PubMed Health⌕ Search

Biomedical subjects

R Engelhardt

Publications and source records attributed to R Engelhardt.

At least 91 records · Page 5Linked to original sources
PubMed1986

Comparison of bleomycin and peplomycin toxicity on clonogenic tumor cells from various human tumors.

The cytotoxic effect of bleomycin and peplomycin was compared using a methylcellulose monolayer assay for the cultivation of human tumor cells. In 3 out of 4 samples from human malignant melanomas peplomycin proved to be more cytotoxic than bleomycin. Peplomycin was more cytotoxic than bleomycin in 1 of 5 myosarcoma samples, whereas 2 samples from squamous cell carcinomas of the lung showed identical dose response curves. In 1 carcinoma of the gall bladder peplomycin was more toxic than bleomycin.

Bleomycin↗
PubMed1986

Pattern of endogenous lectins of a human sarcoma (Ewing's sarcoma) reveals differences to human normal tissues and tumors of epithelial and germ cell origin.

A human sarcoma, Ewing's sarcoma, contains activities of endogenous lectins. Fractionation of salt and detergent extracts by affinity chromatography on columns with immobilized sugars or glycoproteins results in the pattern of endogenous lectins for alpha- and beta-galactosides, alpha-mannosyl- and alpha-fucosyl-moieties. Whereas some lectins are known from normal, non-malignant human tissues or from a human epithelial tumor or a human germ cell tumor, a Ca2+-independent alpha- and beta-galactoside-binding protein at apparent molecular weight of 58 kilodaltons has so far not been characterized from any human source. The patterns for the tumors and human normal tissues reveal various differences in comparison between each other. These differences, documented for the first human sarcoma, human tumors of different histogenetic lineage and normal tissues are a first step to a lectin-based diagnosis and therapy of certain human cancer types.

Apudoma↗
PubMed1986

Comparison of endogenous lectins in human embryonic carcinoma and yolk sac carcinoma.

Salt and detergent extracts of xenografted human embryonic carcinoma and a human yolk sac carcinoma were fractionated on different sets of Sepharose columns covalently derivatized with lactose, asialofetuin, melibiose, mannan and fucose. Successive elution by chelating reagent and specific sugar resulted in isolation of endogenous Ca2+-dependent and Ca2+-independent carbohydrate-binding proteins, as analyzed by gel electrophoresis. The salt extracts of the embryonic carcinoma contained a Ca2+-dependent carbohydrate-binding protein at Mr66,000, that was undetectable in yolk sac tumor extracts. Also, a Ca2+-independent fucose-binding protein at Mr62,000 could be purified. In general, the pattern of carbohydrate-binding proteins showed quantitative and qualitative differences as compared to normal tissue. The carbohydrate-binding proteins were assayable as agglutinin and showed no enzymatic activity. They can thus be defined as lectins. Their presence within certain stages of differentiation and developmental regulation may contribute to improvement of the classification, diagnosis and therapy of this tumor class. These new lectins may also be functionally related to the stage-specific embryonic antigens like SSEA-1.

Adult↗
PubMed1986

Differences in the pattern of endogenous lectins from spontaneous rat mammary tumors.

Three spontaneously occurring rat mammary tumors, a fibroadenoma and two tubulopapillary adenocarcinomas, differing in their degree of histologic differentiation and malignancy, were investigated. They revealed significant differences in the pattern of carbohydrate-binding proteins with specificities for alpha- and beta-galactosyl, alpha-mannosyl, and alpha-fucosyl moieties, respectively. Analysis was performed by affinity chromatography on resins with immobilized sugars or glycoproteins and by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The patterns were divided into categories according to the dependence of binding activity on the presence of Ca2+ and to dependence on extraction conditions. In comparison with both adenocarcinomas, the fibroadenoma contained alpha- and beta-galactoside-binding proteins at apparent molecular weights of 74,000 and 130,000. These proteins were not found in either adenocarcinoma. Comparison between the two adenocarcinomas revealed qualitative differences for all classes of carbohydrate-binding proteins under investigation. These differences between tumors of the same tumor class (mammary tumors) and tumor type (tubulopapillary adenocarcinoma) allow for the proposal that the pattern of endogenous carbohydrate-binding proteins may be potentially useful as a diagnostic marker.

Adenocarcinoma↗
PubMed1985

Archaebacterial phenylalanyl-tRNA synthetase. Accuracy of the phenylalanyl-tRNA synthetase from the archaebacterium Methanosarcina barkeri, Zn(II)-dependent synthesis of diadenosine 5',5'''-P1,P4-tetraphosphate, and immunological relationship of OFFnylalanyl-tRNA synthetases from different urkingdoms.

Phenylalanyl-tRNA synthetase from the archaebacterium Methanosarcina barkeri activates a number of phenylalanine analogues (methionine, p-fluorophenylalanine, beta-phenylserine, beta-thien-2-ylalanine, 2-amino-4-methylhex-4-enoic acid and ochratoxin A) in the absence of tRNA, as demonstrated by Km and kcat of the ATP/PPi exchange reaction. Upon complexation with tRNA, AMP formation from the enzyme X tRNA complex in the presence of ATP, one of the above analogues or tyrosine, leucine, mimosine, N-benzyl-L- or N-benzyl-D-phenylalanine indicates activation of the analogues under conditions of aminoacylation. Natural noncognate amino acids are not transferred to tRNAPhe-C-C-A or tRNAPhe-C-C-A-(3'-NH2). This pretransfer proofreading mechanism, together with the comparatively low ratio of synthetic to successive hydrolytic steps, resembles the mechanism of liver enzymes of vertebrates. In contrast, eubacterial phenylalanyl-tRNA synthetases achieve the necessary fidelity by post-transfer proofreading, a corrective hydrolytic event after transfer to tRNAPhe. Diadenosine 5',5'''-P1,P4-tetraphosphate synthesis is shown to be a common feature for phenylalanyl-tRNA synthetases from all three lineages of descent. The immunological approach demonstrates that aminoacyl-tRNA synthetases do not belong to the group of enzymes in gene expression with high structural conservation.

Adenine Nucleotides↗
PubMed1985

Carbohydrate-binding proteins of tumor lines with different growth properties. I. Differences in their pattern for three clones of rat fibroblasts transformed with a myeloproliferative sarcoma virus.

Three clones of myeloproliferative virus (MPV)-transformed rat fibroblasts (NRK) with different growth properties and morphology were transplanted to athymic nude mice. Presence of carbohydrate-binding proteins was inferred by fluorescence microscopy using fluorescent, glycosylated markers. Salt and detergent extracts of tumors from this model system were fractionated under identical conditions on different sets of Sepharose columns, to which lactose, asialofetuin, melibiose, mannan and fucose had been covalently linked. Successive elution by chelating reagent and specific sugar resulted in isolation of the different Ca2+ -dependent and Ca2+ -independent endogenous carbohydrate-binding proteins that were assayable as agglutinins. In comparison, the different tumors displayed a pattern with qualitative and quantitative alterations. Since protein-carbohydrate interaction mediated by carbohydrate-binding proteins (lectins) is of importance for cognitive processes, it is remarkable that the pattern of membrane glycoproteins, isolated by affinity chromatography on resins with immobilized plant lectins, had also been found to reveal certain individual properties for receptors specific for peanut agglutinin (PNA) and Ulex europaeus agglutinin (UEA). These demonstrated differences within the system of protein-carbohydrate interaction suggest that endogenous lectins and their ligands have potential significance as markers defining a certain phenotype within this tumor model system.

Animals↗
PubMed1985

Cytostatic drug effects on human clonogenic tumor cells and human bone marrow progenitor cells (CFU-C) in vitro.

Human tumor cells from a squamous cell carcinoma of the lung and from a malignant melanoma and human bone marrow progenitor cells were cultured in a methylcellulose monolayer system. To obtain tumor material for repeated experiments with human tumor specimens, human xenografts grown in the nude mouse system were used. The cultures were incubated continuously with adriamycin, actinomycin-D, bleomycin, cisplatinum, and melphalan. Dose response curves for bone marrow and tumor cell colonies were established. A comparison of bone marrow and tumor cell colony dose response curves might be useful for the assessment of the drug sensitivity of tumor cells independent of in vivo pharmacologic data and duration of drug exposure.

Animals↗
PubMed1985

Effects of cytostatic drugs and 40.5 degrees C hyperthermia on human clonogenic tumor cells.

A tumor colony-forming assay was used to investigate the effect of 40.5 degrees C hyperthermia and drugs on the colony-forming ability of human clonogenic tumor cells. In order to be able to perform repeated incubations with identical tumor material, specimens were used that were augmented in the nude mouse system. Five tumor samples (two malignant melanomas, two squamous cell carcinomas of the lung and one small cell carcinoma of the lung) were incubated with seven drugs: doxorubicin, actinomycin-D, bleomycin, melphalan, vincristine, vinblastin and cisplatinum. One additional tumor specimen (chondrosarcoma) was incubated with doxorubicin immediately after resection. The incubation with drugs at 37 degrees C revealed dose response curves typical for each tumor. Incubation at 40.5 degrees C for 2 hr showed enhanced drug effects in five out of the six tumors tested. The drugs, with an enhanced effect and the pattern of enhancement were different in each individual tumor.

Animals↗
PubMed1985

Endogenous tumor lectins: a new class of tumor markers and targets for therapy?

Endogenous lectins of normal tissues can play a functional role in recognition processes and cell adhesion. These functions are areas of particular relevance to tumor growth and metastasis. Our initial results on endogenous lectins of different tumors lead to the working hypothesis that the pattern of endogenous lectins is qualitatively and quantitatively different between different types of tumors and between tumors and normal, nonmalignant tissues. The endogenous lectins may thus prove to be potentially important in establishing a new concept for a rational lectin-based type of diagnosis and therapy of various tumors.

Animals↗
PubMed1985

Empirical development and evaluation of prehospital trauma triage instruments.

The field identification of the patients who should be taken to trauma centers is a major problem of trauma care. This study appears to be the first to use multivariate analysis to systematically design a field triage instrument and to evaluate its performance in terms of a meaningful and plausible criterion for which patients ought to be treated at trauma centers. Four new triage instruments were created and their performance compared to that of two existing measures, the Trauma Score and the CRAMS scale. The new measures appear to perform better than the best of existing instruments tested, although independent validation is necessary. The one purely physiologic instrument tested appeared to be inferior to instruments that included anatomic and historic as well as physiologic indices. Simple checklists performed approximately as well as weighted scales. No instrument was found to be high in both sensitivity and positive accuracy.

Adolescent↗
PubMed1985

Effects of cytostatic drugs and 40.5 degrees C hyperthermia on human bone marrow progenitors (CFU-C) and human clonogenic tumor cells implanted into mice.

Human spontaneous tumors after surgical resection were implanted into NMRI nude mice. Clonogenic cells from these tumors (4 malignant melanomas, 2 squamous cell carcinomas of the lung, and 1 small cell carcinoma of the lung) were cultured in a methylcellulose monolayer assay. Dose-response curves with 7 cytostatic drugs (doxorubicin, bleomycin, dactinomycin, cisplatin, vincristine, vinblastine, and melphalan) were assessed at 37 degrees C and after a 2-hour pulse at 40.5 degrees C. In addition, bone marrow cells (CFU-C) were plated in the same assay. Dose-response curves were assessed with the same drugs under the same conditions. Hyperthermic treatment without drugs did not alter the colony formation of tumor and bone marrow cells. Bone marrow samples from different donors showed homogeneous response patterns; the tumor probes revealed sensitivity patterns typical for each tumor. In 13 of 48 tumor-drug combinations a thermal enhancement of the drug effects was observed, whereas there was no significant difference between normothermic and hyperthermic cultures in the bone marrow cultures. A comparison of colony and bone marrow dose-response curves suggested that a hyperthermic enhancement can occur in single cases. However, this phenomenon seems to be due to individual properties of the tumor.

Animals↗
PubMed1985

Pattern of endogenous lectins in a human epithelial tumor.

Salt and detergent extracts of a malignant epithelial tumor, obtained by extraction of acetone powder, were fractionated on different sets of Sepharose columns covalently derivatized with lactose, asialofetuin, melibiose, mannan, fucose, and heparin. Successive elution by chelating reagent and specific sugar resulted in isolation of different Ca2+-dependent and Ca2+-independent endogenous carbohydrate-binding proteins, as analyzed by gel electrophoresis. It appears from the analysis that certain bands represent newly identified proteins capable of binding to lactose (at Mr 64,000), melibiose (at Mr 28,000), and fucose (at Mr 62,000 and 70,000). Other carbohydrate-binding proteins isolated from this human tumor have been identified in normal, especially embryonic, tissues of different nonhuman vertebrates. The carbohydrate-binding proteins are assayable as agglutinin with rabbit erythrocytes and show no detectable enzymatic activity. They can thus be defined as lectins. The presence of a complex pattern of endogenous lectins and their biochemical characteristics may contribute to an understanding of intercellular interaction during the complex process of metastatic spread and may furthermore allow a new tool for diagnosis and a lectin-based therapy.

Apudoma↗
PubMed1985

Cell surface lectins of transplantable human teratocarcinoma cells: purification of a new mannan-specific endogenous lectin.

Fractionation of detergent extracts of transplanted tumors of human teratocarcinoma cells by affinity chromatography yields one predominant protein with apparent molecular weight of 14,000 and further, for less abundant protein with apparent molecular weight of 35,000 from lactose-sepharose and one protein with apparent molecular weight of 68,000 from mannan-sepharose. No further carbohydrate-binding protein can be isolated on columns derivatized with asialofetuin, melibiose and L-fucose, to which the extract is applied successively. Both proteins agglutinate trypsinized, glutaraldehyde-fixed rabbit erythrocytes in the absence of Ca2+ and can thus be defined as endogenous human teratocarcinoma lectins. Inhibition of heterotypic and homotypic aggregation of human teratocarcinoma cells by D-mannose, D-galactose and glycoproteins rich in one of these sugars is consistent with a functional role of these Ca2+-independent lectins in cell aggregation. Visualization of these activities by fluorescent mannosylated and lactosylated markers on the cell surface further supports the cell surface localization of these detergent extractable lectins. The mannan-specific lectin, in particular, has so far not been detected in any mammalian tissue or tumor and is of potential value for a lectin-based diagnosis and therapy of embryonal carcinomas.

Carbohydrates↗
PubMed1984

Endogenous lectins of bovine pancreas.

Affinity chromatography of salt and detergent extracts from bovine pancreas on glycosylated or glycoprotein-linked Sepharose 4B resulted in purification of different carbohydrate-binding proteins. Three species of proteins with molecular masses of 16 kDa, 35 kDa and 64 kDa exhibiting specificity for beta-galactosides, but none with preferential specificity for alpha-galactosides, were isolated from salt and detergent extracts. No Ca2+ was required for binding. Mannan-binding proteins of 37 kDa, 47 kDa and 94 kDa without Ca2+-requirement were only found in the salt extract. No other mannan-binding activity could be detected. Fucose-binding proteins of 34 kDa, 62 kDa and 70 kDa exhibiting Ca2+-requirement for binding were present in the salt extract and two proteins with 62 kDa and 70 kDa in detergent extract. The different fractions showed agglutination activity when assayed with rabbit erythrocytes. Thus they can be defined as lectins.

Animals↗
PubMed1984

Intensified therapy in acute lymphoblastic and acute undifferentiated leukemia in adults.

One hundred seventy adult patients with acute lymphoblastic leukemia (ALL) or acute undifferentiated leukemia (AUL) were entered into a prospective multicenter therapy trial at 25 hospitals. The aim of the trial was to improve remission duration by using a modified form of an intensified induction regimen that was successful in childhood ALL, to define immunologic subtypes of ALL by use of cell-surface markers, and to extract other possible prognostic factors. The overall complete remission rate was 77.8%. The median overall survival time was 26 months, being 4 months for nonresponders and 32 months for responders. The median remission duration for the 126 patients with complete remission was 20 months. Prognostically favorable factors for remission duration were response to chemotherapy within 4 weeks, age less than 35 years, a low initial leukocyte count, and the immunologic subtypes c-ALL with early response to therapy and T-ALL, where 61% and 58%, respectively, are still in complete remission at 3 years. An adverse influence on remission duration was observed for the subtype null-ALL, with a median survival of 13 months, and for patients with a delayed response to induction therapy, independent of phenotype.

Acute Disease↗