PubMed Health⌕ Search

Biomedical subjects

F Lilly

Publications and source records attributed to F Lilly.

At least 55 records · Page 3Linked to original sources
PubMed1981

Viral protein expression in producer and nonproducer clones of friend erythroleukemia cell lines.

Erythroleukemia cell lines HFL/d and HFL/b, derived from tumors induced in vivo in BALB/c (H-2d) and congenic BALB.B (H-2b) mice, respectively, by a polycythemia-inducing strain of Friend virus, produced both spleen focus-forming virus (SFFV) and its native NB-tropic helper virus (Friend murine leukemia virus [FMuLV]) during early-passage generations in culture. Eventually each line ceased production of both infectious viruses but retained its tumorigenic potential in syngeneic hosts. Virus-producer and -nonproducer clones of these cell lines were examined for expression of proteins encoded by the SFFV or FMuLV genomes. Lysates of labeled cells were treated with various antiviral sera, and the precipitates were examined by gel electrophoresis. Expression of the FMuLV env gene-encoded precursor protein, gPr84env, was observed in all producer and most nonproducer clones, but the FMuLV gag and pol gene products, Pr65gag and Pr200gag-pol, were uniformly undetectable in nonproducer clones. All HFL/d and HFL/b clones expressed appreciable amounts of the SFFV-encoded envelope protein, gp52, including one exceptional clone which had ceased to express any FMuLV-encoded proteins. The molecular weight of this SFFV-encoded envelope protein was consistently smaller in all HFL/b clones than in HFL/d clones, regardless of their producer or nonproducer status. The virus-nonproducer phenotype thus appears to be due to shutdown of expression of the 5' portion of the FMuLV genome in two independent cell lines.

Animals↗
PubMed1981

Construction of a D2.B6-Fv-2r congenic mouse strain: nonlethality of the homozygous Fv-2' genotype.

Starting from the (C57BL/6 x DBA/2)F1 generation (Fv-2s/Fv-2r), 16 serial backcrosses to mice of the parental DBA/2 strain (Fv-2s/Fv-2s) were bred. In each generation, heterozygous Fv-2s/Fv-2r segregants were selected and backcrossed with a DBA/2 parent. In the 16th generation, Fv-2s/Fv-2r heterozygotes were intercrossed, and Fv-2r/Fv-2r homozygotes were selected for interbreeding to establish a congenic strain, D2.B6-Fv-2r. The successful establishment of this congenic strain is in contrast with previous findings suggesting that homozygosity for the Fv-2r allele might be a lethal genotype on the DBA/2 genetic background. At least 10 centimorgans of Fv-2r-linked chromosomal material originating from the C57BL/6 ancestor remains in the D2.B6-Fv-2r genome, as shown by the continued presence of C57BL/6 alleles at the flanking Kfo-1 and Bgl-s loci. The observed recombination frequency for the intervals between Fv-2 and Bgl-s was 6.8%.

Alleles↗
PubMed1980

Fv-2r-mediated resistance of mouse bone-marrow cells to Friend spleen focus-forming virus infecton.

A target cell assay based on the formation of infectious centers (IC) was used to characterize the Fv-2resistance gene of mice. Dose-response curves were obtained for the number of IC generated from incubated mixtures of bone-marrow cells and Friend virus (FV). The hemopoietic stimulus of bleeding increased the frequency of potential "target" cells capable of forming IC in DBA/2 but not in D2.Fv-2r mice; however, even without the bleeding stimulus D2.Fv-2r mice contained fewer target cells in their bone marrow than DBA/2 mice. During the first 48 h postinfection a massive dose of FV overcame the inhibitory effect of the FV-2r gene as measured by the release of FV from the spleen. However, the concentration of IC recoverable from the spleens of these infected mice was still much lower in the D2.Fv-2r strain. When irradiated F1 hybrid hosts were used as recipients for the proliferation of infected donor cells, splenic IC were not generated as efficiently from infected bone-marrow cells of D2.Fv-2r origin as from those of DBA/2 origin. However, the amounts of SFFV recoverable were approximately the same. Similarly, after in vitro infection there was no great difference between the amounts of SFFV released from bone-marrow cells of DBA/2 and D2.Fv-2r mice. We conclude that the primary effect of the Fv-2r gene may be to inhibit the formation and proliferation of IC in vivo, and that SFFV replication could be inhibited secondarily.

Animals↗
PubMed1980

Studies of cloned Friend erythroleukemia tumor cells. Modulation of the tumor-specific cytologic T lymphocyte response by infectious Friend virus production in vitro.

The HFL/b tumor cell line, induced by Friend erythroleukemia virus in BALB.B mice, was used to study the relation between virus production or nonproduction and the antigens recognized by Friend virus-specific cytolytic T lymphocytes (CTL). Analysis of clones and subclones of these tumor cells revealed a high degree of heterogeneity with respect to the production and release into culture fluids of infectious Friend virus in vitro, ranging from high levels to low or undetectable levels of virus production. Although no major differences could be detected among the antibody-defined serotypes of the various clones, the susceptibility of cells of individual HFL/b clones to attack by Friend virus-specific CTL varied widely, and those clones which produced large amounts of infectious virus provided the most sensitive target cells. It was also apparent that production of infectious Friend virus was inhibitory to CTL generation in syngeneic mixed leukocyte-tumor cell cultures. Friend erythroleukemia virus-producing cells thus appeared to interact in a complex manner with the host CTL response by modulating their production of infectious Friend virus.

Animals↗
PubMed1980

Maternally transmitted resistance to lymphoma development in mice of reciprocal crosses of the RF/J and AKR/J strains.

Females but not males of the low-lymphoma RF/J strain transmit a non-Mendelian factor which suppresses the development of lymphoma in F1 crosses with mice of the high-lymphoma AKR/J strain. Suppression of lymphoma was also evident in the first backcross generation to the parental AKR strain, but only when (RF female x AKR male)F1 mice had been the female parent. This "maternal resistance factor" was transmitted independently of the dominant, lymphoma-suppressing Fv-1n allele transmitted by both males and females of the RF strain, but the suppressive capacities of the two factors appeared to be additive. In this cross, F1 progeny of RF females also showed marked suppression of ecotropic murine leukemia virus expression by comparison with mice of the reciprocal F1 cross, but this suppression of virus expression was not detected in the lymphoma-suppressed AKR backcross population. The observation of lymphoma suppression in the absence of ectropic virus suppression in mice of the (RF X AKR)F1 female x AKR male backross generation indicates a qualitative or quantitative difference in the determination of these two effects.

Animals↗
PubMed1980

Expression of viral RNA in Friend virus-induced erythroleukemia cells.

The regulation of expression of the Friend virus complex (FV) was studied in clones of H-2 congenic erythroleukemia cell lines. Molecular probes specific for each of the two FV components were generated and hybridized to RNA extracted from clones differing with respect to virus production or viral envelope antigen expression. Sequences representing the defective component of FV continued to be transcribed in cells regardless of virus production. The presence of helper virus-specific sequences, however, was shown to be directly related to virus expression. Molecular hybridization with cytoplasmic and nuclear RNA extracted from the H-2 congenic clones representing various stages of viral expression demonstrated a direct correlation between the level of transcription of FMuLV-specific sequences and the degree of virus expression. These data suggest that regulation of FV expression is primarily related to the cessation of helper virus transcription in the cell lines studied. In this paper we provide further evidence that the defective viral components is responsible for the rapid malignancy associated with Friend disease.

Animals↗
PubMed1980

Genetically dominant resistance in mice to 3-methylcholanthrene-induced lymphoma.

Mice of the RF/J strain are highly susceptible to induction of thymic lymphoma by skin painting with 3-methylcholanthrene (MCA), whereas mice of the 129/J and I/LnJ strains are resistant. Resistance was the dominant trait in F1 mice of crosses of RF with each resistant strain. Analysis of the lymphoma incidence in MCA-painted backcross populations indicated segregation of a single dominant gene for resistance in both crosses. None of these strains show inducibility of the aryl hydrocarbon hydroxylase enzyme system, a phenotype attributed to the dominant Ahb gene which is also known to influence susceptibility to MCA-induced lymphoma. The occurrence of the disease in these backcrosses was independent of the hosts' phenotype at either the H-2 or Fv-1 locus, both of which have shown an influence on susceptibility to murine leukemia virus-associated lymphoma in other experimental systems.

Animals↗
PubMed1979

Viral specificity of H-2-restricted T killer cells directed against syngeneic tumors induced by Gross, Friend, or Rauscher leukemia virus.

Cytolytic T lymphocytes (CTL) were generated against murine tumors induced by Gross, Friend, or Rauscher leukemia virus (LV) in syngeneic mixed leukocyte-tumor cell cultures. Analogous to the patterns of specificity observed with antibodies to LV-induced cell surface antigens, CTL could be classified into two major groups of specificity. Tumor cells induced by Friend, Moloney, or Rauscher virus and positive for the FMR antigen were killed by syngeneic CTL immune to any one of these three LV; the same CTL, however, were incapable of killing syngeneic tumor cells induced by Gross LV. The converse was true for Gross LV-specific CTL: these CTL were specific for syngeneic tumor cells expressing the Gross virus-associated cell-surface antigen (GCSA), and not the FMR antigen. The H-2 specificities of the two groups of LV-immune CTL were also compared, because in both cases, CTL were restricted in their killing activity to H-2-identical tumor target cells. When CTL from single strains of mice were generated against syngeneic FMR- or GCSA-positive tumor cells, differences were observed with respect both to the requirement for the expression of compatible H-2K or H-2D specificities, and to the intensity of the CTL response in congenic mice of the H-2b, H-2d, and H-2k haplotypes.

AKR murine leukemia virus↗
PubMed1979

Tumors induced by murine sarcoma virus contain precursor cells capable of generating tumor-specific cytolytic T lymphocytes.

Leukocyte fractions extracted from the tumor mass and the lymphoid organs of C57BL/6 (B6) mice carrying murine sarcoma virus-induced tumors contained primed cytolytic T-lymphocyte (CTL) precursor cells, in addition to active cytotoxic T cells. These leukocyte fractions gave a secondary response when stimulated in vitro with syngeneic tumor cells, generating large numbers of specific CTL. The activity of these CTL (H-2b) was apparently H-2-restricted, because it was ineffective on tumor targets bearing strongly cross-reacting tumor-specific antigens but with the H-2d haplotype. Furthermore, only H-2b cells bearing the Friend, Moloney, Rauscher-associated antigen, such as Rauscher leukemia virus-induced RBL-5 cells and Friend leukemia virus-induced HFL/b cells, were lysed efficiently. B male GV cells (H-2b cells induced by Gross leukemia virus) were not affected by the same CTL. We propose the existence of a dynamic state involving the migration of primed CTL precursor cells between the lymphoid organs and the tumor mass, as well as the differentiation of these precursor cells within the tumor mass into highly specific CTL.

Animals↗
PubMed1978

Nonrandom inclusion of H-2K and H-2D antigens in Friend virus particles from mice of various strains.

Friend murine leukemia virus (FV), isolated from infectious serum of several mouse strains, has been examined for the presence of H-2 antigens. Following banding of the virus on a discontinuous sucrose gradient, pelleting, and disruption with Nonidet P-40 detergent, virus preparations were tested for their capacity to inhibit the lysis of target cells mediated by various anti-H-2K or anti-H-2D antisera. Virus from mice homozygous for the H-2b, H-2d, H-2g H-2k, and H-2ol haplotypes or heterozygous for the H-2g/H-2k, H-2b/H-2d, and H-2b/H-2k haplotypes was used. Of the six H-2D or H-2K alleles examined, the products of only two, H-2Db and H-2Kk were detected. Virus preparations contained no, one, or both antigens, depending on the genotype of the host animal. Control preparations from normal mouse serum and preparations in which the virus had not been disrupted demonstrated no H-2 activity. Furthermore, attempts to neutralize FV spleen focus forming activity with anti-H-2Db or anti-H-2Kk antisera yielded negative results.

Animals↗
PubMed1978

The genetic basis of susceptibility to leukemia induction in mice by 3-methylcholanthrene applied percutaneously.

Susceptibility to leukemia induction in mice by skin painting with 3-methylcholanthrene (MCA) is strain-specific, occurring only in strains relatively resistant to MCA-induced skin tumors. The Ah locus, which has a dominant allele (Ahb) for inducibility of the aryl hydrocarbon hydroxylase (AHH) enzyme system and a recessive allele (Ahd) for noninducibility, appears to be the major determinant of this trait. MCA-painted mice of strains and crosses carrying the Ahb allele usually show a high incidence of skin tumors (papillomas which may evolve into malignant tumors) and little or no leukemia, whereas in mice homozygous for the Ahd allele the treatment usually induces a high incidence of leukemia and few or no skin tumors. Among mice of a segregating backcross generation including both Ahb/Ahd heterozygotes and Ahd homozygotes, the occurrence of skin tumors was correlated directly with AHH inducibility and inversely with the leukemic response. Mice of Ahb strains with a high level of endogenous murine leukemia (MuLV) expression (C58, PL) show a much weaker skin tumor response than expected but no increase in leukemia incidence, and this observation tends to confirm the previous finding that MuLV infection of mice of low-MuLV strains results in reduced susceptibility to MCA tumorigenesis.

Animals↗
PubMed1978

Fv-1 regulation of lymphoma development and of thymic ecotropic and xenotropic MuLV expression in mice of the AKR/J x RF/J cross.

The incidence of spontaneous thymic lymphoma has been studied in crosses between AKR/J and RF/J mice. AKR mice develop a high incidence of this disease. RF mice transmit a marked resistance to development of the disease to F1 hybrid mice of the AKR x RF cross. This resistance is associated with a reduction of endogenous ecotropic and xenotropic MuLV expression in the prelymphomatous thymus. The RF gene governing the coordinate suppression of these three phenotypes has been mapped to the Fv-1 locus. These results indicate that the particular Fv-1 allele of AKR mice provides a permissive genetic background for endogenous ecotropic and xenotropic MuLV expression and that these viral activities may be etiologically involved in the development of spontaneous thymic lymphoma in the mouse.

Aging↗