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Biomedical subjects

J Pitha

Publications and source records attributed to J Pitha.

At least 127 records · Page 7Linked to original sources
PubMed1980

Water-soluble, dextran-linked retinal: preparation, vitamin A-like activity in rats, and effects on melanoma cells.

A new, water-soluble, polymer-linked form of retinal was synthesized and tested for its ability to support the growth of vitamin A-deficient noninbred Holtzman rats and to inhibit the proliferation of melanoma cells in culture. Retinal was conjugated to the hydrazide of carboxymethyldextran in the presence of alpha-and beta-cyclodextrins. The aqueous solutions of the product contained between 200 and 1,000 micrograms retinal/ml as opposed to the low water solubility (< 0.01 micrograms/ml) of retinal itself. The retinal-dextran complex, although barely resorbed from the gastrointestinal tract, supported the growth of rats fed a vitamin A-deficient diet when administered ip at 2.3 mumol of retinal equivalent/kg body weight. Retinal and the retinal-dextran complex exhibited differential cytotoxicity toward S91 melanoma cells and caused cell lysis at 10 and 500 microM (retinal residue), respectively. At noncytotoxic doses both free retinal and its dextran-linked derivative reduced the cell proliferation rate in a time- and dose-dependent fashion with median inhibitory doses of 1 and 4 microM (retinal residue), respectively. These data demonstrated that the water-soluble retinal-dextran complex retained certain biologic activities of retinal and was less cytotoxic.

Animals↗
PubMed1979

Mechanism of enhancement of polynucleotide binding to cells by mutagens.

The binding of polyuridylate to cells is substantially increased by proflavine. This enhanced binding is saturable with respect to time and to the concentration of both proflavine and polyuridylate. Enhancement is observed only when cells are exposed to both proflavine and polyuridylate together and depends cooperatively on the proflavine concentration. The resulting complex formed between the cell, proflavine, and polyuridylate can be dissociated with salt but not with sucrose solutions. An increase in the binding of polyuridylate to cells similar to that observed with proflavine was also obtained with cationic dyes such as acridine orange, 9-aminoacridine, and Hoechst 33258, while the introduction of a bulky polysaccharide residue, dextran, into the dyes cancels these effects. Similarly, cationic aromatic compounds such as primaquine and quinacrine which carry bulky nonplanar substituents or aliphatic cationic compounds like ethylenediamine do not enhance binding. Proflavine is unable to augment the binding of a basic macromolecule, diethylaminoethylaminoethyldextran, to cells. The model proposed for the enhanced binding of polyuridylate is based on the cooperative formation of stacked complexes of cationic dye located between the cell surface and the bound polyuridylate.

Cell Line↗
PubMed1979

Adenocarcinoma of rete testis.

Adenocarcinoma of the rete testis is a rare tumor of the genital tract. An advanced case of adenocarcinoma thought to arise from the rete testis is presented. We believe this is the eighteenth reported case.

Adenocarcinoma, Papillary↗
PubMed1979

Opposite effects of dextrans substituted with sulfhydryls or mercury on tumor growth.

Macromolecular dextrans carrying substituents terminated by sulfhydryl groups or terminated by aromatic amines effectively inhibit the growth of a fibrosarcoma and of a mammary adenocarcinoma in a syngeneic mouse model. These compounds have no or very low toxicity to animals and are nontoxic to fibrosarcoma cells in vitro. Small-molecular-weight compounds carrying the same substituents as the above dextrans are without any effect on the growth of these tumors. A dextran substituted with mercury-containing side chains is growth promoting for the same fibrosarcoma in mice at doses which are nontoxic for these animals. However, the mercury-containing compound is toxic to fibrosarcoma cells in vitro. It is hypothesized that these nonpermeating macromolecules do not directly influence the tumor cells in animals but modulate the natural system of defense against tumors; cells of that system are stimulated or poisoned by the substituted dextrans.

Animals↗
PubMed1978

Binding of polynucleotides to fibroblasts. Effects of complex formation with vinyl analogs of nucleic acids.

The binding of polynucleotides or of their vinyl analogs to human fibroblasts is changed when complexes are formed between these compounds. The following polymers have been studied: poly(1-vinylcytosine), poly(1-vinyluracil, poly(9-vinyladenine), polyuridylate, polyadenylate and polyinosinate. Only that complex formation (between poly(1-vinylcytosine) and polyinosinate) which is accompanied by aggregation leads to a considerable increase (30 fold) in binding to cells; all the other complex formations have only moderate effects (0.2-3 fold). Furthermore, a comparison of unordered complexes containing polyinosinate whows that enhanced binding to cells is paralleled by an increased cellular resistance to viral infection.

Cell Line↗
PubMed1978

Reagents specific for cell surface components.

Mercury, diazonium ions and dyes which bind nucleic acids were covalently linked to dextrans using methods that resulted in non-hydrolyzable reagent-dextran bonds without impairing the binding abilities of the reagents, i.e. these dextran derivatives reacted with thiols, phenols/imidazoles and nucleic acids respectively. Since these dextran derivatives cannot penetrate into cells and since dextran itself does not bind to cells, these compounds represent reagents specific for the cell surface. They may be used both to evaluate cell surface constituents of intact cells and to affect viable cells via an interaction with those constituents. Mercury-dextran was found to bind to cells; the amount of mercury thus attached to the cells was about ten times smaller than when an equivalent concentration of free mercury ions was used. Mercury-dextran, bound to cells after a 30-min exposure at room temperature, was localized on the surface of these cells, as sodium borohydride reduced this complex giving rise to the intact cells, elementary mercury and free dextran which was released into medium. When cells were constantly exposed to the mercury-dextran, its toxic effects were comparable to that of free mercury ions. Diazonium-dextran, which also binds tightly to the cell surface, was also considerably toxic. Dextrans substituted with dyes which bind to nucleic acids were less toxic than the parent dyes themselves; it was shown that the attachment of such a dye to dextran decreased the binding of dye to cells under detection limits.

Aniline Compounds↗
PubMed1978

Template specific inhibitors of E. coli RNA polymerase.

Electroneutral analogs of polynucleotides, poly-9-vinyladenine and poly-1-vinyluracil inhibit E. coli RNA polymerase in all combinations where the single stranded polynucleotides are used as templates and the vinyl analogs are complementary to them. As templates both the ribo- and deoxyribopolynucleotides were tested; variation of the template concentration in the presence of vinyl analogs produced a competitive pattern of inhibition. The electroneutral analogs do not inhibit the enzyme activity when non-complementary single stranded polynucleotides or double stranded polynucleotides are used as templates; the latter fully supports transcription even when one of the strands is complementary to the analog.

DNA↗
PubMed1977

Uptake and fate of water-soluble, nondegradable polymers with antiviral activity in cells and animals.

Poly(9-vinyladenine) and poly(1-vinyluracil) which are nondegradable, soluble polymers are taken up partially by mammalian cells grown in culture. The polymers remain associated with cells for several generations. In mice, after ip application, polymers slowly accumulate in liver, spleen, and thymus and remain there for as long as a month. Thus, these polymers which suppress the replication of murine leukemia viruses also accumulate in organs where the virus replicates. However, their antiviral activity does not reflect the amount of polymer found in these animal tissues. We propose that the polymers are gradually segregated into a group of cells or into subcellular organelles away from primary sites of virus replication. The results suggest that for a directly acting polymeric drug, a half-life over 24 h is without advantage.

Adenine↗
PubMed1976

Ionophorous polymers. Interaction with polynucleotides and effects on RNA-directed DNA polymerase activity.

Poly(vinylbenzo-18-crown-6), a water-soluble polymer endowed with ion-binding crown moieties as pendent groups, forms insoluble complexes with polyadenylate in the presence of K+; the corresponding monomeric benzo-18-crown-6, does not form a precipitate under the same conditions. In the presence of Na+ and Mn2+ which in aqueous solution complex weakly to crown compounds, no coprecipitation of the crown polymer and polyadenylate occurs; nevertheless, the crown polymer strongly binds to immobilized polyadenylate even under these conditions. The interactions of crown polymer with the poly-nucleotide result in a loss of templating ability of the latter. Using RNA-dependent DNA polymerase of murine leukemia virus it was found that (1) enzymatic action is efficiently inhibited even in the absence of ions which coprecipitate crown polymer and template, (2) inhibition is reversed by addition of excess polynucleotide and (3) monomeric crown does not inhibit the reaction.

Binding Sites↗
PubMed1976

Template specific inhibitor of mammalian DNA polymerases.

A study of the inhibition of mouse cellular DNA polymerases by poly-nucleotides and their vinyl analogs is presented. Poly(dT)-directed poly(dA) synthesis by representatives of all three classes of cellular DNA polymerase could be completely inhibited by poly(9-vinyladenine), although higher concentrations were required in the case of the gamma class enzyme. Studies on the mechanism of the inhibition using the alpha class DNA polymerase and different templates showed that the enzyme activity was inhibited in all cases where base-pairing between the vinyl polymer and the template occurred; poly(9-vinyladenine) did not interfere with the replication of templates to which it does not bind. The inhibition occurred shortly after addition of poly(9-vinyladenine) to ongoing reactions, yet the enzyme was not displaced from the template - primer complex.

Animals↗
PubMed1976

Effects of Poly(1-vinyluracil) and Poly(9-vinyladenine) on viral RNA-directed DNA polymerase.

The effects of poly(1-vinyluracil) [poly(vU)] and poly(9-vinyladenine) [poly(vA)] on the RNA-dependent DNA polymerase activity of murine leukemia virus (Moloney strain) were studied. Vinyl polymers themselves cannot act as templates for the polymerase. However, if a vinyl polymer is added to a polymerase reaction mixture in which a complementary polynucleotide serves as the template, the reaction is inhibited: thus with polyribocytidylic acid as template and oligodeoxyguanylic acid as primer, neither poly(vU) nor poly(vA) had a significant effect; when polyribouridylic acid was used as template and oligodeoxyadenylic acid as primer, poly(vA) inhibited polymerase activity while poly(vU) had little effect; when polyriboadenylic acid was a template and oligodeoxy thymidylic acid was a primer, poly(vU) was an inhibitor. Complex effects were noted with the latter system and poly(vA); either stimulation or inhibition of the reaction was observed, depending on the concentration of poly(vA). The stimulation brings about a decrease in the amount of lower-molecular-weight materials in the product and is caused by the interaction of poly(vA) with the template-primer. Thus vinyl polymers differ from polynucleotides in their mechanism of inhibition of viral polymerase, since the latter inhibit the enzyme by binding to it.

Adenine↗
PubMed1975

Hydrogen bonding abilities of 2,4-dithiouridine derivatives.

The base pairing ability of a di-2,4-thiouridine derivative was studied in carbon tetrachloride solutions by the methods of infrared spectroscopy. The strength of the association by hydrogen bonding was found to decrease in the following order: adenine-uracil, adenine-di-2,4-thiouracil, uracil-uracil, and di-2,4-thiouracil-di-2,4-thiouracil. These findings contrast with the previously demonstrated fact that poly(s2s4U) is strongly self-associated and does not form a complex with poly(A). To correlate these results, it is proposed that long range stabilizing forces are acting between the di-2,4-thiouracil residues in polynucleotide chains. This assumption also explains the existence of an ordered structure in the alternating copolymer poly(s2s4U-A).

Adenine Nucleotides↗