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Biomedical subjects

W J Calhoun

Publications and source records attributed to W J Calhoun.

45 records · Page 3Linked to original sources
PubMed1990

Bronchoalveolar lavage in stable asthmatics does not cause pulmonary inflammation.

Bronchoalveolar lavage (BAL) has become an important tool for evaluating changes in airway cells and fluid in asthma, and it may give insights into mechanisms of bronchial inflammation. Many factors contribute to airway inflammation in asthma including, possibly, airway instrumentation. To establish whether BAL leads to diffuse airway inflammation in stable asthmatics, we performed paired BAL studies (24 h apart) in eight subjects with mild asthma whose prebronchoscopy spirometric results were similar on both days. Airflow limitation did not occur in any subject after bronchoscopy. We observed no significant changes in BAL volume return, cell differential, lymphocyte subsets, reactive oxygen species metabolism by air-space cells, or BAL total protein. There was a slight increase in second-day BAL total cell return. We conclude that bronchoscopy and BAL in stable asthmatics with mild disease is not associated with evidence of diffuse airway inflammation.

Adult↗
PubMed1990

Modulation of human peripheral blood monocyte superoxide release by interferon-gamma and lipopolysaccharide.

Reactive oxygen species (ROS) have generated increasing interest for their possible role in a wide variety of diseases. Interferon-gamma (IFN-gamma), a potent immunoregulatory lymphokine, is likely involved in control of ROS metabolism. In this study, the superoxide release of cultured human peripheral blood monocytes (PBM) after exposure to IFN-gamma and lipopolysaccharide (LPS) was examined. Compared with controls, adherent monocytes cultured with 80 units of IFN-gamma for 48 hours demonstrated fourfold increased spontaneous and twofold increased PMA stimulated release of superoxide anion. In addition, the enhanced superoxide release was both dose and time dependent. Further experiments showed that bacterial LPS in concentrations as low as 4 ng/mL markedly reduced monocyte superoxide release and abrogated the enhancing effects of IFN-gamma.

Dose-Response Relationship, Drug↗
PubMed1989

Studies of bronchoalveolar lavage cells and fluids in pulmonary sarcoidosis. I. Enhanced capacity of bronchoalveolar lavage cells from patients with pulmonary sarcoidosis to induce angiogenesis in vivo.

Both allogeneic immunocompetent CD4+ lymphocytes and activated macrophages of mice can induce neovascularization when inoculated intradermally into host animals. Because sarcoidosis is associated with an increase in both activated macrophages and CD4+ effector lymphocytes in the lung, we carried out experiments in which cells obtained by bronchoalveolar lavage (BAL) of patients with pulmonary sarcoidosis were tested in a murine intradermal angiogenesis assay. BAL cells from patients with pulmonary sarcoidosis induced a significantly greater degree of angiogenesis than those from normal volunteers or from patients with other lung diseases. Moreover, the degree of angiogenesis induced by BAL cells from patients with sarcoidosis correlated positively with the severity of the disease. When BAL cells were separated into macrophage and lymphocyte subpopulations by flow cytometric techniques, the observed angiogenic activity was restricted primarily or exclusively to macrophages; lymphocytes were unable to induce angiogenesis in this xenogeneic assay system. These experiments suggest that pulmonary macrophages may play a role in the pathogenesis of sarcoidosis by inducing changes in the pulmonary microvasculature. Moreover, we hypothesize that these vascular changes may be induced not only in the lung but also in other organ systems such as skin, muscle, and eye in which microangiopathies are associated with sarcoid disease.

Animals↗
PubMed1989

Studies of bronchoalveolar lavage cells and fluids in pulmonary sarcoidosis. II. Enhanced capacity of bronchoalveolar lavage fluids from patients with pulmonary sarcoidosis to induce cell movement in vitro.

The ability to increase the motility of endothelial cells in vitro is a property common to most if not all angiogenesis-inducing factors. Because bronchoalveolar lavage (BAL) cells from patients with pulmonary sarcoidosis have an enhanced capacity to induce neovascularization, the BAL fluids from these patients were assessed for their effect on human and murine endothelial cells and fibroblasts obtained from a variety of tissue sources. A recently developed computer-assisted image analysis system was used to determine the extent and pattern of cell migration in a microwell screening assay. Data were obtained for BAL fluids from 10 patients with pulmonary sarcoidosis and from five normal volunteers. BAL supernatants from patients with active sarcoidosis showed an enhanced (2- to 8-fold) capacity to induce chemokinesis of both endothelial cells and fibroblasts, as measured by increased area of migration and polarized cell movement. There was a marked heterogeneity in the motility of cells from different organ origins, but enhanced cell movement was observed with both endothelial cells and fibroblasts. In contrast, BAL fluids from normal and sarcoid patients were similar in their effect on muscle cells and urothelial cells, whereas pericytes, which responded to BAL fluids from normal subjects or patients with nongranulomatous pulmonary disease, were inhibited by BAL fluids from patients with pulmonary sarcoidosis. The induction of endothelial cell movement in vitro induced by individual supernatants generally correlated with the capacity of BAL cells from these patients to induce angiogenesis in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Heterogeneity in cell recovery and superoxide production in buoyant, density-defined subpopulations of human alveolar macrophages from healthy volunteers and sarcoidosis patients.

Reactive oxygen species (ROS) are ubiquitous compounds produced by phagocytes with important roles in both host defense and pulmonary inflammation. Enhanced ROS metabolism by alveolar macrophages (AM) has been previously demonstrated in various interstitial lung diseases including sarcoidosis. We studied 17 healthy, nonsmoking volunteers and 10 patients with sarcoidosis by bronchoalveolar lavage, and separated AM on discontinuous Percoll gradients to determine patterns of airspace cell recovery and the corresponding ROS metabolism of density-defined AM subpopulations. AM subpopulations were largely purified from contaminating granulocytes, thereby allowing more accurate estimation of ROS metabolism by AM. In bronchoalveolar lavage material from sarcoidosis patients, increased recovery of cells of high (1.075 gm/ml) density was found, which contrasted with the pattern seen in the volunteers in whom cells of lowest density (1.045 gm/ml) predominated. In addition, dense cells from sarcoidosis patients exhibited enhanced stimulated ROS metabolism compared with cells of similar density obtained from the volunteers or with sarcoid cells of lower density. At least three mechanisms may contribute to increased lung oxidative burden in sarcoidosis. The combination of increased bronchoalveolar lavage cell counts, increased cell recovery at high density, and increased cell function produced substantial increases in the total oxidative burden imposed on the lungs of sarcoidosis patients by airspace cells. We conclude that AM metabolism of ROS is dependent on the density and, by implication, the maturity of the cells and that regulation of AM ROS metabolism differs markedly between sarcoidosis patients and healthy volunteers.

Analysis of Variance↗
PubMed1988

Increased alveolar macrophage chemiluminescence and airspace cell superoxide production in active pulmonary sarcoidosis.

Alveolar macrophages (AMs) and lymphocytes are activated in pulmonary sarcoidosis. Mediators from these cells are potentially important in the pathophysiology and pathogenesis of this disease. To determine whether the enhanced release of reactive oxygen species (ROS) participates in inflammatory events in sarcoidosis, and to explore the relationship between ROS release and clinical parameters, we studied ROS metabolism of AMs and other airspace cells by luminol-enhanced chemiluminescence and by direct biochemical measurement of superoxide anion production. Ten of 17 patients with sarcoidosis were prospectively found to have active disease by objective radiographic, functional, and laboratory criteria. In these subjects, ROS metabolism by AMs was significantly enhanced compared either with healthy control subjects or with patients with inactive sarcoidosis. Abnormalities in ROS metabolism were not seen in peripheral blood monocytes, suggesting that this increased metabolic activity is compartmentalized to the lung. Enhanced ROS metabolism by AMs was associated with recent adverse chest radiographic changes, recent decline in forced vital capacity, and more advanced radiographic type. These data support the hypothesis that ROS generated by airspace cells can promote parenchymal inflammation in sarcoidosis, are associated with physiologic and radiologic changes, and may thereby contribute to the pathogenesis of sarcoidosis.

Adult↗
PubMed1986

Raised immunoglobulin concentrations in bronchoalveolar lavage fluid of healthy granite workers.

Immunoglobulin concentrations and lymphocyte counts were determined in bronchoalveolar fluid obtained from nine symptomless, healthy, non-smoking granite workers (mean age 45.6, range 22-56 years) and nine normal, non-smoking, non industrial controls (mean age 22.8, range 21-32 years). The proteins were measured in unconcentrated lavage fluid by means of a solid phase, enzyme linked immunosorbent assay. IgG and IgA concentrations were three times greater in lavage fluid from granite workers than the samples from non-industrial controls (p less than 0.02). Eight of nine normal volunteers (89%) had no detectable IgM (less than 30 ng/ml) in the lavage fluid whereas eight of nine (89%) granite workers had detectable IgM (chi 2 = 8, p less than 0.01). Lymphocyte counts in lavage fluid from the workers were significantly greater (15.5%) than control counts (5.6%; p less than 0.05). The normal albumin concentration suggests that differences in permeability do not account for all of the increased immunoglobulin concentrations found in granite workers' lavage fluid and that some immunoglobulin is locally synthesised. It is concluded that occupational exposure to granite dust is associated with an increased proportion of lymphocytes and an increased concentration of immunoglobulin in lavage fluid that may reflect a subclinical immune inflammatory response.

Adult↗
PubMed1984

Variable tracheal stenosis related to body position.

We demonstrated a variable extrathoracic tracheal stenosis which developed after technically adequate tracheostomy and was worsened by changes in body position. When the patient's arms were above his head, minimal airway diameter was reduced 31 percent, and maximal inspiratory flow rate 37 percent below values measured with arms down, but expiratory flow rates were preserved. Tracheostomy may disrupt the integrity of tracheal support and allow airway collapse under circumstances of increased extratracheal or decreased intratracheal pressure.

Forced Expiratory Flow Rates↗