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Biomedical subjects

S Spiegelman

Publications and source records attributed to S Spiegelman.

At least 91 records · Page 5Linked to original sources
PubMed1973

Quantitation of RNA tumor viruses and viruslike particles in human milk by hybridization to polyadenylic acid sequences.

RNA tumor viruses and viruslike particles from human milk are quantitated by hybridization of the polyadenylic acid regions in their 60S to 70S RNA to radioactive polyribouridylic acid of known specific activity. The length of the polyadenylic acid region in the 60S to 70S RNA of the human milk particle is identical to that of the known oncogenic RNA viruses.

Avian Leukosis Virus↗
PubMed1973

Particles with RNA of high molecular weight and RNA-directed DNA polymerase in human brain tumors.

We have previously shown that neoplastic cells of human breast cancers, leukemias, lymphomas, and sarcomas contain particles similar to the viruses that have been established as etiologic agents of these diseases in mice. The present paper concerns tumors of the central nervous system for which no suitable animal model or corresponding virus exists. Nevertheless, using the simultaneous detection test, we showed that human brain tumors contain 70S RNA and RNA-directed DNA polymerase encapsulated in a particulate component possessing a density of 1.17 g/ml. These particles satisfy the three diagnostic criteria that characterize RNA tumor viruses of animals. 24 Out of 26 (92%) of the most malignant (glioblastoma and medulloblastoma) brain tumors examined contained these virus-like entities.

Astrocytoma↗
PubMed1973

Biological and biochemical evidence for an interaction between Marek's disease herpesvirus and avian leukosis virus in vivo.

The DNA-containing Epstein-Barr herpesvirus has been implicated in the etiology of Burkitt's lymphoma, a malignant tumor of children in Africa. Recently, however, particles possessing four biochemical characteristics of RNA tumor viruses have also been identified in these tumors. The fact that both types of viruses are found suggests that an interaction between them may be playing a role in the etiology of Burkitt's lymphoma. To explore this possibility with a defined animal model, experiments were performed with the avian Marek's disease, a malignant lymphoproliferative disease associated with a herpesvirus. Controlled contact studies demonstrated that tumorigenesis in a line of isolator-derived, barrier-sustained, specific pathogen-free chickens requires exposure to both the Marek's disease herpesvirus and an avian leukosis virus, Rous-associated virus, type 2. Exposure to either agent alone did not result in tumors. Molecular hybridization experiments to cytoplasmic RNA from similarly contact-exposed conventional Cornell S-line chickens provided further evidence for the occurrence of an interaction between Marek's disease herpesvirus and the avian leukosis virus.

Animals↗
PubMed1973

Unique nuclear DNA sequences in the involved tissues of Hodgkin's and Burkitt's lymphomas.

Previous studies have demonstrated that Hodgkin's, Burkitt's, and other human lymphomas contain particulate elements encapsulating 70S RNA and RNA-dependent DNA polymerase. [(3)H]DNA probes endogenously synthesized by these particles were used to demonstrate that the nuclear DNA of the lymphomas contain particle-related sequences that cannot be detected (less than 1/20th of a copy per genome) in the DNA of normal cells. This result agrees with our earlier findings in human leukemias. The data are inconsistent with any etiologic concept that invokes germ-line transmission of at least one complete copy of the particulate information associated with the malignancy. The unique sequences found in the nuclear DNA of Burkitt's and Hodgkin's tissues are related to each other but not to the DNA of the Epstein-Barr virus.

Base Sequence↗
PubMed1973

Burkitt's tumors contain particles encapsulating RNA-instructed DNA polymerase and high molecular weight virus-related RNA.

Burkitt's lymphomas, linked by previous studies with the DNA-containing Epstein-Barr virus, contain an RNA related in sequence to that of Rauscher leukemia virus. The present study establishes that the viral-related RNA found in Burkitt's tumors is a 70S component encapsulated with RNA-instructed DNA polymerase in a particle possessing a density characteristic of RNA tumor viruses. Further, the DNA synthesized by the Burkitt particles hybridizes specifically to the RNA of Rauscher leukemia virus. Thus, four features characteristic of a known oncogenic RNA agent are also exhibited by particles found with a high (87%) frequency in Burkitt's tumors. The relation between the RNA particle and the Epstein-Barr virus and their etiological roles remains to be elucidated. However, relevant to these issues is the finding reported here that the presence of Epstein-Barr virus information in nonneoplastic cells does not lead to the production of the RNA particles that have been detected now in three different human neoplasias, including leukemias, breast cancer, and Burkitt's disease.

Burkitt Lymphoma↗
PubMed1973

Determination of natural host taxonomy of RNA tumor viruses by molecular hybridization: application to RD-114, a candidate human virus.

The lysogenic bacteriophages and the RNA tumor viruses have in common the ability to add their genetic information to the genome of their host cells. The biological similarity extends further; data summarized here indicate that they both possess homology to the DNA of their uninfected indigenous hosts. Sharing of common sequences with normal host DNA has been established with avian, murine, feline, and primate oncornaviruses. This finding provides a method for determining the taxonomic position of the natural host of any new RNA tumor virus isolated. Application of this approach to RD-114 revealed extensive hybridization to normal cat DNA and little, if any, hybridization to human DNA. We conclude that the data assign a feline origin rather than a human origin to RD-114.

Animals↗
PubMed1973

Decreased globin messenger RNA in thalassemia detected by molecular hybridization.

In previous studies of patients with beta thalassemia, mRNA extracted from reticulocytes in peripheral blood when added to cell-free systems reproduces the deficient beta-chain synthesis characteristic of intact cells. The present studies with specific probes for alpha and beta mRNA were designed to decide whether the decreased beta mRNA activity is due to the presence of abnormal or reduced beta globin mRNA in these cells. Purified alpha and beta complementary DNAs (cDNAs) have been synthesized with RNA-instructed DNA polymerase; alpha and beta mRNAs isolated from heavy (beta-producing) and light (alpha-producing) polyribosomes of rabbit reticulocytes were used as templates. Each of the cDNAs is more than 80% pure by the criterion of biological activity. The alpha cDNA labeled with [(32)P]dCTP and the beta cDNA labeled with [(3)H]dCTP have been added simultaneously to reaction mixtures containing various concentrations of mRNA from thalassemic and nonthalassemic subjects. The extent and rate of hybridization were determined, permitting a comparison of relative alpha and beta mRNA content in the same annealing mixture. In six nonthalassemic patients, relatively equal amounts of hybridizable alpha and beta mRNA appear to be present. In five of seven patients with beta-thalassemia, significantly decreased amounts of beta mRNA compared to alpha mRNA can be demonstrated. In two patients with Hemoglobin H disease, there is a decreased amount of alpha mRNA compared to beta mRNA.

Animals↗
PubMed1973

Further evidence for oncornaviruses in human milk: the production of cores.

Cores, or nucleoids, have been isolated from particles in human milk. The cores have a density of 1.26-1.27 g/ml and contain a 60-70S RNA in association with an RNA-instructed DNA polymerase. The data offer further evidence of similarity between human milk particles and animal RNA tumor viruses. In addition, core isolation provides a new method for detection of these particles by minimizing the difficulties generated by the presence of cell-associated debris often found in the density region (1.16-1.19 g/ml) characteristic of the intact virion. The procedures described now make available preparations of purified subviral components of a putative human RNA tumor virus.

Animals↗