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R Engelhardt

Publications and source records attributed to R Engelhardt.

At least 73 records · Page 4Linked to original sources
PubMed1988

Predicting the sensitivity of human cancers to combined chemotherapy and hyperthermia.

In order to estimate its ability to predict the thermochemosensitivity of human cancers, a rapid in vitro assay based on morphological changes in the nucleus was performed on eight different human tumors (four malignant melanomas, two lung tumors, one renal carcinoma, and leukemia K-562). Nude mice, implanted with tumors, supplied the tumor material, with the exception of leukemia. Nimustine, melphalan, mitomycin C, vincristine and vinblastine were tested. Tumor cells developed karyorrhectic changes after incubation for 4 h with each of the aforementioned five drugs. An increase in the karyorrhectic changes was observed with hyperthermia at 43 degrees C. The individual tumors showed different sensitivities to 43 degrees C. Five of the eight tumors were significantly sensitive to 43 degrees C. However, in two thermosensitive tumors no drug enhancement was recognized at 43 degrees C. In four tumors several drugs were synergistically enhanced by hyperthermia at 43 degrees C. This study suggests that this simple method may be of clinical use in predicting response to thermochemotherapy.

Animals↗
PubMed1988

Sugar receptors of different types in human metastases to lung and liver.

Endogenous sugar receptors of human tumors, supposedly involved in recognitive interactions and growth regulation, were comparatively analyzed from human metastases to lung and liver by affinity chromatography and subsequent sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These profiles of sugar receptors including Ca2+-dependent and Ca2+-independent specificities to alpha- and beta-galactosides, alpha-mannosyl and alpha-fucosyl moieties from salt and detergent extracts were found to be significantly different from the profile of the corresponding normal tissue. Metastatic lesions to lung from three different types of primary tumors revealed primarily tumor-associated mannan- and galactoside-binding proteins, whereas different liver metastases showed a tendency towards preferential expression of additional beta-galactoside-binding proteins and, to a reduced extent, fucose-binding proteins. The patterns of two metastatic lesions to lung and liver from a similar primary tumor, a colon carcinoma, disclose significant differences. Each resembles the pattern of other metastases to the same target organ more than it resembles the pattern of metastatic lesions to the other target organ, derived from a similar primary tumor. Further analyses of two primary liver tumors underscore the significance of changes in such a pattern upon malignant transformation.

Calcium↗
PubMed1987

Intracellular mechanism of action of sympathetic hepatic nerves on glucose and lactate balance in perfused rat liver.

In rat liver perfused in situ stimulation of the nerve plexus around the hepatic artery and the portal vein caused an increase in glucose output and a shift from lactate uptake to output. The effects of nerve stimulation on some key enzymes, metabolites and effectors of carbohydrate metabolism were determined and compared to the actions of glucagon, which led to an increase not only of glucose output but also of lactate uptake. 1. Nerve stimulation caused an enhancement of the activity of glycogen phosphorylase a to 300% and a decrease of the activity of glycogen synthase I to 40%, while it left the activity of pyruvate kinase unaltered. Glucagon, similarly to nerve action, led to a strong increase of glycogen phosphorylase and to a decrease of glycogen synthase; yet in contrast to the nerve effect it lowered pyruvate kinase activity clearly. 2. Nerve stimulation increased the levels of glucose 6-phosphate and of fructose 6-phosphate to 200% and 170%, respectively; glucagon enhanced the levels to about 400% and 230%, respectively. The levels of ATP and ADP were not altered, those of AMP were increased slightly by nerve stimulation. 3. Nerve stimulation enhanced the levels of the effectors fructose 2,6-bisphosphate and cyclic AMP only slightly to 140% and 125%, respectively; glucagon lowered the level of fructose 2,6-bisphosphate to 15% and increased the level of cyclic AMP to 300%. 4. In calcium-free perfusions the metabolic responses to nerve stimulation showed normal kinetics, if calcium was re-added 3 min before, but delayed kinetics, if it was re-added 2 min after the onset of the stimulus. The delay may be due to the time required to refill intracellular calcium stores. The hemodynamic alterations dependent on extracellular calcium were normal in both cases. The activation of glycogen phosphorylase, the inhibition of glycogen synthase and the increase of glucose 6-phosphate can well explain the enhancement of glucose output following nerve stimulation. The unaltered activity of pyruvate kinase and the marginal increase of fructose 2,6-bisphosphate cannot be the cause of the nerve-stimulation-dependent shift from lactate uptake to output. The very slight increase of the level of cyclic AMP after nerve stimulation cannot elicit the observed activation of glycogen phosphorylase.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenine Nucleotides↗
PubMed1987

Expression of endogenous lectins in human small-cell carcinoma and undifferentiated carcinoma of the lung.

Endogenous carbohydrate-binding proteins (lectins) were detected in specimens of tumor tissue (undifferentiated carcinoma and xenografted small-cell carcinoma) from human lung. Fractionation of salt and detergent extracts on different sets of Sepharose columns covalently derivatized with lactose, asialofetuin, melibiose, mannan, and fucose, successive elution with a chelating agent and a specific sugar, and analysis of the eluates by gel electrophoresis, resulted in the characterization of the profiles of endogenous carbohydrate-binding proteins. All preparations were devoid of enzymatic activity. Comparison between the patterns of the two types of lung carcinoma showed significant qualitative differences, e.g. the presence of fucose-binding proteins of apparent molecular weights 60,000 and 80,000 in the undifferentiated carcinoma, and the presence of beta-galactoside-binding proteins of apparent molecular weights 18,000 and 22,000 in the small-cell lung carcinoma. These proteins were not detectable in normal lung tissue. Such differences, documented for the first time for human lung tumors, are of potential importance as a step towards a lectin-based refinement of lung-cancer diagnosis and therapy.

Carcinoma, Small Cell↗
PubMed1987

Preparation of neoglycoprotein-enzyme conjugate using a heterobifunctional reagent and its use in solid-phase assays and histochemistry.

A conjugate of a neoglycoprotein (chemically lactosylated bovine serum albumin) and an enzyme (horseradish peroxidase) has been prepared in solution using a heterobifunctional reagent, N-succinimidyl-3-(2-pyridyldithio)propionate, and has been purified by gel filtration on an Ultrogel AcA-44 column. To preclude any carbohydrate-dependent binding to the sugar residues on the glycoprotein peroxidase, the enzyme has to be treated with sodium periodate and sodium cyanoborohydride prior to coupling, which results in oxidative cleavage of the carbohydrates and reduction of the aldehydes thus formed to primary alcohols. Lactosylated bovine serum albumin-peroxidase conjugate has been employed to detect plastic-bound Ricinus communis agglutinin with dependence of the concentration of the lectin and with dependence of the presence of specific inhibitors. Enzyme-labeled conjugates with unmodified bovine serum albumin are completely ineffective in this assay. Localization of beta-galactoside-specific sugar receptors in connective tissue is used to demonstrate the feasibility of application of such neoglycoprotein-enzyme conjugates in histochemistry with a minimum number of steps.

Adenocarcinoma↗
PubMed1987

Mechanism of action of sympathetic hepatic nerves on carbohydrate metabolism in perfused rat liver.

In the perfused rat liver stimulation of the hepatic nerves around the portal vein and the hepatic artery was previously shown to increase glucose output, to shift lactate uptake to output, to decrease and re-distribute intrahepatic perfusion flow and to cause an overflow of noradrenaline into the hepatic vein. The metabolic effects could be caused directly via nerve hepatocyte contacts or indirectly by the hemodynamic changes and/or by noradrenaline overflow from the afferent vasculature into the sinusoids. Evidence against the indirect modes of nerve action is presented. Reduction of perfusion flow by lowering the perfusion pressure from 2 to 1 ml X min-1 X g-1--as after nerve stimulation--or to 0.35 ml X min-1 X g-1--far beyond the nerve stimulation-dependent effect--did not change glucose output and lowered lactate uptake only slightly. Only re-increase of flow to 2 ml X min-1 X g-1 enhanced glucose and lactate release transiently due to washout of glucose and lactate accumulated in parenchymal areas not perfused during low perfusion flow. In chemically sympathectomized livers nerve stimulation decreased perfusion flow almost normally but without changing the intrahepatic microcirculation; yet it enhanced glucose and lactate output only insignificantly and caused noradrenaline overflow of less than 10% of normal. Conversely, in the presence of nitroprussiate (III) nerve stimulation reduced overall flow only slightly without intrahepatic redistribution but still increased glucose and lactate output strongly and caused normal noradrenaline overflow.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Identification of endogenous sugar-binding proteins (lectins) in human placenta by histochemical localization and biochemical characterization.

Human placentas of different stages of development were histochemically analyzed for expression of endogenous sugar-binding proteins using a panel of biotin-conjugated, chemically glycosylated probes with specificity for beta-galactosides, alpha-galactosides, alpha-mannosides, alpha-fucosides and alpha-glucosides. Temporal differences in the expression of sugar-binding proteins and different patterns of staining of the component cell types of human placenta were discerned, especially pronounced for alpha-fucoside-specific binding in the trophoblast and alpha-glucoside-specific binding in fetal and maternal macrophages. Fractionation of salt and detergent extracts from human placentas by affinity chromatography on columns with immobilized carbohydrates or glycoproteins substantiated the histochemically detectable temporal changes on the basis of alterations in the pattern of individual sugar-binding proteins, as determined by gel electrophoresis under denaturing conditions. Analysis of the trophoblastic layer primarily disclosed the presence of several additional sugar-binding proteins (lectins) in comparison to full-term placenta. The presence and developmental changes of such endogenous sugar receptors may lead to specific carbohydrate-protein interactions of physiological significance with similarly developmentally regulated carbohydrated portions of glyco-conjugates, already detected in human placenta by plant lectins.

Carbohydrate Metabolism↗
PubMed1986

Successful therapy of sarcoidosis-associated thrombocytopenia refractory to corticosteroids by a single course of human gammaglobulins.

Thrombocytopenia developed in a 21-year-old patient with sarcoidosis when corticosteroid therapy was discontinued. Platelet-associated IgGs were elevated. High-dose cortisone did not affect the thrombocytopenia. However, platelet counts remained normal for more than 1.5 years following intravenous treatment with a single course of human gammaglobulins.

Adult↗
PubMed1986

Carbohydrate-binding proteins of tumor lines with different growth properties. II. Changes in their pattern in clones of transformed rat fibroblasts of differing metastatic potential.

A tumor model system of clones of myeloproliferative sarcoma virus (MPV)-transformed rat fibroblasts (NRK) with different growth properties and metastatic potential was studied. The relationship between metastatic behavior and composition of carbohydrate-binding proteins (lectins) was analyzed by affinity chromatography. The metastatic variant differs qualitatively from its parental clone in the presence of galactoside-binding proteins at apparent molecular weight of 42 kDa. The alpha-glucosyl-binding proteins at apparent molecular weights of 67 kDa and 53 kDa and a galactoside-binding protein of apparent molecular weight of 34 kDa, however, are not detectable in the metastatic variant in comparison to its parental clone. In this respect the parental clone shows closer resemblance to the clone 5-8#1 with different growth properties and low metastatic potential than to its own metastatic variant. Furthermore, only the parental clone has a melibiose- and a mannan-binding protein of an apparent molecular weight of 64 kDa and 14 kDa, respectively. Rosette formation as model system for intercellular interaction reveals differences in the inhibition pattern with sugar between the two clones 5-8#1 and 5-20#20, whereas the metastatic variant 5-20#20 (s) exhibits drastically reduced capability to form rosettes. Initial experiments demonstrate the feasibility of drug targeting to transformed fibroblasts via carbohydrate-binding proteins.

Animals↗