CGP 45715 A: a leukotriene D4 analogue with potent peptido-LT antagonist activity.
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Biomedical subjects
Publications and source records attributed to M Kuhn.
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The present study was designed to investigate whether cyclic GMP or cyclic AMP modulates the release of endothelium-derived relaxing factor/nitric oxide (EDRF/NO) in cultured bovine aortic endothelial cells (BAE cells). BAE cell-conditioned medium was transferred onto rat fetal lung fibroblasts (RFL-6 cells) and the increase in cyclic GMP in these cells was used as a sensitive bioassay of EDRF/NO activity. BAE cells released a material that markedly enhanced cyclic GMP in RFL-6 cells. The synthesis of this substance could be stimulated with bradykinin (10 nM) or Ca++ ionophore A23187 (1 microM) and was completely prevented by treatment of the BAE cells with the EDRF/NO synthesis inhibitors NG-nitro-L-arginine (100 microM) or NG-methyl-L-arginine (1 mM). Addition of hemoglobin (10 microM) or incubation of the RFL-6 detector cells with methylene blue (10 microM) also abolished the cyclic GMP increase in the RFL-6 cells. The release of EDRF/NO by bradykinin and A23187 was accompanied by an approximately 2-fold increase in the cyclic GMP content in the producing BAE cells (in the presence of the cyclic GMP phosphodiesterase inhibitor M&B 22,948, 0.1 mM). Incubation of BAE cells with atrial natriuretic peptide (0.1 microM) or sodium nitroprusside (10 microM) enhanced cyclic GMP content of BAE cells 6.5-fold and 4.1-fold, respectively (in the presence of M&B 22,948, 0.1 mM). These increases in the cyclic GMP levels in BAE cells had no effect on basal or bradykinin- and A23187-stimulated release of EDRF/NO. Bradykinin (10 nM) and A23187 (1 microM) also stimulated prostacyclin production in BAE cells 2.4-fold and 5.6-fold, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
This is a report on 55 chemoembolizations (ChE) in 31 patients with primary (n = 10) and secondary (n = 21) liver malignomas. Probing of the segmental arteries was always possible by means of a coaxially placed 3F catheter system. Chemoembolization was effected with a mixture of ivalon particles, 20 mg mitomycin or 40-60 mg epirubicin and an ethibloc solution. More than 75% of the patients showed a decrease in tumour size and/or tumour density. The proportion of surviving patients was 80.6% after 6 months. Within this period, extrahepatic metastases were seen for the first time in 19.4% of the patients. References in literature on techniques and results of chemoembolization are discussed.
The histories of three possible cases of 5-ASA-induced toxic interstitial lung disease are presented. In addition diagnostical methods and procedures for the differential-diagnosis are discussed and as diagnostical program for the identification of remedy-induced toxic lung-damages is explained.
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A quasi-experimental trial, yielding 30 data points per system, was carried out to investigate the influence of component parts on the overall performance of urinary sheath systems. Information was obtained on the effect of changing both the sheath and leg-bag. Data from the trial was supported by accurate stock-taking analysis over two periods of 4 weeks' duration when alternative systems were used in a clinical setting. Results suggest that leg-bag design profoundly influences the performance of urinary sheaths. A significant difference in the performance of two urinary sheaths in the presence of the same leg-bag was also observed. The significance of the findings for nursing practice is discussed since the optimum performance, from the components tested, was a 'hybrid' system. A continuing line of investigation is suggested whereby improvements in the composition of urinary sheath systems could be made from nursing research.
Listeria monocytogenes has the capacity to penetrate and multiply within professional and nonprofessional phagocytic cells, such as the Caco-2 human enterocytelike cell line. It was shown recently that shortly after listeriae have been phagocytosed, the phagosomal membrane is dissolved, probably by the action of the bacterial cytolysin listeriolysin O. The listeriae, which are then lying obviously free in the cytoplasm, become surrounded by a coat of actin filaments within a few hours. Once formed, this layer of actin filaments is reorganized in an as yet unknown way to form polar tails, which seem to be associated to the generation of listerial movement inside the cytoplasm and in intercellular spread. By using transposon Tn916 mutagenesis, a bank of L. monocytogenes mutants was generated and subsequently screened by the plaque assay system in order to select an intracellular, nonmotile mutant of L. monocytogenes. One such mutant was identified. This mutant, called L. monocytogenes M117 Imt- (for intracellular motility), like the wild type, induced actin polymerization but was not able to rearrange the actin coat to generate movement and as a result remained entrapped within the actin cloud. In a mouse virulence assay, this strain was significantly reduced in virulence. L. monocytogenes M117 is the first example to date of a Listeria mutant which is still hemolytic and invasive but reduced in virulence.
The chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) is a constrictor of bronchial smooth muscle. Recently it has also been shown to contract rabbit coronary arteries by an unknown mechanism. This prompted us to investigate whether the chemotactic peptide has an effect on the tone of human coronary arteries obtained during heart transplantation. FMLP was found to be a potent and efficacious myotropic agent on strips of human coronary artery. Contractions were generally transient and subject to tachyphylaxis. The FMLP-induced vasoconstriction was not dependent on the presence of endothelial cells. The response was unaffected by the histamine H1-antagonist diphenhydramine or the antagonist of peptido-leukotrienes FPL 55712. However, the contractions were completely abolished in the presence of the fatty acid cyclooxygenase inhibitors aspirin or indomethacin. Stimulation of rings of human coronary artery with FMLP resulted in a marked production of prostaglandin (PG)F2 alpha, a smaller production of PGD2, and a slight increase in thromboxane B2. All these prostanoids constricted the artery, but the stable thromboxane mimetic U44069 was 100 times more potent than PGF2 alpha or PGD2. These data indicate that FMLP activates cells of unknown identity in the adventitia or media of human coronary arteries to produce a mixture of vasoconstrictor cyclooxygenase products. These compounds are likely to mediate the myotropic effect of FMLP on this artery. The mechanism may participate in the pathogenesis of some forms of coronary vasospasm.
The high mortality rate of pulmonary embolism requires rapid and rational diagnosis especially with regard to the necessary decision about the best possible treatment. Analysis of data published in the literature, and of our own data, show that angiography of the a. pulmonalis according to the i.v. DSA technique is of central importance. This involves fewer hazards than conventional pulmonalis angiography while being comparatively satisfactory in respect of reliability of the results (more than 90%). It is, therefore, a safe basis for deciding on the appropriate treatment: lysis or surgery.
A young man from Sri Lanka developed a suppurative chronic wound on the right foot after a minor trauma. In spite of several surgical interventions a closure of the ulcer did not occur. Only six months later after serious miliary tuberculosis had developed the correct diagnosis was established and tuberculostatic therapy initiated. This manifestation of tuberculosis--rare in recent times--is reviewed. Emphasis is placed on the causal relation between trauma and reactivation of tuberculosis as well as the pathogenesis of secondary miliary tuberculosis.
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Three weeks after starting treatment with the antidepressant trimipramine a 55-year-old man developed increasing cough, fatigue and lack of appetite. The blood count revealed marked eosinophilia (15%) and the chest X-ray showed bilateral pulmonary infiltrates. Later a left spontaneous pneumothorax occurred. When trimipramine was discontinued (as the suspected cause of the described changes) the symptoms quickly subsided and the infiltrate as well as the eosinophilia quickly disappeared.
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Liver diseases are frequently associated with pulmonary complications and acid-base disorders, alterations which are frequently overlooked and thus undiagnosed in these patients. Among the respiratory abnormalities, mention should be made of the numerous functional and anatomic alterations responsible for arterial desaturation, the frequent chronic hyperventilation and the rare plexiform pulmonary hypertension. Acid-base disorders, especially respiratory alkalosis and metabolic alkalosis, are common. These conditions have a number of therapeutic implications since some of them play an important role in the pathophysiology of hepatic encephalopathy. The complications and their specific diagnostic features are reviewed and some therapeutic proposals are made.
We have determined or redetermined the calcium dissociation constants of seven BAPTA-type buffers with KD's in the range from 0.4 microM to about 20 mM in 300 mM KCl. These include four newly synthesized ones: 5-nitro BAPTA; 5,5'-dinitro BAPTA; 5-methyl-5'-nitro BAPTA; and 5-methyl-5'-formyl BAPTA. Moreover, we tabulate dissociation constants or KD's for BAPTA and eleven BAPTA-type buffers, compare most of them with an empirical curve based upon so-called Hammett values, and predict KD's for several still unsynthesized but potentially valuable buffers.
Mutants of Listeria monocytogenes were recently isolated which are impaired in the synthesis of a major extracellular protein (p60). As shown in this investigation, the p60 mutants have lost the capability of invading nonprofessional phagocytic 3T6 mouse fibroblast cells. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of supernatant proteins of these mutants indicated that no other extracellular protein was altered in these mutants. The p60 mutants formed long cell chains which disaggregated to normal-sized single bacteria upon treatment with partially purified p60. These disaggregated bacterial cells were able to invade 3T6 cells. Physical disruption of the cell chains by ultrasonication produced similar single cells which were, however, noninvasive. Treatment of these ultrasonicated mutant cells with wild-type p60 restored their ability to invade 3T6 cells.
Pleural fluid eosinophilia is rare and is commonly considered as an indicator of good prognosis. In a series of 224 patients, pleural eosinophilia was present in four of 84 malignant cases; however, the incidence of malignancy in the presence of pleural eosinophilia was 0.40, being explained by a relatively high prevalence of malignancies in the population studied. Although pleural eosinophilia is rare in malignant effusions, it cannot be considered as indicating a good prognosis without taking into consideration the local prevalence of malignancies.