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Biomedical subjects

M B Gardner

Publications and source records attributed to M B Gardner.

At least 181 records · Page 10Linked to original sources

Acceleration of transformation of rat embryo cells by rat type C virus.

Sprague-Dawley and Fischer rat embryo cells became spontaneously transformed about 20 passages after release of endogenous ecotropic type C virus (SD-RaLV and F-RaLV). The virus-producing transformed cells showed loss of contact inhibition, increased growth rate, and tumorigenicity in vivo. Exogenous infection of other Fischer rat embryo cultures in early passage with SD-RaLV and F-RaLV markedly accelerated their rates of transformation.

Animals↗

Spontaneous release of endogenous ecotropic type C virus from rat embryo cultures.

Type C viruses were isolated from embryo cultures of two different rat strains, Sprague-Dawley and Fischer. Both viruses (termed rat leukemia virus, RaLV) were released spontaneously from rat embryo cells, have a density of 1.14 to 1.15 g/cm(3) based on equilibrium sedimentation in sucrose gradients, contain 60-70S RNA, RNA-directed DNA polymerase, and rat type C virus-specific 30,000 molecular-weight-protein determinants. Molecular hybridization studies using the Sprague-Dawley RaLV 60-70S RNA show that the virus-specific nucleotide sequences are present in the DNA of rat embryos. Both Sprague-Dawley and Fischer RaLV can rescue the murine sarcoma virus genome from Kirsten murine sarcoma virus-transformed nonproducer cells and are neutralized by antisera to the RPL strain of RaLV. In contrast to previous RaLV's, these viruses propagate in their own cells of origin as well as in cells of heterologous rat strains.

Animals↗

Amphotropic host range of naturally occuring wild mouse leukemia viruses.

Seven murine leukemia virus field isolates (uncloned) from wild mice (Musmusculus) of four widely separated areas in southern California show an unusually wide in vitro host range. They replicate well in human, feline, canine, guinea pig, rabbit, rat, and mouse cells, whereas bovine, hamster, and avian cells are resistant. Since this host range includes that of both mouse tropic (ecotropic) and xenotropic murine leukemia viruses, they are designated as "amphotropic". No purely xenotropic virus component is detectable in these field isolates. They may represent the "wild" or ancestral viruses from which the ecotropic and xenotrophic murine leukemia virus strains of laboratory mice have been derived.

Animals↗

Assay for type C virus in mouse sera based on particulate reverse transcriptase activity.

Assay of particulate reverse transcriptase activity in the sera from feral mice naturally infected with type C virus provides a sensitive and rapid procedure for the determination of in vivo virus infection. The results compare well with assays for infectious virus and with complement fixation or competitive radio-immunoassays for the p30 internal antigen of the virus.

Animals↗

The epidemiology and virology of C-type virus-associated hematological cancers and related diseases in wild mice.

In several different populations of wild mice, observed over a 35-month period in laboratory geriatric colonies, a direct correlation was found between the prevalence and titer of spleen complement-fixing gs (p30) antigen and C-type particles in newly trapped healthy mice and a predilection to lymphoma and a hind leg paralytic disease upon aging. Other studies have established the indigenous C-type virus as the essential etiological determinant of both diseases in wild mice. An increased incidence of breast carcinomas, hepatomas, and pulmonary adenomas associated with C-type virus also occurred in the lymphoma-paralysis-prone colony as compared with the tumor-resistant colonies.

Animals↗

Lower motor neuron disease in wild mice caused by indigenous type C virus and search for a similar etiology in human amyotrophic lateral sclerosis.

In certain genetically susceptible populations of wild mice a progressive motor neuron disease with a long latent period is caused by indigenous type C leukemia virus. Neuronal damage appears to be due primarily to a direct neurotropic effect of the virus and not to an immunogenic mechanism. The disease can be prevented by antiviral genetic means. Search for a similar virus in humans with ALS has been negative.

Amyotrophic Lateral Sclerosis↗

Childhood sarcomas and lymphomas. Characterization of new cell lines and search for type-C virus.

Four cell lines were derived from childhood malignancies: rhabdomyosarcoma, sarcoma, lymphosarcoma and an American Burkitt's lymphoma. Cells of the four lines formed tumors in immunosuppressed newborn hamsters. The tumors had a microscopic appearance like that of the tumors from which the cell lines were derived. No virus-like particles were detected by electron microscopy in the cell lines after treatment with bromodeoxyuridine; no hamster type-C virus expression was present in cell lines derived from the hamster tumors. Chromosome constitution and in vitro growth properties of the cell lines were studied as was the fibrinolytic function of the sarcoma lines.

Adolescent↗

Mammary tumor virus particles in the submaxillary gland, seminal vesicle, and nonmammary tumors of wild mice.

Type-B mammary tumor virus particles were detected by electron microscopy in the submaxillary glands of 6 of 27 freshly trapped, pregnant wild mice (Mus musculus). Type-B particles were also detected in 3 9f 24 seminal vesicles and 2 pulmonary adenomas from wild mice. Intracytoplasmic type-A virus particles were found in 7 spontaneous nonmammary tumors (lymphoma, hepatoma, lung adenoma) of aging wild mice. Type-C virus particles were also detected in many of these tissues.

Adenoma↗

Comparative studies on the structural phosphoproteins of mammalian type C viruses.

The major phosphoprotein common to woolly monkey sarcoma virus, gibbon ape lymphosarcoma virus, and type C viruses of the lower mammalian species (mouse, rat, cat), with the exception of the endogenous cat virus (RD-114), is the polypeptide of about 12,000 molecular weight. The protein-phosphate bond in this polypeptide of several viruses is of the phosphoserine variety excepting gibbon ape virus, which contains both phosphoserine and phosphothreonine. The primary phosphoprotein of RD-114 virus and the endogenous baboon type C virus, on the other hand, is the polypeptide of about 15,000 molecular weight which contains phosphothreonine as its phosphoamino acid. A second major phosphoprotein of molecular weight of 10,000 is detected only in viruses genetically related to rat species including those derived from the RPL cell line, from Sprague-Dawley rat embryo cells, and the Kirsten mouse sarcoma virus which was recovered from a mouse erythroblastosis virus after in vivo propagation through rat. These phosphorylated polypeptides of molecular weight 15,000, 12,000, or 10,000 are present in the virion structure in several different but nonrandom phosphorylated states.

Animals↗

Biochemical properties of wild mouse oncornaviruses with lymphomagenic and neurotropic activities.

The close immunologic relation between the group-specific and polymerase proteins of the wild mouse derived and the established strains of mouse type C oncornaviruses, and the lack of any unusual structural polypeptide or RNA components in the wild mouse virions, eliminate the possibility of detectable contamination by a class of virus different from the mouse oncornavirus class in the wild mouse virus preparations. Liquid hybridization studies with a wild mouse viral 70S 3H-RNA and cellular DNA under conditions of DNA excess, suggest that a significant fraction but not all of the virus-specific nucleotide sequences is present in all normal and tumored wild mouse tissues tested. These virus related sequences may possibly be attributed to a hypothetical endogenous inherited type C virus genome(s) carried by all wild mice or to an infection by one or more but not all of the different exogenous strains of wild mouse type C viruses which could possibly be present in the virus preparation used. The findings are consistent with wild mouse derived type C viruses being either entirely exogenous or a mixture of endogenous and exogenous viruses. This interpretation is also consistent with the earlier observation that certain wild mouse type C viruses are exogenously transmitted, transplacentally, and via milk. The possible relation of the virus heterogeneity or the distinct characteristics of the virus surface molecules to the diverse pathogenicity of the wild mouse oncornaviruses is discussed.

DNA Nucleotidyltransferases↗

Immunogenetics of a thymus antigen in lymphoma-prone and lymphoma-resistant colonies of wild mice.

The Thy-1 (theta) antigen was identified in wild mice (Mus musculus), the frequency of its alleles was determined in two natural populations of wild mice, and the possible T-cell origin of spontaneous lymphomas was investigated in one of these populations. Reaction patterns for Thy-1 antigen with the use of direct cytoxicity and indirect absorption assays were identical in wild mice and inbred strains. Between 15 and 55 percent of viable spleen cells from healthy young or old wild mice were Thy-1 positive. Spleen, but not brain, cells from older wild mice were less strongly positive. Wild mice from the lymphoma-prone population were polymorphic for Thy-1alpha and Thy-1beta alleles, whereas wild mice from the lymphoma-resistant populations were homozygous for the Thy-1beta allele. Contrary to expectation, a higher frequency of the Thy-1beta allele was noted in the mice with lymphomas. Alleles at two other loci on chromosome number 9 (Mod-1alpha and Trfbeta) were fixed in both populations. The absence of detectable Thy-1 antigen on spleen cells (despite its detectability in undiminished titer in brain tissue) in 80 percent of mice with lymphomas, along with the absence of thymus involvement in the lymphomatous proliferations, suggested that these tumors are derived from an expansion of non-thymus-derived cells.

Absorption↗