Family-based transmission disequilibrium test (TDT) and case-control association studies reveal surfactant protein A (SP-A) susceptibility alleles for respiratory distress syndrome (RDS) and possible race differences.

A key cause of respiratory distress syndrome (RDS) in the prematurely born infant is deficiency of pulmonary surfactant, a lipoprotein complex. Both low levels of surfactant protein A (SP-A) and SP-A alleles have been associated with RDS. Using the candidate gene approach, we performed family-based linkage studies to discern linkage of SP-A to RDS and identify SP-A susceptibility or protective alleles. Moreover, we performed case-control studies of whites and blacks to detect association between RDS and SP-A alleles. Transmission disequilibrium test (TDT) analysis revealed that the frequency of transmission (from parent to the offspring with RDS) of alleles 6A(2) and 1A(0) and of 1A(0)/6A(2) haplotype in RDS was increased, whereas transmission of alleles 1A(5) and 6A(4) and of haplotype 1A(5)/6A(4) was decreased. Extended TDT analysis further strengthened the observations made. The case-control studies showed that in whites or blacks with RDS the frequencies of specific genotypes, 1A(0) and 6A(2) or 1A(0), were increased, respectively, but the frequency of specific 6A(3) genotypes was increased in certain white subgroups and decreased in blacks. Regression analysis revealed gestational age (GA) and 6A(3) genotypes are significant factors in blacks with RDS. In whites with RDS, GA and antenatal steroids are important factors. The data together indicate linkage between SP-A and RDS; certain SP-A alleles/haplotypes are susceptibility (1A(0), 6A(2), 1A(0)/6A(2)) or protective (1A(5), 6A(4), 1A(5)/6A(4)) factors for RDS. Some differences between blacks and whites with regard to SP-A alleles may exist.

DNA degradation in the kidney of folic acid-treated guinea pigs.

Previous investigators agree on the increased DNA synthesis and destruction of tissues caused by folic acid (FA) administered parenterally. This study aims to clarify whether DNA degradation due to the destruction of cells and nuclei precedes DNA synthesis following FA administration. Forty guinea pigs were divided into four groups: group 1, contained 10 controls; in group 2, ten animals received intraperitoneally 300 mg/kg of body wt FA; in group 3, ten animals received FA and 12 h later frusemide intramuscularly in a dose of 7 mg/kg body wt; and finally in group 4, ten animals received frusemide as in group 3. FA produced necrosis of the epithelial cells of the convoluted tubules as the detection of the beta-aminoisobutyric acid end product of DNA and thymine catabolism indicated. Frusemide administered in group 3 had a favourable effect on the acute renal failure induced by FA.

Synthesis of some new thienyl and 1,3-thiazolyl-aminoketones with anti-inflammatory activity.

Eight thienyl and 1,3-thiazolyl-aminoketones were synthesised and tested as anti-inflammatory agents. pKa and log P were theoretically calculated. The compounds were tested for antioxidant activity, as hydroxyl radical scavengers, as superoxide anion scavengers and for their ability to interact with 1,1-diphenyl-2-picryl hydrazyl stable free radical (DPPH). The effects of the synthesised compounds on inflammation were studied using the carrageenan induced mice paw oedema model. Both anti-inflammatory and antioxidant activities depended on some structural characteristics of the synthesised compounds.

Cellular interactions in pulmonary oxygen toxicity in vitro: II. Hyperoxia causes adult rat lung fibroblast cultures to produce apparently autocrine growth factors.

Mixed lung cell cultures from adult rats were exposed to 21, 50, or 95% O2. In the presence of serum, actively dividing mixed lung cell cultures acutely exposed to 50% O2 had a reduced rate of cell division, while 95% O2 caused growth arrest and cell death. In the absence of serum, 95% O2 again caused cell death, while cell numbers were stable for up to 1 week in 21 or 50% O2. These cells adapted to the nonlethal 50% O2 environment by a 48% increase in superoxide dismutase activity, which was not seen with the lethal 95% O2 environment. Under serum-free conditions, conditioned medium collected from cells exposed to 50% O2, but not 21% O2, contained transferable factors that increased DNA synthesis in other nonhyperoxic mixed lung cell cultures. In a series of studies to determine both the source and target cell types for this growth factor(s), the lung fibroblast was found to release an apparently autocrine growth stimulator, with an apparent molecular weight of approximately 96,000, over the first 3 days of 50% O2 exposure. A separate apparently autocrine growth stimulator, with molecular weight approximately 7000-9000, was released over the second 3 days of a 6-day exposure to 50% O2.

Hormonal and local factors influence antioxidant enzyme activity of rat fetal lung cells in vitro.

Monolayer cultures of fetal rat mixed lung cells respond to sublethal concentrations (50%) of oxygen by a reduced growth rate. Exposure to 95% O2 causes growth arrest and cell loss. In the presence of serum the addition of dexamethasone (5.5 nM), tri-iodothyronine (5.5 nM), or insulin (5 microU/ml) appeared to increase the cytotoxicity of 95% O2. Under growth-arrested conditions, in the absence of serum or elevated O2 concentrations, all three agents influence cellular antioxidant enzyme activities. Dexamethasone (0.055 nM) increased CuZn superoxide dismutase activity by 72% and glutathione peroxidase activity by 94%. Triiodothyronine (5.5 nM) increased CuZn superoxide dismutase activity 93%. Insulin (5 microU/ml) increased CuZn superoxide dismutase activity 90%, and catalase activity 58%. Dexamethasone, but not tri-iodothyronine or insulin, seems to have a protective effect against subsequent acute hyperoxia under serum-free conditions. Local non-hormonal factors may also influence lung cell responses to acute increases in oxygen concentrations, since cells acutely exposed to 50% or 95% O2 release a transferable factor(s) into their culture medium which increases antioxidant enzyme activities of non-hyperoxic lung cells.