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Biomedical subjects

R A Robbins

Publications and source records attributed to R A Robbins.

At least 109 records · Page 6Linked to original sources
PubMed1991

Endotoxin stimulates bronchial epithelial cells to release chemotactic factors for neutrophils. A potential mechanism for neutrophil recruitment, cytotoxicity, and inhibition of proliferation in bronchial inflammation.

To test the effect of endotoxin on bronchial epithelial cells (BEC), BEC were isolated from bovine lungs and cultured in the presence of bacterial endotoxin. The BEC culture supernatant fluids were harvested, and neutrophil chemotactic activity (NCA) was determined with a blindwell chamber technique; cytotoxicity determined by lactate dehydrogenase release and BEC proliferation determined by Coulter counting. Endotoxin caused a dose- and time-dependent release of NCA from BEC cultures compared with media alone (82.3 +/- 8.1 vs 12.0 +/- 3.1 cells/high power field, p less than 0.001). To further characterize this activity, reverse phase HPLC analysis of release eicosanoid metabolites after [3H]arachidonic acid incorporation was performed. Endotoxin stimulated the release of the neutrophil chemoattractants, leukotriene B4 and 12-hydroxyeicosatetraenoic acids. Endotoxin also resulted in a dose and time dependent release of lactate dehydrogenase (42.9 +/- 4.2 vs 20.2 +/- 2.2 U/liter, p less than 0.001) although higher doses were required to cause cytotoxicity than to stimulate chemotaxis. Finally, endotoxin resulted in a dose dependent inhibition of BEC proliferation (176 x 10(3) +/- 16 x 10(3) vs 1,080 x 10(3) +/- 38 x 10(3) cells/ml measured at day 14, p less than 0.001). These data suggest that bacterial release of endotoxin may contribute to the pathophysiologic changes observed in bronchial inflammation by stimulating BEC to release NCA, denuding airway epithelium by causing cytotoxicity of BEC, and inhibiting epithelial repair by inhibiting BEC proliferation.

Animals↗
PubMed1991

Bronchial epithelial cells release monocyte chemotactic activity in response to smoke and endotoxin.

An increase in mononuclear phagocytes occurs within the airways during airway inflammation. Bronchial epithelial cells could release monocyte chemotactic activity and contribute to this increase. To test this hypothesis, bovine bronchial epithelial cells were isolated and maintained in culture. Bronchial epithelial cell culture supernatant fluids were evaluated for monocyte chemotactic activity. Epithelial cell culture supernatant fluids attracted significantly greater numbers of monocytes compared to media alone and the number of monocytes attracted increased in a time dependent manner. Endotoxin and smoke extract induced a dose and time dependent release of monocyte chemotactic activity compared with cells cultured in media (52.5 +/- 2.6 (endotoxin), 30.5 +/- 2.3 (smoke) vs 20.5 +/- 2.2 cells/high power field (HPF) p less than 0.001). The released activity was chemotactic by checkerboard analysis. Stimulation of the epithelial cells by opsonized zymosan, calcium ionophore (A23187), and PMA also resulted in an increase in monocyte chemotactic activity (p less than 0.01). Because the release of activity was blocked by the lipoxygenase inhibitors, nordihydroguaiaretic acid and diethycarbamazine, epithelial cell monolayers were cultured with 3 microCi [3H]arachidonic acid for 24 h and then exposed to A23187, PMA, or both stimuli, for 4, 8, and 24 h. Analysis of the released 3H activity was performed with reverse-phase HPLC and revealed that the major lipoxygenase product was leukotriene B4. These data suggest that monocytes may be recruited into airways in response to chemotactic factors released by bronchial epithelial cells.

Animals↗
PubMed1991

Death anxiety, death competency and self-actualization in hospice volunteers.

A total of 248 hospice volunteers completed the Personal Orientation Inventory, the Templer/McMordie Death Anxiety Scale, the Bugen Coping with Death Scale, and a Death Self-Efficacy Scale constructed for this research. Death anxiety significantly negatively correlated with four Personal Orientation Inventory scales, Coping with Death Scale positively correlated with seven of the twelve Personal Orientation Inventory Scales, and the Self-Efficacy Scale significantly correlated with eleven of them. These findings suggest that death competency constructs may be more useful than the concept of death anxiety in conceptualizing people's emerging self-actualization in the process of confronting mortality.

Adaptation, Psychological↗
PubMed1991

Protease injury in airways disease.

In summary, proteases are present in the airway in inflammatory airways disease. These enzymes can damage the airway epithelium. As a consequence, airway function can be altered, and long-term changes in airway anatomy can result. Although the exact cellular and biochemical mechanisms that lead to these changes are incompletely described, it seems likely that they will play important roles in clinical airways disease. As such, these pathways may represent novel opportunities for therapeutic intervention.

Animals↗
PubMed1991

Complement activation by cigarette smoke.

Lung disease secondary to cigarette smoking is associated with an influx of neutrophils and monocytes into the lower respiratory tract. To determine whether cigarette smoke can generate chemotactic activity, human serum was exposed to cigarette smoke and evaluated for neutrophil and monocyte chemotactic activity. Serum exposed to cigarette smoke attracted significantly greater numbers of neutrophils and monocytes compared with normal human serum exposed to air (P less than 0.01, both comparisons). The increase in chemotactic activity was partially attenuated by EDTA but not by ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) and MgCl2 (P greater than 0.05, both comparisons), suggesting activation of the alternate complement pathway. To evaluate the capacity of cigarette smoke to activate the complement system, smoke-exposed serum was evaluated for cleavage of properdin factor B and C3 using immunoelectrophoresis and for C5a using a radioimmunoassay. Cleavage of properdin factor B and C3 was observed in the smoke-exposed serum and C5a was detected in the smoke-exposed serum (112 +/- 31 ng/ml). These data suggest that complement activation may play a role in directing the influx of neutrophils and monocytes into the lungs of cigarette smokers.

Chemotaxis, Leukocyte↗
PubMed1991

Dibutyryl cAMP, prostaglandin E2, and antioxidants protect cultured bovine bronchial epithelial cells from endotoxin.

Acute bronchitis secondary to bacterial infection in the airway is accompanied by an acute inflammatory response composed predominantly of neutrophils. Mucosal injury with denudation of the airway epithelium to basement membrane frequently occurs. We postulated that endotoxin might explain this cytotoxicity and neutrophil influx. To test this hypothesis, bovine bronchial epithelial cells were cultured, and the culture supernatant fluids were evaluated for neutrophil chemotactic activity (NCA) and lactate dehydrogenase (LDH) after exposure to endotoxin. Escherichia coli endotoxin stimulated the release of NCA and LDH in a dose-dependent manner. Because intracellular augmentation of adenosine 3',5'-cyclic monophosphate (cAMP) has anti-inflammatory effects, we postulated that dibutyryl cAMP (DBcAMP) and prostaglandin E2 (PGE2) might modulate the effect of endotoxin. DBcAMP and PGE2 decreased the release of NCA and LDH. Because cAMP might exert its effect by decreasing intracellular release of oxidants, we investigated the capacity of the antioxidants dimethyl sulfoxide (DMSO) and allopurinol to attenuate the effects of endotoxin. DMSO and allopurinol alone or in combination attenuated the effects of endotoxin-induced NCA and LDH release. These data suggest that endotoxin may account for the pathophysiological changes seen with bronchial bacterial infection or endotoxin inhalation and that the inflammatory responses may be attenuated by DBcAMP, PGE2, and antioxidants.

Allopurinol↗
PubMed1991

Bronchoalveolar lavage fluid obtained from smokers exhibits increased monocyte chemokinetic activity.

Alveolar macrophages, which are cells derived from blood monocytes, accumulate within the lower respiratory tract of cigarette smokers. One mechanism to account for this accumulation of alveolar macrophages may be an increase in the migration of blood monocytes into the lungs of smokers. To evaluate this hypothesis, bronchoalveolar lavage fluid (BALF) was obtained from 15 smokers and 16 nonsmokers. The smokers' BALF possessed a significantly increased capacity to attract normal blood monocytes when evaluated using a blind-well chamber technique (26.2 +/- 7.6 vs 14.8 +/- 6.9 cells/high-power field, P less than 0.01). Checkerboard analysis of the activity revealed that it was predominantly chemokinetic. Partial characterization of the activity in smokers' BALF revealed that it was lipid soluble but only partially sensitive to trypsin and heat. The chemokinetic activity correlated with alveolar macrophage numbers in the BALF (r = 0.4391, P = 0.009). Furthermore, both the chemokinetic activity and alveolar macrophage number correlated with alterations of respiratory function (forced expiratory volume in 1 s, diffusing capacity for carbon monoxide, and forced expiratory flow at 75% of the vital capacity). These results suggest that the increase in alveolar macrophage number present in the BALF of cigarette smokers may be due, at least in part, to an increased amount of chemokinetic factor(s) in the smokers' BALF, and these factor(s) may participate in the decline of respiratory function associated with cigarette smoking, probably by recruiting monocytes into lung.

Adult↗
PubMed1991

Role of neutrophils in endotoxin-mediated microvascular injury in hamsters.

The purpose of this study was to examine the role of circulating neutrophils in endotoxin-induced increase in microvascular permeability in vivo. Fifteen hamsters were anesthetized, and a plastic chamber was placed in each cheek pouch to observe the microvasculature. Fluorescein-labeled dextran (FITC-D, 150 kDa) was injected intravenously, and changes in leaky sites and FITC-D clearance were measured in three groups: control (saline, n = 4), endotoxin suffusion (n = 6), and endotoxin suffusion after neutropenia induction (n = 5). We found a significant increase in leaky sites and FITC-D clearance with endotoxin (45 +/- 18/cm2 and 20 +/- 6 x 10(-6) ml/min, respectively; mean +/- SD, P less than 0.05) in comparison to control (7 +/- 6/cm2 and 7 +/- 5 x 10(-6) ml/min) and endotoxin suffusion in neutropenic animals (19 +/- 11/cm2 and 12 +/- 4 x 10(-6) ml/min). There was a significant correlation between the number of leaky sites and FITC-D clearance (r = 0.91, P less than 0.01) and between the number of circulating neutrophils and FITC-D clearance (r = 0.87, P less than 0.01). We conclude that endotoxin-mediated increase in microvascular permeability in the peripheral circulation is dependent in part on circulating neutrophils.

Animals↗
PubMed1991

Gcglobulin functions as a cochemotaxin in the lower respiratory tract. A potential mechanism for lung neutrophil recruitment in cigarette smokers.

Activation of the complement pathway with generation of the potent chemotaxin C5a may play a significant role in the neutrophil accumulation seen in the lungs of patients with smoking-associated diseases. Although C5a is rapidly degraded to the less potent chemotaxin C5a des Arg, binding of this peptide with its cochemotaxin Gcglobulin (GcG) can restore its chemotactic potency. Therefore, modulation of Gcglobulin levels in smoking-induced lung disease could affect the accumulation of neutrophils seen in this disorder. To test this hypothesis GcG was measured by an enzyme-linked immunosorbent assay in bronchoalveolar lavage fluids (BALF) obtained from non-smokers, asymptomatic smokers, and patients with chronic obstructive pulmonary disease (COPD). Antigenic amounts of GcG in BALF were increased in COPD patients and asymptomatic smokers compared with nonsmokers (6.35 +/- 1.02 and 5.15 +/- 1.07 versus 2.82 +/- 0.37 micrograms/mg albumin, p less than 0.05). In addition, we found that BALF enhanced C5a des Arg-mediated chemotaxis (48.3 +/- 5.6 versus 11.2 +/- 1.6 cells/high power field, p less than 0.05), an effect that was not seen in the presence of GcG antibody. Furthermore, BALF GcG was similar to serum GcG using Western blot analysis, and the interaction of GcG with C5a des Arg was not inhibited by cigarette smoke. These data demonstrate that elevation of BALF GcG levels occurs in smoking-associated lung disease and that this protein is biologically active and capable of increasing C5a des Arg-mediated chemotaxis. This suggests that modulation of GcG levels may be important in smoking-associated lung diseases.

Adult↗
PubMed1991

Bronchoscopy with bronchoalveolar lavage causes neutrophil recruitment to the lower respiratory tract.

Bronchoscopy with bronchoalveolar lavage (BAL) is a technique now widely utilized for both clinical and investigational purposes. At times, it is useful to perform bronchoscopy with BAL in a serial fashion. However, previous work in animals indicates that bronchoscopy with BAL can cause lower respiratory tract inflammation. To determine if BAL also causes lower respiratory tract inflammation in humans, sequential bronchoscopy with BAL was performed in 30 human subjects. Inflammation was evaluated using a quantitative visual assessment of bronchitis and by BAL. BAL was performed by instilling and aspirating five 20-ml aliquots of saline in each of three areas of the lung. The fluid returned from the first aliquot from each site was pooled as the bronchial fraction, and that from the remaining four aliquots was pooled as the alveolar fraction. Each volunteer was restudied at 2, 7, 24 or 72 h. Findings at the second bronchoscopy with BAL included an elevation in visual signs of large airways inflammation, which was greatest at 24 h. Bronchial neutrophils increased significantly, with the greatest effect seen at 7 h (5.3 +/- 2.0 versus 59.5 +/- 11.0%, SEM). The effect was most pronounced in the area of the lung previously lavaged, but was also seen in lobes that had not received BAL at the first bronchoscopy. Alveolar neutrophils also increased, with the maximal effect also seen at 7 h. Visible bronchial inflammation, bronchial neutrophils, and alveolar neutrophils returned to the normal range by 72 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Diffuse pulmonary alveolar hemorrhage after bone marrow transplantation: radiographic findings in 39 patients.

Diffuse alveolar hemorrhage is a life-threatening complication after bone marrow transplantation. We investigated the radiographic abnormalities that occurred in 39 transplantation patients with a diagnosis of diffuse alveolar hemorrhage and correlated the findings with the patients' clinical course. The initial radiographic abnormalities after diffuse alveolar hemorrhage developed an average of 11 days after bone marrow transplantation, and the radiographic abnormalities preceded the clinical diagnosis by an average of 3 days. Twenty-seven patients initially had bilateral radiographic abnormalities; 10 initially had unilateral abnormalities (seven in the right lung, three in the left lung). Two patients had normal chest radiographs throughout their clinical course. All 37 patients with radiographic abnormalities had abnormalities involving the central portion of the lung, primarily the middle and lower lung zones. The initial radiographic pattern was interstitial in 27 and alveolar in 10. In 24 patients, radiographic abnormalities were initially judged to be mild; three were severe from the onset. Radiographic abnormalities rapidly worsened in most patients over 6 days. In 30 patients, diffuse bilateral radiographic abnormalities involving all lung zones developed. Eleven patients persisted in having only interstitial radiographic abnormalities; 26 had a confluent alveolar pattern. At the height of radiographic abnormalities, 27 cases were judged to be severe, and only one case was judged to be mild. The mortality rate in patients with diffuse alveolar hemorrhage was 77%. The radiographic abnormalities of diffuse alveolar hemorrhage are nonspecific and usually precede the clinical diagnosis. The clinical course after hemorrhage is short, often resulting in death.

Adolescent↗
PubMed1990

Chemotactic factor inactivator interaction with Gc-globulin (vitamin D-binding protein). A mechanism of modulating the chemotactic activity of C5a.

Chemotactic factor inactivator (CFI) can decrease the neutrophil chemotactic activity of C5a. Gc-Globulin (GcG) can function as a cochemotaxin for C5a by binding to C5a or C5a des Arg and enhancing its chemotactic potency. We hypothesized that CFI might interact with GcG and thus decrease the chemotactic activity of C5a. CFI was found to markedly inhibit the neutrophil chemotactic activity of partially purified C5a containing GcG (p less than 0.01). Addition of GcG was able to reverse the capacity of CFI to inhibit C5a-directed neutrophil chemotaxis (p less than 0.01). CFI had no significant effect on neutrophil chemotaxis when incubated with C5a depleted of GcG or C5a des Arg. CFI was also able to inhibit the interaction of C5a with GcG adsorbed to plastic. To determine if CFI interacted with GcG, a sandwich ELISA was used. These ELISA tests demonstrated that CFI directly interacted with GcG in a dose-dependent manner that was both heat and pH sensitive. To investigate the possibility of enzymatic degradation of C5a by CFI, CFI preparations were analyzed for carboxypeptidase activity, aminopeptidase activity, and for the capacity to cleave dansylated C5a. No enzymatic activity or cleavage was observed. Furthermore, the direct interaction of CFI with C5a and C5a des Arg was assessed by ELISA tests and column chromatography and no interaction was observed. These results suggest that CFI modulates C5a-directed neutrophil chemotaxis by interacting with GcG and preventing GcG from enhancing the chemotactic potency of C5a.

Aminopeptidases↗
PubMed1990

Signing an organ donor card: psychological factors.

Personality factors related to organ donor card signing were explored in a sample of 94 students. Nondonors scored higher on Templer's Death Anxiety Scale, Collett-Lester Fear of Death of Self, Death of Others, and Dying of Self subscales, and a scale of physical anxiety. Donors scored higher on a Likert scale reflecting acceptance of dying and, not surprisingly, on self-efficacy to sign an organ donor card. When regrouped on the basis of whether they believed in donation, those nondonors who believed they should donate were intermediate in self-efficacy between donors and those who had no interest in donating. This nondonor/believer group may be most likely to donate but may be restrained by the anxiety factors noted above. Further efforts should focus on clarifying these issues, so as to increase donation of greatly needed organs.

Altruism↗
PubMed1990

Inactivation of chemotactic factor inactivator by cigarette smoke. A potential mechanism of modulating neutrophil recruitment to the lung.

Activation of the complement system with generation of the potent neutrophil chemotactic factor C5a has been proposed to play a significant role in the neutrophil accumulation in the lungs of cigarette smokers. Chemotactic factor inactivator (CFI) can inhibit C5a-directed neutrophil chemotaxis by binding to the C5a cochemotaxin GcGlobulin (GcG), a vitamin-D-binding protein, and inhibiting the capacity of GcG to enhance the chemotactic activity of C5a. Because cigarette smoke can inhibit the function of some proteins, a loss of CFI functional activity induced by cigarette smoke would allow an increased capacity of GcG to augment C5a-directed neutrophil chemotaxis. In order to test this hypothesis, cigarette smoke was bubbled through a CFI solution, and the solution was evaluated for its ability to inhibit the chemotactic activity of C5a and GcG. Smoke-treated CFI inhibited only 36% of the C5a-GcG chemotactic activity. In contrast, a CFI solution treated with air inhibited 62% of the chemotactic activity (p less than 0.001). Consistent with these observations, smoke-treated CFI exhibited a decreased capacity to bind to GcG and a decreased capacity to inhibit the binding of C5a des Arg to GcG. CFI contained in the bronchial lavage fluids obtained from patients with chronic obstructive pulmonary disease secondary to cigarette smoking and asymptomatic smokers exhibited a decreased capacity to inhibit C5a-GcG neutrophil chemotaxis and to bind to GcG (p less than 0.05, both comparisons). Furthermore, smoke bubbled through normal bronchial lavage fluid decreased the capacity of CFI to bind to GcG.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminopeptidases↗
PubMed1990

Organic dust toxic syndrome: an acute febrile reaction to organic dust exposure distinct from hypersensitivity pneumonitis.

Organic dust toxic syndrome is a term recently coined to describe a noninfectious, febrile illness associated with chills, malaise, myalgia, a dry cough, dyspnea, headache and nausea which occurs after heavy organic dust exposure. Organic dust toxic syndrome shares many clinical features with acute farmer's lung and other forms of hypersensitivity pneumonitis, including the presence of increased numbers of neutrophils in bronchoalveolar lavage. However, organic dust toxic syndrome differs from acute hypersensitivity pneumonitis in several respects: the chest X-ray does not show infiltrates, severe hypoxemia does not occur, prior sensitization to antigens in the organic dust is not required and there are no known sequelae of physiological significance, such as the recurrent attacks and the pulmonary fibrosis which may be seen with chronic hypersensitivity pneumonitis. Organic dust toxic syndrome is thought to be much more common than farmer's lung. It is important for clinical and investigational purposes that organic dust toxic syndrome be distinguished from acute farmer's lung.

Acute Disease↗
PubMed1990

Modulation of alveolar macrophage leukotriene B4 released by complement component C5.

The release of neutrophil chemotactic activity by the guinea pig alveolar macrophage (AM) is dependent on the fifth component of complement (C5) on the cell surface. Because one potent chemotactic factor released by AMs is leukotriene B4 (LTB4), we hypothesized that cell surface C5 may modulate LTB4 release. To test this hypothesis, human AMs obtained by bronchoalveolar lavage from 12 subjects were cultured for 4 hours in the presence of anti-C5 Fab' antibodies with stimuli. The cultures were harvested and evaluated for LTB4 by radioimmunoassay. The LTB4 levels in supernatants obtained from AMs cultured in media alone were variable (447 +/- 63 pg/ml), but the levels were increased when AMs were cultured with the stimuli-opsonized zymosan, immune complexes, or lipopolysaccharide (233%, 49%, and 114% increase, respectively, compared with macrophages cultured in media alone, p less than 0.05). Culturing the AMs with anti-C5 Fab' antibodies inhibited the release of LTB4 induced by opsonized zymosan, immune complexes, or lipopolysaccharide (78%, 41%, and 82% inhibition, respectively, p less than 0.05). Consistent with these observations, anti-C5 Fab' antibodies also decreased the neutrophil chemotactic activity of culture supernatants obtained from AMs stimulated with the same stimuli (p less than 0.001). These data suggest that AM release of LTB4 may be C5-dependent.

Antibodies↗