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Larry C Lands

Publications and source records attributed to Larry C Lands.

14 recordsLinked to original sources
PubMed2006

Inhibition of IL-8 release from CFTR-deficient lung epithelial cells following pre-treatment with fenretinide.

Cystic fibrosis (CF) is characterized by a biochemical abnormality in the cystic fibrosis transmembrane conductance regulator (CFTR) channel. CFTR-deficient lung epithelial cells may have high constitutive glutathione (GSH) levels that could decrease the intracellular content of the sphingolipid second messenger, ceramide. Altered ceramide levels in CF cells could, in turn, lead to their resistance to apoptosis and an immune hyper-responsiveness. As fenretinide is a ceramide up-regulating drug that inhibits the activation of the pro-inflammatory transcriptional factor, nuclear factor (NF)-kappaB, the impact of fenretinide on unstimulated and tumor necrosis factor (TNF)-alpha stimulated production of NF-kappaB-dependent interleukin (IL)-8 was studied in immortalized wild-type (non-CF; 9HTEo-) and mutant DeltaF508 CFTR (CF; CFTE29o-) tracheal epithelial cells. Despite higher constitutive levels of GSH in CF cells, their intracellular ceramide content showed a greater enhancement following fenretinide and TNF-alpha treatment than non-CF cells. Clinically relevant concentrations of fenretinide (1.25, 2.5 and 5 microM) inhibited TNF-alpha-induced IL-8 production of CF cells by up to 73% but had no effect or increased the IL-8 production in non-CF cells. Although fenretinide treatment was associated with a higher intracellular ceramide content in the mutant DeltaF508 CFTR cells, the fenretinide-mediated decrease in IL-8 secretion was not consistently explained by changes in the intracellular content of this sphingolipid. Fenretinide was ineffective in increasing the susceptibility to apoptosis in CF cells whereas non-CF cells were sensitive to the apoptosis induced by both fenretinide and cisplatin exposure. The fenretinide mediated decrease in IL-8 release in CF cells under TNF-alpha stimulated conditions presents the possibility that the lung inflammation in CF could be attenuated via low dose fenretinide treatment.

Anticarcinogenic Agents↗
PubMed2006

Applying physiology to conventional mechanical ventilation.

It is important to understand the physiology that underlies how patients get into respiratory difficulty and how they can be supported to overcome these difficulties. This article reviews the physiological principles that underpin decision making about support for patients with respiratory difficulties, whether they are related to inadequate oxygenation or ventilation.

Humans↗
PubMed2006

High hydrostatic pressure enhances whey protein digestibility to generate whey peptides that improve glutathione status in CFTR-deficient lung epithelial cells.

Whey protein isolates (WPI) may provide anti-inflammatory benefits to cystic fibrosis (CF), which could be mediated via peptides, as proteolytic digests of WPI enhance intracellular glutathione (GSH) concentrations. The objectives of this study were to investigate whether high hydrostatic pressure can (i) improve the in vitro digestibility of WPI; and (ii) generate low molecular weight (< 1 kDa) peptides from WPI hydrolysates that exert GSH-enhancing and anti-inflammatory properties in wild type and mutant CF transmembrane conductance regulator (CFTR) tracheal epithelial cells. Hydrostatic pressure processing enhanced the in vitro digestibility of WPI to proteolytic enzymes resulting in altered peptide profiles as assessed by CZE and GC-MS. The exposure of mutant CFTR cells to low molecular weight (< 1 kDa) peptides isolated from WPI hydrolysates exposed to pressure processing (pressurized WPI hydrolysates, pWPH), showed increased intracellular levels of reduced GSH and total GSH relative to treatment with peptides obtained from native WPI hydrolysates (nWPH). A tendency for decreased interleukin-8 secretion was associated with the pWPH and nWPH treatments in mutant CFTR cells, which was not observed in wild type cells. Hydrostatic pressure processing of whey proteins appears to enhance their impact on cellular GSH status in cells with the mutant CFTR condition.

Amino Acids↗
PubMed2006

Evaluation of a school-based tuberculosis-screening program and associate investigation targeting recently immigrated children in a low-burden country.

CONTEXT: In countries with a low incidence of tuberculosis (TB), screening programs targeting recent immigrants from TB-endemic countries have been shown to be effective in further reducing TB incidence; however, evaluative data on some aspects of these programs remain sparse. OBJECTIVE: We sought to retrospectively evaluate a school-based screening program targeting children at high risk for TB infection in Montreal, Canada, as well as subsequently investigate family and household associates of the schoolchildren with latent TB infection (LTBI), based on adherence to LTBI therapy and cost-benefit analysis. DESIGN, SETTING, AND PARTICIPANTS: Newly arrived immigrant children (aged 4-18 years) in selected schools were screened for LTBI by using the tuberculin skin test (TST). The TST was defined as positive at an induration of > or =10 mm. Each child who tested positive on the TST was referred for medical evaluation. Family and household associates of the TST-positive child also were screened for LTBI. Classroom attendance sheets and medical charts were reviewed for 16 elementary and secondary schools that comprised the school-screening program of the Montreal Children's Hospital from 1998 to 2003. Medical charts of the child associates (<18 years old) who were screened were reviewed also. MAIN OUTCOME MEASURES: The main outcome measures were TST-positivity rate, rate of adherence to LTBI therapy, estimation of factors associated with adherence, and net cost/benefit of the school-screening and associate-investigation programs, both respectively and as a combined program, compared with the cost of passive treatment of TB disease. RESULTS: Of 2524 immigrant children screened, 542 (21%) were TST-positive. Of 342 children started on therapy, 316 (92%) demonstrated adequate adherence. The only predictor of adherence among the schoolchildren was having > or =2 family members brought in for TB screening (adjusted odds ratio: 2.0; 95% confidence interval: 1.3-3.3). There were 599 associates investigated from the 484 TST-positive schoolchildren seen at the TB clinic. Of 555 associates with TST results, 211 (38%) were found to be TST-positive. Of 136 TST-positive child associates, 131 were seen at the Montreal Children's Hospital TB clinic and had their chart reviewed. Of these, 108 (82%) were started on LTBI therapy, and 78 (79%) of 99 of those children with information complied adequately with their therapy. We found net benefits from both school-based screening and associate investigation, both as stand-alone programs and as 1 coordinated, targeted TB-screening program. CONCLUSION: We demonstrated the effectiveness, including cost-effectiveness, of a targeted, school-based screening program in a low-burden country and the extra benefit given by adding associates to such a program.

Adolescent↗
PubMed2005

Comparison of fingertip to arterial blood samples at rest and during exercise.

OBJECTIVE: The purpose was to determine whether arterialized fingertip blood-gas samples are comparable to arterial samples at rest and at exercise. DESIGN: Repeated measures, with subjects serving as their own controls. SETTING: Department of Anesthesia, Montreal General Hospital, Montreal, Quebec, Canada, (January to April 2004). PARTICIPANTS: Fifteen healthy men (age = 25 +/- 4 y; weight = 76.4 +/- 11.4 kg; height = 180.7 +/- 8.0 cm; peak oxygen uptake or VO2peak = 46.0 +/- 9.0 mL . kg . min). MAIN OUTCOME MEASURES: Arterial blood gases, metabolites, electrolytes. RESULTS: Blood sampled simultaneously from the radial artery and warmed fingertip at rest and during 2 levels of exercise (vigorous 181 W or 70% VO2peak; maximal 261 W or 100% VO2peak) on a electronically braked ergometer. Arterial partial pressure of oxygen in blood combining rest and the 2 exercise levels was on average 13.6 +/- 9.0 mm Hg higher than arterialized fingertip samples, with the largest difference occurring at rest (18.8 +/- 6.5 mm Hg; 95% CI = 15.5, 22.1) and the smallest difference occurring at the highest level of exercise (8.3 +/- 9.2 mm Hg; 95% CI = 3.6, 13.0; P < 0.05). The pattern for oxyhemoglobin saturation was the same, showing statistical differences between the sampling sites with the differences reduced at the highest exercise intensity. In contrast, there was no difference in arterial and arterialized partial pressure of carbon dioxide in blood (-1.0 +/- 1.5 mm Hg; 95% CI = -1.4, -0.6), or plasma lactate, glucose, pH, hemoglobin, and electrolytes between both sampling sites at rest or at the 2 exercise levels. CONCLUSION: Arterialized fingertip blood samples at rest and during exercise can predict arterial carbon dioxide pressure, and can predict arterial plasma lactate, glucose, pH, hemoglobin, and electrolytes; but not arterial oxyhemoglobin saturation or arterial oxygen pressure.

Adult↗
PubMed2004

Lung diffusion capacity for nitric oxide and carbon monoxide is impaired similarly following short-term graded exercise.

Study aimed to determine whether short-term graded exercise affects single-breath lung diffusion capacity for nitric oxide (DLNO) and carbon monoxide (DLCO) similarly, and whether the DLNO/DLCO ratios during rest are altered post-exercise compared to pre-exercise. Eleven healthy subjects (age=29+/-6 years; weight=76.6+/-13.2 kg; height=177.9+/-13.2 cm; and maximal oxygen uptake or V(.-)(O(2max) = 52.7 +/- 9.3 ml kg(-1) min(-1))performed simultaneous single-breath DLNO and DLCO measurements at rest (inspired NO concentration=43.2+/-4.1 ppm, inspired CO concentration=0.30%) 15 min before and 2h after a graded exercise test to exhaustion (exercise duration=593+/-135 s). Resting DLNO and DLCO was similarly reduced 2h post-exercise (DLNO=-7.8+/-3.5%, DLCO=-10.3+/-6.9%, and P<0.05) due to reductions in pulmonary capillary blood volume (-11.3+/-9.0%, P<0.05) and membrane diffusing capacity for CO (-7.8+/-3.5%; P<0.05). The change in DLCO was reflected by the change in DLNO post-exercise such that 68% of the variance in the change in DLCO was accounted for by the variance in the change in DLNO (P<0.05). The DLNO/DLCO ratio was not altered post-exercise (5.87+/-0.37) compared to pre-exercise (5.70+/-0.34). We conclude that the decrease in single-breath DLNO and DLCO from pre- to post-exercise is similar, the magnitude of the change in DLCO closely reflects that of the change in DLNO, and single-breath DLNO/DLCO ratios are independent of the timing of measurement suggesting that using NO and CO transfer gases are valid in looking at short-term changes in lung diffusional conductance.

Adult↗
PubMed2004

Induced sputum in cystic fibrosis: within-week reproducibility of inflammatory markers.

UNLABELLED: Analysis of induced sputum has provided significant insight into the inflammatory response in chronic respiratory diseases such as asthma. The thick, tenacious nature of cystic fibrosis (CF) sputum presents certain challenges to such evaluation. We describe the development of a methodology to assess CF sputum, and the within-week reproducibility (to limit the possibility of any change in clinical status) of cellular and inflammatory markers. METHODS: Seventeen young adults [9 males, 8 females, mean age 24 (5), median (quartile range) years, percentage of predicted FEV(1) = 64.0 (18.0%)] with CF underwent sputum inductions on the Monday and Thursday of the same week. Patients were pretreated with 400 microg salbutamol and subsequently inhaled 5% saline via a breath enhanced nebulizer. Every 3-min nebulization was interrupted to allow for expectoration of sputum into a polypropylene pot. Sputum samples were dispersed with a solution of dithiothreitol (DTT) and deoxyribonuclease to allow for analysis of total cell count (TCC) and percentage neutrophils (%Neut). Measurement of tumor necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8), and neutrophil elastase was performed on samples dispersed with DTT alone. RESULTS: There were no significant differences between the measurements taken in the same week. Values for Day 1 versus Day 2 were as follows: TCC 20.8 (6.4) vs. 17.6 (2.5) x 10(6) cells/ml; %Neut: 94.1 (0.0) vs. 95.4 (0.5) %; TNF-alpha 7.5 (26.0) vs. 21.0 (44.0) pg/ml; IL-8 610.0 (422.0) vs. 524.0 (587.0) ng/ml and neutrophil elastase 110.0 (19.75) vs. 49.75 (60.75) microM. High intraclass correlation coefficients (ICC) for TCC, %Neut, TNF-alpha IL-8 and neutrophil elastase were found (ICC = 0.76, 0.82, 0.93, 0.82, 0.74, respectively). CONCLUSIONS: The method developed here for the analysis of CF sputum shows good reproducibility and can be used to evaluate therapeutic interventions in patients with cystic fibrosis.

Adult↗
PubMed2004

The relationship between single-breath diffusion capacity of the lung for nitric oxide and carbon monoxide during various exercise intensities.

STUDY OBJECTIVES: To determine the relationship between single-breath diffusion capacity of the lung for nitric oxide (DLNO) and single-breath diffusion capacity of the lung for carbon monoxide (DLCO), and to determine the single-breath DLNO/DLCO ratios during rest and at several exercise intensities using a commercial lung diffusion system that uses electrochemical cells to analyze gases. SETTING AND PARTICIPANTS: Eight healthy men (age, 27 +/- 5 years; weight, 83.0 +/- 11.8 kg; height, 180.4 +/- 9.5 cm; maximal oxygen uptake [VO(2)max], 47.6 +/- 10.2 mL/kg/min [mean +/- SD]) performed single-breath DLNO measurements (inspired nitric oxide concentration, 66.5 +/- 10.6 ppm) and carbon monoxide (0.30%) randomized on different days at rest and at various exercise intensities (40%, 75%, and 90% of VO(2)max reserve [VO(2)R]) on a electrically braked load simulator. The DLCO measured on day 1 was compared to the DLCO measured during the DLNO method from another day. RESULTS: The relationship between DLNO and DLCO was linear (DLNO = 4.47 x DLCO; r(2) = 0.91; standard error of the estimate = 0.04; p < 0.05). DLNO was 4.52 +/- 0.24 times greater than DLCO, independent of exercise intensity. DLNO increased from 210.3 +/- 18.2 mL/min/mm Hg at rest to 284.2 +/- 38.6 mL/min/mm Hg at 90% VO(2)R (oxygen uptake = 42.6 +/- 9.8 mL/kg/min; 284.2 +/- 31.6 W; p < 0.05). Stepwise regression demonstrated that DLNO is predicted by alveolar volume (VA) [in liters] and workload (watts) such that DLNO = 13.4 x VA + 0.23 x workload + 107.7 (r(2) = 0.90; SEE = 17.5; p < 0.05). CONCLUSION: (1) Single-breath DLNO and DLCO increase linearly with increasing workload; (2) the single-breath DLNO/DLCO ratios are independent of exercise intensity, suggesting that using either nitric oxide or carbon monoxide as transfer gases are valid in the study of lung diffusion during any level of exercise; and (3) DLNO is mainly predicted by VA and workload.

Adult↗
PubMed2003

Improved glutathione status in young adult patients with cystic fibrosis supplemented with whey protein.

BACKGROUND: The lung disease of cystic fibrosis is associated with a chronic inflammatory reaction and an over abundance of oxidants relative to antioxidants. Glutathione functions as a major frontline defense against the build-up of oxidants in the lung. This increased demand for glutathione (GSH) in cystic fibrosis may be limiting if nutritional status is compromised. We sought to increase glutathione levels in stable patients with cystic fibrosis by supplementation with a whey-based protein. METHODS: Twenty-one patients who were in stable condition were randomly assigned to take a whey protein isolate (Immunocal, 10 g twice a day) or casein placebo for 3 months. Peripheral lymphocyte GSH was used as a marker of lung GSH. Values were compared with nutritional status and lung parameters. RESULTS: At baseline there were no significant differences in age, height, weight, percent ideal body weight or percent body fat. Lymphocyte GSH was similar in the two groups. After supplementation, we observed a 46.6% increase from baseline (P < 0.05) in the lymphocyte GSH levels in the supplemented group. No other changes were observed. CONCLUSION: The results show that dietary supplementation with a whey-based product can increase glutathione levels in cystic fibrosis. This nutritional approach may be useful in maintaining optimal levels of GSH and counteract the deleterious effects of oxidative stress in the lung in cystic fibrosis.

Adolescent↗
PubMed2002

Role of heme oxygenases in sepsis-induced diaphragmatic contractile dysfunction and oxidative stress.

Heme oxygenases (HOs), essential enzymes for heme metabolism, play an important role in the defense against oxidative stress. In this study, we evaluated the expression and functional significance of HO-1 and HO-2 in the ventilatory muscles of normal rats and rats injected with bacterial lipopolysaccharide (LPS). Both HO-1 and HO-2 proteins were detected inside ventilatory and limb muscle fibers of normal rats. Diaphragmatic HO-1 and HO-2 expressions rose significantly within 1 and 12 h of LPS injection, respectively. Inhibition of the activity of inducible nitric oxide synthase (iNOS) in rats and absence of this isoform in iNOS(-/-) mice did alter sepsis-induced regulation of muscle HOs. Systemic inhibition of HO activity with chromium mesoporphyrin IX enhanced muscle protein oxidation and hydroxynonenal formation in both normal and septic rats. Moreover, in vitro diaphragmatic force generation declined substantially in response to HO inhibition both in normal and septic rats. We conclude that both HO-1 and HO-2 proteins play an important role in the regulation of muscle contractility and in the defense against sepsis-induced oxidative stress.

Animals↗
PubMed2002

Isokinetic muscle function in COPD.

AIM: Exercise limitation in patients with COPD has been attributed to impaired ventilation and reduced skeletal muscle function. We have previously used a combination of FEV(1) and leg muscle function (work achieved during a 30-s isokinetic sprint test) to predict progressive exercise capacity. However, the 30-s test may not be well tolerated in patients with advanced lung disease. We studied the relationship between progressive exercise capacity, FEV(1), and isokinetic work in patients with COPD and in healthy control subjects to assess whether the work accomplished at time intervals of < 30 s could also be used to predict progressive maximal exercise capacity (Wmax). METHODS: Twenty-seven patients with COPD and 29 control subjects underwent anthropometric measures, spirometry, progressive cycle ergometry, and 30-s isokinetic cycling. RESULTS: There was no significant difference for weight, height, or body mass index between the groups. The COPD group was slightly older and had a significantly lower FEV(1) than control subjects. They also had a lower Wmax (56 +/- 28.3 W vs 141.9 +/- 46.7 W) and isokinetic work accomplished over 10 s (W10), over 15 s (W15), over 20 s (W20), over 25 s (W25), and over 30 s (W30). Wmax correlated in both patients with COPD and in control subjects with W10, W15, W20, W25, W30, and FEV(1). Combining FEV(1) and isokinetic work (W10, W15, W20, W25, or W30) in a two-factor model to predict Wmax, the coefficients of determination (r(2)) for patients with COPD were 0.57, 0.57, 0.58, 0.59, and 0.58, and for control subjects were 0.69, 0.69, 0.71, 0.71, and 0.73, respectively. Wmax correlated with weight only in control subjects. CONCLUSIONS: Both ventilatory function and leg muscle function contribute to exercise limitation, and a 20-s isokinetic test can be utilized to assess leg function in patients with COPD.

Aged↗
PubMedDate not supplied

Effect of whey protein to modulate immune response in children with atopic asthma.

BACKGROUND: Levels of glutathione (GSH) in antigen-presenting cells promote a T-helper type 2 (Th2) cytokine response in mice. We have previously demonstrated that we can increase intracellular GSH levels in healthy young adults using a whey-based oral supplement (HMS90). We hypothesized that such supplementation in children with atopic asthma, a Th2 cytokine disease, would improve lung function and decrease atopy. METHODS: Eleven children (six females, five males; mean+/-standard deviation age, 12.6+/-3.6 years; baseline forced expired volume in 1 sec (FEV1), 82.4+/-15.4%predicted), underwent spirometry, methacholine provocation testing, and blood analysis for serum IgE and lymphocyte GSH before and after 1 month of supplementation (10 g twice daily). RESULTS: Initially the IgE was 1689+/-1596 microg/l (normal range <or=240 microg/l) and lymphocyte GSH was 1.75+/-0.48 microM (normal range 1.55+/-0.33 microM). IgE significantly decreased to 1379+/-1329 microg/l (P < 0.05) following supplementation. Although no significant changes in lymphocyte GSH or FEV1 were found for the group as a whole, the two patients with significant increases in lymphocyte GSH concentrations were the only two to demonstrate reductions in methacholine provocation doses (provocative concentration causing a 20% fall in FEV1). CONCLUSIONS: These results suggest a modest impact of whey protein supplementation on the cytokine response in atopic asthma. Supplementation for longer periods, or with more potent whey-based supplements, currently under development, may prove more beneficial.

Adolescent↗