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Biomedical subjects

M Oren

Publications and source records attributed to M Oren.

194 records · Page 11Linked to original sources
PubMed1980

Differential affinities of simian virus 40 large tumor antigen for DNA.

The binding of simian virus 40 (SV40) large tumor antigen (T antigen) to DNA was analyzed by using the salt-sensitive affinities of the protein for various DNAs immobilized on cellulose. At least two types of interactions could be distinguished that differed in their stability. Higher salt concentrations were required to elute T antigen from SV40 DNA than from calf thymus DNA; and even greater salt concentrations were required for the lution of T antigen from multiorigin SV 40 DNA compared to wild-type SV40 DNA. This would indicate that T antigen can bind weakly or strongly to DNA, depending on the DNA sequence. It was also found that a greater proportion of rapidly labeled or newly synthesized T antigen binds more efficiently and tightly to multiorigin SV40 DNA than to long-labeled or older forms of T antigen. This approach can be utilized not only to distinguish between different forms of T antigens which vary in their affinities for DNA but also for rapidly obtaining highly enriched T antigen preparations.

Animals↗
PubMed1979

Orchidopexy in cryptorchidism assessed by clinical, histologic and sperm examinations.

A study was undertaken of 187 patients with unilateral and 41 patients with bilateral cryptorchidism before and after orchidopexy. The mean tubular diameter and the mean tubular fertility index were used as quantitative criteria for assessment of the development of the testes. Before orchidopexy, no significant differences were found between scrotal and cryptorchid testes in patients up to six years of age. Thereafter, the scrotal testis showed marked development in distinction to the cryptorchid testis. After orchidopexy, follow-up examinations were carried out when the patients had reached the age, at least, 18 years. Based on the results of the mean tubular diameter and the mean tubular fertility index, a reasonable degree of fertility would be expected in both the unilateral and the bilateral cryptorchid testes. However, histologic assessment of spermatogenesis in the unilateral cryptorchid testes after orchidopexy showed spermatogenic arrest in 81 per cent and in all patients with bilateral cryptorchid testes after orchidopexy. In the unilateral orchidopexy patients, in distinction to the histologic assesment of spermatogenesis, sperm counts gave good results in 80 per cent; evidently, in these patients, the source of the spermatozoa was the contralateral scrotal testis. That spermatogenesis was defective in 20 per cent of the patients after unilateral orchidopexy suggests and underlying systemic factor affecting both testes.

Adolescent↗
PubMed1977

Anterior sacral meningocele: report of five cases and review of the literature.

Five new cases of anterior sacral meningocele are presented, including one secondary to neurofibromatosis, a previously undescribed association. The literature is reviewed, drawing attention to the relationship between anterior sacral meningocele, sacral dysgenesis, and other congenital anomalies. Special consideration is given to the clinical features of this entity, as well as to the techniques and results of surgical management.

Abnormalities, Multiple↗
PubMed1977

Properties of permissive monkey cells transformed by UV-irradiated simian virus 40.

African green monkey cells (CV1 line) were infected with UV-irradiated simian virus 40 (SV40), and permissive lines of stably transformed cells were established. These cell lines display the SV40 T-antigen and the growth characteristics typical of nonpermissive transformed cells (e.g., reduced cell density inhibition, reduced serum dependence, ability to overgrow normal cells, and colony formation in soft agar). The level of permissiveness to superinfecting SV40 is fully comparable with that of nontransformed CV1 and BSC-1 lines. The transformed monkey lines also support SV40 plaque production under agar. By Cot analysis, the transformed permissive cells contain, on an average, 1 to 2 SV40 genome equivalents, and the majority of the viral sequences are associated with the high-molecular-weight cellular DNA. No spontaneous production of infectious SV40 has been observed. The transformed permissive monkey cells failed to support the replication of SV40 tsA mutants at the restrictive temperature. To account for this, it is suggested that the gene A product has separate functions for transformation and initiation of viral DNA synthesis, and only the former function is expressed in the transformed permissive monkey cells.

Animals↗
PubMedDate not supplied

A single gene and a pseudogene for the cellular tumour antigen p53.

The cellular tumour antigen p53 is a protein found in elevated levels in a great variety of transformed cells (reviewed in ref. 1). Overproduction of p53 was observed in cells transformed by a wide spectrum of agents as well as in embryonal carcinoma cells, and in spontaneous transformants. Although initially described in mice, similar p53-like proteins were also observed in cells of other species, including those derived from several human tumours. In non-transformed cells the protein turns over very rapidly and its levels appear to correlate with cell proliferation. Thus far, very little has been known about the precise nature of the protein and of the corresponding genes. We now provide evidence for the existence of a single functional gene for murine p53 and a processed pseudogene. The predicted amino acid sequence of murine p53 is also presented.

Amino Acid Sequence↗
PubMedDate not supplied

Participation of p53 cellular tumour antigen in transformation of normal embryonic cells.

The cellular tumour antigen p53 is found at elevated levels in a wide variety of transformed cells (for reviews see refs 1, 2). Very little is yet known about the precise relationship of p53 to malignant transformation. Although the increase in p53 levels could be a secondary by-product of the transformed state, it is equally possible that p53 is actively involved in altering cellular growth properties, especially as it has been implicated in the regulation of normal cell proliferation. We sought to test whether p53 could behave in a manner similar to known genes in a biological test system, and we demonstrate here that p53 can cooperate with the activated Ha-ras oncogene to transform normal embryonic cells. The resultant foci contain cells of a markedly altered morphology which produce high levels of p53. Cell lines established from such foci elicit tumours in syngeneic animals.

Animals↗
PubMedDate not supplied

Overproduction of p53 antigen makes established cells highly tumorigenic.

The p53 cellular tumour antigen, long known to be overproduced in a variety of neoplastically transformed cells, was recently shown to be directly involved in transformation. Thus, p53 can complement activated Ha-ras in transforming secondary rat embryo fibroblasts into grossly altered, tumorigenic cells. Moreover, p53 can also be shown to possess immortalizing activity. Our previous results indicated, however, that the contribution of p53 to the transformation was not synonymous with immortalization, suggesting that the two activities of the protein are probably separable. We demonstrate here that this is indeed the case, as overproduction of p53 in an established cell line, while not causing gross morphological changes, endows these cells with an overt tumorigenic potential. Furthermore, the tumorigenic efficiency of such cell lines may be correlated with the extent of p53 over-production.

Animals↗
PubMedDate not supplied

Translocation of the p53 gene in t(15;17) in acute promyelocytic leukaemia.

Recent studies have demonstrated that the cellular tumour antigen p53 (ref. 1) can complement activated ras genes in the transformation of rat fibroblasts, suggesting that the gene encoding p53 may act as an oncogene. Here, by using in situ chromosomal hybridization, we have mapped the p53 gene to human chromosome 17, at bands 17q21-q22, the region containing one of the breakpoints in the translocation t(15;17) (q22;q21) associated with acute promyelocytic leukaemia (APL). Hybridization of p53 and erb-A (17q11-q12) probes to malignant cells from three APL patients indicated that the p53 gene is translocated to chromosome 15 (15q+), whereas erb-A remains on chromosome 17. Analysis of variant translocations demonstrates that the 15q+ chromosome contains the conserved junction, suggesting a role for p53 in the pathogenesis of APL. However, rearrangements of the p53 gene were not detected on Southern blotting of DNA from leukaemic cells of four APL patients with t(15;17).

Cell Line↗
PubMedDate not supplied

Localization of gene for human p53 tumour antigen to band 17p13.

Recently the gene for the cellular tumour antigen p53, a phosphoprotein found in increased concentration in a variety of human cells, had been mapped to region 17q22 by in situ hybridization techniques and has been shown to translocate to the chromosome carrying the translocation [t(15; 17)] associated with acute promyelocytic leukaemia (APL). Based on this finding it has been postulated that this gene has a role in the pathogenesis of APL. Here we present evidence that the gene for p53 is not located on the long arm of chromosome 17, but maps to band 17p13. We therefore suggest that this gene is not directly involved in the chromosome translocation observed in APL.

Antigens, Neoplasm↗
PubMedDate not supplied

Specific interaction between the p53 cellular tumour antigen and major heat shock proteins.

The protein p53 is capable of participating in neoplastic transformation and can form specific complexes with the large-T antigen of simian virus 40 (SV40). This interaction probably results in the stabilization of p53 (refs 7,8) and may contribute to SV40-mediated transformation. Several non-SV40-transformed cells also exhibit a stabilized p53 which is present in elevated levels. Recently, this stabilization was shown to coincide with the ability to precipitate a polypeptide (p68) of relative molecular mass (Mr) 68,000-70,000 by anti-p53 monoclonal antibodies. We now report that this co-precipitation indeed represents a specific complex between the two proteins; the complex sediments on a sucrose gradient as a relatively broad peak of 10-14S and can be dissociated in vitro. Furthermore, p68 is the HSP70 heat shock protein cognate, found in elevated levels in a p53-overproducing cell line. On heat-shock treatment of such overproducers, p53 also forms a complex with the related highly inducible HSP68.

Animals↗