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Biomedical subjects

R A Robbins

Publications and source records attributed to R A Robbins.

At least 55 records · Page 3Linked to original sources
PubMed1997

Smoking cessation is associated with an increase in exhaled nitric oxide.

STUDY OBJECTIVES: Nitric oxide (NO), a gas produced by cells lining the respiratory tract, has been reported to be decreased in the exhaled air of cigarette smokers. We hypothesized that smoking cessation would result in an increase in exhaled NO. DESIGN: Comparison of exhaled NO measured from nonsmokers, cigarette smokers, and smokers after smoking cessation. SETTING: University outpatient smoking cessation clinic. PATIENTS OR PARTICIPANTS: Twenty-five cigarette smokers and 23 normal, nonsmokers. INTERVENTIONS: Exhaled NO was measured by three techniques: (1) a peak oral method; (2) a mean oral method; and (3) a nasal method. The smokers were given nicotine patches and instructed to return after 1 and 8 weeks. The exhaled NO determinations were repeated on each visit. MEASUREMENTS AND RESULTS: Compared with nonsmokers, smokers had decreased NO levels measured by all three methods (p<0.05, each comparison). Nineteen smokers returned after 1 week. Fourteen were successfully abstinent from cigarettes and their exhaled NO increased compared with baseline (p<0.01 for each method) but not in the five subjects who had not successfully quit smoking (p>0.05 for each method). Ten subjects returned after 8 weeks. The exhaled NO levels increased further and were not significantly different from the normal nonsmokers for the peak oral and nasal NO methods (p>0.2), but were still lower than the normal nonsmoker mean oral NO (p=0.018). CONCLUSIONS: These data demonstrate that smoking cessation is associated with an increase in exhaled NO.

Administration, Cutaneous↗
PubMed1996

Inhibition of inducible nitric oxide synthase expression by interleukin-4 and interleukin-13 in human lung epithelial cells.

Nitric oxide produced by the inducible enzyme, nitric oxide synthase (iNOS), is implicated in immunological and inflammatory processes. We determined the effects of T-helper (Th)2-derived cytokines on the induction of iNOS from an epithelial A549 cell line and human airway epithelial cells stimulated by a mixture of interleukin-1 beta (IL-1 beta), interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha). Interleukin-4 (IL-4) and interleukin-13 (IL-13) but not interleukin-10 (IL-10) inhibited both iNOS mRNA expression and nitrite release in A549 cells. On human airway epithelial cells, IL-4 and IL-13 reduced iNOS mRNA expression. Dexamethasone also inhibited both iNOS expression and nitrite release. Th2 cytokines, IL-4 and IL-13, inhibit iNOS upregulation by Th1 cytokines, indicating an important reciprocal role of Th1 and Th2 T-cell subsets on lung epithelial cells.

Blotting, Northern↗
PubMed1996

Aprotinin reduces interleukin-8 production and lung neutrophil accumulation after cardiopulmonary bypass.

Pulmonary neutrophil entrapment and resultant oxidative injury is thought to be the primary mechanism of cardiopulmonary bypass (CPB) induced lung injury. Interleukin-8 (IL-8), a potent neutrophil chemoattractant induced by cytokines, including tumor necrosis factor-alpha (TNF), is found in increased concentrations in bronchial alveolar lavage fluid (BALF) in lung inflammation. Since aprotinin reduces TNF release during CPB, the effects of aprotinin on BALF IL-8 concentrations and neutrophil levels were determined after CPB in adult humans. Study patients were equally divided into a control group (n = 8, Group 1) and an aprotin-intreated group (n = 8, Group 2). In vitro neutrophil chemotaxis was done with volunteer neutrophils using three different chemoattractants: 1) N-formyl-1-methionyl-1-leucyl-1-phenylalanine (FMLP); 2) the supernatant of a human bronchial epithelial cell culture line, A549, after 24 h of TNF stimulation with or without aprotinin or N-alpha-tosyl-L-lysine chloromethyl ketone (TLCK) (a potent protease inhibitor), and 3) BALF. Aprotinin treatment significantly (P < 0.05) reduced post-CPB BALF IL-8 concentrations and percentage of neutrophils. In vitro, BALF from Group 1 had significantly greater chemotactic ability when compared with Group 2. The TNF stimulated A549 cell culture supernatant had significantly (P < 0.05) greater chemotactic ability than control supernatant, while aprotinin and TLCK significantly (P < 0.05) reduced this chemotactic ability. These results demonstrate that aprotinin blunts IL-8 production and reduces neutrophil lung accumulation post-CPB.

Adult↗
PubMed1996

Loop diuretics attenuate bradykinin-induced increase in clearance of macromolecules in the oral mucosa.

The purpose of this study was to determine whether loop diuretics attenuate bradykinin-induced increase in clearance of macromolecules in the oral mucosa in situ and, if so, to start to determine the mechanisms that mediated these responses. By using intravital microscopy, we found that bradykinin induced a significant concentration-dependent increase in fluorescein isothiocyanate-labeled dextran (mol mass 70 kDa) leaky site formation in the hamster cheek pouch. These responses were significantly attenuated by topical application of two structurally distinct loop diuretics, furosemide and ethacrynic acid, onto the cheek pouch (P < 0.05). Hydrochlorothiazide, a nonloop diuretic, had no significant effects on bradykinin-induced responses. Furosemide had no significant effects on adenosine-induced leaky site formation. Application of bradykinin after furosemide, but not after hydrochlorothiazide, was associated with a significant concentration-dependent decrease in bradykinin-like immunoreactivity in the cheek pouch suffusate (P < 0.05). Prostaglandins and changes in vasomotor tone did not modulate the effects of furosemide on bradykinin-induced responses. These data indicate that loop diuretics attenuate bradykinin-induced increase in clearance of macromolecules in the oral mucosa in a specific fashion, probably by amplifying local bradykinin catabolism. We suggest that topical loop diuretics could be useful in the treatment of oral mucosa inflammation elicited by bradykinin.

Adenosine↗
PubMed1996

Measurement of exhaled nitric oxide by three different techniques.

The purpose of the study was to compare exhaled nitric oxide (NO) determined by three techniques. Ninety-one subjects performed a slow vital capacity maneuver: (1) through the mouth directly into a NO chemiluminescence analyzer (peak oral NO), (2) through the mouth into a collection bag (mean oral NO), and (3) through the nose into a collection bag (mean nasal NO). Peak oral NO was higher in patients with asthma (n = 18, 174.2 +/- 27.0 ppb), but lower in smokers (n = 36, 39.6 +/- 4.8 ppb) compared with nonsmoking control subjects (n = 23, 105.5 +/- 8.4 ppb, p < 0.05 both comparisons). Mean oral NO levels were significantly lower than peak oral NO levels (p < 0.05), but still higher in patients with asthma in comparison with nonsmoking healthy control subjects and asymptomatic smokers (27.2 +/- 3.5 versus 14.5 +/- 1.1 and 7.3 +/- 0.7 ppb, respectively, p < 0.05). In contrast, there was no significant difference in mean nasal NO levels between the three groups. Peak oral NO and mean oral NO levels correlated (r = 0.772, p < 0.0001). Determination of exhaled oral NO levels is qualitatively independent of the technique used, but nasal exhalation may affect NO determination in conditions associated with airway inflammation.

Adult↗
PubMed1996

The effect of alcohol ingestion on exhaled nitric oxide.

The concentration of nitric oxide (NO) is increased in the exhaled air of patients with inflammatory lung diseases, including asthma, possibly reflecting cytokine-mediated chronic airway inflammation. Endogenous NO is generated from L-arginine by the action of several types of NO synthase (NOS). NOS have structural similarities with cytochrome P450 reductases. Alcohol decreases exhaled NO in animals, but this has not previously been investigated in man. We studied the effect of alcohol ingestion in nine asthmatic and 12 normal subjects, measuring the peak concentration of exhaled NO using a modified chemiluminescence analyser. A significant decrement in NO occurred in asthmatic patients (mean +/- SEM before ethanol 204 +/- 58 to 158 +/- 59 parts per billion (ppb) after ethanol; p < 0.02), without significant change in the normal subjects (122 +/- 14 to 114 +/- 15 ppb). Thus, in our study, alcohol decreased exhaled nitric oxide in asthmatic subjects but not in normal individuals. This may reflect preferential action on inducible nitric oxide synthase which is expressed in asthmatic airways. An inhibitory effect of ethanol on inducible nitric oxide synthase may contribute towards the effect of alcohol in asthma.

Adult↗
PubMed1996

Psychological testing variables as predictors of return to work by chronic pain patients.

After multidisciplinary pain treatment, pretreatment psychological testing variables were compared for 20 chronic pain patients who were working and 42 who were not working. Symptom Checklist-90-R scores for Depression, Anxiety, Phobic Anxiety, Psychoticism, Global Severity, and Positive Symptom Distress were lower for working subjects as were those on the Beck Depression Inventory. In contrast, workers scored higher on self-efficacy to manage pain, self-efficacy to function, self-efficacy to manage other symptoms, and over all self-efficacy.

Accidents, Occupational↗
PubMed1996

Cardiopulmonary function and autologous bone marrow transplantation: results and predictive value for respiratory failure and mortality. The University of Nebraska Medical Center Bone Marrow Transplantation Pulmonary Study Group.

Cardiopulmonary complications are a major cause of morbidity and mortality in patients undergoing high-dose therapy with stem cell transplant support. Since exercise tolerance testing (ETT) assesses the cardiopulmonary reserve of an individual, we hypothesized that ETT performed prior to transplant would predict respiratory failure and mortality and would be a superior predictor over resting cardiopulmonary function tests. We performed a retrospective study of 191 lymphoma patients who underwent ETT prior to transplant between 1 June 1990 and 31 December 1992 and compared the results of ETT with resting pulmonary function tests (PFT) and resting cardiac ejection fraction (EF). ETT revealed that cardiac, pulmonary and combined cardiopulmonary limitation were observed in 31, 20 and 16% of the patients, respectively, with a gas diffusion-type limitation being the most common exercise limitation. Resting PFT were abnormal in 58% of patients with a diffusion defect being the most common abnormality. Low EF was observed in 6.8% of patients. Twelve patients eventually required mechanical ventilation post-transplant with only the resting diffusion PFT predictive of this complication. There were five early deaths that were attributable to respiratory failure and neither resting nor ETT studies were predictive of these deaths. ETT and EF performed prior to transplant in lymphoma patients undergoing autologous transplant do not predict for either respiratory failure or short-term mortality. Our findings may be due to the rather low incidence of respiratory failure (6.3%) and low early mortality from cardiopulmonary complications (2.6%) seen in our patient population.

Adolescent↗
PubMed1995

Neurotensin stimulates neutrophil adherence to bronchial epithelial cells in vitro.

Neutrophils and neuropeptides have both been implicated in airway inflammation. We hypothesized that neurotensin, a neuropeptide found in the airways, would stimulate neutrophil adherence to bronchial epithelial cells. Adherence was assessed using 51Cr-labelled human neutrophils added to confluent monolayers of bovine bronchial epithelial cells. Neurotensin added to bronchial epithelial cells produced a time-and concentration-dependent increase in adherence which was maximal at 4 h and 10(-10)M (17.6 +/- 1.4% vs. 6.1 +/- 0.4%, p < 0.01). Conversely, neurotensin stimulation of neutrophils induced a concentration-dependent and rapid ( < 5 min) increase in adherence which was also maximal at 10(-10)M (27.1 +/- 1.9% vs. 10.1 +/- 1.4%, p < 0.01). The effects were reproduced by the carboxy portion of the molecule. Anti-CD11a, -CD11b or -ICAM-1 antibodies significantly decreased the neurotensin-induced increase in adherence. These data suggest an important role for neurotensin in modulating airway inflammation.

Animals↗
PubMed1995

Aprotinin and methylprednisolone equally blunt cardiopulmonary bypass-induced inflammation in humans.

Cardiopulmonary bypass induces an inflammatory state characterized by tumor necrosis factor-alpha release. Integrin CD11b is a neutrophil surface adhesive glycoprotein integrin that is rapidly and permanently unregulated by tumor necrosis factor-alpha exposure. The CD11b integrin is known to be the primary neutrophil integrin responsible for neutrophil lung and myocardial entrapment after cardiopulmonary bypass and subsequent reperfusion injury. Twenty-four adults admitted to the hospital for myocardial revascularization were equally randomized to one of three groups: group A (control), group B (methylprednisolone before cardiopulmonary bypass), and group C (low-dose aprotinin protocol). Blood was collected at three times: (1) baseline, (2) 50 minutes of cardiopulmonary bypass duration, and (3) 30 minutes after cardiopulmonary bypass termination. Neutrophil CD11b integrin expression was measured by fluorescence-activated cell sorter analysis and plasma tumor necrosis factor-alpha levels measured by enzyme-linked immunosorbent assay. Group A demonstrated significant (p < 0.05) increases in CD11b expression at times 2 and 3 when results were compared with those of the same group baseline and with those of groups B and C at similar times. No significant changes were noted between groups B and C at any time. Group A demonstrated a significant (p < 0.05) increase in levels of tumor necrosis factor-alpha at time 3 when results were compared with those of the same group baseline and of groups B and C at the same time. No significant changes were noted between B and C at any time. These results demonstrate low-dose aprotinin has a similar antiinflammatory effect to that of methylprednisolone in blunting cardiopulmonary bypass-induced systemic tumor necrosis factor-alpha release and neutrophil integrin CD11b upregulation.

Aged↗
PubMed1995

Grain dusts and grain plant components vary in their ability to recruit neutrophils.

Occupational exposure to grain dusts can cause bronchitis, particularly to grain sorghum dust. Bronchitis is associated with the presence of increased numbers of neutrophils. To determine how grain dusts could cause neutrophil recruitment to the airways, extract of whole-grain sorghum, corn, and soybean dusts and of pulverized components of these plants were made with Hanks balanced salt solution (HBSS) and used in direct neutrophil chemotaxis experiments. The glume of the grain sorghum plant, the structure holding the seeds in place, caused the migration of the greatest number of neutrophils compared to HBSS [132 +/- 7 vs. 60 cells/high-power field (hpf) +/- 2 SEM, p < .001], followed by whole-grain sorghum dust (121 +/- 5 cells/hpf). Next, bovine bronchial epithelial cells (BBECs) were obtained from fresh lungs and grown to near confluence before challenge with a 10% solution of grain dust and grain plant extracts. The grain sorghum glume and whole-grain sorghum dusts caused release of the greatest amount of neutrophil chemotactic activity (NCA) from BBECs compared to the medium M199 negative control (141 +/- 6 and 153 +/- 7, respectively, vs. 64 cells/hpf +/- 3 SEM, p < .001). The ability to cause neutrophils to migrate by direct and indirect means did not correlate with levels in the grain dusts of endotoxin, which is known to cause release of NCA from bronchial epithelial cells. Therefore, this article describes additional mechanisms by which grain dusts can cause pulmonary inflammation and that are independent of endotoxin levels.

Animals↗
PubMed1995

TNF-alpha and IL-1 beta upregulate nitric oxide-dependent ciliary motility in bovine airway epithelium.

Airway epithelial cells can be modulated by cytokines such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta that are released from inflammatory cells. Since ciliary motility is an important host defense function of airway epithelium, we hypothesized that cytokines, released from lung macrophages, upregulate ciliary motility. To test this hypothesis, ciliary beat frequency (CBF) was measured by video microscopy in cultured ciliated bovine bronchial epithelial cells (BBECs) incubated for 24 h with bovine alveolar macrophage-conditioned medium (AM-CM). Exposure to AM-CM resulted in a delayed (> or = 2 h) increase in CBF that was maximal after 24 h exposure (13.70 +/- 0.43 for AM-CM vs. 9.44 +/- 0.24 Hz for medium; P < 0.0001) and which was largely blocked by either anti-TNF-alpha or anti-IL-1 beta antibodies. rTNF-alpha or rIL-1 beta similarly increased CBF, which could be blocked by preincubation with either anti-rTNF-alpha or anti-rIL-1 beta antibodies. Preincubation of BBECs with actinomycin D or dexamethasone also blocked rTNF-alpha- and rIL-1 beta-induced cilia stimulation, suggesting that new protein synthesis is required for cytokine-induced upregulation of CBF. Since NO is known to upregulate ciliary motility and cytokines can induce NO synthase (NOS), we hypothesized that TNF-alpha and IL-1 beta increase CBF by inducing NOS in BBECs. The cilia stimulatory effects of TNF-alpha or IL-1 beta were inhibited by NG-monomethyl-L-arginine, a competitive NOS inhibitor, and restored by the addition of either L-arginine, an NOS substrate, or sodium nitroprusside, an NO donor.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗
PubMed1995

Bradykinin stimulates bronchial epithelial cells to release neutrophil and monocyte chemotactic activity.

In the present investigation, we evaluated the potential of bradykinin (BK), histamine, and serotonin to induce the release of neutrophil and monocyte chemotactic activity (NCA and MCA) from bronchial epithelial cells (BEC). BK significantly stimulated BEC to release NCA and MCA in a dose- and time-dependent manner. Histamine weakly but significantly induced the release of both NCA and MCA in a similar fashion. Serotonin did not stimulate BEC. Checkerboard analysis showed that the NCA and MCA released in response to BK were chemotactic. Molecular-sieve column chromatography by Sephadex G-75 revealed that BK induced a single low-molecular-weight peak (approximately 400 Da) for both NCA and MCA. The releases of NCA and MCA in response to BK and histamine were inhibited by lipoxygenase inhibitors (P < 0.01). The released NCA was inhibited by leukotriene B4 (LTB4) receptor antagonist (P < 0.01) and was slightly inhibited by platelet-activating factor receptor antagonist. LTB4 was increased in BK-stimulated BEC supernatant (P < 0.01). BK B2-receptor antagonist attenuated the release of NCA and MCA. These data suggest that BK and histamine may stimulate BEC to release NCA and MCA and may modulate neutrophil and monocyte recruitment into the airways in patients with asthma.

Animals↗
PubMed1995

Bronchial epithelial cells regulate fibroblast proliferation.

Chronic bronchitis frequently leads to irreversible airway obstruction. Alteration of airway architecture with abnormal airway connective tissue is thought to play an important role in this process. We hypothesized that the epithelial cells that line the airways modulate the development of peribronchial fibrosis and fixed airway obstruction by directing fibroblast proliferation. To assess this, we examined stimulatory activities for human lung fibroblast proliferation in bovine bronchial epithelial cell-conditioned medium. The conditioned medium stimulated the proliferation of fibroblasts in a serum-free culture system in a concentration-dependent manner. The fibroblast growth stimulatory activity was heterogenous, with molecular masses of > 50 and approximately 10 kDa. Bronchial epithelial cell-conditioned medium also contained fibroblast growth inhibitory factors, including both transforming growth factor (TGF)-beta and, based on indomethacin sensitivity, cyclooxygenase products. TGF-beta appeared to contribute to the morphological change of fibroblasts induced by the conditioned medium. Co-culture of human lung fibroblasts with bronchial epithelial cells resulted in a stimulation of fibroblast proliferation. In summary, airway epithelial cells appear to regulate fibroblast proliferation and may play a role in peribronchial fibrosis in chronic bronchitis.

Animals↗
PubMed1995

Acute and chronic effects of cigarette smoking on exhaled nitric oxide.

Cigarette smoking is associated with an increased risk of respiratory tract infections, chronic airway disease, and cardiovascular diseases, all of which may be modulated by endogenous nitric oxide (NO). We have investigated whether cigarette smoking reduces the production of endogenous NO. We compared exhalations of 41 current cigarette smokers with normal lung function and 73 age-matched non-smoking controls. Peak exhaled NO levels were measured by a modified chemiluminescence analyzer. The effects of inhaling a single cigarette in smokers were also measured. In control subjects we also measured the effects of inhalation of NO itself and carbon monoxide, both constituents of tobacco smoke. Peak exhaled NO concentrations were significantly reduced in smokers (42 +/- 3.9 compared with 88 +/- 2.7 parts per billion in nonsmokers, p < 0.01), with a significant relation between the exhaled NO and cigarette consumption (r = 0.77, p < 0.001). Smoking a single cigarette also significantly (p < 0.02), but transiently, reduced exhaled NO. Inhalation of carbon monoxide and NO had no effect on exhaled NO in normal subjects. Cigarette smoking decreased exhaled NO, suggesting that it may inhibit the enzyme NO synthase. Since endogenous NO is important in defending the respiratory tract against infection, in counteracting bronchoconstriction and vasoconstriction, and in inhibiting platelet aggregation, this effect may contribute to the increased risks of chronic respiratory and cardiovascular disease in cigarette smokers.

Administration, Inhalation↗
PubMed1995

Effect of a nitric oxide synthase inhibitor and a glucocorticosteroid on exhaled nitric oxide.

Nitric oxide (NO) is produced by a variety of cells within the respiratory tract, including inflammatory epithelial cells. NO has been detected in the exhaled air of normal human subjects, and its concentration is raised in asthmatic patients. To study whether exhaled NO arises from the respiratory tract, we administered a NO synthase (NOS) inhibitor, NG-monomethyl-L-arginine (L-NMMA), by inhalation (490 mg) in a double-blind randomized manner in nine normal and six asthmatic subjects. Because exhaled NO may arise from an inducible isoform of NO synthase that may be inhibited by glucocorticosteroids, we also studied the effects of oral prednisolone (30 mg orally for 3 d) in seven normal and six asthmatic subjects in a separate double-blind crossover study with matched placebo. After nebulized L-NMMA, there was a significant fall in peak exhaled NO compared with saline control values, with a mean fall of 43.6 +/- 5.6% in normal subjects (p < 0.01) and of 39.7 +/- 6.5% (p < 0.01) in asthmatic subjects, which persisted for 4 h. There were no effects of L-NMMA inhalation on heart rate, blood pressure, or FEV1 in either normal or asthmatic patients. Administration of oral prednisolone (30 mg) resulted in a fall in exhaled NO concentrations in asthmatic subjects by 21.6 +/- 5.0% at 48 h (p < 0.01) but no significant change in normal subjects. These data suggest that NOS inhibitors may be safely given in normal and asthmatic patients and that the increased exhaled NO seen in asthmatic patients is likely to be caused by induction of inducible NOS.

Adult↗
PubMed1995

Glucocorticoid reduction of bronchial epithelial inflammation during cardiopulmonary bypass.

Tumor necrosis factor-alpha (TNF-alpha) is released in inflammatory lung conditions, raising airway nitric oxide (NO) concentrations through the cytokine-mediated induction of nitric oxide synthase (NOS). Cardiopulmonary bypass (CPB) creates an inflammatory state, characterized by the release of TNF-alpha, that may result in lung injury following CPB. This study measured plasma levels of TNF-alpha and interleukin-6 (IL-6) as well as airway NO concentrations during CPB, and the effect of methylprednisolone (MPSS) on the levels of these inflammatory products. Twenty adult males scheduled for coronary artery bypass grafting (CABG) were anesthetized and randomized to a group given MPSS at 1 gm intravenously 5 min before CPB (Group S) or a group not given MPSS (Group N). Plasma levels of TNF-alpha and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA) and the airway NO concentration by chemiluminescence. TNF-alpha was significantly (p < 0.05) increased at 30 min after the termination of CPB, while IL-6 was significantly (p < 0.05) increased at 50 min into CPB and 30 min after the end of CPB in Group N as compared with controls in the same group and with Group S at the same time intervals. A group of 10 patients undergoing repair of infrarenal aortic aneurysms, which served as a control group for plasma levels of TNF-alpha, showed no significant changes in TNF-alpha concentrations at any time during aneurysm repair. Airway NO increased significantly (p < 0.01) in Group N as compared with Group S at 5, 20, 35, and 50 min of CPB.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchi↗