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Biomedical subjects

J E Salvaggio

Publications and source records attributed to J E Salvaggio.

At least 19 recordsLinked to original sources
PubMed1997

Immune system alteration in the rat after indirect exposure to methyl mercury chloride or methyl mercury sulfide.

Methyl mercury is a well-recognized health hazard. It is an environmental contaminant that accumulates in the food chain. The primary source of mercury exposure for humans is through the consumption of contaminated fish. We studied the effects of indirect methyl mercury exposure on the immune system of Sprague-Dawley rats. The effects of different forms of methyl mercury on immune system development were studied in Sprague-Dawley rats at 6 and 12 weeks of age. Rats were indirectly exposed to mercury during gestation and during nursing by exposing pregnant rats to either 5 or 500 micrograms/liter of methyl mercury chloride (CH3HgCl) or 5 micrograms/liter of methyl mercury sulfide [(CH3Hg)2S] in their drinking water. Total body, splenic, and thymic weights were measured, and NK cell cytolytic activity and lymphoproliferative response to T and B cell mitogens were evaluated in the offspring. At 6 weeks of age, total body and splenic weights were significantly increased in both high- and low-dose methyl mercury chloride-exposed groups. Rats exposed to methyl mercury sulfide had a significant increase in thymic weight at 6 weeks of age. At 12 weeks, the total body and organ weights were not different from controls. The lymphocyte proliferative response of splenocytes to PWM was enhanced at 6 weeks in both CH3HgCl exposed groups and not affected in the (CH3Hg)2S exposed group. NK cell activity was not affected in either group at 6 weeks of age. At age 12 weeks, NK cell activity was statistically significantly decreased by 56.6% in both CH3HgCl-exposed groups and not affected in the (CH3Hg)2S-exposed rats. The lymphocyte proliferative response of splenocytes to the B cell mitogen pokeweed remained increased in the CH3HgCl groups. Indirect exposure of rats (during gestation and nursing) to different forms of methyl mercury reveals that chloride forms have prolonged predominantly enhancing effects on lymphoproliferative response of splenocytes, followed by significant depression of NK cell activity.

Animals↗
PubMed1996

Understanding clinical immunological testing in alleged chemically induced environmental illnesses.

Some believe that an abnormal immunoregulatory response based on environmental damage to T cells is fundamental to the production of symptoms in patients with alleged "multiple chemical sensitivity" and/or "environmental illness." According to this theory stimulation of T cells or T cell phenotypic subsets by environmental chemicals results in release of cytokines that can effect appropriate target cells of multiple organ systems, resulting in a wide range of symptoms. This concept is reinforced by frequent media reporting of pollution incidents and environmental disasters plus continued isolated reports of immunologic abnormalities in patients with various forms of alleged environmental illness, multiple chemical sensitivities, or other related syndromes. These include reports of slight perturbations in quantity and function of immunoglobulins, complement and its components, B cells, natural killer cells, T cells, phenotypic T cell subsets, and helper suppressor T cell ratios. There are also reports of increased or decreased interleukin levels including IL-1 and IL-2 or their receptors (IL-2R) in these patients. Such assays are not infrequently performed even though there is no evidence for their diagnostic efficacy in these alleged conditions. It is reasonable, however, to anticipate that with the wide development of assays for many of the interleukins and their receptors, these assays may become important in the future diagnosis of many autoimmune, allergic, neoplastic, and infectious diseases. At this time, however, the induction of environmental illness or multiple chemical sensitivity by exposure to trace levels of environmental "immunotoxins" is unproven and remains a matter of speculation. The reproducibility of immunologic test abnormalities reported under these conditions has not been documented, and the data have often not been analyzed statistically. Appropriate controls also have not usually been employed, nor have control values been provided in many cases. Without consideration of these factors, a patient might be erroneously diagnosed as having some form of "immune dysregulation," "environmental immune dysfunction," or "immunotoxic" syndrome on the basis of only a single panel of cellular immunologic profiles or related immunologic tests illustrating slight deviations from the norm and in the absence of overt disease on physical examination. Consideration must also be given to an understanding of biologic variability and diurnal variations in lymphoid cell numbers in interpreting cellular immunologic profiles. For example, the necessity for age and sex-matched controls, test reproducibility, quantitative versus functional assays, and the significance of major versus minor deviations from the norm must be appreciated. In addition, many other conditions can effect immunologic tests, such as medications, psychologic factors, cigarette smoking, and the presence of concurrent disease, including minor viral infections. All of these variables should be appreciated in test interpretation. Certain clinical indications for analysis of cellular components of the immune system, using flow cytometry, have been provided as guidelines although they are by no means accepted by all groups due to their current incomplete evaluation by the clinical immunology community. These suggested indications are discussed. In this article, attempts are made to outline the various quantitative and functional tests used to assess the immune system, with emphasis on "biomarker" tests to detect possible immune system "damage." Dangers involved in attempting to make clinical evaluations based on results of isolated in vitro assessment of quantity or function of immune system cellular and humoral components without considering the results of a good medical history and physical examination, the many pitfalls involved in the tests, and the many confounding variables that affect the tests are emphasized, as well as the need for proper controls...

Autoantibodies↗
PubMed1996

Multiple chemical sensitivity multiorgan dysesthesia, multiple symptom complex, and multiple confusion: problems in diagnosing the patient presenting with unexplained multisystemic symptoms.

Patients are presenting in increasing numbers with multiorgan symptoms allegedly resulting from exposure to environmental chemicals. Among the symptoms expressed by patients with alleged multiple chemical sensitivities (MCS) are profound fatigue, mental confusion, myalgia, depression, anxiety, dizziness, headache, insomnia, loss of appetite, and numbness of the extremities, all in the absence of objective physical signs. Diagnostic criteria to assess the effects of environmental agents on organ systems are sorely needed because patients with MCS often have no tissue pathology or physiological abnormalities, but often do have diagnosable psychiatric illnesses. In treating patients with MCS, the physician should first perform a complete history and physical examination, including a comprehensive evaluation of chemical exposure. If the findings strongly suggest the presence of disease related to particular organ systems, further diagnostic evaluation should be undertaken. If abnormal findings are absent, psychiatric advice may be useful. The physician should keep an open mind about MCS but must also remember that a cause-effect relationship between exposure to multiple chemicals and symptoms has not been established.

Air Pollutants↗
PubMed1995

The identification of hypersensitivity pneumonitis.

The clinical history may point suspicion at a specific sensitizer. Brief, intermittent exposure produces acute, often reversible disease, frequently misdiagnosed as viral or bacterial pneumonia. Long-term exposure fuels the insidious development of chronic, disabling disease with minimal reversibility.

Adult↗
PubMed1995

Fungal allergens.

Airborne fungal spores occur widely and often in far greater concentrations than pollen grains. Immunoglobulin E-specific antigens (allergens) on airborne fungal spores induce type I hypersensitivity (allergic) respiratory reactions in sensitized atopic subjects, causing rhinitis and/or asthma. The prevalence of respiratory allergy to fungi is imprecisely known but is estimated at 20 to 30% of atopic (allergy-predisposed) individuals or up to 6% of the general population. Diagnosis and immunotherapy of allergy to fungi require well-characterized or standardized extracts that contain the relevant allergen(s) of the appropriate fungus. Production of standardized extracts is difficult since fungal extracts are complex mixtures and a variety of fungi are allergenic. Thus, the currently available extracts are largely nonstandardized, even uncharacterized, crude extracts. Recent significant progress in isolating and characterizing relevant fungal allergens is summarized in the present review. Particularly, some allergens from the genera Alternaria, Aspergillus, and Cladosporium are now thoroughly characterized, and allergens from several other genera, including some basidiomycetes, have also been purified. The availability of these extracts will facilitate definitive studies of fungal allergy prevalence and immunotherapy efficacy as well as enhance both the diagnosis and therapy of fungal allergy.

Antigens, Fungal↗
PubMed1994

Inhaled particles and respiratory disease.

This brief discussion of inhaled particles, their manner of deposition and clearance, and their association with many human disease has been designed to remind us of the importance of particulate agents as sensitizers, via their allergen content, as causative agents of lung inflammation via their immunotoxic properties, as inducers of inflammatory alveolitis based on their content of antigens and adjuvant-like material, and as infectious agents. All these properties can play a part in a wide variety of allergic parenchymal, infectious, and industrial lung diseases and in building-related illnesses.

Aerosols↗
PubMed1992

Passive cigarette smoke-challenge studies: increase in bronchial hyperreactivity.

Degree and duration of bronchial hyperreactivity (BHR) after environmental tobacco smoke (ETS) inhalation was assessed in 31 smoke-sensitive subjects with asthma who exhibited lower airway symptoms on ETS exposure (group I) and 39 smoke-sensitive subjects without asthma who manifested only upper airway symptoms on cigarette-smoke exposure (group II). Subjects were challenged with ETS for 4 hours in a static-test chamber. The atmosphere was continuously monitored for airborne particulate levels (800 cpm), total suspended particulates (1266 +/- 283 micrograms/m3), and airborne nicotine levels (226 +/- 49 micrograms/m2). Methacholine challenges were performed before and serially after cigarette-smoke exposure, and the provocative dose causing a 20% fall in FEV1 was determined. Five of the 31 smoke-sensitive subjects with asthma and none of the smoke-sensitive subjects without asthma reacted to cigarette-smoke challenge (greater than or equal to 20% fall from baseline FEV1). Thirty-two percent (10/31) of the subjects with asthma demonstrated increased BHR at 6 hours, 29% (9/31) at 24 hours, and 13% (4/31) up to day 14 after ETS challenge. Of the subjects without asthma, 18% (7/39) demonstrated increased BHR at 6 hours, 10% (4/39) at 24 hours, and 8% (3/39) at 3 weeks. These studies demonstrated an increase in BHR after cigarette-smoke challenge in a number of study subjects (although they were clinically asymptomatic) and suggest that prolonged subclinical airway inflammation can occur in the absence of demonstrable change in airway caliber on exposure to ETS.

Adolescent↗
PubMed1992

Chronological assessment of asbestos exposure on cell composition in murine lung.

To elucidate immune pathogenic mechanisms in asbestosis, lung and spleen lymphoid cell populations were analyzed at defined time intervals (1, 2, 3, 6, and 12 weeks during exposure and 4, 24, and 48 weeks post-exposure) in asbestos-exposed and unexposed (control) mice. Polymorphonuclear leukocytes and macrophages were increased in the lung tissue histologic sections of asbestos-exposed mice compared to controls. No consistent changes were observed in percentages of lung or spleen helper, suppressor, or total lymphocyte populations after asbestos exposure. The numbers of B cells (identified by anti-IgG) in minced lung preparations of asbestos-exposed animals were increased after 12 weeks of exposure. There also was an increase in IgG production in asbestos-exposed mice after 12 weeks exposure and at 4 weeks post-exposure with a return to near baseline levels 24 and 48 weeks after initial exposure. Collectively, these studies demonstrate stimulatory effects of inhaled asbestos fibers on B cells and IgG production after 12 weeks of continuous inhalation of asbestos fibers in a dust generation chamber.

Animals↗
PubMed1991

Asthmatic responses to passive cigarette smoke: persistence of reactivity and effect of medications.

The present study assessed the persistence of cigarette-smoke reactivity and the effects of drug pretreatment on bronchial responsiveness to environmental tobacco smoke (ETS). Two groups of subjects were chosen for the study. Group I consisted of 15 atopic smoke-sensitive subjects with asthma, six of whom were defined "reactors" and nine "nonreactors" to ETS challenge. Group II consisted of 15 atopic subjects without asthma and with documented upper respiratory tract symptoms on exposure to ETS. All subjects were challenged for 2 to 6 hours with mechanically generated ETS in a static inhalation chamber. Five/six subjects in group I, who were previously demonstrated as reactors 24 months earlier, remained reactive within 1 to 2 hours of continuous ETS exposure. Pretreatment with albuterol, cromolyn, and a combination of albuterol and cromolyn 30 minutes before ETS exposure significantly diminished airway reactivity to ETS. All nine previous nonreactors in group I remained nonreactive despite rechallenge with ETS for up to 6 hours. Group II subjects challenged under identical conditions did not reveal a significant decline in FEV1 on challenge with ETS. These studies demonstrate the persistence of ETS reactivity during a 2-year period. Although cromolyn sodium and/or albuterol can protect against reactivity, mechanisms of ETS-induced airway reactivity remain unknown.

Adult↗
PubMed1991

Basidiomycete allergy: identification and characterization of an important allergen from Calvatia cyathiformis.

Basidiomycetes were not considered as major aeroallergen sources until spore traps revealed the prevalence of basidiospores, which were in some cases associated with epidemic outbreaks of asthma. More recently, we established that approximately one third of subjects with respiratory allergic disease were skin prick test positive to basidiospore extracts. Bronchial challenge with these extracts induced reversible immediate and late phase bronchospasm in sensitive subjects. Screening individual RAST-positive sera for reactivity to immunoprinted Calvatia cyathiformis spore extract indicated that a basic component with pI 9.3 reacted with 63% of test sera. Further analysis by RAST and immunoprint (IP) inhibition showed that this component, Cal c Bd9.3, appeared to cross-react with spore extracts from 3 of 5 other species tested. To isolate this component for additional analysis, a protocol was used with two sequential stages of preparative isoelectric focusing (IEF) followed by hydrophobic interaction chromatography. This yielded purified Cal c Bd9.3 that retained IgE-binding activity by IP, was a single band by IEF and SDS-PAGE (16 kD) analysis when stained with Coomassie blue. Double diffusion in gel with rabbit antiserum to Cal c BD9.3 demonstrated a single precipitin band in crude extract that was identical to that obtained with purified Cal c Bd9.3. By IP this antiserum recognized pure Cal c Bd9.3 and the 9.3 band in crude extracts from C. cyathiformis and 3 other species, corroborating the cross-reactivity. However, other bands were also recognized. These studies indicate that basidiospores are major fungal aeroallergens, many of which contain a common basic allergen to which most sensitized subjects react.

Allergens↗
PubMed1991

Immune reactions in allergic alveolitis.

This article discusses newer cellular immunological and immunoregulatory events operative in the pathogenesis of "allergic alveolitis" (aa). An early increase in neutrophils and chemotactic factors followed by an influx of macrophages and lymphoid cells with ultimate production of granulomas have been demonstrated in the bronchoalveolar lavage (BAL) fluids of experimental animals and of man in aa. Transfer of specifically sensitized lymph node and spleen cells intraperitoneally followed by antigen challenge via the respiratory tract route has resulted in production of pulmonary lesions closely resembling those observed in human aa in several animal species. Activated alveolar macrophages and T-cells, local lymphokine production, and elevated immunoglobulin levels in BAL fluid have also been demonstrated repeatedly in experimental animal models of these diseases. High levels of interleukin-1 have also been demonstrated in aqueous extracts prepared from pulmonary granulomatous lesions. Other studies have indicated a role for macrophage-derived lipoxygenase products in production of experimental pulmonary granulomatous inflammation. Mononuclear cell pulmonary infiltrates have been inhibited by corticosteroids, the use of antimacrophage serum, neonatal thymectomy, cobra factor venom, and cyclosporin. A T suppressor factor and other suppressor factors from adherent cell populations have also been shown to dampen or modulate experimental granuloma formation. Appropriately sensitized animals which demonstrate chronic pulmonary granulomatous inflammation can also become "desensitized" following a series of antigen challenges. The desensitization produced is immunospecific and nontransferable with immune serum. Studies of bronchoalveolar lavage fluids in man have demonstrated a very high percentage of lymphocytes in BAL fluids. The percentage of suppressor cytotoxic T-cells is usually above 40% and CD4:CD8 ratios are reversed. Evidence also suggests that suppressor lymphocytic alveolitis is a chronic event in patients with aa. Immunogenetic studies of granulomatous pneumonitis resembling aa in different strains of mice have shown that certain high-responder strains develop intense granulomas after inoculation with killed bacille Calmette-Guérin (BCG), whereas other low-responder strains do not. The intensity of the pulmonary granuloma formation in this model has been shown to be a dominant and polygenic trait and to be linked to the immunoglobulin heavy chain locus (IgH). Strains that develop intense, chronic granulomatous inflammation have usually proved to be anergic, and the anergy also appears to be under genetic control.(ABSTRACT TRUNCATED AT 400 WORDS)

Alveolitis, Extrinsic Allergic↗