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Biomedical subjects

S Spiegelman

Publications and source records attributed to S Spiegelman.

At least 55 records · Page 3Linked to original sources
PubMed1976

Reverse transcriptase in leukocytes of leukemic patients in remission.

A cytoplasmic particulate fraction from human leukemic cells has been shown to contain reverse transcriptase and its associated high-molecular weight RHA template. We attempted to detect the reverse-transcriptase-template complex in morphologically normal peripheral blood leukocytes from patients with acute leukemia in complete remission. Our assay system consisted of a velocity glycerol gradient and cesium sulfate equilibrium gradient analysis of the endogenous reverse transcriptase reaction product. Three of nine patients in remission had positive reactions determined by glycerol gradient analysis, and eight of 10 patients in remission had positive reactions by cesium sulfate gradient analysis. We were unable to detect the template complex in leukocytes of normal persons. Thus, normal-appearing leukocytes in the peripheral blood of some leukemia patients in remission seem to retain a number of biochemical characteristics, possibly viral related, associated with leukemic cells.

Adult↗
PubMed1976

Molecular evidence for a viral etiology of human CNS tumors.

The newer methods of molecular virology, including molecular hybridization and the "simultaneous detection test," were used to examine human brain tumors for evidence of RNA tumor viruses. It was found that they contained 70S RNA and RNA-directed DNA polymerase, both encapsulated in a particle possessing a density of 1.17 g/ml. These particles therefore satisfy the three diagnostic features that characterize the animal RNA tumor viruses. Of 26 of the most malignant (glioblastoma and medullo blastoma) brain tumors examined, 24 (92%) contained these virus-like entities. The possible usefulness of these particles as aids in diagnosis and monitoring therapy is briefly discussed.

Astrocytoma↗
PubMed1976

Plasma levels of a viral protein as a diagnostic signal for the presence of tumor : the murine mammary tumor model.

We used the mouse mammary tumor and its associated virus (murine mammary tumor virus) to examine the possibility of using plasma levels of a viral protein (gp52, the glycoprotein of 52,000 molecular weight) as a diagnostic indicator of the presence of a solid tumor. The following features have emerged from our studies: (a) tumor-bearing animals show markedly elevated (100-1000 ng/ml) plasma levels of gp52 and the mean concentration increases with tumor size; (b) mammary tumor tissues located outside the mammary gland are also detected by the elevated plasma gp52; (c) low (2-10 ng/ml) plasma levels of gp52 are found in tumor-free mice, whether they are derived from strains characterized by high or low frequencies of spontaneous mammary tumors; (d) tumor-free lactating females exhibit the normally low levels of plasma gp52 despite the fact that their milk contains an average of 20,000 ng/ml of this antigen; (e) thus, high levels of plasma gp52 are found only in the presence of tumor and are not induced by either predisposition for the disease or by normal production of the antigen during lactation; (f) the circulatory clearance time of gp52 is sufficiently rapid to require continued replenishment to maintain the high levels observed in tumor-bearing animals, a feature implying that the gp52 concentration can be a responsive parameter of disease status. The information obtained suggests that plasma gp52 is a potentially useful and specific systemic indicator of the presence and extent of murine mammary neoplasia.

Animals↗
PubMed1975

RNA-instructed DNA polymerase activity in a cytoplasmic particulate fraction in brains from Guamanian patients.

Nervous system tissues from a number of patients with idiopathic neurological disorders were examined for biochemical evidence of RNA tumor virus infection. RNase-sensitive DNA polymerase activity was found in a cytoplasmic particulate fraction from two patients with Guamanian amyotrophic lateral sclerosis (ALS) but not in brains from two normal U.S. individuals. The buoyant density of the enzyme-containing fraction was 1.16-1.18 g/ml and could be converted to a denser region of the gradient (1.24 g/ml) by treatment with the nonionic surfactant, Sterox. The cation and detergent requirements for the endogenous RNase-sensitive DNA polymerase reaction were determined. The early (5 min) endogenous reverse transcriptase product was analyzed by cesium sulfate gradient centrifugation. RNase- and heat-sensitive RNA-DNA hybrids were detected in the product analysis of two ALS, one Parkinsonism-dementia (PD) brain, and two brains from asymptomatic Chamorros but not in brains from normal U.S. individuals and a number of patients with neuro-psychiatric disorders. The DNA product was a 4.5S heteropolymer that hybridized more extensively to RNA extracted from the enzyme-containing pellet from PD brain as compared to a similar fraction from normal U.S. brain. The DNA product appeared to be unrelated to Rausvher or visna virus 70S RNA as determined by RNA-[-3H]DNA hybridization.

Amyotrophic Lateral Sclerosis↗
PubMed1975

Purification of RNA-instructed DNA polymerase from human leukemic spleens.

Particles possessing a density of 1.16 g/ml and encapsulating a 70S RNA and a RNA-instructed DNA polymerase (reverse transcriptase) have been prepared from the spleen of a patient with chronic lymphocytic leukemia. These particles have been converted to cores with a density of 1.26 g/ml and containing the enzyme-RNA complex, in complete analogy to the known RNA tumor viruses of avian and murine origin. The reverse transcriptase was purified from the cores by column chromatography to a stage showing a single major protein band of 70,000 daltons in a gel electrophoresis. The enzyme was capable of transcribing heteropolymeric RNA into DNA complements as demonstrated by specific back hybridization to template RNA. The leukemic spleen would appear to represent an important source of this enzyme, as well as other potentially important leukemia-specific reagents.

Enzyme Activation↗
PubMed1975

Oncornavirus-like particles in human skin cancers.

A high-molecular-weight RNA encapsulated with an RNA-instructed DNA polymerase in particles possessing the density characteristic of the RNA tumor viruses has been detected in 13 out of 14 human malignant melanomas. The [3H]DNA synthesized by these particles in an endogenous reaction hybridizes to RNA extracted from the human melanoma particulate structures, but not to RNA from normal skin. Similar particles containing RNA and enzyme have been found in basal cell and squamous cell carcinomas of the skin. The RNA of the melanoma particles is easily distinguishable by hybridization from the RNAs found in the particles of the basal and squamous cell carcinomas.

Basal Cell Carcinoma↗
PubMed1975

Sequences related to the RNA tumor viruses in the RNA and DNA of human leukemias and lymphomas.

DNA-RNA hybridization was used to explore whether human neoplasias contain RNA molecules having sequence homologies to those of the RNA tumor viruses known to cause similar diseases in animals. The pattern of specific RNAs found in the human tumors showed a remarkable concordance with the predictions deducible from the animal systems. Thus human breast cancer contains RNA homologous only to that of the murine mammary tumor virus (MMTV). Human leukemias, sarcomas, and lymphomas (including Hodgkin's and Burkitt's) all contain RNA with sequence homology to the murine leukemia virus (RLV) and not to MMTV RNA. Finally, as in the case of the mouse, none of the human tumors examined contain RNA related in sequence to that of the avian myeloblastosis virus (AMV). The RNA detected in all of the human neoplasias was demonstrated to be of high molecular weight (1 times 10(7) daltons) and encapsulated with a reverse transcriptase in particles having densities between 1.16-1.19 g/ml. Further, the RNA of these human tumor particles was related in sequence to the murine viruses that cause the corresponding neoplasias in mice. Thus, 4 features diagnostic for the murine oncogenic viruses are satisfied by the particles found in the human cancers. Finally, it was shown by "recycling" experiments that the DNA from human leukemic cells and from lymphomatous tissue contained particle-related sequences that could not be detected in normal DNA. This finding was further substantiated by studies with identical twins in which it was shown that the leukemic twin contained particle-related sequences that could not be detected in the leukocytes of his identical healthy sibling. These findings are inconsistent with hypotheses that require chromosomal transmission in the germ line of complete copies of the information required to produce malignancy and the associated virus particles.

Animals↗
PubMed1975

Evidence for an RNA tumor viruses in human milk.

Certain human milks have been shown to contain particles that have the biochemical and biophysical properties that are diagnostic of the known RNA tumor viruses of animals. These properties include 1) a particle density of 1.16-1.19 g/ml 2) a viral reverse transcriptase (RNA-directed DNA polymerase), and 3) a high molecular weight (HMW) 60-70S RNA that contains polyadenylic regions of 200 nucleotides in length. Inner cores, or nucleoids, of these particles have been isolated. They have a density of 1.26-1.27 g/ml and contain the viral reverse transcriptase and 60-70S RNA. Using molecular hybridization, a specific homology was demonstrated between radioactive DNA synthesized from the RNA of the human milk particle and the RNA from human malignant breast tumors. RNA from benign breast tumors and other human tissues were negative in these tests.

Adenocarcinoma↗
PubMed1975

Biochemical characterization of putative subviral particulates from human malignant breast tumors.

Particulates with the properties of cores and/or ribonucleoproteins of RNA tumor viruses have been isolated from Sterox-SL-treated fractions of murine and human mammary adenocarcinomas. These particulates have an RNA-directed DNA polymerase, a 60 to 70 S RNA, and a density of 1.26 g/ml or greater in sucrose equilibrium density gradients. Their uniquely higher densities lead to banding in regions comparatively free of cellular contaminants. These circumstances minimize some of the technical complications of performing the simultaneous detection assay in the presence of cell debris.

Adenocarcinoma↗