PubMed Health⌕ Search

Biomedical subjects

C M Mason

Publications and source records attributed to C M Mason.

At least 19 recordsLinked to original sources

Host defense in respiratory infections.

Respiratory defenses against infection involve a diverse and complex system. Mechanical barriers limit exposure of the respiratory tract to potential pathogenic organisms, whereas the mucociliary apparatus and cough reflexes work to expel any microbes that may bypass the initial defenses. When microorganisms have gained entry to the lower respiratory tract, the alveolar macrophage and recruited phagocytes may eliminate the culprits before active infection can be established. Only after the failure of the innate immune defenses is a specific immune response mounted. Examination of clinical defects in host defense allows one to understand the importance of the multitude of components of the lung's immune defense system.

Antibody Formation↗

CD4+ lymphocyte responses to pulmonary infection with Mycobacterium tuberculosis in naïve and vaccinated BALB/c mice.

The Biostack experiments I and II were flown on board the Apollo 16 and 17 command modules in order to obtain information on the biological damage produced by the bombardment of heavy high-energy (HZE) particles of cosmic radiation during spaceflight. Such data are required for estimating radiation hazards in manned spaceflight. Seven biological systems in resting state (Bacillus subtilis spores, Colpoda cucullus cysts, Arabidopsis thaliana seeds, and eggs of Artemia salina, Tribolium castaneum and of Carausius morosus) were accommodated in the two Biostacks. By using a special sandwich construction of visual track detectors and layers of biological objects, identification of each hit biological object was achieved and the possible biological damage correlated with the physical features of the responsible HZE-particle. In the different systems the degree of damage depended on whether the hit cell was replaceable or not. A high sensitivity to HZE-particle bombardment was observed on Artemia salina eggs; 90% of the embryos, which were induced to develop from hit eggs, died at different developmental stages. Malformations of the abdomen or the extremities of the nauplius were frequently induced. In contrast, the growth of hit Vicia faba radiculae and the germination of hit Arabidopsis thaliana seeds and hit Bacillus subtilis spores were not influenced remarkably. But there was an increase in multicaulous plants and a reduction in the outgrowth of the bacteria] spores. In addition, information was obtained on the fluence of the HZE-particles, on their spectrum of charge and energy loss, and on the absorption by the Apollo spacecraft and the Biostack material itself. This will help to improve knowledge concerning radiation conditions inside of spacecrafts, necessary to secure a The Biostack experiments I and II were flown on board the Apollo 16 and 17 command modules in order to obtain information on the biological damage produced by the bombardment of heavy high-energy (HZE) particles of cosmic radiation during spaceflight. Such data are required for estimating radiation hazards in manned spaceflight. Seven biological systems in resting state (Bacillus subtilis spores, Colpoda cucullus cysts, Arabidopsis thaliana seeds, and eggs of Artemia salina, Tribolium castaneum and of Carausius morosus) were accommodated in the two Biostacks. By using a special sandwich construction of visual track detectors and layers of biological objects, identification of each hit biological object was achieved and the possible biological damage correlated with the physical features of the responsible HZE-particle. In the different systems the degree of damage depended on whether the hit cell was replaceable or not. A high sensitivity to HZE-particle bombardment was observed on Artemia salina eggs; 90% of the embryos, which were induced to develop from hit eggs, died at different developmental stages. Malformations of the abdomen or the extremities of the nauplius were frequently induced. In contrast, the growth of hit Vicia faba radiculae and the germination of hit Arabidopsis thaliana seeds and hit Bacillus subtilis spores were not influenced remarkably. But there was an increase in multicaulous plants and a reduction in the outgrowth of the bacteria] spores. In addition, information was obtained on the fluence of the HZE-particles, on their spectrum of charge and energy loss, and on the absorption by the Apollo spacecraft and the Biostack material itself. This will help to improve knowledge concerning radiation conditions inside of spacecrafts, necessary to secure a The Biostack experiments I and II were flown on board the Apollo 16 and 17 command modules in order to obtain information on the biological damage produced by the bombardment of heavy high-energy (HZE) particles of cosmic radiation during spaceflight. Such data are required for estimating radiation hazards in manned spaceflight. Seven biological systems in resting state (Bacillus subtilis spores, Colpoda cucullus cysts, Arabidopsis thaliana seeds, and eggs of Artemia salina, Tribolium castaneum and of Carausius morosus) were accommodated in the two Biostacks. By using a special sandwich construction of visual track detectors and layers of biological objects, identification of each hit biological object was achieved and the possible biological damage correlated with the physical features of the responsible HZE-particle. In the different systems the degree of damage depended on whether the hit cell was replaceable or not. A high sensitivity to HZE-particle bombardment was observed on Artemia salina eggs; 90% of the embryos, which were induced to develop from hit eggs, died at different developmental stages. Malformations of the abdomen or the extremities of the nauplius were frequently induced. In contrast, the growth of hit Vicia faba radiculae and the germination of hit Arabidopsis thaliana seeds and hit Bacillus subtilis spores were not influenced remarkably. But there was an increase in multicaulous plants and a reduction in the outgrowth of the bacteria] spores. In addition, information was obtained on the fluence of the HZE-particles, on their spectrum of charge and energy loss, and on the absorption by the Apollo spacecraft and the Biostack material itself. This will help to improve knowledge concerning radiation conditions inside of spacecrafts, necessary to secure a maximum possible protection to the astronauts.

Animals↗

Keratinocyte growth factor attenuates hydrostatic pulmonary edema in an isolated, perfused rat lung model.

Hydrostatic pulmonary edema is a common complication of congestive heart failure, resulting in substantial morbidity and mortality. Keratinocyte growth factor (KGF) is a mitogen for type II alveolar epithelial and microvascular cells. We utilized the isolated perfused rat lung model to produce hydrostatic pulmonary edema by varying the left atrial and pulmonary capillary pressure. Pretreatment with KGF attenuated hydrostatic edema formation. This was demonstrated by lower wet-to-dry lung weight ratios, histological evidence of less alveolar edema formation, and reduced alveolar accumulation of intravascularly administered FITC-labeled large-molecular-weight dextran in rats pretreated with KGF. Thus KGF attenuates injury in this ex vivo model of hydrostatic pulmonary edema via mechanisms that prevent increases in alveolar-capillary permeability.

Animals↗

Identifying all suspects: case studies.

Case presentations are one of the most instructive formats for learning. They allow the healthcare practitioner to identify and discuss patients who are at risk for a disease and then discuss appropriate therapy. Two patients who have dyslipidemia and are at risk for a coronary event are described here, along with treatment goals and options, audience responses, and discussions of appropriate therapy choices. Both patients require aggressive lipid management. One has had an angioplasty with placement of a stent. His case is an example of a patient at risk for a secondary coronary event; we refer to these cases as secondary-prevention patients. The other patient has high blood pressure and type 2 diabetes; her risk for a future coronary event based on Framingham risk data is greater than 20% in 10 years and therefore her risk for a future coronary event is equal to someone with established coronary heart disease (CHD). Her case is an example of what we refer to as a primary-prevention patient at high risk. Several large-scale primary- and secondary-prevention trials have demonstrated that aggressive lipid management can reduce the risk of future coronary events. In this supplement, we review some of those trials, the new guidelines, the concept of CHD-equivalent risk, and we will discuss the Framingham risk scoring system to predict the 10-year risk of coronary events in individual patients.

Anticholesteremic Agents↗

The role of the inflammatory response in chronic bronchitis: therapeutic implications.

Chronic bronchitis is diagnosed clinically by a chronic productive cough. As implied by the term "bronchitis," chronic airway inflammation is typically found in the central airways in patients with persistent cough and mucous hypersecretion. Although the exact pathogenesis of chronic bronchitis remains unclear, bacterial colonization and the resulting inflammatory response are thought to be of central importance. The generation of pro-inflammatory cytokines and chemotactic stimuli by the airway epithelium likely play central roles in propagating the inflammatory response in patients with chronic bronchitis. Further insights into the initiating events and underlying mechanisms that result in the clinical syndrome of chronic bronchitis will likely provide novel opportunities for therapeutic interventions.

Anti-Bacterial Agents↗

Keratinocyte growth factor protects against Pseudomonas aeruginosa-induced lung injury.

We have previously reported that keratinocyte growth factor (KGF) attenuates alpha-naphthylthiourea-induced lung injury by upregulating alveolar fluid transport. The objective of this study was to determine the effect of KGF pretreatment in Pseudomonas aeruginosa pneumonia. A 5% bovine albumin solution with 1 microCi of (125)I-labeled human albumin was instilled into the air spaces 4 or 24 h after intratracheal instillation of P. aeruginosa, and the concentration of unlabeled and labeled proteins in the distal air spaces over 1 h was used as an index of net alveolar fluid clearance. Alveolocapillary barrier permeability was evaluated with an intravascular injection of 1 microCi of (131)I-albumin. In early pneumonia, KGF increased lung liquid clearance (LLC) compared with that in nonpretreated animals. In late pneumonia, LLC was significantly reduced in the absence of KGF but increased above the control value with KGF. KGF pretreatment increased the number of polymorphonuclear cells recovered in the bronchoalveolar lavage fluid and decreased bacterial pulmonary translocation. In conclusion, KGF restores normal alveolar epithelial fluid transport during the acute phase of P. aeruginosa pneumonia and LLC in early and late pneumonia. Host response is also improved as shown by the increase in the alveolar cellular response and the decrease in pulmonary translocation of bacteria.

Albumins↗

Keratinocyte growth factor prevents ventilator-induced lung injury in an ex vivo rat model.

Mechanical ventilation has been shown to produce lung injury characterized by noncardiogenic pulmonary edema. Keratinocyte growth factor (KGF) is a heparin-binding growth factor that causes alveolar type II pneumocyte hyperplasia. KGF pretreatment and the resultant pneumocyte hyperplasia reduce fluid flux in models of lung injury. We utilized the isolated perfused rat lung model to produce lung injury by varying tidal volume and the level of positive end-expiratory pressure during mechanical ventilation. Pretreatment with KGF attenuated ventilator-induced lung injury (VILI). This was demonstrated by lower wet-to-dry lung weight ratios and less lung water accumulation in the KGF group. Further, KGF prevented the decline in dynamic compliance and alveolar protein accumulation in VILI. KGF pretreatment reduced alveolar accumulation of intravascularly administered fluorescein isothiocyanate-labeled high-molecular-weight dextran. Thus, pretreatment with KFG attenuates injury in this ex vivo model of VILI via mechanisms that prevent increases in permeability.

Animals↗

Ethanol and murine interleukin (IL)-12 production.

BACKGROUND: Interleukin (IL)-12 is a cytokine with protean effects against bacterial and intracellular pathogens. Induction of IL-12 at the time of infection has salient effects on elimination of various microbes. This work describes the effect of exposure to ethanol on lipopolysaccharide (LPS)-induced production of IL-12 in mice and whether ethanol-induced increases in IL-10 mediates these changes in IL-12 production. METHODS: BALB/c mice were pretreated with ethanol and then challenged with LPS either intravenously (iv) or intratracheally (it), and blood and lung production of IL-12 (p70 and p40 components) and serum IL-10 were assayed. Splenic and lung mRNA for IL-12 p35 and p40 components was determined. RESULTS: Ethanol pretreatment suppressed LPS-induced IL-12 p70 and p40 protein production in blood and lung. In spleen and lung, p40 mRNA was induced to a greater extent than p35 mRNA, and there was greater suppression of p40 mRNA compared with p35 mRNA in ethanol-treated animals. Ethanol up-regulated the production of IL-10, and pretreatment of these animals with a polyclonal anti-IL-10 antibody resulted in significant increases in IL-12 p70 and p40 levels, but not completely to those of control animals. CONCLUSIONS: Ethanol suppresses the production of murine IL-12 in response to LPS in blood and lung, with both the p70 and the p40 components affected. This suppression is accompanied by reductions of p40 mRNA in both spleen and lung. IL-10 may play a role in ethanol-induced suppression of IL-12, as neutralization of IL-10 partially attenuated the suppression of IL-12.

Animals↗

Methicillin-resistant Staphyloccocus aureus: evaluation of five selective media.

This study evaluates the performance in isolating methicillin-resistant Staphylococcus aureus (MRSA) of three media: the reduced salt formulation of mannitol salt agar plus oxacillin (MMSAO); CHROMagar Staph aureus plus ciprofloxacin (CHRAC); and Halifax MRSA medium (HMO), against the previously recommended mannitol salt agar (7% salt) plus oxacillin (OMSAO) and Baird-Parker medium plus ciprofloxacin (BPC). MRSA screening swabs were plated out onto the five selective media and the plates examined at 24 and 48 h. Suspected colonies were confirmed as MRSA by detection of heat-labile DNase, coagulase and/or protein A, and by confirming resistance to methicillin. Of 719 specimens examined, 191 grew MRSA on at least one medium. The relative sensitivities of the five media at 48 h were as follows: BPC, 94%; CHRAC, 70%; OMSAO, 61%; HMO, 56%; and MMSAO, 46%. In addition, BPC gave the least number of unnecessary investigations for non-MRSA isolates. The current advantage of BPC when performing direct culture for MRSA was confirmed. The other ciprofloxacin-containing medium also produced reasonable results. Of the two mannitol salt agar media, the formulation with 7% salt gave better results. HMO proved unreliable at isolating MRSA.

Anti-Infective Agents↗

Pulmonary host defenses. Implications for therapy.

Pulmonary host defenses comprise a redundant system of protective mechanisms against invasion of the lungs by pathogenic microbes. The upper and lower airways are uniquely suited to contain and remove organisms that gain access to the respiratory mucosa. If the balance between host and organism is disputed, however, microbial clearance may be ineffective, and infection established. Pulmonary host defense mechanisms, which provide the basis for several current therapeutic strategies, are reviewed.

Anti-Bacterial Agents↗

Pulmonary stress injury within physiological ranges of airway and vascular pressures.

PURPOSE: The aim of this study was to assess the respective role of a small elevation in pulmonary capillary pressure, airway pressure, or both on alveolar capillary barrier permeability in an isolated perfused rat lung model. MATERIALS AND METHODS: Four groups were studied with low or high airway pressure (LA: 10 mL/kg (tidal volume); HA: 20 mL/kg), low or high pulmonary artery pressure (LP: 9 mm Hg; HP: 12 mm Hg): LALP, HALP, LAHP, and HAHP. The lungs were ventilated and perfused ex vivo for 30 minutes. Quantification of fluorescein isothiocyanate-labeled (FITC) dextran in bronchoalveolar lavage (BAL) fluid and radiolabeled tracers assessed alveolar capillary barrier permeability. RESULTS: BALF FITC-dextran was similar in the three groups with either one or two low-pressure parameters (LALP, LAHP, HALP), but high amounts were found in the HAHP group (375.2 x 10(-6) mg/mL v, respectively, 21.4, 26.2, and 30 x 10(-6) mg/mL, P = .0001). These results were consistent with the albumin space and extravascular lung water: higher values only in the HAHP group statistically different from the other groups (P < .002). Interalveolar pore examined with scanning electron microscopy showed an increase in diameters between LALP and HAHP (P < .0001). CONCLUSIONS: We can conclude that elevation of either the pulmonary artery pressure from 8 to 11 mm Hg or the alveolar pressure from 10 to 15 mm Hg alone does not change the permeability of the alveolar capillary membrane; however, there is an additive effect of these pressures.

Air Pressure↗

Comparative phenotypic characteristics of Staphylococcus aureus isolates from line and non-line associated septicaemia, CAPD peritonitis, bone/joint infections and healthy nasal carriers.

This study compared specific phenotypic and potential virulence characteristics of Staphylococcus aureus isolates from invasive infections and nasal carriers. Three hundred and sixty isolates were studied; 154 from septicaemia (69 line associated, 85 non-line), 79 from continuous ambulatory peritoneal dialysis (CAPD) peritonitis, 64 from bone/joint infections and 64 from healthy nasal carriers. The isolates were tested for production of enterotoxins (SE) A, B, C or E, toxic shock syndrome toxin-1 (TSST-1) protein A, and also for lipolytic, proteolytic, fibrinolytic and haemolytic activities. In addition phage typing, crystal violet reaction, urease and galactose breakdown were studied. Seventy-one percent of isolates were enterotoxigenic. Production of SEA was significantly lower amongst the bone/joint isolates. Production of SEB, was lower among the control group compared with CAPD, bone/joint, and non-line septicaemia isolates. SEE production was higher among the bone/joint isolates compared with the CAPD and non-line septicaemias and production of TSST-1 was significantly higher among nasal isolates compared with isolates causing infection. Almost all of the isolates were lipolytic, with highest activity amongst nasal and bone/joint isolates. Fibrinolytic activity was similar in the five groups of isolates. Proteolytic activity ranged from 35 to 62% of isolates with the lowest frequency among septicaemia isolates. In all, 80-90% of isolates were haemolytic, although CAPD isolates were less likely to be haemolytic. Isolates from the control and CAPD group more frequently belonged to phage group I. TSST-1 does not appear to be an important requirement for invasive infections, but SEB may be. Proteolysis and intensity of lipolysis appear to be less important in septicaemia, and haemolysis may not be important in CAPD peritonitis.

Bacterial Toxins↗

Fluorescein-labeled dextran concentration is increased in BAL fluid after ANTU-induced edema in rats.

Several methodologies have been developed to assess alveolocapillary membrane permeability in acute lung injury. The purpose of this study was to determine the reliability of FITC-dextran compared with radioactive tracers to assess lung permeability alterations. After intraperitoneal administration of alpha-naphthylthiourea (ANTU, 50 mg/kg) or DMSO-ANTU vehicle, the animals were euthanized and their lungs were studied in an isolated-lung preparation. FITC-dextran or radiolabeled tracers were added to the perfusate. At 2 h the bronchoalveolar lavage (BAL) fluid from the ANTU group showed a significantly greater amount of fluorescence in the supernatant after centrifugation of BAL fluid compared with the DMSO group. Consistent results were observed with the radioactive tracers: there was an increase in extravascular albumin space and extravascular lung water compared with the control group. No cleavage of the FITC from the dextran molecule was evident by chromatography comparing samples recovered from the BAL fluid to the pure FITC-dextran molecule. In conclusion, measurement of FITC-dextran in the supernatant of BAL fluid after intravascular administration is a reliable method of assessing lung permeability changes in vivo and ex vivo.

Animals↗

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↗

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↗

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↗

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↗