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J Schindler

Publications and source records attributed to J Schindler.

At least 73 records · Page 4Linked to original sources
PubMed1986

[Measuring cyclosporin in immunosuppressive treatment following liver and heart transplantation].

Selective suppression of the immune system in graft recipients is now achieved in most cases by treatment with cyclosporine A. Due to large individual differences in absorption, utilization and metabolisation of this drug, therapeutic blood levels (immunosuppression/toxicity) can be maintained only by frequent measurements of the cyclosporine concentrations in blood samples and dosage readjustments. In the present study, we measured cyclosporine in whole blood samples from 37 patients (23 liver and 14 heart transplant recipients) using an high pressure liquid chromatographic method for native cyclosporine A which has been developed in our laboratory and a radioimmunoassay method (cyclosporine A + metabolites). By comparison of the results of HPLC and RIA-measurements (n = 520) we found a relatively stable metabolization rate (RIA/HPLC-ratio) of 4.23 +/- 1.30 for heart transplant recipients. In contrast RIA/HPLC ratios were highly variable in liver graft recipients ranging from 1.3-9 for the same patient in the posttransplant period. The liver recipients could be classified into two groups according to their mean RIA/HPLC-ratios: for 11 patients we observed a mean ratio of 2.65 +/- 0.35, for another 12 patients one of 4.35 +/- 0.75. Lower metabolisation rates seem to be associated with low donor age. No direct correlation was found between changes in RIA/HPLC-ratios and liver function, rejection and infection periods. Rejection treatment with high doses of methylprednisolone had no systematic influence on cyclosporine metabolisation in our patients. Since cyclosporine metabolites, at least those ones which are most abundant, have less immunosuppressive and toxic effects we recommend measurements of cyclosporine blood concentrations with any HPLC-method specific for the unchanged drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, High Pressure Liquid↗
PubMed1986

alpha-Difluoromethylornithine induces differentiation of a human embryonal carcinoma cell line in vitro.

Human embryonal carcinoma cells could serve as a useful model system for analysis of early human development. A limited number of human embryonal carcinoma cell lines have been generated from in vivo tumors. We report here that alpha-difluoromethylornithine, a specific enzyme-activated inhibitor of ornithine decarboxylase activity, can induce differentiation in human embryonal carcinoma cells. The differentiated phenotype could be distinguished from undifferentiated cells by altered cellular morphology, biochemical and cell surface antigenic properties. These results suggest that alterations in the intracellular levels of polyamines may play a role in human embryonal carcinoma cell differentiation, and possibly human embryogenesis.

Actins↗
PubMed1985

The response of several murine embryonal carcinoma cell lines to stimulation of differentiation by alpha-difluoromethylornithine.

In an attempt to better establish the relationship between polyamine levels and the differentiation of embryonal carcinoma cells, we have examined the ability of alpha-difluoromethylornithine (DFMO), a known inducer of differentiation in one embryonal carcinoma cell line, to stimulate the differentiation of embryonal carcinoma cells from a variety of cell lines. Differentiation was monitored using a variety of criteria including morphological alterations and changes in biochemical and antigenic parameters. Depending on their response to difluoromethylornithine, three classes of cell lines could be identified, those which 1) differentiate extensively, 2) differentiate poorly, and 3) fail to differentiate. Three different classes of embryonal carcinoma cell lines reflect differential changes in polyamine levels resulting from inhibition of ornithine decarboxylase enzyme activity by DFMO. The specific cell lines which exhibit large decreases in both ornithine decarboxylase activity and polyamine levels also show extensive differentiation. The cell lines which show only moderate decreases in enzyme activity and polyamines differentiate poorly while the cell lines which fail to respond to DFMO in that polyamines do not drop below the threshold level necessary to induce differentiation fail to differentiate. These studies suggest that decreases in intracellular polyamines induce EC cell differentiation in vitro.

Animals↗
PubMed1985

Alterations in polyamine metabolism during embryonal carcinoma cell differentiation in vitro.

Murine embryonal carcinoma (EC) cells can be stimulated to differentiate by several chemical inducers. Since the response of EC cells to induction is likely to occur shortly after exposure to the inducer, we report here the changes that occur in polyamine levels in a number of EC cell lines shortly after exposure to two chemical stimuli, alpha-difluoromethylornithine (DFMO) and retinoic acid (RA). Our results suggest that polyamine levels are important in determining the state of EC cell differentiation, but that reduction in these levels alone is not sufficient to induce differentiation in all the EC cell lines tested. Also, it is apparent that RA does influence levels of polyamines. However, this influence does not seem to be mediated through direct interaction with ODCase.

Animals↗
PubMed1985

[Plasma amino acid pattern in gastrointestinal carcinoma].

We evaluated the free-plasma amino acid patterns of 156 patients with various gastrointestinal carcinomas at different tumor stages. As a control group, the plasma amino acid pattern of 73 healthy volunteers at different ages was determined. From out results we were able to compute a linear model of seven amino acids using computer-based stepwise discriminant analysis. This formula in the form of a Tumor-Index can be used as a prognostic indicator for the presence or absence of a gastrointestinal carcinoma.

Adenocarcinoma↗
PubMed1985

[Changes in plasma amino acid level as a possible tumor marker in cancers of the gastrointestinal tract].

We evaluated the free-plasma amino acid pattern in 73 healthy volunteers and 156 patients with gastrointestinal carcinomas after an overnight fast. None of the examined persons showed a sign of malnutrition or metabolic illness. Differences of more than +/- 40% in the concentrations of methionine, phenylalanine, glutamic acid, ornithine, taurine, and phosphoserine were found in cancer patients compaired to healthy volunteers. Tumorstage but not localization or grading correlated significantly with most amino acids. From our results we were able to compute a linear model of seven amino acids using computer-based stepwise discriminant analysis. This formula in the form of a tumor-index can be used as a prognostic indicator for the presence or absence of a gastrointestinal carcinoma.

Adenocarcinoma↗
PubMed1984

[Imbalances of neutral plasma amino acids as a pathogenetic factor in anorexia].

Studies in anorectic tumor-bearing rats indicate that anorexia is correlated to imbalances of neutral amino acids in blood and CNS. Consequently plasma amino acids of patients with neoplastic and non-neoplastic internal diseases were studied during phases of anorexia; special regard was given to the precursors of dopamine and serotonin. Anorectic patients were compared to non-anorectic patients with neoplasia. During anorexia, plasma levels of valine and leucine and hence the ratio of the molar concentrations of Val + Leu + Ile/Phe + Tyr were significantly decreased in each anorectic patient as compared to non-anorectic patients whose ratios were always within the normal ranges. As aromatic and branched-chain amino acids compete for penetration of the blood brain barrier, the decrease of the amino acid ratio may induce a raised flux of phenylalanine and tyrosine into the CNS which results in an increased activation of dopaminergic neurons--known to cause anorexia.

Amino Acids, Branched-Chain↗
PubMed1984

Changes in protein synthetic profiles during retinoic-acid induction of differentiation of murine embryonal carcinoma cells.

Analysis of two-dimensional gel electrophoretic patterns of proteins labeled with [35S]methionine was undertaken to investigate changes in gene expression in embryonal carcinoma cell line Nulli-SCC1 during the induction of differentiation in vitro by retinoic acid. The results indicate that changes in protein profiles occur long before overt morphological differentiation is observed. Studies utilizing the antimetabolite, alpha-amanitin, coupled with those involving the cell-free translation of poly(A)+ -RNA, suggest that gene expression is controlled post-transcriptionally as well as transcriptionally. In this respect, embryonal carcinoma cells appear to resemble early embryonic cells, which show evidence of multiple levels of control of gene expression during the initial stages of development and differentiation.

Amanitins↗
PubMed1984

Inducer-dependent phenotypic divergence in an embryonal-carcinoma cell line.

In monolayer cultures, embryonal carcinoma (EC) cells from the cell line Nulli-SCCl can be induced to differentiate at high efficiency by exposure to either retinoic acid or hexamethylenebisacetamide. Depending on which inducing agent is used, two distinct differentiated phenotypes result. These phenotypes resemble two of the earliest differentiated derivatives of the cells of the inner cell mass of a mouse blastocyst, i.e., parietal and visceral endoderm. Both differ from EC cells as well as from each other on the basis of their morphology, antigenic expression, secretion of plasminogen activator, and protein-synthetic profiles.

Acetamides↗
PubMed1983

Inhibition of ornithine decarboxylase induces embryonal carcinoma cell differentiation.

Murine embryonal carcinoma cells can be induced to differentiate in vitro by various physical and chemical means. We report here that inhibition of ornithine decarboxylase activity with a specific enzyme-activated inhibitor, alpha-difluoromethylornithine, can induce differentiation in embryonal carcinoma cells. The differentiated phenotype can be distinguished from undifferentiated embryonal carcinoma cells by altered cellular morphology, biochemical and cell surface antigenic properties. These results suggest that alterations in the levels of cellular polyamines may play a role in embryonal carcinoma cell differentiation.

Animals↗
PubMed1983

Numerical identification of microorganisms using the HP-41C calculator.

A program is described, which implements the algorithm of numerical identification of bacteria based on Bayes' theorem. The hand-held calculator HP-41C enables one to handle identification matrices containing more than 600 elements, which are packed in groups of five into one storage register. A part of the available storage is reserved for alpha-numeric designation of tests and species. Databases for different bacterial groups are stored on magnetic cards. Computation time does not exceed 400 s.

Bacteria↗
PubMed1983

A hydrogen sulphide producing Gram-negative rod from water.

The biochemical properties of a hydrogen sulphide-producing Gram-negative rod, provisionally designated HG group, were compared with those of the known H2S-producing and H2S-negative Enterobacteriaceae and related organisms. Sixty-four tests were used as a basis for numerical identification. All these tests demonstrated a distinctness of the HG group from other members of Enterobacteriaceae and related organisms. Results of numerical identification are discussed. According to the guanine-plus-cytosine molar content in DNA the bacterium could belong to the tribe Escherichiae of the family Enterobacteriaceae. Plasmids of different molecular size or linear fragments of DNA were found in 17 of 19 strains which indicates that the H2S production is not in correlation with the occurrence of a plasmid of definite size. So far, the only habitat of the HG group had been water, and it seems to be no rarity. Among 28 HG strains a single isolate HG16 was found which differs from HG group in biochemical properties. The distinctness of this single isolate has been confirmed also by numerical identification. Note: On the basis of DNA-DNA hybridization performed by Dr. P.A.D. Grimont and coworkers the HG group has been established as a new genus and a single species. The authors accordingly propose for the group the generic name Budvicia and the specific epithet aquatica.

Cytosine↗