Search PubMed⌕ Search

Biomedical subjects

E Stockert

Publications and source records attributed to E Stockert.

At least 91 records · Page 5Linked to original sources
PubMed1978

Source and hormone-dependence of Gix-gp70 in mouse serum.

The gp70 family of glycoproteins is distinguished by the role of these molecules as constituents of C-type viral envelopes and also as Mendelian cellular constituents expressed independently of virus production. The source of G(IX)-gp70 in the serum of 129 strain mice, which are not overt producers of virus, could not be traced to any organ or tissue that is known to be G(IX)-positive by serological tests. Hematopoietic tissues were excluded as source of serum G(IX)-gp70 by tests with reciprocal radiation chimeras made from 129 and 129-G(IX)(-) donors and recipients. Thymus and spleen were excluded because excision of these organs did not affect levels of G(IX)-gp70 in the serum. The serum of young adult 129 males contains roughly four times as much G(IX)-gp70 as adult 129 females and the levels rise in both sexes with increasing age. Castration of 129 males reduced the level of serum G(IX)-gp70 to that of females, and the level was fully restored by testosterone. Thus the epididymis and seminal fluid, though rich in G(IX)-gp70, do not contribute significant amounts of G(IX)-gp70 to the serum. The level of G(IX)-gp70 in the serum of testosterone-treated females, though more than double that of untreated females, did not reach the level of normal males, under the conditions tested. This may signify that G(IX)-gp70 production by males is subject to imprinting by testosterone in early life. Evidently the main source of serum G(IX)-gp70 is a tissue or organ that is common to males and females, is directly or indirectly responsive to testosterone, and has not so far been identified serologically as G(IX)- positive.

Animals↗
PubMed1978

G(RADA1): a new cell surface antigen of mouse leukemia defined by naturally occurring antibody and its relationship to murine leukemia virus.

A new cell surface antigenic system of the mouse, designated G(RADA1), is described. The antigen is defined by cytotoxic tests with the A strain X-ray-induced leukemia RADA1 and naturally occurring antibody from random-bred Swiss mice and can be distinguished from all other serologically detected cell surface antigens of the mouse. Absorption tests indicate that G(RADA1) is present in the normal lymphatic tissue and leukemias of mouse strains with high spontaneous leukemia-incidence, e.g., AKR, C58, and C3H/Figge. Low leukemia-incidence strains, e.g., C57BL/6, BALB/c, and A lack G(RADA1) in their normal tissues, but a proportion of leukemias and solid tumors arising in these strains are G(RADA1)+. The relation of G(RADA1) to MuLV is shown by G(RADA1) appearance after MuLV infection of permissive cells in vitro; four of five N-tropic MuLV isolates, one of four B-tropic MuLV, and none of four xenotropic MuLV induce G(RADA1). Two MCF MuLV, thought to represent recombinants between N-ecotropic and xenotropic MuLV, also induce G(RADA1). Serological and biochemical characterization indicates that G(RADA1) is a type-specific determinant of the gp70 component of certain MuLV. The presence of natural antibody to RADA1 in various mouse strains and the emergence of G(RADA1)+ leukemias and solid tumors in mice of G(RADA1)- phenotype suggest widespread occurrence of genetic information coding for this antigen.

Animals↗
PubMed1978

Antitumor tests of amygdalin in spontaneous animal tumor systems.

In a series of 6 experiments with CD8F1 mice with spontaneous mammary adenocarcinomas Sugiura noted by macrovisual observation with some histology an overall average of 21% of mice with lung metastases when treated with 1,000--2,000 mg/kg/day of amygdalin compared with 90% of the control mice. The significance attributed to those early observations is seriously challenged by the negative findings of 3 independent investigators, by 2 out of 3 negative cooperative experiments in which Sugiura participated, and particularly by the blind experiment in which he and others under blind readings found no anticancer activity. Treatment of Swiss albino mice showed no destructive effect upon their spontaneous mammary adenocarcinomas. Of the treated mice, 22% were found by macrovisual observation to have lung metastases while 91% were noted among the controls. The results are subject to questions raised in the discussion. Amygdalin at 2,000 mg/kg/day was ineffective both in treating and preventing the development of spontaneous leukemia in AKR mice. At 1,000 mg/kg/day it was not found effective in preventing or significantly delaying the development of spontaneous mammary tumors in CD8F1 mice. In summary, we do not have evidence to support taking amygdalin to clinical trial, although other considerations may require that one be conducted.

Adenocarcinoma↗
PubMed1978

Abelson antigen: a viral tumor antigen that is also a differentiation antigen of BALB/c mice.

We report here the serologic detection of a cell surface antigen common to cells transformed by the Abelson murine leukemia virus (A-MuLV) and to normal hematopoietic cells from certain strains of mice. Serum from C57BL/6 mice hyperimmunized with syngeneic A-MuLV lymphoma cells was cytotoxic for the immunizing cells; this reaction was used as the serologic test system for recognition of A-MuLV antigens. Absorption analysis using 40 tumors and 21 cell lines revealed that two serologic specificities were detected by this test system: (i) FMR antigen(s) related to the Moloney MuLV helper (the virus from which A-MuLV was originally derived), and (ii) an antigen expressed on all cells transformed by A-MuLV. The A-MuLV-specific antigen was also present on uninfected cells from BALB/c bone marrow, spleen, and fetal liver but not from adult liver, thymus, lymph nodes, or peripheral blood. Abelson antigen was not expressed on bone marrow or spleen cells of 12 other mouse strains. In light of the original isolation of A-MuLV from a BALB/c mouse infected with Moloney virus, it is possible that Abelson antigen is a serologic marker for a gene of BALB/c mice, normally encoding a cell surface molecule, that was incorporated into the Moloney virus genome during the generation of A-MuLV.

Animals↗
PubMed1977

Preleukemic expression of TL antigens in x-irradiated C57BL/6 mice.

Anomalous appearance of TL (thymus-leukemia) antigens is a characteristic feature of radiation-induced leukemias of C57bl/6 mice. We now report that thymocytes of irradiated C57BL/6 mice express TL antigens long before the development of overt leukemia. Thus, TL is a marker for preleukemic changes occurring during radiation leukemogenesis. Low levels of murine leukemia virus (MuLV)-related antigens are also detected on preleukemic thymocytes. Comparative tests on individual mice show no direct correlation between TL and MuLV antigen expression.

Animals↗
PubMed1977

Characterization of molecular species carrying gross cell surface antigen.

The Gross cell surface antigen (GCSA), associated with expression of endogenous Gross-type murine leukemia virus (G-MuLV) in tissues of mice, is defined by the cytotoxic reaction of a C57BL/6 antiserum, anti-AKR spontaneous leukemia K36, with cells of the Gross virus-induced C57BL/6 leukemia, Emale symbolG2. Sequential lactoperoxidase-catalyzed radioiodination of Emale symbolG2 cells, Nonidet P-40 lysis, precipitation with anti-K36 serum, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis identified molecules with properties of polyproteins encoded by the gag region of the viral genome. These cell surface species could also be labeled by in vitro culturing of Emale symbolG2 with radioactive glucosamine. The viral specificity of these molecules and their participation in the GCSA typing system were established as follows. (i) Absorption of anti-K36 serum with GCSA(+), but not GCSA(-), leukemias led to a marked decrease in precipitation of these proteins. (ii) The same Emale symbolG2 cell surface proteins were also precipitated by antisera against the MuLV virion proteins p30 and p15. (iii) Anti-K36 was shown to possess antibodies against Gross virus p30 and p15. (iv) "Clearing" the Emale symbolG2 lysate of molecules reactive with anti-p30 or anti-p15 sera removed molecules reactive with anti-K36 serum. (v) Absorption of anti-K36 serum with disrupted G-MuLV virions or with Gross p30 or p15 removed GCSA cytotoxic antibodies; partial absorption was achieved with disrupted Rauscher-MuLV (R-MuLV) or with R-MuLV p30, and no absorption was found with R-MuLV p15. These data show that Emale symbolG2 cells express, on their surfaces, MuLV core polyproteins that apparently can be glycosylated and on which the determinants of GCSA are located.

AKR murine leukemia virus↗
PubMed1976

Spontaneous autoimmunization to GIX cell surface antigen in hybrid mice.

The GIX antigen expressed on the thymocytes of GIX+ mice is a type-specific constituent of glycoprotein gp70, which forms the major envelope component of murine leukemia virus. In the prototype GIX+ mouse strain 129, this glycoprotein is a Mendelian character expressed independently of virus production. In the intact thymocyte plasma membrane, part of this glycoprotein, bearing group-specific (gs) antigen, is inaccessible to antibody. The moiety bearing the type-specific GIX determinant is accessible to GIX antibody, which may be an important factor in determining the consequences of autoimmune responses involving GIX. Previously, all attempts to induce GIX antibody in mice had failed. We now find that the hybrid mouse (B6-GIX+ X 129) spontaneously produces substantial amounts of GIX antibody, presumably of the IgM class appearing as early as 2 mo of age. The specificity of the GIX natural mouse antibody is the same as that recognized by the conventional GIX typing serum produced in rats ("anti-NTD"). As neither parent strain produces appreciable GIX antibody, we surmise that this autoimmune response requires two dominant genes, each parent contributing a high-response allele to the hybrid. These can be envisaged as two immune response loci, controlling different immunocompetent cells which must cooperate to produce GIX antibody. Production of GIX antibody by the hybrids increases progressively with age. This is accompanied by decreased expression of GIX antigen on their thymocytes. We attribute this to antigenic modulation. Antibody to gs antigen of gp70 is also found in autoimmune (B6-GIX+ X 129) hybrids but not in either parent strain. We are investigating evidence of a pathological autoimmune syndrome in these hybrids. The special interest of this syndrome is that it presumably signifies the consequences of autoimmunization to a single C-type virus component, expressed without significant virus production, in a mouse with no evident genetic predisposition to such disease in the absence of that antigen.

Animals↗
PubMed1976

Age-related changes in cell surface antigens of preleukemic AKR thymocytes.

Thymocytes from preleukemic AKR mice aged 5-6 mo have an altered pattern of cell surface antigens. The expression of four MuLV-related antigens on the cell surface (GIX, GCSA, gp70, p30) is markedly increased in comparison to 2-mo-old AKR mice and approximates the heightened levels of these antigens found on thymic leukemia cells. H-2 and Thy-1 alloantigens also show characteristic modifications in relation to age and leukemia development. In contrast to the high Thy-1/low H-2 levels on 2-mo-old AKR thymocytes, thymocytes from 6-mo-old mice and thymic leukemia cells frequently show a low Thy-1/high H-2 surface phenotype. As thymocytes from mouse strains with a low incidence of leukemia do not show these changes, they appear to represent a stage in the conversion of normal cells to leukemia cells.

Aging↗
PubMed1976

Relationship of infectious murine leukemia virus and virus-related antigens in genetic crosses between AKR and the Fv-1 compatible strain C57L.

In a further genetic study of murine leukemia virus (MuLV) and its components we examined the backcross C57L X (C57L X AKR). This population was selected because strains AKR and C57L are both Fv-1n, and the restriction which the Fu-1b allele imposes on the output of virus was thereby obviated. The segregants were scored for three characters: (a) infectious Gross-AKR-type MuLV (V), in the tail; (b) group-specific antigen indicative of p30 internal viral protein, in spleen; and (c) GIX antigen, now thought to be indicative of gp69/71 viral envelope glycoprotein, on thymocytes. Our conclusions are: (a) It is confirmed that the AKR mouse has two unlinked chromosomal genes, Akv-1 and Akv-2, each of which can independently give rise to the life-long high output of MuLV that is characteristic of AKR mice. (b) Of the eight phenotypes that could possibly be derived from segregation of the three pairs of independent alternative traits, seven were observed, but on progeny testing only three were shown to reflect stably heritable genotypes; these were V+p30+GIX+ and V-p30-GIX- (the parental types) and V-p30+GIX+. A third, newly identified AKR gene, designated Akvp, segregating independently of Akv-1 and Akv-2, also determines expression of p30 and GIX but in this case independently of XC-detectable MuLV. (c) The four remaining observed phenotypes, which did not breed true on progeny testing, involved mostly antigen-negative parents yielding antigen-positive progeny; it is likely that these discrepancies represented suppression of phenotype by a maternal resistance factor.

Animals↗
PubMed1976

Changes in expression of murine leukemia virus antigens and production of xenotropic virus in the late preleukemic period in AKR mice.

We recently reported that thymocytes from 6-month-old preleukemic AKR mice express higher levels of murine leukemia virus (MuLV)-related antigens that thymocytes from 2-month-old mice. We have now found that the level of xenotropic MuLV (defined operationally as MuLV able to infect mink cell cultures) is also markedly increased in thymus of 6-month-old AKR mice and that this increase in virus correlates closely with increased MuLV-antigen expression. There is no increase of MuLV antigen or xenotropic virus in spleen or lymph nodes. Production of ecotropic MuLV remains unchanged with age in thymus, lymph nodes, and spleen. Thymic grafts from 6-month-old AKR mice, but not from 2-month-old mice, induce both amplified MuLV-antigen expression and xenotropic virus production in the thymus of young AKR recipients. Experiments with lethally irradiated AKR mice reconstituted with syngeneic bone marrow cells indicate that age-related changes in the thymus rather than in bone marrow precursor cells are responsible for MuLV-antigen amplification.

Aging↗
PubMed1976

Heredity of the GIX thymocyte antigen associated with murine leukemia virus: segregation data simulating genetic linkage.

The GIX antigen is a feature of the gp70 envelope glycoprotein of murine luekemia virus (MuLV). This GIX-gp70 molecule is found on the thymocytes of some (GIX+) strains of mice, where its expression is controlled by two mendelian genes, Gv-1 and Gv-2. Previous recombination data involving the prototype GIX+ strain 129 indicated that the H-2 (chromosome 17) and Gv-1 loci are linked, at a distance of 36 units from one another. New data indicate that the association of H-2 and GIX phenotypes is an example of quasi-linkage, evidently dependent in this instance on heterozygosity at a locus or loci in the vicinity of H-2. Other previous recombination data, involving the GIX+ strain AKR, had indicated that the Gpd-1 (chromosome 4) and Gv-1 loci are linked at a distance of 19 units from one another. New data from other crosses show that this association of Gpd-1 (glucose-6-phosphate dehydrogenase 1) and GIX phenotypes also constitutes quasi-linkage, evidently due to heterozygosity at the Fv-1 locus. An important theoretical consequence of quasi-linkage in general is that it should enhance the heritability of particular constellations of unlinked genes, and so influence population structure. Our new data are discussed from the viewpoint that MuLV genomes are apparently concerned in quasi-linkage, and therefore by the same arguments may influence the genetic structure of populations. This in turn may strengthen the view that integrated MuLV genomes are not simply intruded into a self-sufficient cellular genome, but are themselves elements of the cellular genome with primary functions, perhaps in reproduction or embryogenesis.

Animals↗
PubMed1976

Induction of GIX antigen and gross cell surface antigen after infection by ecotropic and xenotropic murine leukemia viruses in vitro.

A number of ecotropic and xenotropic murine leukemia viruses were examined for their ability to induce the GIX antigen and Gross cell surface antigen (GCSA) in tissue culture fibroblasts. GIX appears to be a constituent of murine leukemia virus gp70; a molecular characterization of GCSA has not yet been reported. Antigen induction was measured by the ability of productively infected cells to absorb cytotoxic activity from the standard GIX- and GCSA-typing antisera. Cells infected by ecotropic viruses displayed four distinct phenotypes GIX:+/GCSA++, GIX-/GCSA++, GIX++/GCSA+, and GIX-/GSCA+; cells infected by xenotropic viruses were either GIX-/GCSA+ or GIX-/GCSA-. GIX induction appeared to be a type-specific property of some but not all Gross-AKR type ecotropic viruses. Differences in the degree of absorption of the GCSA antiserum by ecotropic virus- and xenotropic virus-infected cells indicated that GCSA may comprise multiple antigenic determinants.

AKR murine leukemia virus↗
PubMed1976

Radiation-induced murine leukemia ERLD in cell culture.

The lymphoblastic leukemia ERLD, induced by radiation in a C57BL/6 mouse, was established in culture. Three cell lines, ERLD/Y3, ERLD/T ERLD/Two, have been in culture for nearly three years. Their isolation and growth depended upon the presence of 2-mercaptoethanol, glutamine, and asparagine in the medium. The cell lines, except ERLD/T, possess the TL antigen, a characteristic of ERLD and of other murine leukemia cells in vivo and of normal thymus cells of certain mouse strains, but not of C57BL/6. A distinctive submetacentric marker chromosome is also common to ERLD and the derived cell lines. The successful establishment of ERLD in culture provides a malignant thymocyte-related cell system for studies in nutrition and immunobiology.

Animals↗
PubMed1976

A comparative study of the antitumor effectiveness of E. coli and Erwinia asparaginases.

The relative antineoplastic effectiveness of E. coli and Erwinia asparaginases was tested against lymphoid leukemias EARAD-1 and L5178Y/CA55. E. coli and Erwinia asparaginases had similar clearance rates from plasma in mice, and at a dose of 250 IU/kg body weight both enzymes lowered plasma asparagine to undetectable levels. Nevertheless, the dosage of Erwinia asparaginase needed to cause similar prolongation of median survival time in leukemic mice was at least twice that of E. coli asparaginase. The factors which may be responsible for the more potent therapeutic effectiveness of the E. coli asparaginase are discussed.

Animals↗
PubMed1975

New mutant and congenic mouse stocks expressing the murine leukemia virus-associated thymocyte surface antigen GIX.

For several reasons the G(IX) antigen (1) has a prominent place in current work on murine leukemia virus (MuLV): In the prototype G(IX+) mouse strain 129, the G(IX) trait is mendelian, and is expressed selectively (though not exclusively) on thymocytes. Thus, expression of this cell surface component is under the control of cellular genes and is subject to the controls governing the differentiation of T lymphocytes (2). Although the 129 mouse produces no demonstrable leukemia virus such as that found in the AKR strain, it was soon realized that G(IX) antigen must in some way be related to MuLV, because productive infection with MuLV is frequently associated with appearance of G(IX) antigen on cells that are genotypically G(IX-), most notably on MuLV-infected rat cells, or cells that belong to other differentiation pathways (1). The basis of this connection between G(IX) and MuLV has recently become clear from the demonstration that G(IX) is one of MuLV envelope. Therefore, our working hypothesis is that the presence of G(IX) is one of the antigens present on gp69/71 (3,4), the major glycoprotein component of the MuLV envelope. Therefore, our working hypothesis is that the presence of G(IX) antigen always denotes the presence of gp69/71 (though not all variants of gp69/71 need necessarily carry G(IX)). Study of the circumstances under which G(IX) is expressed on the cell surface is thus potentially a powerful approach to understanding how the expression of C-type viral genomes is controlled. Such studies are greatly facilitated by the availability of mutant and congenic strains of inbred mice which differ from the nonmutant or partner strains only with respect to one or another manifestation of the viral genome. It is for this reason that we record here (Table I) some details of two G(IX) mutant and two G(IX) congenic stocks derived in our colonies at Memorial Sloan-Kettering Cancer Center (MSKCC). In addition, to these four strains, Table I includes data for the three relevant partner strains, and for strain AKR, for comparison. These eight strains all differ from one another with respect to one or more MuLV-related traits.

Animals↗
PubMed1975

Relation of GIX antigen of thymocytes to envelope glycoprotein of murine leukemia virus.

Expression of Gix surface antigen on thymocytes is an inherited mendelian train of certain strains of mice. We report here the following new findings: (a) Gix antigen was found free in the serum of Gix+ mouse strains. (b) Expression vs. nonexpression of Gix antigen was invariably correlated with presence or absence of the group-specific antigen of Murine leukemia virus (MuLV) gp69/71 in the serum of mice of inbred and segregating populations. (c) Gix antigen could be removed from normal Gix+ mouse serum by precipitation with antiserum to MuLV gp 69/71. (d) Anti-gp69/71 serum was weakly cytotoxic for Gix+ thymocytes, and partially blocked the cytotoxic activity of Gix antibody for Gix+ thymocytes. (e) Purified AKR virus absorbed Gix activity, and disruption of the virions did not increase their absorbing capacity. These serological data indicate that Gix antigen is a constituent of gp69/71, the glycoprotein which is the major component of the MuLV envelope. On present evidence, Gix antigen is represented in intact virions and is probably accessible to Gix antibody.

Absorption↗