HemaMax™, a recombinant human interleukin-12, is a potent mitigator of acute radiation injury in mice and non-human primates.

HemaMax, a recombinant human interleukin-12 (IL-12), is under development to address an unmet medical need for effective treatments against acute radiation syndrome due to radiological terrorism or accident when administered at least 24 hours after radiation exposure. This study investigated pharmacokinetics, pharmacodynamics, and efficacy of m-HemaMax (recombinant murine IL-12), and HemaMax to increase survival after total body irradiation (TBI) in mice and rhesus monkeys, respectively, with no supportive care. In mice, m-HemaMax at an optimal 20 ng/mouse dose significantly increased percent survival and survival time when administered 24 hours after TBI between 8-9 Gy (p<0.

Expression of intracellular filament, collagen, and collagenase genes in diabetic and normal skin after injury.

Reports have shown differences in gene expression in the skin of diabetic and normal mice both at baseline and after injury. Cluster analysis identified distinct expression patterns within intermediate filaments and extracellular proteins. This report addresses the effect of diabetes and injury on the expression of keratin-associated proteins, keratin complexes, procollagen, and collagenase (matrix metalloproteinase; MMP) genes.

Effect of NorLeu3-A(1-7) on scar formation over time after full-thickness incision injury in the rat.

Previous studies have shown that the angiotensin peptide NorLeu3-A(1-7) accelerates dermal healing and reduces scar formation. In this report, the effect of this peptide on scar formation is more fully delineated. The effect of surgical day, time after injury, and observer on the clinical appearance of the incision were determined.

Synergistic effects of co-administration of angiotensin 1-7 and Neupogen on hematopoietic recovery in mice.

Purpose: Angiotensin 1-7 [A(1-7)] is a seven amino acid peptide that has been shown to increase the proliferation of epidermal stem cells after dermal injury and the number of hematopoietic progenitors in the bone marrow of myelosuppressed mice. In this study, the effect of combining A(1-7) with Neupogen on hematopoietic recovery and bone marrow progenitors was evaluated.

Materials And Methods: Intravenous 5-fluorouracil (5FU) was administered to induce myelosuppression.

Polar clustering of the chemoreceptor complex in Escherichia coli occurs in the absence of complete CheA function.

Bacterial chemotaxis requires a phosphorelay system initiated by the interaction of a ligand with its chemoreceptor and culminating in a change in the directional bias of flagellar rotation. Chemoreceptor-CheA-CheW ternary complexes mediate transduction of the chemotactic signal. In vivo, these complexes cluster predominantly in large groups at the cell poles.

TNP-ATP and TNP-ADP as probes of the nucleotide binding site of CheA, the histidine protein kinase in the chemotaxis signal transduction pathway of Escherichia coli.

The interaction of CheA with ATP has important consequences in the chemotaxis signal transduction pathway of Escherichia coli. This interaction results in autophosphorylation of CheA, a histidine protein kinase. Autophosphorylation of CheA sets in motion a chain of biochemical events that enables the chemotaxis receptor proteins to communicate with the flagellar motors.

Genetic analysis of the catalytic domain of the chemotaxis-associated histidine kinase CheA.

Escherichia coli cells express two forms of CheA, the histidine kinase associated with chemotaxis. The long form, CheA(L), plays a critical role in chemotactic signal transduction by phosphorylating two chemotaxis-associated response regulators, CheY and CheB. CheA(L) first autophosphorylates amino acid His-48 before its phosphoryl group is transferred to these response regulators.

pH dependence of CheA autophosphorylation in Escherichia coli.

Chemotaxis by cells of Escherichia coli and Salmonella typhimurium depends upon the ability of chemoreceptors called transducers to communicate with switch components of flagellar motors to modulate swimming behavior. This communication requires an excitatory pathway composed of the cytoplasmic signal transduction proteins, CheAL, CheAS, CheW, CheY, and CheZ. Of these, the autokinase CheAL is most central.

Modulation of postsurgical cell infiltration and fibrinolytic activity by tolmetin in two species.

Previous studies showed that tolmetin administered as a single instillate intraperitoneally at the end of surgery can reduce adhesion formation. In this report, studies on the mechanism by which this occurs were conducted. The effects of tolmetin administered intraperitoneally on red (RBC) and white blood cell (WBC) number, macrophage and polymorphonuclear neutrophil infiltration, protease activity in lavage fluid, and the fibrinolytic activity of a biopsy of nonsurgical and traumatized peritoneal sidewall were examined.

Peritoneal lavage fluid protease levels after in vivo administration of tolmetin in hyaluronic acid.

Tolmetin sodium in a hyaluronic acid carrier (tolmetin-HA) was previously shown to reduce adhesion formation and alter the rate and extent to which wound repair cells enter the peritoneal cavity after surgery. In this study, the effect of tolmetin-HA on the levels of protease activities present in lavage fluid from the peritoneal cavity was determined at various postsurgical times. Collagenase activity in peritoneal lavage fluid was suppressed at 6, 12, and 24 hr after administration of tolmetin-HA in comparison to control.

In vivo administration of tolmetin in hyaluronic acid modulates protease levels in postsurgical macrophage-conditioned media.

Tolmetin sodium in a hyaluronic acid carrier (tolmetin-HA) was previously shown to reduce adhesion formation and alter the kinetics and levels of cellular influx into the peritoneal cavity after surgery. In this study, the effect of tolmetin-HA on the level of protease activity in macrophage-conditioned media was determined. The level of collagenase activity in macrophage-conditioned media was suppressed at 12 and 24 h after administration of tolmetin-HA.

Protease and protease inhibitor secretion by postsurgical macrophages following in vitro exposure to tolmetin.

Tolmetin sodium was shown previously to reduce the level of adhesions formed after peritoneal surgery. In addition, when tolmetin was administered to rats at the time of surgery, the level of macrophage activity (phagocytosis, superoxide anion production and tumoricidal activity) was elevated. In this study, the level of neutral protease activity in the culture supernatant of peritoneal macrophages from postsurgical rabbits.

Mechanism of the modulation of murine peritoneal cell function and mast cell degranulation by low doses of malathion.

Malathion is a widely used organophosphate pesticide that modulates immune function at noncholinergic doses. Previous studies showed that this alteration in immune function was the result of enhanced macrophage function. In the present study, the effects of low doses of purified malathion (as low as 0.

Kinetics of interleukin-1 and tumor necrosis factor secretion by rabbit macrophages recovered from the peritoneal cavity after surgery.

Macrophages play a crucial role in wound healing after surgical injury, both as scavenger cells responsible for wound debridement and as cells that secrete soluble factors such as interleukin-1 (IL-1) and tumor necrosis factor (TNF). IL-1 and TNF alter many of the biological activities of cells that appear in postsurgical wounds. In this study, we determined the kinetics of IL-1 and TNF production by rabbit macrophages harvested from postsurgical peritoneal exudate (postsurgical macrophages) at several time points after peritoneal surgery.

The effect of intraperitoneal administration of sodium tolmetin-hyaluronic acid on the postsurgical cell infiltration in vivo.

Intraperitoneal administration of sodium tolmetin-hyaluronic acid reduced the formation of adhesions at early postsurgical time points. In addition, at 6, 48, 72, and 96 hr following surgery, there was a significant reduction in the number of red blood cells (RBC) recovered from peritoneal lavage. This effect was not the result of fluid or viscous solution in the peritoneal cavity since intraperitoneal administration of Ringer's lactate or Hyskon (a 32% solution of Dextran 70) did not affect RBC recovery.

Follicle regulatory protein: a novel marker for granulosa cell cancer patients.

Follicle regulatory protein (FRP) is secreted by the granulosa cell of the ovary and plays a role in modulating follicle development. A dual epitope immunoassay using two murine monoclonal antibodies, isotype IgG1 (raised against porcine FRP), in tandem was developed to measure FRP in serum. The levels of FRP in the serum of women with granulosa cell tumors, normal, menstruating women, and postmenopausal women were determined.

Modulation of macrophage protease activity by acute administration of O,O,S trimethyl phosphorothioate.

Previous studies showed that acute administration of O,O,S trimethyl phosphorothioate (OOS-TMP), a contaminant in malathion, acephate and fenitrothion, led to increases in metabolic activities, such as, secretion of interleukin 1 and nonspecific esterase, of splenic and peritoneal macrophages. In this report, the effect of OOS-TMP administration on the levels of the neutral proteases, elastase, collagenase and plasminogen activator, in cultures supernatants of peritoneal and splenic macrophages is presented. Acute administration of OOS-TMP elevated collagenase levels only at day 3 following treatment with 10 or 20 mg/kg OOS-TMP.

Modulation of respiratory burst activity and mitogenic response of human peripheral blood mononuclear cells and murine splenocytes and peritoneal cells by malathion.

Previous studies showed that acute administration of noncholinergic doses of malathion in vivo elevated the humoral immune and mitogenic responses but did not alter the generation of the cytotoxic T lymphocyte (CTL) response to alloantigen of splenocytes from treated mice. However, in vitro exposure to malathion suppressed the generation of a CTL response. In this study, the effects of in vivo and in vitro (with and without an NADPH-regenerating liver enzyme system) exposure to malathion on the mitogenic responses of murine splenocytes or respiratory burst activity of peritoneal cells were examined.

Kinetics of interleukin-1 secretion by murine macrophages recovered from the peritoneal cavity after surgery.

Macrophages play a central role in wound healing after surgical injury possibly through the secretion of soluble factors like interleukin-1 (IL-1). IL-1 has many biological activities which regulate most of the cell types that appear in postsurgical wounds. In this study, we determined the levels of IL-1 production by murine macrophages harvested from postsurgical exudate at several time points after standardized peritoneal surgery.

Effects of acute administration of O,O,S-trimethyl phosphorothioate on the respiratory burst and phagocytic activity of splenic and peritoneal leukocytes.

An impurity in malathion, O,O,S-trimethyl phosphorothioate (OOS-TMP), was previously shown to be immunosuppressive. The immune cell type which induced immune suppression caused by OOS-TMP at 24 hrs after administration was found to be splenic macrophages. Further characterization of macrophages from OOS-TMP treated mice indicated that OOS-TMP led to macrophage differentiation.

Effects of tolmetin sodium dihydrate on normal and postsurgical peritoneal cell function.

Recent studies utilizing intraperitoneal (i.p.) administration of NSAIDs to rabbits after surgical injury to the parietal peritoneum demonstrated macrophage involvement.

Influence of H-2 haplotypes on poly IC induction of xanthine oxidase and poly IC induced decreases in P-450 mediated enzyme activities.

Polyriboinosinic-polyribocytidylic acid (poly IC), a potent interferon inducer, induced xanthine oxidase 24 hours after treatment with 5 mg/kg ip to different degrees among four H-2 congenic mice (P less than 0.05): B10 (H-2b: 236 +/- 27% of the control value) greater than B10.RIII (H-2r: 171 +/- 29%) = B10.