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M Doser

Publications and source records attributed to M Doser.

29 records · Page 2Linked to original sources
PubMed2001

High density culturing of porcine hepatocytes immobilized on nonwoven polyurethane-based biomatrices.

OBJECTIVE: Hepatocytes are increasingly used as functional units in bioartificial liver devices. The objective of the present study was to investigate the feasibility of culturing porcine hepatocytes in high density on a novel polyurethane-based nonwoven three-dimensional matrix. We investigated (1) the optimal cell density within this culture configuration, (2) the maintenance of liver-specific morphology and cell functions over long-term periods and (3) the necessity to apply an additional extracellular matrix component (collagen gel). METHODS: Nonwoven polyurethane matrices were manufactured by a specially developed fiber extrusion technology. Pig hepatocytes were cultured at various cell densities of 0.1, 0.25, 0.5, 0.75, 1 and 2 x 10(6) cells/cm(2) on three-dimensional networks of nonwoven polyurethane matrices and cell adhesion as well as functional parameters (DNA of nonattached/attached cells, lactate dehydrogenase release and cytochrome P450 activity) were determined. To assess the performance of cells within this configuration albumin and urea excretion was measured over 8 days. The potentially beneficial effect of an additional extracellular matrix configuration was evaluated by comparing the average albumin synthesis in groups of identical cell numbers. RESULTS: The optimal cell density in this three-dimensional culture configuration was 1 x 10(6) cells/cm(2). The functional capacity of hepatocytes was stable for 8 days at an average level of 53.7 +/- 5.6 ng/h/microg DNA and of 1.8 +/- 0.14 microg/h/microg DNA for albumin and urea excretion, respectively. The supplementation of an extracellular matrix configuration did not improve functional activity of cells. Average albumin synthesis was 35.6 ng/h/microg DNA (28.7, 42.8) and 32.7 ng/h/microg DNA (23.4, 49.2) for collagen-immobilized and control cultures, respectively. CONCLUSION: The results of the study indicate that nonwoven polyurethane sheets supply a biocompatible support structure for functionally active high density cultures. Thus, nonwoven polyurethane matrices should be further investigated on with respect to their role in the development, optimization and design of bioartificial liver systems.

Animals↗
PubMed2000

High-precision measurement of the left-right Z Boson cross-section asymmetry.

We present a measurement of the left-right cross-section asymmetry ( A(LR)) for Z boson production by e(+)e(-) collisions. The measurement includes the final data taken with the SLD detector at the SLAC Linear Collider during the period 1996-1998. Using a sample of 383 487 Z decays collected during the 1996-1998 runs we measure the pole value of the asymmetry, A(0)(LR), to be 0.150 56+/-0.002 39 which is equivalent to an effective weak mixing angle of sin (2)straight theta(eff)(W) = 0.231 07+/-0.000 30. Our result for the complete 1992-1998 data set comprising approximately 537 000 Z decays is sin (2)straight theta(eff)(W) = 0.230 97+/-0.000 27.

Journal Article↗
PubMed2000

New non-woven polyurethane-based biomaterials for the cultivation of hepatocytes: expression of differentiated functions.

A new non-woven polyetherurethane support suitable to host cultured hepatocytes has been developed. Prior to its use in bioreactors and artificial liver devices, the biocompatibility of this new material was investigated. The experiments have shown that the survival and functionality of hepatocytes entrapped in the non-woven polymer were longer than that of monolayer cultured hepatocytes, under serum-free culture conditions. Hepatic specific metabolic functions, namely, synthesis of urea and synthesis and secretion of plasma proteins, were well maintained by hepatocytes entrapped in non-woven polyetherurethane sheets. Cells also retained the expression of biotransformation activities of 7-ethoxycoumarin-O-deethylase as well as CYP2A1, CYP2B1 and CYP3A1. The results presented in this paper point to non-woven polyetherurethane sheets as a suitable biocompatible support for functional, three-dimensional hepatocyte cultures.

Journal Article↗
PubMed1996

Metabolic neutrality of perindopril: focus on insulin sensitivity in overweight patients with essential hypertension.

To assess the effects of antihypertensive treatment with the angiotensin-converting enzyme (ACE) inhibitor perindopril on insulin sensitivity, plasma insulin, and lipoprotein metabolism in overweight hypertensive patients, we measured the insulin sensitivity index (SI, determined according to the minimal model method of Bergman), fasting plasma insulin and glucose concentrations, serum total triglyceride and lipoprotein cholesterol fractions, and blood pressure (BP) in 30 overweight [mean body mass index (BMI) 30.9 kg/m2], nondiabetic patients with essential hypertension after a 4-week run-in period and after 6 weeks of perindopril (n = 20) or placebo (n = 10) administered in a double-blind fashion. Furthermore, we estimated their state of physical fitness using the Conconi bicycle ergometer test before and after perindopril or placebo administration. SI was low in our study population (3.2 vs. 13.3 10(-4) ml.microU-1.min-1 in normal lean control subjects). It did not differ between the perindopril and placebo group after the placebo run-in period (3.1 vs. 3.3 x 10(-4) ml.microU-1.min-1) and was not influenced by perindopril (3.3 x 10(-4) ml.microU-1.min-1) or placebo (3.6 x 10(-4) ml.microU-1.min-1) treatment. Moreover, no significant changes were apparent in fasting plasma insulin and glucose, the areas under the glucose and insulin curves, the glucose disappearance rates, serum total triglycerides (TG), or cholesterol or lipoprotein cholesterol fractions between run-in and active treatment phases in the perindopril or the placebo group, respectively. Heart rate (HR), body weight, and anaerobic threshold remained stable in both groups. Compliance, assessed by pill counting was > 90% in both groups at all visits. Therefore, the ACE inhibitor perindopril is neutral with regard to insulin sensitivity, plasma insulin and glucose, and lipoprotein metabolism in overweight, nondiabetic patients with essential hypertension.

Adult↗
PubMed1989

Influence of carbohydrates on the cytotoxicity of an aqueous mistletoe drug and of purified mistletoe lectins tested on human T-leukemia cells.

Partially and highly purified lectins from Viscum album L. (mistletoe) cause a dose-dependent decrease of viability of human leukemia cell cultures, MOLT-4, after 72 h treatment. The LC50 of the partially purified lectin was 27.8 ng/ml, of the highly purified lectin 1.3 ng/ml. Compared to the highly purified lectin a 140-fold higher protein concentration of an aqueous mistletoe drug was required to obtain similar cytotoxic effects on MOLT-4 cells. Cytotoxicity of the highly purified lectin was preferentially inhibited by D-galactose and lactose, cytotoxicity of the mistletoe drug and the partially purified lectin were preferentially inhibited by lactose and N-acetyl-D-galactosamine (GalNAc). Two lectin fractions with almost the same cytotoxic activity on MOLT-4 cells but with different carbohydrate affinities were isolated by affinity chromatography from the mistletoe drug: mistletoe lectin I with an affinity to D-galactose and GalNAc and mistletoe lectin II with an affinity to GalNAc. The lectin fractions and the mistletoe drug inhibited protein synthesis of MOLT-4 cells stronger than DNA synthesis. Furthermore a subpopulation of MOLT-4, resistant to cytotoxic doses of both the mistletoe drug and the mistletoe lectins, was shown to exhibit a reduced amount of GalNAc and N-acetyl-D-glucosamine in their cellular glycoproteins which are probably responsible for the binding of the cytotoxic lectins. These results indicate that lectins are the main toxins in the mistletoe drug.

Carbohydrates↗