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Biomedical subjects

M Glass

Publications and source records attributed to M Glass.

At least 55 records · Page 3Linked to original sources
PubMed1992

Specificity and sensitivity of the assay for elastin-derived peptides in chronic obstructive pulmonary disease.

One prediction of the protease-antiprotease hypothesis of chronic obstructive pulmonary disease (COPD) pathogenesis is the appearance of elastin-derived degradation products in the plasmas of affected patients that are due to the breakdown of alveolar interstitial elastin by an excess of elastolytic activity in the lung. We previously demonstrated a significant elevation of plasma elastin-derived peptides (EDP) in subjects with COPD in comparison with asymptomatic smokers with normal spirometry or normal nonsmokers. To better determine the selectivity of the assay for EDP as a marker of COPD, we measured plasma EDP levels in different patient populations. These included subjects with COPD, subjects with diseases that may involve accelerated elastolysis (pneumonia, atherosclerotic vascular disease, and inflammatory arthritis), subjects with diseases hypothesized to involve pulmonary inflammation without elastolysis (asthma and acute tracheobronchitis), asymptomatic smokers with normal spirometry, and healthy, nonsmoking subjects. Mean plasma EDP levels in subjects with COPD were elevated above those in all other subjects (p less than 0.01). The prospective analyses of specificity and sensitivity of plasma EDP levels as markers of COPD gave values of 91 and 65%, respectively. Utilizing receiver operating characteristic curve analysis to assess the diagnostic and screening performance of plasma EDP as a test for COPD (perfect test equals an area under the curve of 1.0), the area under the curve was 0.87, which compares favorably with many widely used clinical tests. These data demonstrate that the assay for plasma EDP is a quantitative, easily measured, and highly specific marker for subjects with COPD.

Adult↗
PubMed1991

The effect of the oral leukotriene antagonist, ICI 204,219, on leukotriene D4 and histamine-induced cutaneous vascular reactions in man.

Eighteen normal male subjects were recruited for a double-blind, placebo-controlled, randomized, two-period crossover study to determine the effects of a new, potent, highly selective, oral peptide leukotriene antagonist (ICI 204,219) on cutaneous vasculature. Skin testing for leukotriene D4 (LTD4) and histamine was performed at three different time intervals after receiving ICI 204,219 or placebo. The LTD4 threshold dose responses were recorded in duplicate to verify reproducibility. These data confirm known remarkable dose-response variation of cutaneous vascular reactions to LTD4 since some subjects reacted to a dose as low as 0.001 fmol. Twelve subjects (67%) demonstrated a more than one-half log increase in their threshold response after receiving ICI 204,219. Five of these 12 subjects (28%) had greater than 1 log-dose response after ICI 204,219. Two of these subjects (11.1%) had a 5 or 10 log increase in their threshold response after receiving ICI 204,219. Given the role of leukotrienes as potentially important mediators in immediate-type reactions, our results raise the possibility for additional investigation of the antagonistic effect of ICI 204,219 in nonallergic and allergic cutaneous diseases.

Adolescent↗
PubMed1990

Inhibition of leukotriene D4-induced bronchoconstriction in normal subjects by the oral LTD4 receptor antagonist ICI 204,219.

The sulfidopeptide leukotrienes may play a role in the pathogenesis of asthma. Previous clinical trials with leukotriene antagonists have shown only minimal protection from subsequent challenge with inhaled LTD4. Using a double-blind, placebo-controlled crossover design, we tested the hypothesis that the LTD4 receptor antagonist, ICI 204,219, could inhibit LTD4-induced bronchoconstriction in normal subjects. On separate days, 3 to 7 days apart, a single oral 40-mg dose of ICI 204,219 or placebo was ingested. At 2 h (Group I), 12 h (Group II), or 24 h (Group III) after the dose, six subjects in each group underwent bronchoprovocation testing with aerosolized LTD4. The airway response was assessed by measuring specific airway conductance (SGaw) and the FEV1. ICI 204,219 had no effect on baseline pulmonary function. When given 2 h before the LTD4 challenge, ICI 204,219 increased by 117-fold the concentration of LTD4 required to reduce SGaw 35%: 34 +/- 10 versus 3,965 +/- 894 micrograms/ml (placebo versus ICI 204,219; p less than 0.05). When given 12 h before the LTD4 challenge, ICI 204,219 increased by ninefold the concentration of LTD4 required to reduce SGaw 35%: 33 +/- 11 versus 304 +/- 125 micrograms/ml (p less than 0.05). When given 24 h before the LTD4 challenge, a smaller effect was found: 12 +/- 3 versus 60 +/- 24 micrograms/ml (p less than 0.05). Plasma levels of ICI 204,219 correlated with efficacy across groups (r = 0.83, p less than 0.001), but imperfectly within groups. No adverse effects (symptoms or abnormal laboratory test results) were noted after ingesting the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Acute cigarette smoke exposure in dogs: the inflammatory response.

Acute cigarette smoke causes polymorphonuclear leukocyte (neutrophil, PMN) recruitment to the lung followed by loss of elastase from the recruited cells. Dogs were exposed to cigarette smoke with different oxidant content, bronchoalveolar lavage (BAL) was performed, and the cell distribution in the recovered alveolar lining fluid was analyzed. Exposures were 1, 3, or 6 cigarettes on one or multiple days with a maximum dose of 42 cigarettes. The mean percent PMN present in control lavage was 2.01%, while the mean percent PMN recovered in BAL after a dose of 42 1R1 cigarettes was 13.05%. Recoverable PMN, after a single exposure to three 1R1 cigarettes, also increased from 1.7 to 10.4% by 15 h after cessation of smoke exposure. The cell response for multiple (2 and 7) day exposures was similar. The elastase content per BAL neutrophil decreased relative to peripheral blood PMN from the same animals. No free elastolytic activity was found in BAL, but PMN elastase antigen was present. Increased frequency of cigarette smoke exposure delayed the return to homeostatic cell conditions. The increased PMN accumulation observed may result in an increased proteolytic load in the pulmonary interstitium and contribute to the pathogenesis of emphysema.

Animals↗
PubMed1986

An ultrastructural study of the renal juxtaglomerular apparatus and extraglomerular mesangium in patients with systemic lupus erythematosus.

Experimental studies have indicated that the glomerular mesangium may function by phagocytosis of various circulating substances which are then processed and flow to the juxtaglomerular apparatus (JGA) region and into the intercellular spaces of the macula densa. An electron-micrographic study of the juxtaglomerular apparatus and extramesangial region in systemic lupus erythematosus (SLE) was undertaken. In only five of 39 cases (13%) of SLE were discrete electron-dense "immune-type" deposits noted in the JGA region. In four of those patients, there were also a large number of variously-sized electron-dense deposits in the glomerular mesangial and capillary wall regions, Bowman's capsule, tubular basement membranes, renal interstitium, or in the nearby periglomerular arterioles. The paucity of demonstrable discrete electron-dense deposits in the JGA regions in this study suggests that the deposits noted in SLE in humans may not be commonly processed in this fashion, or alternatively, that the discrete electron-dense deposits are processed and undergo lysis within the glomerular mesangial regions before they are transported to the extraglomerular mesangial regions of the JGA.

Adolescent↗
PubMed1985

Oxygen toxicity: loss of lung macrophage function without metabolite depletion.

Hyperoxia inhibited concanavalin A stimulated O2- release (respiratory burst) of alveolar macrophages obtained by bronchoalveolar lavage from rats. After 36 h of normobaric 100% O2, a partial reversal (48%) of the inhibition was produced by addition of glucose. Since oxidant-induced, reversible NADPH depletion correlates with reversible inhibition of the respiratory burst, intracellular NADPH was assayed to determine whether irreversible inhibition of the respiratory burst was related to persistent changes in this metabolite. The cellular concentrations of ATP, glutathione, and ascorbate were also measured. After 36 h of hyperoxia, NADPH concentration in alveolar macrophages rose slightly while ATP and glutathione content remained at control levels. Ascorbate levels fell significantly but were not responsible for respiratory burst inhibition. Thus, irreversible loss of cellular function in hyperoxia is not due to persistent alterations in these metabolites. Significant amounts of both glutathione and ascorbate were found in extracellular fractions of lung washings, indicating high concentrations in the aqueous subphase in the lung fluid lining. There was no change in total content of these extracellular antioxidants following O2 exposure.

Animals↗
PubMed1985

Selenium deficiency potentiates paraquat-induced lipid peroxidation in isolated perfused rat lung.

Glutathione peroxidase (GSHPx), a seleno-enzyme, reduces lipid hydroperoxides while producing oxidized glutathione (GSSG), which can efflux from cells. To study the role of GSHPx in antioxidant defense, isolated lungs from selenium-deficient rats were perfused for 2 h with or without 1 mM paraquat. Perfusate GSSG was measured as an index of GSHPx activity, and malondialdehyde (MDA) as an index of lipid peroxidation. Selenium deficiency decreased lung GSHPx activity 75-80%. During perfusion control lungs showed GSSG efflux of 8.5 +/- 4.5 nmol/h and with paraquat 49.1 +/- 12.1 nmol/h. Selenium-deficient lungs with or without paraquat showed GSSG efflux of 16.4 +/- 5.3 and 13.7 +/- 8.9 nmol/h, respectively. MDA efflux occurred only in paraquat-perfused selenium-deficient lungs (7.8 +/- 2.7 nmol/h). Lung homogenates from this group had lower GSH + GSSG than the other three groups. These results indicate an inverse correlation between GSSG efflux and MDA accumulation from paraquat-perfused lungs and suggest that increased turnover of the GSHPx reaction protects paraquat-perfused lungs from lipid peroxidation.

Animals↗
PubMed1984

Serum fibronectin is elevated during normobaric and hyperbaric oxygen exposure in rats.

Serum fibronectin concentration was measured by immunoelectrophoresis in rats exposed to 1 atmosphere absolute (ata) of oxygen for 24 to 72 h and at 30-min intervals during 1 to 5 h of exposure to 4 ata O2. At 1 ata O2, there was a progressive increase in serum fibronectin, which became significant at 48 h and was 2.5 times the control value by 72 h (p less than 0.01). At 4 ata O2, the rise in serum fibronectin was significant at 2 h, and was followed by an accelerated rate of increase to 5 h, at which time serum fibronectin concentration was 1.75 times the control value (p less than 0.05). By SDS-polyacrylamide gel electrophoresis and crossed immunoelectrophoresis, there was no evidence of fragmentation of fibronectin. This study demonstrated a progressive increase in serum fibronectin in the oxygen-exposed rat. The magnitude and course of the increase suggest increased synthesis and secretion of intact fibronectin molecules.

Animals↗
PubMed1981

Growth of the turtle Chrysemys scripta under constant controlled laboratory conditions.

The purpose of this study was to determine 1) growth of the turtle shell and change in weight under constant controlled laboratory conditions and 2) whether under these constant conditions there were seasonal changes. Fifty unfed refrigerated eight-week-old hatchling turtles Chrysemys scripta were received in October and maintained in aquaria with 16 hours of artificial light and eight hours of darkness, at 24-27 degrees C and a humidity of 30% and fed twice weekly. Gross linear measurements of the width and length of the plastron and carapace, and total body weights, were taken at eight weeks and thereafter at about six-week intervals. During the two-year period the mean increase of the plastron length was from 30.79 +/- 0.19 mm to 68.32 +/- 1.58 mm, plastron width from 24.23+/- 0.20 mm to 50.43 +/- 1.03 mm; carapace length from 32.47 +/- 0.24 mm to 75.21 +/- 1.82 mm, carapace width from 31.81 +/- 0.28 mm to 67.12 +/- 1.29 mm, and body weight from 6.94 +/- 0.15 gm to 80.63 +/- 5.02 gm. Calculated daily percent changes revealed that strongly correlated with its value at 786 days of age. No seasonal differences in growth were noted between the summer and winter periods when turtles would enter winter dormancy in certain natural environments. Environmental factors are reflected in the growth of the turtle.

Animals↗
PubMed1978

Ventilation in an aquatic and a terrestrial chelonian reptile.

1. Periods of breath-holding are interrupted by episodes of continuous breathing in the aquatic turtle Pelomedusa subrufa, whereas single breaths and short periods of breath-holding alternate in the terrestrial tortoise Testudo pardalis. This implies that partial pressures of O2 and CO2 in expired air are stable in Testudo in contrast to cyclic fluctuations in Pelomedusa. 2. In spite of this, air convection requirements (VA/VO2, ml BTPS/ml STPD) are not significantly different for the two species (25.4 in Testudo, 27.3 in Pelomedusa), and differences in weight-specific ventilation between the mean body weight. 3. The end-tidal PCO2 in Pelomedusa (mean 15.2 mmHg) is lower than in Testudo (mean 24.7 mmHg), which reflects aquatic CO2 elimination in Pelomedusa. 4. In Testudo, the time course of ventilation correlates with the time course of increase of end-tidal PCO2 during CO2 breathing, but no simple relationship is evident between ventilation and blood PCO2 in Pelomedusa. 5. In both species tidal volume as well as respiratory frequency increase approximately in proportion to the end-tidal PCO2, although the response to 6% CO2 breathing could be less than expected from extrapolation of the responses to 2 and 4% CO2. Both species also increase ventilation during hypoxia, but hyperoxia depresses ventilation.

Animals↗