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J F Burke

Publications and source records attributed to J F Burke.

At least 37 records · Page 2Linked to original sources

The lymnaea cardioexcitatory peptide (LyCEP) receptor: a G-protein-coupled receptor for a novel member of the RFamide neuropeptide family.

A novel G-protein-coupled receptor (GRL106) resembling neuropeptide Y and tachykinin receptors was cloned from the mollusc Lymnaea stagnalis. Application of a peptide extract from the Lymnaea brain to Xenopus oocytes expressing GRL106 activated a calcium-dependent chloride channel. Using this response as a bioassay, we purified the ligand for GRL106, Lymnaea cardioexcitatory peptide (LyCEP), an RFamide-type decapeptide (TPHWRPQGRF-NH2) displaying significant similarity to the Achatina cardioexcitatory peptide (ACEP-1) as well as to the recently identified family of mammalian prolactin-releasing peptides. In the Lymnaea brain, the cells that produce egg-laying hormone are the predominant site of GRL106 gene expression and appear to be innervated by LyCEP-containing fibers. Indeed, LyCEP application transiently hyperpolarizes isolated egg-laying hormone cells. In the Lymnaea pericardium, LyCEP-containing fibers end blindly at the pericardial lumen, and the heart is stimulated by LyCEP in vitro. These data confirm that LyCEP is an RFamide ligand for GRL106.

Action Potentials↗

A rabbit model for metabolic studies after burn injury.

BACKGROUND: A rabbit burn model was developed and characterized, which will allow conduct of repeated, noninvasive and more sophisticated in vivo metabolic studies to explore the pathophysiology of burn injury, owing to its larger blood volume and tissue mass than the rat. MATERIALS AND METHODS: A 20% body surface, full thickness burn was applied to the backs of six anesthetized rabbits by immersion into a boiling-water bath for 10 s, followed by resuscitation with saline. Resting energy expenditure (REE) was measured daily in pre- and postburn periods. Whole body protein kinetics were evaluated using L-[1(-13)C]leucine tracer, on the preburn and the third postburn day. Fasting plasma glucose was also measured. RESULTS: A significant elevation of REE began on the second postburn day and reached 34 +/- 8% above the preburn level (P < 0.05, paired t test) on the third postburn day. The fasting plasma leucine flux and oxidation were significantly elevated from their preburn levels (both P < 0.05), indicating an accelerated proteolysis and a more negative body protein balance (P < 0.05); however, the rate of whole body protein synthesis did not differ significantly pre- and postburn injury. Fasting plasma glucose also increased (P < 0.001). on the third postburn day. The burn scar remained intact during the study, without any sign of infection. CONCLUSIONS: The metabolic changes observed in this animal model can be attributed to burn injury per se and they mimic those for flow phase in burn patients. This rabbit burn model should be suitable for exploring mechanistic aspects of the burn-induced changes in metabolism and nutrient balance.

Animals↗

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Computer Communication Networks↗

Molecular cloning and characterization of an invertebrate homologue of a neuropeptide Y receptor.

Neuropeptide Y is an abundant and physiologically important peptide in vertebrates having effects on food intake, sexual behaviour, blood pressure and circadian rhythms. Neuropeptide Y homologues have been found in invertebrates, where they are very likely to play similar, important roles. Although five neuropeptide Y-receptor subtypes have been identified in mammals, none has been reported from invertebrates. Here we describe the cloning of a neuropeptide Y-receptor from the brain of the snail Lymnaea stagnalis. The identity of the receptor was deduced by expressing the neuropeptide Y-receptor-encoding cDNA in Chinese Hamster Ovary cells, which were subsequently challenged with size-fractionated Lymnaea brain extracts. An active peptide, selected on the basis of its ability to induce changes in cAMP levels, was purified to homogeneity, analysed by mass spectrometry and amino acid sequence determination, and turned out to be a Lymnaea homologue of neuropeptide Y.

Amino Acid Sequence↗

Both C3a and C3a(desArg) regulate interleukin-6 synthesis in human peripheral blood mononuclear cells.

Synthesis of complement components is part of the acute-phase response. Interleukin-6 (IL-6) is a critical mediator of the acute-phase response during infections and injuries. Plasma levels of C3a and IL-6 have been proposed as prognostic indicators in sepsis and trauma. The effects of C3a and C3a(des)Arg on IL-6 gene expression and protein production in human peripheral blood mononuclear cells (PBMC) were investigated. Neither C3a nor C3a(des)Arg alone induced detectable IL-6 protein or mRNA levels. However, C3a and C3a(des)Arg affected endotoxin-induced IL-6 synthesis in a dose-dependent manner. In nonadherent PBMC, C3a or C3a(des)Arg suppressed, while in adherent PBMC, C3a or C3a(des)Arg enhanced IL-6 protein and mRNA levels. These results suggest that C3a and C3a(des)Arg may provide a control mechanism of acute-phase responses by enhancing IL-6 synthesis in adherent monocytes at local inflammatory sites and by inhibiting IL-6 synthesis in circulating monocytes.

Cell Adhesion↗

Neural modulation of gut motility by myomodulin peptides and acetylcholine in the snail Lymnaea.

Families of peptide neuromodulators are believed to play important roles in neural networks that control behaviors. Here, we investigate the expression and role of one such group of modulators, the myomodulins, in the feeding system of Lymnaea stagnalis. Using a combination of in situ hybridization and antibody staining, expression of the myomodulin gene was confirmed in a number of identified behaviorally significant neuronal types, including the paired B2 motor neurons. The B2 cells were shown to project axons to the proesophagus, where they modulate foregut contractile activity. The presence of the five myomodulin peptide structures was confirmed in the B2 cells, the proesophagus, and the intervening nerve by mass spectrometry. Using a sensitive cell culture assay, evidence that the B2 cells are cholinergic also is presented. Application of four of the five myomodulin peptides to the isolated foregut increased both contraction frequency and tonus, whereas the main effect of acetylcholine (ACh) application was a large tonal contraction. The fifth myomodulin peptide (pQIPMLRLamide) appeared to have little or no effect on gut motility. Coapplication of all five myomodulin peptides gave a greater increase in tonus than that produced by the peptides applied individually, suggesting that corelease of the peptides onto the gut would produce an enhanced response. The combined effects that the myomodulin peptides and ACh have on foregut motility can mimic the main actions of B2 cell stimulation.

Acetylcholine↗

A human gene encoding morphine modulating peptides related to NPFF and FMRFamide.

FMRFamide-related peptides have been isolated from both invertebrates and vertebrates and exhibit a wide range of biological effects in rats. We show here that in humans 2 FMRFamide-related peptides are encoded by a single gene expressed as a spliced mRNA. The larger predicted peptide (AGEGLNSQFWSLAAPQRFamide) differs from the peptide isolated from bovines (AGEGLSSPFWSLAAPQRFamide) by the substitutions of 2 amino acids. The shorter predicted peptide (NPSF, SQAFLFQPQRFamide) is 3 amino acids longer than the bovine 8 amino-acid NPFF (FLFQPQRFamide) or the human NPFF peptide isolated from serum [5], suggesting that the encoded protein is subject to cleavage by a tripeptidyl peptidase or by a novel processing mechanism. On rat spinal cord, the larger peptide is indistinguishable in activity from the equivalent bovine peptide whereas the smaller extended peptide is inactive.

Action Potentials↗

Cloning, characterization, and expression of a G-protein-coupled receptor from Lymnaea stagnalis and identification of a leucokinin-like peptide, PSFHSWSamide, as its endogenous ligand.

Neuropeptides are known to be important signaling molecules in several neural systems of the pond snail Lymnaea stagnalis. Although the functions of these peptides have been studied in many neurons, the nature of the postsynaptic signal transduction is mainly unknown. The cloning and characterization of neuropeptide receptors in Lymnaea thus would be very valuable in further elucidating peptidergic pathways. Indirect evidence suggests that these neuropeptides operate via G-protein-coupled mechanisms indicating the presence of G-protein-coupled receptors as the initial postsynaptic targets. Here we describe the cloning of a neuropeptide receptor from Lymnaea and the isolation of an endogenous ligand. This peptide, PSFHSWSamide, belongs to the leucokinin family of peptides, and, thus, this Lymnaea receptor is the first example of a leucokinin-like neuropeptide receptor, representing a new subfamily of G-protein-coupled neuropeptide receptors.

Amino Acid Sequence↗

A 6-month study of low-dose recombinant human erythropoietin alone and in combination with androgens for the treatment of anemia in chronic hemodialysis patients.

Two previous short-term studies (12 weeks and up to 16 weeks) that used androgens to supplement recombinant human erythropoietin (rHuEPO) for the treatment of the anemia associated with end-stage renal disease showed divergent results. Both studies were limited by their brief duration, since the hematopoietic effect of androgens does not peak until 5 months. Therefore, we conducted a 6-month, prospective, randomized trial comparing low-dose rHuEPO alone and in combination with androgens for the treatment of the anemia of end-stage renal failure. Nineteen anemic chronic hemodialysis patients were randomized into two groups. Group A (n = 10) received 1,500 U rHuEPO intravenously three times a week for 26 weeks. Group B (n = 9) received the same dose of rHuEPO plus nandrolone decanoate 100 mg intramuscularly weekly. Baseline transferrin saturation, serum ferritin, intact serum parathyroid hormone, plasma aluminum, and hematocrit levels were not significantly different between the groups. At study completion, both groups showed a significant increase in mean hematocrit compared with baseline (group A: 24.8% +/- 1.4% to 28.3% +/- 2.8%, P = 0.003; group B: 25.1% +/- 1.5% to 33.2% +/- 4.5%, P = 0.001). The increase in hematocrit in the rHuEPO plus androgen-treated group was statistically greater than in the rHuEPO-alone group (8.2% +/- 4.4% v 3.5% +/- 2.8%; P = 0.012). With the exception of mild discomfort at the injection site, there were no significant side effects from nandrolone. We conclude that the combination of low-dose rHuEPO and nandrolone decanoate is effective treatment for the anemia of end-stage renal failure.

Anabolic Agents↗