Biomedical subjects

D R Moller

Publications and source records attributed to D R Moller.

28 records · Page 2Linked to original sources

PubMed1990

Increased numbers of T lymphocytes with gamma delta-positive antigen receptors in a subgroup of individuals with pulmonary sarcoidosis.

Individuals with sarcoidosis were evaluated for preferential usage of T cells with the gamma delta-positive (+) type of T cell antigen receptor. Compared with normal subjects (n = 19), the group with sarcoidosis had increased numbers of CD3+ alpha beta-negative (-) T cells in the blood (normal, 58 +/- 12 cells/microliters; sarcoid, 192 +/- 45 cells/microliters, P less than 0.05) and in the epithelial lining fluid of the lung (normal, 78 14 cells/microliters; sarcoid, 240 +/- 60 cells/microliters, P less than 0.04) and a concomitant elevated number of blood and lung CD3+ gamma delta+ T cells, owing to a striking increase in the number of CD3+ gamma delta+ T cells in a subgroup (7 of 20) of sarcoid individuals. The elevated numbers of sarcoid blood gamma delta+ T lymphocytes were mostly Ti gamma A+ and delta TCS1-, a pattern also seen in normal individuals, consistent with the majority of gamma delta+ T cells expressing one gamma-chain variable region, V gamma 9. The observation of an increase in the total gamma delta+ T cell numbers in a sarcoid subgroup suggests that various specific stimuli may trigger the expansion of different T cell subpopulations within different groups of individuals with sarcoidosis.

Adult↗

PubMed1988

Pulmonary and immunologic evaluation of foundry workers exposed to methylene diphenyldiisocyanate (MDI).

A cross-sectional evaluation was performed of workers in a steel foundry in which methylene diphenyldiisocyanate (MDI) was used as a component of a binder system used to make cores and molds. Preshift and postshift spirometry and clinical evaluations were performed on 26 currently exposed (group I), on six formerly exposed (group II), and on 14 nonexposed workers to MDI (group III). Serum samples were assayed for total antibody binding, specific IgG by ELISA, and specific IgE by the RAST method to MDI-human serum albumin (HSA). Symptoms compatible with occupational asthma were elicited from seven (27%) of 26 group I workers and from three of six group II workers. No symptoms were reported by group III workers. Intrashift change in FEV1 (a mean decrease of 0.049 L) in group I workers was significantly decreased compared to that in unexposed group III workers (a mean increase of 65 ml; p = 0.043). Specific IgG and total antibody responses to MDI-HSA were detected only in workers with current or former exposure to MDI. Only one worker was identified with IgE-mediated occupational asthma exhibiting a positive prick test and elevated RAST to MDI-HSA of 25.5% bound. In this occupational setting, polyclonal immune responses to MDI-HSA and clinical sensitization to MDI were demonstrated to occur.

Adult↗

PubMed1988

Spontaneous expression of the interleukin 2 receptor gene and presence of functional interleukin 2 receptors on T lymphocytes in the blood of individuals with active pulmonary sarcoidosis.

Current concepts of the pathogenesis of sarcoidosis suggest that the expanded numbers of activated T-helper/inducer cells at sites of disease activity result, at least in part, from their proliferation in the local milieu. Normal clonal proliferation of T cells involves activation and expression of the IL 2 receptor (IL 2R) gene. Thus, knowing that IL 2R mRNA transcripts are relatively long lived, we hypothesized that sarcoid blood T cells may contain IL 2R mRNA transcripts and express functional surface IL 2R, although the cells are probably activated elsewhere. Northern analysis using a 32P-labeled cDNA probe for the IL 2R p55 protein demonstrated that blood T cells of patients with active sarcoidosis, but not of normal patients, express 3.5- and 1.5-kb IL 2R mRNA transcripts, the same as those observed in normal T cells activated in vitro. Consistent with this, using flow cytometry and an MAb directed against the IL 2R p55 protein (2A3), we observed detectable levels of IL 2R surface protein on increased numbers of blood T cells of active sarcoidosis patients (4.7 +/- 0.9%) compared with blood T cells of normal patients (0.9 +/- 0.2%). Importantly, when the sarcoid blood T cells were exposed to IL 2 in vitro, they proliferated at a rate greater than that of normal blood T cells under the same conditions, suggesting that the IL 2R spontaneously expressed by sarcoid blood T cells were functionally active. In the context of the known compartmentalization of spontaneous IL 2 production and T cell proliferation at sites of disease in active pulmonary sarcoidosis, these IL 2R positive blood T cells would probably have a proliferative advantage if they trafficked to sites of active sarcoidosis, such as the lower respiratory tract.

Adult↗

PubMed1988

Bias toward use of a specific T cell receptor beta-chain variable region in a subgroup of individuals with sarcoidosis.

To evaluate the concept that biases in the usage of T cell antigen receptor beta variable (V) regions may be manifested in T lymphocytes that accumulate in nonmalignant, T cell-mediated human disorders, a V beta 8-specific antibody (anti-Ti3A, 5REX9H5) was used to evaluate lung and blood T cells in pulmonary sarcoidosis, a chronic granulomatous disorder of unknown etiology. Whereas normal patients had less than 5% Ti3A+ lung (n = 7) and/or blood (n = 9) lymphocytes, strikingly, a subgroup (8 of 21) with active pulmonary sarcoidosis had greater than 7% Ti3A+ lung and/or blood T cells and a higher proportion of Ti3A+ lymphocytes in the lung compared with blood. Dual-color flow cytometry demonstrated compartmentalization of Ti3A+ CD4+ lymphocytes to lung and Ti3A+ CD8+ lymphocytes to blood. Analysis with a 32P-labeled V beta 8 probe revealed that sarcoid lung T lymphocytes contained higher amounts of V beta 8+ mRNA than autologous blood T cells. However, Southern analysis of sarcoid lung and blood T cell DNA demonstrated no evidence of clonal rearrangements of V beta 8 genes. These observations demonstrate a clear bias toward the use of at least one V beta region in sarcoidosis, and suggests T cells accumulate secondary to external selective pressure, rather than in a random polyclonal fashion or by clonal expansion of one or few T cell clones.

Antibodies, Monoclonal↗

PubMed1987

Clinical and immunologic studies among egg-processing workers with occupational asthma.

Twenty-five workers in an egg-processing factory were evaluated for respiratory sensitization to inhaled egg proteins by a physician evaluation, serial peak expiratory flow rate (PEFR) measurements for a 1-week period, and immunologic tests. Immunologic studies included skin prick tests, serum-specific IgE (RAST), and specific IgG (ELISA) to solutions prepared from commercial food allergens: factory-powdered egg white and yolk products and purified egg white fractions, including ovalbumin, ovomucoid, lysozyme, and conalbumin. Six workers had significant daily PEFR lability (greater than 20%) of whom five had associated cutaneous reactivity to at least one egg allergen. A diagnosis of "definite asthma" was established in five workers suspected by the physician of having asthma. These five workers exhibited significant decrements in daily PEFR that were accompanied by bronchial symptoms. Occupational asthma was diagnosed by the physician in four of the five latter workers. Definite asthma was significantly associated with both cutaneous reactivity to egg allergens (p less than 0.01) and RAST binding (p less than 0.01). Of eight workers with cutaneous reactivity to at least one egg reagent, four workers (50%) were positive to only purified egg white fractions. The highest levels of RAST binding were detected in four workers, and the best binding activity was to ovomucoid and ovalbumin fractions. Elevated specific IgG responses were significantly higher in egg-factory workers to whole egg (p less than 0.005), lysozyme (p less than 0.002), and conalbumin (p less than 0.002) allergens compared to responses of nonexposed control subjects. However, no differences in specific IgG were detected between symptomatic and asymptomatic workers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1986

Delayed anaphylactoid reaction in a worker exposed to chromium.

A 29-year-old male welder reported systemic reactions after exposure to chromium. Inhalation challenge testing to 29 micrograms/m3 of sodium chromate aerosol resulted in late appearing systemic urticaria, angioedema, and severe bronchospasm that occurred at the same time as a threefold rise in plasma histamine. A direct leukocyte inhibitory factor test to 5.5 X 10(-6)mol/L Na2CrO4 was positive. Although the mechanism of this reaction is unknown, the positive leukocyte inhibitory factor and the general acceptance of hexavalent chromium as a contact skin sensitizer suggest that cell-mediated mechanisms could be involved.

Adult↗

PubMed1986

Persistent airways disease caused by toluene diisocyanate.

The natural history of isocyanate-induced asthma is not well documented. We evaluated a patient who developed persistent shortness of breath, wheezing, and cough after a massive exposure to toluene diisocyanate (TDI). Despite no further occupational exposures to isocyanates, he continued to have symptoms of asthma and variable airway obstruction 12 yr later. A methacholine inhalation challenge test was markedly positive, and a bronchial challenge test to TDI produced a dual asthmatic response. This report demonstrates that sensitivity to TDI can persist for many years in the absence of further occupational exposure and suggests that some patients with TDI-induced asthma do not recover from their disease after being removed from isocyanate exposure.

Asthma↗

PubMed1986

Chronic asthma due to toluene diisocyanate.

Twelve subjects were studied with inhalation challenge testing to toluene diisocyanate (TDI) because of suspected TDI asthma based on a consistent clinical and occupational history. In seven cases, TDI asthma was documented by a positive inhalation challenge to low levels of TDI. Six of the seven TDI reactors had persistent respiratory symptoms and required daily treatment even though they had been removed from isocyanate exposure for intervals as long as 12 years (mean 4.5 years). These six TDI reactors had either dual (four cases) or late bronchospasm (two cases) to less than 20 ppb TDI, and all had a positive methacholine or cold air challenge prior to study. The one TDI reactor with a negative methacholine challenge had a positive (immediate) bronchospastic response to a TDI challenge performed one week after removal from isocyanate exposure. Five workers had a negative TDI challenge, two of whom had persistent respiratory symptoms and positive methacholine challenges at the time of TDI inhalation testing. We conclude that respiratory symptoms may persist following long-term removal from occupational exposure to TDI and are associated with nonspecific bronchial hyperreactivity. The TDI sensitivity may also persist for a long time even in the absence of any additional occupational exposure. Long-term prospective studies of symptomatic isocyanate workers are needed to fully define the extent of this problem.

Adult↗

PubMed1985

Detection of IgE-mediated respiratory sensitization in workers exposed to hexahydrophthalic anhydride.

Twenty-seven workers with occupational exposure to hexahydrophthalic anhydride (HHPA) from an epoxy resin molding system were studied to evaluate the nature of their reported respiratory complaints. The workers were evaluated by questionnaire, pulmonary function tests, and serologic investigations. The presence of serum-specific IgE and IgG to an HHPA-human serum albumin (HSA) conjugate was measured by use of RAST and ELISA assays. Estimates of exposure to HHPA were made for each worker on the basis of job description and environmental sampling. Seven workers reported symptoms of asthma and rhinitis; four workers had symptoms consistent with occupational asthma. Fourteen of the remaining 20 workers reported nasal or ocular symptoms while they were at work. No worker demonstrated a significant (greater than 20%) pre-to postshift decrement in FEV1. Twelve workers had significant levels of specific IgE to HHPA-HSA; 11 had elevated levels of specific IgG to HHPA-HSA. A group of workers estimated to have higher exposures to HHPA had a significantly higher mean total IgE level (p less than 0.05) and significant titers of HHPA-HSA-specific IgE or IgG, or both (p = 0.048) as compared to a group with lower exposure to the anhydride. All four workers with occupational asthma/rhinitis had significant levels of specific IgE to HHPA-HSA (ranging from 8.7% to 23.4% RAST binding); three workers did not work directly in the HHPA area but were located in nearby sections of the plant with lower exposures to HHPA. Three workers with symptoms of asthma not clearly associated with the workplace did not have significantly elevated specific IgE levels. Another radioimmunoassay with the use of beads coated with mouse monoclonal antihuman IgE was used to quantitate the amount of specific anti-HHPA-HSA binding (range 1.0 ng to 32.6 ng/ml) present in workers' sera. The solid-phase bead radioimmunoassay was inhibited by the homologous HHPA-HSA conjugate but not by HHPA hapten alone in two workers, suggesting that these workers were sensitized to new antigenic determinants. We conclude that HHPA is a potent industrial sensitizer and is capable of inducing IgE-mediated disease. Prospective investigations are required to define the incidence and severity of clinical sensitivity.

Antibody Specificity↗

PubMed1985

Asthma and rhinitis due to ethylcyanoacrylate instant glue.

A 32-year-old man developed asthma due to a cyanoacrylate ester instant glue used in building remote control model airplanes. Typical asthma and rhinitis symptoms developed after 1 year using the adhesive. Delayed onset of symptoms was consistently related to the application of the glue to balsa wood. Bronchial provocation to the glue vapors in a manner simulating his home exposure resulted in a late asthmatic response with rhinorrhea and lacrimation. Increased bronchial hyperreactivity to methacholine occurred after bronchial challenge and persisted for several weeks. Complete resolution of the patient's asthma symptoms occurred with avoidance of the glue. Reversion to a negative methacholine challenge test occurred after 6 months of continued avoidance.

Adhesives↗