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Biomedical subjects

T N Fredrickson

Publications and source records attributed to T N Fredrickson.

At least 55 records · Page 3Linked to original sources
PubMed1988

Evolution of B cell lineage lymphomas in mice with a retrovirus-induced immunodeficiency syndrome, MAIDS.

Mice infected with LP-BM5 murine leukemia virus develop lymphadenopathy, splenomegaly, hypergammaglobulinemia, and profound immunosuppression associated with enhanced susceptibility to infection. In this study, molecular genetic analyses of spleen and lymph node cells from infected mice showed the early course of disease was associated with polyclonal proliferations of both B and T cells but that by 12 wk oligoclonal expansions of B or T cells could be detected. When near death, the mice were killed and almost all exhibited clonally restricted populations of B cells, and continuous cultures of B lineage cells were established from three of 19 mice. Histologically, lymph nodes with polyclonal lymphoproliferative lesions were indistinguishable from nodes with clonally restricted populations of cells. However, aggressive immunoblastic lymphomas of characteristic morphology were seen in nonlymphoid organs, particularly in the brain. The demonstration of terminal B cell lymphomas in murine AIDS extends the similarities between this syndrome and AIDS in humans.

Animals↗
PubMed1988

Histogenesis and clonality of pancreatic tumors induced by v-myc and v-raf oncogenes in NFS/N mice.

Newborn NFS/N mice were inoculated with pseudotypes of murine retroviruses containing murine v-raf, avian v-myc, or both v-raf and v-myc within a single construct. Foci of dysplastic acinar cells, similar to those observed in rats given chemical carcinogens, were induced in 77% of mice inoculated with the raf/myc construct with a latency as short as 15 days. However, all animals given this construct also developed fibrosarcomas, erythroblastosis, and lymphomas and died within 70 days of infection, before pancreatic acinar carcinomas developed. Dysplastic foci were also observed in mice infected with viruses containing v-raf or v-myc alone with latencies of 3-4 weeks, and carcinomas were seen after an average latency of 150 days in 31% of mice infected with either of two viruses expressing v-myc alone. Two primary carcinomas were transplanted in mice, and in vitro cell lines were developed from one of the transplants. DNA prepared from seven primary carcinomas, the two transplanted tumors, and the in vitro cell lines was hybridized with a v-myc probe. Each tumor had a unique pattern of proviral integrations that was retained, with the gain or loss of single sites, in the transplants and derivative cell lines. The clonal nature of the advanced pancreatic acinar carcinomas is discussed in relation to their histogenesis and the transforming potentials of the raf and myc oncogenes.

Animals↗
PubMed1987

Phenylhydrazine stimulates lymphopoiesis and accelerates Abelson murine leukemia virus-induced pre-B cell lymphomas.

Infection of bone marrow or fetal liver cells with Abelson murine leukemia virus (A-MuLV) results in the transformation of pre-B cells and the development of erythroid colonies, indicating that the abl oncogene can affect the growth characteristics of immature cells in both the B cell and erythroid lineages. By comparison, infection of mice with A-MuLV results primarily in the development of pre-B cell lymphomas. To determine whether A-MuLV could induce erythroid disease in vivo, NFS/N mice were pretreated with phenylhydrazine (PHZ) to stimulate erythropoiesis and increase the frequency of potential target cells for A-MuLV. No erythroleukemias developed in mice treated with PHZ. Instead, the latency for pre-B cell lymphomas was reduced by half. This acceleration of disease could be attributed to a marked increase in pre-B cells as targets for transformation by A-MuLV in the bone marrows but not the spleens of treated mice. Increases in the frequencies of T cells in bone marrow and spleen also followed treatment with PHZ. These results show that although PHZ-induced anemia stimulates the production of T and B cells as well as erythroid progenitors, PHZ-treated mice do not develop erythroleukemia or T cell lymphomas. It was also found that the genetically determined resistance of adult C57BL/6 mice to lymphoma induction by A-MuLV could not be overcome by pretreatment with PHZ even though the frequency of pre-B cells in bone marrow was greatly increased by this treatment.

Abelson murine leukemia virus↗
PubMed1987

Abrogation of resistance to severe mousepox in C57BL/6 mice infected with LP-BM5 murine leukemia viruses.

Strain C57BL/6 (B6) mice infected with LP-BM5 murine leukemia virus (MuLV) develop a disease which combines abnormal lymphoproliferation with profound immunosuppression and has many features in common with human acquired immunodeficiency syndrome induced by HTLV-III/LAV retroviruses. To determine whether this LP-BM5 MuLV infection would affect the innate resistance of B6 mice to a naturally occurring, highly virulent murine pathogen, mice were exposed to ectromelia virus at various times after treatment with LP-BM5 viruses. At week 4 after infection with LP-BM5, mice challenged with ectromelia virus were unable to generate a humoral immune response to this virus, and between weeks 8 and 10 after infection, challenged mice lost the ability to generate an ectromelia virus-specific cytotoxic-T-cell response. Loss of the cellular immune responses to ectromelia virus was associated with an increased susceptibility to the lethal effects of the virus.

Animals↗
PubMed1987

Biologic and molecular characterization of two newly isolated ras-containing murine leukemia viruses.

A murine sarcoma virus (MSV) was recovered from an (NFS X NS.C58v-1) F1 mouse which developed splenic sarcoma and erythroleukemia 6 months after inoculation with a mink cell focus-inducing murine leukemia virus (MuLV) isolated from an NFS mouse infected with a wild mouse ecotropic MuLV. The MSV, designated NS.C58 MSV-1, induced foci of transformation in mouse and rat fibroblasts, and inoculation of mice of various strains 2 weeks of age or younger resulted in erythroleukemia and sarcomatous lesions in spleen, lymph node, and brain. The MSV provirus was molecularly cloned from a genomic library prepared from transformed non-producer rat cells. The 8.8-kilobase proviral DNA contained a 1.0-kilobase p21 ras coding segment which replaced most of the gp70-encoding portion of an MuLV, most likely the endogenous C58v-1 ecotropic virus. The ras oncogene is closely related to v-Ha-ras by hybridization, expression of p21 protein, and nucleotide sequence. It is nearly identical in sequence to v-bas, the only previously described transduced, activated mouse c-ras. At position 12 in the p21 coding region, arginine is substituted for the naturally occurring glycine present in c-ras. A second MSV isolate is described which is similar to NS.C58 MSV-1 except for a 100- to 200-base-pair deletion in the noncoding region of the ras-containing insert.

Animals↗
PubMed1987

Ovarian tumors of the hen.

Present available information regarding ovarian tumors in hens is incomplete in most aspects, and this lack of knowledge hampers use of hens as models for study of ovarian cancer. A study of 466 hens ranging from 2 to 7 years of age and covering a period of more than 3 years has provided much needed information relative to reproductive tract neoplasia. On the basis of this study, it is apparent that hens have a high rate of ovarian tumors, but that such tumors are uncommon in hens less than 2 years of age. Adenocarcinomas with a high degree of morphologic variability are the most common ovarian tumors in hens. Hormonal imbalance does not appear to be a factor in the development of these adenocarcinomas. Steroidogenic and morphologically distinctive granulosa cell tumors originating from follicles in atrophic ovaries represent another common ovarian tumor type. Unique to the hen are oviductal adenocarcinomas. These tumors arise from the albumin-secreting glands of the oviduct, occur with relatively high frequency, and must be differentiated from ovarian adenocarcinomas.

Adenocarcinoma↗
PubMed1986

Analysis of neoplasms induced by Cas-Br-M MuLV tumor extracts.

Cas-Br-M is an ecotropic murine leukemia virus isolated from wild mice that induces a wide spectrum of hematopoietic neoplasms, including T and B cell lymphomas, myelogenous leukemias, and erythroleukemias. The purpose of this study was to determine if the induction of neoplasms belonging to multiple lineages was due to the ecotropic virus itself or to the generation of cell lineage-specific recombinant viruses. The results demonstrate that in some instances (two of 12 tumor extracts tested), recombinant viruses can be recovered from primary Cas-Br-M-induced tumors that will induce lymphomas of single lineages in mice inoculated as newborns. One of these viruses is a recombinant mink cell focus-forming virus that induces T cell lymphomas, and the other is a replication-defective, fibroblast-transforming virus that induces early B lineage lymphomas in mice. Histologic and flow microfluorometric cell surface antigen analyses of primary and in vitro adapted tumors are presented in support of a modified scheme of hematopoietic cell development.

Animals↗
PubMed1986

Interaction between Raf and Myc oncogenes in transformation in vivo and in vitro.

3611 MSV, a raf-oncogene-transducing murine retrovirus, induces fibrosarcomas and erythroid hyperplasia in newborn mice after a latency of 4-8 wk. In contrast, new recombinant murine retroviruses carrying the myc oncogene (J-3, J-5 construct viruses) do not induce tumors before greater than 9 wk. A combination of both oncogenes in an infectious murine retrovirus (J-2) induces hematopoietic neoplasms in addition to less prominent fibrosarcomas and pancreatic adenocarcinoma 1-3 wk after inoculation. The hematologic neoplasms consist of immunoblastic lymphomas of T and B cell lineage and erythroblastosis. If animals were inoculated with a variant of the J-3 virus, which induces altered foci in cultures of NIH 3T3 cells, carcinoma developed in the pancreas with a 2-6 mo latency. In parallel to the synergistic action of both oncogenes on hematopoietic cells in vivo, we find that raf-oncogene-induced transformation of bone marrow cells in culture is enhanced by the addition of myc, which by itself does not transform these cells when grown in standard media. We conclude that concomitant expression of raf and myc oncogenes in hematopoietic and epithelial cells alters their respective transforming activities. The contribution of v-myc in this synergism was examined by use of a series of recombinant murine retroviruses capable of expressing the avian v-myc to study the effect of altered myc expression on hematopoietic/lymphoid cells. With either interleukin 3- or interleukin 2-dependent cell lines, introduction of the recombinant viruses abrogated the requirement for IL 3 or IL 2 for growth, and associated with this was the suppression of c-myc expression. The findings suggest that myc is a component in the signal transduction pathway for IL 3 and IL 2 and support an autoregulatory mechanism of c-myc expression. In contrast to v-myc, expression of v-raf in primary lymphoid/hematopoietic cells has an immortalizing function without abrogating the requirement for IL 3 for growth. This suggests that v-raf and v-myc affect different components of growth regulation, as, for example, commitment (v-myc) and cell cycle progression (v-raf).

Animals↗
PubMed1986

Recombinant murine retroviruses containing avian v-myc induce a wide spectrum of neoplasms in newborn mice.

NFS/N mice were infected within 48 hr of birth with pseudotypes of recombinant murine leukemia viruses containing avian v-myc developed T-cell, pre-B-cell, and B-cell lymphomas and epithelial tumors including pancreatic and mammary adenocarcinomas. Primary hematopoietic and epithelial tumors and continuous in vitro cell lines derived from some of these tumors, established in the absence of added growth factors, exhibited clonal integrations of v-myc and expressed v-myc RNA. These results show that deregulated expression of the myc oncogene in mammalian cells can initiate a wide variety of neoplasms.

Adenocarcinoma↗
PubMed1985

Abnormalities induced by the mutant gene, lpr. Patterns of disease and expression of murine leukemia viruses in SJL/J mice homozygous and heterozygous for lpr.

SJL/J mice heterozygous or homozygous for the lpr mutation were compared with SJL/J-+/+ mice for longevity, histopathology, antigenic characteristics of lymphocytes and expression of murine leukemia viruses (MuLV). In comparison to +/+ mice, lpr homozygotes had a markedly shortened life span, died with infiltrative pulmonary disease, but little or no renal disease, and expressed high levels of infectious ecotropic MuLV in lymphoid tissues. SJL-lpr/+ mice had a life span intermediate between SJL-+/+ and -lpr/lpr mice, died with lymphomas that histologically resembled the neoplasms of +/+ mice, and sometimes expressed high levels of ecotropic MuLV. The lymphomas of lpr/+ could be transplanted to +/+ recipients in 78% of cases, and continuous in vitro lines were established from some of them. Similar effects on virus expression or lymphoma development were not observed in other strains homozygous or heterozygous for the lpr mutation. These results indicate that the diseases expressed by mice homozygous for the lpr mutation are highly strain-dependent, and that this gene can have an effect in the heterozygous state in SJL mice.

Animals↗
PubMed1985

Greying with age in mice: relation to expression of murine leukemia viruses.

Some strains of C57BL/10 H-2-congenic mice were found to exhibit greying with age, whereas others did not. Two patterns of greying were observed, diffuse greying beginning at 4 to 6 months of age and patterned greying beginning at 4 to 6 weeks. Strains exhibiting either greying pattern expressed high levels of infectious ecotropic and mink cell focus-inducing murine leukemia viruses (MuLV) in tests of thymus and spleen and in cultures from skin or tail biopsies, whereas nongreying strains expressed little virus until late in life. Electron microscopy demonstrated large accumulations of MuLV in grey, but not in black areas, of skin from a mouse with patterned greying. Infectious MuLV was produced spontaneously by embryos of greying, but not of nongreying, mice and pups of nongreying strains fostered on greying mothers turned grey after 3 months. These results suggest that greying with age results from melanocyte dysfunction that occurs subsequent to pre- or early postnatal infection with MuLV.

Aging↗
PubMed1985

Correlation of cell-surface phenotype with the establishment of interleukin 3-dependent cell lines from wild-mouse murine leukemia virus-induced neoplasms.

The wild mouse ecotropic virus, Cas-Br-M murine leukemia virus, induces myeloid and erythroid leukemias as well as T-cell and B-cell lymphomas in NFS mice. The ability to establish long-term cell lines from these tumors in the presence or absence of the T-cell-derived lymphokine interleukin 3 (IL-3) was examined. IL-3-dependent cell lines were readily obtained from the majority of the myeloid or erythroid leukemias and immunoblastic lymphomas. In the absence of IL-3, only one long-term factor-independent cell line was obtained from a myelogenous leukemia. The majority of the thymic T-cell lymphomas or B-lineage lymphomas could not be cultured in the presence or absence of IL-3. The results suggest that transformation of hematopoietic lineages does not necessarily obviate the requirement for normal growth factors. The acquisition of independence from growth factors may require additional transforming events.

Animals↗
PubMed1985

Rapid induction of hemopoietic neoplasms in newborn mice by a raf(mil)/myc recombinant murine retrovirus.

3611 MSV, a raf oncogene-transducing murine retrovirus, induced fibrosarcomas in newborn mice after a latency of 4 to 8 weeks. In contrast, newly constructed recombinant murine retroviruses carrying the myc oncogene did not induce tumors before greater than or equal to 9 weeks. A combination of both oncogenes in an infectious murine retrovirus induced hematopoietic neoplasms in addition to less prominent fibrosarcomas and pancreatic acinar dysplasia 1 to 3 weeks after inoculation. The hematological neoplasms consisted of immunoblastic lymphomas of T- and B-lineage cells and erythroblastosis. Cell lines from these tumors could be readily established in culture in regular medium, whereas culture of cells from raf oncogene-induced tumors required the addition of interleukin 3. In parallel to the synergistic action of both oncogenes on hematopoietic cells in vivo, we found that raf oncogene-induced transformation of fibroblast cell lines in culture was enhanced by the addition of myc, which by itself did not morphologically transform these permanent cell lines. We conclude that concomitant expression of raf and myc oncogenes in hematopoietic cells and fibroblastic cell lines enhances their respective transforming activities.

Animals↗
PubMed1985

Relationship of oestrogen and progesterone and their oviductal receptors in laying and non-laying 5-year-old hens.

This study focuses on the relationship of ageing to reproductive function in the domestic hen. Reproductive function was assessed by egg-laying records of hens from the same flock of 4, 5 and 6 years of age. Egg laying decreased with advancing age and the percentage of non-laying hens increased. During an ovulatory cycle, plasma levels of oestrogen and progesterone (including the preovulatory surge) were similar in both the 5-year-old and 1-year-old laying hens. In both young and old non-laying hens, the preovulatory surge of progesterone was absent. Levels of oestrogen were similar for all hens, but the oestrogen-dependent oviduct was atrophied in non-laying 5-year-old hens. This reduction in oviductal size was correlated with reduced levels of magnal nuclear oestrogen receptor and cytosol progesterone receptor. These results suggest a refractoriness of the oviduct to oestrogen stimulation in the ageing hen.

Aging↗
PubMed1985

Multiparameter analyses of spontaneous nonthymic lymphomas occurring in NFS/N mice congenic for ecotropic murine leukemia viruses.

Mouse strains congenic for ecotropic retrovirus genes have a much higher frequency of spontaneous lymphomas than the background NFS/N strain. In this study, most of these lymphomas have been identified as B-cell in origin by morphologic features, identification of immunoglobulin class, and cell-surface antigens. The classification suggested by Pattengale and Taylor proved to be applicable to the lymphomas studied. Most were of large follicular center cells and are considered typical of the type formerly designated as "reticulum cell sarcoma, type B." Many lymphomas contained a large proportion of nonneoplastic cells which partially obscured their neoplastic component. The role of ecotropic murine leukemia viruses as etiologic agents for B-cell lymphomas remains equivocal. However, because the only difference between the NFS/N and congenic mice is the expression of viruses in the latter, it appears that these viruses are somehow involved in induction of B-cell lymphomas.

Animals↗
PubMed1985

Erythroid progenitors in Rauscher leukemia virus variant-A-induced erythropoietic dysplasia in mice.

In vitro erythropoiesis by bone marrow and spleen cells was assessed in normal mice and during progression of Rauscher leukemia virus, variant-A (RLV-A) disease in mice. As RLV-A disease progressed from early through terminal stages, there was a marked increase in the numbers of in vitro splenic CFU-E and BFU-E. Conversely, bone marrow CFU-E and BFU-E demonstrated a concomitant decrease in numbers with disease progression. At no time were erythropoietin-independent (endogenous) erythroid colonies generated. The results suggest that compartmental alterations in erythroid precursors occur during progression of RLV-A.

Animals↗