Less severe retinopathy of prematurity induced by surfactant replacement therapy

To assess the effect of surfactant replacement therapy (SRT) on the prevalence and severity of retinopathy of prematurity (ROP), we compared data from 160 SRT-treated preterm infants with data from 230 historic controls. The prevalence of ROP was 30.6% in the treatment group and 23.4% in the control group. Severe ROP (stages 3-4) was seen in 6.1% of the infants with ROP in the treatment group and 20.3% of the ROP patients in the control group. Surfactant therapy had no influence on the prevalence of ROP (odds ratio 1.4, 95% confidence interval 0.797-2.459, p = 0.242). However, SRT was associated with a decreased risk for severe ROP, compared to mild ROP (odds ratio 0.226, 95% confidence interval 0.056-0.905, p = 0.036). These data suggest that SRT is associated with a decreased risk for severe ROP.     

Stimulation of oxidant production in alveolar macrophages by pollutant and latex particles

Air pollutant dusts as well as chemically defined particles were examined for their activating effect on oxidant production (O₂^? and H₂O₂) in guinea pig alveolar macrophages (AM). Oxidant production was measured as chemiluminescence of albumin-bound luminol. All particles examined stimulated the AM in a dose-dependent manner to different maximal levels of oxidant production. Amphibole asbestos samples were the most active of all agents studied. Various immune reactants as well as silica, metal-oxide-coated fly ash, polymethyl methacrylate beads, and chrysotile asbestos had intermediate activity, while fugitive dusts, polybead carboxylate microspheres, glass and latex beads, uncoated fly ash, and fiberglass had the lowest activity. In addition to direct stimulatory action on AM, particles also lowered the subsequent responsiveness of the cells to the bacterial peptide stimulant, N-formylmethionyl phenylalanine. This effect was only partially due to the cytotoxicity of the particles. While some relationship appeared to exist between stimulatory activity and cytotoxicity of the particles, the exact role of O₂^? in mediating cytotoxic effects is still open to question. Oxidant production in AM is a parameter which may be important in determining the pathological effects of particles as well as of materials adsorbed to their surfaces.     

Protein O-carboxylmethyltransferase in spermatozoa from normal and infertile men

In confirmation of several reports, suspensions of normal washed human spermatozoa exposed to a nonionic detergent exhibited considerable activity of the enzyme protein O-carboxylmethyltransferase (PCM), which catalyzes the methyl esterification of carboxyl groups of dicarboxylic amino acid residues in proteins. Various methods for assay of human spermatozoal PCM levels were evaluated, and some properties of the enzyme were studied. Normal human spermatozoa appear to be devoid of other types of protein methyltransferases that catalyze N-methylations of arginyl or lysyl residues in proteins. Spermatozoal PCM levels in infertile patients with motile sperm cells tended to be somewhat higher than those of normal control subjects, especially in those instances where the spermatozoal populations contained abnormally high proportions of immature forms of spermatozoa. Although totally immotile spermatozoa obtained from certain patients exhibited very low PCM activities (as recently reported by other investigators), in this study no invariant relationship between zero motility indexes and spermatozoal PCM was observed. These results are discussed in light of various current hypotheses regarding the functions of PCM in animal cells.     

Immediate toxicity of high multiplicities of Chlamydia psittaci for mouse fibroblasts (L cells).

One hour after suspensions of mouse fibroblasts (L cells) were exposed to 500 to 1,000 L-cell 50% infectious doses of Chlamydia psittaci (6BC), the L cells failed to attach to and spread out on solid substrates, phagocytosed polystyrene latex spheres at reduced rates, incorporated less [14C]isoleucine into protein, and had smaller soluble pools of nucleoside triphosphates. The infected L cells began to die at 8 h and were all dead by 20 h. Lower multiplicities of infection took correspondingly longer to kill the L cells. These effects of high multiplicities of C. psittaci on L cells will be referred to collectively as immediate toxicity. Similar effects were obtained with other strains of C. psittaci and C. trachomatis and with other cell lines. Ultraviolet-inactivated C. psittaci retained the ability to cause immediate toxicity, but heat-inactivated chlamydiae did not. C.psittaci cells had to be ingested by L cells before they were immediately toxic but, once they were phagocytosed, they did not need to multiply or to synthesize macromolecules in order to cause immediate injury to their hosts. Immediate toxicity was not the result of depression of energy metabolism, changes in the levels of intracellular cyclic nucleotides, or release of hydrolases from lysosomes. It was suggested that a lesion is produced in the plasma membrane of the L cell every time it ingests a chlamydial cell, that each act of ingestion produces an independent lesion, and that their injurious effects are additive. Thus, the more ingestion lesions there are, the faster the host cell dies. It was also suggested that induced phagocytosis, inhibition of lysosomal fusion, and death of mice and of cells in culture may all depend on a single activity of C. psittaci.     

Complications of abdominal exploration and splenectomy in staging children with Hodgkin's disease.

Until alternate diagnostic methods are discovered, the staging procedure seems to be the most reliable method to establish the presence or absence of abdominal involvement in Hodgkin's disease. Our experience with staging laparotomy in 22 children raises serious questions as to both the risk of operation and the prognostic value of a negative abdominal exploration. Routine use of the staging laparotomy may not be justified in clinical Stage IA patients with lymphocyte-predominant cell type. Because of the hazards and limitations of the staging procedure, vigorous attempts would seem to be indicated to identify subcategories of patients in whom the likelihood of intraabdominal involvement is so small as to negate the value of surgical staging.     

Acute ozone-induced differential gene expression profiles in rat lung

Ozone is an oxidant gas that can directly induce lung injury. Knowledge of the initial molecular events of the acute O3 response would be useful in developing biomarkers of exposure or response. Toward this goal, we exposed rats to toxic concentrations of O3 (2 and 5 ppm) for 2 hr and the molecular changes were assessed in lung tissue 2 hr postexposure using a rat cDNA expression array containing 588 characterized genes. Gene array analysis indicated differential expression in almost equal numbers of genes for the two exposure groups: 62 at 2 ppm and 57 at 5 ppm. Most of these genes were common to both exposure groups, suggesting common roles in the initial toxicity response. However, we also identified the induction of nine genes specific to 2-ppm (thyroid hormone-beta receptor c-erb-A-beta; and glutathione reductase) or 5-ppm exposure groups (c-jun, induced nitric oxide synthase, macrophage inflammatory protein-2, and heat shock protein 27). Injury markers in bronchoalveolar lavage fluid (BALF) were used to assess immediate toxicity and inflammation in rats similarly exposed. At 2 ppm, injury was marked by significant increases in BALF total protein, N-acetylglucosaminidase, and lavageable ciliated cells. Because infiltration of neutrophils was observed only at the higher 5 ppm concentration, the distinctive genes suggested a potential amplification role for inflammation in the gene profile. Although the specific gene interactions remain unclear, this is the first report indicating a dose-dependent direct and immediate induction of gene expression that may be separate from those genes involved in inflammation after acute O3 exposure.