Search PubMed⌕ Search

Biomedical subjects

C M Mason

Publications and source records attributed to C M Mason.

At least 37 records · Page 2Linked to original sources
PubMed1998

Effect of alcohol on bacterial translocation in rats.

Bacterial translocation has been proposed to be important in the pathophysiology of sepsis, as well as to be a consequence of sepsis. To study the effect of alcohol on bacterial translocation from the gut, normal Sprague-Dawley rats were administered alcohol by gavage by two regimens: Acute (3.7 g/kg, one dose) or Subacute (1 of 2 doses, 2.4 or 3.7 g/kg/day once daily for 14 days). Mesenteric lymph node cultures were performed, and portal venous blood was assayed for endotoxin. Ileal and cecal permeability studies were performed in the Acute and Subacute groups using fluorescein isothiocyanate-labeled dextrans of either 4,000 or 70,000 kDa size. As an index of the effect of systemic endotoxin, tissues from mesenteric lymph nodes, liver, and intestinal Peyer's patches were assayed for the presence of mRNA for tumor necrosis factor. Additionally, because extrapulmonary sepsis has been shown to suppress pulmonary antibacterial defenses, animals in the Subacute group were challenged by aerosol inoculation with Pseudomonas aeruginosa to determine bacterial clearance and alveolar cellular responses. The results show that neither of the alcohol regimens resulted in bacterial growth from mesenteric lymph nodes or portal blood. Animals in the Subacute group had more endotoxin present in portal blood than did the Control group (92.9 pg/ml vs. 40.2 pg/ml; p < 0.02). None of the animals had demonstrable mRNA for tumor necrosis factor in any of the tissues assayed. There were no demonstrable increases in ileal or cecal permeability for either the small or large molecular weight dextran in either alcohol group. Furthermore, there was no delay in the clearance of P. aeruginosa from the lung in the Subacute group, but these animals recruited fewer neutrophils into the airspaces in response to this challenge than did the Control animals. Thus, alcohol intoxication does not result in bacterial translocation from the gut in this model. Despite higher levels of portal venous endotoxin in the animals in the Subacute alcohol group, no adverse systemic consequences of this phenomenon could be demonstrated.

Alcohol Drinking↗
PubMed1997

Phase 1 safety trial of Filgrastim (r-metHuG-CSF) in non-neutropenic patients with severe community-acquired pneumonia.

The objectives of the present study were to: (1) evaluate the safety of Filgrastim therapy in non-neutropenic patients with severe community-acquired pneumonia; (2) determine the absolute neutrophil count (ANC) response to various dosages of Filgrastim in non-neutropenic patients with active infection; and (3) describe the impact of therapy with Filgrastim in combination with antibiotics on selected pneumonia-related clinical parameters. The study design was an open-label, dose-ranging, clinical trial, set in the General Clinical Research Unit of a large, public community hospital. The study population consisted of 30 patients who had presented to the Emergency Department with severe, community-acquired pneumonia. One of five dosages (75, 150, 300, 450 or 600 micrograms day-1) of Filgrastim (r-metHuG-CSF) was given subcutaneously daily for 10 days, until discharge or until the absolute neutrophil count > 75 x 10(9) l(-1), whichever was earlier. Vital signs, pulse oximetry, arterial blood gases, daily complete blood counts with differential, serum chemistries, coagulation profiles, electrocardiograms, chest radiographs, plasma G-CSF concentrations and duration of hospitalization were measured. There was no evidence of Filgrastim-related lung injury or evidence of extra-pulmonary toxicity. There was no apparent dose-response effect of Filgrastim on pneumonia-related clinical variables. Dosages of Filgrastim between 150 and 600 micrograms day-1 had similar effects on increasing the ANC. Filgrastim appeared to be safe in non-neutropenic patients with severe, community-acquired pneumonia when given in dosages of 75-600 micrograms day-1 in combination with appropriate antibiotic therapy. Further study is needed to determine the effect of Filgrastim on morbidity, mortality and duration of symptoms in this patient population.

Adult↗
PubMed1997

Intraportal lipopolysaccharide suppresses pulmonary antibacterial defense mechanisms.

Translocation of enteric bacteria or their components (or both) has been postulated to play a role in precipitating sepsis or the systemic inflammatory response syndrome. To simulate the effects of translocation on pulmonary host defenses, lipopolysaccharide was injected into the portal vein of normal rats that were subsequently challenged by aerosol inoculation with Pseudomonas aeruginosa. Injection of LPS into the portal vein resulted in increased serum tumor necrosis factor (TNF)-alpha levels and reduction in lung clearance of P. aeruginosa after aerosol challenge. There were corresponding reductions in alveolar neutrophil recruitment, diminished alveolar macrophage phagocytosis and superoxide anion (O2-) production, and diminished lung TNF recovered by bronchoalveolar lavage. Furthermore, prior intravenous injection of recombinant TNF-alpha reproduced the defective bacterial clearance, the altered recruitment of airspace neutrophils, and the defective alveolar macrophage phagocytosis. Thus, systemic TNF-alpha is important in altering pulmonary defenses, and this work supports the concept that bacterial translocation may adversely affect host defenses in distant organs.

Animals↗
PubMed1997

Keratinocyte growth factor increases transalveolar sodium reabsorption in normal and injured rat lungs.

Keratinocyte growth factor (KGF) prevents alpha-naphthylthiourea (ANTU)-induced permeability edema ex vivo. To explore the mechanisms in this involved effect, we administered KGF (5 mg/kg, intratracheally) 48 h prior to ANTU (50 mg/kg, intraperitoneally). Several groups were studied: phosphate-buffered saline/dimethylsulfoxide (PBS/DMSO) (vehicles), PBS/ANTU, and KGF/ANTU. At 90 min after ANTU injection the lungs were removed, ventilated, and perfused ex vivo for 180 min. Quantification of fluorescein isothiocyanate (FITC)-labeled dextran in bronchoalveolar lavage fluid (BALF) was used to assess alveolar capillary barrier permeability. KGF attenuated ANTU-induced edema and blockade of sodium transport, with ouabain (10(-3) M) or amiloride (10(-4) M) added ex vivo reversed this effect. FITC-dextran was increased in the PBS/ANTU group as compared with the PBS/DMSO group, indicating permeability edema. In the KGF/ANTU group, there was concentration of BALF FITC-dextran, consistent with permeability edema and increased alveolar fluid export. Albumin space measurements showed similar increases in permeability in the PBS/ANTU and KGF/ANTU groups. Extravascular lung water (measured with radiolabeled erythrocytes) was decreased in the KGF/ANTU group. Following KGF pretreatment, uninjured lungs exported more intratracheal PBS than normal lungs following terbutaline stimulation ex vivo. In conclusion, KGF, through type II alveolar pneumocyte hyperplasia with increased sodium-potassium-adenosine triphosphatase (Na,K-ATPase) activity, attenuated ANTU-induced edema formation by potentiating alveolar fluid clearance.

Absorption↗
PubMed1996

Keratinocyte growth factor attenuates lung leak induced by alpha-naphthylthiourea in rats.

OBJECTIVE: To investigate the effect of pretreatment with keratinocyte growth factor on acute permeability pulmonary edema. DESIGN: Prospective, randomized, controlled animal study. SETTING: University research laboratory. SUBJECTS: Specific pathogen-free Sprague-Dawley rats. INTERVENTION: Acute permeability pulmonary edema was induced with an injection of alpha-naphthylthiourea, and lung leak was assessed in an isolated perfused lung model over 180 mins. Leak was confirmed with wet/dry lung weight ratios, and the alveolar fluid protein concentration was measured after bronchoalveolar lavage. The effect of pretreatment with keratinocyte growth factor (injected intratracheally 48 hrs before the experiment) on alpha-naphthylthiourea-induced pulmonary edema was assessed (keratinocyte growth factor/alpha-naphthylthiourea group). Control groups (Control and keratinocyte growth factor/Control) were also studied. Histopathology was performed for each of the four groups. MEASUREMENTS AND MAIN RESULTS: The alpha-naphthylthiourea produced an acute permeability pulmonary edema detected by lung leak over the 180-min ex vivo period of monitoring the isolated perfused lung (leak = 8+/-mL; wet/dry weight ratio 14.7+/-2; lavage protein 3.1+/-1 mg/mL). Pretreatment with keratinocyte growth factor significantly attenuated these parameters (leak = 2.3+/-0.4 mL; wet/dry weight ratio 7.1 +/- 0.5; lavage protein 0.28 +/-0.03 mg/mL), which were not significantly different from the control group and the keratinocyte growth factor/control group. Histopathology showed abundant type II pneumocyte hyperplasia in the lungs of animals pretreated with keratinocyte growth factor, and marked pulmonary edema in animals pretreated with alpha-naphthylthiourea. Less edema was apparent in the keratinocyte growth factor/alpha-naphthylthiourea group. All data are expressed as mean +/- SEM. CONCLUSIONS: Pretreatment with keratinocyte growth factor significantly attenuates pulmonary edema induced by alpha-naphthylthiourea. The mechanisms of this protection are likely related to type II pneumocyte hyperplasia, but remain to be specifically elucidated.

Animals↗
PubMed1996

Targeting to intestinal M cells.

The specialised, antigen-transporting, epithelial M cells in the follicle-associated epithelium (FAE) overlying gut-associated lymphoid tissues constitute the primary target for oral delivery of vaccines. Our studies have shown that polystyrene microspheres selectively bind to, and are efficiently transcytosed by, rabbit Peyer's patch M cells in closed intestinal loops. Binding of biodegradable poly(DL-lactide-co-glycolide) microspheres to rabbit Peyer's patch FAE is an order of magnitude lower than that of polystyrene microspheres. Although poly(DL-lactide-co-glycolide) microspheres are not selectively targeted to M cells, a high proportion of those which bind to M cells are transcytosed, supporting the potential of such microspheres as vehicles for oral vaccine delivery. Comparison of the binding of polystyrene microspheres by murine FAE revealed this to be markedly less extensive than by rabbit FAE. These data demonstrate that microsphere binding by M cells depends on the surface properties of both cells and microspheres and suggest that surface modification may enhance the efficacy of microsphere delivery vehicles. One such approach is the incorporation of molecules with inherent binding specificity for M cells. Lectin-binding studies have revealed that M cells exhibit pronounced regional and species variation in glycoconjugate expression. In murine intestine, certain lectins bind selectively to M cells either in Peyer's patches or caecum, or at both sites. Selective targeting to, and transcytosis of, lectin-conjugates by M cells in ligated segments of murine intestine have also been demonstrated. While several lectins display strong selectivity for rabbit caecal M cells, none to date have been identified with specificity for rabbit or rat Peyer's patch M cells. Knowledge of human M cells is limited and no lectin has yet been identified with specificity for these cells. However, at least one lectin exhibits binding specificity for FAE in the human ileum. In the future, knowledge of the regional patterns of M cell carbohydrate expression within a species may allow lectins to be utilised to target selectively antigenic material to the mucosal immune system at specific locations.

Administration, Oral↗
PubMed1995

Enterocytes in the follicle-associated epithelia of rabbit small intestine display distinctive lectin-binding properties.

Glycoconjugate expression in follicle-associated epithelia has been examined by application of a panel of lectins to fixed preparations of rabbit small intestine, including Peyer's patches. Each of the lectins examined (wheat germ agglutinin, peanut agglutinin, Ulex europaeus agglutinin I and Bandeiraea simplicifolia agglutinin II) exhibited a lower affinity for the apical surface of the specialised M cells than to columnar enterocytes within the Peyer's patch follicle-associated epithelium. Peanut agglutinin differed from the other lectins examined in that it displayed a markedly higher affinity for enterocytes within the follicle-associated epithelium than the neighbouring villi. This observation reveals that the specialised development of the follicle-associated epithelium involves expression of distinctive surface properties within the enterocyte population in addition to the more widely documented heterogeneous development of enterocytes and the specialised M cells.

Animals↗
PubMed1995

Exacerbation of acute and chronic murine tuberculosis by administration of a tumor necrosis factor receptor-expressing adenovirus.

Tumor necrosis factor (TNF) plays a pivotal role in inflammatory phenomena that culminate in either pathogenesis or resistance in mycobacterial disease. The regulatory role of TNF in murine tuberculosis was examined by administering a recombinant adenovirus encoding a fusion protein consisting of the human 55-kDa TNF receptor extracellular domain and the mouse IgG heavy chain domain (AdTNFR). During acute infections with Mycobacterium tuberculosis, AdTNFR pretreatment induced elevated mycobacterial burdens of 1 log10 in the tissues of H37Ra-infected mice and 2 log10 (spleen and liver) and 4 log10 (lungs) in H37Rv-infected mice. In mice infected chronically with H37Rv, AdTNFR treatment induced a 3-log10 increase of M. tuberculosis in the lungs, in which a tuberculous bronchopneumonia developed with numerous acid-fast bacilli visible in alveoli and bronchi. Administration of AdTNFR may serve as a useful model for studying the pathogenesis and chemotherapy of progressive primary tuberculosis.

Acute Disease↗
PubMed1995

Effect of granulocyte colony-stimulating factor on acute lung injury in the rat.

The effect of G-CSF pretreatment on experimental acute lung injury was studied in Sprague-Dawley rats receiving one of the following treatments: (1) G-CSF 50 micrograms/kg subcutaneously twice daily beginning 2 d prior to being killed; (2) ANTU 50 mg/kg intraperitoneally; (3) ANTU+G-CSF 50, 25, or 12.5 micrograms/kg; (4) HCl 0.6 ml of a 0.1 N solution intratracheally; (5) HCl+G-CSF 50 or 25 micrograms/kg; (6) control solutions. Lung injury was quantified by measurement of lung wet/dry weights, by histopathologic scoring, and by measurement of fluid flux during ex vivo perfusion. G-CSF pretreatment elevated the baseline blood neutrophil counts as much as 6-fold compared with Control, and it increased the numbers of lung neutrophils and caused a mild histologic lung injury, but it did not significantly alter wet/dry weight ratios or fluid flux. ANTU alone and HCl alone caused a moderate histologic lung injury, increased wet/dry weight ratio, and resulted in a small increase in flux. The combination injuries, ANTU+G-CSF and HCl+G-CSF, caused a more severe lung injury manifested by increased wet/dry weight ratios and increase in flux when compared with ANTU alone and HCl alone, respectively. We conclude that pretreatment with G-CSF potentiates ANTU- and HCl-induced lung injury in non-neutropenic rats. The potential for G-CSF to aggravate acute lung injury in patients remains speculative.

Animals↗
PubMed1995

Variations in lectin binding properties of intestinal M cells.

Glycoconjugate expression in follicle-associated epithelia has been examined by application of a panel of lectins to fixed, whole tissue preparations of mouse and rabbit Peyer's and caecal patches. Of those examined, only alpha-L-fucose-specific lectins such as Ulex europaeus agglutinin I bound selectively to M cells in murine Peyer's patches and this selectivity did not extend to mouse caecal patch M cells. In common with a variety of other lectins (wheat germ agglutinin, peanut agglutinin and Bandeiraea simplicifolia agglutinin II), Ulex europaeus agglutinin I exhibited selective binding to M cells in rabbit caecal patch and to enterocytes in rabbit Peyer's patch. The marked regional and species variation in M cell surface characteristics documented here has implications for the normal antigen-sampling function of M cells and to the rational design of particulates for transepithelial delivery via the M cell portal.

Animals↗
PubMed1995

Pathophysiology of pneumonia.

The care and management of the pneumonia patient are formidable challenges to the physician. As long as the basic underlying host defense defects in these patients remain elusive, the clinician's approach will remain symptomatic and empirical. Further knowledge of the underlying pathophysiology of pneumonia will undoubtedly provide innovative approaches to both the prevention and the early and effective treatment of this infection. Clearly, the development of a multimodal approach, including components of immune modulation and immune restoration, is needed to improve the multiple defects in the host defense system; however, the normal host defense system operates in a delicate balance. Efforts to stimulate the immune system nonselectively may prove to be as deleterious to the patient as are the negative effects of their immunocompromised state.

Antibody Formation↗
PubMed1995

Pathogenesis and host defense in pulmonary infections.

The development of pneumonia typically results from an overwhelming bacterial inoculum or a breakdown in the integrity of the host's pulmonary defense mechanisms. Augmentation of pulmonary defenses is one means of reducing the incidence, morbidity, and mortality from pneumonia. Strategies to enhance pulmonary or systemic defenses are actively being investigated. Selected established and investigational measures enhancing host defense mechanisms against various pathogens are reviewed.

Humans↗
PubMed1994

Heterogenous Na+, K(+)-ATPase expression in the epithelia of rabbit gut-associated lymphoid tissues.

Na+, K(+)-ATPase expression in the epithelia of rabbit gut-associated lymphoid tissue was measured using indirect immunofluorescence and confocal laser scanning microscopy. All four major sites of aggregated lymphoid tissue, i.e. Peyer's patch, sacculus rotundus, caecal patch and appendix, were studied. Na+, K(+)-ATPase expression was localized to the basolateral surface of cells of the follicle-associated epithelium (FAE) and adjacent villous or surface epithelia (non-FAE), where increased expression during enterocyte migration was evident. In the FAE, expression of Na+, K(+)-ATPase appeared to be lower in the specialized M cells than in enterocytic-type cells, although expression in both cell types was lower than in adjacent non-FAE. Quantification of immunofluorescent staining of Na+, K(+)-ATPase by confocal laser scanning imaging showed a reduction of expression in the FAE to approximately 20-60% relative to that in the adjacent non-FAE. These results are consistent with a primary role of the FAE in mucosal immunity with minimal involvement in active solute absorption.

Animals↗
PubMed1994

Loss of compartmentalization of alveolar tumor necrosis factor after lung injury.

Tumor necrosis factor (TNF), a compartmentalized cytokine, is a key mediator in the systemic inflammatory response syndrome and may play a role in multiorgan failure. To assess whether compartmentalization of alveolar TNF is preserved following lung injury, isolated perfused lungs from Sprague-Dawley rats were given intratracheally 1 ml/kg of phosphate-buffered saline (PBS), 0.1 mg/kg of lipopolysaccharide (LPS), or 125,000 units of murine recombinant TNF (mrTNF). To induce lung leak, one group of rats was given 50 mg/kg of alpha-naphthylthiourea (ANTU) intraperitoneally. Then, 125,000 units mrTNF was given intratracheally to these lungs. Samples of perfusate were assayed for TNF by the L929 cytotoxicity assay before (0 min) and 180 min after the intratracheal challenge, and bronchoalveolar lavage (BAL) was performed for TNF assay. ANTU increased lung leak but intratracheal TNF and LPS did not. The isolated perfused lung preparation expressed small amounts of perfusate TNF and underwent minimal leak that was not caused by TNF release. Endogenous or exogenous intrapulmonary TNF remained predominantly compartmentalized, but following ANTU, TNF readily appeared in the perfusate. Compartmentalization of alveolar TNF is lost during alveolar-capillary injury, suggesting that the injured lung may contribute to a systemic inflammatory response and subsequent multiorgan failure.

Animals↗
PubMed1992

Co-expression of vimentin and cytokeratins in M cells of rabbit intestinal lymphoid follicle-associated epithelium.

Membranous epithelial (M) cells within the follicle-associated epithelium which overlies gut-associated lymphoid tissue in Peyer's patches and of appendix have been shown by immunocytochemical staining, in rabbit, to contain both vimentin- and cytokeratin-type intermediate filaments. The specificity of vimentin immunostaining has been confirmed by blocking with purified vimentin and by immunoblotting. No evidence was obtained for the expression of vimentin in rat, mouse or human M cells. The possible significance of vimentin-expression in these specialized epithelial cells and the potential use of vimentin as a positive marker for M cells are discussed.

Animals↗
PubMed1992

Normal host defenses and impairments associated with the delayed resolution of pneumonia.

The lung is constantly exposed to infectious challenges and depends on a complex system of defense mechanisms to facilitate the clearance of pathogens and prevent the development of infection. Both the upper airway and lower respiratory tract have mechanical, humoral, and cellular mechanisms in place to protect the airways from diverse microorganisms. Impairment in any arm of this system can result in the predisposition of the host to respiratory infections, which may be of a recurrent nature. Defects may be congenital or acquired, and may be iatrogenic in the hospitalized patient. An understanding of these defects may lead to more effective therapies and preventive modalities for decreasing the number and severity of respiratory infections.

Aging↗
PubMed1992

Respiratory epithelial carbohydrate levels of rats with gram-negative bacillary colonization.

One mechanism by which severe illness or stress might facilitate adherence and colonization of GNB to respiratory epithelium is by altering epithelial cell surface carbohydrates. To investigate this possibility we used radiolabeled lectins to quantitate carbohydrate levels on intact buccal and tracheal epithelium. A rat model of GNB colonization, in which renal infarction was performed to produce colonization, was used. Buccal and tracheal epithelial surface carbohydrate levels from normal rats and rats 48 hours after renal infarction were compared. Buccal and tracheal epithelium from the renal infarction animals had decreased amounts of sialic acid and fucose, and decreased levels of these sugars occurred at the same time that heavy oropharyngeal GNB colonization developed. Tracheas obtained from the infarcted animals bound three times more Type 1 piliated GNB than normal tracheas. Sialic acid and fucose levels are decreased early after stress, and we speculate that altered epithelial carbohydrates may predispose to GNB colonization by exposing binding sites for GNB.

Animals↗