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Biomedical subjects

J Torday

Publications and source records attributed to J Torday.

12 recordsLinked to original sources
PubMed2003

Hyperoxia augments pulmonary lipofibroblast-to-myofibroblast transdifferentiation.

Bronchopulmonary dysplasia (BPD) remains a major cause of morbidity and mortality in premature infants, and despite many advances, its pathophysiology remains incompletely understood. Exposure of the premature lung to hyperoxia is commonly implicated in its pathogenesis. However, the exact link between hyperoxia and BPD, particularly its role in the generation of myofibroblasts, the signature cell-type for lung fibrosis, is undetermined. There is increasing evidence that lipid interstitial fibroblasts play an important role in injury-repair mechanisms in various organ systems. This study demonstrates that exposure to hyperoxia augments the transdifferentiation of pulmonary lipofibroblasts to myofibroblasts. Fetal rat lung fibroblasts (FRLF) from embryonic (e) (term = e22) 18 and e21 gestation were studied. After initial culture in minimum essential medium (MEM) and 10% fetal bovine serum (FBS) in 21% O2 / 5% CO2 at 37 degrees C, FRLF were maintained in MEM and 10%FBS at 37 degrees C under control (21% O2 / 5% CO2) and under experimental conditions (24-hour exposure to 95% O2 /5% CO2) at passage (P) 1 and 5. At each passage, cells were allowed to attach to 100 cm2 culture dishes and grow in 21% O2 before being subjected to the experimental conditions. Passage 1 and 5 cells were analyzed for the expression of well-characterized lipogenic and myogenic markers based on semiquantitative competitive RT-PCR (for parathyroid hormone-related protein receptor [PTHrPR]), adipose differentiation related protein (ADRP), and alpha smooth muscle actin (alphaSMA), triglyceride uptake, and leptin assay. Serial passage and maintenance of cells in 21% O2 resulted in a significant decrease in the expression of the lipogenic markers from P1 to P5, spontaneously. This decrease was greater for e18 than for e21 FRLF. However, exposing cells to 95% O2 augmented the loss of the lipogenic markers and gain of the myogenic marker from P1 to P5 in comparison to cells maintained in 21% O2. These changes were also greater for e18 vs e21 lipofibroblasts. These changes in mRNA expression were accompanied by decreased triglyceride uptake and leptin secretion on exposure to hyperoxia. These results suggest that exposure to hyperoxia (95% O2) augments the transdifferentiation of pulmonary lipofibroblasts to myofibroblasts.

Actins↗
PubMed1999

Syntaxin 1A is transiently expressed in fetal lung mesenchymal cells: potential developmental roles.

Lung development is a complex process in which epithelial-mesenchymal interactions play a key role. A conserved secretory apparatus, the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex, is essential for exocytosis in many cell types. Syntaxins, located on the terminal plasma membrane (T-SNAREs), are a critical component of the secretosomal complex involved in vesicular docking, fusion, and exocytosis. We analyzed syntaxin 1A mRNA and protein in fetal rat lung ontogeny, demonstrating peak expression on about day 19 of embryonic development, immediately preceding type II pneumocyte differentiation. Syntaxin 1A is predominantly expressed by lipofibroblasts, which are required for bombesin-like peptide-induced surfactant phospholipid synthesis (choline uptake) by isolated type II cells. In organ cultures, anti-syntaxin 1A antibody HPC-1 blocks choline uptake both at baseline and when induced by bombesin-like peptide or dexamethasone. HPC-1 also promotes thymidine uptake in parallel in a dose-dependent fashion. These observations indicate a potential role for syntaxin 1A during fetal lung development, possibly through involvement in secretion of mesenchymal cell-derived factors that induce terminal type II cell differentiation.

Animals↗
PubMed1995

Metabolism and fate of neutral lipids of fetal lung fibroblast origin.

Fetal rat lung fibroblasts characteristically increase their triacylglycerol (TG) stores during development. Both fibroblasts and alveolar type II (TII) cells can synthesize TG de novo, but only fibroblasts can absorb TG from culture medium, and retain the TG in a stable state. When fibroblasts pre-labelled with [3H]triolein are recombined with TII cells in organotypic culture the radiolabel appears in TII cell disaturated phosphatidylcholine (disatPC). When fibroblasts are preloaded with increasing amounts of TG there is a commensurate increase in TII cell disatPC following organotypic culture. Comparison of [3H]triacylglycerol and [14C]glucose incorporation into type II cell phospholipids revealed preferential use of TG for the surface-active phospholipids disatPC (10-fold greater) and phosphatidylglycerol (23-fold greater). These in vitro data suggest that fibroblasts provide lipid substrate for TII cell surfactant phospholipid synthesis.

Animals↗
PubMed1992

Association of intrauterine cigarette smoke exposure with indices of fetal lung maturation.

The timing of fetal lung maturation is regulated, at least in part, by the fetal endocrine milieu, which in turn may be influenced by environmental factors. Infants of smoking mothers are at decreased risk of neonatal respiratory distress syndrome (RDS), a disease of lung immaturity. Therefore, we measured fetal lung maturity and cigarette smoke exposure to determine whether the lungs of smoke-exposed fetuses mature more quickly and whether changes in maturation are associated with alterations in amniotic fluid (AF) cortisol levels. Amniotic fluid lecithin-sphingomyelin ratio (L/S) and saturated phosphatidylcholine levels were used as measures of lung maturity, while smoke exposure was assessed by measuring AF cotinine, a stable nicotine metabolite. Lung maturity was more advanced in smoke-exposed fetuses as measured by saturated phosphatidylcholine (P = .02) and L/S ratio (P = .04). Smoke-exposed fetuses attained sufficient lung maturity to minimize the risk of RDS approximately 1 week earlier than in unexposed fetuses. The AF of smoke-exposed fetuses also had higher levels of free, conjugated, and total cortisol. Acceleration of lung maturation in smoke-exposed fetuses is consistent with the decreased risk of RDS in infants of smoking mothers. Maternal smoking could influence lung maturation by directly or indirectly enhancing the production and/or secretion of cortisol. Despite the decreased risk of RDS, the developmental process by which smoke-exposed fetuses attain early pulmonary maturity is abnormal and may contribute to the decreased lung function and increased respiratory illness noted in infants of smoking mothers.

Adult↗
PubMed1982

The effects of vaginal contamination on two pulmonary phospholipid assays.

During the examination to confirm premature rupture of membranes, amniotic fluid unavoidably contaminated with cervical mucus and other vaginal debris can often be obtained from the posterior fornix. This study was undertaken to determine the validity of phospholipid measurements on contaminated amniotic fluid. Fifteen paired amniocentesis and vaginally contaminated samples of amniotic fluid were used to measure the lecithin/sphingomyelin ratio and saturated phosphatidylcholine (SPC). The amniocentesis specimens had a mean L/S ratio of 3.94 +/- 0.22 (mean +/- SEM), and contaminated samples had a mean L/S ratio of 3.82 +/- 0.29 (mean +/- SEM). Paired t-test was unable to demonstrate a significant difference (p greater than 0.10), and the correlation coefficient between paired L/S samples was r = 0.79. SPC measurements on the amniocentesis fluid had a mean value of 1,243 microgram/DL +/- 217 (mean +/- SEM) as compared to the contaminated-specimen mean of 1.375 micrograms/dl 223 (mean +/- SEM). Paired t-test likewise was unable to demonstrate a significant difference (p greater than 0.10), and the correlation coefficient between paired SPC samples was r = 0.93. Within the design of this study, we were unable to demonstrate a statistically significant effect of brief vaginal contamination on the measurement of the L/S ratio or SPC.

Amniocentesis↗
PubMed1979

Saturated phosphatidylcholine in amniotic fluid and prediction of the respiratory-distress syndrome.

The lecithin/sphingomyelin (L/S) ratio in amniotic fluid is widely used to predict the risk of respiratory-distress syndrome. However, the results are unreliable if the specimen is contaminated or obtained during a complicated pregnancy. We therefore compared the predictive value of the L/S ratio with that of the concentration of saturated phosphatidylcholine (SPC) in 322 amniotic-fluid samples, 75 per cent of which were contaminated or obtained during complicated pregnancies or both. A positive result is one that predicted the development of respiratory-distress syndrome, taken as an L/S ratio equal to or less than 2/1 or an SPC below 500 mug per deciliter. The respiratory-distress syndrome was correctly predicted in 25 of 45 cases (55.5 per cent) with L/S ratios equal to or less than 2/1, and in 35 of 42 cases (82 per cent) with SPC's less than 500 mug per deciliter. When L/S ratios were greater than 2/1, there were 13 of 277 (4.7 per cent) false negatives, and when SPC's were above 500 mug per deciliter, there were three of 280 (1.1 per cent) false negatives. We conclude that determination of SPC is both more specific and more sensitive as a predictor of the respiratory-distress syndrome than the techniques currently in use.

Acetone↗