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Biomedical subjects

H Greten

Publications and source records attributed to H Greten.

At least 181 records · Page 10Linked to original sources
PubMed1986

Characterization of CA 19-9 bearing mucins as physiological exocrine pancreatic secretion products.

The monoclonal antibody CA 19-9 reacts with a carbohydrate epitope (sialylated lacto-N-fucopentaose II), which was shown to be part of a ganglioside extracted from a colon carcinoma cell line as well as of a mucin isolated from gastrointestinal tract tumor patients' sera. Recently, when we compared CA 19-9 levels in pancreatic juices and corresponding serum samples from a large group of patients, we showed the high serum values to be indicative solely for a malignant disease. In contrast, the overall high CA 19-9 content in pancreatic juices from all diagnostic groups raised the question about the antigenic moieties in these samples. By means of thin layer chromatography of glycolipids with subsequent antibody overlay, gel chromatography, and density gradient analysis, we found only the mucin form in all sources investigated. Thus we conclude that the discrimination potential of the CA 19-9 assay in serum is based on an altered secretion or distribution in pancreatic tumors.

Antibodies, Monoclonal↗
PubMed1985

The prostacyclin analogue iloprost and prostaglandin E1 suppress sterol synthesis in freshly isolated human mononuclear leukocytes.

The effects of the stable prostacyclin analogue iloprost, prostaglandin E1 and prostaglandin F2 alpha on sterol synthesis were investigated in freshly isolated human mononuclear leukocytes. Incubation of cells for 6 h in a medium containing lipid-depleted serum led to a 3-fold rise in the rate of sterol synthesis from [14C]acetate or tritiated water. Iloprost and prostaglandin E1 added in increasing concentrations at zero time resulted in an inhibition of the synthesis of sterols, the suppression being 50 and 55% at a concentration of 1 mumol/1, respectively. Both prostaglandins yielded a sigmoidal log dose-effect curve. In contrast, prostaglandin F2 alpha had no influence on sterol synthesis up to a concentration of 1 mumol/1. The action of the prostacyclin analogue and prostaglandin E1 on the relative rate of sterol synthesis was not immediate, since the prostaglandins had no effect when given at 6 h to the incubation medium, and the incorporation of [14C]acetate into sterols was measured thereafter. The results suggest that prostacyclin and prostaglandin E1 affect cholesterol synthesis and therefore may play a role in the regulation of cellular cholesterol homeostasis and in the development of atherosclerosis.

Alprostadil↗
PubMed1985

Monoclonal antibody defines CA 19-9 in pancreatic juices and sera.

In a retrospective study pancreatic juice samples (n = 213) and corresponding serum samples (n = 110) were assayed for their concentration of monoclonal antibody defined CA 19-9/GICA (gastrointestinal cancer associated antigen). Serum CA 19-9 values were found to be good diagnostic and discriminating markers for pancreatic disorders and were raised (greater than 50 u/ml) in more than 80% of the pancreatic cancer patients compared to 8.5% of the pancreatitis group and none of the control group. In contrast pancreatic juice CA 19-9 values showed a considerable overlap between groups. On the basis of recent molecular data on the monoclonal antibody 19-9 defined antigen(s)--that is, monosialoganglioside, mucin--it is proposed that the discrepancies between serum and pancreatic juice findings are due to a specific undirected endocrine release of the mucin into sera in pancreatic tumour patients while in pancreatic juices of all diagnostic groups high CA 19-9 activities are either owing to coexistence of glycolipid and mucin or that the latter is a physiologically exocrine product.

Antibodies, Monoclonal↗
PubMed1985

[Immunoscintigraphy and radioimmunotherapy of transplanted pancreatic carcinoma. Experimental animal studies with 131I-labeled monoclonal antibodies against CA 19-9, CEA and CA 125].

The immunoscintigraphic results in 12 human pancreatic carcinomas established on nude mice (Nu-Nu-Balb-C) are reported. The transplanted tumors corresponded to the human cancers concerning histology, grading, immunohistochemistry and secretion of tumor-associated antigens. 131I-labeled monoclonal antibodies against CA 19-9, CEA and CA 125 were used. These antigens are found in the serum of more than 90% of patients with pancreatic carcinoma at the time of first diagnosis. The result show that pancreatic carcinomas are detectable with the antibodies applied here. The quality of the scintigraphic detection depends, among other factors, on the antibody affinity to the tumor, the localization and the size of the tumor. Preliminary results of the studies on radioimmunotherapy of pancreatic cancer with 131I-anti-CA 19-9 indicate that effective absorbed doses in the tumor may be achieved via intravenous application only in cases with a rather high expression of the tumor antigen. But direct instillation into the tumor enables therapeutic radiation doses to the tumor even with moderate affinity and a low whole-body burden, as shown by experiments in 8 mice bearing 4 different human pancreatic carcinomas, 3 with positive and 1 with negative affinity to CA 19-9: the tumor retentions and the effective half-lives of 131I-anti-CA 19-9 were measured after intratumoral (100 microCi/mg tumor) or intravenous (30 and 190 microCi/g body weight) application.

Animals↗
PubMed1985

Monoclonal antibody-defined human pancreatic cancer-associated antigens.

Three pancreatic cancer-associated antigens were characterized by use of monoclonal antibodies in immunobinding studies with various cellular and soluble target antigens, in immunoprecipitation, and in immunoperoxidase staining. C54-0 represents a tumor-associated Mr 122,000 antigen, which appears to be widely distributed on various epithelial tumors and to a lower extent on normal tissue. C1-N3 antigen exhibited a more restricted distribution, reacting with pancreatic and various gastrointestinal tract tumors as well as with chronically inflamed pancreatic tissue. The most specific antigen expression was observed for C1-P83 antigen, found on all exocrine tumors of the pancreas, but not on normal or chronically inflamed pancreatic tissue.

Animals↗
PubMed1985

Characterization and catabolism of rat very high density lipoproteins.

A previously unrecognized lipoprotein of very high density was isolated from rat serum. During zonal ultracentrifugation of whole serum or of fractions from Sepharose 4B chromatography, a peak comigrating with a peak of cholesterol was found between the typical high density lipoproteins and the residual serum proteins. Centrifugation of chylomicrons, very low density lipoproteins, and high density lipoproteins, radio-iodinated in their lipid and protein moieties and mixed with serum, did not yield this peak. The pooled fractions contained about 85% protein. The remainder was lipid comprising cholesteryl esters, free cholesterol, triglycerides, phosphatidylcholine, and sphingomyelin. Polyacrylamide gel electrophoresis revealed bands in the region of apolipoproteins E and C as the major components. The composition suggested a lipoprotein, and this was substantiated by electron microscopy which showed particles with a mean diameter of 150 A. Their average hydrated density was 1.23 g/ml and the apparent molecular weight was 1.35 X 10(6). These very high density lipoproteins are characterized by a rapid catabolism as compared to high density lipoproteins. Within 10 min, 84% and 70% of intravenously injected 125I-labeled very high density lipoproteins were removed from plasma of male and female rats, respectively, and did not appear to be converted to lipoproteins of a different density class. Ninety-five percent of the removed 125I was recovered in the liver and the radioactivity per gram of tissue was also highest for the liver. Accordingly, the rate of clearance of 125I-labeled very high density lipoproteins was markedly reduced in functionally eviscerated rats. Radioautography revealed that most of the silver grains representing very high density lipoproteins were associated with hepatocytes and only about 1% was found over v. Kupffer cells. Uptake and degradation by freshly isolated rat hepatocytes were mediated by a saturable and specific binding site. Composition and metabolic pathway are compatible with a function of very high density lipoproteins in the transport of protein and lipids to the liver.

Animals↗
PubMed1984

[CA 12-5 in cancer of the digestive tract. A comparison with CA 19-9 and CEA in cancer of the pancreas and colon].

In 42 control subjects and 134 patients with benign or malignant disease of the pancreas or large intestine, the recently produced tumour-associated antigen CA 12-5 was determined together with CEA and CA 19-9. Only 4% of controls and patients with benign disease (except those with acute pancreatitis) had CA 12-5 values above 35 U/ml, compared with 60% of patients with pancreas carcinoma and 21% with colon carcinoma. For the former (pancreas carcinoma) there was also a good correlation to stage of tumour (0 of 6 tumours stage TxN0M0, 7 of 11 TxN1M0, 16 of 20 TxN1M1 greater than 35 U/ml) and progression of the malignancy. Simultaneous determination of all three antigens increased the rate of tumour-marker positive patients from 87% (CA 19-9) to 92% for pancreas carcinoma and from 25% (CEA) to 51% for colon carcinoma.

Acute Disease↗
PubMed1984

Stimulation of beta 2-adrenergic receptors suppresses sterol synthesis in human mononuclear leukocytes.

The beta-adrenergic receptor mediating the inhibition of sterol synthesis by catecholamines in freshly isolated human mononuclear leukocytes was defined pharmacologically by using selective beta 1- and beta 2-agonists and -antagonists. Incubation of cells for 6 h in a medium containing lipid-depleted serum resulted in a 3-fold increase in the incorporation of [14C]acetate or tritiated water into sterols. The beta-agonist (-)-isoproterenol was approximately equipotent with (-)-epinephrine and (-)-norepinephrine in suppressing sterol synthesis, yielding a sigmoidal log-dose-effect curve. Accordingly, the effects of the catecholamines were reversed by the beta-antagonist (+/-)-propranolol. The beta 2-agonists terbutaline and salbutamol inhibited sterol synthesis by 42 and 26%, respectively, at a concentration of 0.1 mmol/l. Contrary to that, the beta 1-agonists prenalterol and dobutamine had no effect. In accordance with the influence of the agonists, the beta 2-antagonist butoxamine, but not the beta 1-antagonists atenolol, metoprolol and practolol, reversed the catecholamine action on sterol synthesis. The results provide evidence that catecholamines may regulate sterol synthesis by stimulating beta 2-adrenergic receptors.

Adrenergic beta-Agonists↗
PubMed1984

[Antihypertensive therapy and lipid metabolism].

Hypertension, hyperlipidaemia and cigarette smoking are major risk factors in coronary heart disease. Since many antihypertensive drugs alter plasma lipid levels it is a subject of current discussion that these agents may increase associated coronary risk and therefore offset the beneficial effects of lowering blood pressure. The purpose of this paper is to review clinical and experimental data in the literature on the influence of data in the literature on the influence of antihypertensive drugs on lipid metabolism. The thiazides hydrochlorothiazide and chlorthalidone cause an elevation of plasma triglycerides and very low density lipoprotein (VLDL) but have little effect on total cholesterol, low density lipoprotein (LDL) and high density lipoprotein (HDL). The unspecific beta-blockers, e.g. propranolol, do not affect total cholesterol and LDL but increase total triglycerides and VLDL and decrease HDL. The changes of plasma lipids and lipoproteins caused by cardio-selective beta-blockers, e.g. atenolol and metoprolol, and unspecific beta-blockers with intrinsic sympathomimetic activity (ISA), e.g. oxprenolol and pindolol, appear to be qualitatively similar but less pronounced. The alpha 1-blocker prazosin reduces total triglycerides and slightly lowers total cholesterol. The concentration of VLDL plus LDL decreases while HDL may increase. Only very few studies have been reported on the effects of other antihypertensive drugs, e.g. clonidine, hydralazine, on plasma lipids. Several experimental studies reveal that antihypertensive agents exert direct effects on triglyceride and cholesterol metabolism. Although the pathophysiological mechanisms and the significance of the alterations of lipid metabolism induced by antihypertensive drugs are not yet clear, the following guidelines for the clinical use of these agents are recommended: (1) before initiating drug treatment in hypertensive patients, blood lipid levels should be measured to exclude a preexisting hyperlipidaemia, (2) during long-term therapy with antihypertensive agents, lipoprotein fractions should be controlled in order to reconsider the therapeutic regime if major alterations of blood lipid levels are observed.

Adrenergic alpha-Antagonists↗
PubMed1984

Evidence for post-transcriptional regulation by insulin of 3-hydroxy-3-methylglutaryl coenzyme A reductase and sterol synthesis in human mononuclear leucocytes.

Incubation of freshly isolated human mononuclear leucocytes in lipid-depleted serum for 4 h resulted in a two-fold increase in 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity. Insulin, when added to the incubation medium at concentrations of 10 and 100 nmol/l at zero time, caused additional increases in the enzyme activity of 30% and 37%, respectively. The hormone action was not immediate because no effect was observed when insulin was added at 4 h and activity examined thereafter. Under these conditions sterol synthesis from 14C-acetate and tritiated water was strictly proportional to the activity of HMG-CoA reductase. Cycloheximide (20 micrograms/ml), a translational inhibitor of protein synthesis, prevented the insulin-mediated increase in the enzyme activity and the incorporation of 14C-acetate into sterols. Cordycepin (50 micrograms/ml) inhibited messenger RNA synthesis by greater than 50%, but had no inhibitory effect on the induction of HMG-CoA reductase and sterol synthesis. Low density lipoprotein (80 micrograms protein/ml) and complete serum blocked the induction of the enzyme and sterol synthesis from 14C-acetate caused by lipid-depleted serum. The insulin-effect, however, remained unchanged. The results suggest that insulin may regulate the de novo synthesis of HMG-CoA reductase and accordingly sterol synthesis at a post-transcriptional level.

Acetates↗
PubMed1984

Plasma apoprotein changes after selective inhibition of hepatic triglyceride lipase in rat.

Selective inhibition of hepatic triglyceride lipase (HTGL) by specific antibodies in rats led to an altered VLDL apoprotein composition. Apoprotein analysis by isoelectric focusing revealed a new protein band in VLDL and an increase in apoprotein E (apo E) content. Apoproteins in LDL and HDL remained unchanged. Electronmicroscopy showed a significant increase in particle size of VLDL from 452 to 497 A with no significant changes in LDL and HDL diameters.

Animals↗