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Biomedical subjects

N J Doll

Publications and source records attributed to N J Doll.

At least 19 recordsLinked to original sources
PubMed1985

Pulmonary manifestations of the rheumatic diseases.

The collagen vascular diseases represent a heterogeneous group of multisystem disorders with a wide range of clinicopathologic features. Although these diseases represent distinct clinical entities, a great deal of overlap exists between them. For example, the diffuse interstitial fibrosis of SLE, RA, DM-PM, PSS, and MCTD are indistinguishable clinically, radiographically, and histologically. Conversely, the pulmonary manifestations of the various vasculitides all differ significantly from each other in their clinicopathologic presentation, as well as in their response to therapy. For diagnostic purposes, histologic evidence will usually be required for the pulmonary manifestations of the rheumatic diseases. Therapy must then be individualized for each of these entities, as the protocol and response are variable.

Arthritis, Rheumatoid↗
PubMed1984

Studies on the anti-inflammatory properties of thalidomide: effects on polymorphonuclear leukocytes and monocytes.

The effects of thalidomide on polymorphonuclear leukocyte (PMN) and monocyte function were studied in vitro. Phagocytosis of latex beads by both PMNs and adherent monocytes was significantly depressed (p less than 0.01) after a 1-hour incubation of cells with 10 microgram/ml of thalidomide. Concentrations of 1 microgram/ml stimulated monocyte phagocytosis (p less than 0.01) but did not influence PMNs. Incubation of monocytes with 10 micrograms/ml resulted in a significant reduction of chemiluminescence (CL) but had no effect at 1 microgram/ml concentrations. There was no significant action on PMN CL at either concentration. Finally, 10 micrograms/ml concentrations of thalidomide were not cytotoxic for either cell type after 18-hour incubations. In conclusion, the results of these studies may at least partially explain the efficacy of thalidomide in some inflammatory conditions.

Adult↗
PubMed1984

Immunologic techniques utilized in the diagnosis of occupational lung disease.

Humoral and/or cell-mediated immune responses may contribute to the tissue injury in patients with certain types of occupational asthma, hypersensitivity pneumonitis, silicosis, and asbestosis. Numerous diagnostic modalities are available to the clinician investigating the etiology of these disorders. Among the current immunologic techniques discussed in this article are immunoassays for specific anti-IgE antibody, gel diffusion reactions, immunoelectrophoresis, ANA assays, complement studies, and immune complex assays.

Antibodies, Antinuclear↗
PubMed1983

Humoral immunologic abnormalities in workers exposed to asbestos cement dust.

Serum specimens from 144 workers exposed to asbestos cement dust were examined for the presence of ANA, RF, immunoglobulins, and IC. These immunologic findings were compared with chest radiographic changes. A high percentage of workers had polyclonal hypergammaglobulinemia, and there was a statistically significant association between elevated levels of IgG and IgM and radiographic classification. Although a significant number of workers had an increased prevalence of ANA and elevated levels of IC, there was no correlation between these parameters and chest radiographs. These findings support B cell hyperactivity in workers exposed to asbestos and suggest that autoantibody production and IC are not directly involved in disease pathogenesis.

Adult↗
PubMed1983

Immunopathogenesis of asbestosis, silicosis, and coal workers' pneumoconiosis.

From these discussions, it is apparent that immunologic aberrations occur in several inorganic dust diseases. Although the role of these immunologic mechanisms in disease pathogenesis remains speculative, recent studies demonstrating the regulation of fibroblast proliferation by macrophage and asbestos or silica interaction support a role for this cell type in the immunopathogenesis of disease. Future cellular and humoral investigations of the bronchoalveolar lavage in workers with pneumoconiosis may clarify the immunologic contributions in the development of fibrosis observed in these diseases.

Antibodies, Antinuclear↗
PubMed1983

Immunologic techniques utilized in the diagnosis of occupational lung disease.

Numerous immunologic diagnostic modalities are available to the clinician investigating the etiology of occupational lung disorders. Certain tests--immunoassays for specific anti-IgE antibody, gel diffusion reactions, and immunoelectrophoretic techniques--may aid in the identification of specific antigens or analysis of antigens involved in the pathogenesis of environmental lung diseases. Other techniques--ANA assays, complement studies, and immune complex assays--should be regarded as complementary. For example, a specific non-histone nucleoprotein "marker," ANA has not been identified in any of the environmental fibrotic lung diseases, and ANA positivity does not always correlate with severity or progression of disease. Additionally complement assays and detection of circulating immune complexes do not identify specific antigens. Clearly, there are other assays useful in determining immunologic mechanisms that may be important in occupational lung diseases but were not discussed in this article. Bronchoalveolar lavage with cellular identification and therapeutically important when considering the activity of various lung disorders. Also, lymphokine and leukotriene identification, lymphocyte transformation studies, and assessment of macrophage function are contributing greatly to our understanding of the possible immunologic mechanisms involved in different environmental pulmonary diseases. Thus, the investigation of immunologic mechanisms offers an exciting and rewarding future in the evaluation of the pathologic mechanisms of occupational and environmental pulmonary disease.

Antibodies, Antinuclear↗
PubMed1982

Spur cell anemia.

The clinical and laboratory findings in eight patients with spur cell anemia are presented and compared with other cases gathered from the literature. Although there is no specific clinical or laboratory abnormality, the condition can be recognized by a constellation of findings. The majority of patients have a long history of ethanol abuse with clinical and laboratory manifestations of hepatocellular dysfunction. All patients have anemia, a reticulocyte count usually greater than 5%, and indirect hyperbilirubinemia. The sine qua non for the diagnosis of spur cell anemia is an increased percentage (usually greater than 20%) of acanthocytes on a peripheral smear. The prognosis of spur cell anemia is poor, the majority of patients dying within a year. From our study, spur cell anemia appears to be more prevalent than is generally reported.

Acanthocytes↗
PubMed1982

In vitro effect of asbestos fibers on polymorphonuclear leukocyte function.

Incubation of chrysotile and amphibole asbestos fibers with normal human peripheral blood polymorphonuclear leukocytes (PMN) resulted in a significant stimulation of PMN metabolic activity and generation of toxic oxygen by-products as measured by chemiluminescence (CL). Although all asbestos fibers tested were cytotoxic to PMN, cytotoxicity and CL varied disproportionately with fiber type. Anthophyllite asbestos produced the greatest PMN cytotoxicity. It also depressed PMN phagocytosis of latex beads the most and induced the greatest PMN CL response of the fiber types examined. We postulate that asbestos-induced release of toxic oxygen by-products from PMN which have infiltrated into the pulmonary alveoli may contribute to disease pathogenesis in asbestosis.

Asbestos↗
PubMed1982

Asbestos-induced alteration of human peripheral blood monocyte activity.

Incubation of chrysotile and anthophyllite asbestos fibers with normal human peripheral blood monocytes resulted in significant suppression of monocyte metabolic activity as measured by chemiluminescence. Both fiber types were cytotoxic to monocytes and depressed monocyte phagocytosis of latex beads. We conclude that asbestos-induced monocyte cytotoxicity could result in release of lysosomal enzymes and/or degradation products which contribute to fibrosis in asbestosis. The depression of phagocytosis and microbicidal function may contribute to the increased incidence of carcinogenesis observed in asbestosis.

Asbestos↗
PubMed1981

Immune complexes and autoantibodies in silicosis.

Serum specimens from 53 patients with silicosis were examined for the presence of antinuclear antibodies (ANA), rheumatoid factor (RF), immunoglobulins, and immune complexes. These humoral immunologic parameters were compared with radiographic changes and pulmonary function studies. A significant percentage of patients had an increased prevalence of ANA, RF, and immunoglobulin elevation (IgG, IgA). Immune complexes determined by the Raji-cell assay were detected in 31% of the patients. However, there was no significant correlation between any humoral immunologic abnormality and radiographic changes or declines in pulmonary function tests. These findings suggest that humoral immunologic abnormalities are not directly responsible for the lung changes in silicosis and cannot be used as "guides" to predict severity or progression of disease.

Adult↗
PubMed1981

Stroke and gangrene: complications of therapeutic plasma exchange therapy.

Two patients underwent therapeutic plasma exchange therapy. One patient with advanced rheumatoid arthritis developed a stroke after his fifth exchange. The other patient, with progressive systemic sclerosis, required a below the knee amputation secondary to shunt problems. These cases are presented to caution physicians in selecting patients for pheresis procedures and suggest that major complications can occur with this technique.

Adult↗
PubMed1981

Diminished suppressor cell function in patients with asbestosis.

Epidemiological and immunological studies of asbestos workers documented abnormalities in humoral and cell-mediated immunity which could result from defective immunoregulation. This study tests this hypothesis with comparison of lymphocyte function in age-, sex- and smoking-matched subjects with asbestosis. In vivo measure of delayed hypersensitivity (i.e. skin test response) was significantly depressed to two recall antigens, SKSD and Candida, in asbestosis patients. Skin reaction to dinitrochlorobenzene (DNCB) was not depressed, although lymphocytes of patients giving positive skin test reactions demonstrated a significantly lower (P less than 0.001) proliferative response to dinitrobenzene sulphonic acid (DNBSO3) in vitro. T cell counts (E-rosettes) were normal in patients with asbestosis, although a subset of T cells, those forming sheep erythrocyte rosettes after prolonged incubation (Elate), were significantly depressed (P less than 0.003). This population has been equated with 'suppressor' cells (Grossi et al., 1978). Numbers of B cells were increased nearly two-fold over controls. Mitogen response of lymphocytes was normal except at suboptimal doses of mitogens where the response is known to be influenced by suppressor cell activity, which was significantly elevated. Suppressor cell function, as determined by stimulation of peripheral blood lymphocytes preincubated with concanavalin A, was also significantly decreased in asbestosis patients (P less than 0.01).

Aged↗
PubMed1980

Inhibition of polymorphonuclear leukocyte chemiluminescence for detection of immune complexes in human sera.

An assay for the detection and quantitation of immune complexes is described. Experimental immune complexes or aggregated human gamma globulin (AHG) were incubated with polymorphonuclear leukocytes (PMN). After challenge of the PMN with opsonized zymosan, chemiluminescence was recorded in a scintillation spectrometer. A quantitative inhibition of chemiluminescence could be demonstrated by the interaction of PMN with immune complexes or AHG. Experimental immune complexes of bovine serum albumin-anti-bovine serum albumin were formed and tested by this assay, and immune complexes formed near antigen excess were best described by this technique. The technique was used to demonstrate immune complexes in the sera from patients with systemic lupus erythematosus, rheumatoid arthritis, and vasculitis. Immune complexes were quantitated by reference to a standard curve using AHG. By this technique, normal human sera had < 10 micrograms of AHG per milliliter of serum. Immune complexes at levels above this were detected in 9/15 patients with systemic lupus erythematosus, 18/30 patients with rheumatoid arthritis, and 2/5 patients with vasculitis. Therefore, this assay is a sensitive, simple method for measurement of circulating immune complexes in the sera of patients with certain connective tissue diseases.

Antigen-Antibody Complex↗
PubMedDate not supplied

The effect of in vitro immune complexes on polymorphonuclear leukocyte chemiluminescence.

Chemiluminescence (CL) responses were measured following addition of heat-aggregated human gamma globulin (AHG) or bovine serum albumin/antibovine serum albumin (BSA/Anti-BSA) complexes to resting PMNL. These CL responses were two to four fold greater over control values using normal human serum. Furthermore, preincubation of the PMNL suspension with either AHG or BSA/Anti-BSA complexes inhibited the CL response to subsequent stimulation by serum-opsonized zymosan. These results suggest that immune complexes may be detected by PMN-CL.

Adult↗