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Biomedical subjects

M B Gardner

Publications and source records attributed to M B Gardner.

At least 127 records · Page 7Linked to original sources
PubMed1983

Feline oncornavirus-associated cell membrane antigen: a viral and not a cellularly coded transformation-specific antigen of cat lymphomas.

The feline oncornavirus-associated cell membrane antigen (FOCMA) was defined as a tumor antigen common to cat lymphomas and fibrosarcomas induced by feline leukemia virus (FeLV) and feline sarcoma virus (FeSV), respectively. The antigen was recognized by sera from cats thought to be resistant to leukemogenesis. We report here that a common denominator in the activity of naturally occurring viremic cat antisera to FOCMA is, in fact, their reactivity to FeLV C antigenic determinants. The cat antisera, monoclonal antibodies to FOCMA, and monoclonal antibodies to FeLV C, all reacted in immunofluorescence assays with FeLV C-infected cells and immunoprecipitated a molecule electrophoretically indistinguishable from envelope glycoprotein of FeLV. Viremic cat antisera to FOCMA bound to budding virus particles of FeLV C-infected cells, even though some of them could not be absorbed by mature virion proteins. Thus, the unusual feature of cat antibodies to FOCMA is their binding to nascent but not to mature virus particles. FOCMA-positive cat lymphomas expressed antigenic determinants of FeLV-C gp70, with or without productive infection. FeLV-negative tumors not expressing FeLV C gp70 were also FOCMA negative. Furthermore, most of the viremic cat sera and the monoclonal antibodies to FOCMA did not react with FeSV-transformed nonproducer cells. The absence of FOCMA from these cells and from FeLV-negative lymphoid tumors and its presence in FeLV-C infected fibroblasts indicated that this antigen is virus encoded and not a cellular tumor-specific antigen.

Animals↗
PubMed1983

Wild mouse retrovirus-induced neurogenic paralysis in laboratory mice. I. Virus replication and expression in central nervous system.

Ecotropic wild mouse retrovirus (1504 M)-induced neurogenic paralytic disease has been studied in inbred strains of mice. The major criterion for the successful transmission of the disease in the laboratory strains of mice is inoculation of high titer ecotropic virus in FV-1n strains of mice at newborn stage (less than or equal to 1 day old), Hybridization studies using 1504 M viral cDNA as probe indicate that in nonparalyzed mice, the inoculated virus replicates primarily in spleen tissue, whereas virus replication is evident in both spleen and central nervous system (CNS) tissue of paralyzed mice. Our studies on virus gene expression indicate that both viral gag gene product p30 and env gene product gp70 are expressed in brain, spinal cord and spleen tissues of paralyzed mice. Together, these results indicate that inoculation of neurotropic wild mouse virus into FV-1n strains of newborn laboratory mice is necessary for the establishment of infection in CNS tissue leading to virus replication and expression and resulting in the paralytic disease.

Animals↗
PubMed1983

Molecular cloning of integrated Gardner-Rasheed feline sarcoma virus: genetic structure of its cell-derived sequence differs from that of other tyrosine kinase-coding onc genes.

Gardner-Rasheed feline sarcoma virus (GR-FeSV) is an acute transforming retrovirus which encodes a gag-onc polyprotein possessing an associated tyrosine kinase activity. The integrated form of this virus, isolated in the Charon 21A strain of bacteriophage lambda, demonstrated an ability to transform NIH/3T3 cells at high efficiency upon transfection. Foci induced by GR-FeSV DNA contained rescuable sarcoma virus and expressed GR-P70, the major GR-FeSV translational product. The localization of long-terminal repeats within the DNA clone made it possible to establish the length of the GR-FeSV provirus as 4.6 kilobase pairs. The analysis of heteroduplexes formed between lambda feline leukemia virus (FeLV) and lambda GR-FeSV DNAs revealed the presence of a 1,700-base-pair FeLV unrelated segment, designated v-fgr, within the GR-FeSV genome. The size of this region was sufficient to encode a protein of approximately 68,000 daltons and was localized immediately downstream of the FeLV gag gene coding sequences present in GR-FeSV. Thus, it is likely that this 1.7-kilobase-pair stretch encodes the onc moiety of GR-P70. Utilizing probes representing v-fgr, we detected homologous sequences in the DNAs of diverse vertebrate species, implying that v-fgr originated from a well-conserved cellular gene. The number of cellular DNA fragments hybridized by v-fgr-derived probes indicated either that proto-fgr is distributed over a very large region of cellular DNA or represents a family of related genes. By molecular hybridization, v-fgr was not directly related to the onc genes of other known retroviruses having associated tyrosine kinase activity.

Animals↗
PubMed1983

Murine retroviral restriction genes Fv-4 and Akvr-1 are alleles of a single locus.

The two murine retroviral restriction genes, Fv-4 and Akvr-1, are very similar in their effects, distributions, ranges of action, and phenotypes. Akvr-1 has been shown to segregate independently in backcrosses with a variety of retroviral restriction loci, including Fv-1, Fv-2, Ril-1, and Ril-2. An allelism test cross of FRG (Fv-4R) X LCRR (Akvr-1R) hybrids mated to AKR mice failed to produce any viremic offspring. These results suggested that Akvr-1R and Fv-4R are alleles of a single locus, Fv-4, on mouse chromosome 12.

Alleles↗
PubMed1982

Characterization of a highly oncogenic murine leukemia virus from wild mice.

We have isolated a highly lymphomagenic wild mouse virus by passage of a weakly oncogenic amphotropic murine leukaemia virus (MuLV-A) in NIH Swiss mice. This virus is similar in host range, interference and neutralization properties to that of the inoculated amphotropic virus but is distinct from it biochemically and causes lymphomas in 90-100% of mice within 1-2 months. Our results indicate that this highly oncogenic virus is a recombinant of wild mouse MuLV-A and sequences related to env gene region of the endogenous xenotropic virus of NIH Swiss mice.

Animals↗
PubMed1982

Viruses as environmental carcinogens: an agricultural perspective.

Under natural circumstances tumor viruses can be considered as risk factors which in themselves are neither necessary nor sufficient to produce cancer; they may do so, however, if provided with suitable genetic and environmental conditions. It follows that a reduction in amount of virus or other environmental cofactors may prevent the associated tumors. In this paper we will consider four major families of viruses associated with cancer in animals and man, and will highlight the exogenous cofactors and related preventive measures. We will mention those agricultural practices that have resulted in significant economic loss from virus induced cancer in farm and domestic animals and will summarize some of the occupational hazards from environmental agents other than tumor viruses.

Agriculture↗
PubMed1982

Characterization of genome structure of amphotropic and ecotropic wild mouse retroviruses.

We studied the RNA genomes of several wild mouse type C retroviruses by using RNase T1-oligonucleotide fingerprinting. The amphotropic and ecotropic viruses of field strain 1504 produced very similar oligonucleotide fingerprints, but each also had several unique oligonucleotides. All of these unique oligonucleotides were located in the env gene region and were probably responsible for the host range differences between these viruses, as well as the lymphomagenic and paralytogenic properties of the viruses. We obtained similar results with the amphotropic and ecotropic viruses of another field strain (4070), which was isolated from a mouse from a different trapping area. The amphotropic viruses of several field strains (strains 1504, 4070, and 1313) were more closely related than the ecotropic viruses of different strains (strains 1504, 4070, and 4996). These findings suggested that the genetic sequences of the amphotropic viruses are more conserved than those of ecotropic viruses isolated from the same wild mice.

Animals↗
PubMed1981

Natural killer cell activity in a population of leukemia-prone wild mice (Mus musculus).

Natural cell-mediated cytotoxicity against YAC-I targets was measured in splenocytes from leukemia-prone wild mice trapped near Lake Casitas (LC) in southern California. Cytotoxicity was mediated by cells that were non-adherent to nylon wool, non-phagocytic and resistant to thy-1.2 antiserum plus complement. Natural MuLV viremia in LC mice did not impair splenic cytotoxicity against TAC-I target cells, Cells infected with amphotropic and ecotropic MuLV of wild mouse origin were not appreciably lysed by LC splenic effectors. Although variable levels of cytotoxicity were detected against TAC-1 by normal spleen cells, consistently low levels of cytotoxicity against allogenic LC lymphoma, sarcoma and carcinoma targets were found using the same splenocytes. These results indicate that LC mice possess splenocytes with the characteristics of natural killer (NK) cells as defined in inbred mice. The resistance of LC-derived targets to lysis by LC NK cells suggests that NK cells may not be involved in natural tumor immunosurveillance or that the development of spontaneous tumors may involve escape from NK-mediated effector mechanisms.

Animals↗
PubMed1981

The U3 portion of feline leukemia virus DNA identifies horizontally acquired proviruses in leukemic cats.

The presence and location of DNA sequences related to the U3 and U5 portions of the infectious exogenous feline leukemia virus (FeLV) long terminal repeat (LTR) in various cat DNAs have been determined by hybridization experiments. In uninfected cat DNAs, the U5 LTR segment from the Gardner-Arnstein strain B virus is present at approximately 150 copies per cell. This level is approximately 10-fold greater than that of endogenous internal FeLV sequences. The U5 sequences differ in copy number and, to some extent, in location from one animal to another. For any one animal, the sequence organization of the U5 segments is the same among different tissues, showing that the pattern is inherited through the germ line. Most importantly, the viral U3 LTR probe hybridizes only very weakly with uninfected cat DNAs. Both the U3 and the U5 regions of the LTR from the Gardner-Arnstein strain of virus cross-hybridize with DNA derived from four other infectious FeLVs representing A, B, and C subtypes. Thus, the C3 region may be used as a probe for studying the number and location of exogenously acquired FeLV proviruses in infected cat tissues. In some cases exogenously acquired proviruses are present in unique sites in the genome of virus-positive cat lymphosarcomas, indicating a monoclonal origin for the tumor. In other tumors, the proviral sequences are randomly distributed over many sites. Lymphosarcomas of virus-negative cats have no exogenous U3 sequences despite epidemiological evidence of an association of virus-negative leukemia with exposure to FeLV.

Animals↗
PubMed1981

Immunopathology of natural and experimental lymphomas induced by wild mouse leukemia virus.

Naturally occurring lymphomas of Lake Casitas (LC) wild mice, and the lymphomas induced by LC murine leukemia virus (MuLV) in Swiss mice from the National Institutes of Health, displayed remarkably similar gross, microscopic, and functional characteristics. They spared the thymus, arose primarily in the splenic red pulp, became leukemic, and were comprised of stem cells lacking classic T- and B-cell markers. Cytoplasmic and surface immunoglobulin were undetectable in 34 of 35 spontaneous LC lymphomas and in any of ten LC MuLV-induced lymphomas in NIH Swiss mice. Assays for immunoglobulin secretion, complement (C'3) and Fc receptors, Thy 1.1,2 antigens, Ly 1,2 antigens, and erythroid and myeloid markers were negative on all of the spontaneous and experimental lymphomas. Cell lines were derived from five spontaneous lymphomas of LC mice. Three lines were characterized as null cells, one line as B cells, and one line as macrophages. All cell lines were diploid. The wild mouse spontaneous lymphomas, and lymphomas experimentally induced by LC MuLV in laboratory mice, provide a useful model for childhood acute lymphoblastic leukemia and for study of the early steps of B-lymphocyte differentiation.

Animals↗
PubMed1981

Growth properties and susceptibility to viral transformation of skin fibroblasts from individuals at high genetic risk for colorectal cancer.

Growth characteristics and susceptibility to viral transformation were compared in cultured skin fibroblasts from patients with Gardner's syndrome (GS), those with familial polyposis coli (FP), asymptomatic family members, and unrelated controls. Compared to cells from unrelated controls, cells from 4 of 5 GS patients were transformed by Kirsten murine sarcoma virus at 100- to 1,000-fold increased efficiency. The transformation efficiencies of fibroblasts from 2 of 3 FP patients were 10- to 100-fold greater than those of unrelated controls. However, because the fibroblasts from some of the young asymptomatic GS and FP family members also transformed at higher efficiency than did cells from unrelated controls, long-term observation of these families is required. This would determine whether or not these members develop clinical manifestations of GS or FP and thus establish the specificitiy of this assay for detection of individuals bearing the mutant gene. Compared to fibroblasts from unrelated controls, GS and FP fibroblasts showed a twofold to threefold increased saturation density and plating efficiency, but this difference was not noted with fibroblasts from most of the asymptomatic family members.

Adolescent↗
PubMed1980

Genetic diversity in leukemia-prone feral house mice infected with murine leukemia virus.

The Lake Casitas (LC) mouse population located in south western Ventura county in California is unusual insofar as 85% of these mice are persistently viremic with congenitally transmitted murine leukemia virus (MuLV). The virus has been identified as the etiological agent responsible for lymphoma and neuromotor paralysis in large numbers of the mice. The majority of other wild mouse populations are generally free of infectious MuLV despite the presence of endogenous cellular DNA sequences homologous to infectious virus isolated from wild mice. Electrophoretic variation in 46 gene-enzyme systems was surveyed using mice from Lake Casitas and from a virus-negative population located in Bouquet Canyon (BC) approximately 40 miles from Lake Casitas. The LC and BC populations are genetically very similar to each other and to feral mouse populations previously studied in California and Europe. In the LC population 24% of the loci are polymorphic compared to 17% in the BC population. The average heterozygosities for the LC and Bc populations are 0.094 and 0.073, respectively. The large amount of genic variation in LC fails to support the concept of the derivation of the colony from a small number of founders. Tests for linkage disequilibrium and/or selective association of viremia and polymorphism at 15 loci located on nine mouse chromosomes did not reveal any nonrandom assortments. The viremic LC population, then, appears indistinguishable within the limits of experimental resolution from the virus-negative BC population in its population genetic structure.

Animal Population Groups↗
PubMed1980

Akvr-1, a dominant murine leukemia virus restriction gene, is polymorphic in leukemia-prone wild mice.

We describe a restriction gene (Akvr-1, for AKR virus restriction) that is polymorphic for two alleles, Akvr-1R (restrictive) and Akvr-1r (susceptible), in a feral population of mice (Mus) musculus domesticus) at a squab farm near Lake Casitas (LC) in southern California. Akvr-1k is a dominant allele that exhibits 100% penetrance in prevention of viremia of AKR endogenous retrovirus and of virus-mediated lymphoma in LC (Akvr-1RR) X AKR F1 hybrids. The restriction phenotype segregates as a single Mendelian locus in backcrosses to AKR mice. Akvr-1R likewise is effective in restriction of NB-tropic Moloney murine leukemia virus-induced viremia and NB-tropic Friend virus-induced splenomegaly but fails to restrict expression or pathogenesis of LC-derived amphotropic retrovirus. Pleiotropic restriction of AKR, Friend, and Moloney ecotropic viruses, but not of amphotropic virus, suggests that the viral targets of Akvr-1 in the three ecotropic viruses are similar to each other and distinct from the target in the LC-amphotropic virus. The relationship of Akvr-1 to previously reported murine restriction loci Fv-1, Fv-2, and Fv-4 is discussed.

AKR murine leukemia virus↗