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M M Dunn

Publications and source records attributed to M M Dunn.

30 records · Page 2Linked to original sources
PubMed1989

Contrasting effects of inflammatory stimuli on neutrophil and monocyte adherence to endothelial cells.

Leukocyte adherence to endothelial cells (EC) is an important early event in inflammatory responses, which are often characterized by a predominance of either neutrophils (PMN) or monocytes. However, there is little information concerning the molecular events important in leukocyte adherence to EC. Intracellular activation of protein kinase C and the calcium-second messenger system leads to the stimulation of a number of important functions in PMN and monocytes. We compared the effects of members of these pathways on human PMN and monocyte adherence to cultured bovine aortic EC. We observed that phorbol myristate acetate, phorbol, 12,13-dibutyrate, L-alpha-1-oleoyl-2-acetoyl-sn-3-glycerol, and ionomycin each induced significant dose-dependent increases in PMN adherence to EC monolayers. In contrast, similar concentrations of each of these agents induced significant decreases in EC adherence of monocytes enriched by countercurrent centrifugal elutriation. Separate experiments determined that the differences in PMN and monocyte adherence to EC were not related to differences in oxidant production because 1) phorbol myristate acetate and L-alpha-1-oleoyl-2-acetoyl-sn-3-glycerol caused similar marked increases in both PMN and monocyte superoxide anion and hydrogen peroxide production and 2) ionomycin, which had opposing effects on PMN and monocyte adherence, had no effect on PMN and monocyte superoxide anion or hydrogen peroxide release. We conclude that activators of protein kinase C and the Ca-second messenger pathway have opposite effects on PMN and monocyte adherence to EC and that these effects are mediated by O2 radical-independent mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

The pulmonary clearance of smooth and rough strains of Pseudomonas aeruginosa.

Upper airway colonization with rough strains of Pseudomonas is associated with clinical deterioration in patients with cystic fibrosis. These rough strains are less toxic than smooth strains in the burned mouse model and in vitro assays. We measured the 4-h pulmonary clearance of 10(4) and 10(6) rough and smooth Pseudomonas after intrabronchial inoculation. After 10(4) Pseudomonas, rough strains were cleared more efficiently than smooth strains (89 +/- 13% versus 140 +/- 19% of the original inoculum, respectively, p less than 0.05). This was associated with more total bronchoalveolar lavage PMNs after inoculation with rough as compared with smooth Pseudomonas (1.60 +/- 0.38 x 10(5) versus 0.55 +/- 0.09 x 10(5), respectively, p less than 0.05). After inoculation with 10(6) Pseudomonas, rough were cleared less efficiently than smooth Pseudomonas (380 +/- 45% versus 134 +/- 12% of the original inoculum, respectively, p less than 0.05). There was no difference in the BAL PMNs of the animals inoculated with either bacterial strain at this inoculum (8.1 +/- 0.6 x 10(5) and 9.4 +/- 1.0 x 10(5) for the rough and smooth Pseudomonas, respectively). When PMN differences were abolished in C5-deficient mice, 10(4) rough were cleared less efficiently than smooth Pseudomonas. The relatively poor clearance of rough Pseudomonas could not be explained by in vitro differences in PMN killing or BAL toxicity or by intrinsic growth rates.

Animals↗
PubMed1989

The interaction of asbestos and neutrophils injures cultured human pulmonary epithelial cells: role of hydrogen peroxide.

Asbestos exposure causes diffuse interstitial pulmonary fibrosis. Since alveolar epithelial cell injury is hypothesized to precede the fibrotic response in asbestosis, we investigated whether asbestos, either alone or in conjunction with neutrophils (PMNs), injured cultured human pulmonary epithelial cells (HPECs). HPEC cytotoxicity was assessed with a standard 51chromium release assay after a 16-hour incubation with asbestos and PMNs. Negligible HPEC cytotoxicity was observed after incubation with either amosite asbestos (500 micrograms/ml) or PMNs alone in serum-free media. However, incubation with both asbestos and PMNs caused significant HPEC injury, which was asbestos dose-dependent; causing 25% +/- 4% detachment and 52% +/- 8% 51chromium release with 500 micrograms/ml asbestos. The cytotoxic effects of asbestos plus PMNs were nearly completely attenuated with serum (20%) or catalase (100 micrograms/ml) but were not prevented with scavengers of superoxide anion, hydroxyl radical, or hypochlorous acid. A role for hydrogen peroxide (H2O2) in mediating HPEC injury was also suggested by the demonstration of asbestos-induced generation of H2O2 by PMNs. Furthermore, H2O2 alone (10(-4)mol/L) caused significant HPEC damage. Intimate contact between asbestos-activated PMNs and HPECs was a necessary requirement for PMN-mediated HPEC cytotoxicity. These data suggest that pulmonary epithelial cell injury is mediated in part by H2O2 release from asbestos-activated PMNs as well as intimate contact between the epithelial cell, PMNs, and asbestos.

Asbestos↗
PubMed1988

Comparison between externally stented and unstented PTFE vascular grafts.

It has been suggested that external stenting of synthetic vascular prosthetic material may improve patency rates in the low flow situation or across joints. This study compared externally stented polytetrafluoroethylene (PTFE) vascular grafts placed across the hip joint in dogs with nonstented PTFE grafts in regard to patency. Twenty animals underwent bilateral common iliac to common femoral artery bypass with proximal ligation of the femoral artery. In each animal one groin was randomly assigned to receive stented PTFE and the other nonstented PTFE. One animal was sacrificed at 2 weeks for graft infection. Nineteen animals received 38 grafts that remained in place 90-120 days. Patency was confirmed with angiography prior to sacrifice. Overall patency was 65 per cent with no significant difference between the two types of graft. Eighteen of 19 dogs (95%) had both the stented and nonstented PTFE grafts either open or closed. It is concluded that intrinsic factors, rather than external graft support, are a more important influence on graft patency in this model.

Animals↗
PubMed1987

Pulmonary clearance of Pseudomonas aeruginosa in neutropenic mice. Effects of systemic immunization.

Systemic immunization with killed Pseudomonas improves pulmonary clearance of these bacteria in normal mice. To test the effects of active systemic immunization on early pulmonary clearance of Pseudomonas in neutropenic mice, Balb/c mice were intraperitoneally immunized with 10(8) Pseudomonas or injected with saline twice weekly for 2 wk. Ten days after the last immunization, immunized and control mice received tail vein injections with either nitrogen mustard or saline daily for 3 days. Two days after the last nitrogen mustard injection, mice were intrabronchially challenged with 10(6) or 10(4) live Pseudomonas and clearance was assessed 4 h later. With the higher inoculum, immunization (neutrophil-replete and neutropenic mice) augmented pulmonary clearance. The improvement in clearance with the higher inoculum was associated with a marked increase in bronchoalveolar lavage anti-Pseudomonas IgG. However, bacteria grew in the lungs of all neutropenic mice. Immunization did not alter pulmonary clearance of the lower inoculum of Pseudomonas, and bacterial growth occurred in the neutropenic mice. Gentamicin was administered to mice 2 h after intrabronchial challenge with 10(6) Pseudomonas to determine whether its effects were additive to immunization. Gentamicin improved pulmonary clearance effected by immunization only in the neutrophil-replete mice; immunization provided no additional benefit to gentamicin in the neutropenic mice. These data show that both neutrophils and immunization contribute to Pseudomonas clearance. Immunization improves pulmonary clearance of Pseudomonas in neutropenic mice with a sufficiently high inoculum, but bacterial growth still occurs. Gentamicin treatment is effective in eliminating bacteria in this model and immunization has no additional benefit.

Agranulocytosis↗
PubMed1987

CT of the lung parenchyma and the pulmonary function test.

Computed tomography (CT) views of the lung parenchyma were compared with the corresponding pulmonary function tests (PFTs) in 39 patients. Scans were assigned a quantitative degree of involvement based on previously described CT findings. CT was fairly successful in confirming a normal appearance of the lungs in patients with normal PFTs (ten cases). CT was accurate in detecting the presence of a chronic interstitial pattern in patients with restrictive defects on PFTs (15 cases). CT was generally less successful in both the detection and quantitation in patients with PFT criteria of chronic obstructive lung disease (14 cases).

Humans↗
PubMed1987

Guidelines for an effective personal fitness prescription.

The growing popularity of personal fitness can be observed in the increasing number of exercise centers and spas, and the burgeoning amount of lay literature. It is estimated that 50 percent of adult Americans engage in some form of regular exercise, but many have little or no concept of what constitutes a safe, effective fitness program. Many advertisements make attaining fitness look almost effortless. This leads the novice to unrealistic expectations. Few health care providers receive formal training in fitness management. As a result, their instructions are often vague. This article discusses the components and importance of personal fitness. Possible risks of exercise are also discussed. The normal physiologic responses to exercise and training are reviewed and the necessary ingredients of an effective fitness prescription presented. Motivational aspects are explored, using the health-belief model as a framework.

Adult↗
PubMed1986

The effects of hyperoxia on pulmonary clearance of Pseudomonas aeruginosa.

Among the toxic effects of hyperoxia may be impaired pulmonary clearance of gram-negative bacteria. To better define this effect, we exposed BALB/c mice to 100% O2 for 24, 48, or 72 hr and intrabronchially inoculated them with 10(6) Pseudomonas aeruginosa. Clearance was assessed 4 hr later by quantitative lung cultures of air- and O2-exposed mice. Clearance was first reduced at 48 and 72 hr in mice exposed to O2. To determine the mechanism responsible, we measured bronchoalveolar lavage neutrophil (PMN) counts and neutrophil chemotactic activity at 0, 2, and 4 hr after instillation of P. aeruginosa into mice first exposed to air or O2 for 48 hr. Air-exposed mice had more PMNs than did O2-exposed mice after challenge (13.3 +/- 2.1 X 10(5) vs. 4.4 +/- 0.6 X 10(5)). There was no difference in neutrophil chemotactic activity between air- and O2-exposed mice at any time, although chemotactic activity increased in both groups after challenge. Our data suggest that hyperoxia impairs pulmonary clearance of P. aeruginosa by decreasing the influx of PMNs and that this effect is not due to diminished chemotactic activity in bronchoalveolar lavage fluid.

Animals↗
PubMed1986

Effects of irradiation on endothelial cell-polymorphonuclear leukocyte interactions.

Prominent early effects of irradiation include neutrophilic vasculitis and interstitial inflammation. To examine the role of the endothelium in these events, bovine aortic endothelial cells (EC) were irradiated (5 Gy) under ambient conditions followed by measurements of neutrophil chemotaxis toward conditioned media and adherence to EC. Neutrophil chemotactic activity increased at 4, 24, and 72 h in both the sham-treated (4.2 +/- 2.5, 15.2 +/- 4.8, and 20.0 +/- 2.7 microns, respectively) and irradiated EC-conditioned media (5.0 +/- 2.1, 18.7 +/- 4.5, and 24.1 +/- 3.4 microns, respectively), and the difference between them was significant at 72 h. The chemoattractant was trypsin sensitive, heat resistant, and chemotactic. It was not present in the EC sonicate. Adherence of neutrophils to EC that were irradiated 4 h earlier (19.3 +/- 4.2%) increased compared with controls (11.1 +/- 2.4%) and was similar to EC pretreated with zymosan-activated serum (22.0 +/- 4.0%), which is a potent inducer of adherence. Thus, following irradiation, bovine aortic EC have greater neutrophil chemotactic activity in their media and are more adherent to polymorphonuclear leukocytes.

Animals↗
PubMed1985

The effects of systemic immunization of pulmonary clearance of Pseudomonas aeruginosa.

Systemic immunization with gram-negative organisms enhances the subsequent pulmonary clearance of these organisms. We studied the early time course of this phenomenon and related it to the time of appearance of polymorphonuclear leukocytes (PMN) and anti-Pseudomonas antibody in bronchoalveolar lavage (BAL). Mice were immunized intraperitoneally twice, separated by 1 wk, with 10(8) formalin-treated Pseudomonas aeruginosa. Two weeks later, they received an intrabronchial inoculum of 2.9 X 10(6) or 4.6 X 10(7) Pseudomonas organisms. Two, 4, and 6 h later, clearance and total PMN and anti-Pseudomonas antibody in the BAL were assessed. Clearance was enhanced in immunized mice at the lower inoculum. At the higher inoculum, bacteria were growing in lungs of both groups, although they were inhibited in immunized mice. Total PMN in the BAL increased progressively in both groups of mice, but net recruitment was diminished with the high inoculum. There were significant differences in the PMN in the BAL between control and immunized mice with high inoculum. Anti-Pseudomonas IgG first appeared in the BAL at 2 h, anti-Pseudomonas IgM at 6 h. These data suggest that anti-Pseudomonas IgG is an effective early pulmonary opsonin. Further, with high inoculums, immunization may aid pulmonary defenses by diminishing the magnitude of the decrement of PMN in the lung.

Animals↗
PubMed1984

The accessory cell function of human alveolar macrophages in specific T cell proliferation.

The capacity of alveolar macrophages to support mitogen- and antigen-induced proliferation of autologous, monocyte-depleted T cells in normal, nonsmoking volunteers was studied. Purified T cells failed to proliferate in response to mitogen or antigen, whereas co-culture with peripheral blood monocytes restored responsiveness. Alveolar macrophages (AM) reconstituted the response of T cells to mitogen, indicating that AM can deliver a second proliferative signal. AM, however, were markedly inferior to monocytes in supporting antigen-induced proliferation. Thus, in 19 normal volunteers, the mean response of immune T cells to diphtheria toxoid in cultures reconstituted with normal AM was only 25% of the proliferative response to diphtheria in cultures with monocytes. Although four volunteers demonstrated antigen-presenting function equivalent to monocytes, in the remaining 15 antigen-presenting ability of AM was less than 15% that of monocytes. The difference in antigen-presenting function between AM and monocytes was not due to a difference in their display of HLA-D/DR determinants because 80% of AM were HLA-DR positive. The role of suppression in the diminished antigen-presenting function of AM was assessed in 12 volunteers utilizing mixing experiments. Eight volunteers demonstrated suppressor AM but four did not, suggesting that AM from at least some normal individuals have a faulty antigen-processing mechanism. Taken together, these studies demonstrate that AM may play three different roles in modulating T lymphocyte responses, i.e., they may present antigen, they may suppress normal responses, or they may remain immunologically inert. The factors that determine which function is expressed in vivo may determine the pulmonary response to inhaled antigen.

Adult↗