Search results for "DRUG DISCOVERY"
showing 10 items of 3927 documents
Oncogene overexpression in non-small-cell lung cancer tissue: prevalence and clinicopathological significance.
1994
In contrast to small-cell lung cancer, few data are available on the role of oncogene overexpression in non-small-cell lung cancers (NSCLC). To determine the prevalence and extent of the transcriptional activation of cancer genes in NSCLC we investigated the level of mRNA of the three important cellular oncogenes — erbB2, Ki-ras, and c-myc — in 39 surgically or endoscopically obtained tumor samples and 24 samples of normal bronchopulmonary tissue taken from the same patients. Tissue RNA was prepared and the specific mRNA analyzed by the highly sensitive nuclease S1 protection assay. Oncogene mRNA in the tumors was quantified by comparison with the homogeneously weak signals in normal lung t…
A macrophage-suppressing 40-kD protein in a case of pulmonary alveolar proteinosis.
1987
Pulmonary alveolar proteinosis (PAP) is a rare disease of unknown etiology. Macrophage dysfunctions are claimed to be involved in the pathogenesis. We investigated phagocytosis and oxidative metabolism of alveolar macrophages in a case of pulmonary alveolar proteinosis. These cells phagocytize normally and phagocytizable stimulants cause a normal oxidative burst. In response to the membrane signals phorbolmyristate acetate and aggregated immunoglobulin, however, no stimulated turnover of the oxidative metabolism can be observed. A 40-kD protein found in the lavage fluid mediates this macrophage-inhibiting effect. This phenomenon may contribute to the frequent opportunistic infections seen i…
Pro-inflammatory gene variants in myocardial infarction and longevity: implications for pharmacogenomics.
2008
Inflammation and genetics play an important role in the pathogenesis of coronary heart disease (CHD). However, despite the increasing appreciation of the role of genetics in CHD and myocardial infarction (MI) pathogenesis, pharmacogenomic approaches to uncover drug target have not been extensively explored. Cyclo-oxygenases (COXs) and 5-lipoxygenase (5-LO) are the key enzymes in the conversion of arachidonic acid to prostaglandins (PG) and leukotrienes (LT) and are implicated in a wide variety of inflammatory disorders, including atherosclerosis. In fact, PGE2 activates Matrix Metallo-proteinases whereas LTB4 is a chemoactractant for monocytes and activates gene expression in inflammatory c…
Detection of gamma-hydroxybutyrate in hair: Validation of GC–MS and LC–MS/MS methods and application to a real case
2012
A gas chromatography-mass spectrometry (GC-MS) and a liquid chromatography tandem mass spectrometry (LC-MS/MS) method were validated for quantifying endogenous and exogenous hair concentrations of gamma-hydroxybutyrate (GHB). The GC-MS method is based on overnight extraction of 25 mg hair in NaOH at 56 °C, liquid/liquid extraction in ethylacetate and trimethylsylil derivatization; analysis is by electron ionization and single ion monitoring of three ions. The LC-MS/MS method entails a rapid digestion of 25 mg hair with NaOH at 75 °C for 40 min, liquid/liquid extraction in ethylacetate and reconstitution of the extract in the LC mobile phase; negative ion electrospray ionization and multiple…
Antiplatelet effects of intravenous iloprost in patients with peripheral arterial obliterative disease
1986
The dose-dependent inhibition of platelet aggregation by the chemically stable, prostacyclin-mimetic, iloprost, was studied in patients suffering from stage II-III peripheral arterial obliterative disease (PAOD). The study was designed as a randomized placebo-controlled cross-over trial. Iloprost was administered i.v. to six patients at doses of 0.5, 1.0, 2.0 or 3.0 ng/kg X min for 4 h, with an interval of 2-3 days between the infusions. During iloprost infusion, systolic and diastolic arterial blood pressure, heart rate and blood flow in the affected limb remained unchanged. In contrast, there was a considerable, dose-dependent inhibition of ADP- and thrombin-induced platelet aggregation a…
Significance of hyperlactatemia in acute hypnotic drug poisoning
1981
Lactate concentration, fibrinogen and fibrin(ogen) -- degradation-products in central venous blood were analysed in 35 unconscious patient with acute hypnotic drug poisoning (HDP) and compared with the results in 13 healthy control persons undergoing the same degree of forced diuresis via central venous catheters. Blood samples were taken on admission and at 12 h intervals up to 36 h after admission. Patients with HDP were attributed to the categories of moderate intoxications (n = 17) and severe intoxications (n = 18) according to their clinical condition. On admission, blood lactate was significantly higher in severe intoxication (3.90 +/- 2.94 mmol/l) as compared to the control group (1.…
Inverse regulation of vascular endothelial growth factor and VHL tumor suppressor gene in sporadic renal cell carcinomas is correlated with vascular …
1999
Tumors associated with the VHL (von Hippel-Lindau) disease, such as hemangioblastomas and renal carcinomas and their sporadic counterparts, are cystic and well vascularized. Mutations of the VHL tumor-suppressor gene and elevated levels of vascular endothelial growth factor (VEGF) have been described in these tumors. The upregulation of VEGF has been shown in vitro as a consequence of alteration of the VHL gene. No comprehensive in vivo analysis has yet been carried out of the factors affecting tumor growth, vascularization, VEGF, and VHL expression. We performed immunohistochemistry and mRNA studies on primary sporadic renal carcinomas and matching normal renal tissue. We semiquantitativel…
Retinol oxidation to retinoic acid in human thyroid glandular cells.
2014
Abstract Retinoic acid is regarded as the retinol metabolite that controls proliferation and differentiation of epithelial cells. In the present study, we investigated the potential role of xanthine dehydrogenase (XDH) in retinoic acid biosynthesis in human thyroid glandular cells (HTGC). In particular, we observed that cellular retinoids binding proteins (CRBPs) are also implicated in the biosynthetic pathway leading to retinoic acid formation in primary cultures of HTGC, as we have already reported for human mammary epithelial cells (HMEC). After partial protein purification, the enzyme responsible for retinoic acid biosynthesis was identified and quantified as XDH by immunoassay, by its …
Effect of intravenous flecainide on atrial vulnerability in man.
1983
Sixteen patients were investigated by means of programmed atrial stimulation at two different driving rates: 100 and 120/min. All patients had an increased atrial vulnerability at both driving rates. After intravenous flecainide application (1 mg/kg body weight as a bolus followed by the same amount given by infusion over a period of 20 min) the increased vulnerability was abolished in 11 and 9 patients respectively. In the remaining patients the rate of induced atrial tachyarrhythmia decreased. These findings correlate with a significant prolongation of the effective refractory period of the right atrium and a significant shortening of the relative refractory period of the right atrium. It…
Esophageal dysfunction and its pathogenesis in progressive systemic sclerosis
1978
In 25 patients with progressive systemic sclerosis esophageal involvement was studied prospectively by analysing subjective symptoms and radiological and manometric criteria. In all patients abnormal motility could be demonstrated by X-ray and/or manometry: radiologically in 18 (72%), manometrically in 22 (88%) cases. Dysphagia was present only in 11 patients (44%). Six patients (24%) had no subjective symptoms in spite of severe objective esophageal abnormalities. Therefore, the absence of esophageal symptoms does not exclude advanced affliction of the esophagus. To determine the pathogenesis of esophageal dysfunction the effects of 3.5 microgram/kg carbachol and of 0.6 microgram/kg pentag…