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Biomedical subjects

E F Hays

Publications and source records attributed to E F Hays.

At least 55 records · Page 3Linked to original sources
PubMed1980

A lipid mobilizing factor in serum of tumor-bearing mice.

There is considerable evidence that the growing tumor requires a source of unsaturated fatty acids, but the nature of this source and the mechanism of mobilizing the fatty acids from it are obscure. These experiments make use of AKR mice with implanted adipose tissue labeled with 1-14C linoleic acid. With this experimental animal, it has been found that: (a) in the normal, fed mouse, fat is mobilized slowly and appears largely as respiratory CO2, following oxidation, (b) in the normal, fasted mouse, fat is mobilized rapidly and appears largely as respiratory CO2; (c) in the tumor-bearing, fed mouse, fat is mobilized rapidly and appears largely in the tumor; and (d) the serum from tumor-bearing mice, when injected into normal mice, produces an immediate massive fat mobilization that does not respond to feeding, whereas the serum from normal, fed mice does not. It is concluded that a mobilizing factor of unknown nature is present in the serum of tumor-bearing AKR mice.

Adipose Tissue↗
PubMed1980

Characterization of virus produced by a lymphoma induced by inoculation of AKR MCF-247 virus.

We report the characterization of the virus produced by a lymphoid cell line derived from a lymphoma of an AKR mouse after injection of the polytropic AKR virus MCF-247. The virus displays polytropic host range properties and is indistinguishable from MCF-247 as judged by analysis of the large RNase T1-resistant oligonucleotides of the RNA genome. Restriction enzyme analysis of cellular DNA revealed the presence of sequences homologous to MCF-247 genomic RNA. The EcoRI cleavage fragments were characteristic of MCF-247 DNA provirus cleavage products.

AKR murine leukemia virus↗
PubMed1980

AKR murine leukemia viruses and long-term bone marrow cultures from AKR and SJL mice.

We have evaluated the effects of AKR mouse retroviruses on a system of long-term bone marrow cultures which allows prolonged replication of hemopoietic stem cells (CFUs) and granulocyte-monocyte progenitors with production of mature granulocytes. Ecotropic-nononcogenic virus is expressed in all cultures and does not adversely effect stem cell replication. We found, however, that cultures established from mice treated in vivo with lymphomagenic AKR viruses (Gross murine leukemia virus and AKR SL3 murine leukemia virus) showed a more rapid decline in CFUs and CFUc than cultures from "normal" AKR mice. Only the former cultures were found to produce lymphomagenic viruses. Furthermore, it was shown that addition of lymphomagenic virus to three-week marrow cultures established from AKR and SJL mice also caused a prompt decline in progenitor cell production and granulopoiesis when compared to medium-treated control cultures. The fate of all cultures was a loss of CFUc and granulocytes with a continuous production of macrophages. The change to macrophage production occurred earlier in the cultures treated with lymphomagenic virus or in those derived from lymphomagenic virus-treated animals. A study of these bone marrow-drived macrophage cultures, as well as cultures of similar morphology but of thymic origin, showed that they could be maintained as continuous lines. Cells from three of the cultures from lymphomagenic virus-treated animals plroduced locally growing sarcoma when inoculated into mice. The macrophages from the declined marrow cultures differed in certain properties from those of the established lines.

AKR murine leukemia virus↗
PubMed1979

Factors promoting colony stimulating activity (CSA) production in macrophages and epithelial cells.

The regulation of colony stimulating activity (CSA) release from CSA producing cells is a poorly understood process. Using freshly isolated mouse peritoneal cells and a continuous line of mouse thymic epithelial cells a precise and reproducible method of short term culture was developed to study this phenomenon. Serum, endotoxin, lithium, and cyclic GMP stimulated CSA release from both cell types. Particles such as zymosan, inulin, latex, and iron filings stimulated CSA release from mouse peritoneal cells but not from thymic epthelial cells. Theophylline and cyclic AMP inhibited CSA release from both cell types. Trypsin activated guinea pig C3 and C5 did not stimulate CSA release. Cycloheximide, an inhibitor of protein synthesis, completely inhibited CSA release. We believe these findings may reflect mechanisms of in vivo regulation of CSA release.

Animals↗
PubMed1978

Liver and thymus lipid composition in AKR mice with and without lymphomas.

Lipid composition of liver and thymus in controls, early stage lymphoma, and advanced stage lymphoma-bearing AKR mice was studied. There was a significant decrease in the liver total lipid content in mice with advanced lymphoma, whereas in the early stages, no quantitative change was seen. In livers of mice with advanced stage lymphoma, there was a significant decrease in the nonpolar fraction. The decrease was in triglyceride, whereas the cholesterol fractions were relatively increased though hig,ly variable. There was an increase in the polar lipid/nonpolar lipid ratio in the advanced lymphoma livers and a very large increase in the polar lipid/triglyceride ratio, indicating that the decrease in total lipid in these livers was largely in the triglyceride fraction. Similar changes were seen in the thymus, in which the lipid composition reflected the transformation from normal to malignant cells.

Animals↗
PubMed1978

Oncogenicity of AKR endogenous leukemia viruses.

Four biologically distinct groups of endogenous murine leukemia virus (MuLV) have been isolated from AKR mice. These viruses included (i) ecotopic XC+ MuLV that occur in high titer in normal tissues and serum of AKR mice throughout their life span, (ii) ecotropic XC- MuLV that are produced in high titers by leukemia cells, (iii) xenotropic MuLV that are readily demonstrable only in aged mice, and (iv) polytropic MuLV thatarise in the thymuses of aged mice as a consequence of genetic recombination between ecotropic and xenotropic MuLV. Virus of each of these biological classes were assayed in AKR mice for their ability to accelerate the occurrence of spontaneous leukemia. Certain isolates of ecotropic XC- MuLV and polytropic MuLV were found to have high oncogenic activity. These viruses induced 100% leukemias within 90 days of inoculation. In contrast, ecotropic XC+ MuLV that were obtained from AKR embryo fibroblasts and xenotropic MuLV that were obtained from the lymphoid tissues of aged AKR mice did not demonstrate oncogenic activity. These findings demonstrate fundamental differences between XC- and XC+ ecotropic MuLV that are found in leukemic and normal tissues, respectively. Furthermore, these findings point to the role of ecotropic XC- and polytropic MuLV in the spontaneous leukemogenesis of AKR mice.

AKR murine leukemia virus↗
PubMed1978

Colony-stimulating activity.

Hemopoietic cells, when placed in single-cell suspension in a semisolid growth medium for seven to 14 days, have been found to form visible colonies of granulocytes and monocytes. Colony growth appears only in cultures to which a source of colony-stimulating activity (CSA) is added. Because of these in vitro effects, CSA is thought to be an in vivo regulator of granulocyte and monocyte production from progenitor cells in the bone marrow.

Animals↗
PubMed1977

Effect of hypertransfusion on granulopoiesis in bone marrow depression: studies in the irradiated mouse.

The response of granulopoietic activity in bone marrow depression to a reduction in the demand for erythropoiesis has been examined by means of hypertransfusing C-57B mice which had been exposed to sublethal whole body irradiation. Multiple intraperitoneal injections of 0.5 ml packed red cells from irradiated donors were employed to maintain the haematocrit sufficiently above the normal range to produce significant suppression of erythropoietic activity for the duration of the bone marrow depression. This was associated with elevation above control values of 32--102% in the blood granulocyte count, 22--78% in total cells of the granulocytic series per femur, and up to 44% in total agar colony forming units per femur. Restoration of essentially normal values occurred 13 d after irradiation in contrast to 17--18 d in controls. Single transfusions which produced less suppression of erythroblast numbers per femur resulted in an intermediate degree of improvement in these parameters. Such changes in the granulocyte compartment indicate improved granulopoietic capacity in the hypertransfused group. It is suggested that this effect reflects increased production of granulocyte progenitors due to the reduction in competing demands on the compromised multipotential stem cell compartment for progenitors of the erythroid series. The findings raise the possibility that hypertransfusion might be capable of producing a beneficial effect on granulopoiesis in human bone marrow depression.

Agranulocytosis↗
PubMed1977

A discrepancy in XC and oncogenicity assays for murine leukemia virus in AKR mice.

Studies of murine leukemia virus expression in AKR mice are presented. Material from in vivo and in vitro sources of normal tissues and lymphomas was assayed for in vitro infectivity, using the XC plaque assay, and for oncogenicity, by assessing lymphoma-accelerating capacity after inoculation into newborn animals. Normal tissues from healthy young AKR mice up to 7 months of age were found to have XC but not oncogenic activity. XC activity persisted, and weak oncogenic activity appeared in older mice. Cocultivation of normal young cells with NIH Swiss mouse embryo cells did not result in the appearance of oncogenic activity, although XC virus increased in titer. A cell-free filtrate of a virus-accelerated lymphoma was studied for host range. Virus as measured by polymerase and gs antigen was found to be propagated on NIH Swiss mouse embryo and wild mouse embryo cells, but not on human rhabdomyosarcoma, normal rat kidney, rabbit corneal, and BALB/c embryo cells. Virus as measured by the XC assay grew better on NIH Swiss mouse than on BALB/c embryo cells. Both of these cell lines propagated virus as measured by the oncogenicity assay. Supernatants from an in vitro cell line from a virus-accelerated lymphoma did not produce XC plaques but were oncogenic. Those from two cell lines of spontaneous lymphomas were negative with both assays. Cultivation of supernatants from these cultured lymphoma cells with NIH Swiss mouse embryo cells resulted in material which produced small plaques on the XC assay. These findings are interpreted as showing the presence of two viruses in AKR mice. One is XC positive and present throughout life. The other is oncogenic, appears later in life, and could be a separate virus or a variant of the first one.

AKR murine leukemia virus↗
PubMed1976

Therapy of transplanted lymphomas.

Allogeneic cells or cell products containing murine leukemia virus were effective in curtailing growth of a transplanted CBA lymphoma, which was originally induced by Gross virus and then maintained by syngeneic cell passage. All allogeneic cells or products effective in therapy of this lymphoma expressed virus as tested by the XC cell in vitro infectivity assay. Some of the materials also expressed virus as assayed by oncogenicity in vivo. A therapeutic effect was not demonstrated with allogeneic cells or cell products laking these virus activities. Syngeneic lymphoma cells were ineffective. Protected animals did not develop lymphoma when rechallenged several months later. Mechanisms for this therapy with virus were proposed.

AKR murine leukemia virus↗
PubMed1976

In vitro colony-forming cells in the marrow of leukemic and preleukemic mice.

In vitro colony-forming cells (CFUc) were evaluated in preleukemic and leukemic AK mice. Increased concentrations of CFUc were found in normal appearing marrow of superinfected animals 2-3 wk prior to the onset of lymphoma. CFUc were present in marrows of mice with virus-accelerated, spontaneous, and transplanted lymphoma. CFUc concentration was often increased in mice with advanced disease and marrow replacement by lymphoblasts. When calculated on the basis of CFUc per normal marrow cells, this increase was marked. The colonies developed only in the presence of added colony-stimulating activity (CSA) and had the morphologic features of colonies from normal marrow. Leukemic cells did not form colonies. Lymphoma cells, from virus accelerated, spontaneous and transplanted lymphoma, did not produce CSA in feeder layers or conditioned medium. Leukemic and nonleukemic AK bone were found to produce similar small amounts of CSA. These studies showed that the preleukemic state as well as marrow replacement by lymphoblasts resulted in increased marrow CFUc's. No evidence for increased local production of CSA by lymphoblasts or the marrow microenvironment was found to account for this.

Animals↗