PubMed Health⌕ Search

Biomedical subjects

M Goerig

Publications and source records attributed to M Goerig.

At least 73 records · Page 4Linked to original sources

Rapid increase in the activity of enzymes of eicosanoid synthesis in hepatic and extrahepatic tissues after experimental liver transplantation.

Previous studies have demonstrated a marked release of prostanoids from hepatic tissue after liver grafting. In addition, eicosanoid synthesis was shown to be regulated at the level of key enzymes. The present study addressed changes of the local availability of these enzymes during and after porcine orthotopic liver transplantation. We determined kinetic parameters of cyclooxygenase (CO), the initial enzyme of prostaglandin synthesis, of prostacyclin and thromboxane synthase (PCS, TXS), two more peripheral enzymes, in microsomal preparations of hepatic and gluteal muscle biopsies, and the activity of 5-lipoxygenase (5-LO), the key enzyme of leukotriene synthesis. Maximal velocity (Vmax) of CO and PCS showed a 4-fold increase both in liver and gluteal muscle tissue 1 hr after reperfusion of the grafted liver and a more than 20-fold increase after 24 hr (P less than 0.001), whereas apparent affinities (Km) remained unchanged. In contrast, Vmax of TXS and the activity of 5-LO disclosed a striking increase only within the hepatic graft (P less than 0.001). No changes of enzymatic activity could be observed during donor operation, cold storage, and 5 min after reperfusion. Results were independent of the duration of preservation (3 hr and 20 hr with Euro-Collins) and the addition of Iloprost, a prostacyclin-analogue. These results suggest that after liver grafting, abnormalities at the level of local enzyme expression in hepatic and extrahepatic tissues might contribute to preservation damage and systemic injury of the host.

6-Ketoprostaglandin F1 alpha↗

[Pollution of the workplace by anesthetic gases. Causes and prevention].

Waste anesthetic gas concentrations were measured in areas corresponding to the breathing zones of the anesthetists and operating room nurses for personal exposure (n = 27, time-weighted values) and during special work practices (n = 65). Leaks related to anesthetic machines and high-pressure nitrous oxide components were investigated during (n = 60) and after anesthesia (n = 85). The effect of a local scavenging system on occupational exposure during inhalation induction of anesthesia in children was studied (n = 60). Concentrations of nitrous oxide, halothane, isoflurane, and enflurane were determined by using active dosimeters (SKC 222) and different infrared gas-analyzers. Factors that increase waste anesthetic gas concentrations in operating rooms can be divided into several categories, such as low air conditioning systems, anesthetists' work practices, equipment leakage, including leakage from high-pressure nitrous oxide systems, and inadequate scavenging devices. Equipment leakage is almost invariably present in low-pressure components of the anesthesia machine because so many seals and joints are necessary to permit disassembly for cleaning and replacement. Waste anesthetic gases are also distributed in the exhaled air of patients recovering from anesthesia. To restrict the levels, exposure must be as low as can be achieved with reasonable efforts. Thus, the anesthetic equipment should be designed to avoid leakage, leakage tests should be performed before the use of anesthetic machines, and waste anesthetic gases should be scavenged by central as well as by local systems. Regular and periodic use of a trace gas analyzer permits direct observation of gas leakage and enables anesthetists to modify their work technique in order to reduce avoidable leakage.

Air Pollutants, Occupational↗

The LDL receptor pathway delivers arachidonic acid for eicosanoid formation in cells stimulated by platelet-derived growth factor.

Animal cells can convert 20-carbon polyunsaturated fatty acids into prostaglandins (PGs) and leukotrienes. These locally produced mediators of inflammatory and immunological reactions act in an autocrine or paracrine fashion. Arachidonic acid (AA), the precursor of most PGs and leukotrienes, is present in the form of lipid esters within plasma lipoproteins and cannot be synthesised de novo by animal cells. Therefore, AA or its plant-derived precursor, linoleic acid, must be provided to cells if PGs or leukotrienes are to be formed. Because several classes of lipoproteins, including low-density lipoproteins (LDL), very-low-density lipoproteins, and chylomicron remnants, are taken up by means of the LDL receptor, and because LDL and very-low-density lipoproteins, but not high-density lipoproteins, stimulate PG synthesis, we have suggested previously that PG formation is directly linked to the LDL pathway. Using fibroblasts with the receptor-negative phenotype of familial hypercholesterolaemia and anti-LDL receptor antibodies, we show here that LDL deliver AA for PG production and that an LDL receptor-dependent feedback mechanism inhibits the activity of PGH synthase, the rate-limiting enzyme of PG synthesis. These results indicate that the LDL pathway has a regulatory role in PG synthesis, in addition to its well-known role in the maintenance of cellular cholesterol homeostasis.

Animals↗

Prostanoid release in experimental liver transplantation.

Prostanoids are biologically active mediators of inflammation and tissue injury. To investigate the role of prostanoids in orthotopic liver transplantation we used a porcine model and determined prostaglandin E2, 6-keto-prostaglandin F1 alpha, and thromboxane B2 in arterial, portal, and hepatic venous blood during organ harvesting, the recipient operation, and the early postoperative period. There were no significantly increased serum levels during the donor operation or at the end of cold storage. As early as 1 or 5 min after initiation of reperfusion of the transplanted organ, prostanoids in hepatovenous blood increased dramatically (100-500-fold). Changes in arterial and portal blood (10-50-fold) were less pronounced but still statistically significant. In surviving animals these values returned to normal within 24 hr. The hepatic release of metabolites of the arachidonic acid cascade after liver grafting indicates that the synthesis of prostanoids might contribute to morphological and functional alterations of the transplanted graft. In addition, the increased arterial values of circulating prostanoids may potentially participate in severe cardiovascular, hemostatic, and immunological alterations known to occur after liver transplantation.

6-Ketoprostaglandin F1 alpha↗

[Georg Perthes--a pioneer of modern regional anesthesia technics?].

In regional anesthesia, the localization of peripheral nerves and plexuses is possible by means of mechanical or electrical stimulation. Electrical stimulation for this purpose was first described in 1912 by the surgeon Georg Perthes (1869-1927) of Tübingen, who reported his own experiences. The original description and results of electrostimulation are transposed upon a modern point of view of regional anesthesia.

Anesthesia, Conduction↗

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↗

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↗

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↗

[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↗

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↗

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↗