Search PubMed⌕ Search

Biomedical subjects

M D Rossman

Publications and source records attributed to M D Rossman.

At least 55 records · Page 3Linked to original sources
PubMed1987

Chronic beryllium disease: diagnosis, radiographic findings, and correlation with pulmonary function tests.

Patients with suspected chronic beryllium disease underwent bronchoscopy and bronchoalveolar lavage. Their bronchoalveolar lymphocytes were incubated with beryllium salts, and quantitative lymphocyte transformation was measured. Seventeen patients with a positive lymphocyte proliferation test were evaluated radiographically with the International Labour Office classification. The most common radiographic abnormalities included diffuse small round and reticular opacities. Hilar adenopathy, linear scars, lung distortion, bullae, and pleural thickening were found less commonly. Specific radiographic findings were compared with pulmonary function abnormalities. The extent of radiographic profusion of small opacities and the presence of linear scars did not correlate with pulmonary function abnormalities. There was, however, a significant correlation between extensive pleural disease and reduced vital capacity in this small group of patients.

Adult↗
PubMed1987

Chronic beryllium disease in a precious metal refinery. Clinical epidemiologic and immunologic evidence for continuing risk from exposure to low level beryllium fume.

Five workers at a precious metal refinery developed granulomatous lung disease between 1972 and 1985. The original diagnosis was sarcoidosis, but 4 of the workers were subsequently proved to have hypersensitivity to beryllium by in vitro proliferative responses of lymphocytes obtained by bronchoalveolar lavage. Review of medical records of coworkers and extensive industrial hygiene surveillance of the plant demonstrated that 4 cases occurred in the furnace area where air concentrations of beryllium fume were consistently below the permissible exposure limit of 2 micrograms/M3. A single case has been recognized from parts of the refinery where exposures to cold beryllium dust often exceeded the standard by as much as 20-fold. These data demonstrate that chronic beryllium disease still occurs and confirm the importance of specific immunologic testing in patients suspected of having sarcoidosis but with potential exposure to beryllium. The data raise concern about the adequacy of modern industrial controls, especially in the setting of exposure to highly respirable beryllium fume.

Adult↗
PubMed1987

Phenotypic variability among density-fractionated human lung fibroblasts.

To determine if there is phenotypic variability within apparently homogeneous human lung fibroblast lines, growth-arrested lung fibroblasts were separated according to cell density. Three fibroblast fractions of specific gravity 1.023 to 1.035, 1.036 to 1.049, and 1.052 to 1.059 were obtained. These fractions differed in their cell volume and proliferative response to serum, but not in their response to growth-inhibiting soluble factors from lung mononuclear cells. The differences in proliferative capacity were not maintained during in vitro culture, and were not the result of the fractionation procedure selecting for cells at a particular point in the cell cycle. However, the fractionation procedure did separate cells based in part on their propensity to traverse the cell cycle. The least dense fraction was enriched for larger cells that were noncycling or slowly cycling, whereas the densest fibroblast fraction was enriched for small, rapidly cycling cells. Thus, there is morphologic and functional variability within adult human lung fibroblast lines. This phenotypic variability may be an important factor controlling the pulmonary fibrotic response.

Cell Cycle↗
PubMed1987

Alveolar macrophages, blood monocytes, and density-fractionated alveolar macrophages differ in their ability to promote lymphocyte proliferation to mitogen and antigen.

We compared the relative abilities of alveolar macrophages (AM), blood monocytes (BM), and density-fractionated AM to support antigen- and mitogen-induced proliferation of autologous T cells in normal volunteers. The AM were able to promote the T-cell proliferative response to antigen, but they did so less effectively than did the BM. Density-fractionated AM were heterogeneous in their ability to support T-cell responses. More proliferation occurred with the densest AM than with the least dense AM. In contrast to antigen-induced responses, mitogen-induced responses were supported more effectively by AM and density-fractionated AM than by BM. The ability of AM, density-fractionated AM, and BM to support T-cell responses did not correlate with surface expression of class II major histocompatibility determinants. Addition of purified IL-1 resulted in a partial restoration of T-cell proliferation when low-density AM were used but no augmentation when unfractionated AM were used. This suggests that reduced IL-1 activity may partially explain the decreased ability of low density AM to promote T-cell responses, but that other processes may also contribute to differences in accessory cell function among AM, BM, and density-fractionated AM.

Antigens↗
PubMed1987

Carbohydrate differences in HLA-DR molecules synthesized by alveolar macrophages and blood monocytes.

Two-dimensional gel electrophoresis was used to compare immunoprecipitated, radiolabeled HLA-DR molecules synthesized by alveolar macrophages (AM) and blood monocytes (BM) of the same healthy, nonsmoking volunteers. No charge differences were noted by isoelectric focusing. Molecular weight analysis of HLA-DR from AM revealed a complex pattern of radioactive spots differing slightly in molecular weight. This pattern was apparent in both the alpha and the beta chains. In contrast, a simpler pattern without the slight molecular weight differences was noted in HLA-DR from BM. The differences were eliminated by labeling AM and BM in the presence of tunicamycin, a specific inhibitor of protein-carbohydrate linkages of the N-glycosidic type. Thus, it appears that neutral, N-linked carbohydrate moieties account for the differences in HLA-DR molecules between AM and BM. The differential glycosylation of HLA-DR molecules in AM and BM may relate to mononuclear phagocyte development as well as antigen-presenting function.

Carbohydrate Metabolism↗
PubMed1986

Increased monocyte Fc(IgG) receptor expression in sarcoidosis.

Since the macrophage Fc(IgG) receptor appears to be modulated by inflammatory stimuli, we measured the binding of monomeric IgG to monocytes and alveolar macrophages from patients with pulmonary sarcoidosis. Equilibrium binding studies were performed, and the number and affinity of Fc(IgG) receptors were calculated from Scatchard plots of the data. Monocytes from patients with sarcoidosis had nearly twice the number of binding sites for monomeric IgG as did the monocytes from normals. In contrast to the findings with monocytes, alveolar macrophages from patients with sarcoidosis did not have a greater number of monomeric IgG binding sites than did normal alveolar macrophages. These findings are consistent with those on the activation of circulating monocytes in sarcoidosis. That the number of Fc(IgG) receptors on sarcoid alveolar macrophages was not greater than that on normal alveolar macrophages suggests that Fc(IgG) receptor activity on alveolar macrophages does not reflect the activated state of sarcoidosis.

Adult↗
PubMed1986

The binding of monomeric IgG to human blood monocytes and alveolar macrophages.

Macrophage receptor sites for IgG are important in the immune clearance of particles both from the blood and lung. We studied the number, affinity, and density of binding sites for monomeric IgG on human blood monocytes and alveolar macrophages. Monocytes and alveolar macrophages had a similar affinity for monomeric IgG at 37 degrees and 4 degrees C. The half-time for dissociation of the IgG-receptor complex was also similar for both cells. However, alveolar macrophages expressed approximately 5-fold more IgG binding sites than monocytes at both 37 degrees and 4 degrees C. Nevertheless, when cell surface area was estimated, these cells expressed a similar density of IgG binding sites (monocytes = 110 +/- 14.8 IgG binding sites/square micron; pulmonary macrophages = 138 +/- 46.9 IgG binding sites/square micron; p greater than 0.50). Gamma interferon increased the number and density of monocyte binding sites for monomeric IgG by 162 +/- 89%. Furthermore, patients with sarcoidosis, a disorder in which gamma interferon is spontaneously elaborated, expressed a similar increase in the number of IgG binding sites per monocyte, from 24,968 +/- 1,361 for normal subjects to 44,860 +/- 6,652 for patients with sarcoidosis. However, alveolar macrophages from 5 patients with sarcoidosis expressed a normal number of IgG binding sites. These data suggest that there is no major alteration in the Fc(IgG) receptor as monocytes differentiate into alveolar macrophages. Both gamma interferon treatment and sarcoidosis are associated with enhanced expression of the Fc(IgG) receptor on monocytes.

Binding Sites↗
PubMed1985

Human alveolar macrophage inhibition of lung fibroblast growth. A prostaglandin-dependent process.

The processes controlling fibrosis in the human lung are poorly understood. Mononuclear cells may be important regulators of fibroblast function, and the alveolar macrophage (AM) is the major mononuclear phagocyte of the human lung. To further understand AM-fibroblast interactions in the lung, supernatants from unstimulated and stimulated adherent human AM were obtained and their effect on the log phase growth of human lung fibroblasts was characterized. Alveolar macrophage supernatants inhibited fibroblast growth in a dose-dependent fashion. This inhibition was the result of a heat-stable (56 degrees C, 1 h), nondialyzable (molecular weight cutoff, 12,000 daltons), soluble factor(s), which was preferentially elaborated by smaller and denser macrophage subpopulations. The inhibitory capacity of an AM supernatant was directly related to its capacity to stimulate fibroblast prostaglandin production. Blocking fibroblast prostaglandin production reversed the inhibition of fibroblast growth caused by AM supernatants. Thus, AM inhibition of fibroblast growth may be mediated in part by fibroblast prostaglandin production. Alveolar macrophage inhibition of fibroblast growth may be important in preventing fibrosis in normal persons and/or in inhibiting the fibrotic response seen with pulmonary inflammation.

Biomechanical Phenomena↗
PubMed1985

Bronchoalveolar lavage: role in the pathogenesis, diagnosis, and management of interstitial lung disease.

Bronchoalveolar lavage has emerged as a useful technique for the study of pulmonary interstitial disorders. Several types of information are provided by the evaluation of lavage fluid. First, the identification of cellular constituents helps to separate inflammatory processes in which lymphocytes predominate (for example, sarcoidosis, hypersensitivity pneumonitis, and berylliosis) from those in which neutrophils or macrophages predominate (for example, idiopathic pulmonary fibrosis and histiocytosis X). Second, the cells removed during lavage can be studied for their immune properties and function; tested with specific antigens, in diseases such as berylliosis and hypersensitivity pneumonitis; and examined for the presence of unique surface antigens with monoclonal antibodies (for example, histiocytosis X). Third, in conjunction with scanning electron microscopy and electron probe analysis, lavage makes possible the identification of inorganic particles in alveolar macrophages of patients with pneumoconiotic lung disease. Finally, although lavage is still an investigative procedure for most pulmonary disorders, it has an established role in the diagnosis of opportunistic infections in the immunocompromised patient.

Alveolitis, Extrinsic Allergic↗
PubMed1985

Differential interleukin 1 elaboration by unfractionated and density fractionated human alveolar macrophages and blood monocytes: relationship to cell maturity.

The elaboration of interleukin 1 (IL 1) by mononuclear phagocytes is important in the regulation of human inflammatory and fibrotic reactions. Mononuclear phagocytes are morphologically and functionally heterogeneous cells. To further understand the processes controlling inflammation and fibrosis, in particular that in the human lung, we studied the elaboration of IL 1 by unfractionated and density-fractionated human alveolar macrophages and blood monocytes. Stimulated blood monocytes elaborated more IL 1 than stimulated alveolar macrophages. In addition, denser alveolar macrophages and blood monocytes elaborated more IL 1 than less dense alveolar macrophages and monocytes. Lastly, as monocytes matured in vitro, they lost their ability to elaborate IL 1 and became less dense. Thus, there is variability between and within mononuclear phagocyte cell populations in their ability to elaborate IL 1. These differences may result in part from differences in cell maturation.

Cell Differentiation↗
PubMed1984

Inhibition of lung fibroblast growth by human lung mononuclear cells.

Mononuclear cell-fibroblast interactions in the normal human lung are poorly understood. To investigate these interactions, we characterized the effect on lung fibroblast growth of supernatants from nonadherent lung mononuclear cells cultured with or without phytohemagglutinin (PHA). Supernatants from unstimulated cells had no effect on fibroblast growth. Supernatants from lung mononuclear cells stimulated by PHA inhibited fibroblast growth in a dose-dependent fashion. This inhibition was mediated by a nondialyzable, noncytotoxic, soluble factor(s) that was partially heat labile and sensitive to digestion with trypsin. Production of this factor(s) was dependent on T-lymphocytes and occurred within 4 h of the initiation of lung mononuclear cell-PHA cultures. Because prostaglandins can mediate mononuclear cell effects on fibroblast growth, we examined the relationship between the inhibition of fibroblast growth caused by PHA-stimulated nonadherent lung mononuclear cells and lung fibroblast prostaglandin production. The nonadherent lung mononuclear cell supernatants stimulated fibroblast PGE2 production, and exogenous PGE2 was capable of inhibiting fibroblast growth. However, the inhibition of fibroblast growth caused by nonadherent lung mononuclear cells stimulated by PHA was not mediated by fibroblast prostaglandin production. Inhibition of lung fibroblast growth by stimulated lung mononuclear cells may be important in regulating fibrosis in the human lung.

Cell Extracts↗
PubMed1984

Blood and lung mononuclear cell inhibition of fibroblast growth in sarcoidosis.

A defect in mononuclear cell inhibition of fibroblast growth may be important in the pathogenesis of tissue fibrosis in sarcoidosis. To test this hypothesis, supernatants were prepared from unstimulated and phytohemagglutinin (PHA) stimulated peripheral blood and nonadherent lung mononuclear cells of patients with sarcoidosis. The effect of these supernatants on human lung fibroblast log phase growth was compared with the effect of similar supernatants from normal persons and patients with other lung diseases. Supernatants from normal persons and the majority of patients with sarcoidosis had similar effects on fibroblast growth. Unstimulated blood and nonadherent lung mononuclear cells had no consistent effect on fibroblast growth, whereas PHA stimulated cells inhibited fibroblast growth in a dose-dependent fashion. However, unlike that in normal persons, the blood and/or lung mononuclear cells from approximately one third of the patients with sarcoidosis appeared to be activated in vivo because supernatants from these cells inhibited fibroblast growth without in vitro mitogen stimulation. Spontaneous inhibition of fibroblast growth was not seen in supernatants from blood or nonadherent lung mononuclear cells from patients with other lung diseases. Age, sex, lavage cell yield and differential, peripheral lymphocyte count, and percentage of activated T-lymphocytes did not differentiate patients whose mononuclear cells spontaneously inhibited fibroblast growth from those patients whose cells did not. However, patients whose lung mononuclear cells spontaneously inhibited fibroblast growth had fewer pulmonary function abnormalities than did patients whose cells did not.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

DR framework antigens and 63D3 antigens on human peripheral blood monocytes and alveolar macrophages.

The expression of surface antigens on human peripheral blood monocytes and alveolar macrophages was compared using the monoclonal antibodies 63D3, which react with monocytes, and OKIa, which reacts with DR framework antigens. Fluorescence-activated cell-sorter analysis revealed that 71.5 +/- 4.6% of peripheral blood monocytes reacted with 63D3 and showed a uniform distribution of binding. Alveolar macrophages also reacted with 63D3 and displayed uniform binding. Furthermore, the relative fluorescence intensity was very similar to that of monocytes. These data suggest that 63D3 antigen expression is similar on peripheral blood monocytes and alveolar macrophages and may be a stable marker in the differentiation of monocytes to macrophages. Analysis showed that 45.8 +/- 4.9% of peripheral blood monocytes reacted with OKIa and showed a nonuniform distribution of binding, while 74 +/- 8.4% of alveolar macrophages reacted with OKIa and exhibited uniform binding. The relative fluorescence intensity of alveolar macrophages which were reacted with OKIa was significantly greater than that of blood monocytes (P less than 0.001). Size analysis suggested that alveolar macrophages express approximately five times more DR antigens per unit surface area than do peripheral blood monocytes. The expression of DR antigens on the alveolar macrophage surface suggests an important role for macrophages in antigen presentation in the lung.

Antibodies, Monoclonal↗
PubMed1983

Spontaneous production of interleukin-1 by human alveolar macrophages.

A culture system was developed in which human peripheral blood mononuclear cells depleted of monocytes did not proliferate in response to the lectin mitogen phytohemagglutinin (PHA). The response of these cells to PHA was reconstituted with both autologous and heterologous alveolar macrophages. In addition, a partial restoration of PHA responsiveness was seen when the monocyte-depleted cells (MDC) were cultured with supernatants from purified alveolar macrophages, indicating the presence of Interleukin-1 (IL-1) activity in these supernatants. This is the first evidence suggesting the production of IL-1 by tissue macrophages from normal human subjects. In contrast to previous studies of IL-1 production by blood macrophages, it was found to be unnecessary to stimulate the alveolar macrophages in vitro to generate soluble factor activity. It was also found that alveolar macrophages produced active supernatants after only 2 hr in culture, whereas previous studies have indicated that blood monocytes must be cultured for at least 24 hr before active supernatants are produced. These differences may provide evidence that macrophages within the alveolar spaces are in an activated state.

Cells, Cultured↗
PubMed1983

Cavitary pulmonary sarcoidosis.

A 25-year-old woman was initially seen with hilar adenopathy and bilateral cavitary lesions. No cause for these roentgenographic abnormalities other than sarcoidosis could be determined. In contrast to what is usually found in acute sarcoidosis, the bronchoalveolar lavage fluid from this patient contained a normal number of lymphocytes and an increased number of multinucleated giant cells. These findings raise the possibility that patients with acute sarcoidosis and cavitation have an atypical form of this disease. Even though cavitation in acute sarcoidosis is rare, this disorder must be considered in making the differential diagnosis of cavitary lung disease.

Adult↗