bluuebunny/crossref_metadata_2025 huggingface dataset:
Neoplastic transformation of rat embryo cells with herpes simplex virus
Authors: Darai Gholamreza , Munk Klaus
Published: February 2007

Sprague Dawley rat embryo cells (REF) were transformed by inoculation with herpes simplex virus (HSV) and incubation at 42°C for 8 days. The infected cultures were subsequently returned to 37°C and two types of cell clone were isolated from foci of growing cells after 4 weeks. One of the clones consisted of epithelial‐like cells and did not produce HSV (TEF‐tep‐NP). The second consisted of spindle‐shaped cells and cultures of these cells persistently developed small areas of degeneration where production of infectious HSV (REF‐Tsp‐P) took place. An additional clone which did not produce any more HSV (REF‐Tsp‐NP) was isolated from REF‐Tsp‐P in the presence of HSV‐antiserum. REF‐Tsp‐P and REF‐Tsp‐NP grew more rapidly than REF and also formed foci in soft agar. REF‐Tep‐NP had a growth rate between that of normal rat embryo cells and that of both REF‐Tsp‐NP and REF‐Tsp‐P and did not form foci in soft agar. REF‐Tsp‐NP cells, in contrast to REF‐Tep‐NP cells, were resistant to superinfection with HSV types 1 and 2. REF‐Tsp‐P and REF‐Tsp‐P and REF‐Tsp‐NP produced metastasizing sarcomas in rats. After inoculation of 103 REF‐Tsp‐NP cells into 1‐day‐old rats tumours developed rapidly. REF‐Tep‐NP cells did not induce tumours in rats. The parental REF cells produced no tumours, even when 108 cells were inoculated into the rats. Positive immunofluorescence was observed in all three transformed cells only with the hyperimmune rabbit sera but not with human anti‐HSV reconvalescence immune sera.
Canine testicular tumors: Epidemiologic features of 410 dogs
Authors: Hayes Howard M. , Pendergrass Thomas W.
Published: February 2007

Histologically confirmed testicular tumors were diagnosed in 410 dogs from 12 North American veterinary university hospitals and clinics. Three tumor‐cell types, Sertoli cell tumor, interstitial cell tumor and seminoma, were about equally represented. Several breeds were identified with high risk for different testicular tumor‐cell types. Cytogenetic and immunogenetic studies of these dog families could offer leads applicable to familial testicular cancer in man. The multiplicity of breeds within the series suggests that, as in man, other factors, in addition to heredity, play a role in etiology. Cryptorchid dogs appear to have a 13.6 times higher risk of testicular tumor than normal dogs. Additionally, male dogs with an inguinal hernia have an increased risk (4.7) of testis tumors. There were no detectable excesses of other urogenital anomalies or urogenital tumors among the series. The Shetland Sheepdog is suggested as an appropriate model for research into the mechanisms responsible for testicular maldescent and tumorigenesis.
In vitro generation of primary and secondary cytotoxic cell‐mediated immune responses to chemically induced mouse sarcomas
Authors: Kall Mary Ann , Hellström Ingegerd , Hellström Karl Erik
Published: February 2007

Mixtures of lymph node and spleen cells from normal (untreated) BALB/c mice and from BALB/c mice whose syngeneic tumors had been excised 7–28 days previously (“tumor‐excised mice”), were sensitized in vitro by cultivation for 9 days with cells from syngeneic, methylcholanthrene‐induced sarcomas. The in vitro‐ sensitized lymphoid cells were tested in a 36‐h microcytotoxicity assay for reactivity against target cells carrying the sensitizing tumor antigens, as well as against control target cells lacking these antigens. After co‐cultivation with tumor cells, lymphoid cells from both normal and tumor‐excised mice were cytotoxic to tumor cells carrying the sensitizing antigens. The cytotoxicity was generally specific, and occurred at low effector: target cell ratios (in some experiments down to 1:1). When lymphoid cells from tumor‐excised mice were exposed in vitro for 9 days to cells carrying the same antigens as those which were originally present on the surgically excised tumors, the effector cells obtained gave a dose‐dependent cytotoxic response suggestive of a linear relationship. When lymphoid cells from normal mice were similarly sensitized for 9 days, specifically cytotoxic lymphoid cells were generated but no linear dose‐dependent response was detected.
Serum antibodies to herpesvirus early antigens in patients with cervical carcinoma determined by anticomplement immunofluorescence technique
Authors: Ito Hisao , Tsutsui Fumio , Kurihara Soju , Akabayashi Tomoko , Tobe Takashi , Nishimura Chiaki
Published: February 2007

Sera from patients with carcinoma of the uterine cervix were used with the anticomplement immuno‐fluorescence (ACIF) technique to develop a simple procedure for detection of antibodies to herpes simplex virus type 2 (HSV‐2) early antigens. Test cells used in the ACIF assay were HEp‐2 cells infected with HSV‐2 sequentially treated with inhibitors of protein and of DNA synthesis. The cells were first treated for 7 h with cycloheximide (100 μg/ml) and then for 3 h with hydroxyurea (150 μg/ml). In this assay serum titers giving more than 21.5% ACIF‐positive cells correlated to invasive carcinoma of the cervix. Using these criteria 18 out of 43 patients with invasive carcinoma, none of 8 patients with carcinoma in situ, and only 1 of 43 controls, were 'diagnosed as positive. Thus an elevated titer of antibodies against HSV‐2 antigens correlated to cervical carcinoma.
Antigens on melanoma cells detected by leukocyte dependent antibody assays of human melanoma antisera
Authors: Hersey P. , Honeyman M. , Edwards A. , Adams E. , McCarthy W. H.
Published: February 2007

Antibody‐dependent cell‐mediated cytotoxic assays have been used to examine antigens on human melanoma cells obtained either directly from patients or from long‐term melanoma cell lines. A panel of melanoma antisera was selected from human subjects which could be shown not to have significant reactivity to histocompatibility antigens. With these antisera extensive cross‐reactions between melanoma cells were found. However, the cross‐reactivity was incomplete and the pattern of reactivity was different for each antiserum tested. These results were not consistent with a common melanoma antigen on human melanoma cells but rather indicated heterogeneity of melanoma antigens and multiple antibody specificities in the sera tested. This appeared to be confirmed by extensive cross‐absorption studies which indicated limited cross‐reactivity of antigens on melanoma cells from either long‐term or short‐term cultures. Several changes in the antigenic profile of melanoma cells in vitro from both long‐term and short‐term cultures were documented which resulted from contamination of the melanoma cell lines with non‐melanoma cells and fibroblasts. Melanoma antisera may therefore be useful to monitor changes in long‐term cultures which would otherwise give spurious results in in vitro tests. These results appear to have considerable significance for understanding tumour/host relationships and for the establishment of rational immunotherapeutic procedures and diagnostic tests in melanoma.
Demonstration of a phase (stage)‐specific embryonic brain antigen in human meningioma
Authors: Kehayov I. , Botev B. , Vulchanov V. , Kyurkchiev S.
Published: February 2007

The water‐soluble antigens of human embryonic brain were studied using a rabbit antiserum to human 8‐ to 10‐week embryonic brain (non‐absorbed and absorbed with extracts of human embryonic and adult organs). A phase (stage)‐specific brain antigen (s) characteristic for the human 8‐ to 10‐week‐old embryo was detected by double immunodiffusion and immunoelectrophoresis in agarose gel. The testing of this anti‐embryonic brain serum against saline extracts of human brain tumours (meningiomas, glioblastomas, astrocytomas, neurinomas and brain metastasis of carcinoma) revealed the presence of an “embryonic” antigen in the human meningioma only. Immunochemically this meningioma‐associated antigen is identical to a phase (stage)‐specific antigen of the 8‐ to 10‐week embryo.
Indomethacin enhancement of spleen‐cell responsiveness to mitogen stimulation in tumorous mice
Authors: Pelus Louis M. , Strausser Helen R.
Published: February 2007

Spleen cells removed from C57Bl/6J mice bearing a methylcholanthrene‐induced fibrosarcoma (MC‐16) demonstrate suppressed responsiveness to phytohemagglutinin (PHA) and bacterial lipopolysaccharide (LPS) induced mitogenesis as compared to non‐tumorous mice. A similar depression of PHA‐induced mitogenesis was observed with spleen cells from C3H/HeJ mice bearing syngeneic mammary adenocarcinomas (C3HBA). The administration of indomethacin, a non‐competitive irreversible prostaglandin (Pg) synthesis inhibitor, (75 or 100 μg/mouse, IP) on an alternate day basis to groups of tumor‐bearing mice of both strains, significantly enhanced immune cell responsiveness to mitogenic stimulation. The addition of indomethacin (10 μg/ml) to cultures of spleen cells from these tumor‐bearing mice, as well as to DBA/1J mice bearing the Cloudman S‐91 melanoma, enhanced spleen‐cell responsiveness to mitogen‐induced DNA synthesis by as much as 156%. Indomethacin administration in vivo or in vitro had no significant effect on mitogen‐induced DNA synthesis of spleen cells from non‐tumor‐bearing animals. It is hypothesized that tumors, or tumor‐cell antigens, increase Pg production of a population of spleen cells, and that the increased Pg content of the spleen may be important in controlling immune responsiveness in mice.
Expression of feline type‐C virus in normal and tumor tissues of the domestic cat
Authors: Levin Reuven , Ruscetti Sandra K. , Parks Wade P. , Scolnick Edward M.
Published: February 2007

Tumor and normal tissues from domestic cats were examined for FeLV and RD‐114 specific nucleic acids and proteins. Virus‐positive tissues showed a 100‐ to 200‐fold higher level of FeLV and a 200‐ to 400‐fold higher level of FeLV p30 than virus‐negative tumors and normal cat tissues. In contrast, the levels of RD‐114 viral RNA and p30 antigen were comparable in the majority of tumorous and normal tissues examined. When the DNA of these tissues was examined for FeLV‐related sequences, the virus‐positive tumors were found to contain extra copies of FeLV DNA. Virus‐negative tumors contained DNA sequences homologous with FeLV but the copy number of these sequences could not be distinguished from normal tissues. The results indicate that in certain FeLV‐induced type‐C lymphoproliferative diseases, extra type‐C sequences not present in normal tissues can be identified.
Antibody responses to membrane antigens in monkeys infected with herpesvirus saimiri
Authors: Prevost Jean‐Marie , Pearson Gary R. , Wallen William C. , Rabin Harvey , Qualtiere Louis F.
Published: February 2007

The antibody response to Herpesvirus saimiri (HSV)‐induced membrane antigens (MA) was followed in HSV‐infected owl monkeys using the membrane immunofluorescence (MF) and antibody‐dependent lymphocyte cytotoxicity (ADLC) assays. These responses were correlated with the loss of T‐cell responsiveness to general mitogens. Antibody titers to MA as determined by ADLC but not MF increased to remarkably high titers in those monkeys that developed malignant disease following virus infection, while remaining at relatively low and constant levels in those monkeys that developed a chronic virus infection in the absence of malignant disease. This disease‐related antibody response pattern was paralleled by the loss of T‐cell function in diseased animals. The development of leukemia in HVS‐infected owl monkeys did not suppress the ability of peripheral blood lymphocytes to act as effector cells in the ADLC assay. The relationship of these immune response patterns to the development of malignant disease in this system is discussed.
Affinity of estradiol mustard for estrogen receptors and its enzymatic degradation in uterine and breast cancer cytosols
Authors: Leclercq Guy , Deboel Marie‐Christine , Heuson Jean‐Claude
Published: February 2007

Estradiol mustard (EM) is the 3,17β‐diester of estradiol‐17β (E2) with the nitrogen mustard derivative chlorphenacyl. The ability of EM to bind to cytoplasmic estrogen receptors was tested by inhibition of the binding of 3H‐E2 to rat uterine cytosol at 18°C and 30°C. At both temperatures an inhibition curve was observed in the presence of a large excess of drug, suggesting that the latter has a very weak binding affinity (100,000 times lower than E2). Incubation of uterine cytosol with increasing amounts of 3H‐E2 in the presence and absence of an excess of EM indicated that the drug interacted with the receptors at the same sites as E2 (competitive inhibition). Preincubation of uterine cytosol at 18°C with EM induced a progressive reduction of 3H‐E2 binding capacity. This reduction also occurred, although to a lesser extent, when long‐term incubation of the cytosol with EM was performed in the presence of labelled E2 from the start. The process was faster at 18°C than at 4°C and did not occur with EM preincubated in homogenization buffer. Exchange assays by 3H‐E2 of uterine receptors preincubated with labelled E2 and excess EM indicated that the drug‐induced inhibition of binding capacity was reversible and produced no apparent alteration of the receptors. Furthermore, the rate of exchange was similar to that observed with receptors previously filled with unlabelled E2. In 9 “receptor‐positive” cytosols from human breast cancers, time‐course study of the binding of 3H‐E2 in the presence of excess of EM yielded similar results as those obtained with rat uterine cytosol. These results show that EM has a very low binding affinity for the estrogen receptors and that it is metabolized into one or several compounds of higher binding affinity. They suggest that EM is probably not significantly concentrated by the estrogen target tissues such as mammary cancers. Therefore, the drug is unlikely to be very valuable in the treatment of breast cancer through a specific mechanism involving concentration by the estrogen receptors.
Properties of a baboon lymphotropic herpesvirus related to Epstein‐Barr virus
Authors: Falk Lawrence , Deinhardt Friedrich , Nonoyama Meihan , Wolfe Lauren G. , Bergholz Carolyn , Lapin Boris , Yakovleva Lelita , Agrba Viola , Henle Gertrude , Henle Werner
Published: February 2007

Three lymphoblastoid cell lines were established from splenic lymphocytes of a lymphomatous baboon (Papio hamadryas) by co‐cultivation of the lymphocytes with X‐irradiated cells of marmoset or baboon lymphoblastoid cell cultures; the baboon splenic lymphocytes failed to grow when cultured alone. A herpesvirus, associated with each cell line, was identified by immunofluorescence, molecular hybridization and electron microscopy. Antigenic comparison with Epstein‐Barr virus (EBV) showed that the baboon herpesvirus and EBV shared cross‐reacting viral capsid antigens (VCA): 20 of 20 (100%) anti‐VCA(EBV)‐positive human sera and 55 of 62 (89%) baboon sera reacted with the baboon lymphoblastoid cells and baboon sera stained EBV VCA in P3HR‐1 and EB‐3 cells. No nuclear antigen, as assayed by anti‐complement immunofluorescence tests, was detected in baboon lymphoblastoid cells when human or baboon anti‐VCA positive sera were used. Baboon anti‐VCA‐positive sera also failed to stain EBV nuclear antigens (EBNA) in Raji or P3HR‐1 cells. Preliminary molecular hybridization studies showed only approximately 40% homology between viral DNA of baboon cell lines and DNA of EBV derived from P3HR‐1 cells.
Tumor antigen extracts stimulate cytotoxicity against unrelated target cells
Authors: Lopez Diana M. , Sigel M. Michael
Published: February 2007

A new cytotoxicity assay for the study of tumor antigens is described. Splenocytes from normal and mammary‐tumor‐bearing BALB/c mice were depleted of glass‐adherent cells, exposed to various concentrations of tumor extracts and mixed with 51Cr‐labelled chick red blood cells. Cytolysis evidenced by 51Cr release was determined 20 h after incubation at 37°C. Lymphocytes from tumor bearers exerted no cytotoxic action per se, but became cytolytic after confrontation with immunogenic tumor extracts. Although this cytotoxicity is expressed against targets other than the cells containing the sensitizing antigen, i.e., a non‐specific activity, its induction is strictly specific as evidenced by the following: (1) extracts of D1‐DMBA‐3 tumors exerted an inductive effect only in lymphocytes from mice bearing this tumor and not in lymphocytes from normal mice; and (2) extracts of normal tissues or of a non‐immunogenic mammary tumor, D1‐DMBA‐2, did not induce cytotoxicity in lymphocytes from normal or tumor‐bearing mice. This approach may provide a useful method for in vitro determination of cell‐mediated immunity in which specific reactions can be induced by tumor extracts as opposed to intact tumor cells.
Kinetics of the response of spleen cells from tumor‐bearing animals in an in vivo tumor neutralization assay
Authors: Gabizon A. , Small M. , Trainin N.
Published: February 2007

The behavior of spleen cells from tumor‐bearing mice, vis‐à‐vis isologous tumor cells, was investigated by means of an in vivo adoptive neutralization test. C3H/eB mice were challenged with tumor cells from a chemically induced fibrosarcoma. Spleens from these animals were removed at weekly intervals following tumor inoculation, mixed with tumor cells, and tested for their influence on tumor growth in syngeneic recipient mice. Two phases in the reactivity of spleen cells from tumor‐bearing mice were clearly distinguishable. In a first stage of tumor growth, these mice yielded specific tumor‐inhibitory cells conferring protection. Subsequently, the protective activity declined leading to a second phase characterized by tumor enhancement. Both protective and enhancing activities were shown to be mainly dependent on the presence of T cells.
In vitro sensitization to embryonic antigens
Authors: Friend Kathleen , Hellström Ingegerd , Hellström Karl Erik
Published: February 2007

Lymphoid cells from virgin, untreated BALB/c mice cultured 5 days on 12‐ or 13‐day syngeneic mouse embryo fibroblasts (MEF) or on cells from a syngeneic 3‐methylcholanthrene‐induced mouse sarcoma (1315) were cytotoxic for 1315 tumor target cells when tested with a microcytotoxicity assay. They did not kill embryo or skin fibroblast target cells. Lymphoid cells cultured with 11‐, 14‐ or 17‐day MEF were not cytotoxic for cells from the 1315 tumor, from embryo or from adult skin. Lymphoid cells from multiparous BALB/c mice cultured on 11‐, 12‐ or 13‐day MEF, on line 1315 sarcoma cells or on skin fibroblasts were cytotoxic for tumor target cells. MEF were killed by multipara lymphoid cells that had been cultured on 11‐, 12‐ or 13‐day MEF or on the 1315 tumor line. Multipara lymphoid cells cultured on 1315 cells or 12‐day MEF were cytotoxic for adult skin fibroblasts, while multipara lymphoid cells cultured on 14‐ or 15‐day MEF were not cytotoxic for any of the target cells. The data thus indicate that lymphoid cells can mediate both primary and secondary immune reaction in vitro to antigens shared by neoplastic and normal embryonic cells, and that the primary reactions appear to be more specific to putatively embryonic tumor antigen(s) than the secondary ones.
Immunoglobulin complexes in sera of patients with malignancy
Authors: Samayoa Edwardo A. , McDuffie Frederic C. , Nelson Audrey M. , Go Vay L. W. , Luthra Harvinder S. , Brumfield Hilton W.
Published: February 2007

Sera frour 146 patients with malignancy, 59 normal controls and 42 patients hospitalized with non‐malignant diseases were examined by a precipitin test with monoclonal rheumatoid factor (mRF) for the presence of circulating immune complexes containing IgG. Forty‐two (29%) of the sera from cancer patients but only two of the sera from patients in each of the control groups contained such material. Similar results were obtained with a radioimmuno‐assay for immune complexes based on the same mRF. Sera from 23 of 65 patients with metastatic malignancy (35%) had elevated levels of immune complexes by this latter test. The presence of the material was not related to the source of malignancy, presence of carcinoembryonic or hepatitis antigens or of such autoantibodies as rheumatoid factor or anti‐DNA. By density gradient ultracentrifugation the reacting material was identified as being of molecular size 19s or greater. It has not yet been further characterized with regard to the nature of any antigens present.
A case control study on immunity to two epstein‐barr virus‐associated antigens, and to herpes simplex virus and adenovirus in a population‐based group of patients with hodgkin's disease in denmark, 1971–73
Authors: Hesse J. , Ebbesen P. , Levine P. H. , Connelly R. R. , Mordhorst C. H.
Published: February 2007

One hundred and eighty‐five patients with untreated Hodgkin's disease (HD) comprising 86% of all new cases diagnosed in Denmark over a 2‐year period, were individually matched with healthy controls of the same age, sex and social class. In comparison to controls, HD patients showed significantly elevated mean antibody titres to Epstein‐Barr viral capsid antigen (EB‐VCA) and to herpes simplex virus, whereas no significant differences in mean titres were found for adenovirus common antigen. Subdivision of the patients by age, sex, social class, HL‐A antigens, stage of disease and histology did not alter this pattern, except that significant case‐control differences in EB‐VCA titres could be demonstrated only for the nodular sclerosis and lymphocyte predominance subgroups. After 1 year of treatment, a significant rise in EB‐VCA mean titre had taken place. Splenectomy seemed to promote this titre elevation. Neither the initial titres to EB‐VCA and EBV‐EA nor changes in titres over time were related to prognosis. The results of our study, which are more representative of a population of HD patients and controls than previously reported studies, confirm that the reported relationship between EBV and HD exists, but that the elevated EBV titres are probably not of etiologic significance in most HD patients.
Somatic cell hybrids between human lymphoma lines. III. Surface markers
Authors: Klein George , Rosén Anders , Terasaki Paul , Billing Ron , Honig Ron , Jondal Mikael , Zeuthen Jesper , Clements Geoffrey
Published: February 2007

Hybrids between two human lymphoma lines, Raji and Daudi (8A) and Raji and BJAB (83) were examined for genetically determined and/or differentiation‐related surface markers. HL‐A, B cell alloantigens, Fc and complement receptors, EBV receptors and β2 microglobulin showed an autonomous (“codominant”) expression in the hybrid. This is in contrast to most previous studies on other differentiation markers, involving as a rule crosses between cells of different lineages, where the differentiated pattern usually became “eclipsed” in the hybrid. Staining of activated complement and complement consumption tests showed intermediate or partially suppressed expression in the hybrids. This may be viewed in relation to the fact that these reactions do not merely depend on complement binding to the receptor, but also on subsequent activation and binding of the activated complement. A more complex interaction is also suggested for immunoglobulin production. Surface immunoglobulin showed a suppressive or intermediate pattern in both hybrids, whereas intracellular kappa chain production showed an amplification in the 83 hybrid. The β2 microglobulin deficiency of the Daudi parent was corrected in the Raji/Daudi hybrid. Two new HL‐A specificities, A10 and BW17, appeared on this hybrid which were not present on the parental lines. This suggests that the HL‐A deficiency of the Daudi cell is due to its lack of β2 microglobulin.
A dose‐response study on urethane carcinogenesis in rats and mice
Authors: Schmähl D. , Port R. , Wahrendorf J.
Published: February 2007

Sprague‐Dawley rats and NMRI mice were treated with urethane in the drinking water for 2 years. In both species the daily doses were: 100, 500, 2,500, and 12,500 μg/kg. The frequency of animals with malignancies increased steadily with increasing doses, beginning from 500 μg/kg/day for rats, and from 100 μg/kg/day for mice. To evaluate the possible cancer risk for man due to urethane in beverages, the observed response rates were used to extrapolate responses at lower doses. At a daily dose of 0.14 μg/kg/day (corresponding to daily consumption of a beverage with 10 ppb urethane by a 70‐kg man) the upper risk limits were estimated to be 3.2 in 100,000 for rats, and 470 in 100,000 for mice (modified Mantel‐Bryan procedure). Problems in calculating a possible cancer risk for man on the basis of animal observations are discussed. Since treatment of beverages with diethyldicarbonate leads to the formation of urethane, and since a cancer risk to man from urethane cannot be excluded, replacement of diethyldicarbonate by a toxicologically unobjectionable compound is called for.
Horizontal transmission of feline leukemia virus under natural conditions in a feline leukemia cluster household
Authors: Essex M. , Cotter S. M. , Sliski A. H. , Hardy W. D. , Stephenson J. R. , Aaronson S. A. , Jarrett O.
Published: February 2007

Ten post‐weanling 4‐month‐old cats, designated “tracers”, were placed in a feline leukemia cluster household to determine the efficiency of horizontal transmission of feline leukemia virus (FeLV). The tracer cats were confirmed as negative for prior exposure to FeLV. Following placement in the leukemia cluster environment, the tracer cats were serologically monitored at intervals of 3–6 weeks for a total period of 1 year. The tests employed included the detection of FeLV using fixed‐cell immunofluorescence and the detection and titration of antibody to: (1) the feline oncorna‐virus‐associated cell membrane antigen (FOCMA), as detected by membrane immunofluorescence; (2) viable FeLV, using serum neutralization; (3) virion core protein p30, using radioimmunoprecipitation; and (4) virion glycoprotein gp70, using radioimmunoprecipitation. All of the tracers had evidence of horizontal infection by FeLV, by several criteria. Seven of the 10 had virus that could be isolated from plasma. All of these 7 developed a terminal illness within 18 months; 3 developed aplastic anemia, 3 infectious peritonitis, and 1 lymphoma. The remaining 3 were negative for FeLV by both virus isolation and fixed‐cell immunofluorescence. These 3 did, however, develop high antibody titers by all four criteria and they remained healthy throughout the examination period. These results clearly indicate that unprotected post‐weanling cats brought into a leukemia exposure household environment have a high risk of becoming infected with FeLV. Furthermore, a large proportion of the cats are at risk for development of persistent viremia and FeLV‐related diseases.
Genetic association of the humoral and cellular immune responses of rats to moloney sarcomas
Authors: Veit Bruce C. , Jones Joe M. , Miller Glenn A. , Feldman Joseph D.
Published: February 2007

Brown Norway (BN), Lewis (Le), F1 hybrids of Le × BN (LBN) and parent‐to‐LBN backcross rats were tested for cellular and humoral responses to a BN Moloney sarcoma. Regardless of AgB phenotype, BN backcrosses produced low levels of cell‐mediated cytotoxicity (CMC) that were comparable to those of BN parents. Le backcrosses developed high levels of CMC similar to those produced in Le parents. An inverse relationship between levels of CMC and serum antibodies (cytotoxic for tumor cells and anti‐p30 of MuLV) was observed; BN parents and backcrosses produced high levels of serum antibodies whereas levels in Le parents and backcrosses were low. LBN hybrids developed relatively high levels of CMC and serum antibodies. An additional finding was that the CMC response in Le parents and back‐crosses was directed primarily against tumor‐associated antigens rather than histocompatibility antigens expressed on the tumor cells. The results suggest that humoral and cellular responses to Moloney sarcoma in rats are not determined solely by the major AgB histocompatibility locus but do have a genetic association. This genetic association was detected with a 51Cr release assay which detects T‐cells, suggesting that select populations of effector T‐cells may be genetically regulated.
Human pancreatic carcinoma (mia paca‐2) in continuous culture: Sensitivity to asparaginase
Authors: Yunis Adel A. , Arimura Grace K. , Russin David J.
Published: February 2007

An undifferentiated human pancreatic carcinoma has been established in continuous culture and is grown in Dulbecco's modified Eagle's medium fortified with 10% fetal calf serum and 2.5% horse serum. The established cell line (MIA PaCa‐2) has a doulbing time of 40 h. The cells are large with abundant cytoplasm, exhibit a high degree of aneuploidy and have a tendency to grow on top of other cells. MIA PaCa‐2 grows in soft agar with a colony‐forming efficiency of 19%. Both MIA PaCa‐2 cells and a cell line from another pancreatic carcinoma obtained from National Cancer Institute (NCI) are sensitive to asparaginase, a property not shared by several other human tumor cell lines tested.
Molecular interactions between adriamycin and x‐ray damage in mammalian tumor cells
Authors: Byfield John E. , Lee Young C. , Tu Lorna
Published: February 2007

The effect of the anthracycline antibiotic, Adriamycin (Ad), on the sedimentation properties of pre‐labelled mammalian DNA has been studied. Ad induces DNA degradation in vivo in both excision repair‐competent (HeLa and Me‐180) cells and in excision repair‐deficient (REQ) cells. When X‐irradiated cells are exposed to Ad during the period of repair of DNA single‐strand breaks, small numbers of residual breaks persist following completion of repair. These are attributable to those induced by Ad alone. The effects of Ad and X‐rays therefore appear to be similar and additive. No clear‐cut evidence that Ad can inhibit the repair of X‐ray‐induced DNA single‐strand breakage was found. Ad also induces the formation of DNA double‐strand breaks and inhibits the repair of X‐ray‐induced base damage (repair replication). The induction of DNA strand breakage may be responsible for Ad cell toxicity and may contribute to its capacity to enhance primary X‐irradiation damage when the two types of lesions co‐exist.
Murine sarcoma virus (msv)‐induced tumors in mice. I. Distribution of msv‐immune cytolytic t lymphocytes in vivo
Authors: Plata F. , Sordat B.
Published: February 2007

Quantitative studies using a 51Cr release assay were performed to analyse the time‐course of appearance and specificity of cytolytic cells in C57BI/6 mice inoculated with Moloney murine sarcoma virus (MSV). Various lymphoid organs were studied including spleen, mesenteric lymph nodes (MLN), lymph nodes regional to the MSV‐induced tumor (RLN), and peripheral blood. Furthermore, the kinetics of appearance of cytolytic cells within the MSV‐induced tumor was determined. In agreement with previous studies, it was found that cytolytic T lymphocytes (CTL) specific for MSV‐associated antigens were present among the cells extracted from the tumor and from the lymphoid organs. However, differences in the kinetics of CTL activity could be documented: lymphoid cells from spleen, RLN and peripheral blood showed peak activity at the time of maximum tumor diameter, while intratumoral cells showed peak activity at the onset of tumor regression. MLN cells showed cytolytic activity only when tumor regression had begun. Naturally cytotoxic cell populations of thymus‐independent origin, present in normal control mice, were also detected in MSV‐infected mice.
Polyoma genome transcription in transformed mouse cells growing in culture and as tumors in syngeneic mice
Authors: Grady Leo J. , North Arlene B. , Campbell Wayne P.
Published: February 2007

The strands of the polyoma genome coding for early and late viral RNA were separated by means of asymmetric cRNA synthesized under high salt conditions by Escherichia coli RNA polymerase. Each strand was then employed in RNA‐DNA hybridization experiments to determine the degree to which it is transcribed in transformed cells under several conditions. Except for a concanavalin‐A‐selected revertant, approximately one‐quarter of the early strand was expressed in all of the situations investigated. In contrast, while no significant late strand transcription was detected in transformed cells in culture, the tumors induced by these cells contained transcripts complementary to about 12% of this strand. The results are discussed in terms of current knowledge of the amount of the virus genome required to transform cells.
Comparative studies on ebv antigens by immuno‐fluorescence and immunoperoxidase techniques
Authors: Stephens R. , Traul K. , Gaudreau P. , Yeh J. , Fisher L. , Mayyasi S. A.
Published: February 2007

Three groups of EBV antigens, VCA, MA and EA, were compared by the techniques of electron microscopic immunoperoxidase (IP) and immuno‐fluorescence (IF). P3HR‐1 and EBV superinfected Raji cells served as targets for labelled sera from patients with BL, NPC and IM or from healthy donors. 125I peroxidase‐labelled antibodies were also prepared to determine, autoradiographically, the penetration of the complex into the cell system, and to monitor the incubation and washing procedures. The development of a gentle sedimentation technique proved critical in handling the fragile target cells. VCA and MA were readily identified and localized by both procedures without significant modification of the basic techniques. Indentification of early antigens by IP required modification of the fixation method to include a brief treatment in acetone. The diffuse early antigen (EAD) was found to be associated with cellular ribosomes.
Tumorigenicity of human hematopoietic cell lines in athymic nude mice
Authors: Nilsson Kenneth , Giovanella Beppino C. , Stehlin John S. , Klein George
Published: February 2007

Human hematopoietic cell lines, which had been classified on the basis of studies on clonality, and morphological, chromosomal and functional parameters as lymphoblastoid cell lines (LCL) of presumed non‐neoplastic origin, and lymphoma, myeloma and leukemia lines of proven malignant origin, were tested for tumorigenic potential on subcutaneous transplantation to nude mice and for capacity to grow in semi‐solid medium in vitro Recently established LCL failed to grow both in nude mice and in agarose. In contrast, some of the LCL which had developed secondary chromosomal alterations during continuous cultivation for periods exceeding several years were tumorigenic and/or had the capacity to form colonies in agarose. Most lymphoma lines formed colonies in agarose and tumors in the mice. One of the two myeloma lines formed subcutaneous tumor which, however, showed no progressive growth. The other myeloma line failed to grow. Both myeloma lines, however, formed colonies in agarose. The myeloid leukemia line was tumorigenic while two of the three tested lymphocytic leukemia lines failed to grow in the mice. All leukemia lines formed colonies in agarose. We conclude from this study that: (1) Of the two types of Epstein‐Barr virus containing cell lines [LCL and Burkitt lymphoma (BL) lines], only BL lines were shown to form tumors when inoculated subcutaneously in nude mice and had the capacity to grow in agarose in vitro. This shows that EBV transformation per se does not necessarily render lymphocytes tumorigenic in nude mice. The capacity to form colonies in agarose is not acquired either. (2) Changes of the karyotype and several phenotypic characteristics which occur in the originally diploid LCL during prolonged cultivation in vitro may be accompanied by the acquisition of the potential to grow subcutaneously in nude mice and in agarose in vitro. (3) The inconsistency with regard to the capacity of some of the neoplastic cell lines to grow in nude mice or in agarose seems to underline that neither of the two tests is a reliable criterion for malignancy of human lymphoma, leukemia and myeloma cell lines.
Surface membrane changes in lymphocytes from patients with infectious mononucleosis
Authors: Mintz Uri , Sachs Leo
Published: February 2007

Peripheral blood lymphocytes from 20 patients with acute infectious mononucleosis (IM) were studied for cell aggregation and for cap formation by concanavalin A (Con A). The lymphocytes from these patients showed 5.2±1.5% cells with a Con‐A‐induced cap and a high degree of cell aggregation without Con A, compared to 27.7±3.2% caps and a low degree of cell aggregation with normal lymphocytes. The lymphocytes from IM patients were fractionated to enrich for T and B cells. There was a low frequency of cap formation in both T and B cells, but the high degree of cell aggregation without Con A only occurred with B cells. Studies with four patients in clinical remission from acute IM have shown that the frequency of Con‐A‐induced cap formation only returned to normal more than 3 months after the beginning of clinical remission and that even at 6 months the cells still showed a high degree of cell aggregation. The results indicate that a high degree of B‐cell aggregation and a low percentage of B and T cells with a Con‐A‐induced cap were associated with acute IM and that the changes associated with a high degree of B‐cell aggregation were by themselves not sufficient to cause the disease.
Detection of cellular immunity to tumor‐associated antigen(s) in mice by the macrophage spreading inhibition test
Authors: Svoboda Ivna , Mažuran Renata , Rabatić Sabina , Silobrčić V.
Published: February 2007

Soluble preparations of antigens from a methyl‐cholanthrene‐induced fibrosarcoma of C57BI mice were prepared by homogenization of tumor tissue and high‐speed centrifugation of the homogenate. These preparations were able to sensitize syngeneic mice to tumor‐associated antigens (TAA) of the fibrosarcoma, and to provoke a delayed hypersensitivity reaction when injected into the footpad of sensitized mice. Furthermore, the same soluble preparations could inhibit in vitro the spreading of peritoneal macrophages from mice sensitized to TAA. A similar inhibition of macrophage spreading was obtained when peritoneal cells from C57BI mice, bearing transplants of the fibrosarcoma, were incubated with the preparations. We conclude that the macrophage spreading inhibition test, like other in vitro assays, can detect cell‐mediated immunity to tumor‐associated antigens.
Transformation of rabbit kidney cells by bkv(mm) human papovavirus
Authors: Mason David H. , Takemoto Kenneth K.
Published: February 2007

Primary rabbit kidney cells were transformed by BKV(MM), a papovavirus isolated from the urine of a child with the Wiskott‐Aldrich syndrome. The transformed cells contained BK T‐antigen, but no antigen that reacted with SV40 U‐antiserum. The transformed cells failed to produce tumors in nude mice, and BKV (MM) was not rescued from transformed cells by cell fusion or chemical induction methods. The transformed cells supported the growth of rabbit kidney vacuolating virus (RKV), and could be used to quantitate RKV by plaque formation under an agar overlay.
Isolation from a transmissible lymphoid tumour (tlt) lymphoblastoid cell line of a herpesvirus similar to marek's disease virus
Authors: Nazerian K. , Lee Lucy F. , Witter R. L.
Published: February 2007

A chicken lymphoblastoid cell line (TLT)‐6855 originally established from an avian oncornavirus‐induced lymphoma (Siegfried and Olson, 1972) was studied for the presence and expression of Marek's disease virus (MDV) genome. By nucleic acid hybridization a significant amount of MDV DNA was found in this cell line. This virus DNA, however, was not expressed in either virus‐specific intracellular or membrane antigens or the MD‐associated tumour‐specific surface antigen (MATSA). Moreover, MDV‐specific antigens could not be activated in this cell line by treatment with 5‐IdUrd. In several experiments, when chickens were inoculated with the cell line a herpesvirus was repeatedly isolated from the kidneys. This herpesvirus was antigenically similar to MDV but was low in oncogenicity for chickens.
Evidence that mulv‐induced thymic lymphoma cells possess specific cell membrane binding sites for mulv
Authors: Baird S. , Raschke W. , Weissman I. L.
Published: February 2007

Cell‐surface binding sites specific for thymotropic murine leukemia viruses were found in high concentrations on thymic lymphoma cell lines induced by this class of virus, but were detectable in much lower concentrations (if at all) in several non‐T leukemias, plasmacytomas, and normal thymocytes or spleen cells. By specific comparison, Moloney leukemia virus (M‐MuLV) binds to a lymphoma induced by M‐MuLV, but not to a thymic lymphoma induced by Gross leukemia virus (G‐MuLV); and G‐MuLV binds to an AKR lymphoma but not to the M‐MuLV‐induced lymphoma. The material which binds to these T‐lymphoma membrane sites is input virus, rather than a contaminant which copurifies with virus. Autoradiographic analysis demonstrates that a high proportion of T‐lymphoma cells possess binding sites, whereas only a rare cell in the thymus binds murine leukemia virus to the same degree. We raise and discuss the hypothesis that each T lymphoma induced by thymotropic leukemia viruses may represent the clonal descendants of the few rare cells in the normal thymocyte population which also bind these viruses.
Column separation of viral capsid antigen (vca)‐positive cells from vca‐negative cells in an epstein‐barr virus (ebv)‐producing lymphoid line
Authors: Dalianis Tina , Klein George , Andersson Birger
Published: February 2007

Virus producing, VCA (viral capsid antigen)‐positive cells could be selectively removed from Epstein‐Barr virus (EBV)‐carrying, virus‐producer P3HR‐1 cultures by two different methods of column passage. In the first, the virus‐producing cells were covered with human EBV antibody and subsequently passaged through anti‐human‐Ig columns. In the second method, untreated P3HR‐1 cells were allowed to pass through columns of EBV receptor‐positive cell lines or, as controls, EBV receptor‐negative cells. The majority of the VCA‐positive cells were selectively removed by both techniques. The second method involves the attachment of EBV‐producer cells, known to accumulate viral envelope material in their plasma membrane, to EBV receptors. In view of recent evidence indicating an association between EBV and complement receptors, human and mouse complement were tested for their ability to block this attachment. Fresh mouse and human complement regularly exerted blocking activity, whereas heat‐inactivated human serum did not block. Heat‐inactivated mouse serum did block occasionally, but the effect was more irregular than with fresh mouse serum. Trypsin treatment of the EBV‐receptor column abolished its ability to retain VCA‐positive cells.
Genetics of murine sarcoma virus (msv)—induced tumors in akr mice: Evidence that late progressing and early regressing tumors are controlled by different genes
Authors: Colombatti A. , Chieco‐Bianchi L. , De Rossi A. , D'andrea E. , Collavo D.
Published: February 2007

The genetics of late appearing MSV tumors showing a progressive growth pattern in AKR mice was investigated. The late MSV tumor response in F1 hybrids depended on the genetic background of the non‐AKR parent. Within the 4‐month observation period following virus injection, (CBA × AKR)F1 (DBA/2 × AKR)F1, and (NIH × AKR)F1 developed progressing MSV tumors, which exhibited latency and growth behavior comparable to that seen in AKR mice. (BALB × AKR)F1, (B6 × AKR)F1, and (B10BR × AKR)F1 mice did not show any late MSV tumors. In contrast to early regressing M‐MSV tumors, whose development is independent of Fv‐1 genotype, late MSV tumor progression is largely a function of this gene, since all late tumors which appeared in (B10BR × AKR) × AKR were observed in Fv‐1n homozygous mice. H‐2k haplotype is a further factor in the occurrence of late MSV tumors, at least in (B6 × AKR) × AKR mice. In crosses of AKR with Fv‐1 compatible mice, tumor appearance was strongly associated with inheritance of AKR‐MuLV, and MSV recovered from late tumors of first back‐cross animals appeared to be a new pseudotype with the endogenous AKR‐MuLV. It is suggested that the host genetic control in both early and late MSV tumors is exerted mainly on the helper component of the leukemia‐sarcoma complex.
Morphological transformation of early passage Golden Syrian Hamster embryo cells derived from cryopreserved primary cultures as a reliable in vitro bioassay for identifying diverse carcinogens
Authors: Pienta R. J. , Poiley J. A. , Lebherz W. B.
Published: February 2007

Cryopreserved primary cultures of golden Syrian hamster embryo cells were used as the source of target and feeder cells for establishing an in vitro carcinogenesis bioassay. The primary culture giving the best overall response in a pretest before freezing gave positive results in 20 consecutive experiments when retested with 3‐methylcholanthrene after cryopreservation, indicating that pretested cryo‐preserved cultures can serve as a source of susceptible target cells in an in vitro carcinogenesis bioassay. Similarly prepared and cryopreserved cultures served satisfactorily as feeder cells. Susceptible positive cultures were used to test a large number of carcinogenic and non‐carcinogenic chemicals in this system. The results showed a very high positive correlation (90.8%) between morphological transformation and the reported carcinogenic activity of the chemicals. Transformation was not observed when cells were treated with a few carcinogens that may not be metabolized to their active forms by early passage hamster embryo cells. N‐2‐acetylaminofluorene transformed cells only when tested in the presence of hamster liver micro‐somes. No false positive results were obtained when non‐carcinogens were bioassayed, nor was spontaneous transformation observed in control cultures treated with medium alone, 0.2% dimethylsulfoxide or other solvents. Cultures derived from morphologically transformed colonies arising after treatment of cells with several known carcinogens were tumorigenic in vivo, confirming the correlation of morphological transformation with tumorigenicity and the validity of altered morphology as an in vitro criterion for carcinogenicity in vivo.
Cellular and humoral anti‐tumor immune responsiveness in chickens bearing tumors induced by avian sarcoma virus
Authors: Wainberg M. A. , Yu M. , Schwartz‐Luft E. , Israël E.
Published: February 2007

A systematic comparison was undertaken of the respective abilities of normal chicken embryo fibroblast (CEF) cells, Rous sarcoma virus (RSV)‐ transformed CEF cells, avian Rous sarcoma (RS) tumor cells and murine RS cells to serve as targets and antigen donors in various assays for the detection of cellular and humoral anti‐tumor immunity in chickens bearing tumors induced by Rous sarcoma virus. As measured by a cytotoxicity procedure, avian and murine RS cells were more susceptible to the killing effects of sensitized lymphocytes than were transformed CEF which in turn were more reactive than normal CEF. In contrast, sera from tumor‐bearing animals were able to stain by indirect immuno‐fluorescence only the avian RS and transformed CEF cell types. Extracts of both transformed CEF cells and avian RS cells but not normal CEF were equally effective as inhibitors of migration of peritoneal exudate cells derived from tumor‐bearing animals. Transformed CEF were found to produce far higher quantities of transforming virus progeny than avian RS cells, although the latter were apparently able to synthesize defective viral particles. These data indicate the significant variations which may occur under experimental conditions, depending on the types of assays and target cells employed.