Search PubMed⌕ Search

Biomedical subjects

G Kiefer

Publications and source records attributed to G Kiefer.

At least 37 records · Page 2Linked to original sources
PubMed1984

Antitumor cell and antimetabolic effects of 5-ethyl-2'-deoxyuridine and 5'-substituted 5-ethyl-2'-deoxyuridine derivatives.

A series of forty 5'-ester derivatives of 5-ethyl-2'-deoxyuridine (EDU) have been evaluated for their inhibitory effects on the growth and metabolism of murine leukemia L1210 cells. Several EDU esters proved as potent as EDU in their inhibitory effects on L1210 cell growth (inhibitory dose-50:5-10 micrograms/ml), suggesting that these esters were readily hydrolyzed to release the parent compound EDU. That the EDU esters had to be hydrolyzed first to EDU was further suggested by the dependence of their antiproliferative action on the thymidine kinase activity of the cells. It was further ascertained that EDU and its esters acquired their antiproliferative effects by an interaction with dCTP biosynthesis, possibly at the CDP ribonucleotide reductase step. Under conditions where thymidine was readily incorporated, we were unable to demonstrate any incorporation of EDU into L1210 cell DNA.

Animals↗
PubMed1982

2-14C-1-Allyl-3,5-diethyl-6-chlorouracil I: Synthesis, absorption in human skin, excretion, distribution, and metabolism in rats and rabbits.

With 14C-potassium cyanate as the starting material, 2-14C-1-allyl-3,5-diethyl-6-chlorouracil was synthesized for in vitro and in vivo absorption studies in human skin and for metabolic studies in rats and rabbits. The radioactivity in the horny layer, epidermis, and dermis of the human skin was determined after different intervals of time, and the radioactivity excreted in the urine was measured by collecting samples for 5 days from a patient and also under occlusion conditions. Almost 90% of the radioactivity remained on the surface and approximately 6.28% penetrated and was systemically absorbed. Over a 5-day period, a total of 3.25% was excreted. Almost 3% was systemically absorbed and cumulated in the system. After intraperitoneal application in male and female rats, most of the radioactivity was excreted in the feces and urine, with female rats excreting more in the urine than male rats. The radioactivity rose in the organs in the first 3 hr and then decreased. At the end of 144 hr, no appreciable radioactivity could be found in the organs and tissues, except in the carcass where the cumulation was maximum (1%). After intravenous injection in rabbits, most of the radioactivity (80%) was excreted in the urine and only 4% in the feces. At the end of 96 hr, approximately 3% was cumulated in the body. The drug was quantitatively metabolized in both rats and rabbits: Metabolite 1 (70-85%), Metabolite 2 (10-15%), Metabolite 3 (5-10%), and Metabolite 4 (0.3%).

Administration, Topical↗
PubMed1982

2-14C-1-Allyl-3,5-diethyl-6-chlorouracil II: Isolation and structures of the major sulfur-free and three minor sulfur-containing metabolites and mechanism of biotransformation.

The metabolites of 1-allyl-3,5-diethyl-6-chlorouracil in rabbit urine were isolated by preparative thick-layer, liquid-column, and gas chromatography. With the aid of mass and 1H-NMR spectra, and by comparison with an authentic sample, the major metabolite, 1, was identified as 6,8-diethyl-2-hydroxymethyl-tetrahydrooxazolo-[3,2-c]-pyrimidine-5,7(4H,6H)-dione, Metabolite 2 as 1-allyl-3-ethyl-5-(1-hydroxyethyl)-6-methylthiouracil, Metabolite 3 as 1-allyl-3,5-diethyl-6-methylthiouracil, and Metabolite 4 as 6,8-diethyl-2-hydroxymethyl-tetrahydrothiazolo-[3,2-c]pyrimidine-5,7(4H,6H)-dione. The mechanism of the formation of sulfur-containing metabolites is discussed, and a new metabolic pathway for the formation of methylthio compounds is proposed.

Animals↗
PubMed1981

A simple method for the use of gallocyanin-chrome alum as an electron strain.

A method has been elaborated for the demonstration of DNA in the electron microscope. The method uses glutaraldehyde fixed tissue pieces from which RNA has been removed by incubation with RNase. DNA is stained by gallocyanin-chrome alum in the tissue block. Embedding and cutting is done in the usual manner. The method is based on histochemical observations at the light microscope level which show sufficient specificity and a good stoichiometry of the staining reaction.

Animals↗
PubMed1980

2-14C-1-(2'-deoxy-beta-D-ribofuranosyl)-5-ethyluracil: synthesis and biotransformation in rats.

With 14C-urea as the starting material, 2-14C-1-(2'-deoxy-beta-D-ribofuranosyl)-5-ethyluracil [2-14C-beta-5-ethyl-2'-deoxyuridine] was synthesized for metabolic studies. After intravenous administration in rats, the radioactivity disappeared in the blood within 72 hr, being eliminated primarily in the urine (97%). The major elimination took place in the first 24 hr (92%). Little radioactivity was detected in the organs and tissues after 3 days. Approximately 50% of the urine radioactivity probably was due to an unidentified conjugate, 30% was due to Metabolite II, and 20% was unchanged drug. Metabolite II was identified as 5-ethyluracil by mass and 1H-NMR spectra and by comparison with an authentic sample.

Animals↗
PubMed1979

Attempts to standardize the screening for antiviral drugs by in vitro tests.

Plaque reduction (PR) and persistent infection cell culture (PICC) tests were used as a standard procedure for the selection of effective and well-tolerated antiviral compounds. Antiviral activity and cytotoxicity as well as other characteristics of the test compound, i.e., the development of drug resistance or the potential for activating the multiplication of other viruses can be examined by this method. In the described system analogues of 2'-deoxyuridine were tested against herpes simplex virus.

Antiviral Agents↗
PubMed1978

[Florid oral papillomatosis. A contribution to cytostatic therapy].

Based on the recent clinical experience in treating florid oral papillomatosis (FOP), the only successful therapy appears to be the use of cytostatic agents. The case report of a patient with clinically and histologically confirmed FOP is described to emphasize the advantages of administering Bleomycin intra-arterially (external carotid artery) by means of a Holter catheter. This catheter is used to release pressure in the treatment of internal hydrocephalus and is designed to remain in place for a number of years. The successful treatment of FOP points out the possibility of employing a Holter catheter for administering cytostatic agents in the treatment of malignant neoplasms in the facial area. Cytophotometric examinations of the prickle cells within the FOP mass showed a diploid pattern of DNA distribution similar to that of benigh tumors. However, it is not possible to definitely establish the malignant or benign nature of FOP in this manner.

Alopecia↗