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Biomedical subjects

M Goerig

Publications and source records attributed to M Goerig.

At least 37 records · Page 2Linked to original sources
PubMed1989

Increased bioavailability of enzymes of eicosanoid synthesis in hepatic and extrahepatic tissues after portacaval shunting.

Metabolites of arachidonic acid have been attributed to severe circulatory, metabolic and hormonal alterations in patients with chronic liver disease. In order to study changes of the tissue-specific availability of enzymes of eicosanoid synthesis, we used portacaval-shunted rats, as this model exhibits many clinical and biochemical similarities to patients suffering from cirrhosis of the liver. Microsomal mass and maximal velocity of prostaglandin H synthase, the initial enzyme of prostaglandin synthesis, were markedly and permanently increased after shunting in both hepatic and extrahepatic tissues as compared to those of sham-operated rats. Maximal velocity of thromboxane synthase and prostacyclin synthase, two more peripheral enzymes of the arachidonic acid cascade, were tissue-specifically enhanced, whereas the apparent affinities (Km) remained unchanged. Determination of 5-lipoxygenase activity in tissue preparations disclosed a preferential increase in the liver, lung and renal cortex after portacaval shunting. Furthermore, exposure to endotoxin closely mimicked the shunting-induced changes. These results suggest that after portacaval shunting and possibly in patients with advanced liver disease, profound abnormalities at the level of local enzyme expression might play a pathophysiologically important role in the control of eicosanoid synthesis.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Early reversible induction of leukotriene synthesis in chicken myelomonocytic cells transformed by a temperature-sensitive mutant of avian leukemia virus E26.

We used chicken myelomonocytic cells transformed by a temperature-sensitive mutant of the myb/ets oncogene-containing avian leukemia virus E26 to study the regulation of leukotriene (LT) synthesis during macrophage differentiation. Cells exposed to arachidonic acid and the Ca2+ ionophore 23187 produced up to 180 times more LTs at the nonpermissive temperature (42 degrees C) than at the permissive temperature (37 degrees C). Induction of LT synthesis was detectable within 2 hr after temperature shift, whereas conventional macrophage markers became evident after 2-3 days. N-Formylmethionylleucylphenylalanine, opsonized zymosan, and complement factor C5a induced LT synthesis in temperature-sensitive mutant-transformed cells only when the cells were maintained at 42 degrees C, and this effect was blocked by pertussis toxin. When cells were kept at 42 degrees C for 48 hr and then shifted back to 37 degrees C to induce retrodifferentiation, LT synthesis rates declined within 8 hr and reached near control values within 36 hr. Retrodifferentiation also led to decreased LT synthesis in response to N-formylmethionylleucylphenylalanine, opsonized zymosan, and C5a. These results indicate that activation of the 5-lipoxygenase pathway is a very early event in the macrophage differentiation pathway that is directly or indirectly controlled by the temperature-sensitive v-myb protein.

Animals↗
PubMed1988

Evidence for coordinate, selective regulation of eicosanoid synthesis in platelet-derived growth factor-stimulated 3T3 fibroblasts and in HL-60 cells induced to differentiate into macrophages or neutrophils.

We used Swiss 3T3 fibroblasts stimulated with platelet-derived growth factor and HL-60 cells induced to differentiate into macrophages or neutrophils to study the regulation of prostaglandin and leukotriene synthesis. Addition of platelet-derived growth factor to quiescent 3T3 fibroblasts led within 4 h to a dramatic and preferential increase in prostacyclin synthesis from endoperoxide prostaglandin H2, and microsomal assays showed a strong platelet-derived growth factor-dependent increase in the maximal velocities (Vmax) of both prostaglandin H synthase and prostacyclin synthase. In contrast, addition of phorbol ester to HL-60 cells to induce differentiation into macrophages led within 4 h to a strong and preferential increase in thromboxane synthesis from prostaglandin H2, and microsomal assays disclosed a major rise in Vmax for both prostaglandin H synthase and thromboxane synthase. No comparable changes occurred in HL-60 cells that were differentiating into neutrophils, though upregulation of 5-lipoxygenase pathway enzymes occurred in both differentiation systems. Actinomycin D and cycloheximide prevented the appearance of all of these enzymes of eicosanoid synthesis in all three model systems. Thus, the distinctive patterns of eicosanoid synthesis that are seen in replicating fibroblasts and in differentiating macrophages and neutrophils appear to depend on a coordinate, selective upregulation of several enzymes of eicosanoid biosynthesis that is specific for each cell system.

Animals↗
PubMed1988

[Joseph O'Dwyer--a pioneer in endotracheal intubation and pressure respiration].

The oro- and nasotracheal intubation has been developed into one of the most important techniques in anaesthesiology. Originally, intubations were carried out for overcoming acute diphteric airway obstruction in children. As late as the end of the 19 century, the only life saving chance was to perform tracheotomy. Although the technique for this operation at that time was well developed, it was very often impossible to save the life of those moribund patients. The famous American paediatrician Joseph O'Dwyer re-initiated the technique of intubation and his excellent results became great success and promoted world-wide use, although it was a well-known procedure at that time. His intubation method - also called the O'Dwyer-Method-was first published in the N. Y. Medical Journal as "Intubation of the Larynx" 100 years ago. Working together with the surgeon George Fell, O'Dwyer designed an apparatus, for artificial respiration. As Fell-O'Dwyer Apparatus it was widely used in cases of asphyxia, - even in those caused by overdosage of anaesthetics. Further developments of the apparatus permitted positive pressure ventilation and the combination with a funnel for narcotics increased the repertory of anaesthesiological possibilities.

History, 19th Century↗
PubMed1988

Effects of nicotine on eicosanoid synthesis of differentiating human promyelocytic leukemia cells.

We studied the conversion of arachidonic acid or prostaglandin H2 into eicosanoids in promyelocytic leukemia cells (HL-60) that were differentiating into macrophages or neutrophils. Our results indicate that several enzymes of eicosanoid synthesis are coordinately and differentially upregulated early in the neutrophil and macrophage differentiation pathways. They also provide evidence for a preferential upregulation of thromboxane synthase in the macrophage differentiation pathway that contrasts with a preferential upregulation of enzymes of the 5-lipoxygenase pathway during neutrophil differentiation. Nicotine at 100 nM selectively inhibited the formation of thromboxane in HL-60 cells induced to differentiate into macrophages. Nicotine therefore alters the pattern of activity of the eicosanoid-synthesizing enzymes in HL-60 cells undergoing macrophage differentiation.

Arachidonic Acid↗
PubMed1987

sn-1,2-Diacylglycerols and phorbol diesters stimulate thromboxane synthesis by de novo synthesis of prostaglandin H synthase in human promyelocytic leukemia cells.

We studied the regulation of thromboxane (TX) synthesis in promyelocytic leukemia cells during macrophage differentiation. Cells treated with 12-O-tetradecanoylphorbol-13-acetate (TPA) showed rates of TXB2 synthesis from exogenous arachidonic acid that exceeded that of control cells by a factor of up to 81. Cells treated with sn-1,2-dioctanoylglycerol (diC8) showed similarly high TXB2 synthesis rates when diC8 was added concomitantly with a subthreshold concentration of TPA or when given in multiple doses. These activities depended on de novo synthesis of prostaglandin H (PGH) synthase because: microsomal PGH synthase activity showed large increases in Vmax values, and mass measurements of PGH synthase revealed the presence of PGH synthase in differentiating cells whereas the enzyme was undetectable in control cells. These results indicate that macrophage differentiation is associated with stimulation of TXB2 synthesis that requires both activation of protein kinase C and de novo synthesis of PGH synthase.

Arachidonic Acid↗
PubMed1986

Low density lipoprotein receptor-dependent prostaglandin synthesis in Swiss 3T3 cells stimulated by platelet-derived growth factor.

We studied the effects of human plasma lipoproteins on the synthesis of prostaglandin (PG) E2 in Swiss 3T3 mouse fibroblasts. Quiescent cells, maintained in medium deficient in both platelet-derived growth factor (PDGF) and lipoproteins, synthesized less than 8 ng of PGE2 per 10(6) cells per 22 hr, and this rate did not change in response to the addition of lipoproteins. In contrast, PDGF-stimulated cells, incubated in medium deficient in lipoproteins, synthesized 45-110 ng of PGE2 per 10(6) cells during the same period of time, and this rate increased 2- to 5-fold in the presence of added low density lipoproteins (LDL). This stimulatory effect of LDL seemed to depend on LDL receptor-mediated binding, uptake, and degradation of the lipoproteins because: both LDL and very low density lipoproteins were active, whereas high density lipoproteins were not; low concentrations of LDL were effective; the effect of native LDL was blocked by acetylation of the LDL; PDGF increased both the expression of LDL receptors and the cellular uptake of LDL; chloroquine blocked the effect of LDL but not that of exogenous arachidonic acid. These results provide evidence that the LDL pathway is critically linked to PG synthesis in PDGF-stimulated cells.

Acetylation↗
PubMed1986

[The history of tracheotomy. I].

Tracheotomy is one of the oldest operations. Indications for and methods of the operative technique are reported already from the ancient times. The following outline - subdivided in three parts - tries to give a comprehensive survey of the development of tracheotomy throughout the centuries. The first part is concerned with the role of tracheotomy in antiquity, in Greek and Roman medicine and in the medicine of the Arabians at the turn of the millennium according to our time. The first tracheotomy is said to have been performed by Asklepiades of Bythinien, who lived in Rome during the last century before the Christian era. The question whether tracheotomy would be of use or not was highly controversal in the following centuries. There were advocates of the operation (for example Antyllus, Paulus von Aegina), but there were strict antagonists, too (for example Aretaeus). In Arabian medicine finally, tracheotomy had an important rank in theory, but probably it had never been performed in humans. The second part of this paper is occupied with the establishment of tracheotomy in the medicine of the European middle ages. Despite many ethical reservations, it became generally accepted as the last live-saving method in certain syndromes. Protagonists of the method included Ambroise Paré, Thomas Fienus, Hieronymus Fabricius ab Aquapendente, Julius Casserius, and Johannes Scultetus. A new method of performing tracheotomy, the opening of the trachea with the use of a trocar, was first described by Sanctorius Sanctorius (1561-1636). The third part of this outline describes the development of the method of tracheotomy in the last 400 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Ethics, Medical↗
PubMed1985

[Eicosanoids and phospholipases].

Prostaglandins, thromboxanes, and leukotrienes have been implicated to play an important role in physiology as well as in a growing list of pathophysiologic conditions. These oxidation products of 8.11.14-eicosatrienoic-, 5.8.11.14.-eicosatetraenoic-, and 5.8.11.14.17.-pentaenoic acids have been collectively designated eicosanoids. Many clinically important diseases are associated with altered eicosanoid biosynthesis. Furthermore, a series of hormones are known to induce acutely formation of eicosanoids, suggesting a crucial role in a multitude of tissue responses including phenomena such as secretion, platelet aggregation, chemotaxis, and smooth muscle contraction. The major precursor for the eicosanoids seems to be 5.8.11.14.-eicosatetraenoic acid or arachidonic acid. Virtually all of arachidonic acid however is present in esterified form in complex glycerolipids. Since cyclooxygenase and the lipoxygenases utilize arachidonic acid in its free form, a set of acylhydrolases is required to liberate arachidonic acid from membrane lipids before eicosanoid formation can occur. It became only recently apparent that a minor acidic phospholipid, phosphatidylinositol, comprising only 5%-10% of the phospholipid mass in mammalian cells, plays an important role in arachidonic acid metabolism. Phosphatidylinositol--after phosphorylation to phosphatidylinositolphosphate and phosphatidylinositolbisphosphate--appears to be hydrolyzed by specific phospholipases C generating 1-stearoyl-2-arachidonoyl-diglyceride. Diglyceride serves as substrate for diglyceride lipase to form monoglyceride and free fatty acid. Alternatively diglyceride is phosphorylated by diglyceride kinase yielding phosphatidic acid, which is believed to be reincorporated into phosphatidylinositol. In addition to phosphatidylinositol phosphatidylcholine, phosphatidylethanolamine and phosphatidic acid may contribute to arachidonic acid release. These phospholipids are substrates for phospholipases A2 generating free arachidonic acid and the respective lysophospholipid. Understanding of the biochemistry of arachidonic acid liberation may be critical in developing strategies of pharmacological intervention in a variety of pathological conditions.

Animals↗
PubMed1985

Cell cycle-dependent changes in arachidonic acid and glycerol metabolism in Swiss 3T3 cells stimulated by platelet-derived growth factor.

Quiescent Swiss 3T3 cells stimulated to divide by human platelet-derived growth factor (PDGF) were used to investigate cell cycle-dependent changes in arachidonic acid, stearic acid, and glycerol metabolism. PDGF at 12 ng/ml stimulated incorporation of labeled arachidonic and stearic acid into phosphatidic acid and phosphatidylinositol within 60 min. With similar kinetics PDGF stimulated glycerol incorporation into phosphatidic acid and phosphatidylinositol indicating early growth factor-dependent stimulation of de novo phosphatidylinositol synthesis. This early effect of PDGF was specific for the phosphatidylinositol synthesis pathway since no comparable changes were noted in other glycerolipids. After a lag of 4-6 h, PDGF strongly stimulated arachidonic acid incorporation into triacylglycerol: at 6 h, arachidonate radioactivity in triacylglycerol exceeded that in phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol. This effect of PDGF was not associated with de novo triacylglycerol synthesis since no increase in the rate of glycerol incorporation into this lipid was noted. Finally, PDGF stimulated incorporation of glycerol into all major phospholipids and triacylglycerol during S-phase. These results disclose three novel effects of PDGF on glycerolipid metabolism in Swiss 3T3 cells: 1) early selective activation of the phosphatidylinositol synthesis pathway; 2) delayed strong stimulation of arachidonic acid incorporation into triacylglycerol; and 3) late induction of de novo phosphatidylcholine, phosphatidylethanolamine, and triacylglycerol synthesis. These PDGF effects are likely to play important roles in phosphatidylinositol metabolism, membrane biosynthesis, and fatty acid turnover in rapidly growing cells.

Animals↗
PubMed1985

Human platelet-derived growth factor stimulates prostaglandin synthesis by activation and by rapid de novo synthesis of cyclooxygenase.

Human platelet-derived growth factor (PDGF) stimulated prostaglandin (PG) E2 synthesis in the cell cycle of Swiss 3T3 cells at two distinct time intervals, with a first plateau within 10 min and a second plateau within 2-4 h after addition of PDGF. At 4 h, the concentration of PGE2 in PDGF-stimulated cultures exceeded the quiescent control cells by a factor of 10-15. Quiescent cells incubated with up to 16 microM exogenous arachidonic acid (AA) synthesized only small amounts of PGE2. In contrast, 4 h after addition of PDGF, the concentration of PGE2 synthesized from exogenous AA exceeded that in quiescent cultures by a factor of 28. The effect of PDGF stimulation on PG synthesis from exogenous AA could not be explained by growth factor-mediated increase in the cellular free AA pool as shown in experiments using [14C]AA. PDGF also stimulated synthesis of PGI2 (prostacyclin), thromboxane, and PGF2 alpha from exogenous AA. While inhibition of protein synthesis by 10 micrograms/ml cycloheximide had no effect on the early increase in PGE2 synthesis, the second increase was completely prevented. Additionally, cycloheximide treatment at 6 h after PDGF stimulation resulted in rapid decline of PGE2 synthesis from exogenous AA. Quiescent cultures pretreated with 100 microM aspirin and stimulated by PDGF thereafter recovered from cyclooxygenase inhibition within 180 min. Our results suggest that phospholipase activation and resultant AA release is not sufficient to induce the burst of PG synthesis observed in PDGF-stimulated cells. Instead, PDGF stimulates PG synthesis by direct effects on the PG-synthesizing enzyme system, one involving a protein synthesis-independent mechanism and another that requires rapid translation of cyclooxygenase.

Arachidonic Acid↗
PubMedDate not supplied

Release of prostanoids into the portal and hepatic vein in patients with chronic liver disease.

Arterial and hepatovenous concentrations of circulating prostaglandin E2 and prostaglandin F2 alpha, the stable metabolites of prostacyclin and thromboxane A2 were measured in patients with chronic liver disease and compared with those in control patients with coronary artery disease but without hepatic dysfunction. Specific radioimmunoassays were used after extraction on octadecyl C 18-silica gel columns and thin-layer chromatography. While low levels of all cyclooxygenase products were found in hepatic arterial blood in patients with proven cirrhosis (n = 10) and fibrosis (n = 8), significantly higher concentrations were detected in the hepatic vein. A similar concentration profile was observed in controls (n = 4). Thus, there is a marked but comparable release of prostanoids from the normal as well as the diseased liver. Hepatovenous prostaglandin E2 was 11.6-fold, prostaglandin F2 alpha was 7.5-fold, prostacyclin was 12.2.-fold and thromboxane B2 was 3.9-fold above the level in the artery in both groups of patients. The hepatovenous concentrations of all arachinodate metabolites were unrelated to changes of liver morphology, biochemical abnormalities or the presence of ascites. No correlation could be demonstrated between hepatic venous pressure gradient and the concentration of prostanoids in the hepatic vein with the exception of thromboxane B2 (r = 0.55, p less than 0.05). The occurrence of esophageal varices was not associated with a specific pattern of circulating prostanoids in the posthepatic vasculature. Moreover, the portal-venous concentrations of all prostanoids (five patients: two with fibrosis, three with cirrhosis) exceeded the level in the hepatic vein substantially.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗