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Biomedical subjects

R Marz

Publications and source records attributed to R Marz.

At least 19 recordsLinked to original sources
PubMed2000

The process of defining a profile of student competencies at the University of Vienna Medical School.

CONTEXT: A new law enabling curriculum reform led a small circle of interested faculty members at the University of Vienna medical school to launch the Medizin Curriculum Wien project (MCW) to plan a new curriculum under the supervision of the Committee on Educational Affairs (Studienkommission). OBJECTIVE: The first stage of the project dealt with the definition of a profile of competencies (Qualifikationsprofil), which describes all the competencies we want our students to possess upon graduation. METHOD: This paper presents the approach to and process of defining this profile at one of Europe's largest medical schools, currently enrolling over 1500 new students per year. The procedure involved: preparing materials; communication with stakeholders; information dissemination; feedback gathering; information structuring, and formulating the profile of competencies. RESULTS: Application of the outlined steps in two rounds proved successful for the development of a profile of student competencies for Vienna. General acceptance and awareness of the new profile as well as commitment for a further reform process was engendered. The distinct characteristics of the profile are discussed. CONCLUSION AND UTILIZATION: A profile of student competencies must balance the demanding objectives of curriculum planners and the actual challenges presented by many local parameters; this can be done by employing the process outlined in this paper. The defined profile serves as an accepted reference point in the further development of the medical curriculum.

Austria↗
PubMed1996

Effects of prenatal treatment with betamethasone, L-carnitine, or betamethasone-L-carnitine combinations on the phosphatidylcholine content and composition of the foetal and maternal rat lung.

Pregnant rats received 0.10 or 0.20 mg/kg body weight betamethasone, or 100 mg/kg body weight L-carnitine, or L-carnitine 100 mg/kg plus betamethasone 0.05 or 0.10 mg/kg body weight, or saline (controls) for three days before delivery of foetuses at day 19 of gestation. Dose-related effects on the dipalmitoyl phosphatidylcholine content and the phosphatidylcholine species composition of foetal and maternal lungs were determined. Betamethasone (0.10 and 0.20 mg/kg) or L-carnitine (100 mg/kg) significantly increased (p < 0.05) the dipalmitoyl phosphatidylcholine content in the foetal lungs, while only small changes were found in relative terms. Combinations of betamethasone (0.05 or 0.10 mg/kg) with L-carnitine (100 mg/kg) also significantly increased the dipalmitoyl phosphatidylcholine content of the foetal lungs above control values (p < 0.01) and above the values achieved with betamethasone alone (p < 0.05). In the maternal lungs a significant increase of the dipalmitoyl phosphatidylcholine content above the control values was only found after treatment with betamethasone-carnitine combinations, whereas compared with the foetal lung the relative increase of dipalmitoyl phosphatidylcholine as a fraction of total phosphatidylcholine was more pronounced after betamethasone treatment. The gas chromatographic method used separates two monoenoic phosphatidylcholine species with 32 carbon atoms in the acyl residues. These two phosphatidylcholine species showed striking differences between adult and foetal lungs. Palmitoleyl palmitoyl phosphatidylcholine predominates in the maternal lung, whereas palmitoyl palmitoleyl phosphatidylcholine is the major monoenoic phosphatidylcholine species with 32 carbon atoms in the foetal lung. These two species were not affected in maternal or foetal lung by betamethasone or L-carnitine treatment. In contrast, after treatment with betamethasone-carnitine combinations, a significant increase of the fraction of palmitoyl palmitoleyl phosphatidylcholine was found in foetal but not in the maternal lung. The results of the present study demonstrate that maternal glucocorticoid and carnitine treatment affects the maternal as well as the foetal lung but with different effects on the dipalmitoyl phosphatidylcholine content and phosphatidylcholine species composition.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1995

Membrane transport of nucleobases: interaction with inhibitors.

1. The kinetic properties and the mechanism of nucleobase transport and transport inhibition are briefly reviewed. 2. Many purine derivatives even when bearing large substituents on N9 and C6 are inhibitors of nucleobase transport, some are also substrates. 3. Papaverine and other benzyl-isoquinolines are efficient inhibitors of facilitated transport of nucleobases. 4. Papaverine is a noncompetitive inhibitor of nucleobase transport in human erythrocytes. 5. Reduction of the aromatic isoquinoline to the tetrahydro form causes loss of inhibitory activity whereas replacement of methoxy groups by ethoxy groups leads to increased activity. 6. Papaverine also inhibits sodium dependent active nucleobase transport in pig kidney cells. 7. The nucleoside transport inhibitors dipyridamole and dilazep have no effect on facilitated diffusion transport of nucleobases, but inhibit in micromolar concentrations active sodium dependent nucleobase transport in pig kidney cells.

Animals↗
PubMed1995

Pregnancy-related changes of carnitine and acylcarnitine concentrations of plasma and erythrocytes.

Total-, free-, and acylcarnitine concentrations were determined in whole blood, plasma, and red blood cells of 88 women during pregnancy. Already in the 12th week of gestation the mean whole blood carnitine level was significantly (p < 0.01) lower than those of the controls. From the 12th gestational week up to parturition there was a further significant (p < 0.01) decrease. This reduction of total carnitine in whole bloods was mainly caused by a significant (p < 0.01) decrease of free carnitine levels, since no marked changes of short chain acylcarnitine values were found throughout pregnancy. The contribution of red blood cell L-carnitine to whole blood carnitine increased significantly (p < 0.05) to 61% at delivery versus 39% (controls). In umbilical cord blood free and total carnitine levels were significantly (p < 0.05) higher than the corresponding maternal levels. The contribution of red blood cell L-carnitine to whole blood carnitine was higher in cord blood than in maternal blood. The results of the present study demonstrate that during pregnancy whole blood and plasma carnitine levels decrease to those levels found in patients with carnitine deficiency. Also the percentage of acylcarnitine on total carnitine, found in the present study, is characteristic for a secondary carnitine deficiency. Thus L-carnitine substitution in pregnant women, especially in risk pregnancies, may be advantageous.

Acylation↗
PubMed1995

Nucleobase and nucleoside transport in mammalian cells.

Membrane transport of nucleobases and nucleosides has been an actively pursued research field for the past 25 years. Not only are these substances of physiological interest; derivatives are in clinical use or under investigation for their pharmacological activity against viral and neoplastic disease. An understanding of the molecular pharmacology of these substances includes a detailed knowledge of how they reach their intracellular targets. Membrane transport systems which have so far been found in all cells examined play an important role in this process. Since the transporters are minor membrane components, little is known about them on a molecular basis. This review discusses methodological approaches used to measure initial rates of membrane transport and summarizes current knowledge of the various transport systems which have been characterized with these kinetic methods.

Adenosine↗
PubMed1994

Inhibition of purine nucleobase transport in human erythrocytes and cell lines by papaverine. Investigation of structure-activity relationship.

Papaverine was found to be an effective inhibitor of hypoxanthine transport not only in human erythrocytes, but also in the human cell lines HL60 (myeloic) and U937 (monocytic). IC50 values for inhibition of hypoxanthine influx ranged from 6 to 20 microM. In erythrocytes papaverine was found to be a non-competitive inhibitor of hypoxanthine equilibrium-exchange transport with a Ki value of approximately 13 microM, which is in close agreement with the respective IC50 values estimated for zero-trans influx of hypoxanthine. In addition papaverine also had a slight inhibitory effect on unmediated nucleobase transport, most likely due to a perturbation of the membrane lipid environment. Several papaverine analogs were tested for their inhibitory effect on nucleobase transport. Only ethaverine was as effective as papaverine. Drotaverine and berberine were moderately inhibitory while laudanosine had no inhibitory effect at all. Isoquinoline acted as a very weak inhibitor.

Biological Transport↗
PubMed1994

Effects of hypolipidaemics cetaben and clofibrate on mitochondrial and peroxisomal enzymes of rat liver.

Clofibrate or cetaben was administered to male rats for 10 days. Peroxisomal and mitochondrial enzymes were assayed in liver subcellular fractions. Clofibrate affected the specific activities of both mitochondrial enzymes (glycerol-3-phosphate dehydrogenase and nicotinamide-linked isocitrate dehydrogenase) and peroxisomal enzymes (fatty acyl-CoA oxidase, glycerone phosphate acyltransferase, urate oxidase, and D-amino-acid oxidase). In contrast, cetaben raised only the peroxisomal enzymes, acyl-CoA oxidase, glycerone-phosphate acyltransferase, D-amino-acid oxidase, catalase, and urate oxidase. Thus, the hypolipidaemic activity of these drugs may be exclusively related to stimulated peroxisomal functioning, while mitochondria play only a minor role.

4-Aminobenzoic Acid↗
PubMed1993

Allopurinol transport in human erythrocytes.

The mechanism of allopurinol [4-hydroxypyrazolo(3,4-d)pyrimidine] transport into human erythrocytes was investigated with an inhibitor stop assay. Allopurinol transport could be resolved into two components: (1) a saturable system and (2) a non-saturable process, which most likely represents non-facilitated diffusion. Allopurinol transport had a Km of 268 mumol/L and a Vmax of 28 pmol/microL intracellular volume/sec; the non-saturable component was 0.0195/sec. Mutual inhibition studies showed that the competitive Ki values of hypoxanthine and adenine on allopurinol transport were 120 and 3 mumol/L, respectively. These Ki values as well as the IC50 values of 100-150 mumol/L for hypoxanthine and 3-10 mumol/L for adenine were similar to the corresponding transport Km values of these bases, which are 128 and 8 mumol/L, respectively. The Ki of allopurinol on hypoxanthine transport was 274 mumol/L and thus nearly identical to its Km. Thus in erythrocytes the uricostatic agent allopurinol is an alternative substrate for the purine transport system, but lacks the exceptional high affinity it has for xanthine oxidase. This could explain the paradoxical clinical side effect of allopurinol, namely that it can provoke an attack of gout. Theophylline, a methylated purine, inhibited allopurinol transport with an IC50 of 200-400 mumol/L. Oxypurinol [4,6-dihydroxypyrazolo(3,4-d)pyrimidine], the main metabolite of allopurinol, also inhibited allopurinol transport with an IC50 of 20-40 mumol/L. This is noteworthy, since allopurinol and oxypurinol do not share the same transport system in the kidney.

Allopurinol↗
PubMed1992

Screening for Epstein-Barr and human cytomegalovirus in normal and abnormal cervical smears by fluorescent in situ cytohybridization.

Using the routine Papanicolaou test for grouping, 35 normal and 148 abnormal cervical smears were screened by fluorescent in situ cytohybridization for Epstein-Barr (EBV) and human cytomegalovirus (HCMV). Viral presence was detected in 55% of all hybridized smears while routine Papanicolaou tests exposed no morphological evidence for HCMV or EBV. Thus in situ cytohybridization is necessary and suitable for direct identification of EBV and HCMV. The prevalence of viral infection for women with normal cervical smears was 29% for HCMV and 34% for EBV. Even smears of three of the four virgins were positive for HCMV and two had a mixed infection with EBV. The infection rate with at least one of these two herpesviruses was 51% in the control group, 56% in smears with reactive and reparative cell changes, 54% in mild (slight) dysplasias and 56% in moderate or severe dysplasias. Thus infection with HCMV and EBV did not differ significantly in controls and prevention groups. Both viruses were most frequently found in the age group 20 to 29 years. These data suggest that HCMV and EBV are not involved in the etiology of intraepithelial neoplasias and carcinomas of the uterine cervix.

Adolescent↗
PubMed1991

Adenine and hypoxanthine transport in human erythrocytes: distinct substrate effects on carrier mobility.

Transport of adenine and hypoxanthine in human erythrocytes proceeds via two mechanisms: (1) a common carrier for both nucleobases and (2) unsaturable permeation 4-5-fold faster for adenine for hypoxanthine. The latter process was resistant to inactivation by diazotized sulfanilic acid. Carrier mediated transport of both substrates was investigated using zero-trans and equilibrium exchange protocols. Adenine displayed a much higher affinity for the carrier (Km approximately 5-8 microM) than hypoxanthine (Km approximately 90-120 microM) but maximum fluxes at 25 degrees C were generally 5-10-fold lower for adenine (Vmax approximately 0.6-1.4 pmol/microliters per s) than for hypoxanthine (Vmax approximately 9-11 pmol/microliters per s). The carrier behaved symmetrically with respect to influx and efflux for both substrates. Adenine, but not hypoxanthine reduced carrier mobility more than 10-fold. The mobility of the unloaded carrier, calculated from the kinetic data of either hypoxanthine or adenine transport, was the same thus providing further evidence that these substrates share a common transporter and that their membrane transport is adequately described by the alternating conformation model of carrier-mediated transport.

Adenine↗
PubMed1981

Facilitated transport of 6-mercaptopurine and 6-thioguanine and non-mediated permeation of 8-azaguanine in Novikoff rat hepatoma cells and relationship to intracellular phosphoribosylation.

6-Mercaptopurine and 6-thioguanine strongly inhibited the zero-trans entry of hypoxanthine into Novikoff rat hepatoma cells which lacked hypoxanthine/guanine phosphoribosyltransferase, whereas 8-azaguanine had no significant effect. 6-Mercaptopurine was transported by the hypoxanthine carrier with about the same efficiency as its natural substrates (Michaelis-Menten constant = 372 +/- 23 microM; maximum velocity = 30 +/- 0.7 pmol/microl cell H2O per s). 8-Azaguanine entry into the cells, on the other hand, showed no sign of saturability and was not significantly affected by substrates of the hypoxanthine/guanine carrier. The rate of entry of 8-azaguanine at 10-100 microM amounted to only about 5% of that of hypoxanthine transport and was related to its lipid solubility in the same manner as observed for various substances whose permeation through the plasma membrane is believed to be non-mediated. Only the non-ionized form of 8-azaguanine (pKa = 6.6) permeated the cell membrane. Studies with wild type Novikoff cells showed that permeation into the cell was the main rate-determining step in the conversion of extracellular 8-azaguanine to intracellular aza-GTP and its incorporation into nucleic acids. In contrast, 6-mercaptopurine was rapidly transported into cells and phosphoribosylated; the main rate-determining step in its incorporation into nucleic acids was the further conversion of 6-mercaptopurine riboside 5'-monophosphate.

Animals↗
PubMed1979

Thymidine transport in cultured mammalian cells. Kinetic analysis, temperature dependence and specificity of the transport system.

The transport of thymidine has been characterized kinetically and thermodynamically in Novikoff rat hepatoma cells grown in culture and, less extensively, in mouse L cells, Chinese hamster ovary cells, P388 murine leukemia cells and HeLa cells. That the characterizations pertained to the transport system per se was ensured, (i) by employing recently developed methods for rapid sampling of cell/substrate mixtures in order to follow isotope movements within a few seconds after initial exposure of cells to substrate; (ii) by utilizing cells rendered, by genetic or chemical means, incapable of metabolizing thymidine; and (iii) by demonstrating conformity of the transport data to an integrated rate equation derived for a simple, carrier-mediated system. The results indicate that thymidine is transported into mammalian cells by a functionally symmetrical, non-concentrative system for which the carrier : substrate dissociation constant ranges from about 100 microM in Chinese hamster ovary cells, to 230 microM in Novikoff hepatoma cells. In all cell lines investigated, the velocity of transport was sufficient to nearly completely equilibrate low concentration of thymidine across the membrane membrane within 15 s. Temperature dependence of transport velocity and substrate : carrier dissociation were continuous (EA = 18.3 kcal/mol, delta H0' = 9.3 kcal/mol, respectively), and showed no evidence of abrupt transitions. Several natural and artificial nucleosides and nucleic acid bases inhibited influx of radiolabeled thymidine, apparently by competing with thymidine for the transport carrier.

Animals↗
PubMed1979

Purine and pyrimidine transport and phosphoribosylation and their interaction in overall uptake by cultured mammalian cells. A re-evaluation.

The zero-trans uptake of purines and pyrimidines was measured in suspensions of Novikoff rat hepatoma, mouse L, P388 mouse leukemia, and Chinese hamster ovary cells by a rapid kinetic technique which allows the determination of uptake time points in intervals as short as 1.5 s. Kinetic parameters for purine/pyrimidine transport were determined by measuring substrate influx into cells in which substrate conversion to nucleotides was negligible either due to lack of the appropriate enzymes or to depletion of the cells of ATP (5'-phosphoribosylpyrophosphate), and by computer fitting exact, integrated rate equations derived for various carrier-mediated transport models directly to zero-trans influx data. The results indicate that different carriers function in the transport of hypoxanthine/guanine, adenine, and uracil with substrate:carrier association constants (K) at 24 degrees C of 300 to 400 muM, 2 to 3 mM, and about 14 mM, respectively, for Novikoff cells. K and Vmax for hypoxanthine transport by L and P388 cells are similar to those for Novikoff cells, but the transport capacity of Chinese hamster ovary cells is much lower and K = 1500 muM. All transport systems are completely symmetrical. Hypoxanthine transport is so rapid that an intracellular concentration of free hypoxanthine (90%) close to that in the medium is attained within 20 to 50 s of incubation at 24 degrees C, at least at extracellular concentrations below K. In cells in which conversion to nucleotides is not blocked free hypoxanthine accumulates intracellularly to steady state levels with equal rapidity and thereafter the rate of hypoxanthine uptake into total cell material is strictly a function of the rate of phosphoribosylation. The low Km systems for hypoxanthine (1 to 9 muM) and adenine (0.2 to 40 muM) uptake detected previously in many types of cells reflect the substrate saturation of the respective phosphoribosyltransferases rather than of the transport system.

Animals↗
PubMed1978

Properties of the thymidine transport system of Chinese hamster ovary cells as probed by nitrobenzylthioinosine.

The transport of thymidine into Chinese hamster ovary cells grown in suspension culture was measured under conditions in which thymidine was not metabolized, namely, when cells had been depleted of ATP. The system transporting thymidine was saturable (Kztm = 70 micron), rapid 50% of transmembrane equilibrium level attained within 8 sec), and was apparently shared by other nucleosides, but not thymine or hypoxanthine. 6([4-nitrobenzyl]thio)-9-beta-D-ribofuranosylpurine, "nitrobenzylthioinosine", inhibited thymidine transport in a simple, noncompetitive fashion with an apparent Ki = 1.0 nM (based on total concentration of inhibitor, which significnatly overestimates that of free inhibitor). The rate of expression of inhibition was slow (t 1/2 = 17 sec) relative to the rate of association of thymidine with its transporter, and thymidine partially protected the transport system against inhibition by nitrobenzylthioinosine. The dissociation constant for the inhibitor-transporter complex was estimated at about 0.1 nM, and the number of binding sites per cell at about 6 x 10(4). HeLa, P388 murine leukemia, and mouse L cells were as sensitive to nitrobenzylthioinosine inhibition of thymidine transport as Chinese hamster ovary cells; Novikoff rat hepatoma cells were much less sensitive.

Animals↗
PubMed1978

Metabolic stability of the nucleoside transport system of Novikoff rat hepatoma cells.

Rates of transport of uridine and thymidine, estimated with a rapid sampling technique, did not change with culture age. Inhibition of cellular RNA and protein synthesis for periods up to 6 h, did not lead to a loss of nucleoside transport activity. Mild treatment of cell suspensions with trypsin or neuraminidase had no effect on the kinetics of thymidine transport. Thus we conclude, contrary to previous reports, that nucleoside transporters are metabolically stable and that the decreases in nucleoside uptake rates observed with decreased protein synthesis reflect loss of nucleoside kinase activities. These kinases (which have narrow substrate specificity) rather than the membrane-associated, transport apparatus (which has broad substrate specificity) are the most likely sites for regulation of nucleoside uptake.

Animals↗