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Biomedical subjects

K E Harris

Publications and source records attributed to K E Harris.

At least 55 records · Page 3Linked to original sources
PubMed1990

The use of an immunoassay index for antibodies against isocyanate human protein conjugates and application to human isocyanate disease.

Serum IgG and IgE to isocyanate haptenized human serum albumin (HSA) were estimated by ELISA in 55 isocyanate workers who underwent isocyanate inhalation challenge studies in Montreal, Canada. The challenges were negative in 29 workers and positive in 26 workers. Isocyanate antibodies were estimated by ELISA index. The mean IgG indices were found to be significantly higher in the challenge-positive workers, and there was a similar trend for the IgE indices. Antibody specificities for toluene diisocyanate-HSA, diphenylmethane diisocyanate-HSA, and hexamethylene diisocyanate-HSA were determined by inhibition studies with a variety of isocyanate haptenized carriers. The other isocyanate substituted carriers were either noninhibitory or caused only partial inhibition as contrasted with the complete inhibition achieved by HSA conjugated to the isocyanate to which the worker was exposed. We interpret these specificity studies as indicating that the inhalation of isocyanates results in production of antibody that recognizes new antigenic determinants that develop from the coupling of isocyanates to homologous proteins.

Antibodies↗
PubMed1990

Rhesus monkey airway responses to substance P.

The tachykinin, substance P (SP), was used as a model to study airway and cutaneous responses in a group of normal rhesus monkeys or animals with IgE-mediated cutaneous reactions to Ascaris antigen (AA) alone or animals with both IgE-mediated cutaneous and airway responses to AA. Aerosolized SP (10 mg/ml) resulted in airway responses qualitatively similar in duration and pulmonary function abnormalities to AA. These SP airway responses were most closely associated with the presence of IgE antibody to AA and were not increased in animals with airway reactivity to AA. A dose response to aerosolized SP can be established. An enkephalinase inhibitor, thiorphan, did not potentiate SP airway responses but appeared to potentiate SP cutaneous responses in some animals. SP cutaneous reactions could be demonstrated and did not correlate with the IgE-mediated cutaneous dilution titers to AA.

Administration, Inhalation↗
PubMed1990

Immunologic hemorrhagic pneumonia caused by isocyanates.

The occurrence of hemoptysis, dyspnea, and bilateral pulmonary opacities progressed to respiratory failure in a 34-yr-old man. Recovery occurred with corticosteroid therapy. In the absence of evidence for an infectious etiology, the possibility of immunologic trimellitic anhydride (TMA) hemorrhagic pneumonitis was considered when the lung biopsy excluded Goodpasture's and other diseases and because the patient was a spray painter. Serologic evaluation for antibodies against TMA was requested. Because the immunologic studies for TMA were negative, and because the patient was a spray painter, immunoassays for three isocyanates conjugated to human serum albumin (HSA) were carried out although there was no specific history of isocyanate exposure at that time. High levels of IgG and IgE antibodies were detected against hexamethylene diisocyanate (HDI)-HSA and toluene diisocyanate (TDI)-HSA. Further investigation documented exposure to spray paint that contained HDI and another isocyanate. The paint was sprayed on warm metal, and subsequently the worker developed an acute illness. Further plant studies were not possible. We propose that the pathogenesis of this case of hemorrhagic pneumonitis is immunologic because of uncontrolled exposure to HDI and TDI, is analogous to the immunologic hemorrhagic pneumonia caused by TMA, and should be considered as a possible cause of a similar acute lung disease after isocyanate exposure.

Acute Disease↗
PubMed1990

Evaluation of ketotifen in corticosteroid-dependent idiopathic anaphylaxis.

To study the possible efficacy of ketotifen (K) in the treatment of idiopathic anaphylaxis (IA), K was administered in an open-label trial to six patients with IA who required corticosteroids at doses below which their disease could not be controlled. During the study, patients continued to receive noncorticosteroid medications (eg, antihistamines, oral adrenergic agents) that had been used on a regular basis for treatment of IA before study, but periodic attempts to reduce corticosteroid doses were made. A reduction of prednisone dose with continued control of disease was judged to be evidence for a beneficial effect of K. After 7 to 16 months of K administration, three patients were judged to have had probable benefits from K (reductions in alternate day prednisone dose requirement from 40 mg to none, 35 mg to 15 mg, and 30 mg to none), and one patient had a possible benefit from K (dose reduction from 100 to 120 mg to 77 mg). Two other patients were unable to tolerate major decreases in prednisone without developing symptoms or signs of IA. Within the limitations of this study design, we conclude that K may be efficacious in the treatment of some patients with IA, and that further trials of K in the treatment of IA are indicated.

Adult↗
PubMed1989

IgG antibody against formaldehyde human serum proteins: a comparison with other IgG antibodies against inhalant proteins and reactive chemicals.

Immune responses to formaldehyde (F) have been recorded for seven decades. More recently, sensitive assays for antibody against F-human serum albumin (HSA) have been reported. IgG antibody against F-HSA has been said to correlate with symptoms against F-HSA. We report on 61 serum samples analyzed for IgG antibodies against F-HSA. IgG antibodies against F-HSA were most prevalent in subjects who had received intravenous F. In no case (either presumed symptomatic to F or with IgG antibody against F-HSA) was there a correlation of serologic results with symptoms. We also reviewed inhalation disease caused by chemicals and proteins acting as immunogens and report that at this time there is no evidence that gaseous F meets the criteria for causation of inhalational IgG-mediated lung disease by clinical or serologic studies. Very high IgG antibody levels occur in respiratory immunologic inhalational disease, and the absence of these high IgG levels against F is strong evidence against F or F proteins being an inhalational antigen of significance.

Allergens↗
PubMed1989

Effects of combined receptor antagonists of leukotriene D4 (LTD4) and platelet-activating factor (PAF) on rhesus airway responses to LTD4, PAF and antigen.

Rhesus monkeys with IgE-mediated asthmatic-type responses to Ascaris suum antigen were pretreated with a combination of 2 receptor antagonists to leukotriene D4 (LTD4) and platelet-activating factor (PAF). This combination of anti-LTD4 and anti-PAF was shown to inhibit airway responses to either LTD4 or PAF in separate experiments in these Ascaris airway-reactive animals. When the same combination of LTD4 and PAF receptor antagonists was used to pretreat the same animal prior to aerosol challenge with Ascaris antigen we could not demonstrate inhibition of the antigen-induced airway response. Thus, combined receptor blockade for LTD4 and PAF did not alter IgE-mediated acute airway responses to antigen in this species. We review the current status of rhesus asthma and LTD4 and PAF receptor antagonist activity in this model.

Animals↗
PubMed1988

The laboratory evaluation of IgE antibody to metabisulfites in patients skin test positive to metabisulfites.

An immediate-type hypersensitivity reaction has been proposed as one possible mechanism in which metabisulfites (MBSs) cause reactions. As demonstrated with certain occupational chemicals, we proposed that MBS might conjugate with human proteins, such as human serum albumin, and then cause an immunologic response. Because we had identified no reactions to MBS at the Northwestern Allergy Service, we used sera from four patients reported elsewhere as having positive skin tests and positive oral challenges to sulfites. We attempted to demonstrate, both in vitro by ELISA and in vivo by passive cutaneous transfer to monkey, evidence for IgE-mediated hypersensitivity to MBSs. Our results demonstrated that there is evidence of IgE antibody by passive transfer for one patient studied, but no evidence of IgE antibody by ELISA to an MBS-albumin conjugate in any of the four patients. This study illustrates the complexities involved in the evaluation and mechanism of MBS-induced disease and the caution with which results must be interpreted.

Animals↗
PubMed1988

Irritant symptoms and immunologic responses to multiple chemicals: importance of clinical and immunologic correlations.

An evaluation of workers in a plant was conducted because of multiple complaints of ocular, nasal, skin and chest symptoms. Antibody activity against 4 different chemicals was identified: an aliphatic diisocyanate, 4-vinylcyclohexene dioxide, trimellitic anhydride (TMA) and an unknown chemical present in a plasticizing ester known as n-octyl-n-decyl-trimellitate. The source of TMA which resulted in immunization in the plant is unknown. The presence or absence of antibodies did not correlate with the presence or absence of symptoms and it was concluded that no occupational allergic disease was present in these workers. Antibody studies alone do not make a diagnosis of occupational allergic disease and clinical correlation is required. Immunoassays may be useful in identifying exposures to immunizing chemicals in the workplace for potential clinical correlation or for exposure monitoring in the workplace.

Air Pollutants, Occupational↗
PubMed1988

Effect of a leukotriene D4 (LTD4) antagonist on LTD4 and ascaris antigen-induced airway responses in rhesus monkeys.

An acute airway response to aerosolized leukotriene D4 (LTD4) qualitatively simulates an IgE-mediated ascaris antigen-induced airway response. The LTD4 airway response is completely inhibited by the LTD4 antagonist, ICI 198615, in normal monkeys. This LTD4 antagonist was then evaluated to determine whether it could inhibit the IgE-mediated ascaris antigen response using the threshold antigen dose-response system or the single antigen dose-response system. In 6 ascaris airway-reactive monkeys, the LTD4 antagonist demonstrated partial inhibition in 2 animals by either the threshold dose system in 1 animal or the single dose system in another animal. In the remaining animals there was no inhibition of the antigen-induced response by the LTD4 antagonist.

Animals↗
PubMed1988

Induction of antigen-specific bronchial reactivity to trimellityl-human serum albumin by passive transfer of serum from humans to rhesus monkeys.

A rhesus monkey model was developed to demonstrate the pathogenetic role of IgE to chemical hapten-protein conjugates in causing human occupational asthma from reactive chemicals. Serum from a worker with trimellitic anhydride (TMA) asthma that contained high titers of IgE, IgG, IgM, and IgA to trimellityl-human serum albumin (TM-HSA) was aerosolized into the lungs of two monkeys to afford passive airway sensitization. After the monkeys were challenged with aerosolized TM-HSA, pulmonary functions demonstrated acute airway responses similar to that of Ascaris antigen-induced, IgE-mediated bronchospasm in Ascaris-sensitive monkeys. The monkeys had no airway reactivity when challenged with TM-HSA 1 week after the first positive TM-HSA response elicited with passive sensitization. Passive cutaneous reactivity to TM-HSA was also elicited by the donor serum, but heat-treated donor serum failed to confer cutaneous or bronchial reactivity. These results indicate that airway reactivity in this passive-transfer monkey model of TMA asthma is an antigen-specific response mediated by heat-labile serum factors, presumably IgE to TM-HSA, and does not occur by irritant mechanisms. This experimental model could become a valuable system for evaluating the role of IgE to hapten-protein conjugates in the immunopathogenesis of asthma caused by other reactive chemicals capable of acting as haptens. We postulate that immunologic and clinical features should be consistent with asthma caused by such reactive chemicals and mediated by such mechanisms.

Animals↗
PubMed1987

Trimellitic anhydride exposure in a 55-gallon drum manufacturing plant: clinical, immunologic, and industrial hygiene evaluation.

Nine workers at a 55-gallon drum manufacturing plant had history of exposure to a paint powder that contained trimellitic anhydride (TMA). Environmental monitoring revealed airborne levels of TMA to be over 100 times the OSHA permissible exposure limit of 0.04 mg/m3. The exposed workers were evaluated in a cross-sectional study by questionnaire, physical examination, screening pulmonary function tests, serial peak expiratory flow rates (PEFR), and serum antibody levels. Four workers had symptoms consistent with TMA-induced irritant effects. Three had symptoms and IgG levels consistent with TMA late respiratory systemic syndrome (LRSS). Two of these three had PEFR changes that showed significant drops (greater than 20%) 12-18 hours after the end of a work shift. The material safety data sheet for the paint powder failed to list TMA as an ingredient. Despite the well-described toxic effects of TMA, the present study documents that TMA-related illness may continue to be a problem in situations where workers and management are not properly notified of the potential hazards. The measurement of PEFR may be useful in identifying TMA-exposed workers with LRSS.

Adult↗
PubMed1987

Six-year clinical and immunologic follow-up of workers exposed to trimellitic anhydride.

We report a 6-year study from 1979 through 1985 of workers exposed to trimellitic anhydride (TMA) in three groups of volunteers. Twenty-nine percent of workers (5/17) originally studied had immunologically induced respiratory disease. Subsequent to this evaluation, increased environmental control of TMA exposure was instituted. Since that time, there have been decreasing clinical symptoms and decreasing levels of antibody against TMA conjugated to human serum albumin. These long-term studies originally used radioimmunoassays, but enzyme-linked immunoassays against TMA-conjugated proteins are now demonstrated to be equally appropriate and are more cost-effective. With appropriate clinical and immunologic studies, immunologic airway reactions to TMA may be identified and then prevented by environmental control to decrease inhalation exposure to TMA. This is likely applicable to certain other chemical antigens that immunize by inhalation.

Air Pollutants, Occupational↗
PubMed1987

Toluene diisocyanate respiratory reactions. I. Reassessment of the problem.

A series of workers with exposure to and respiratory symptoms from toluene diisocyanate (TDI) was compared with a group of exposed, asymptomatic workers and with normal controls using immunologic and clinical evaluations. Improved understanding of TDI-induced respiratory disease may best be achieved by categorizing the symptomatic workers into at least 3 and possibly 4 groups: immunologic TDI asthma; pre-existing chronic respiratory disease exacerbated or unaffected by TDI; asthma coincidental with TDI exposure, and possibly TDI respiratory disease secondary to toxic or inflammatory mechanisms.

Adult↗
PubMed1987

Evaluation of the effect of a platelet activating factor antagonist on platelet activating factor and Ascaris antigen-induced airway responses in rhesus monkeys.

An acute airway response to aerosolized platelet activating factor (PAF) can be induced in certain rhesus monkeys. This PAF airway response is completely inhibited by the PAF antagonist, SRI 63-441, in normal monkeys. After the completion of these studies showing inhibition of the PAF airway response, we evaluated whether the PAF antagonist could inhibit three types of acute IgE-mediated airway responses to Ascaris suum (A) in rhesus monkeys. The A aerosol test protocols used the following: a single A aerosol challenge system; a threshold dose of A challenge system, which consists of increasing A aerosol exposure until an airway response occurs; and two sequential A challenges in which the response to the second A challenge always occurs if there is a response to the first A challenge. When SRI 63-441 was tested as a potential antagonist of the A airway response in any of these three systems, no inhibition was shown.

Aerosols↗
PubMed1987

Establishing clinical and immunologic criteria for diagnosis of occupational immunologic lung disease with phthalic anhydride and tetrachlorophthalic anhydride exposures as a model.

Using a questionnaire and serum antibody studies, we evaluated 13 workers exposed to phthalic anhydride (PA) and tetrachlorophthalic anhydride (TCPA). The questionnaire was designed to identify symptoms compatible with anhydride-induced immunologic or irritant syndromes. Specific IgG and IgE for both PA-human serum albumin (PA-HSA) and TCPA-HSA were determined by enzyme-linked immunosorbent assay in two different laboratories. In addition, 11 workers had cutaneous testing with PA-HSA and TCPA-HSA, and nine workers were interviewed. One worker was found to have PA-associated asthma and rhinitis. We conclude that a questionnaire and serologic assays for specific IgG and IgE are helpful to identify workers who have or are at risk for developing occupational immunologic lung disease such as those induced by anhydrides. However, additional evaluation may be necessary in those workers with such diseases as intrinsic asthma that may be difficult to differentiate from occupational immunologic lung disease.

Air Pollutants, Occupational↗
PubMed1986

Aerosolized leukotriene D4 converts monkeys that are negative aerosolized ascaris responders to positive airway responders.

We designed studies to determine if Leukotriene D4 (LTD4) could alter airway reactivity such that rhesus monkeys with positive skin reactivity and consistently negative airway responses would respond to ascaris airway challenge. The experiments were complicated by the observation that aerosolized LTD4 would occasionally increase airway hyperreactivity in some monkeys used as controls such that an airway response occurred to saline, the diluent for ascaris antigen. In spite of this, we were able to demonstrate induction of airway responsiveness to ascaris antigen. These results demonstrate that LTD4 will induce airway hyperreactivity to a nonspecific stimulus such as aerosolized saline or to an allergen.

Aerosols↗