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Biomedical subjects

R Patterson

Publications and source records attributed to R Patterson.

At least 397 records · Page 22Linked to original sources

Evaluation and standardization of polymerized ragweed extracts by chromatography, radioimmunoassay inhibition, and end point cutaneous titration.

The standardization procedures for polymerized ragweed (PRW) must evaluate activity of PRW with assessments that differ from those used for standard unmodified extracts. This is because PRW allergens are different from conventional ragweed extracts in that they are much greater in average molecular weight and much lower in allergenicity for equivalent immunogenicity. We have evaluated seven samples of PRW for three parameters: allergenicity as determined by cutaneous end point titration, molecular weight distribution as determined by Sephadex G-200 chromatography, and availability of antigen E (AgE) determinants as measured by the ability of an extract to inhibit AgE binding to antibody by using a modification of the Farr technique. The skin test titers and molecular weight profiles provide information as to the safety of a PRW preparation and antigen-binding inhibitory activity gives information about allergenicity and immunogenicity. Appropriate limits may be set for each of these parameters to standardize PRW for clinical use.

Allergens↗

A double-blind histamine placebo-controlled trial of polymerized whole grass for immunotherapy of grass allergy.

Twenty-six patients were recruited for a study of the safety and efficacy of immunotherapy with IPG. They were randomly assigned to two groups based on skin test titrations to grass allergens. One group was treated in a double-blind fashion before the 1982 grass season with 12 weekly injections totaling approximately 48,000 PNU, and the other group was treated with 12 weekly injections of caramelized glucose histamine placebo. Daily symptom and medication score sheets were completed by all patients each day of the grass season. Blocking antibody rose ninefold in the IPG group (p less than 0.007) but was unchanged in the placebo group. There was no significant change in IgE against rye grass group I in either the IPG or the placebo group. Symptom-score mean in the IPG group was 217 +/- 71 (S.E.M.), statistically lower (p less than 0.02) than the mean in the placebo group 496 +/- 117 (S.E.M.). There were no systemic reactions and only minor local reactions. There was no change in routine laboratory tests in either group. Although two prior studies with grass allergen immunotherapy reported efficacy, these studies did not use symptom-score analysis. This is the first double-blind, histamine placebo-controlled study of grass immunotherapy that demonstrates efficacy by symptom-score index evaluation. IPG is a safe, clinically effective, and potentially cost-effective therapy for grass pollinosis.

Clinical Trials as Topic↗

Antibodies against toluene diisocyanate protein conjugates. Three methods of measurement.

With the use of canine antisera against toluene diisocyanate (TDI)-dog serum albumin (DSA), techniques for measuring antibody against TDI-DSA were evaluated. The use of an ammonium sulfate precipitation assay showed suggestive evidence of antibody binding but high levels of TDI-DSA precipitation in the absence of antibody limit any usefulness of this technique. Double-antibody co-precipitation techniques will measure total antibody or Ig class antibody against 125I-TDI-DSA. These techniques are quantitative. The polystyrene tube radioimmunoassay is a highly sensitive method of detecting and quantitatively estimating IgG antibody. The enzyme linked immunosorbent assay is a rapidly adaptable method for the quantitative estimation of IgG, IgA, and IgM against TDI-homologous proteins. All these techniques were compared and results are demonstrated by using the same serum sample for analysis.

Ammonium Sulfate↗

The relationship of airborne trimellitic anhydride concentrations to trimellitic anhydride--induced symptoms and immune responses.

Eighteen workers exposed to trimellitic anhydride (TMA) powder were evaluated in 1979. Twelve of these workers were available for longitudinal study until 1982. Annual clinical evaluations and serum radioimmunoassays for total antibody binding and specific IgE binding to 125I-TM-HSA were performed. In 1979, five workers had antibody against TM-HSA. Of these, three workers were diagnosed with the late respiratory systemic syndrome (LRSS) and one worker with TMA-induced allergic rhinitis. The LRSS workers had significantly elevated total antibody binding of 125I-TM-HSA and the worker with rhinitis had significantly elevated specific IgE binding of 125I-TM-HSA per milliliter of serum. Although TMA handling was intermittent throughout the year, average airborne dust concentrations from 1974 to 1978 at job stations of the two heaviest TMA-exposed occupations, operator and assistant operator, were 2.1 and 0.82 mg/m3, respectively. After local exhaust ventilation had been improved, average airborne dust concentrations of TMA at the two latter job stations fell to levels of 0.03 and 0.01 mg/m3, respectively, in 1982. The decrease in TMA exposure coincided with a gradual fall in total antibody binding of 125I-TM-HSA per milliliter in 1982 and symptomatic improvement in the three individuals with the LRSS. The continuous low-level exposure of the worker with TMA rhinitis was sufficient to elicit a rise in specific IgE against TM-HSA from 1.1 ng of 125I-TM-HSA bound per milliliter in 1979 to 2.12 in 1982.(ABSTRACT TRUNCATED AT 250 WORDS)

Air Pollution↗

The relationship of total serum IgE and blocking antibody in trimellitic anhydride--induced occupational asthma.

Clinical and immunologic evaluations were performed on workers who manufacture trimellitic anhydride (TMA), a chemical used widely in the plastics industry. Serum samples of 29 workers exposed to TMA dust and fumes were assayed for total IgE, as well as specific IgE and total antibody binding to radiolabeled trimellityl human serum albumin (TM-HSA). Fifteen workers were determined to have significant specific IgE to TM-HSA (greater than or equal to 1 ng of 125I-TM-HSA bound per milliliter). Of these 15 individuals, seven workers had immediate asthma and rhinitis and positive cutaneous prick tests and eight were nonasthmatic and skin test negative. Mean peak total serum IgE was significantly higher in the prick test positive group (p less than 0.02) and higher than in 12 exposed asymptomatic IgE antibody-negative workers (p less than 0.001). Total serum IgE followed rises and falls in TM-HSA--Specific IgE binding, correlating to the onset of allergic symptoms in all seven workers. Total antibody binding of 125I-TM-HSA, as determined by the ammonium sulfate precipitation technique, was higher in the skin test-negative group of eight (mean 12,062 ng per milliliter 125I-TM-HSA bound) than in the seven symptomatic skin test-positive workers (mean 2930, p less than 0.004). Determinations of total antibody divided by specific IgE (both in nanograms of 125I-TM-HSA bound per milliliter) or blocking ratios clearly discriminated the seven skin test-positive workers with TMA-induced asthma (range 10 to 666) from the eight skin test-negative workers (range 1580 to 16,000).(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies↗

Mould counts and exacerbations of allergic bronchopulmonary aspergillosis.

The purpose of this study was to determine whether exacerbations of allergic bronchopulmonary aspergillosis (ABPA) were associated with the total outdoor mould counts in the Chicago area. From 1976-1980, forty-nine flares of ABPA (new pulmonary infiltrate with elevation in total serum IgE) occurred in nineteen patients. Thirty-eight (77.5%) of flares occurred during months June through November in association with increased outdoor mould counts in Chicago. This association confirms earlier observations from the U.K. where during the peak mould season which occurs in winter months, there was an increased number of pulmonary infiltrates and average prednisone doses required in ABPA.

Air Microbiology↗

Airway response to leukotriene D4 in rhesus monkeys.

We studied the effect of leukotriene D4(LTD4) given by aerosol challenge on asthmatic and normal monkeys. The response to LTD4 occurred within 2 min., was prolonged at higher concentrations, was reversed by epinephrine, and more closely resembled an antigen response than a histamine response. Since LTD4 concentrations of 30-100 micrograms/ml produced a response similar to 2-20 mg/ml of histamine, the LTD4 was 300-900 times as potent as histamine on a molar basis. Thus, LTD4, which appears to reproduce an antigen-induced response in rhesus monkeys, may be a mediator of allergic asthma in these animals.

Airway Obstruction↗

Elevated creatine phosphokinase levels associated with influenza A/Texas/1/77 infection.

24 patients admitted to hospital between December 1, 1977 and March 3, 1978 with cultural or serological evidence of influenza A infection were retrospectively analyzed for evidence of elevated creatine phosphokinase (CPK) levels. 14 patients had elevated CPK levels not attributable to usual causes. Muscle biopsies from 2 patients showed focal necrosis and myopathic changes. Influenza A/Texas/1/77 was isolated from the biopsy specimen of 1 patient. Patients with elevated CPK levels tended to have greater per day hospital costs and more complications than patients with normal CPK levels. Elevated CPK levels are relatively common in hospitalized patients with influenza and may be due to influenza virus involvement of skeletal muscle.

Biopsy↗

Syndromes in workers exposed to trimellitic anhydride. A longitudinal clinical and immunologic study.

A longitudinal study of workers involved in the manufacture of trimellitic anhydride has been in progress since 1977. Trimellitic anhydride is a low-molecular-weight, reactive chemical used in the manufacture of plastics. Initial studies done in 1976 defined three syndromes due to inhalation of trimellitic anhydride: asthma-rhinitis, a late respiratory systemic syndrome, and an irritant response. Also, serologic techniques were developed to measure total antibody and IgE antibody to trimellityl human serum albumin. From 1977 to 1981, 64 workers were assessed. Six workers presented with asthma-rhinitis, high levels of IgE antibody, and skin test reactivity to trimellityl human serum albumin; five workers developed the late respiratory systemic syndrome; and one worker had both immunologic syndromes. These serologic measurements detected or were predictive of an immunologic respiratory illness and were useful in monitoring workers involved in the manufacture of trimellitic anhydride.

Asthma↗

Beclomethasone diproprionate for severe asthma during pregnancy.

The safety of using inhaled beclomethasone dipropionate for the treatment of severe asthma during pregnancy was evaluated during 45 pregnancies in 40 women. Despite chronic administration of theophylline and, in some women, ephedrine, the asthma was so severe that corticosteroids were essential to prevent emergency room visits and status asthmaticus. At conception, beclomethasone dipropionate was being used regularly during 38 pregnancies and was initiated during the first trimester in 4 other pregnancies. The range of beclomethasone dipropionate inhalations was 4 to 16/d with a mean of 9.5/d (336 micrograms). Prednisone administration was necessary during 37 pregnancies. Status asthmaticus occurred in five women but no mothers or fetuses died. Cardiac malformations occurred in an infant born to a woman who was diabetic and schizophrenic whose pregnancy was complicated by diabetic ketoacidosis and status asthmaticus. It is not known whether beclomethasone dipropionate was the cause of these malformations. The prevalence of congenital malformations (1 of 43 live births) is within the normal range and shows that treatment with beclomethasone dipropionate is safe during pregnancy when recommended doses are used.

Abnormalities, Drug-Induced↗

A radioimmunoassay index for allergic bronchopulmonary aspergillosis.

Differentiating patients with allergic bronchopulmonary aspergillosis from those with asthma who have immediate cutaneous reactivity to Aspergillus fumigatus may be difficult. Both groups have IgE and IgG antibodies against aspergillus antigen. We describe methods for establishing IgE and IgG antibody indices using sera from asthmatic patients as a control serum pool. The IgE and IgG antibody indices are usually both positive and at least one index was positive in all patients during the acute stage. The indices had diagnostic value in individual patients during the other four stages, but were not consistently positive in patients in any other stage. In a patient with a suspected case, serodiagnosis should be attempted before corticosteroid therapy is started; thus, acute-phase serum should be obtained and stored before therapy.

Acute Disease↗

Induction of IgE-mediated cutaneous, cellular, and airway reactivity in rhesus monkeys by Ascaris suum infection.

In order to maintain a colony of rhesus monkeys with IgE-mediated Ascaris asthma, we evaluated the response of four animals to infection with Ascaris suum ova. All four animals developed immediate-type cutaneous reactivity and airway responses. Serum IgE and IgG antibody responses against Ascaris antigen, as quantitated by the ELISA, were seen in all animals. Peripheral blood histamine release after stimulation with Ascaris antigen was positive in all animals. Airway reactivity to aerosol challenge with Ascaris antigen became positive in all animals and has remained positive for 6 months in three of four animals. Both standard and threshold dose airway types of responses were present. Except for transient eosinophilia, the animals remained in good health. The studies demonstrate that infection with A. suum results in rhesus monkeys with IgE-mediated immediate-type reactivity that simulates the naturally occurring model of asthma.

Animals↗

Dissociation of IgE from receptors on human basophils. I. Enhanced passive sensitization for histamine release.

Leukocytes of only one of 11 nonatopic donors could be passively sensitized for histamine release elicited by ragweed extract. A short incubation in an unbuffered isotonic saline at pH 3.9 or in an 0.01 M lactic acid/lactate-buffered isotonic saline at pH 3.9 dissociated from 4 X 10(5) to less than 3 X 10(4) IgE molecules per basophil from washed leukocytes of several in a series of six atopic and 11 nonatopic donors. After such treatment, leukocytes of only one of the 11 nonatopic donors could not be sensitized for histamine release. Basophils of the four ragweed-sensitive donors lost their sensitivity to ragweed after the treatment, but all could be passively resensitized; for three of these donors the level of release approximated their original reactivity. Leukocytes of the two mold-sensitive donors could be passively sensitized to ragweed allergens after but not before treatment. Four plasma samples from histamine release-positive volunteers were used for sensitization of treated leukocytes of each cell donor; three were consistently effective and one was consistently ineffective. The positive plasmas had concentrations of antigen E-specific IgE of over 100 ng/ml, which accounted for 17 to 23% of the total IgE; the inactive one had less than 5 ng/ml of specific IgE. For each cell donor, all three samples of active plasma mediated quite similar histamine release, but there was a spectrum of donor cell reactivity ranging from 23 to 70% release. These results suggest that basophils from each donor, atopic or nonatopic, had a maximal potential for in vitro sensitization, which was only attained if the plasma contained appropriate, but yet to be fully defined, concentrations of specific and total IgE. Several unexpected results were obtained. Treated leukocytes from some individuals were sensitized for mediator release to a greater extent by sixfold diluted than undiluted plasma. In addition, a 4-hr incubation with plasma at 37 degrees C, but not at 25 degrees C or 0 degrees C, was less effective than were shorter incubation periods. Treated leukocytes should be useful in studying kinetic and equilibrium parameters of IgE binding to specific receptors on human basophils. Analogous treatments should also be useful in sensitization and measurement of IgE-receptor interactions of mast cell populations.

Basophils↗