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Biomedical subjects

T Wagner

Publications and source records attributed to T Wagner.

At least 235 records · Page 13Linked to original sources
PubMed1989

Erythropoietin/haemoglobin relationship in leukaemia and ulcerative colitis.

The erythropoietin level was measured, by bioassay in polycythaemic mice, in the serum of anaemic patients suffering from different types of leukaemia. Comparative measurements were carried out in patients with ulcerative colitis. Serum erythropoietin was less well-correlated with the haemoglobin concentration in leukaemia than in ulcerative colitis. While serum erythropoietin did not exceed 200 mU/ml in patients with ulcerative colitis (lowest blood haemoglobin concentration 56 g/l), several of the leukaemic patients had serum erythropoietin levels above 500 mU/ml at comparable degrees of anaemia. Bone marrow biopsy showed that erythropoiesis was severely impaired in the leukaemic patients whose erythropoietin values were relatively high. These findings are in accord with the hypothesis that the plasma level of erythropoietin depends not only on the haemoglobin concentration of the blood but also on the bone marrow responsiveness to the hormone.

Adolescent↗
PubMed1989

Expression of the glycoprotein hormone alpha-subunit gene in the placenta requires a functional cyclic AMP response element, whereas a different cis-acting element mediates pituitary-specific expression.

The single-copy gene encoding the alpha subunit of glycoprotein hormones is expressed in the pituitaries of all mammals and in the placentas of only primates and horses. We have systematically analyzed the promoter-regulatory elements of the human and bovine alpha-subunit genes to elucidate the molecular mechanisms underlying their divergent patterns of tissue-specific expression. This analysis entailed the use of transient expression assays in a chorionic gonadotropin-secreting human choriocarcinoma cell line, protein-DNA binding assays, and expression of chimeric forms of human or bovine alpha subunit genes in transgenic mice. From the results, we conclude that placental expression of the human alpha-subunit gene requires a functional cyclic AMP response element (CRE) that is present as a tandem repeat in the promoter-regulatory region. In contrast, the promoter-regulatory region of the bovine alpha-subunit gene, as well as of the rat and mouse genes, was found to contain a single CRE homolog that differed from its human counterpart by a single nucleotide. This difference substantially reduced the binding affinity of the bovine CRE homolog for the nuclear protein that bound to the human alpha CRE and thereby rendered the bovine alpha-subunit promoter inactive in human choriocarcinoma cells. However, conversion of the bovine alpha CRE homolog to an authentic alpha CRE restored activity to the bovine alpha-subunit promoter in choriocarcinoma cells. Similarly, a human but not a bovine alpha transgene was expressed in placenta in transgenic mice. Thus, placenta-specific expression of the human alpha-subunit gene may be the consequence of the recent evolution of a functional CRE. Expression of the human alpha transgene in mouse placenta further suggests that evolution of placenta-specific trans-acting factors preceded the appearance of this element. Finally, in contrast to their divergent patterns of placental expression, both the human and bovine alpha-subunit transgenes were expressed in mouse pituitary, indicating differences in the composition of the enhancers required for pituitary- and placenta-specific expression.

Animals↗
PubMed1989

[Teratogen-modified palatogenesis in the Uje: WIST rat. 4. Scanning electron microscopic morphology of the epithelium during the formation of the secondary palate].

In normal morphogenesis age-dependent and regional differences in the surface structure of epithelial cells appear, whereas in teratogenesis no qualitative changes can be observed. During the horizontal adjustment of the palatal shelves the pronounced marking of the cellular borders with microvilli has disappeared. The reduced number of microvilli in the subsequent phase of adhesion might affect the cell-cell identification and thus disturb the further cell differentiation.

Animals↗
PubMed1988

Tissue-specific expression and dietary regulation of a chimeric phosphoenolpyruvate carboxykinase/bovine growth hormone gene in transgenic mice.

A series of transgenic mice was produced by microinjection of a segment of DNA, containing 460 base pairs of the phosphoenolpyruvate (P-enolpyruvate) carboxykinase promoter-regulatory region ligated to the bovine growth hormone structural gene, into the male pronucleus of fertilized mouse eggs. Founder animals which contained the gene were selected for further analysis and for breeding. The concentration of bovine growth hormone in the serum of animals which were shown to contain the gene ranged from a low of 5 ng/ml serum to approximately 2300 ng/ml serum. Mice with high levels of bovine growth hormone had growth rates double that of their litter mates which did not contain the transgene. The transgene was expressed only in the liver and kidney of the animals studied, and the level of specific mRNA for bovine growth hormone in these tissues could be regulated by diet in a manner similar to the endogenous P-enolpyruvate carboxykinase gene. Feeding the animals a diet high in carbohydrate for 1 week caused a 90% decrease in the concentration of bovine growth hormone in the blood, suggesting that the expression of the chimeric P-enolpyruvate carboxykinase/bovine growth hormone gene is sensitive to insulin. When the same animals were then refed a diet high in protein, but devoid of carbohydrate, the concentration of bovine growth hormone in their blood was induced 30-fold within a week. The administration of dibutyryl cyclic AMP to the transgenic mice caused a 2-fold induction in the level of bovine growth hormone in the serum within 90 min. Thus the region between -460/+73 in the P-enolpyruvate carboxykinase promoter-regulatory region contains sequences which can direct the tissue-specific expression, as well as hormonal and dietary responsiveness, of a linked structural gene.

Amino Acid Sequence↗
PubMed1988

Effects of fosfomycin, mesna, and sodium thiosulfate on the toxicity and antitumor activity of cisplatin.

Fosfomycin and mesna were investigated in rats and mice concerning their detoxifying effects on cisplatin toxicity in comparison to sodium thiosulfate, a known protector against cisplatin nephrotoxicity. After separate i.p. injection of cisplatin and fosfomycin (500 mg/kg) or mesna (800 mg/kg) a slight increase in the 50% lethal dose of cisplatin was found in all animals. In mice sodium thiosulfate proved to be far more effective in preventing lethal toxicity and nephrotoxicity as measured by blood urea nitrogen increase. Fosfomycin and mesna were almost without influence on cisplatin treatment of L-1210 leukemia whereas their inhibition of the antitumor effect against S-180 ascites sarcoma (increase of in cisplatin dose to cure 50% of animals from 2.0 mg/kg to 3.5/4.7 mg/kg cisplatin) was similar to thiosulfate, which showed a strong inhibiting effect in the treatment of both tumors. In rats fosfomycin distinctively reduced the antitumor efficacy of cisplatin against Yoshida ascites sarcoma. Thus the concurrent injection of fosfomycin and mesna reduced both the toxicity and the antitumor activity of cisplatin. Therefore their simultaneous administration in addition to cisplatin via the same injection route should be avoided. Due to the weak detoxifying efficacy of fosfomycin and mesna they cannot be used instead of sodium thiosulfate for renal protection against cisplatin toxicity in local i.p. treatment modalities.

Animals↗
PubMed1988

[Blood coagulation and fibrinolytic factor activities in the amniotic fluid].

Plasma and 138 samples of amniotic fluid were obtained from 129 patients during the 15th to 39th pregnancy week and during parturition. Factor activities of the coagulation and fibrinolytic system were studied by means of enzymatic-kinetic measurement methods to differentiate the haemostaseological properties of the amniotic fluid. The factor X activity drops in the amniotic fluid during the third trimester and during parturition. The activities of plasminogen, alpha 1-antitrypsin, alpha 2-antiplasmin, antithrombin III and alpha 2-macroglobulin in the amniotic fluid do not change significantly during gestation and parturition. None of these factors seems to show any difference between the activities in the maternal placenta and in the amniotic fluid. The most striking change in activity was seen with prothrombin. There is a marked increase between the second and third trimester. In the maternal plasma the activity is relatively constant within the standard range of non-pregnant women. Further studies will be necessary to find out whether the increase in prothrombin activity in the amniotic fluid correlates with the increased surfactant production in the fluid and may thus be of diagnostic importance.

Amniocentesis↗
PubMed1988

Cysteamine protects against diarrhoea induced by castor oil. This protective effect can be potentiated by SH-alkylator treatment.

Cysteamine given orally or subcutaneously protects against diarrhoea induced by castor oil. Pretreatment with N-EM, an SH-alkylator, does not influence the occurrence of diarrhoea. Furthermore, N-EM pretreatment does not influence the protective effect of loperamide or difenoxilate. However, N-EM pretreatment potentiates the protective effects of cysteamine or indomethacin against diarrhoea. These findings indicate that sulfhydryl-sensitive processes may also be involved in the mechanisms of diarrhoea.

Alkylating Agents↗
PubMed1987

[Congenital protein C deficiency and thromboembolic diseases].

Besides its cofactor protein S and antithrombin III, protein C is one of the most important inhibitors of plasma coagulation. In seven members of a family as well as in three further unrelated patients, a congenital protein C deficiency with thromboembolic diseases including a coumarin necrosis was observed in two cases. Deficiency of protein C predisposes to the occurrence of thromboembolism, but the severity of the underlying heterozygotic genetic defect can also vary within the family. Long-term oral anticoagulation with phenprocoumon is the therapy of choice. Genetic counselling should always be carried out.

Adult↗
PubMed1987

CpA containing oligoribonucleotides specifically inhibit protein synthesis in rabbit reticulocytes.

The diribonucleoside monophosphate CpA (and no others) inhibits polypeptide chain elongation in rabbit reticulocyte lysates at 10-50 microM. Furthermore, all the trinucleotides containing CpA, i.e., XpCpA and CpApX (X = U, C, A or G) block polypeptide chain elongation as well. At 10 microM the inhibition by XpCpA and not CpApX is transient because a 3'-exonucleolytic activity destroys the critical CpA moiety. The inhibitors do not appear to interfere with the aminoacylation of tRNAs or disrupt the interaction of amino-acyl-tRNAs with the protein synthetic machinery. High levels (200 microM) of CpA or the trinucleotides containing CpA have no effect on translation in a wheat germ cell-free system.

Adenosine↗
PubMed1987

Influence of mesna and cysteine on the systemic toxicity and therapeutic efficacy of activated cyclophosphamide.

Presumably the coadministration of the uroprotector mesna in cyclophosphamide treatment does not influence the systemic activity of its activated metabolite. This was newly investigated in a mouse model. The LD50 values of i.p. administered mafosfamide, a derivative of act. CP, were increased by the simultaneous i.p. administration of mesna (mafosfamide: mesna 1:2 on a molar weight basis) from 590 mg/kg to 750 mg/kg, and after i.v. injection of cytostatic and thiol from 505 mg/kg to 810 mg/kg. Administration of 2 X molar cysteine i.v. or i.p. to mafosfamide-treated animals was even more effective against its lethal toxicity (LD50 i.p. 1800 mg/kg and i.v. 1130 mg/kg). Bone marrow toxicity (severe leukocytopenia) was partially abolished by both thiols. Also the therapeutic efficacy of act. CP against L1210 leukemia in DBA2 mice was reduced by 50% in the presence of cysteine and of mesna. Compared with mesna the higher detoxification effect of cysteine is attributed to its longer half-life (t1/2 20 min vs 12 min of mesna) and presumably an accumulation of cysteine in some cell systems (distribution coefficient 1.20 ml/g vs 0.68 ml/g of mesna). Nevertheless, our study clearly demonstrates a distinct systemic deactivation of act. CP by mesna, which might be of clinical relevance.

Animals↗
PubMed1987

Repeated high-dose cyclophosphamide administration in bone marrow transplantation: exposure to activated metabolites.

Blood levels of cyclophosphamide (CP) and activated metabolites were measured in 11 patients undergoing a 2- to 4-day conditioning chemotherapy for bone marrow transplantation. Urinary excretion of CP was determined in five patients. CP half-life decreased after pretreatment from an average of 7.1 h on the 1st day to 5.5 h on the 2nd day (P less than 0.005) and to 4.3 h on the 4th day (P less than 0.005). No characteristic changes in urinary excretion could be observed. At the same time the exposure to non-protein-bound activated metabolites increased from 10.5 to 19.5 and 26.0 nmol x h/ml respectively (P less than 0.005 and P less than 0.04). Thus, in contrast to in vitro and animal studies, no evidence for an inhibition of activating enzymes could be found. On the contrary, pretreatment seems to enhance the production of the cytotoxic metabolites. The possible explanation of these changes by enzyme induction and by the role of saturated protein binding sites is discussed. Exposure to active metabolites might be altered by dose splitting or even by a change in the duration of the infusion.

Adolescent↗