Biomedical subjects

R E Crowell

Publications and source records attributed to R E Crowell.

25 records · Page 2Linked to original sources

PubMed1990

Responses of isolated pulmonary arteries to the C5a anaphylatoxin.

The anaphylatoxin C5a possesses spasmogenic activity in smooth muscle tissues. In this study, we examined the effect of C5a on isolated rabbit pulmonary artery (PA) ring segments under a variety of experimental conditions. C5a (1-100 nM) caused transient constriction of PA at resting tension. C5a-induced PA constriction was not affected by the histamine H1-receptor antagonist pyrilamine (1 microM) but was significantly decreased by the cyclooxygenase inhibitor indomethacin (1 microM). Disruption of the endothelial layer of the vessel had no effect on C5a activity in resting PA. PA, which had been preconstricted with norepinephrine (5 microM), exhibited a different response to C5a than PA at resting tension, however. C5a (1-10 nM) induced a biphasic response in preconstricted PA, initially causing further constriction followed by a greater degree of relaxation resulting in an overall decrease in PA tension. All responses of preconstricted PA to C5a were completely eliminated by indomethacin and significantly depressed by endothelial disruption. These data indicate that C5a interacts directly with isolated rabbit PA, but the nature of the PA response to this peptide depends on several variables including the presence or absence of active PA tension and cyclooxygenase metabolites, and the presence of intact endothelium.

Anaphylatoxins↗

PubMed1990

Pentoxifylline relaxes isolated pulmonary arteries after preconstriction with norepinephrine.

Pentoxifylline (PTX) is a methylxanthine derivative which improves systemic microvascular flow and tissue oxygen delivery, presumably through actions on platelet aggregation and erythrocyte deformability. Although PTX also improves pulmonary vascular flow, recent evidence suggests that part of this improvement may be due to pulmonary vasodilation. To evaluate these effects we studied isolated rabbit lobar pulmonary artery (PA) ring segments to determine if PTX had direct effects on PA tissues and whether these effects could be modulated pharmacologically or by endothelial disruption. PTX had no effect on PA at resting tension. However, if the PA tension was actively increased by norepinephrine (5 microM), subsequent PTX application caused concentration-dependent PA relaxation. Relaxation occurred promptly and was maximal within 45-60 s. The threshold PTX concentration necessary for relaxation was 1 microM. PTX-induced relaxation was not affected by pretreatment with the cyclo-oxygenase inhibitor indomethacin (1 microM). Endothelial disruption by gentle rubbing of the intimal PA surface abolished relaxation of preconstricted PA by acetylcholine, but had no effect on relaxation by PTX. Although PA at resting tension displayed no response to PTX, PA constriction by norepinephrine in the presence of PTX concentrations greater than 10 microM was significantly decreased. These data indicate that PTX has direct actions on isolated rabbit PA which are not blocked by indomethacin nor require the presence of intact endothelium. Furthermore, PTX can suppress norepinephrine-induced constriction of isolated PA.

Animals↗

PubMed1989

Responses of isolated pulmonary arteries to synthetic peptide F-Met-Leu-Phe.

The chemoattractant formyl-methionine-leucine-phenylalanine (FMLP) has recently been shown to possess spasmogenic properties in smooth muscle preparations from various organs. In this study we have investigated the actions of this peptide on isolated rabbit pulmonary artery (PA) ring segments. FMLP stimulated concentration-dependent constriction of PA at resting tension. However, in PA that had been preconstricted by norepinephrine, FMLP stimulated concentration-dependent relaxation. FMLP-stimulated PA constriction was inhibited by earlier exposure to indomethacin or to furegrelate, a thromboxane synthetase inhibitor, but not by earlier exposure to the H1 histamine receptor antagonist pyrilamine. FMLP-stimulated relaxation of PA was totally abolished by indomethacin but not by furegrelate or pyrilamine. Disruption of the endothelium in PA preparations decreased both the constriction and relaxation response to the peptide, suggesting that these cells were involved in these responses. These results indicate that the chemotactic factor FMLP can elicit constriction or relaxation of isolated PA, depending on the underlying active PA tension. In addition, both constriction and relaxation are dependent on cyclooxygenase products and intact endothelium.

Animals↗

PubMed1988

Regionally variable pulmonary artery responses to C3a.

Products of the complement (C) cascade may have direct effects on pulmonary vascular tissue and contribute to pulmonary vasoconstriction in states of C activation. We studied the effects of C3a, a C-derived vasoactive peptide, on isolated rabbit hilar (HPA) and main pulmonary arteries (MPA). C3a elicited concentration-dependent constriction of HPA (10(7) M to 5 x 10(7) M) but minimal response in MPA at all concentrations tested. The difference between HPA and MPA responses was significant (P less than 0.05, paired t test). To evaluate HPA desensitization to C3a, the peptide was reapplied at 60 min in some tissues and at 120 min in others. All tissues consistently exhibited less constriction at 60 min than observed with previous exposures. Histamine contribution to the HPA response to C3a was determined by exposing the tissues for 30 min before C3a application to pyrilamine (1 x 10(-5) M), an histamine H1-receptor antagonist. Pyrilamine reduced the HPA response to C3a by 70-85%. We conclude that 1) isolated rabbit PA responses exhibit regional variability to C3a over a range of concentrations; 2) C3a desensitizes HPA for at least 60 min, but the tissue demonstrates variable recovery within 120 min; and 3) HPA responses to C3a are reduced by pyrilamine, an H1-receptor antagonist.

Animals↗

PubMedDate not supplied

Concurrent fluorescence in situ hybridization and immunocytochemistry for the detection of chromosome aberrations in exfoliated bronchial epithelial cells.

OBJECTIVE: A procedure was developed to allow concurrent detection of chromosome aberrations and identification of bronchial epithelial cells. STUDY DESIGN: Fluorescence in situ hybridization for chromosome 7 and immunocytochemistry for cytokeratin were performed on exfoliated bronchial epithelial cells in a sputum sample from a cancer patient. RESULTS: The Spectrum Orange-labeled alpha satellite probe for chromosome 7 produced red fluorescence, nuclei were counterstained with 4,6-diamidino-2-phenylindole (blue), and cytokeratin was visualized using a fluorescein isothiocyanate (FITC)-conjugated secondary antibody (green). CONCLUSION: This procedure allowed the rapid identification of airway epithelial cells with numerical chromosome aberrations in this sample. Ultimately, this procedure could increase the sensitivity and specificity of sputum cytology as a laboratory diagnostic tool for the early detection of lung cancer.

Antibodies, Monoclonal↗

PubMedDate not supplied

Alveolar and interstitial macrophage populations in the murine lung.

Pulmonary macrophages (PM) exist in two general anatomical compartments in the lower respiratory tract: the alveolar space (alveolar macrophages, AM) and the interstitium (interstitial macrophages, IM). We determined the relative contribution that macrophages in each of these compartments make to the size of the total PM population found in the lungs of C3H/OUJ mice, while also evaluating how efficiently bronchoalveolar lavage (BAL) removes AM from the murine lung. These objectives were accomplished by combining extensive BAL with subsequent mechanical and enzymatic dissociation of the lungs in conjunction with in situ and in vitro phagocytic assays involving opsonized erythrocytes (EA) to identify mononuclear phagocytes. On average, 2.5 x 10(6) cells were recovered by extensive BAL, and approximately 78% of these cells ingested EA in vitro. To determine the efficiency of BAL in removing PM from the alveolar space, EA were instilled intratracheally into intact lungs, which had been removed from the chest cavity, and allowed to incubate for 60 min; this was followed by exhaustive BAL and subsequent lung digestion. After these procedures, approximately 4% of the dissociated lung cells contained EA, indicating that these cells were alveolar in origin but had not been removed despite extensive BAL. Subtraction of these AM from the total EA+ cells in lung cell suspensions following a second in vitro incubation with EA indicated that approximately 37% of all PM were within the interstitium. These results suggest that, while AM comprise the majority of lung macrophages, IM constitute a larger component of the total PM population in murine lungs than previously reported. In addition, this study, like several previous investigations using other species, indicates that a significant proportion of AM remain in the lung despite attempts to remove them with BAL. Accordingly, residual AM significantly contaminate the IM population present in murine lung cell suspensions even after extensive lavage.

Animals↗

PubMedDate not supplied

Individuals at high risk for lung cancer have airway epithelial cells with chromosome aberrations frequently found in lung tumor cells.

Identification of individuals at greatest risk of developing lung cancer could enhance the efficacy of intervention modalities, thereby greatly reducing mortality from this disease. One strategy for identifying these people is to establish molecular markers which reflect the severity of their cancerization field. Thus, investigations were initiated to determine of cells with chromosome aberrations frequently exhibited by lung tumor cells, i.e., trisomy 7, trisomy 20, and deletion of 9p23, are prevalent within the uninvolved airways of cancer patients. As a result, cells containing these aberrations were consistently found at significantly elevated levels by using fluorescence in situ hybridization (FISH). In contrast, cells collected from non-smokers who had never smoked were normal by this assay. The next objective was to determine of cells exhibiting these alterations are also present in upper airways of exposed, but cancer-free smokers and ex-uranium miners. The results showed that, although only a subset of these people will develop lung cancer in their lifetimes, they universally harbor increased numbers of abnormal cells within their airway epithelium. However, the number of sites with multiple verities of abnormal cells tended to be fewer compared with the cancer patients. Thus, quantifying cells with molecular alterations within the cancerization field of a smoker may delineate those with a lesser grade of damage, and these individuals may be at a lesser risk of developing disease. However, differences in the extent of genetic damage afforded by these assays may not clearly define individuals with pending disease, and additional molecular assays must be devised.

Bronchi↗