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Biomedical subjects

J A Rankin

Publications and source records attributed to J A Rankin.

At least 37 records · Page 2Linked to original sources
PubMed1992

Effects of in vitro amiodarone exposure on alveolar macrophage inflammatory mediator production.

Administration of amiodarone, although often lifesaving, is associated with pulmonary side effects. Patients with amiodarone pulmonary toxicity can present with either a chronic disorder that suggests pulmonary fibrosis or a more acute process. Mechanisms of acute pulmonary injury resulting from amiodarone are unclear. Previous studies have demonstrated that the drug is preferentially concentrated in alveolar macrophages. In the present study, the authors examined whether in vitro exposure to amiodarone resulted in alteration of rat alveolar macrophage superoxide, leukotriene B4, or fibronectin release. In addition, the authors assessed whether macrophages were ultrastructurally altered by in vitro amiodarone exposure. Twenty four hour exposure to therapeutic tissue concentrations of amiodarone resulted in enhancement of phorbol myristate acetate-stimulated macrophage superoxide release. In addition, 48 hours exposure to amiodarone caused a dose-dependent inhibition of spontaneous fibronectin release by macrophages. Macrophages exposed to 48 hours of 10 micrograms/ml amiodarone were ultrastructurally abnormal, containing lamellar inclusions and demonstrating a large degree of vacuolization. The authors concluded that alveolar macrophages are very sensitive to therapeutic tissue concentrations of amiodarone. Alteration of macrophage mediator release by amiodarone may be one mechanism for lung damage induced by the drug.

Amiodarone↗
PubMed1992

Human airway macrophages. A technique for their retrieval and a descriptive comparison with alveolar macrophages.

We developed a technique to isolate and lavage a segment of a large human airway in vivo. Airway lavage and BAL were performed without significant complications 18 times on 17 normal volunteers. The mean +/- SEM volume of instillate used on all subjects totaled 31.3 +/- 2.7 ml with 47.1 +/- 3.8% of the fluid recovered. A total of 1.5 +/- 0.3 x 10(6) cells were retrieved. Cell viability averaged 71.3 +/- 4.6%. The majority of the cells were macrophages, 27.9 +/- 2.7%, and neutrophils, 28.4 +/- 6.0%. A descriptive comparison of airway macrophages using transmission electron microscopy with those retrieved from paired bronchoalveolar lavage (BAL) samples revealed that airway macrophages possessed more vacuoles (p less than 0.0001), fewer long microvilli (p less than 0.0001), and more membrane undulations (p less than 0.0001). In contrast, macrophages from both lavage locations demonstrated similar staining characteristics when stained with a panel of monoclonal antibodies. During lavage, all subjects experienced mild dyspnea that was relieved when the lavage was completed. One of three subjects tested during the procedure revealed O2 desaturation that was prevented by the inhalation of O2. We conclude that viable macrophages can be retrieved safely from airways of normal subjects and that, compared with macrophages present in BAL, these cells bear both similarities and dissimilarities that may portend differing functional capabilities.

Adult↗
PubMed1992

Problem-based medical education: effect on library use.

Problem-based learning (PBL) is being adopted by U.S. medical schools. Information-seeking skills are central to the PBL curriculum, which emphasizes self-directed learning and the acquisition of problem-solving and lifelong learning skills. The purpose of this study is to begin exploring the relationship between the PBL curriculum and student information and library use. Medical students in PBL and conventional medical school curricula were compared on library and information-seeking competencies, behaviors, and perceptions. A survey was sent to second-year students in four medical schools, two schools with two curricular tracks (one PBL and one conventional), one PBL school, and one conventional school. The results showed certain significant differences (P less than 0.05) between PBL and conventional curriculum students, suggesting that PBL students were the more frequent library users, used information resources that supported the independent learning process, acquired information-seeking skills at an earlier stage in their medical education, and reported greater ease in using these skills.

Curriculum↗
PubMed1991

An analysis of the inter-relationships among multiple bronchoalveolar lavage and serum determinations, physiologic tests, and clinical disease activity in patients with sarcoidosis.

Analysis of epithelial lining fluid from the lungs of patients with sarcoidosis frequently suggests the presence of an alveolitis. Several markers of this inflammatory response were quantitated in bronchoalveolar lavage fluid and serum from 45 non-smoking patients with sarcoidosis. All markers were elevated significantly compared to those from 19 normal controls. The degree of statistical correlation among all data was assessed. Pulmonary function tests, 67Gallium lung scans, and a clinical index of disease activity also were quantitated. When patients were grouped by the number of abnormal BAL lavage and serum markers, those patients with elevated values of five or more of these markers had significantly worse clinical disease and lower carbon monoxide diffusing capacities. These results indicate that pulmonary sarcoidosis is an immunologically heterogeneous disease and that measurement of several markers of disease activity may be required to accurately estimate the activity of the lung disease.

Adult↗
PubMed1990

U937 and THP-1 cells do not release LTB4, LTC4, or LTD4 in response to A23187.

U937 and THP-1 cells possess some characteristics of human mononuclear phagocytes, cells which synthesize and release LTB4, LTC4, and LTD4. Incubation of these cells with recombinant human interferon-gamma (IFN-gamma) or Phorbol Myristate Acetate (PMA) induces a more differentiated cell state. We hypothesized that U937 and THP-1 cells would release LTB4, LTC4, and LTD4 in response to stimulation with the non-physiologic agonist, calcium ionophore A23187 and that preincubation with IFN-gamma or PMA might alter leukotriene release by these cells. We cultured both cell lines for 48 hours in the presence and absence of IFN-gamma (1000 units/ml) and for 120 hours in the presence and absence of PMA (160 nM) and then challenged them with A23187 (5uM) for 30 minutes at 37 degrees C. The supernatants were deproteinated and assayed by RIA for LTB4 and LTC4 and by RP-HPLC for LTB4, LTC4, and LTD4. Neither U937 nor THP-1 cells released quantities of leukotrienes detectable by RIA, less than 0.3ng/5 X 10(6) cells. Peripheral blood mononuclear phagocytes from normal volunteers, cultured and challenged in vitro at under identical conditions, released 11.3 +/- 2.9 ng LTB4 and 2.0 +/- 1.5 ng LTC4/10(6) viable monocytes. The lack of leukotriene production by U937 and THP-1 cells was not altered by preincubation for 48 hours with IFN-gamma (n = 3) nor by preincubation with PMA for 120 hours (n = 3). We conclude 1) U937 and THP-1 cells do not appear to be appropriate in vitro models for the examination of leukotriene release from normal mononuclear phagocytes. 2) Pre-incubation of U937 and THP-1 cells with IFN-gamma or PMA under the conditions tested, does not induce the ability of these cell lines to release leukotrienes.

Calcimycin↗
PubMed1990

Sensitivity of basophils to histamine releasing factor(s) of various origin: dependency on allergic phenotype of the donor and surface-bound IgE.

Certain species of histamine-releasing factor (HRF) have been demonstrated to distinguish a select group of allergic patients from healthy subjects. An IgE-dependent mechanism of action has been suggested. The donor and IgE dependency of HRF produced by peripheral blood mononuclear cells (PBMCs) has not been clearly demonstrated. In this study, we have compared the response of basophils from normal subjects versus allergic patients with and without asthma. In addition, we have addressed the IgE dependency of HRF recovered from cultures of PBMCs, T cells, B cells, macrophages, and bronchoalveolar lavage fluid. We have demonstrated that basophils from allergic as well as normal subjects respond to PBMC-HRF. The response of basophils from allergic patients with asthma is significantly increased. This heightened response to HRF does not correlate with the severity of disease as assessed by baseline spirometry, medication, and skin test scores. Stripping of the membrane-bound IgE by incubating basophils with lactic acid causes a significant loss of sensitivity to HRF generated by PBMCs, T cells, B cells, and macrophages, as well as to HRF recovered from bronchoalveolar fluid. The loss of response can be restored by sera from patients with asthma but not from normal subjects or by myeloma IgE. In addition, poorly responsive basophils from normal subjects can be rendered sensitive by incubating with sera from patients with asthma. The capacity of a given serum from a patient with asthma to restore the response to HRF is not correlated with the total concentration of IgE in the serum.(ABSTRACT TRUNCATED AT 250 WORDS)

Asthma↗
PubMed1990

Detection of histamine release inhibitory factor- and histamine releasing factor-like activities in bronchoalveolar lavage fluids.

Histamine releasing factors (HRF) are a group of cytokines that cause degranulation of basophils and mast cells. Recently we have described a histamine release inhibitory factor (HRIF) that inhibits HRF-induced histamine release from basophils and mast cells. The objective of this study was to investigate the presence of these cytokines in bronchoalveolar lavage (BAL) fluid from normal subjects. We found that BAL fluids from 12 to 17 volunteers contained a dialyzable (molecular weight cutoff 3500) factor that inhibited basophil histamine release by HRF, anti-IgE, concanavalin A, and N-formyl-methionyl-leucyl-phenylalanine (FMLP). In addition, BAL fluids from 83% of the tested donors contained a nondialyzable inhibitor that blocked HRF-induced histamine release from basophils. The molecular weight of this inhibitor was estimated to be 20 to 30 and 8 to 10 kD by Sephadex G-50 chromatography and TSK 2000 size-exclusion HPLC. None of the unconcentrated BAL fluids showed any HRF activity on initial screening using basophils from allergic subjects. However, when the BAL fluids were concentrated, all BAL samples that were tested (N = 10) demonstrated significant HRF activity. The molecular weight of BAL HRF has been estimated to be in the range of 15 to 25 kD by size-exclusion HPLC, similar to the HRF synthesized by mononuclear cells. Thus we have demonstrated the presence of both HRF and HRIF in the BAL fluids. We speculate that these cytokines may be involved in the local regulation of basophil and mast cell activation.

Adult↗
PubMed1990

Secretion of neutrophil attractant/activation protein by lipopolysaccharide-stimulated lung macrophages determined by both enzyme-linked immunosorbent assay and N-terminal sequence analysis.

Alveolar macrophages contribute to acute pulmonary inflammation by secretion of neutrophil chemoattractants. We determined if one of these attractants is neutrophil attractant/activating protein (NAP-1), which is secreted by blood monocytes stimulated by lipopolysaccharide (LPS). Alveolar macrophages were stimulated in tissue culture with 10 micrograms/ml LPS. Culture fluids collected at 24 h were assayed for both neutrophil chemotactic activity and the concentration of NAP-1 as determined by a sandwich ELISA. The concentration of NAP-1 in culture fluid to LPS-stimulated macrophages was 860 +/- 40 ng/ml (SEM for six normal subjects). NAP-1 in fluid of unstimulated macrophages was 40 +/- 15 ng/ml. We confirmed the presence of NAP-1 in culture fluid of LPS-stimulated lung macrophages by immunoaffinity and HPLC-CM column purification. The HPLC-CM elution profile of macrophage NAP-1 was identical to that of monocyte NAP-1, and the N-terminal sequence of the protein in one of the isolated peaks corresponded to that of monocyte-derived NAP-1 beta. Two lines of evidence show that NAP-1 does not account for all neutrophil chemotactic activity in culture fluid of 24-h, LPS-stimulated macrophages. At a dilution of culture fluid that elcited the same chemotactic response as a known concentration of pure NAP-1, the concentration of culture fluid NAP-1 was only one-tenth that of pure NAP-1. (ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Macrophages cultured in vitro release leukotriene B4 and neutrophil attractant/activation protein (interleukin 8) sequentially in response to stimulation with lipopolysaccharide and zymosan.

The capacity of lipopolysaccharide (LPS), zymosan, and calcium ionophore A23187 to induce neutrophil chemotactic activity (NCA), leukotriene B4 (LTB4), and neutrophil attractant/activation protein (NAP-1) release from human alveolar macrophages (AM) retrieved from normal nonsmokers was evaluated. LPS induced a dose-dependent release of LTB4 that began by 1 h, 4.0 +/- 3.2 ng/10(6) viable AM; peaked at 3 h, 24.7 +/- 13.5 ng/10(6) viable AM; and decreased by 24 h, 1.2 +/- 1.0 ng/10(6) viable AM (n = 8). Quantities of LTB4 in cell-free supernatants of AM stimulated with LPS were determined by reverse-phase high-performance liquid chromatography and corresponded well with results obtained by radioimmunoassay. By contrast, NAP-1 release began approximately 3-5 h after stimulation of AM with LPS, 197 +/- 192 ng/ml, and peaked at 24 h, 790 +/- 124 ng/ml. Release of NAP-1 was stimulus specific because A23187 evoked the release of LTB4 but not NAP-1, whereas LPS and zymosan induced the release of both LTB4 and NAP-1. The appearance of neutrophil chemotactic activity in supernatants of AM challenged with LPS for 3 h could be explained completely by the quantities of LTB4 present. After stimulation with LPS or zymosan for 24 h, AM had metabolized almost all generated LTB4. Preincubation of AM with nordihydroguiaretic acid (10(-4) M) completely abolished the appearance of NCA, LTB4, and NAP-1 in supernatants of AM challenged with LPS. Therefore, LPS and zymosan particles were potent stimuli of the sequential release of LTB4 and NAP-1 from AM.

Calcimycin↗
PubMed1990

Nursing students' preferences in the use of computer assisted learning.

One hundred and ten student nurses in the second year of a 3-year diploma program were surveyed following their use of computer assisted learning (CAL) programs. The questionnaire was designed to elicit responses concerning the preferred number of users per terminal, the level of supervision (supervised/unsupervised) and their general affective response to this type of learning. The results showed that the majority (56.4%) of students preferred to work in a group (a group constituted no more than three students per terminal). Whereas 31.8% preferred to work through the program alone, just over 50% would rather be supervised while running the program, and 26.4% expressed a preference for no supervision. There was no relationship found between program content and running the program alone or with others. However, in 10% of the sample there was a positive relationship found between the need for supervision and program content. The reasons given for these preferences and the advantages and disadvantages of CAL, as perceived by the students, are also discussed.

Adolescent↗
PubMed1990

Phagocyte enzymes in bronchoalveolar lavage from patients with pulmonary sarcoidosis and collagen vascular disorders.

The balance between proteases and antiproteases in the lower respiratory tract is believed to play a role in the outcome of interstitial lung diseases. In this cross-sectional study, we measure several phagocyte derived enzymes, namely plasminogen activator, neutrophil elastase and an ill-defined protease active on the trialanine chromophore substrate succinyl-alanine3-nitroanilide (SLAPN) in bronchoalveolar lavage (BAL) fluid from 42 patients with pulmonary sarcoidosis and from 43 patients with collagen vascular disease (CVD), 22 without lung disease (group I) and 21 associated with parenchymal lung disease (group II). The results show: a) that sarcoidosis is associated with increased plasminogen activator activity and with the presence of enzymatic activity against SLAPN corresponding at least in part to a metalloprotease; b) that CVD in the absence of radiographic lung disease is associated with an increase of plasminogen activator activity and increased levels of alpha 1-antiprotease-neutrophil elastase complexes; c) that the majority of untreated CVD (group II) patients have detectable levels of neutrophil elastase activity. These data show that patients with pulmonary sarcoidosis and CVD have different enzymatic profiles in their lower respiratory tract as assessed by BAL. Thus, sarcoidosis (mostly lymphocytic) is associated with enhanced macrophage-derived proteolytic activity in BAL, while CVD patients both with and without lung disease have increased neutrophil counts and neutrophil elastase complexed to alpha 1-protease inhibitor and presumably inactive in BAL. Finally, only BAL from untreated CVD patients with interstitial lung disease contain neutrophil elastase activity. This latter activity could contribute to the lung lesions frequently observed in these disorders.

Adult↗
PubMed1989

The contribution of alveolar macrophages to hyperreactive airway disease.

Thus, there is substantial evidence that favors a role for macrophages in subjects with atopic asthma. The precise manner in which these cells participate and the relative degree to which these cells contribute to, or orchestrate, events remains to be delineated. Research on the potential role of macrophages in asthma syndromes remains in its infancy. In time we will discover new roles for mononuclear phagocyte-derived mediators and many more new mediators that will play a role in the complex immunologic events ongoing in the airways of patients with asthma. Also, future research will continue to explore what promises to be a productive area of research, namely, cell-cell interactions and the manner in which many cells participate together in the pathophysiology of asthma. If macrophages can be demonstrated to influence airway inflammation associated with atopic disease, they may be appropriate targets for therapeutic intervention.

Asthma↗
PubMed1989

The development of a practising nursing faculty.

Practice is where skills are developed and where theory must pass testing. This is best done by observing and responding to human needs so that theory generated will have a precise fit. A variety of joint appointments with a focus on nursing have been established between the Faculty of Nursing at The University of Calgary and nursing service agencies in Calgary, Alberta, Canada. The expected outcome is congruence between teaching, theory development, and practice. This paper differentiates faculty practice as scholarship from other forms of faculty involvement in practice settings. The nature of faculty practice is examined and various models of faculty practice are discussed. The Calgary model, designed to fit faculty member's focus on care to specific practice settings is described.

Canada↗
PubMed1989

Methotrexate pneumonitis. Bronchoalveolar lavage findings suggest an immunologic disorder.

Methotrexate (MTX) is used widely for the treatment of a variety of tumors as well as for non-neoplastic conditions. Its association with pneumonitis is well established, but the mechanism of lung injury is unknown. To clarify this issue, we performed bronchoalveolar lavage (BAL) in six patients with MTX pneumonitis and in three control groups. In those with drug-induced pneumonitis, there was a significant increase in the total number of lavage cells recovered as well as in the percentage and absolute number of lymphocytes compared with those in the other groups. Patients receiving the drug without evidence for pulmonary toxicity had lavage findings that were not different from those in the other control groups. The ratio of BAL phenotypic helper/suppressor T-cells was studied in three patients with MTX toxicity and was found to be increased compared with that in normal healthy control subjects. Our findings show that MTX pneumonitis is characterized by a lymphocytic alveolitis with a predominance of phenotypic helper T-cells and a relative deficiency in the percentage of suppressor T-cells. The presence of increased lavage lymphocytes suggests that an immunologically mediated injury rather than a direct toxic effect of this drug may be a significant pathophysiologic mechanism in this disorder.

Adult↗
PubMed1989

Recombinant interferon-gamma primes alveolar macrophages cultured in vitro for the release of leukotriene B4 in response to IgG stimulation.

The capacity of interferon-gamma to regulate the generation and release of leukotriene B4 (LTB4) from human alveolar macrophages of normal nonsmoking individuals was evaluated. When alveolar macrophages were incubated for 60 min with heat aggregated IgG (HAIgG), they generated and released 5.7 +/- 1.7 ng of LT B4 per 10(6) cells compared to 1.9 +/- 0.4 ng from cells incubated with buffer alone, P = 0.02. When alveolar macrophages were preincubated with interferon-gamma for 24 h before activation for 60 min with heat-aggregated IgG, the soluble IgG aggregates became a significantly more effective stimulus for LTB4 release, 17.0 +/- 3.9 ng/10(6) cells, P = 0.001, compared to cells incubated in the absence of interferon-gamma and challenged with HAIgG. Interferon-gamma did not alter the response to A23187. This effect of interferon-gamma was both time and dose dependent; it also was specific since neither interferon-alpha nor interferon-beta had a regulatory effect on the release of LTB4 from cells in response to challenge with HAIgG. Preincubation of the alveolar macrophages with interferon-gamma augmented the density of IgG1 receptors by 81.5 +/- 17.3%; neither interferon-alpha nor interferon-beta effected this parameter. Furthermore, monomeric IgG1 blocked HAIgG induced LTB4 release from alveolar macrophages primed with interferon-gamma. Therefore, at least one of the mechanisms by which interferon-gamma primes alveolar macrophages for the production and release of LTB4 in response to stimulation by aggregates of IgG is that of increasing the number of receptors for this stimulus.

Antigens, Differentiation↗