Hypersensitivity pneumonitis: current concepts of etiology and pathogenesis.
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Biomedical subjects
Publications and source records attributed to J Salvaggio.
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The blastogenic response of lymphocytes from patients with malignant neoplasms was evaluated by stimulation with three phytomitogens (PHA, PWM, and Con A). The response of patient lymphocytes to all three mitogens was significantly lower than that of control lymphocytes, and most patients with abnormal PHA responses also responded abnormally to PWM and Con A. However, a few patients with normal PHA responses were abnormal to Con A, suggesting the suppression of a Con A-sensitive population. The observation that PWM responses were abnormal in patients with lowered PHA lymphocyte stimulation indicates that both T and B lymphocyte mitogen responses were suppressed in these patients. Plasma from patients was capable of either inhibiting or enhancing lymphocyte mitogen stimulation. However, inhibitory plasmas were generally from patients with abnormal mitogen responses.
Chronic mucocutaneous candidiasis in two siblings of consanguineous parents suggested an autosomal recessive transmission of the disease. We evaluated the two affected persons and 21 members of their kindred for an inherited immunological defect. Six members of the kindred, including both patients, had negative skin-delayed hypersensitivity to Candida. The lymphocytes of both patients and three asymptomatic relatives had diminished in vitro blastogenic response when cultured with Candida albicans. Because the defect occurred in clinically unaffected relatives, we concluded that the lack of blastogenic response to C. albicans was not the only determinant for or may be unrelated to the clinical manifestations of the disease.
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Rabbits were sensitized with either a soluble protein antigen (BSA) or a particulate thermophilic actinomycete antigen (Micropolyspora faeni) via the respiratory route, followed by monitoring of sequential morphologic changes and the humoral plus cellular immunologic response. Primary respiratory tract sensitization with BSA resulted in a humoral anti-BSA response, Arthus and delayed skin reactivity, and in some cases specific antigen-induced alveolar macrophage migration inhibition, all in the absence of pulmonary lesions. Lesions characterized by mild multifocal perivascular mononuclear cell infiltrates in the lungs developed only after secondary BSA aerosol challenge. In contrast to these findings, "primary" respiratory tract sensitization with M. faeni particulate antigen in saline solution resulted in the gradual development of extensive and progressive pulmonary interstitial and alveolar mononuclear cell infiltrates. These lesions were uniformly associated with specific serum precipitating antibody and delayed skin reactivity. Alveolar macrophage migration was significantly inhibited by Micropolyspora faeni in virtually of these animals. These results, while not excluding a primary irritant effect or Type II or III alergic tissue injury, suggest a role for delayed (cell-mediated) hypersensitivity in the pathogenesis of particulate actinomycete-induced pulmonary lesions. They also indicate that primary immunization with soluble purified protein antigens via the respiratory route can lead to systemic humoral and cell-mediated immunity without production of pulmonary lesions.
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A new plant manufacturing toluene diisocyanate (TDI) has provided a unique opportunity to investigate the effects of TDI vapor inhalation on respiratory health in a group of exposed workers who have been studied prior to the start of plant operation. In order to establish dose-response relationships and determine host factors, complete biologic monitoring, including pulmonary function and immunologic studies, has been performed concurrently with a comprehensive environmental monitoring program including continuous sampling for atmospheric concentrations of TDI. Study groups include workers with regular exposure to TDI in production jobs (83), workers with intermittent contact with this vapor, usually in maintenance (28), and a control group of workers employed outside the TDI area (55). This population is being followed for a period of 5 yr. The plant began operations in August 1973 with start-up procedures completed by the end of October. TDI spills occurred for numerous reasons, usually attributed to pump failure and resultant line blockage. Significant exposures also occurred in the drumming operation. The influence of these malfunctions is noted in the continuous monitoring data on atmospheric TDI concentrations which continue to reveal frequent excursions above the threshold limit value (TLV) of 0.02 ppm ceiling. These data are presented in relation to time and plant location. Although the first full year follow-up following initial exposure was not complete, certain preliminary clinical observations were made. A number of workers had episodes of acute respiratory symptoms related to single exposure to an irritant gas at work, usually either TDI or phosgene. It appears that two or three workers in the study population have become "clinically sensitized" to TDI and have been removed from regular TDI exposure. To date, the total number of workers who report the presence of recurring respiratory symptoms has not increased in comparison with the pre-exposure survey. Pulmonary function data after one full year of TDI exposure are not yet available. Pre- and post-shift ventilatory function studies do not indicate significant differences between the exposed and control groups. Selected individuals had carefully controlled inhalation challenge tests to monitored concentrations of TDI vapor under laboratory conditions. In workers suspected of having become "sensitized", immediate and/or late air flow obstruction was demonstrated and could be related to dose of inhaled TDI.
The incidence of serum antidust and antifungal precipitins was determined by counterimmunoelectrophoresis in 317 atopic and nonatopic subjects of three geographic areas (north central, southern, and western United States). The selected lyophilized crude antigens employed were from house dust, Micropolyspora faeni, Candida albicans, Alternaria tenuis, Aspergillus fumigatus, Puccinia coronata, Cantharellus cibarius, and Amborsia trifida. Antidust precipitins were detected with high frequency in atopic and nonatopic subjects of each geographic area (48 to 71 percent of different population subgroups). Precipitin reactions were generally intense and often multiple, in keeping with the marked heterogeneity of the crude dust antigen employed. Antidust precipitins were also present in serum fractions precipitated with ammonium sulfate and in IgG-rich fractions obtained by gel filtration (Sephadex G-200) and diethylaminoethyl-cellulose chromatography. Precipitins against crude somatic fungal and actinomycetic antigens were detected with considerably less frequency in all populations surveyed, considerably less frequency in all populations surveyed, and antiragweed precipitins were not detected. Our results suggest that prolonged environmental exposure to diverse, ubiquitous organic dusts results in a "normal" serum precipitating-antibody response. They also extend our previous finding of a high precipitin response against organic dusts in residents of the Gulf south area compared to other geographic areas.
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