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Biomedical subjects

R C Murphy

Publications and source records attributed to R C Murphy.

At least 217 records · Page 12Linked to original sources
PubMed1981

Tetraene and pentaene leukotrienes: selective production from murine mastocytoma cells after dietary manipulation.

A neoplastic mast cell tumor was grown in mice which had been raised since birth on a diet enriched with eicosapentaenoic acid. Intact harvested mastocytoma cells were stimulated with calcium ionophore A23187 to produce lipoxygenase products from the polyunsaturated fatty acids liberated from the cellular membranes. Leukotriene B4, B5, C4, and C5 were isolated and characterized by HPLC retention time, ultraviolet absorption spectrometry and mass spectrometry. The arachidonic acid content of the mast cell tumor lipids was altered from 9.2 to 3.9 mole % while eicosapentaenoic acid increased from 0.5 to 4.5 mole % in response to the fish oil-supplemented diet. The relative amounts of arachidonic and eicosapentaenoic acids (3.9 and 4.5 mole % respectively) were associated with similar amounts of LTB4 and LTB5 synthesized by the cells. These results suggest that the epoxide leukotriene (LIA) derivative can be made efficiently from either arachidonic or eicosapentaenoic acids when both are present in cellular lipids. In contrast, the ratio of LTC4 to LTC5 (10 to 1) indicates that the reaction of LTA with glutathione may be critically dependent upon the structure of the unsaturated fatty acid with the ratio of LTC4/LTB4 (2.0) more than 10 times greater than that (0.16) for LTC5/LTB5.

Animals↗
PubMed1981

Prostacyclin produced by the pregnant uterus in the dog may act as a circulating vasodepressor substance.

Uterine production of PGI2 (prostacyclin) was quantitated in late pregnant dogs to evaluate if PGI2 could act as circulating vasodepressor substance in pregnancy. In five anesthetized, laparotomized dogs, the uterine venous plasma concentration of 6-keto PGF1 alpha (the in vitro hydrolysis product of PGI2) was 6.7 +/- 1.9 ng/ml and the arterial plasma concentration was 2.6 +/0 0.8 ng/ml. In four nonpregnant female dogs the arterial plasma concentration of 6-keto PGF1 alpha was consistently below 0.2 ng/ml. In eight pregnant dogs we also evaluated the ability of the pregnant uterus to inactivate PGI2 by comparing the hypotensive response to increasing doses of PGI2 infused into the uterine artery to the hypotensive response to increasing doses of PGI2 infused into the inferior vena cava. In addition, the effect of PGI2 infused into the uterine artery on uterine blood flow and intraamniotic fluid pressure was evaluated. The dose-response curves of intrauterine and intravenous PGI2 in causing systemic hypotension were identical suggesting that the pregnant uterus does not inactivate infused PGI2. Intrauterine PGI2 had no consistent effect on uterine hemodynamics although it did increase intraamniotic fluid pressure significantly. These data demonstrate that the pregnant uterus has the capacity to produce large quantities of PGI2 which is not inactivated in the uterus and therefore can appear in the arterial blood to exert a systemic vasodepressor effect.

Animals↗
PubMed1981

Electrophysiological response of cerebellar Purkinje neurons to leukotriene D4 and B4.

The biological effects of leukotrienes B4 and D4, two recently characterized products of arachidonic acid metabolism, were studied on the guinea-pig ileum in vitro and on rat cerebellar Purkinje cells in vivo. Leukotriene D4 induced contraction of the ileum and a prolonged excitation of Purkinje cells. Both of these effects were antagonized by the "slow reacting substance" end-organ antagonist, FPL 55712. Leukotriene B4 had no central electrophysiological effects at the doses used and no effects on the guinea-pig ileum at doses below 0.2 microM. Taken together with previous studies, these data suggest that leukotrienes with slow reacting substance activity may modulate the excitability of central neurons as well as peripheral smooth muscle tone.

Action Potentials↗
PubMed1980

Prostaglandin production by intact isolated gastric parietal cells.

An enriched population of isolated gastric parietal cells was obtained from canine gastric mucosa. Parietal cells incubated with [14C]arachidonic acid produced radiolabelled PGF2 alpha, PGE2, PGD2 and 6-keto PGF1 alpha (acid hydrolysis product of PGI2). The prostaglandin synthesis was inhibited by indomethacin. Prostaglandin production, as measured by gas chromatography-mass spectrometry demonstrated that PGF2 alpha was produced in the highest quantity followed by PGE2 and 6-keto PGF 1 alpha. This demonstrates that isolated prietal cells are capable of producing prostaglandins. Since prostaglandins have a potent effect on gastric acid secretion, local prostaglandin synthesis could modulate parietal cell function.

Animals↗
PubMed1980

Leukotriene C elicits a prolonged excitation of cerebellar Purkinje neurons.

Leukotriene C-1 (LTC-1), a recently characterized potent agonist in bioassays for the slow reacting substance of anaphylaxis (SRS-A), was tested for electrophysiological effects on central neurons. LTC-1 consistently elicited a unique prolonged excitatory action on cerebellar Purkinje (P) cells when administered locally by pressure ejection from a multibarreled micropipette. This excitation could be reversed by subsequent pressure ejection of FPL 55712 (FPL), a SRS-A end-organ antagonist. Prior application of FPL prevented the LTC-1-induced responses altogether. Heat-inactivated LTC-1 had no effect on P cell discharge. These data suggest that LTC-1, as has been recently found with many other peripherally acting neurohormones, may also function to regulate excitability of central neurons.

Action Potentials↗
PubMed1979

New procedure for isolation of amino acids based on selective hydrolysis of trimethylsilyl derivatives.

A rapid procedure for the isolation of amino acids from physiological fluids by class separation suitable for gas chromatographic and gas chromatographic-mass spectrometric analysis is described. A physiological fluid such as plasma is adjusted to pH 2 and extracted with diethyl ether to remove organic acids and neutrals. After precipitation of proteins with trichloroacetic acid, the aqueous plasma is dried and derivatized by trimethylsilylation. Organic compounds like sugars and amino acids are rendered soluble in petroleum ether leaving inorganic salts when the soluble layer is transferred. Separation of sugars from amino acids is achieved by taking advantage of the different rates of aqueous hydrolysis of the trimethylsilyl (TMS) derivatives. Mixing the petroleum ether extract with a small volume of water results in two phases. The petroleum ether layer contains TMS-Sugar constituents of plasma and the aqueous layer contains free amino acids and amines. This procedure was used to isolate L-dopa, 3-O-methyldopa and tyrosine from human plasma in a quantitation assay using 18O-labelled amino acids and gas chromatography-mass spectrometry.

Amino Acids↗
PubMed1979

Synthesis and back exchange of 18O labeled amino acids for use as internal standards with mass spectrometry.

Amino acids with two oxygen-18 atoms in the carboxyl moiety can be synthesized easily from the amino acids and H2 18O through exchange. The exchange conditions are simply solution of the amino acid (1-4 mg) in acidic H2 18O (0.1-0.2ml) followed by heating at 60-70 degrees C for several days. Eighteen oxygen-18 amino acids with incorporations typically greater than 90% 18O2 have been achieved and characterized by mass spectrometry. The exchange conditions do not lead to racemization. Loss of the oxygen-18 atoms through back exchange was found to be pH and temperature dependent, but yet slow enough to allow these isotopimers to be used in most studies as internal standards for quantitative mass spectrometry. The 18O carboxylic atoms were not exchanged upon incubation in plasma for three days at 37 degrees C, PH 7.4. The exchange reaction is general enough to allow the simultaneous synthesis of several [18O] amino acids.

Amino Acids↗
PubMed1979

Leukotriene C: a slow-reacting substance from murine mastocytoma cells.

Murine mastocytoma cells treated with calcium ionophore A23187 produced a slow-reacting substance (SRS) that caused guinea pig ileum to contract. The response was reversed by the SRS antagonist FPL 55712. On the basis of isotope incorporation experiments, spectroscopy, and chemical degradations, the SRS was identified as a cysteine-containing derivative of 5-hydroxy-7,9,11,14-icosatetraenoic acid. This amino acid was attached in thioether linkage at C-6. The SRS is structurally related to previously identified epoxy and dihydroxy metabolites of arachidonic acid in leukocytes. A common feature is the presence of a conjugated triene, and the name "leukotriene" has been introduced to designate these compounds. Leukotriene A (5,6-epoxy-7,9,11,14-icosatetraenoic acid) is an intermediate in the formation of leukotriene B (5,12-dihydroxy-6,8,10,14-icosatetraenoic acid) and is proposed to be a precursor also of leukotriene C, which is the SRS identified here.

Animals↗
PubMed1979

Gastric carcinoid and gastric carcinoma. Morphologic correlates of survival.

The clinical and histologic material of 140 patients with gastric carcinoma resected more than 5 years previously was examined and 10 tumors with a previous diagnosis of adenocarcinoma showed atypical carcinoid differentiation. The clinical extent of tumors in this carcinoid group was similar to that of the ordinary gastric adenocarcinoma. The 5-year survival was 15% in patients with adenocarcinoma and 70% in those with carcinoid (P less than 0.01 by chi 2 test). These findings indicate the need to distinguish atypical carcinoids from ordinary gastric adenocarcinoma. The most commonly encountered histologic feature suggesting carcinoid, and leading to confirmatory histochemical studies, was found to be regular interlacing trabeculae of tumor and fibrovascular stroma.

Adenocarcinoma↗
PubMed1978

Mass spectrometry and gas chromatography of trimethylsilyl derivatives of catecholamine related molecules.

The trimethylsilyl derivatives of approximately 50 compounds related in structure to biogenic catecholamines have been studied in terms of their gas chromatographic and mass spectrometric behavior. The electron impact mass spectra of the trimethylsilyl derivatives of 3,4-dihydroxyphenylethylamine, 3,4-dihydroxyphenylacetic acid and 3,4-dihydroxyphenylethylamine and deuterated isotopic variants were compared to determine fragmentation characteristics of the amines, acids, alcohols and amino acids within this class of compounds. Analysis of shifts in the masses of major diagnostic ions in the spectra of structural analogs of these compounds has shown that structural modification of the structure can be identified and localized within these molecules. The gas chromatographic characteristics of these derivatives are reported, in terms of methylene unit values.

Catecholamines↗
PubMed1978

Application and evaluation of limited mass monitoring with a gas chromatograph mass spectrometer computer system.

The technique of scanning a preselected set of ions employing a combined gas chromatography mass spectrometer computer system has been investigated to ascertain the advantages and disadvantages of such a procedure. This technique allows one to determine gas chromatographic retention data with with a high degree of precision and accuracy, in rapid temperature programming operation, due to shortening of the mas spectral scanning interval. Signal-to-noise ratio in ion abundance recordings can be enhanced by increasing the dwell time for as many as 100 ions without lenghtening the scanning interval. The utility of such an approach was demonstrated by analysis of complex mixtures isolated form human urine and cerebrospinal fluid.

Carboxylic Acids↗