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Biomedical subjects

K E Harris

Publications and source records attributed to K E Harris.

At least 91 records · Page 5Linked to original sources
PubMed1982

An animal model of occupational immunologic asthma due to diphenylmethane diisocyanate, with multiple systemic immunologic responses.

Inhalation of MDI in the plastics industry may produce hypersensitivity pneumonitis or immediate-type asthma in workers. A suspension of MDI was given intrabronchially to dogs to determine whether any of the clinical and immunologic human responses could be duplicated, Results showed that dogs produce a systemic immune response to MDI-DSA. Serum MDI-125I-DSA binding was shown by the ammonium sulfate binding technique. Antibody activity of IgG, IgA, and IgM antibody classes was shown by a solid-phase enzyme-linked immunoassay. Precipitating antibodies were detected in he dog serum against MDI-DSA. Immediate-type skin reactivity to MDI-DSA consistent with a canine IgE response occurred. The skin reactivity appeared to correlate with an immediate-type airway response characterized by an increase in pulmonary resistance after intrabronchial MDI. There was transient peripheral blood lymphocyte reactivity to MDI-DSA. The results indicate that a large animal model of human immune response to MDI is available for various immunopathogenic studies.

Airway Resistance↗
PubMed1981

Inhibition of immunoglobulin E-mediated, antigen-induced monkey asthma and skin reactions by 5, 8, 11, 14-eicosatetraynoic acid.

The immediate-type, IgE-mediated rhesus monkey model of asthma due to aerosol challenge with ascaris has been developed to the status of an analytic system for agents capable of inhibiting the antigen-induced airway response. Two antigen-challenge systems have been developed. The standard ascaris challenge uses a dose of antigen that will induce an airway response in all reactive animals. In the threshold antigen-challenge system, the threshold dose of antigen that will induce an airway response is determined and is relatively constant for the individual animal. Both of these types of response were inhibited by 5,8,11,14-eicosatetraynoic acid (ETYA). This action may be through the inhibition of the lipoxygenase and cyclooxygenase metabolic pathways of arachidonic acid and possibly through inhibition of production of slow-reacting substance. ETYA also inhibits cutaneous immediate-type reactivity to ascaris antigen in a dose-response relationship. This may be the result of inhibition of mast cell histamine release or the inhibition of production of other vasoactive mediators. An alternative explanation for the action of ETYA in the airway and skin responses is that ETYA may act as an end-organ antagonist to released bioactive mediators. ETYA is the first agent, other than beta agonists or cromolyn, that we have been able to demonstrate as clearly having an inhibitory action on the rhesus monkey model of asthma.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1981

An agent that releases basophil and mast cell histamine but blocks cyclooxygenase and lipoxygenase metabolism of arachidonic acid inhibits immunoglobulin E-mediated asthma in rhesus monkeys.

An inhibitor of the lipoxygenase and cyclooxygenase pathways of arachidonic acid metabolism, BW755C, was evaluated with the rhesus monkey model of IgE-mediated asthma. BW755C was found to release histamine from human and rhesus peripheral blood leukocytes and rhesus bronchial lavage cells. BW755C did not induce a rhesus airway response but inhibited antigen-induced airway changes in pulmonary resistance and dynamic compliance. The results demonstrated that a lipoxygenase and cyclooxygenase inhibitor that is a histamine releaser may inhibit some pulmonary function abnormalities of an IgE-mediated response and suggested that histamine has a minor role as a stimulator of airway reaction in this model. This was supported by studies showing failure of the histamine H1 blocker pyrilamine maleate to inhibit the antigen-induced airway response. Although BW755C has been shown to be a lipoxygenase and cyclooxygenase inhibitor, it is not established that the inhibiting action of this agent on an antigen-induced airway response is due to an effect on arachidonate metabolism in the lung.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1980

Effect of prostaglandin D2 and I2 on the airways of rhesus monkeys.

Prostaglandin (PG) D2 and PGI2 were evaluated to determine their effect on pulmonary function parameters when aerosolized in anesthetized rhesus monkeys. PGD2 resulted in an increase in frequency (f) and pulmonary resistance (rl) and a decrease in peak expiratory flow rate (PEFR), tidal volume (VT), and dynamic compliance (Cdyn), with the major effect on RL. PGI2 primarily effected an increase in f and a decrease in PEFR and VT. PGI2 had a variable effect, generally a decrease, on RL. The metabolite of PGI2, 6-keto-PGF 1 alpha, had no effect on the rhesus airway. PGF 2 alpha responses were similar to PGD2 except that the PGF 2 alpha produced a less strikingly consistent increase in RL. When PGI2 and PGD2 were aerosolized simultaneously, they simulated previously described antigen responses. Further, PGI2 plus PGD2 produced an airway response at 1/10 the concentration of either agent alone.

Animals↗
PubMed1980

Antibodies in hemodialysis patients against hapten-protein and hapten-erythrocytes.

Serum samples obtained from hemodialysis patients with immediate-type hypersensitivity reactions and hemodialysis patients with no reactions were analyzed for antibody activity against hapten-protein complexes prepared from PA and MDI. These chemicals, used in preparation of plastics, have been shown to be associated with immunologically mediated disease in other studies. IgE and IgG antibodies against P-HSA and MDI-HSA were detected in several sera, but symptomatic patients could not be differentiated from asymptomatic patients by antibody levels. Antibodies capable of agglutinating or hemolyzing P-E were also detected in some sera from hemodialysis patients. These studies demonstrate that although no clinical disease has yet been correlated with these antibodies, sufficient exposure of hemodialysis patients to protein-reactive chemicals occurs to elicit an immunologic response against hapten-protein or hapten-cells. Such antibodies may have immunopathogenetic significance in subjects systemically exposed to fluids which have been in contact with plastics.

Albumins↗
PubMed1979

Ionophore and arachidonic acid stimulation of airway responses in rhesus monkeys.

Aerosolized doses of the ionophore, A23187, and arachidonic acid individually resulted in no airway response in rhesus monkeys. When these two agents were given simultaneously, by aerosol, an airway response occurred. The pulmonary function abnormalities that occurred qualitatively simulated those of an antigen-induced airway response. This is the first demonstration in our laboratory of two agents which singly will not produce a response but which are reactive when delivered in combination. Other fatty acids did not produce a similar response. The response to A23187 and arachidonic acid occurred only in rhesus monkeys from our colony which had been demonstrated to have airway responses to aerosolized antigen challenge, a response shown previously to be associated with hyperreactive airways to pharmacologic stimuli. The A23187 and arachidonic acid response was inhibited by aerosolized 5,8,11,14-eicosatetraynoic acid, an inhibitor of the cyclooxygenase and lipoxygenase pathways of arachidonic acid metabolism. Further, indomethacin, a prostaglandin synthetase inhibitor of the cyclooxygenase pathway, inhibited the response, although previous studies showed that this drug will potentiate an antigen-induced response in this animal model of asthma. The slow-reacting substance of anaphylaxis antagonist, FPL 55712, did not inhibit the A23187-arachidonic acid response under the conditions of these experiments. The mechanism of the A23187-arachidonic acid airway response in rhesus monkeys may or may not be the same as the antigen-induced response.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1978

A study of the effect of slow-reacting substances of anaphylaxis on the rhesus monkey airway.

Slow-reacting substance of anaphylaxis (SRS-A) generated from rat peritoneal mast cells was aerosolized to the airways of a group of rhesus monkeys with established airway responses to ascaris antigen. A selective effect of SRS-A on pulmonary resistance and a lesser but significant effect on compliance was observed which differed from antigen, histamine, carbocholine, or prostaglandin (PG) F2alpha responses. The airway recovery from the PR change is slower than that from histamine and simulated PGF2alpha and some antigen experiments. The cutaneous reactions in rhesus monkeys due to SRS-A could be blocked in a dose response pattern by FPL55712 which did not affect histamine responses in rhesus skin.

Aerosols↗
PubMed1978

The qualitative evaluation of airway responses to immunologic and pharmacologic stimuli in rhesus monkeys.

This report describes the current status of a colony of rhesus monkeys composed of a group of animals with consistent asthmatic responses to Ascaris antigen challenge, a variable group and a negative group. The cumulative experience with the consistent group of 5 animals totals 144 months of observation with 86 positive respiratory responses to 86 aerosol challenges. Further studies compare rhesus airway responses to Ascaris antigen, anti-IgE, histamine, prostaglandin (PG)F2alpha, carbocholine, and physostigmine. We report that two abnormalities of pulmonary function which occur as a result of aerosol challenge, an increase in breathing frequency (f) and pulmonary resistance (PR), differ in degree of abnormality and time of onset following challenge with different agonists. These results indicate that the f and PR changes in response to these agonists are controlled by different physiologic mechanisms in rhesus monkeys. We suggest that the f changes may occur as a result of reflex afferent vagal stimulation and PR changes as a result of direct effect on smooth muscle receptors. The effect of histamine and PGF2alpha on the airway of rhesus monkeys more closely simulates the airway response to immunologic stimuli than does the effect of cholinergic type agonists.

Aerosols↗
PubMed1978

The in vivo transfer of antigen-induced airway reactions by bronchial lumen cells.

Rhesus monkeys with airway responses to aerosol challenge with Ascaris antigen constitute a primate model of inhalant asthma. Previous studies have shown that bronchial lavage cells from airway-reactive animals will release histamine or a slow-reactive substance of anaphylaxis after challenge with antigen. Because these bronchial lumen cells are the first cells in contact with inhaled antigen, they may play a role in induction of antigen-induced airway responses. To evaluate this possibility, bronchial lumen lavage cells from animals with airway reactivity were transferred to the bronchial lumens of animals with negative airway responses to antigen challenge. The transfer of the bronchial lumen cells resulted in transient airway reactivity of the recipients to aerosol antigen challenge. It is suggested that the mast cells which constitute a component of the bronchial lumen cells may be the active cell alone, or in combination with other cells, which results in this primate immunoglobulin E-mediated airway response and its transfer to nonreactivie recipients.

Animals↗
PubMed1978

Aerosolized antigen dose-response studies in asthmatic monkeys.

This study used rhesus monkeys which had consistent respiratory responses to a standard (single dose) aerosolized concentration of A. Beginning at lower concentrations of A which did not produce an airway response, fourfold increases in concentrations of A were aerosolized until an airway response occurred. Compared with the single-dose SAC after the TAC, some consistently reactive animals did not respond to the SAC, the maximal concentration of A used for testing. Thus the TAC may result in an acute form of airway desensitization. Animals vary in the threshold concentrations of A required to produce an airway response. A repeat challenge with the threshold antigen concentration during the same experiment resulted in a second response generally greater than the initial response at the same concentration. When the SAC system was similarly evaluated by repeat challenges with the same A concentration, the second response was generally less than the first. Different methods for evaluation of pharmacologic inhibitors of IgE-mediated airway responses may be developed from this rhesus model of asthma.

Aerosols↗
PubMed1977

Acute urticaria and bronchospasm following radiographic contrast media in a dog.

An immediate-type systemic reaction in a dog following intravenous radiographic contrast media (RCM) manifested by urticaria and wheezing on one occasion and urticaria alone on another occasion is described. This reactivity disappeared spontaneously and plans to study the mechanisms of such a reaction were not possible. If such reactivity is more persistent in certain other dogs, a model for study of immediate type reactivity to RCM would be available.

Acute Disease↗
PubMed1977

Mitogen-induced lymphocyte and cutaneous reactions in dogs.

The lymphocyte response of dogs to mitogens was determined using separated lymphocyte and whole blood lymphocyte proliferation techniques. Reactivity to optimal doses of the following mitogens was demonstrated in decreasing order of intensity: phytohemagglutinin, Pokeweed mitogen, conconavalin A and sodium periodate. The canine cutaneous reactivity to these mitogens was also determined. Grossly, erythema and induration with all mitogens was maximal at 24 h. Microscopically, lesions using all mitogens consisted of edema, hyperemia and diffuse dermal infiltration with polymorphonuclear leukocytes and mononuclear cells. These mitogen-induced lesions may represent a specific lymphocyte-mediated inflammatory response, although a nonspecific reaction cannot be excluded.

Animals↗
PubMed1977

Sequential immunologic stimuli to the respiratory tract: a paradox in the degree of potentiation of airway responses depending on the sequence of reverse passive and active immunologic stimulation.

Immunologic stimuli to the airway of rhesus monkeys were given by aerosol challenge with ascaris antigen or anti-IgE. Both of these stimuli produce immediate-type airway responses. When 2 sequential aerosol challenges were given during the same experiment, the response following the second stimulus was always less than or equal to the first response following any combination of stimuli except the anti-IgE-ascaris sequence. The second response following the latter challenge was always greater than or equal to the first response. The possibility that this exception was the result of anti-IgE priming mediator releasing cells for antigen was not supported by in vitro experiments. It is suggested that the results obtained with the anti-IgE-ascaris sequence may relate to the presence of intralumenal mast cells in the bronchi and the molecular weights of the 2 immunologic stimuli.

Animals↗