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Biomedical subjects

U Bachrach

Publications and source records attributed to U Bachrach.

At least 55 records · Page 3Linked to original sources
PubMed1985

Opiates and cultured neuroblastoma x glioma cells. Effect on cyclic AMP and polyamine levels and on ornithine decarboxylase and protein kinase activities.

In cultured NG 108-15 neuroblastoma x glioma cells, opiates decreased cellular cyclic AMP and polyamine levels. This decrease was related to the inhibition of ornithine decarboxylase and cyclic AMP-dependent protein kinase activities during the acute exposure of the cells to the drugs. Growing the cells in the presence of opiates for several days led to drug addiction. In the tolerant-addicted cells, polyamine and cyclic AMP levels were close to normal values as were the activities of ornithine decarboxylase and cyclic AMP-dependent protein kinase. Removal of the opiate from 'addicted' cells, by either washing or by adding the antagonist naloxone, resulted in an increase in cyclic AMP and polyamine levels and the activities of ornithine decarboxylase and cyclic AMP-dependent protein kinase. The effect of opiates was closely related to their biological activities. Inactive enantiomorphs did not affect cyclic AMP or polyamine levels; neither did they decrease ornithine decarboxylase and cyclic AMP-dependent protein kinase activities.

Cell Line↗
PubMed1985

Activation and de novo synthesis of transglutaminase in cultured glioma cells.

The activity of transglutaminase (TGase) was measured in cultured C6 glioma cells after their stimulation by either isoproterenol and isobutyl-methylxanthine or by a serum-containing medium. The activity fluctuated in a biphasic manner, with the peaks at 2-3 hr and 7-8 hr poststimulation. The first peak of TGase activity was affected neither by cycloheximide nor by actinomycin D, which inhibited protein synthesis. The second peak, on the other hand, was completely eliminated by cycloheximide and was reduced by actinomycin D. Immunological procedures were employed to find out whether or not the activity of TGase corresponded with the presence of the TGase antigen in the cultured cells. Indirect immunofluorescent staining and radioimmunoblot techniques suggested that unstimulated cells contained an inactive enzyme. This inactive, or cryptic, enzyme had the same molecular weight as its active counterpart. Activation of the enzyme was mediated by cell stimulation, probably by its release from the membrane. This step did not require protein synthesis, unlike the second step, which was dependent on de novo protein synthesis.

1-Methyl-3-isobutylxanthine↗
PubMed1985

Polyamines and Root Formation in Mung Bean Hypocotyl Cuttings : II. Incorporation of Precursors into Polyamines.

The incorporation of [(14)C]arginine and [(14)C]ornithine into various polyamines was studied in mung bean (Vigna radiata [L.] Wilczek) hypocotyl cuttings with respect to the effect of indole-3-butyric acid on adventitious root formation.Both [(14)C]arginine and [(14)C]ornithine are rapidly incorporated into putrescine, spermidine, and spermine, with similar kinetics, during 5- to 24-hour incubation periods. The incorporation of arginine into putrescine is generally higher than that of ornithine. The biosynthesis of putrescine and spermidine from the precursors, in the hypocotyls, is closely related to the pattern of root formation: a first peak at 0 to 24 hours corresponding to the period of root primordia development, and a second peak of putrescine biosynthesis at 48 to 72 hours corresponding to root growth and elongation. Indole-3-butyric acid considerably enhances putrescine biosynthesis in both phases, resulting in an increase of the putrescine/spermidine ratio.It is concluded that the promotive effect of indole-3-butyric acid on putrescine biosynthesis, from both arginine and ornithine, supports the hypothesis that auxin-induced root formation may require the promotion of polyamine biosynthesis.

Journal Article↗
PubMed1985

Formation of cadaverine as an effect of alpha-difluoromethylornithine on chick embryo fibroblasts transformed by rous sarcoma virus.

Chick embryo fibroblasts grew normally in the presence of 1 X 10(-3) to 10 X 10(-3) M alpha-difluoromethylornithine (DFMO). This drug did not interfere with protein and DNA synthesis of normal fibroblasts and of cells transformed by Rous sarcoma virus. The morphological appearance of normal and transformed cells was not altered by DFMO, as determined by scanning electron microscopy. Flow microfluorometric analyses also confirmed the notion that normal or transformed cells were not blocked by DFMO in the G1 phase of the cell cycle. As expected, DFMO reduced cellular putrescine levels. This diamine, however, was replaced by the analogue cadaverine (1,5-diaminopentane), which accumulated mainly in the transformed cells. The increase in cellular cadaverine levels was also demonstrated during the infection of chick embryo fibroblasts with a temperature-sensitive mutant of Rous sarcoma virus under permissive conditions. Under restrictive conditions (42 degrees C), less cadaverine accumulated in the infected cells. These findings suggest that diamines and polyamines are necessary for the transformation process and that blocking one pathway by DFMO leads to the activation of an alternative biosynthetic pathway.

Animals↗
PubMed1984

Polyamine levels and the activity of their biosynthetic enzymes in human erythrocytes infected with the malarial parasite, Plasmodium falciparum.

Human erythrocytes contain only trace amounts of polyamines and lack active polyamine biosynthetic enzymes. A remarkable increase in polyamine content, and in the activity of ornithine and S-adenosyl-L-methionine decarboxylases, is noted in synchronous cultures of the malarial parasite, Plasmodium falciparum. Polyamine biosynthesis reached peak values during the early trophozoite stage, whereas nucleic acid and protein synthesis occurred later in mature trophozoites. DL-alpha-Difluoromethylornithine, an irreversible inhibitor of ornithine decarboxylase, did not interfere with merozoite invasion and with ring-form development, but prevented the transformation of trophozoites to schizonts. Concomitantly, the synthesis of proteins and nucleic acids was significantly inhibited. These inhibitory effects could be readily reversed by the diamine putrescine. Macromolecular synthesis and schizogony were normal when 5-10 mM-DL-alpha-difluoromethylornithine and 0.1 mM-putrescine were added to the cultures simultaneously.

Adenosylmethionine Decarboxylase↗
PubMed1983

The effect of diaminoalkyl-anthraquinone derivatives on the growth of the promastigotes of Leishmania tropica minor, L. t. major, L. donovani and L. aethiopica.

By combining knowledge of polyamine biosynthesis and its inhibition by various analogues with that on the activity of synthetic anthraquinones, a series of six anthraquinone derivatives were synthesized. Their ability to inhibit the growth of leishmanial promastigotes in vitro was used as a preliminary screen to check their potential as new antileishmanial chemotherapeutics. They were tested against four strains, representing four different species; Leishmania tropica major, L. tropica minor, L. aethiopica and L. donovani, associated with four separate disease syndromes. All six derivatives exhibited a fair degree of antileishmanial activity, some being more effective than others. They all inactivated cultures at 100 micrograms/ml and some did so at 10 micrograms/ml and even 1 microgram/ml; but taking different lengths of time to achieve this. Antileishmanial activity associated with anthraquinone derivatives might provide a new approach to the chemotherapy of leishmaniasis.

Anthraquinones↗
PubMed1983

Leishmania tropica major: effect of paromomycin and pentamidine on polyamine levels in the skin of normal and infected mice.

The polyamine content of the skin of BALB/c and C3H mice was determined at intervals, after injecting Leishmania tropica major. In BALB/c mice, putrescine and spermidine levels increased three- to seven-fold; in C3H mice, spontaneous recovery occurred after 3 weeks, accompanied by a reduction in putrescine and spermidine levels. Ornithine decarboxylase activity was negligible in normal, uninfected skin of both BALB/c and C3H mice, but increased steadily during infection. Treatment with drugs that inhibit the growth of leishmanial amastigotes in the skin of mice also reduced polyamine levels and ornithine decarboxylase activity of previously infected skin. There was a close correlation between the therapeutic activity of the drugs and their effect on polyamine content and synthesis. The aminoglycoside paromomycin, which was chemotherapeutically more effective than pentamidine, also had a greater effect on polyamine levels. S-adenosyl-L-Methionine decarboxylase activity in the skin of BALB/c and C3H mice was only slightly affected by the parasites. Polyamine levels and ornithine decarboxylase activity could possibly serve as means for measuring the growth of leishmanial parasites in skin and other tissues and as a measure of the efficacy of anti-leishmanial chemotherapeutics.

Adenosylmethionine Decarboxylase↗
PubMed1983

Ability of Daphnia Cell-Free Extract to Damage Escherichia coli Cells.

A cell-free extract of Daphnia magna was found to lyse Escherichia coli cells as shown by leakage of the enzymes alkaline phosphatase and beta-galactosidase from the bacteria. The cell-free extract was separated on Sephadex G-200, and the fractions showing an ability to lyse E. coli cels were isolated. The factor which was responsible for the lysis of the bacterial cells was probably a protein with a molecular weight of several thousands. Mg and Ca ions augmented the activity of the Daphnia extract on E. coli cells.

Journal Article↗
PubMed1982

Effect of 5'-deoxy-5'-isobutylthioadenosine on putrescine uptake and polyamine biosynthesis by chick embryo fibroblasts.

The effect of 5'-deoxy-5'-S-isobutylthioadenosine (SIBA) on polyamine biosynthesis has been studied by using cultured chick embryo fibroblasts. It has been shown that the drug inhibits the uptake of [14C]putrescine and its conversion into labelled spermidine or spermine. The inhibitory effect is reversed by removing the inhibitor after exposing the cells to the drug for 24 h. SIBA also caused a significant decrease in cellular spermine levels and an accumulation of putrescine. These changes are reversed by removing the inhibitor. SIBA had the same effect on chick embryo fibroblasts transformed by Rous sarcoma virus; a decrease in cellular spermine levels in SIBA-treated cells was observed. In all the experiments SIBA caused a reduction in the spermine/putrescine and spermidine/putrescine ratios. It is suggested that SIBA is not only an inhibitor of transmethylation but also interferes with polyamine biosynthesis, probably by blocking aminopropyltransferase.

Animals↗
PubMed1982

Study of storage iron in cultured chick embryo fibroblasts and rat glioma cells, using Mössbauer spectroscopy.

57Fe Mössbauer spectra of normal and Rous sarcoma virus-infected cultured chick embryo fibroblasts and rat glioma cells have been measured between 0.08 and 318 K. Ferritin-like iron and bacterio-ferritin-like iron have been found in these cells, in various relative amounts, indicating a close relationship between the two storage materials. The bacterio-ferritin-like iron was found to be predominantly membrane-bound. Above 260 K very wide lines were observed in the Mössbauer spectra, yielding an effective viscosity of about 1 poise in the normal chick embryo fibroblasts and about 0.5 poise in the virus-infected chick embryo fibroblasts.

Animals↗
PubMed1982

Inhibition by lithium of PGE1-sensitive adenylate cyclase in neuroblastoma X glioma hybrid cells: approach to the attenuation of the opiate withdrawal syndrome.

Exposure of neuroblastoma X glioma hybrid cells to LiCl (Li+) for 48 h significantly reduces prostaglandin E1 (PGE1)-dependent cyclic adenosine monophosphate (AMP) accumulation. When applied simultaneously with morphine for the same period, Li+ inhibits the excessive accumulation of cyclic AMP in response to PGE1 characteristically exhibited by these cells upon opiate withdrawal. Likewise, Li+ inhibits, in vitro, PGE1-dependent cyclic AMP accumulation in tissue slices from rat corpus striatum. Prophylactic administration of Li+ in the diet attenuates the withdrawal symptoms in morphine-addicted rats. These findings support clinical reports that suggest that prophylactic treatment with Li+ attenuates the severity of the opiate withdrawal syndrome.

Adenylyl Cyclase Inhibitors↗
PubMed1982

Polyamines and root formation in mung bean hypocotyl cuttings : I. Effects of exogenous compounds and changes in endogenous polyamine content.

The effect of several polyamines (putrescine, spermidine, and spermine), their precursors (l-arginine and l-ornithine), and some analogs and metabolic inhibitors (l-canavanine, l-canaline, and methylglyoxal-bis [guanylhydrazone]) on root formation have been studied in mung bean (Vigna radiata [L.] Wilczek) hypocotyl cuttings.Exogenously applied polyamines did not promote adventitious root formation. Rooting was inhibited by l-canavanine and l-canaline, and this inhibition was reversed by the corresponding amino acids l-arginine and l-ornithine. Methylglyoxal-bis (guanylhydrazone), an inhibitor of S-adenosylmethionine decarboxylase and polyamine biosynthesis, was also found to inhibit root formation. All compounds at concentrations of >10(-4) molarity completely inhibited natural root formation, whereas at <10(-5) molarity only the indole-butyric acid-induced root formation was inhibited.Indole-butyric acid-induced root formation was accompanied by a considerable increase in polyamine levels, more than 2-fold of the control. Whereas senescing (unrooted) cuttings evinced a rapid decline in polyamine content during 48 hours, indole-butyric acid treatment resulted in elevated levels of putrescine and increased putrescine to spermidine ratio. The changes in polyamines were dependent on indole-butyric acid concentration and were organ specific.

Journal Article↗
PubMed1981

Formation of acetylpolyamines and putrescine from spermidine by normal and transformed chick embryo fibroblasts.

Polyamine uptake and metabolism were studied in cultures of normal and Rous sarcoma virus-transformed chick embryo fibroblasts. The uptake of radioactive putrescine and spermidine by the transformed cells was faster than that of the normal controls. The amount of radioactive putrescine and polyamines taken up by the transformed cells also exceeded that observed with normal fibroblasts. The intracellular levels of putrescine, spermidine, and spermine were considerably higher in the transformed cells than in the normal controls. Radioactive spermidine was converted into N-acetylputrescine and N1-acetylspermidine by the transformed cells. The extent of this conversion by the normal fibroblasts was significantly lower. Radioactive putrescine and spermine were also formed from radioactive spermidine added to cultures of transformed fibroblasts. The rate of this conversion was significantly slower in normal chick embryo fibroblasts.

Acetylation↗
PubMed1981

Polyamines and the growth of leishmanial parasites.

The relation between the grown of leishmanial parasites and polyamine biosynthesis was studied. Polyamines, mainly putrescine and spermidine, accumulated in macrophages infected with Leishmania tropica major promastigotes grown in vitro. Similar results were obtained, when tissues of BALB/C mice infected with L. tropica major were examined. A consistent increase in cellular putrescine and spermidine levels was observed in infected skin and spleen. With the accumulation of putrescine, a concomitant increase in ornithine decarboxylase activity was detected in growing leishmanial promastigotes and in macrophages supporting the growth of leishmanial amastigotes. An increase in the activity of ornithine decarboxylase was also observed in Leishmania-infected skin and spleen from BALB/C mice.

Animals↗