Search PubMed⌕ Search

Biomedical subjects

D Baron

Publications and source records attributed to D Baron.

At least 163 records · Page 9Linked to original sources
PubMed1975

[Fumaric acid monoethylester: Effect on DNA-synthesis and preliminary findings in experimental studies in animals (author's transl)].

The incorporation of 14C-Thymidin into DNA of cultured human lymphocytes is depressed by added fumaric acid monoethylester (FSME) depending on the dosage of FSME. The decreased radioactivity in DNA as measured by scintillation counting is paralleled by a concomitant decrease in the labelling index in autoradiograms. Decreasing radioactivity is therefore due to a lower number of DNA synthesizing cells. No selective inhibition of proliferation during one of the cell cycle phases was observed. Especially a G2-block known from other cytostaties is absent. A mean dosis of 6.88 mg FSME per g body weight administered intraperitoneally is lethal to mice. The animal die from diffuse necroses of heart muscle cell. Alterations of other organs are less prominent. At lower doses of FSME the morphology of the organs investigated is altered to a smaller degree.

Animals↗
PubMed1975

Further in vitro studies on the biochemistry of the inhibition of nucleic acid and protein synthesis induced by arsenic.

Human lymphocytes, stimulated by PHA, and exposed to increasing Na2HAsO4 concentrations, show an identical incorporation rate for 14C thymidine and 14C-TTP into the DNA. 14C uridine is incorporated 3--4 per cent less at an As concentration of 1.0 mug/ml medium, above this however approximately 15 per cent less into the RNA as compared to 14C-UTP. In free pyrimidine bases, the incorporation of labelled triphosphates into the DNA and RNA is significantly reduced above 1 mug and 10 mug Na2HAsO4. Corresponding to its approximately uniform distribution into DNA and RNA, the incorporation rate of 14C-ATP above 10 mug Na2HAsO4/ml culture medium lies between that of 14C-UTP and 14C-TTP. The incorporation of 14C alanine and 14C leucine into cellular protein is not reduced below 10 mug Na2HAsO4/ml. The incorporation rate is 41 per cent at a concentration of 100 mug Na2HAsO4/ml medium. Compared to 14C-UTP, 14C-ATP and 14C-TTP it is increased by the factor of 1.8; 2.5 and 6.8 respectively. The inhibition of enzymes of the dark repair mechanisms and the synthesis of biopolymers together with their altered sequence and the involvement of long-lived messenger RNA serve as an explanation of the observed alterations of the lymphocyte metabolism, caused by arsenic.

Adenosine Triphosphate↗
PubMed1975

Spectroscopic evidence for the formation of a 4-keto intermediate in the UDP-apiose/UDP-xylose synthase reaction.

Uridine diphospho-D-glucose (UDP-Glc) and UDP-methyl-D-glucuronate (UDP-GlcUAMe) have been shown to be competitive inhibitors for the UDP-apiose/udp-xylose synthase from cell suspension cultures of parsley. The apparent Ki values for these substrate analogues were of the same order of magnitude as the apparent Km value for the substrate UDP-D-glucuronic acid (UDP-GlcUA). The difference spectrum of the incubation mixture containing UDP-GlcUA, NAD+ and the highly purified enzyme showed a transient absorption with a maximum at 292 nm which disappeared upon addition of sodium hydroxide. The incubation with UDP-Glc or UDP-GlcUAMe also showed and NAD+-dependent absorption at 292 nm. However, in these cases a strong enhancement of the absorption at alkaline pH and a shift of the absorption maximum to longer wavelength were observed. Upon addition of 0-phenylenediamine to the enzyme incubation with UDP-Glc or UDP-GlcUAe a strong absorption with a maximum at respectively 335 and 315 nm appeared. The results show the transient formation of a 4-keto derivatives in the synthase reaction with the normal substrate UDP-GlcUA. The substrate analogues UDP-Glc and UDP-GlcUAMe can also be oxidized at C-4 by the enzyme in the presence of NAD+ to stable 4-keto derivatives which give rise to a strong absorption at alkaline pH or after reaction with o-phenylenediamine.

Binding Sites↗
PubMed1975

[The effect of fumaric acid monoethylester on the synthesis of nucleic acids and proteins of PHA-stimulated human lymphocytes (author's transl)].

Fumaric acid monoethylester (FAME) inhibits the incorporation of 14C-Thymidin, 14C-Uridin, 14C-Alanin and 14C-Leucin into acid-insoluble biopolymers of cultivated PHA-stimulated human lymphocytes. At high concentrations of FAME (500 mug/ml culture medium) the inhibition of nucleic acid synthesis is 6 times higher on the average than the inhibition of protein synthesis. However, the application of the cis-isomer, maleic acid monoethylester (MAME), results in an increase of the incorporation rate of the labelled precursors into the RNA and DNA. This is 3.5--9.3 times higher than after application of FAME. The results demonstrate the specific inhibition by FAME. The rate of labelling of nucleic acids is decreased above 10 mug FAME/ml culture medium and in the case of MAME above 50 mug/ml medium. As an explanation of the specific action of FAME its influence on the enzymes of the nucleic acid synthesis, the citric acid cycle or a faulty synthesis of enzymes are discussed.

Alanine↗
PubMed1975

[Effect of arsenic on the incorporation of 14C-thymidine into DNAP of phytohaemagglutinin-treated lymphocytes (author's transl)].

In lymphocyte cultures stimulated with PHA Na2HAsO4 is able, independent of the arsenic doses used (10 mug, 30 mug, 50 mug/ml culture medium), to increase the 14C-thymidine incorporation in acid precipitable biopolymers. The increase was 17 plus or minus 4% at 1 hr exposure to arsenic, compared with control cultures which were not exposed to arsenic. The administration of 30 mug and 50 mug Na2HAsO4/ml medium at incubation periods between 2 and 18 hrs resulted in a decrease in the radioactive incorporation rate into the DNA which was dependent on dose and time. Using 10 mug Na2HAsO4 per ml medium, the 1 hr stimulation is followed by an inhibition (up to approximately 35%, control equals 100%), which lasts for approximately 3 hrs. This is followed by an increase in the 14C-thymidine incorporation into the DNA for a further 2 hrs. The course of the inhibition curve with 10 mug Na2HAsO4 and with exposure times between 6 and 18 hrs the decreases again dependent on dose and time. As an explanation of the stimulation of the 14C-thymidine utilisation by arsenic, we suppose an increased repair activity. This may lead to a situation where (labelled) bases which are added outside the synthesis phase are incorporated into the DNA. The inhibition of 14C-thymidine incorporation which is dependent on dosage and time, with larger doses of arsenic can be explained by a prevailing influence of enzymes of the synthesis system (e.g. polymer arsenic), while the unusual course of the inhibition curve under the influence of 10 mug Na2HAsO4 shows that an activation and inhibition of enzyme systems (synthesis and repair) which is displaced in time is taking place. Apart from this, disturbances of regulation processes of the DNA replication and the initiation overlap can also be suspected as a cause of the phenomena observed.

Arsenates↗