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J L Ohman

Publications and source records attributed to J L Ohman.

At least 37 records · Page 2Linked to original sources

Immunotherapy in cat-induced asthma. Double-blind trial with evaluation of in vivo and in vitro responses.

The efficacy of immunotherapy in cat-induced asthma was studied by use of a purified fraction of cat-pelt extract and a double-blind protocol. Nine active-treatment subjects who received a mean cumulative dose of cat allergen, 1 of 10.9 units, and eight placebo-treatment subjects completed the study. Active treatment resulted in significant reductions in bronchial sensitivity (p less than 0.05) and prick test titer (p less than 0.01). In addition, active treatment resulted in a significant delay in the onset of ocular (p less than 0.05) and pulmonary (p less than 0.02) symptoms on exposure to living cats. Significant increases in IgG antibody to cat allergen 1 (p less than 0.001) and cat albumin (p less than 0.01) also occurred with active treatment. There was no significant change in bronchial reactivity to methacholine or in the sensitivity of circulating basophils. These results confirm the validity of immunotherapy in allergic asthma where there is careful patient selection and well defined treatment preparations.

Allergens↗

Cat allergen 1: Biochemical, antigenic, and allergenic properties.

Cat allergen 1, an important agent in human allergic reactions, has been partially purified by affinity chromatography. Heating the purified allergen at 100 degrees C for 30 min resulted in a 28% loss in the antigenicity of the allergen molecule (determined by Laurell rocket assay), although lower temperatures had little effect. Its allergenicity (determined by passive transfer skin test) was diminished slightly after heating to 56 degrees C or 100 degrees C. Reduction with dithiothreitol or 2-mercaptoethanol resulted in greater losses of antigenicity and allergenicity but did not obliterate these properties. Three forms of the affinity-purified allergen (isoallergens) differing slightly in isoelectric point were demonstrated by isoelectric focusing followed by crossed immunoelectrophoresis. The molecular weight of cat allergen 1 under physiologic conditions was 35,000 +/- 2000 as determined by gel filtration in Sephadex G-75. Under the dissociative conditions of sodium dodecyl sulfate-polyacrylamide gel electrophoresis, with or without prior reduction by dithiothreitol, cat allergen 1 appeared to exist as an antigenically active subunit with a molecular weight of 18,000 +/- 2000. This subunit molecular weight estimate was confirmed by gel filtration in 6M guanidine hydrochloride. The stability of the allergenic and antigenic activity of cat allergen 1 suggests that this activity may be determined partially by the primary sequence of allergenic sites on the molecule. The separation and purification of molecular subunits may allow sequence analysis of these sites.

Allergens↗

Distribution of cat allergen 1 in cat tissues and fluids.

The distribution of the major allergen of the domestic cat, cat allergen 1, was studied in 22 different tissues obtained from a male and female cat and in samples of saliva and urine. Of the cat tissues studied, only extracts of pelt and female brain contained amounts of cat allergen 1 in excess of 0.50 U/ml. Smaller amounts of cat allergen 1 were found in extracts of eye, thyroid, ovary, sublingual gland and large intestine. Unstimulated cat saliva contained a mean of 1.08 U/ml cat allergen 1. Saliva stimulated with ketamine HCl alone, or with ketamine HCl plus pilocarpine, contained 0.68-8.16 U/ml cat allergen 1. In all of the stimulated saliva collections, the total quantity of cat allergen 1 obtained was relatively constant (between 40 and 80 U). These results suggested that the elaboration of cat allergen 1 in saliva is independent of parasympathetic control. Cat allergen 1 could only be detected in cat urine that had been concentrated 9-fold in concentrations of less than 0.5 U/ml. The above results support the hypothesis that the major source of cat allergen 1 is the saliva, and that the presence of cat allergen 1 in the pelt is due to deposition of the allergen during grooming.

Allergens↗

Surface washes of living cats: an improved method of obtaining clinically relevant allergen.

Washing the surface of live anesthesized cats with water results in a solution rich in allergen 1 and low in albumin. CIE and CRIE analysis showed the presence of at least seven antigens. All were shown to be immunologically identical to antigens that occur in pelt extracts and saliva. The only allergens that could be detected in surface washes were allergen 1 and albumin. The animals could be washed at monthly intervals to yield approximately the same quantity of allergen 1. This simple procedure could provide an excellent source of potent cat allergen extracts.

Allergens↗

Allergens detected in association with airborne particles capable of penetrating into the peripheral lung.

Extrinsic asthma is caused by exposure to airborne allergens. The diameter of airborne particles influences the depth of penetration and deposition fraction in the lung. In this study, we used an Andersen sampler to collect 9 different size ranges of airborne particles from a cat-containing and a cat-free room. We detected cat allergen 1 (CA1), the major cat allergen, using a rocket immunoelectrophoretic technique in larger particle size ranges (more than 5 mu). Using in vitro cat allergic donor basophil histamine release, cat-associated allergen activity was detected in particle size ranges from 10 to less than 1 mu in aerodynamic diameter. Control collections of airborne particles from a cat-free room showed little or no allergen activity, and nonatopic donor basophils did not release histamine in response to any of these samples. The P-K test (positive transfer test) confirmed findings of the other assays. We conclude that cat-derived allergens are associated with a large range of airborne particle sizes that penetrate into the peripheral lung.

Air↗

Cat allergy.

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Animals↗

Antibody responses following immunotherapy with cat pelt extract.

IgG antibody responses to a major allergen, cat allergen 1 (cat 1), and to a minimally allergenic protein, cat albumin (alb), were studied in patients who had received 4 to 11 mo of immunotherapy with three concentrations of crude cat pelt extract. A double-antibody radioimmunoassay utilizing 125I-labeled antigen was used to measure IgG and IgE antibody. The high-dose group (HDG)(n = 5), which was composed of the active-treatment group of a previously reported double-blind study, received a mean cumulative dose of 3440 microgram cat 1 and 10,660 microgram alb. The intermediate-dose group (IDG) (n = 6) and low -dose group (IDG)(n = 5) received 70 and 0.930 microgram of cat 1 and 217 and 2.86 microgram of alb. IgE antibody to cat 1 before treatment was measurable in most patients. IgE antibody to alb was either no measurable or of a low level. Mean (geometric) before-and-after IgG levels (U/ml) to cat 1 in the HDG, IDG, and LDG were 420 and 7794, 158 and 1388, an 191 and 1365, respectively. Mean before-and-after IgG levels (U/ml) to alb in the HDG, IDG, and LDG were 72 and 348, 1.9 and 4584, and 0.4 and 508, respectively. Two patients (HDG) had no IgG antibody to alb after treatment. Another patient (HDG) had 82,364 U/ml IgG antibody to alb and precipitating antibody by gel diffusion. Very intense IgG antibody response to both cat 1 and alb were seen over a wide range of immunizing doses.

Adult↗

Parathyroid hormone and 25-hydroxyvitamin D levels in glucocorticoid-treated patients.

Abnormalities in parathyroid hormone (PTH) secretion or vitamin D action or metabolism have been suggested as pathogenetic factors in the bone disease associated with chronic glucocorticoid therapy. We have found normal plasma PTH values in forty-eight adult asthmatic patients on chronic glucocorticoid therapy, twelve asthmatics treated without glucocorticoids and ten adults on short-term, high-dose glucocorticoid therapy for non-asthmatic illnesses. The mean serum 25-OHD level in the glucocorticoid-treated asthmatics was not significantly different from a disease control group of asthmatic patients not on glucocorticoids, but nine such patients had abnormally low 25-OHD levels. Our results indicate that in asthmatic patients on chronic glucocorticoid therapy: (1) PTH and 25-OHD values are usually normal regardless of dose or duration of therapy and (2) there is a subset of patients with low 25-OHD values which may reflect unusual sensitivity to glucocorticoids.

Adult↗

Myths, morbidity, and mortality in asthma.

Persistence of outmoded concepts or "myths" concerning the diagnosis and treatment of asthma probably is responsible for large economic losses, overutilization of hospital beds, and many preventable deaths. There have been many worthwhile studies refuting these myths, leading to the following conclusions: Asthma consists of much more than wheezing and in many cases must be treated long after wheezing stops. There is no convincing evidence relating the chronic pulmonary changes of asthma to the psyche. Modern methods of prescribing theophylline have not made it universally effective and safe. Intermittent postive-pressure breathing is rarely justified in asthma. Respiratory acidosis may be corrected only by improving alveolar ventilation. Corticosteroids are usually essential for control of severe asthma and may be used safely. Severe asthmatics need careful monitoring because sudden respiratory failure may occur.

Acidosis, Respiratory↗

Immunotherapy in cat-induced asthma. Double-blind trial with evaluation of bronchial responses to cat allergen and histamine.

Ten asymptomatic patients with normal pulmonary function were selected for a double-blind trial of immunotherapy in cat-induced asthma. Each patient had a positive prick test to cat pelt extract and also a positive bronchial challenge response to the same extract. Patients were randomly assigned to active treatment or placebo groups and received weekly or biweekly injections over a 3 to 4-month period. The 5 patients who received the active treatment received a cumulative dose of cat pelt extract that ranged from 16.4 to 44.8 mg of total solid containing 1.7 to 4.7 mg of cat allergen 1. Apparent systemic reactions were observed in 3 patients who received the placebo and 3 patients who received the active treatment. The 5 patients who received the active treatment showed a reduction in skin reactivity to cat pelt extract as well as a significant mean reduction in bronchial sensitivity to the same extract. The 5 patients who received the placebo showed no significant changes in skin reactivity or bronchial sensitivity to cat pelt extract. Bronchial response to histamine did not change significantly in either the active treatment of the placebo group.

Allergens↗

Insulin antibodies in the pathogenesis of insulin allergy and resistance.

Insulin allergy developed in a patient treated with beef/pork insulin. Desensitization therapy led to cessation of the allergy, but it was associated with the development of diabetic ketoacidosis with apparent insulin resistance which was successfully treated with fish insulin. The patient's initial serum contained a high titer of anti-insulin immunoglobulin E (IgE) antibody directed primarily against beef insulin. Desensitization therapy with pork insulin was associated with the production of anti-insulin immunoglobulin G (IgG) antibody with highest immunologic reactivity to pork insulin. This IgG antibody may have blocked the interaction of insulin with tissue-fixed IgE antibody but, in addition, led to significant increases in total serum insulin-binding capacity and transient insulin resistance. The favorable clinical response to fish insulin was likely due to the negligible immunologic reactivity of this patient's anti-insulin antibodies with fish insulin. This report suggests that desensitization therapy for insulin allergy can lead to insulin resistance of the immune type.

Animals↗

Allergens of mammalian origin. IV. Evidence for common allergens in cat and dog serum.

IgE antibodies present in serum from 3 patients clinically sensitive to cat and dog were shown to combine with whole cat and dog sera linked to cellulose particles. Employing a modified radioallergosorbent technique (RAST), it was shown that cat and dog sera inhibited the binding of IgE antibodies to insolubilized cat serum and to insolubilized dog serum. These findings suggest that cat and dog sera have common allergens. Other mammalian sera were also tested and found to have little inhibitory activity. Cat and dog sera did not inhibit the binding of IgE antiragweed antibodies to an insolubilized ragweed fraction. Following separation of cat serum by gel filtration on Sephadex G-200 or electrophoresis in acrylamide gel, several fractions were found to inhibit the binding of IgE antibodies to insolubilized cat and dog sera. Whether the heterogeneity observed reflects the presence of single allergens with diverse size and charge properties or multiple allergens remains to be determined.

Allergens↗

Allergens of mammalian origin V. Properties of extracts derived from the domestic cat.

Eight commercial cat dander extracts and two pelt extracts derived from mongrel and Siamese cats were compared. Cat allergn 1 and cat albumin were measured by radial immunodiffusion. Allergenic activity was evaluated by prick test and a modified radioallergosorbent test. In the latter, the dilution of each extract that produced 50% inhibition of binding of IgE antibodies to insolubilized cat allergen 1 (RAST 1) and insolubilized cat serum (RAST 2) was determind. The total non-dialysable solid content of the extracts did not correlate with any other parameter. Cat allergen 1 content determined by radial immunodiffusion correlated with average prick test results in ten cat-sensitive subjects and with RAST 1 activity. Cat albumin content correlated weakly with RAST 2 activity but not with any other measure of allergenic activity. Absorption of each extract with the gamma-globulin fraction of rabbit antiserum to cat allergen 1 significantly reduced prick test reactivity and RAST 1 activity, but not RAST 2 activity. These results indicate that cat allergen 1 is an important allergen in cat dander extracts and its measurement may be used to standardize the allergenic activity of such extracts.

Albumins↗

Allergens of mammalian origin. II. Characterization of allergens extracted from rat, mouse, guinea pig, and rabbit pelts.

Aqueous extracts prepared from lyophilized, defatted rat, mouse, guinea pig, and rabbit pelts elicited intense wheal-and-flare responses in the skin of a high proportion of patients who were clinically sensitive to these animals. The major allergens in each extract were nondialyzable. Skin test reactions to rat, mouse, and guinea pig serum were common in patients allergic to these animals. The fractions of rat, mouse, and rabbit pelt extract showing maximum allergenic activity contained proteins with the electrophoretic mobility of serum albumin. Fractions of guinea pig pelt extract with maximum allergenic activity were of prealbumin mobility and contained little stainable protein. On Sephadex G-100 gel filtration, most allergen from rat, mouse, and guinea pig pelt extracts was recovered in fractions containing proteins with a molecular weight range of 10,000 to 25,000 daltons. Allergen in rabbit pelt extract had a slightly higher molecular weight range of 18,000 to 38,000 daltons.

Allergens↗