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Biomedical subjects

E F Hays

Publications and source records attributed to E F Hays.

At least 37 records · Page 2Linked to original sources
PubMed1984

Differences in lymphomagenic properties of AKR mouse retroviruses.

Long-term studies on lymphomagenicity of several AKR mouse retroviruses have shown that the biologically cloned ecotropic SL3-3c virus is the most lymphomagenic of all viruses tested. This fact was demonstrated by lymphomagenicity in five mouse strains SJL, C3Hf/Bi, C3H/HeJ, CBA/H, and NFS, and lymphoma acceleration in AKR mice. The incidence was higher and latent periods shorter than that found with the other retroviruses tested (SL3-1c, SL3-2c, MCFc, and GMuLVc). In addition, it was the only retrovirus found to be highly oncogenic in the C3H/HeJ and CBA/H strains. Lack of lymphomagenicity of MCFc in CBA/H strain was shown to be due to a block in viral replication. Addition of nononcogenic Akv ecotropic virus did not affect this lack of oncogenicity. The lymphomas developing in CBA/H and SJL mice after neonatal inoculation of SL3-3c virus only produced lymphomagenic ecotropic virus. Thus, SL3-3c lymphomagenesis is most likely due solely to the action of that virus. These studies indicate that pure ecotropic AKR viruses can be highly leukemogenic.

Animals↗
PubMed1984

Immunologic effects of human thymic stromal grafts and cell lines.

These experiments report a method of preparing stromal remnants from human thymus. The remnants were composed of epithelial cells, fibroblasts, and macrophages. They were grafted under the renal capsule of nude mice. Some of the grafts were reconstituted with lymphocytes to obtain the microscopic morphology of the thymus. The mice with reconstituted grafts survived in a conventional environment, had increased numbers of T cells in their spleen, and showed improvement of T-cell mediated immunologic function. This was measured by a positive allogeneic effect, a mixed lymphocyte reaction, and cell-mediated lysis. In vitro cell lines were established from thymic remnants of two separate individuals. These lines grew as attached monolayers. One of them was composed of fibroblasts. The other had an epithelial morphology. This epithelial cell line (HT-7) was shown to produce factors which promoted thymocyte differentiation in vitro.

Animals↗
PubMed1984

Thymic stroma in AKR mice: its function and virus production.

This study reports experiments with thymic stromal remnants in AKR mice, a strain with a high natural incidence of thymic lymphoma. A method has been developed in which thymic stromal cells which survive a 4-week culture period, 1 week at 24 degrees C and 3 weeks at 37 degrees C are suitable for grafting. Most thymic lymphocytes die under these conditions. Stromal remnants were studied by culturing and grafting under the kidney capsule of 2-month-old syngeneic mice. Their in vitro morphology and virus production, their ability to reconstitute a new thymus from host progenitors and their eventual lymphoma development was evaluated. The stromal remnants were from: 1- and 3-month-old normal mice; 6-10-month-old normal mice; 21-28-day-old animals treated with the lymphomagenic virus, SL3-3, at 3 days of age. Our data show that thymic stromal function as measured by lymphoid reconstitution of thymic stromal grafts of AKR mice is not impaired with age or by the presence of oncogenic virus. Oncogenic viruses are found in the thymic stroma of old mice and in thymic stroma of young virus-treated mice. Oncogenic viruses are not found in thymic stroma of young normal mice. Lymphoma can develop in the grafted stromal remnants expressing lymphomagenic virus.

Animals↗
PubMed1984

Leukemia-derived growth factor (non-interleukin-2) produced by murine lymphoma T-cell lines.

Autocrine growth factor activity was found in supernatants of AKR T-cell lymphoma lines cultured in serum-free medium. This factor was designated leukemia-derived growth factor (LDGF). Active supernatants stimulated the growth of the AKR murine T-cell lymphoma line SL 12, its cloned derivatives, and all other murine T-cell lymphoma lines tested. Growth factor activity in conditioned medium was found to be different from interleukin 2 (IL-2) and several other known growth factors. LDGF was able to stimulate growth of the human leukemia T-cells MOLT4f, and the LDGF from MOLT4f cells stimulated the mouse cells. Because mouse T-cell lymphoma lines produced and respond to this factor, it may support the continued proliferation of these cells and could be responsible for their malignant in vivo properties.

Animals↗
PubMed1984

Several classes of retroviruses are produced by an AKR mouse T lymphoma cell line.

Characterization of the viruses produced by the spontaneous T lymphoma cell line SL3 is presented. Using supernatant fluids or direct co-cultivation of cells, the SL3 cell line was found to produce replication-defective viruses in excess of replication-competent viruses. The replication-competent viruses released were predominantly those negative in the XC plaque assay (XC-); XC+ viruses represented a minor population. However, when the SL3-derived viruses were passed in mouse embryo fibroblasts, XC- viruses were rarely recovered, and XC+ viruses were readily isolated. These viruses were all ecotropic and lymphomagenic. Viruses with dual host range and non-oncogenic ecotropic viruses were not isolated from the lymphoma cells. Two replication-defective viruses from SL3 cells were studied. Both could be rescued by non-oncogenic retroviruses and were then lymphomagenic. One defective virus appeared related to XC+ viruses. In these studies, the XC+ and XC- viruses appeared to represent two different interference classes using separate cell receptors. Taken together, these experiments show that the SL3 T lymphoma cells replicate a variety of viruses most of which are lymphomagenic. Virus replication and/or virus integration may be the means of maintaining the malignant phenotype of these T lymphoma cells.

Animals↗
PubMed1984

Presence of prelymphoma cells in the bone marrow of the lymphomagenic virus-treated AKR mouse.

Prelymphoma cells (PLC) are defined as cells which give rise to lymphoma cells but are not in themselves autonomous. They are present in the bone marrow of young AKR mice, a strain with a high natural incidence of thymic lymphoma. PLC are identified by transfer of AKR bone marrow into 400-rad-treated F1 recipients, one of the parents being AKR. Normal 1-month-old AKR bone marrow cells result in thymic lymphomas of AKR type in the hybrid recipients after latent periods of 6 to 16 months. In the present study, PLC resulting in lymphoma of AKR type 3 to 4 months after inoculation to irradiated hybrids are described. They are consistently found in the bone marrow of 21- to 28-day-old AKR mice treated at 3 to 5 days of age with a lymphomagenic virus, SL3-3. Long-term culture of these bone marrow cells allows the survival of totipotent hemopoietic stem cells but not of PLC. Thymic stromal remnants prepared from the 21- to 28-day-old virus-treated mice efficiently replicate oncogenic virus; however, they do not contain PLC. This was determined by grafting the remnants to irradiated and nonirradiated hybrid recipients. No AKR type lymphomas developed in the grafted mice. We conclude that the bone marrow of young oncogenic virus-treated AKR mice contains PLC modified by oncogenic virus so that they can produce thymic lymphomas after a shorter latent period than can PLC found in 1-month-old normal AKR mice. The modified PLC are not derived from totipotent marrow stem cells or sequestered in the thymic stroma of virus-treated mice.

Animals↗
PubMed1984

A new murine model system for the in vitro development of thymoma cell heterogeneity.

We have established and characterized a continuous T-cell line derived from the bone marrow of an AKR mouse with disseminated lymphoma. The original tumor cell line is heterogeneous with respect to several markers of thymocyte differentiation. Clones from the line differ in the expression of ThB, Pgp-1, and H-2Kk surface antigens. These clones also differ in their sensitivity to glucocorticoid-induced cell lysis. The quantity, affinity, and nuclear translocation properties of the glucocorticoid receptor are similar in the hormone-sensitive and -resistant clones. Furthermore, dexamethasone-resistant T-cells can be selected in vitro from freshly cloned cells sensitive to hormone-induced lysis at high frequency and without mutagenesis. Of several randomly sampled, spontaneously arising, independently derived dexamethasone resistant clones, all show a coordinate reduction in cell surface Thy-1 and ThB expression with no detectable changes in glucocorticoid receptor properties. Following treatment with the DNA-demethylating agent 5-azacytidine, the original dexamethasone-resistant T-cell line as well as the dexamethasone-resistant derivatives obtained in vitro regain sensitivity to lysis. These results collectively suggest a role of DNA methylation in hormone resistance and are consistent with a model of thymocyte differentiation in which a glucocorticoid-sensitive cell is the progenitor of hormone-resistant T-cells.

Animals↗
PubMed1983

Induction of T-cell maturation by a cloned line of thymic epithelium (TEPI).

A cloned cell line of thymic origin has been characterized as epithelial in nature. A description of the procedures for derivation and cloning of the cell line includes use of epidermal growth factor. The thymic epithelial (TEPI) cell line is Ia antigen positive, forms desmosomes, and produces an extracellular fibronectin matrix. The supernatant from confluent monolayers of TEPI was tested for its ability to promote thymocyte functional activity. TEPI supernatant (TEPI SN) was demonstrated to greatly enhance the response of peanut agglutinin-positive thymocytes to alloantigen, as measured by cell-mediated lympholysis. Furthermore, preincubation of peanut agglutinin-positive thymocytes with TEPI SN prior to allostimulation resulted in marked enhancement, thus distinguishing it from interleukin 2. Finally, TEPI SN was demonstrated to induce interleukin 2 production by peanut agglutinin-positive thymocytes in the presence of concanavalin A. This activity was demonstrated not to be due to interleukin 1, which is absent in TEPI SN. Preliminary biochemical analysis indicates that the biological activity is associated with a Mr 50,000 entity. The data suggest that TEPI produces a soluble factor capable of inducing function of an immature thymocyte subpopulation into an IL 2 producer.

Animals↗
PubMed1983

Gentamicin reduces the self-renewal capacity of murine pluripotent hemopoietic stem cells.

This study pursues our initial observation of an association between prophylactic treatment of irradiated mice with gentamicin sulfate, and the subsequent low self-renewal capacity exhibited by transplanted marrow CFUS which they host. Either drug treatment of the host before engraftment, or exposure of marrow cells in vitro prior to their inoculation, produced suppressed CFUS self-renewal with respect to paired controls. Characteristics of primary spleen colonies (number, size, histology) were not altered, suggesting a specific deficit in secondary stem cell production or maintenance.

Animals↗
PubMed1983

In vivo antitumor activity of the bitter melon (Momordica charantia).

The in vivo antitumor activity of a crude extract from the bitter melon (Momordica charantia) was determined. The extract inhibited tumor formation in CBA/H mice which had been given i.p. injections of 1.0 X 10(5) CBA/Dl tumor cells (77% of the untreated mice with tumors versus 33% of the treated mice with tumors after 6 weeks). The extract also inhibited tumor formation in DBA/2 mice which had been given i.p. injections of either 1 X 10(5) P388 tumor cells (0% of untreated mice survived after 30 days versus 40% survival of the treated mice) or 1 X 10(5) L1210 tumor cells (0% survival of untreated mice versus 100% of treated mice after 30 days). The in vivo antitumor effect required both the prior exposure of tumor cells to the extract (2 hr) in vitro and i.p., biweekly injections of the extract into the mice. The optimum dose for tumor inhibition (8 micrograms protein, biweekly, i.p.) was not toxic to mice for at least 45 days of treatment. This same treatment caused a marked enhancement of C3H mouse thymic cell response to concanavalin A in vitro. When compared to the untreated control mice, the bitter melon-injected animals exhibited a 4-fold-higher incorporation of tritiated thymidine into trichloroacetic acid-precipitable material after 48 hr of exposure to 50 micrograms of concanavalin A. Nylon wool-purified spleen cells from these same bitter melon-treated mice exhibited an enhanced mixed lymphocyte reaction when exposed to irradiated P388 stimulator cells (186% of the untreated control mice). These data indicate that in vivo enhancement of immune functions may contribute to the antitumor effects of the bitter melon extract.

Animals↗
PubMed1983

Merocyanine 540 alters the self-renewal capacity of murine pluripotent hemopoietic stem cells.

Merocyanine 540 (MC 540), an impermeant photoreactive dye with a high affinity for the plasma membrane of hemopoietic precursors, was examined for effects on the self-replicative capacity (SR) of CFUS from normal mouse marrow, and on various CFUS subpopulations fractionated by velocity sedimentation. Brief exposure (30 s) of whole marrow to MC 540 resulted in a reduction in overall CFUS self-renewal in primary recipient spleens. Reduced self-renewal was also observed when fractionated CFUS subpopulations were used. Reduced self-renewal was not accompanied by obvious changes in primary spleen colony number or composition. MC 540 may interact with specific superficial membrane sites relevant to the SR process. Upon longer exposure, further MC 540 effects appear restricted to a reactive subpopulation of large (low SR) CFUS. Self-renewal was enhanced in this fractionated pool, without evidence of primary colony reduction, by intermediate staining. This strongly suggests that under certain conditions the dye can alter a fundamental functional property of susceptible stem cells, without their inactivation. Still more prolonged staining apparently leads to the selective elimination of this reactive low SR CFUS subset. A marked reduction in whole marrow-derived spleen colonies was accompanied by an enhanced self-renewal capacity among the survivors. These two MC 540 effects--stem cell modification, and stem cell elimination--may reflect different stages in an ongoing membrane photo-oxidation process.

Animals↗
PubMed1982

Lipolysis induction in adipocytes by a protein from tumor cells.

Extracts of thymic lymphoma that are obtained from AKR mice and are kept in the cold for at least several days can induce lipolytic activity in rat adipocyte suspensions. Freshly prepared extracts have low activity but contain a low molecular weight material of less than 10,000 daltons that aggregates on standing in the cold and becomes active. Treatment of aged extracts with trypsin causes a loss in activity indicating that the active material is a protein. It has been obtained in partially purified form, is relatively heat stable, and is not a lipase. Activity was also demonstrated in AKRXDBA/2 lymphoma (induced by AKR SL3-3 virus) and in transplanted lymphomas from a Friend-virus-induced erythroleukemia cell line in DBA/2 mice, but was not detected in normal thymus, spleen, liver, or other tissues. The partially purified material produced a massive fat mobilization when injected into normal mice.

Adipose Tissue↗
PubMed1982

Growth of normal hemopoietic cells in cultures of bone marrow from leukemic mice.

Bone marrow from mice with spontaneous leukemia was studied in long-term culture in the presence of 10(-7) M hydrocortisone. These conditions resulted in a complete loss of leukemia cells from marrows which initially showed 95% or greater replacement with lymphoblasts. The culture conditions were also found to favor the growth of hemopoietic stem cells and the surviving cultured cells produced sufficient numbers of these cells to protect lethally irradiated (950 rads) syngeneic mice. The irradiated recipients of the cultured marrow did not develop leukemia during the 180 days of observation post-irradiation, indicating the absence of leukemia cells in the inocula. A loss of leukemia cells in vitro occurred in cultures with and without the addition of hydrocortisone to the medium. Hydrocortisone was shown to have a stimulating effect on maintenance of hemopoietic stem cells, granulocyte progenitors and granulopoiesis in these cultures.

Animals↗
PubMed1982

Expression of the H-2 antigenic complex on murine haematopoietic stem cells.

We used hybridoma-derived monoclonal antibody to H-2Kk antigens and xenoantibodies to beta 2-microglobulin (beta 2 m) to study the expression of the H-2 antigenic molecular complex on murine hematopoietic stem cells and the effect of long-term culture in vitro on the expression of these antigens. Monoclonal anti-H2Kk antibody produced potent complement-dependent inhibition of pluripotent (CFU-S), myeloid (CFU-C), and erythroid (CFU-E) stem cells from the bone marrow of C3H and AKR(H-2k) mice and was without effect on stem cells from Balb/C (H-2d) mice. Anti-beta 2m xenoantibodies inhibited stem cells from all three strains. Stem cells could not be 'rescued' from the inhibitory effects of the antibodies by the addition of thymocytes to marrow cells after antibody treatment. Both the anti-H-2Kk monoclonal antibody and the anti-beta 2m xenoantibodies produced potent inhibition of AKR (H-2k) CFU-C that had been maintained in culture for up to 6 weeks. These results indicate that murine CFU-S, CFU-C, and CFU-E express H-2 antigens and that the expression of these antigens by CFU-C is not altered during long-term culture.

Animals↗
PubMed1982

Structure of retroviral RNAs produced by cell lines derived from spontaneous lymphomas of AKR mice.

The retrovirus expression of eight independent lymphoid cell lines derived from spontaneous thymomas of AKR mice was investigated. The RNase T1 fingerprints of viral 70S RNA produced by these cell lines were compared with genome structures of the non-leukemogenic Akv virus and with two types of cloned leukemogenic viruses derived from one of the thymoma cell lines. Viral RNAs from three cell lines, SL3, 4, and 7, were indistinguishable from one another. The fingerprint patterns indicated that these cell lines produce equal amounts of two prototype, leukomogenic SL viruses that were previously isolated from the SL3 cell line. Viral RNA produced by the SL1 and SL2 cell lines contained similar components, but at a different ratio. Two other cell lines (SL5 and SL11) produced viral RNAs that resemble those of AKR mink cell focus-forming viruses. One additional line, SL9, produced viral RNA of a novel structure. The complex pattern of viral RNA expression observed for these lymphoid cell lines can be interpreted in terms of recombination among three types of endogenous viral sequences: the Akv virus, a xenotropic virus, and an SL (for spontaneous leukemia) virus.

AKR murine leukemia virus↗
PubMed1982

Spontaneous leukemia viruses: lymphomagenic ecotropic viruses of AKR mice.

The spontaneous leukemia (SL) viruses are ecotropic lymphomagenic viruses isolated from AKR spontaneous lymphomas. These viruses are produced stably by continuous cell lines from spontaneous lymphomas and by a cell line derived from the bone marrow stroma of an AKR mouse neonatally inoculated with an SL virus. All cell lines cloned from the parent lymphoma cell lines consistently produce SL viruses. These viruses can be passaged in vivo and maintain their leukemogenic properties. Cloned isolates of SL viruses accelerate lymphoma in AKR mice and induce thymic lymphoma in mice of other strains. Thus their lymphomagenic properties are conclusively shown. In a study with the use of a sensitive host range assay, xenotropic and/or dual-host range viruses are consistently found in spontaneous lymphoma and cell lines derived from them. However, viruses able to replicate in mink lung cells are not expressed in SL virus-induced lymphomas or their derived cell lines.

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