Human umbilical cord blood progenitor cells are attracted to infarcted myocardium and significantly reduce myocardial infarction size.

We are investigating the effects of human umbilical cord blood mononuclear progenitor cells (HUCBC) for the treatment of acute myocardial infarction because human cord blood is a readily available and an abundant source of primitive cells that may be beneficial in myocardial repair. However, there is currently no scientific consensus on precisely when to inject stem/progenitor cells for the optimal treatment of acute myocardial infarction. We used an in vitro assay to determine the attraction of infarcted rat myocardium at 1, 2, 2.

Cytotoxicity of heavy metals on primary cultured alveolar type II cells.

The lung is the primary target organ of airborne heavy metal-induced toxicity. The aims of this study were to investigate differential acute lung cytotoxicity caused by heavy metals using a primary culture of alveolar type II cells and to establish an in vitro assessment model of lung toxicity. The cytotoxicity of heavy metals was determined by measuring the lactate dehydrogenase release and (51)chromium release from lyzed cells.

Detection of hydroxyl radicals upon interaction of ozone with aqueous media or extracellular surfactant: the role of trace iron.

As part of a study on mechanisms modulating ozone-induced surfactant perturbations, we used the electron paramagnetic resonance (EPR) spin trapping technique to determine the type and origin of radicals generated following interaction of ozone with aqueous solutions and cell-free bronchoalveolar lavage fluid (BAL) fractions. All aqueous media were exposed to ozone at 25 degrees C with or without added chelator, 1 mM diethylenetriaminepentaacetic acid, and spintrap, 100 mM 5,5'-dimethyl-1-pyrroline-1-oxide (DMPO). Exposure of distilled water to 0.

Depletion of surfactant tubular myelin with pulmonary dysfunction in a rat model for acute endotoxemia.

Although prolonged Gram-negative sepsis with high permeability alveolar edema, a well documented cause of adult respiratory distress syndrome, has been shown to result in surfactant alterations, the effects of acute endotoxemia on the lung surfactant system are largely unknown. In this study, lethal endotoxemia (> 80% mortality at 24 h) resulting in severe, rapid leukopenia with progressive thrombocytopenia was achieved through intraperitoneal injection of adult Fischer 344 rats with 3.5 mg of Escherichia coli endotoxin/kg.

Acute ozone-induced lung injury in rats: structural-functional relationships of developing alveolar edema.

As part of a study on the effects of acute ozone stress on the lung surfactant system, we correlated morphometric, biochemical, and functional indices of lung injury using male rats exposed to 3 ppm ozone for 1, 2, 4, and 8 hr. Evaluation of lung mechanics, using the Pulmonary Evaluation and Diagnostic Laboratory System, revealed a significant decrease in dynamic lung compliance (ml/cmH2O/kg) from a control value of 0.84 +/- 0.

Immunocytochemical localization of lysozyme and surfactant protein A in rat type II cells and extracellular surfactant forms.

Using immunogold labeling of fixed, cryosubstituted tissue sections, we compared the distribution of lysozyme, an oxidant-sensitive lamellar body protein, with that of surfactant protein A (SP-A) in rat Type II cells, extracellular surfactant forms, and alveolar macrophages. Morphometric analysis of gold particle distribution revealed that lysozyme and SP-A were present throughout the secretory and endosomal pathways of Type II cells, with prominent localization of lysozyme in the peripheral compartment of lamellar bodies. All extracellular surfactant forms were labeled for both proteins with preferential labeling of tubular myelin and unilamellar vesicles.

Recovery of lung pyridine nucleotides following acute exposure of adult and aged rats to ozone.

Male, pathogen-free Fischer 344 rats aged 6 and 24 mo were exposed to 1.5 or 3.0 ppm for 8 h and recovery rates of diphosphonucleotides (NAD+ and NADH) and triphosphonucleotides (NADP+ and NADPH) were measured and compared to controls.

Lysozyme is an ozone-sensitive component of alveolar type II cell lamellar bodies.

Exposure of rats to 3 ppm ozone for up to 8 h results in significant changes in lamellar bodies, the surfactant storing organelles of type II cells. We have previously shown that a 14 kDa lamellar body protein is decreased as early as 4 h after the onset of ozone exposure. We have isolated this ozone-sensitive protein from rat lung lamellar bodies and identified it as lysozyme by immunochemical methods, as well as by its amino acid composition, N-terminal amino acid sequence and bacteriolytic activity.

Ozone stress initiates acute perturbations of secreted surfactant membranes.

To identify the early changes of surfactant secretion in response to acute oxidant stress, the authors evaluated morphometrically centriacinar type II cells and lavage fluid surfactant forms obtained immediately after exposure of adult rats to 3 ppm ozone for 1, 2, 4, or 8 hours. In this model, the rat lung develops progressive alveolar edema with significant elevation of lavage fluid proteins at 2 to 8 hours of exposure. Ultrastructural changes in type II cells at 1 and 2 hours included enhanced lamellar body (LB) fusion with significant increase in the compound and vacuolated LB compartments.

Surfactant-associated glycoproteins accumulate in alveolar cells and secretions during reparative stage of hyaline membrane disease.

Surfactant-associated (SA) glycoproteins are lung-specific proteins produced in the human lung by alveolar type II cells and Clara cells. The distribution of these proteins was studied immunohistochemically in lung tissue obtained postmortem from 12 stillborn fetuses and 49 infants with hyaline membrane disease (HMD). By 21 weeks of gestation, SA glycoproteins were detected in the fetal alveolar epithelium and within Clara cells.

Ozone-induced alterations of lamellar body lipid and protein during alveolar injury and repair.

Alveolar Type II cells in the rat respond to severe, acute ozone injury (3 ppm ozone for eight hours) by increasing their intracellular pool of surfactant; however, the newly stored surfactant is abnormal in composition. Lamellar bodies isolated between 24 and 96 hours after ozone exposure contained significantly more cholesterol in relation to phosphatidylcholine than did controls. By contrast, the cholesterol content of surfactant isolated from alveolar lavage remained unchanged throughout an 8-day post-ozone period.

Sequential changes of lamellar body hydrolases during ozone-induced alveolar injury and repair.

Lamellar body hydrolases in acutely damaged and regenerating type II cells were determined using an established rat model with well-defined stages of bronchiolo-alveolar injury and repair. Lamellar bodies were isolated from control and ozone-exposed (3.0 ppm for 8 hours) adult male rats by sucrose density gradient centrifugation and analyzed for their content of six different lysosomal hydrolases.

Prenatal relationship of surfactant lipid and protein constituents in infants with respiratory distress syndrome: a preliminary communication.

The prenatal relationships between surfactant disaturated phosphatidylcholine (DSPC) and surfactant-associated proteins of preterm infants with respiratory distress syndrome (RDS) have not been well documented. In the present study we measured the concentration of DSPC, surfactant glycoproteins (GP), and surfactant proteolipids (PLP) in amniotic fluids obtained within 6 hours prior to delivery of 16 newborn infants with gestational ages between 27 and 32 weeks. In control infants of 27-32 weeks gestation without RDS, the values of DSPC, GP, and PLP per milliliter of amniotic fluid were 20 +/- 2.

Age-related difference in bioenergetics of lung and heart mitochondrial from rats exposed to ozone.

Bioenergetics of isolated lung and heart mitochondria from adult and aged rats were examined in the presence of glutamate (NAD-linked substrate) or succinate + rotenone (FAD-linked substrate) following ozone exposure (3.0 ppm, 8 hr). In controls, several differences were observed between adults and aged in both organ preparations.

Ozone-induced lamellar body responses in a rat model for alveolar injury and repair.

Exposure of adult rats to 3 ppm ozone for 8 hours results in diffuse alveolar damage with well-defined sequential stages of bronchiolo-alveolar injury and repair. This model is characterized by acute pulmonary edema showing high concentration of lavage fluid protein that is maximally elevated at 24 hours with return to control level at recovery (96 hours). Using techniques that enable optimal preservation of lamellar body ultrastructure, it was demonstrated morphometrically that expansion of the vacuolated lamellar body (LB) compartment is an early, transient LB response of the type II cell to acute injury.

Lung surfactant-associated glycoproteins and proteolipids in human amniotic fluids evaluated by dot immunobinding assays.

Dot immunobinding assays for the quantitation of two classes of proteins associated with lung surfactant phospholipids in human amniotic fluid are described. With the use of these assays it was determined that the two classes of surfactant proteins accumulate in the amniotic fluid at the same rate. The concentrations of disaturated phosphatidylcholine and the surfactant-associated proteins are less closely correlated.

Age-related difference in pulmonary response to ozone.

Acute exposure to 1.5 ppm O3 produced different responses in adult and aged rat lungs. Total triphosphonucleotides were only slightly decreased in adult animals, but were markedly decreased in aged animals.

Distribution and subcellular localization of surfactant-associated glycoproteins in human lung.

Human surfactant contains lung-specific, high molecular weight glycoproteins which are composed of disulfide-linked 34-kilodalton peptide subunits. We prepared antibodies to both isolated HMW glycoproteins and 34-kilodalton peptides and tested the antisera for specificity with immunochemical procedures. In the present study we have investigated the cellular distribution and subcellular localization of these glycoproteins in surgically excised human lung tissue with or without type II cell hyperplasia.

Pregnancy-induced hypertension: development of a model in the pregnant primate (Papio anubis).

Experiments were performed on two groups of pregnant baboons. In the experimental group, the subrenal aortic blood flow was reduced by 58% of its original value at 100 days of gestational age. In the control group, the blood flow was measured but not restricted.

Immunologically related multimeric forms of 30-40 kDa peptides associated with lung surfactant in various mammalian species.

A comparative study of lung surfactant associated proteins was undertaken to determine which mammalian species would best serve as models for investigating alterations of the human lung surfactant system. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of purified surfactants in the presence of dithiothreitol revealed that surfactant invariably contains at least one peptide with molecular weight of 30 000-40 000. In the absence of disulfide reducing agents, the above peptides were in the form of high-molecular-weight proteins (greater than 400 kDa) in primates and cat, whereas in dog, rat and rabbit, the protein was a 72 kDa dimer.

Efficacy of S-2441, a synthetic oligopeptide, in a rat model for gram-negative bacteremia.

In vitro effects of S-2441, H-D-Pro-Phe-Arg-NH-Heptyl, include potent anti-bradykinin activity and broad-spectrum inhibition of serine proteases involved in the coagulation cascade. In this study, rats infused with 7.8 X 10(8) viable Escherichia coli were treated either with saline (group A) or with intravenous (0.