The antigenicity of Murine Sarcoma Virus ( M S V ) transformed mouse, rat and hamster cells has been studied by several techniques designed to detect surface antigens. Antigens were readily demonstrated on neoplastic mouse and rat cells. There was complete cross-reactivity between cells induced by the Harvey ( M S V-H) or Moloney ( M S V -M ) strains of MSV and by Moloney Leukemia Virus ( M L V ) . No evidence of a distinct or separate '' MSV-non-MLV" antigen could be obtained by cross absorptions of'MSV/MLV antisera and cells, or by tests designed to break M L V tolerance. Such results favor the view that MSV and M L V are closely related entities. With the 8303 line of MSV-M transformed hamster cells serological tests revealed little if any reactivity with strongly positive mouse anti-MSVIML V antisera. In 465CHUAT Er AL.would distinguish it from the leukemia viruses, either by kinetics of inactivation (Mahy et al., 1966;Moloney, 1966a, b), size (Mahy, 1966; Hartley and Rowe, 1966), electron microscopic appearance (Mitchiner, 1967;Dalton, 1966;Leclerc et a/., 1967), or immunology (Moloney, 1966a, b ; Hartley and Rowe, 1966;Law et al., 1968; Fefer et a/., 1967a, b). Immunologic studies have shown that anti-MLV sera will neutralize focus and tumor formation by MSV (Moloney, 1966a, b ; Hartley and Rowe, 1966), anti-MSV sera will stain surface antigens on MLV-induced lymphoma cells (Fefer et a/., 1967a, b), and mice immunized against MLV or MSV will show specific resistance to the growth of MLV lymphomas or MSV sarcomas (Fefer et al., 1967a;Law et al., 1968). The purpose of the present work was to characterize the specificity of surface antigens on MSV tumor cells with the aid of various immunological techniques. Attention was focused on cross-reactions between antigens induced by MSV-M and MSV-H and between MSV and MLV, and on attempts to detect virus-determined antigen(s) on MSV hamster cells. MATERIAL AND METHODS AnimalsFrom the colonies of the Institute for Tumor Biology and the National Institute for Medical Research, the following lines of inbred mice and their F, hybrids were used: A/%, C57BL, C3H, C57 Leaden, BALB/c, CBA and dba/2. Tumor linesLines of MLV-induced lymphomas and MSVinduced sarcomas were utilized. The former were maintained in mice in either solid or ascitic form. The latter, of mouse, rat and hamster origin, were induced by MSV-M or MSV-H and were maintained in in vivo and/or in vitro passage. The transplant lines were well-established autonomous neoplasms that grew progressively in host animals. The culture lines originated from either in vitro-transformed cells or tumors. A complete summary of all tumor lines is given in Table I. MH-199 medium with 10% fetal calf serum (FCS) was used for mouse and rat MSV lines and the hamster thyroid SV40 lines. It consists of equal proportions of Parker's 199 and Eagle's Minimal Essential Medium (MEM) with additional vitamins and amino acids. All of the other cells were grown on MEM with 10% FCS, except the human MAS line which was grown in Parker's 19...
Antibodies to aminoacyl-tRNA synthetases (anti-Jo-i, anti-PL-7, anti-PL-12) have been found in the serum of some patients with polymyositis (PM). Patients with these antibodies have an unusually high rate of interstitial lung disease (ILD) in association with their PM. Two patients (K.J. and B.T.) with severe ILD and PM were found to have antibodies to a cytoplasmic antigen, but tests to determine whether the antigen was an aminoacyl-tRNA synthetase were negative, including tests of LJ serum for inhibitory effects on the 20 synthetases. KJ immunoprecipitates did not contain tRNA, in contrast to antisynthetase sera. When IgG samples were added to a reticulocyte in vitro translation system at a concentration of 0.3 mg/mi, KJ IgG inhibited globin mRNA translation by 98%, while anti-Jo-i IgG inhibited 62% and normal IgG had little effect. Thus, both anti-LJ and the antisynthetases are directed at antigens that are involved in translation and protein synthesis, and both are associated with the syndrome of lung disease and PM. This syndrome may be associated with antibodies to translation-related proteins in general, which may have implications for the link of PM and enteroviruses, which are mRNA viruses.
The clinicopathologic features of nine cases of peripheral T-cell lymphoma were analyzed. Although the youngest patient was 18 years old, the median age was 59.8 years. They usually presented with widespread disease and had an aggressive course. Seven have died with a median survival of 10.9 months. Five cases were of mixed cell type, sharing certain histopathologic features that we believe are characteristic of peripheral T-cell lymphomas. Three cases were of large cell type; one was a small cell (PDL) type. This latter patient lived symptom-free without treatment for over 3 years, despite stage III disease. Another patient, whose tumor had nodular sclerosis-like fibrosis, is in complete remission two years after chemotherapy for stage III B disease. Because peripheral T-cell lymphoma is morphologically heterogeneous, it may be clinically heterogeneous as well. We believe that classification according to a modified Rappaport system may clarify possible variations in biologic behavior.
Anatomic lesions produced by the Molonev and Harvey strains o f Murirre Sarcoma Virus ( M S V -M and M S V -H ) in mice have becn compared. Erythroblastic splenomc~galy is a distinctive feature of disease produced by MSV-H. Solid tumors induced by both viruses were quite similar in morphology, although sonic consistent difliwnces were noted. The tumors appear to arise by niassive recruitment of primitive mesenchynial cells rather than by clonal proliferatioti. The morphological fiaturcs of these lesions would suggest that, although MSV-M and MSV-H are similar entities, they arc not quite iden tical. Four transplant lines have been established from the mouse tumors; three MSV-H and one MSV-M. The MSV-M line ( C B A strain) was initiated with difficulty and did not release sarcoma virus. The MSV-H lines (two CBA and one BALBIc) MATERIAL AND METHODS VirusThe Moloney strain of MSV (MSV-M) obtained from Dr. J. B. Moloney and Dr. R. Bassin (Nat. Cancer Tnst., NIH, Bethesda, Md., USA), was passaged by intramuscular inoculation in newborn mice, and viral stocks consisted of either crude aqueous 10% tumor extracts clarified by low-speed centrifugation, or semi-purified extracts prepared by a procedure similar to that described by Moloney (1956).The Harvey strain of MSV (MSV-H), obtained from Dr. J. J. Harvey (MRC Clinical Res. Centre, Mill Hill, London, N.W.7, UK) was passaged by intraperitoneal inoculation in newborn mice, and viral stocks consisted of pooled plasma and crude or semi-purified 10% aqueous extracts of spleens and tumors from diseased animals. Some stocks were also prepared from filtered supernatant fluids from tumors established in tissue culture. AnimalsThese included inbred CBA, IC and BALB/c mice of the colonies of the National Institute for Medical Research, and the Centre National de la Recherche Scientifique, and outbred SwissWebster mice obtained from the Charles River Breeding Laboratories and from Dr. R. Siegler (Boston University School of Medicine, Boston, Mass., USA). InoculationsNewborn or older animals were inoculated by the intramuscular, intraperitoneal, or subcutaneous routes with 0.05-0.1 ml of virus. Tumors and organs were fixed in 5 % corrosive aqueous trichloracetic acid and stained with hematoxylin and eosin, or phosphotungstic acid hematoxylin (PTAH). All inoculated legs were cut and stained at three levels. Serial sections of some enlarged spleens were also examined, and splenic imprints were stained with May-GriinwaldGiemsa. Transplantation and tissue culturing techniquesMinced tumor fragments were implanted subcutaneously by trocar. Titrations of tumor cells were performed by subcutaneous inoculation of single-cell suspensions obtained by trypsinization. Tumors were grown in tissue culture by trypsinization, or explantation in growth medium. Lightly trypsinized tissueculture-grown cells were also reinoculated to isologous host animals. MediaCells were cultured in a 50% mixture of modified Eagle's Minimal Essential Medium (8 X vitamins; 2 xamino acids), and Medium 199, with 10% c...
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