Leukotrienes, thromboxane A2, and prostaglandins during systemic anaphylaxis in sheep.

We investigated the roles of eicosanoid mediators in acute systemic anaphylaxis in anesthetized sheep. Sheep were sensitized with dinitrophenylated Ascaris suum extract and were challenged with an intravenous injection of dinitrophenylated bovine serum albumin. During anaphylaxis, cyclooxygenase inhibitors eliminated the elevation of arterial plasma levels of thromboxane B2 and 6-ketoprostaglandin F 1 alpha but markedly elevated the levels of leukotriene E4 in lung lymph without significantly eliminating elevation of plasma levels of histamine.

Recombinant gene expression in pulmonary vascular endothelial cells: polarized secretion in vivo.

A unique, spontaneously immortalized rat pulmonary endothelial cell line was transfected with a human growth hormone (hGH) fusion gene generating a line of stably transfected cells that expresses high levels of hGH (Ec/XGH-1). These cells produced significant serum levels of hGH when implanted intraperitoneally, subcutaneously, or intravenously into nude mice. Implantation of Ec/XGH-1 cells under the renal capsule resulted in the formation of large cysts that contained concentrations of hGH that were several thousand times greater than those in serum assayed simultaneously from the same animals.

Dose-dependent effects of a pyridoquinazoline thromboxane synthetase inhibitor on arachidonic acid metabolites and hemodynamics during E. coli endotoxemia in anesthetized sheep.

We investigated the effects of a new pyridoquinazoline thromboxane synthetase inhibitor infused before administering Escherichia Coli endotoxin into 18 anesthetized sheep with lung lymph fistulas. In normal sheep increasing plasma Ro 23-3423 concentrations were associated with increased plasma levels of 6-keto-PGF1 alpha, a reduced systemic vascular resistance (SVR, r = -0.80) and systemic arterial pressure (SAP, r = -0.

Implantation of genetically engineered fibroblasts into mice: implications for gene therapy.

In a variety of human genetic diseases, replacement of the absent or defective protein provides significant therapeutic benefits. As a model for a somatic cell gene therapy system, cultured murine fibroblasts were transfected with a human growth hormone (hGH) fusion gene and cells from one of the resulting clonal lines were subsequently implanted into various locations in mice. Such implants synthesized and secreted hGH, which was detectable in the serum.

Induction of MHC-determined antigens in the lung by interferon-gamma.

Recombinant murine interferon-gamma (IFN-gamma) was administered in 6 to 9 daily intraperitoneal injections to B10.BR (H-2k) mice. The distribution of some selected class I and II major histocompatibility complex-determined antigens was localized by immunocytochemistry with the use of anti-H-2Kk and anti-IAk monoclonal antibodies and avidin-biotin-peroxidase in unfixed, frozen lungs for light microscopy and in fixed lungs for electron microscopy.

Cyclooxygenase blockade elevates leukotriene E4 production during acute anaphylaxis in sheep.

We examined changes in the levels of eicosanoids in blood and pulmonary lymph of anesthetized sheep undergoing acute anaphylaxis. Within 1-3 min of intravenous antigenic challenge of previously sensitized sheep, there were approximately 7-30-fold elevations in mean arterial plasma levels of thromboxane B2 and 6-ketoprostaglandin F1 alpha, respectively, as measured by RIA. Negligible changes in levels of these cyclooxygenase products were found in both nonsensitized sheep and in sensitized sheep treated with indomethacin before antigenic challenge.

Regulation of human insulin gene expression in transgenic mice.

Insulin is a polypeptide hormone of major physiological importance in the regulation of fuel homeostasis in animals (reviewed in refs 1,2). It is synthesized by the beta-cells of pancreatic islets, and circulating insulin levels are regulated by several small molecules, notably glucose, amino acids, fatty acids and certain pharmacological agents. Insulin consists of two polypeptide chains (A and B, linked by disulphide bonds) that are derived from the proteolytic cleavage of proinsulin, generating equimolar amounts of the mature insulin and a connecting peptide (C-peptide).

Widespread and selective induction of major histocompatibility complex-determined antigens in vivo by gamma interferon.

gamma Interferon (IFN-gamma) caused remarkable increases in class I (H-2Kk) and class II (I-Ak) antigens throughout the body by 6-9 d. Heart, kidney, and adrenals showed increases of 4-8 times their previous levels of class I antigen content, while the pancreas and small intestine increased 13-17-fold. Lesser increases were found in spleen, liver, and lung, which showed higher resting antigenic potency.

Cannulation of the proximal aorta during long-term membrane lung perfusion.

Prolonged extracorporeal oxygenator support for acute respiratory failure is a clinical reality. Recent experience with 4 patients has demonstrated an advantage in delivery of saturated blood to the root of the aorta during venoarterial (VA) bypass. We have been able to perfuse the heart and bilateral cerebral hemispheres by advancing the tip of a large perfusion cannula to the aortic root from the common femoral artery.