Search PubMed⌕ Search

Biomedical subjects

A Burger

Publications and source records attributed to A Burger.

205 records · Page 12Linked to original sources
PubMedDate not supplied

The effect of (+/-)-dobutamine on adrenergic nerve endings.

Possible effects of (+/-)-dobutamine on adrenergic nerve endings were determined in experiments with ghosts of bovine chromaffin granules, with rat phaeochromocytoma (PC-12) cells and with the rat vas deferens. Dobutamine inhibited the vesicular uptake of a mixture of 70% adrenaline + 30% 3H-noradrenaline into ghosts, with an IC50 of 1.7 mumol/l. Dobutamine inhibited uptake1 of 3H-noradrenaline in PC-12 cells (with an IC50 of 0.38 mumol/l) without being a substrate. However, dobutamine easily entered PC-12 cells by diffusion. After inhibition of MAO, COMT and vesicular uptake dobutamine (15 and 45 mumol/l) released tritium from rat vasa deferentia preloaded with 3H-noradrenaline. Equi-inhibitory concentrations of dobutamine and desipramine (against uptake1) were equi-releasing. On the other hand, when MAO and vesicular uptake were intact, dobutamine (15 mumol/l) increased the efflux of tritium from preloaded vasa deferentia much more than did an equi-inhibitory concentration of desipramine. Most of the released tritium was then 3H-DOPEG. Dobutamine is a potent inhibitor of uptake1 as well as of vesicular uptake; moreover, it easily diffuses into adrenergic nerve endings. Hence, it blocks the neuronal and the vesicular re-uptake of noradrenaline; consequently, when MAO and vesicular uptake are intact, dobutamine increases the net leakage of noradrenaline from the storage vesicles, thereby leading to an efflux of deaminated metabolites. However, dobutamine is virtually unable to release noradrenaline into the extracellular space.

Adenosine Triphosphate↗
PubMedDate not supplied

The use of recombinant adeno-associated viral vectors for the transduction of epithelial tumor cells.

Using hight-titer recombinant adeno-associated viral vectors (rAAV), we have investigated the feasibility of cancer vaccines from tumor explants. In a first set of experiments, rAAV vectors expressing firefly luciferase reporter genes were used to transduce different human tumor cell lines. At day three post transduction, all of the human tumor cell lines tested showed high levels of luciferase expression. To further evaluate rAAV-mediated gene transfer efficiency into primary tumor cells, we transduced freshly isolated tumor cells from malignant melanoma and ovarian carcinoma patients. As a remarkable result, reporter gene expression in primary tumor cells was significantly higher than in the tested established tumor cell lines. These data could also be reproduced with a rAAV/lacZ vector, since the portion of successfully transduced primary tumor was higher than 90%. Taken together, our data demonstrate that rAAV-mediated gene transfer is a very efficient method for the transduction of freshly isolated human tumor cells and may allow the generation of potent autologous cancer vaccines.

Adenoviridae↗
PubMedDate not supplied

Preparation of 1-(3-C-(propa-1,2-dienyl)-D-ribo-pentofuranosyl)uracil, an allenic nucleoside.

The Crabbé reaction was extended to the preparation of C-3'-allenyl-uridine. The effects of solvent and protecting group on the reaction were studied. The conversion in refluxing dioxan of disilyl either 3 proceeds to the corresponding allenic nucleoside 7; whereas, in refluxing THF the Mannich base 5 was obtained. Fully deprotected Mannich base and allenic uridines 6 and 9 were tested for their antitumor activity.

Alleles↗
PubMedDate not supplied

Evaluation of the antitumor activity of 1-(3-C-ethynyl-beta-D-ribofuranosyl) (PJ272), a recent ribonucleoside analogue.

The antiproliferative properties of a new ribonucleoside derivative, 1-(3'-C-ethynyl-beta-D-ribofuranosyl)uracil (PJ 272) that we synthesized a few years ago, were investigated in vitro on a variety of tumor cell lines from human and murine origins and in vivo, in tumor bearing mice. Using the 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, we showed the ability of this compound to depress, at nanomolar concentrations, the growth of leukemia and lymphoma cultured cells. In 7 out of 8 tumor cell lines tested concentration of 50% inhibition (IC50) was found to be less than 25 nM. PJ 272 was also shown to present the same cytotoxicity against K562 Adriamycin-resistant cell line, which express a multi-drug resistance (MDR) phenotype, and its Adriamycin-sensitive parent cell line. Moreover, when injected intraperitoneally at 20 mg/kg every three days, PJ 272 was found to significantly increase the survival rate (T/C = 149%) of DBA/2 mice injected intraperitoneally with L1210 leukemic cells. Taken together, these results suggest that PJ 272 could be considered as a potentially very active drug against lymphoma and leukemia.

Animals↗