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Biomedical subjects

G J Todaro

Publications and source records attributed to G J Todaro.

At least 19 recordsLinked to original sources
PubMed1979

Effect of interferon on chronic infection of human cells by xenotropic type-C viruses.

Different preparations of human interferon inhibit virus production in human cells chronically infected by a variety of type-C xenotropic viruses. Some of these viruses have been incriminated in the development of leukemia in primates. The characteristics of blocking of viral multiplication are similar to those described for the effect of mouse interferon on ecotropic viruses. The amount of free virus in culture supernatants is strongly decreased while intracellular protein p30 stays unchanged or is slightly increased. On the other hand, the inhibitory effect is reversible. The withdrawal of interferon results in a rapid increase in virus production as detectable in supernatant fluids. In the light of these results it is suggested that human interferon might be useful in the treatment of some blood malignancies suspected of being related to infection with xenotropic type-C viruses.

Animals↗
PubMed1979

Increased levels of a nerve-growth-factor cross-reacting protein in "central" neurofibromatosis.

Nerve-growth factor (N.G.F.) from serum was assayed in 9 affected individuals from three kindreds with the trait "central neurofibromatosis". The hallmark of this disease is bilateral acoustic neuromas. Antigenic activity, as measured by radioimmunoassay, was significantly elevated. However, functional activity for N.G.F.; as measured by radioreceptor assay, was normal or low. This indicates that the central form of neurofibromatosis is characterised by high circulating N.G.F. levels which show low to normal function. These changes in N.G.F. differ from those in peripheral neurofibromatosis and suggest that the two hereditary conditions involve different alterations in N.G.F. synthesis and/or regulation.

Adolescent↗
PubMed1979

Rapid release of fibronectin from human lung fibroblasts by biologically active phorbol esters.

A sensitive radioimmunoassay technique has been used to study the effects of several phorbol esters on their ability to release fibronectin from cultured human lung fibroblasts into medium. The biologically active phorbol esters studied rapidly released fibronectin from cells into medium, with concomitant changes in the cellular morphology within 2 h. The quantity of fibronectin released was dose-, time- and promoter-dependent. The earliest release of fibronectin was seen within 30 min of onset of the incubation. Alterations in membrane topology elicited by phorbol esters appear to be responsible for the rapid release of fibronectin molecules from cells into the medium.

Cells, Cultured↗
PubMed1979

Human fibrosarcoma cells produce fibronectin-releasing peptides.

A sensitive radioimmunoassay, specific for human fibronectin, was used to measure the ability of certain biologically active polypeptides to release fibronectin from cultured human lung fibroblasts into their culture media. Concentrated, serum-free supernatant from a human fibrosarcoma cell line was fractionated by gel filtration chromatography in the presence of acetic acid. Various polypeptides with molecular weights between 46,000 and 6,000 were tested for their ability to release fibronectin from cells. The column fraction, containing polypeptides with an apparent molecular weight of 10,000, exhibited the ability to rapidly release fibronectin from target cells. The activity could be inhibited by phenylmethyl sulphonylfluoride. Several other hormonal factors, tested in parallel with the column fractions, failed to show this effect. The 10,000 dalton molecular weight polypeptides may represent a family of cellular gene products responsible for maintenance of low levels of surface associated fibronectin in fibrosarcoma cells and thus be related to their infiltrating properties by preventing the formation of the extracellular matrix.

Animals↗
PubMed1979

A murine sarcoma virus-associated protein kinase: interaction with actin and microtubular protein.

A low molecular weight (LMW) protein phosphokinase enzyme that binds to actin has been isolated from murine sarcoma virions; this kinase activity is not present in nontransforming murine leukemia viruses. Sephadex G-75 gel filtration and affinity chromatography on actin-Sepharose conjugates allow a significant level of purification of this enzyme. The enzyme associates with microtubular proteins and inhibits the in vitro polymerization of microtubules. This study represents the first isolation of a sarcoma virus-associated protein that possesses the ability to interact directly with two major components of the cytoskeletal system.

Actins↗
PubMed1979

A new endogenous primate type C virus isolated from the Old World monkey Colobus polykomos.

A new, genetically transmitted retrovirus has been isolated from the Old World monkey Colobus polykomos. This virus, designated CPC-1, is readily transmitted to both feline and human cells in culture. Nucleic acid hybridization studies reveal that there are 50-70 copies of the CPC-1 genome in colobus cellular DNA. Related virogene sequences can be detected in the DNA of all other Old World monkeys, as well as in the DNA of at least one ape species, the chimpanzee, indicating that this virus has been genetically transmitted in primates for 30-40 million years. CPC-1 is partially related to the type C virus previously isolated from stumptail monkeys (MAC-1). These two viruses have nucleic acid sequence homology, antigenic crossreactivity in their major viral structural protein, and a very similar host range in vitro. CPC-1 and MAC-1 therefore belong to the same class of genetically transmitted primate type C viruses and, as such, represent the first example in primates of analogous endogenous retroviruses isolated from two distantly related species.

Animals↗
PubMed1979

Human melanoma cells have both nerve growth factor and nerve growth factor-specific receptors on their cell surfaces.

Human melanoma cells were examined in an indirect membrane immunofluorescence assay for surface nerve growth factor (NGF) and NGF receptors. This assay revealed that human melanoma cells have various levels of NGF and NGF receptors on the plasma membrane, whereas a variety of human sarcoma and carcinoma tumor cells and normal human fibroblasts are negative. Surface NGF could be detected on melanoma cells with a rabbit antiserum directed to NGF at titers as high as 1:64; prior adsorption of this antibody with mouse 2.5S NGF resulted in a loss of fluorescence. The melanoma cells were positive whether or not they were grown in the presence of fetal calf serum. NGF production by human melanomas is a previously unrecognized property of this differentiated cell type. Although other cells in culture have been shown to produce NGF, the association of NGF production with the presence of NGF receptors on the cell surface is rare among tumor cells, and may represent an opportunity for "autostimulation" of melanoma cells by this growth factor.

Cell Line↗
PubMed1979

Thermolabile protein kinase molecules in a temperature-sensitive murine sarcoma virus pseudotype.

Murine sarcoma virus-associated protein kinases that bind to actin have been purified by affinity chromatography on actin coupled to Sepharose. Heat inactivation studies showed the presence of thermolabile enzyme activity in pseudotypes containing a temperature-sensitivity mutant of murine sarcoma virus (MSV) but not in two independent wild-type MSV pseudotypes. Studies with Sephadex G-75 column fractions showed that a low molecular weight form, approximately 15,000, is the major thermolabile kinase in the temperature-sensitive MSV virions. Antibodies raised against the MSV-coded p60 protein, when added to the in vitro reaction mixtures, showed specific phosphorylation of the IgG heavy chain and a simultaneous reduction in the extent of phosvitin phosphorylation catalyzed by the various MSV pseudotype kinases. Thus a transforming retrovirus-coded enzyme activity that interacts directly with a major cytoskeletal protein and whose activity parallels the transforming ability of a conditional MSV mutant has now been identified.

Actins↗
PubMed1979

Isolation of an endogenous type C virus related to the infectious primate type C viruses from the Asian rodent Vandeleuria oleracea.

A tissue culture line derived from the Asian rodent Vandeleuria oleracea has been shown to release an infectious, xenotropic type C virus. The virus-associated reverse transcriptase (RNA-dependent DNA nucleotidyltransferase) and the major internal protein p30 are immunologically related to the respective proteins of the woolly monkey-gibbon ape group of infectious primate viruses. By these criteria the V. oleracea viral isolate is similar to the murine type C-I class of endogenous retroviruses and has been designated Vand C-I. Nucleic acid homology studies show that V. oleracea cellular DNA shares similar levels of homology with DNA from members of the Mus and Rattus genera and lower levels of homology with other rodent genera. The Vand C-I viral genome is present in V. oleracea cellular DNA in multiple copies, and partially related sequences can be detected in other rodent genera. These results support the conclusion that the Vand C-I viral genome is genetically transmitted in V. oleracea and that the type C-I class of endogenous retroviral genes has been highly conserved during evolution.

Animals↗