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Biomedical subjects

Y Becker

Publications and source records attributed to Y Becker.

At least 145 records · Page 8Linked to original sources

The internal organization of the varicella-zoster virus genome.

DNA was extracted from varicella-zoster (VZ) virions prepared in sucrose gradients. Thirty-eight molecules examined by electron microscopy were found to have a mean length of 46.7 micrometers. Examination of self-annealed VZV DNA molecules revealed that the virus genome was composed of a unique linear large sequence with a mol. wt. of 74.4 X 10(6) to 78.4 X 10(6), and a unique short sequence of mol. wt. approx. 9.8 X 10(6) flanked by inverted repeat sequences of 4.7 X 10(6) mol. wt.

Base Sequence↗

Cellular hypersensitivity to neocarzinostatin in ataxia-telangiectasia skin fibroblasts.

Cellular sensitivity of human skin fibroblast strains from three healthy donors, eight ataxia-telangiectasia (A-T) patients belonging to six sibships, and two A-T heterozygotes to the lethal action of the antitumor antibiotic neocarzinostatin was tested, using colony-forming ability as the criterion for survival. All the A-T strains were significantly more sensitive to killing by neocarzinostatin than were the control strains. The average D0 for the A-T strains following neocarzinostatin treatment was 14.6 ng/ml, as compared to 37.9 ng/ml for the normal strains. The two A-T heterozygous strains showed intermediate sensitivity with an average D0 of 26.9 ng/ml. Neocarzinostatin sensitivity of A-T cells could therefore serve as a convenient aid for the laboratory diagnosis of A-T. Since A-T cells are also known to be hypersensitive to ionizing radiation and bleomycin, it would appear that they are primarily hypersensitive to DNA-breaking agents.

Adolescent↗

An apparent correlation between the inhibition of induced ornithine decarboxylase activity by gamma radiation and the capacity for DNA repair synthesis in normal and ataxia telangiectasia human fibroblasts: no correlation with cell survival.

Exposure of normal human fibroblasts (F107) in stationary phase to gamma radiation inhibited the appearance of induced ornithine decarboxylase (ODC) activity. Skin fibroblasts derived from two ataxia telangiectasia (AT) patients (F184 and F182) displayed a similar response. The level of DNA repair synthesis was also similar in the three cell strains. Fibroblasts from another apparently normal donor (F196) were very sensitive to inhibition of induced ODC activity by gamma radiation and were also deficient in radiation-induced DNA repair synthesis. However, the two strains derived from normal donors displayed the same degree of cellular sensitivity towards X-rays, whereas the two AT strains showed the typical hypersensitivity to the cytotoxic effect of X-irradiation. The results suggest a possible correlation between the inhibition of induced ODC activity by gamma radiation and the extent of DNA repair synthesis at high radiation doses, but there is no correlation between these two parameters and cellular survival at low radiation doses.

Ataxia Telangiectasia↗

Effect of the flavonoid (+)cyanidanol-3 on procollagen biosynthesis and transport in normal and ataxia telangiectasis cultured skin fibroblasts.

The synthesis and secretion of procollagen into the medium of cultures of human skin fibroblasts from normal individuals and from patients with the genetic disorder, ataxia telangiectasia, are markedly inhibited by the flavonoid (+)cyanidanol-3. Those proteins which were secreted into the medium in the presence of cyanidanol were resistant to collagenase treatment (noncollagenous proteins). Polyacrylamide gel electrophoresis revealed the presence of only one noncollagenous protein of 66,000 daltons in the medium of cyanidanol-treated cells as compared with the nine other polypeptides found in the medium of untreated cells.

Ataxia Telangiectasia↗

Kinetics of O6-methylguanine repair in human normal and ataxia telangiectasia cell lines and correlation of repair capacity with cellular sensitivity to methylating agents.

Human lymphoblastoid cell lines from normal individuals and from patients with ataxia telangiectasia were either proficient or deficient in their ability to repair the mutagenic DNA adduct O6-methylguanine that is induced by methylating carcinogens. There was no relationship between the capacity to repair O6-methylguanine and the ataxia telangiectasia phenotype. Time-course studies done following a short pulse (2 min) of alkylation with 0.5 microgram of N-[3H]methyl-N'-nitro-N-nitrosguanidine per ml revealed that the repair of O6-methylguanine in human lymphoblastoid lines proficient in this ability is a rapid process, which proceeds with a half-life of 10 to 15 min. Lymphoblastoid lines with deficient capacity to repair this DNA adduct were hypersensitive to the cytotoxic effect of the methylating carcinogens N-methyl-N'-nitro-N-nitrosoguanidine, N-methyl-N-nitrosourea, and methyl methanesulfonate, and this hypersensitivity was correlated with the relative amount of O6-methylguanine induced by each of the three chemicals. This was taken as an indication of the lethality of unrepaired O6-methylgluanine. The extent of DNA repair synthesis induced by the three carcinogens was the same in cell lines proficient and deficient in O6-methylguanine repair, indicating no major deficiency in an excision repair pathway in the hypersensitive cell lines.

Adolescent↗

Structure-activity relationships of pyrrole amidine antiviral antibiotics III: preparation of distamycin and congocidine derivatives based on 2,5-disubstituted pyrroles.

Isomers of distamycin A and tripyrrole congocidine containing 2,5-disubstituted pyrroles were synthesized along with distamycin and congocidine homologs containing a single pyrrole ring. Selected compounds were evaluated for their cytotoxicity and antiviral activity. All of the tripyrrole derivatives tested in this series were nontoxic but were less active than distamycin A. The monopyrrole derivative, N-methyl-5-nitropyrrole-2-carboxamido-beta-propionamidine hydrochloride, was nontoxic and was almost as active antivirally as distamycin A.

Antiviral Agents↗

Structure-activity relationships of pyrrole amidine antiviral antibiotics. 2. Preparation of mono- and tripyrrole derivatives of congocidine.

Representatives of three types of congocidine (1) analogues were synthesized. These were tested for cytotoxicity, inhibition of herpes simplex virus (HSV) replication in cultured cells, and effects on the synthesis of HS DNA in isolated nuclei in vitro, as well as on DNA synthesis by purified HSV DNA polymerase. All synthesized tripyrrole derivatives of congocidine were less cytotoxic and more active than the parent drug in all the three ant iviral tests.

Antiviral Agents↗

A diffusable clastogenic factor in ataxia telangiectasia.

Cocultivation of plasma and lymphocytes from ataxia telangiectasia (AT) patients with those of normal individuals resulted in a significant increase in chromosomal damage in the normal cells. Tissue culture medium used to cultivate AT skin fibroblasts also significantly increased chromosome breakage in PHA-stimulated normal lymphocytes. This clastogenic effect was maximal when the "conditioned medium" was 8-9 days old. A similar effect was not observed with medium derived from normal skin fibroblasts. These observations suggest the presence of a clastogenic factor in the plasma of AT patients which may also be produced by AT skin fibroblasts in culture.

Ataxia Telangiectasia↗