin increased to 10 +/- 1.2% at 12 months versus increases in binding of 125I pork insulin in pork insulin-treated patients to 12.6 +/- 1.4% (NS). Mean percentages of species-specific binding tended to reach a plateau in the human insulin-treated group but continued to increase in the pork insulin group (p less than 0.001). Median bound values were nil throughout in patients treated with human insulin, but increased to 52 mU/l in the pork insulin group with significantly less bound insulin seen in the former group at all visits (p less than 0.001). The percentage of individuals who remained antibody free at 12 months, as indicated by bound insulin, was 56% in the human insulin-treated patients and 40% in the patients treated with pork insulin (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Effects of species of origin, purification levels, and formulation on insulin immunogenicity.

The immunogenicity of purified pork insulins (PPI) with and without (groups 1 and 2, respectively) trace contamination of beef insulin was contrasted with mixed beef pork insulin of lower purity (MBP, group 3) in 137 patients who had not previously been treated with insulin. Patients and physicians were blinded with regard to the species source of insulin and studies were conducted for a minimum of 1 yr. Antibody development to insulin was assessed by species-specific binding of 125I-insulin by acid charcoal extracted sera, as well as by measurement of insulin prebound to immunoglobulins by a polyethylene glycol precipitation method. NPH- and lente-treated individuals had equivalent antibody responses with regard to the rate of development of antibodies, and maximum immune responses to insulin. In all patient groups, antibody bound insulin as well as species-specific binding of 125I-insulin increased significantly over time (all P less than 0.01 for specific binding of pork and beef insulins SBP and SBB, as well as bound insulin). Maximum bound insulin and SBB as well as bound insulin and SBB over the entire course of the study were significantly greater in group 1 than in group 2 patients (both P less than 0.05). The rate of development and magnitude of antibodies' responses in both PPI-treated groups were significantly less than that seen in the MBP group (all P less than 0.01). New formation of antibeef proinsulin antibodies was seen in one patient from groups 1 and 3, but not in group 2. In all groups, insulin dose per day and fasting serum glucose concentrations increased by about 5 U/day and 10 mg/dl over 1 yr, but groups did not differ. MBP insulin used in these studies proved to be significantly less immunogenic than previously available Argentine pure beef insulin, purified by gel filtration. PPI containing even trace contamination of beef insulin was more immunogenic than PPI alone.

Adult↗

Dermal hypersensitivity reactions to insulin: correlations of three patterns to their histopathology.

Fifteen diabetics with recurrent painful local reactions to insulin were studied. Reactions occurring after intradermal insulin injection were observed in nine patients over 48 hr and biopsies were taken at intervals for microscopic study using the 1 mu Giemsa technique. Insulin-specific IgE and IgG levels were measured on all patients. Five patients had biphasic reactions in which wheal and flare (WFR) were followed by an indurated lesion 4 to 6 hr later. These reactions lasted up to 24 hr and were histopathologically identical to similar "late-phase reactions" seen with ragweed. They were transferable with Prausnitz-Küstner (P-K) testing. Three patients had reactions that developed 8 to 12 hr after injection, peaked around 24 hr, and were not preceded by WFR. These reactions were morphologically delayed hypersensitivity reactions and were not transferred by P-K testing. One patient had a reaction that developed in 4 to 6 hr after injection and peaked by 12 hr. Histologically, this reaction was "Arthus" in type and was not transferred by P-K testing. Specific insulin antibody determinations were not helpful in distinguishing patients with different types of reactivity. These data show that recurrent local reactions to insulin may be of three distinct types: "late-phase reactions" (which are IgE dependent), "Arthus" local vasculitic reactions, or tuberculin-type delayed hypersensitivity reactions. These findings may influence the approach to management of these reactions.

Animals↗

Pork insulin.

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Animals↗

Insulin treatment in diabetes.

Efficacy of and indications for the use of purer forms of insulin have now been established, and arguments showing the relation of blood glucose control to the development and progression of complications have been strengthened.

Adipose Tissue↗

GLC determination of acetohexamide and hydroxyhexamide in biological fluids.

A sensitive and specific GLC assay was developed for acetohexamide and hydroxyhexamide, its major metabolite, in plasma and urine. The assay uses tolbutamide as a mass internal standard. Compounds are extracted from acidified plasma or urine with toluene, converted to methylated derivatives with dimethyl sulfate, and measured by GLC using a flame-ionization detector. With GLC-mass spectrometry, the compounds measured are the N-methylsulfonamides resulting from GLC pyrolysis. Plasma and urine data are presented from a bioavailability study to demonstrate the utility of this method.

Acetohexamide↗

The immunogenicity of insulin preparations.

Patients who had never received insulin were administered porcine or bovine Lente insulins prepared from either conventional USP-grade insulin, "single-peak" insulin (SPI), or "single-component" insulin (SCI) in an attempt to determine if insulin immunogenecity was related to the purity of various insulin preparations. Serum insulin antibody titers were monitored by a sensitive I125-insulin binding procedure. All six groups of patients had some degree of antibody formation after six months of continuous insulin administration. Based upon the percent of I125-insulin bound by the serum, the least immunogenic insulin preparation was the porcine SCI. The most immunogenic insulins were the bovine preparations, all three of which gave comparable antibody responses. The patients who received porcine USP insulin and porcine SPI had similar antibody titers, both of which were significantly higher than the titers from the patients on porcine SCI, but significantly lower than the antibody titers from the patients treated with any of the bovine preparations. The immunogenicity of bovine SCI was significantly reduced by administering multiple daily doses of the neutral regular form instead of one or two daily injections of the Lente form, Although these purer insulin preparations (SPI and SCI) are still associated with various degrees of immunogenecity, they are significant improvements for the treatment of insulin lipoatrophy and insulin allergy.

Adolescent↗

The insulins.

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Diabetes Mellitus↗