bluuebunny/crossref_metadata_2025 huggingface dataset:
Antibody reactions to herpesvirus saimiri (HVS)‐induced early and late antigens (EA and LA) in HVS‐infected squirrel, marmoset and owl monkeys
Authors: Klein George , Pearson Gary , Rabson Alan , Ablashi Dharam V. , Falk Lawrence , Wolfe Lauren , Deinhardt Friedrich , Rabin Harvey
Published: February 2007

Vero cells were infected with Herpesvirus saimiri. Early (EA) and late (LA) viral antigens were distinguished by inhibiting viral DNA synthesis with cytosine arabinoside (Ara C), or allowing it to proceed uninhibited until CPE was visible. The difference in the antigenic specificity of EA and LA was confirmed by direct fluorescence tests, in combination with blocking experiments. Sera that were anti‐EA positive according to the indirect test were capable of blocking the EA staining reaction with direct EA+‐ conjugates, whereas anti‐LA+EA— sera were unable to do so. Healthy adult squirrel monkeys had antibodies to late antigens (LA) but not to early antigens (EA), as judged by immunofluorescence tests. Isolation‐reared, antibody‐free squirrel monkeys responded with anti‐EA and anti‐LA antibodies after HVS inoculation. Uninoculated, cage‐mate squirrel monkeys became infected by horizontal transmission and responded with LA and EA antibodies approximately 2 months after being housed together with the infected animals. Simultaneously isolated controls remained antibody‐free. HVS‐inoculated, tumor‐bearing marmoset and owl monkeys developed antibodies to both LA and EA in the majority of the cases studied, although in some owl monkeys there was only LA and no EA antibody development. Two different patterns of EA staining could be distinguished, trabecular and punctate. There was a conspicuous difference between the species with regard to the timing of antibody development. Squirrel monkeys, the natural host species of the virus, but resistant to its oncogenic action, responded with antibody development within 14–17 days after inoculation. Marmoset and owl monkeys did not respond until 28–80 days. Conceivably, the natural host species has been selected for a high degree of genetic responsiveness against virus‐determined antigens. This may be partly or entirely responsible for its resistance to the oncogenic effect of this virus.
New antigens in cells transformed by the SV40 virus. III. Presence of an SV40‐coded antigen on the surface of different cell lines transformed by this virus
Authors: Duthu‐Herbet A. , Kress M. , Saint Cyr Ch. De Vaux
Published: February 2007

The sera of hamsters carrying tumours induced by injection of TSV5Cl2 cells and the sera of animals immunized with these cells or with SV40 itself or its purified capsids have a slow cytotoxicity activity in the presence of fresh guinea pig complement on SV40‐transformed cell strains of any origin. The responsible antigen is dependent on the SV40 genome and is associated with the cytoplasmic membranes of the transformed cells. By means of absorption of the antisera with subcellular fractions it has been correlated with antigen “C” present in the cytoplasm of SV40‐transformed cells. It is different from antigen “S” shown by the immunofluorescence test, and its relation with TSTA is discussed.
Expression of the major group‐specific antigen (GS‐A) of avian type‐C viruses in normal chicken cells and tissues
Authors: Vaheri Antti , Ruoslahti Erkki
Published: February 2007

The major group‐specific antigen (gs‐a) of avian type‐C viruses was detected by radioimmunoassay in all tissue samples and cultured cells from leukosts‐free chickens. Visceral tissues of individual embryos contained 7–36 ng antigen per mg protein. The mean values in adult tissues were 2–5 times lower than those of the embryos, except for spleen which gave exceedingly high values of about 50 ng per mg protein. The identity of the endogeneous gs‐a with viral gs‐a was established by several criteria. The gs‐a levels of tissues and cells producing avian type‐C viruses were 100–1,000 times higher. In such cells up to 1% of cellular protein can be gs‐a. Differences in expression of gs‐a and other malignancy‐associated proteins in normal tissues may prove useful indicators of loosened gene regulation as an initial step towards malignancy.
Cell‐surface and virion‐envelope antigens shared by radiation leukemia virus (RadLV) and other murine C‐type viruses
Authors: Ferrer Jorge F.
Published: February 2007

The present studies demonstrate that rats recognize a tumor‐specific transplantation antigen (s) shared by tumors induced by Radiation Leukemia Virus (RadLV), Gross Leukemia Virus (GLV), Moloney Leukemia Virus (MLV) or Moloney Sarcoma Virus (M‐MSV), which is different from the type‐specific transplantation antigen (s) detected by mice. Direct cytotoxic tests and absorption experiments with specific antisera confirm and extend previous studies indicating that rats also form antibodies to a cell‐surface cross‐reacting antigenic determinant present in tumors induced by these viruses. Results ofcytotoxic tests with a monospecific guinea‐pig antiserum for the intraspecies group‐specific (gs‐1) antigen of murine leukemia viruses, suggest that this antigen is present at the cell surface of tumors induced by RadLV, GLV, or MLV, and hence that it may be responsible for the cross‐reactions observed between these tumors in the present study. The data indicate that the rat typing system also recognizes a type‐specific MLV antigen (s) and support the idea that some MLV‐induced leukemias may be superinfected and antigenically converted by GLV. Virus neutralization studies show that rats form antibodies to virion‐envelope antigens shared by RadLV, GLV and MSV.
Sensitivity to ebv superinfection and IUdR inducibility of hybrid cells formed between a sensitive and a relatively resistant burkitt lymphoma cell line
Authors: Nyormoi Okot , Klein George , Adams Alice , Dombos Laszlo
Published: February 2007

The sensitivity of Burkitt lymphoma‐derived cell lines to Epstein‐Barr virus (EBV) superinfection and the inducibility of the latent EBV genome in these lines were studied by somatic cell hybridization. Two non‐EBV producer lines; AG R3, an adherent, 8‐azaguanine‐resistant variant of the Rajiline; and Namalwa, a non‐adherent, 8‐azaguanine‐sensitive line, were fused with the aid of β‐propiolactone‐inactivated Sendai virus. The resident EBV genome in Raji is inducible with 5‐iododeoxyuridine and the line is also sensitive to EBV superinfection. Namalwa is relatively resistant to both super‐infection and induction, and synthetizes surface‐associated IgM‐lambda. Cytological studies showed that hybrid cells appear to be much larger than either parent and attach to culture plates less firmly than the adherent Raji variant parent. Karyological analyses showed that hybrids contain the expected sum of the parental chromosome markers. Membrane immunofluorescence tests also showed that hybrids synthetize IgM. All the hybrid cells appear to be non‐EBV producers, but they are sensitive to both EBV super‐infection and induction of latent EBV. These findings suggest the following explanations: (1) there is no evidence of any complementation between the two non‐EBV producer lines (Raji and Namalwa) to elicit spontaneous EBV production in hybrid cells; (2) Namalwa is deficient in some factors required for the synthesis of EBV‐specified early antigens after EBV superinfection and after induction of latent EBV by IUdR; these factors are supplied by the Raji parent in the hybrids; or (3) Raji, Namalwa and hybrid cells or EBV all produce a substance which inhibits activation of a productive viral cycle, but whose action is antagonized in Raji and hybrid cells to allow the synthesis of EBV‐specific early antigens.
BCG immunotherapy of local subcutaneous growths and post‐surgical pulmonary metastases of a transplanted rat epithelioma of spontaneous origin
Authors: Baldwin R. W. , Pimm M. V.
Published: February 2007

The potential value of BCG immunotherapy in the treatment of pulmonary metastases had been evaluated using a weakly immunogenic transplanted rat epithelioma. Subcutaneous injection of tumour cells in admixture with viable BCG retarded tumour development at this site and reduced the development of pulmonary metastases. Partial control of metastatic disease following surgical removal of subcutaneous tumour was obtained by intravenous injection of BCG, the main response being an increase in survival and reduction in the number of pulmonary metastases. Treatment was not rendered more effective by concomitant immunostimulation with irradiated tumour cells in admixture with BCG. These studies illustrate the potential of BCG adjuvant therapy, but support the concept that localization of BCG at the tumour site is a necessary requirement for effective tumour suppression.
Characteristics of murine C‐type viruses. I. Independent assortment of infectivity in one in vivo and four in vitro assays
Authors: Fenyö Eva Maria , Grundner Gertrud
Published: February 2007

The infective properties of mouse C‐type viruses produced by two Moloney lymphoma lines, mouse L cells (A9 and A9HT sublines) and their hybrids were investigated in one in vivo and four in vitro assays. While differences were found in the ability of the two lymphoma‐derived viruses to convert antigenically JLS‐V9 cells, they were equally efficient in the XC‐plaque test. The same viruses also transformed BALB/3T3 cells, similarly to the virus produced by A9 cells. On the other hand, transformation by the A9 virus was not accompanied by plaque formation on XC cells (except distinct single giant‐cell formation). The reverse situation, positive plaque test without transformation, was also encountered. Whether plaque forming, antigen inducing, or transforming, all viruses were immunogenic. The results indicate that virus released by a given cell line may be detected by one test and not by the other. The characteristic infectivity pattern of a virus produced by a certain cell line remained stable over a period of 7 months.
Transformation of mouse cells infected with akr leukemia virus by benzene‐extract fractions of city air particles
Authors: Rhim J. S. , Gordon R. J. , Bryan R. J. , Huebner R. J.
Published: February 2007

Fractions of benzene extract of particles from city air have been studied for their transforming activity in the AKR leukemia‐virus‐infected NIH Swiss mouse embryo (AKR‐NIH‐ME) cell system. Mouse embryo cells chronically infected with AKR leukemia virus were transformed by benzene smog extracts, most of its fractions, and certain chemicals, whereas uninfected mouse embryo cultures were not transformed. Most of the transformed cells produced tumors when transplanted into newborn NIH Swiss mice. The three neutral fractions: AE0S2 (tetracyclics), AE0S3 (pentacyclics, including benzo(a)pyrene) and AE0S5 (unknown structural type) and two acid, phenol fractions, AE4 and AE4B, had the strongest transforming activity in vitro. One fraction, AE1B(CHCl3 back extract of water washes from AE1) appeared to be inactive in in vitro systems at the concentrations tested.
Reversible splenomegaly with low virus production induced in hyperimmune mice by parabiosis with friend‐virus‐infected mice
Authors: Takizawa Kiyoshi , Yoshikura Hiroshi , Sugano Haruo , Yamamoto Tadashi
Published: February 2007

Ten‐day parabiosis with Friend virus(FLV)‐infected mice induced marked splenomegaly in hyperimmune mice. Infectious center assay showed that only a small fraction of such proliferated spleen cells in the hyperimmune mice were virus producers. In the hyperimmune mice with splenomegaly, no suppression of primary immune response to sheep erythrocytes was induced by FLV infection. The splenomegaly of the hyperimmune mice regressed if the mice were separated from the FLV‐infected partners within 10 days of parabiosis. However, the prolongation of parabiosis in the hyperimmune mice caused an increase in virus‐producing cells, the suppression of primary immune response to sheep erythrocytes, persistent splenomegaly after separation from the FLV‐infected partners, and appearance of typical Friend cells in the spleen.
Expression of fetal antigens and tumor‐specific antigens in SV40‐transformed cells. II. Tumor transplantation studies
Authors: Ting Chou‐Chik , Rodrigues Dennis , Herberman Ronald B.
Published: February 2007

The effect of immunization with fetal antigens and tumor‐specific antigens on the transplantation of SVT2, a BALB/c mouse tumor induced by Simian virus 40 (SV40), has been studied. Hyperimmunization with 5,000 R X‐irradiated, syngeneic fetuses of 1–2 weeks' gestation or syngeneic spleen cells gave no protection to SVT2 cell challenge. In contrast, immunization with SV40 or SV40‐transformed cells gave a 100‐ to 1,000‐fold protection. These results gave additional evidence that fetal antigens are different from tumor‐specific transplantation antigen (TSTA).
Immunological studies of membrane glycoproteins isolated from human breast carcinomas
Authors: Kuo Tseng‐Tong , Rosai Juan , Tillack Thomas W.
Published: February 2007

Glycoproteins were isolated from membrane preparations of human breast cancer using lithium di‐iodosalicylate followed by phenol partition as described for the isolation of CEA from colonic carcinoma. The glycoprotein isolated from breast cancer‐(BCGP) differed from colonic CEA in extraction yield, antigenicity, molecular weight on SDS acrylamide gel electrophoresis and on immunoelectrophoresis. Rabbit anti‐serum raised against BCGP and absorbed with red blood cells and normal breast tissue showed a reaction of identity on Ouchterlony immunodiffusion between BCGP and CEA. However, antiserum to CEA absorbed with red blood cells and normal colonic mucosa showed cross‐reaction of BCGP with CEA. The anti‐BCGP activity in anti‐CEA could be removed by absorption with BCGP, leaving activity directed only against CEA. Therefore, BCGP appears to be a CEA‐like antigen that shares antigenic determinants with CEA and may be responsible for the elevated radioimmunoassays for CEA in breast cancer patients. Whether there is a breast‐cancer‐specific antigen associated with the cell membrane remains to be demonstrated.
Mammary tumor virus (MTV) antigens in normal and mammary tumor‐bearing mice
Authors: Hilgers J. H. M. , Theuns G. J. , Van Nie Robertha
Published: February 2007

Quantitative immunofluorescence tests were used to study MTV‐antigen production in normal and mammary tumor‐bearing mice of two low (BALB/c and C3Hf) and two high (C3H and GR) mammary cancer strains. Mammary tumors could be distinguished on the basis of MTV‐antigen expression in two groups; (1) a group of positive and (2) a group of negative tumors occurring in BALB/c mice. While the tumors of the first group in this study were all adenocarcinomas, the tumors of the second group were adenoacanthomas. MTV‐antigen production was comparatively high in tumors of the C3Hf and C3H strains, as well as in the MTV‐induced tumors of the BALB/c strain, but low in GR‐strain tumors. Sera from mice bearing MTV‐antigen producing mammary tumors (as well as from some pregnant and lactating GR mice) contained excess MTV‐antigens. Spleens of BALB/c mice bearing MTV‐antigen‐induced tumors often contained detectable amounts of MTV‐antigens, while normal and mammary tumor‐bearing C3Hf and C3H mice also occasionally showed detectable amounts of MTV‐antigens in their spleens. In contrast, spleens of GR mice were always MTV‐antigen negative by immunofluorescence absorption tests. Thymuses, livers and kidneys of the various strains tested were invariably negative.
Differences in cytochalasin B inhibition of 3‐O‐methylglucose uptake between BALB/3T3 cells and a murine sarcoma virus transformed clone
Authors: Graff Jon C. , Hanson David J. , Hatanaka Masakazu
Published: February 2007

Cytochalasin B, a mold metabolite, in concentrations of 10 μg per ml, showed a different inhibitory effect on the uptake of 3‐O‐methylglucose between a cell line transformed by the Kirsten strain of murine sarcoma virus, and its non‐transformed parent line. When the overall uptake of 3‐O‐methylglucose by the non‐transformed BALB/3T3 cells in the presence of cytochalasin B was compared to the sarcoma‐transformed cell under the same conditions, it was found that the sugar “infiltrated” into the transformed cells despite the inhibitory effect of cytochalasin B, but not into the control cells. This difference in the infiltration of 3‐O‐methylglucose in the presence of 10 μg/ml of cytochalasin B in the cells occurred despite an almost complete inhibition of the uptake of 2‐deoxyglucose in both cells caused by that same concentration of cytochalasin B. The rate of uptake of 3‐O‐methylglucose was found to be more rapid in the transformed cell line than in the parental, non‐transformed cell line. Neither the increased rate of 3‐O‐methylglucose uptake nor the “infiltration” of the sugar in the presence of cytochalasin B in the transformed cell was caused by a newly induced system for metabolizing 3‐O‐methylglucose. The 3‐O‐methylglucose uptake system was found to be a carrier‐mediated facilitated diffusion system. This system had, at least in part, a common carrier with 2‐deoxyglucose.
A study of herpes simplex type 2 antibody status in groups of patients with cervical neoplasia in Czechoslovakia
Authors: Janda Z. , Kanka J. , Vonka V. , Svoboda B.
Published: February 2007

Sera collected from patients with cervical epithelial atypia, carcinoma in situ and invasive carcinoma, as well as from control subjects, were examined for the presence of HSV‐1 and HSV‐2 antibodies. All these subjects came from one district of Prague. In agreement with results reported from other laboratories, the serological findings indicated that the prevalence of HSV type 2 antibodies was markedly higher in the groups of patients with different stages of neoplastic process in the cervix, than in control groups of comparable age and socioeconomic status. The geometric mean titres for both HSV type 1 and type 2 antibodies were higher in the invasive carcinoma patient group than in other groups of patients.
Influence of interferon on virus particle formation in different oncornavirus carrier cell lines
Authors: Billiau A. , Sobis H. , De Somer P.
Published: February 2007

Three types of oncornavirus‐carrying mouse cell lines were studied. Replication of endogenous sarcoma or leukemia viruses in cell lines producing the infectious viruses was as sensitive to inter feron as that of exogenous vesicular stomatitis virus (VSV). Replication of non‐infectious C‐type virus in S+L− cells which carry a rescuable Moloney sarcoma virus (MSV) genome did not respond to interferon. However, this cell line was also found to be 70 times less responsive to interferon when tested by an exogenous VSV challenge. Finally, after exposure to interferon, M04 cells, which carry a rescuable MSV genome and produce non‐infectious A‐type particles, developed normal resistance to VSV. Yet, high doses of interferon could not prevent the induction of surplus A‐type particles by bromodeoxyuridine (BDU) and dimethylsulfoxide (DMSO). The results are interpreted as indicating that non‐infectious A‐type particles are synthetized by a mechanism different from that by which infectious C‐type particles are generated.
Spontaneous production of a C‐type rna virus in rat tissue culture lines
Authors: Klement V. , Nicolson M. O. , Nelson‐Rees W. , Gilden R. V. , Oroszlan S. , Ronoey R. W. , Gardner M. B.
Published: February 2007

Recently we demonstrated the induction of a C‐type RNA virus (XCIV) in tissue culture line XC derived from Wistar random‐bred rats. In this article two other rat C‐type virus isolates (NRKAV and RPLAV) are described. They were associated with, and isolated from, NRK and RPL lines originating in Osborne‐Mendel and Lewis rat strains, respectively. The main biological characteristics shared by the three viruses were buoyant densities in sucrose gradients in the range of 1.14 to 1.15 g/ml, endogenous DNA polymerase activity, high molecular weight (60 to 70S) RNA, rat major speciesspecific (gs‐1) antigen and gs‐3 interspecies antigen. Two of the isolates (NRKAV and RPLAV) were able to rescue mouse sarcoma virus (MSV) genome from a rat MSV‐transformed non‐productive line. The NRK line was assayed for virus release at various in vitro passage levels. In lower passages (43–73) spontaneous virus release was absent or minimal but the virus could be induced by treatment of cells with 5‐bromodeoxyuridine. At higher passage levels the cells produced a large amount of virus spontaneously, but in these treatment with 5‐bromodeoxyuridine decreased virus production. The results of karyological analysis suggested that clonal selection was taking place in the NRK line during consecutive in vitro passages and simultaneously with the process of increasing spontaneous virus release.
Serum effects on cell‐mediated destruction of rous sarcomas
Authors: Hayami Masanori , Hellström Ingegerd , Hellström Karl Erik
Published: February 2007

A microcytotoxicity test was used to study various effects of serum from tumorbearing and tumor‐free Japanese quails on cell‐mediated destruction of allogeneic sarcomas induced by the Schmidt‐Ruppin strain of the Rous sarcoma virus (SR‐RSV). Spleen cells from quails whose sarcomas had regressed (regressors) were used as the source of immune cells, since they had been previously shown to be cytotoxic to cultivated Rous sarcoma cells. Fourteen of 24 progressor sera (58.3%) gave more than 25% blocking of cell‐mediated cytotoxicity to Rous sarcoma cells when tested at dilution 1:6, and seven of these sera (29.2%) had more than 50% blocking activity. The mean blocking index of all progressor sera was 35.5% at dilution 1:6, and the mean titer of those seven sera which gave more than 50% blocking when diluted 1:6 was 25.6. Six of 18 regressor sera (33.3%) had more than 25% blocking activity at dilution 1:6 and three of them (16.7%) gave more than 50% blocking at that dilution. The mean blocking activity of the 18 regressor sera at dilution 1:6 was 16.9%, and the mean titer of the three sera which gave more than 50% blocking at that dilution was 22.8. Absorption of progressor sera with cultivated Rous sarcoma cells, but not with normal quail fibroblasts, decreased their blocking activity. Some sera from normal quails decreased the cytotoxic effect of immune spleen cells. The blocking effect of these sera was less, however, than that seen with progressor and regressor sera, and it was not removed by absorption with tumor cells. None of nine sera from bursectomized regressors was blocking at dilution 1:6, while a blocking effect was detected with three out of four sera from bursectomized progressors. The blocking effect of sera from bursectomized progressors could not be removed by absorption with Rous sarcoma cells. Its titer was lower than that of concomitantly tested progressors with intact bursa. Furthermore, sera from bursectomized progressors did not block when tested by pre‐incubation with the target cells. Four of 10 regressor sera tested could abrogate the blocking activity of progressor sera and, hence, were characterized as unblocking. On the other hand, none of five sera from bursectomized regressors had any unblocking effect. Some diluted sera from regressors, from bursectomized regressors and from progressors conferred a cytotoxic activity on normal spleen cells (“arming” effect). In addition, some sera, particularly from regressors (normal or bursectomized), potentiated the cytotoxic effect of regressor spleen cells.
The delayed rejection of tumors formed from the administration of tumor cells mixed with killed corynebacterium parvum
Authors: Likhite Vilas V. , Halpern Bernard N.
Published: February 2007

The effect of killed Corynebacterium parvum was studied on two different tumors; the syngeneic CAD2 mammary adenocarcinoma. transplantable only in DBA/2 mice and the Shay chloroma carried in outbred albino rats. The results show that if killed C. parvum is mixed with the tumor‐cell inoculum, the formed solid tumors undergo rapid rejection beginning 2 weeks later in both animal systems. The animals remain tumor‐free and are protected against challenges of large doses of the same tumor cells, a protection that can be eventually overwhelmed when the challenge dose is massive. Histological sections of tumors from similarly inoculated animals revealed minimal necrosis and infiltration with macrophages and lymphocytes. Groups of tumor‐inoculated animals receiving intraperitoneal injections of killed C. parvum alone or with killed tumor cells demonstrated an inhibition of tumor growth when compared to similar animals receiving saline. An enhancement of tumor growth was observed in animals receiving injections of killed tumor cells alone.
The histogenesis of tumours induced in golden hamsters by murine sarcoma virus‐harvey (MSV‐H)
Authors: Hallowes R. C. , Chesterman F. C. , West D. G.
Published: February 2007

Newborn golden hamsters were inoculated subcutaneously with a cell‐free filtrate of cultured mouse 3T3 cells infected with murine sarcoma virus‐Harvey (MSV‐H). An electron microscopical study was made of the lesions that subsequently developed in these hamsters. Two weeks after inoculation, cysts developed eccentrically in the hila of lymph nodes draining the inoculation site. Type H (radial) virus‐like particles were seen in the endothelial cells that lined the cysts and in the serous fluid that filled the cysts. During the 3–6 weeks after inoculation, nodules appeared in lymph nodes, subcutaneous and muscle fascia. They were composed of pleomorphic cells that interlocked with each other and resembled the fixed phagocytic histiocytes of normal lymph nodes. The pleomorphic interlocking cells infiltrated and replaced lymph nodes and perinodal tissues. Some lymph nodes were replaced by abnormal mast cells. During the 12–24 weeks after inoculation tumours were found that involved the paws or limb muscles. The predominant cells in these tumours were similar to the pleomorphic interlocking cells seen in early developing lesions. Similar cells were also found in lymph nodes draining the tumours. It is concluded that tumours induced in golden hamsters by MSV‐H are mesenchymal tumours of histiocytic origin.
Tumour metastasis in mice with reduced immune reactivity. I. Studies with two MCA‐induced sarcomas in radiation and thymectomized radiation C57BL/6J chimeras
Authors: Boeryd Bernt , Suurküla Mart
Published: February 2007

Spontaneous metastasis formation from two MCA‐induced sarcomas with different degrees of antigenicity was studied in radiation and thymectomized radiation C57BL/6J chimeras. The immune reactivity of the thymectomized chimeras was tested with one of the tumours and it disclosed no specific immune response. Tumour growth was decreased in the chimeras. Spontaneous metastasis formation was not influenced in either of the tumours by the immune suppressive treatment. The results could mean that immune factors have no influence on metastasis formation in the two systems tested, or that the immune suppressive treatment might not have influenced an interplay between presumed facilitating and inhibiting immune factors.
Wide host range of murine sarcoma virus
Authors: Rhim Johng S. , Vernon Mina L. , Duh Fuw G. , Huebner Robert J.
Published: February 2007

Cultures of canine, rabbit, porcine, avian, feline, bovine, simian and human origin were tested for their susceptibility to the Kirsten murine sarcoma virus (Ki‐MSV). Data indicated that Ki‐MSV replicates and transforms the cultures of canine embryo, rabbit kidney, porcine kidney, feline embryo, bovine embryo and human tumor cells. These morphologically altered cells contained infectious virus and group‐specific (gs) complement‐fixing (CF) antigen characteristic of viruses of the murine sarcoma‐leukemia complex. The infected cultures produced type‐C virus particles. RNA‐dependent DNA polymerase activity was also demonstrable in the altered cells. The present results indicate that members of the murine sarcoma‐leukemia virus complex, particularly Ki‐MSV, exhibit a wider host range than was hitherto believed.
Viral‐related DNA sequences before and after transformation by RNA tumor viruses
Authors: Goodman N. C. , Ruprecht R. M. , Sweet R. W. , Massey R. , Deinhardt F. , Spiegelman S.
Published: February 2007

Marmoset monkey fibroblasts transformed by non‐indigenous RNA tumor viruses (RSV or FeSV) acquire viral DNA sequences not present in normal cells. The newly gained sequences are always related to those of the transforming virus, a result in agreement with the proviral hypothesis. In contrast, the nucleic acid of the indigenous simian RNA tumor virus, SSV‐1, exhibits partial homology with the DNA of normal marmoset fibroblasts as well as with SSV‐1‐transformed cells. Since a similar situation has been observed with avian and lower mammalian systems, it would appear that homology with normal cellular DNA can be used to provide a tool for determining the species of origin of newly isolated RNA tumor viruses.
Statistical methods for the identification and use of prognostic factors
Authors: Armitage P. , Gehan Edmund A.
Published: February 2007

This is an expository paper which reviews the rationale for determining prognostic factors and the statistical methods for finding and allowing for such factors in the design and analysis of clinical studies. The delineation of prognostic factors in clinical studies is useful: in possibly providing insight into the mechanism of disease; in the determination of stratifications of patients for planning clinical trials; in facilitating the comparison between the outcomes of disease in different groups of patients; in assisting in the allocation of treatment to an individual patient and in permitting remedial action. A response variable is a measure of the future health or illness of the patient and its value is usually dependent on one or more prognostic variables. Statistical methodology for determining prognostic factors is reviewed for the case in which response is dichotomous, continuous or a measure of time (with the possibility of censored observations) and when the predictor variables are discrete or continuous (or a combination of both types). Methods of allowing for known prognostic variables in the analysis of a study are reviewed. These include: grouping of patients according to prognostic variables and comparing treatments separately within each group; covariance analysis and maximum likelihood. Knowledge of prognostic factors is useful in defining a control group which is to be compared with a treated group in non‐randomized studies. Three examples of studies designed to elucidate prognostic factors are described, one each in breast cancer, cancer of the prostate and Hodgkin's disease.
Further studies on the ability of regressor sera to block cell‐mediated destruction of rous sarcomas
Authors: Hayami Masanori , Hellström Ingegerd , Hellström Karl Erik , Lannin Donald R.
Published: February 2007

Previous studies have shown that most sera from Japanese quails with growing sarcomas induced by the Schmidt‐Ruppin strain of the Rous virus (SR‐RSV) can block cell‐mediated destruction of Rous sarcoma cells in vitro, and that sera from some quails whose Rous sarcomas have spontaneously regressed (regressors) also have that ability. Six regressor sera, previously shown to be blocking when added to the mixture of target and effector (=regressor spleen) cells in vitro, were tested for blocking effect at either the target or the effector cell level. Three sera could block only when incubated with the target cells, while three other sera blocked at both the target cell and the effector cell level. Two of three regressor sera which had previously been shown to be unblocking (abrogating the blocking activity of progressor sera when mixed with these in vitro) increased cell‐mediated cytotoxicity at a low dilution (potentiation) but had a slight blocking activity at dilution 1:128–1:512, which disappeared upon further dilution. The blocking effect seen at these dilutions appeared to occur at the target cell level and was not detectable after incubation of the effector cells with serum. After incubation of the target cells for 24 h with one of these two regressor sera diluted 1:256, a blocking activity detectable at the effector cell level appeared in the culture medium. The blocking activity of serum from bursectomized progressors (previously reported) increased, after regressor serum diluted 1:16 had been added to it; at that dilution, the regressor serum had no blocking activity by itself. More concentrated regressor serum, on the other hand, was unblocking, i.e. it decreased the blocking activity of serum from bursectomized progressors. The data are compatible with the hypothesis that the blocking factors operating in this system are complexes between antigens released from the tumor and antibodies formed by the host (and, occasionally, free antigen).
Early chromosome changes in diploid Chinese hamster cells after infection with simian virus 40
Authors: Lehman John M.
Published: February 2007

Primary and secondary Chinese hamster (ChH) embryo cells infected with SV40 exhibited chromosomal changes within one cell generation (24 h). The initial change seen is an increase in the number of polyploid metaphases (>10%). The majority of the polyploid cells are tetraploid (8×), however, higher ploidy values were also observed (16 ×, 32 × and 64 ×). In approximately 20–30% of the polyploid metaphases there were chromosome changes such as breaks, abnormal chromosomes and loss and addition of chromosomes. The remaining polyploids were normal in regard to chromosome number and chromosome morphology. A primary mouse embryo cell system also responded to SV40 infection with an increase in the number of polyploid cells within 48 h.
Kinetics of the anti‐tumor delayed hypersensitivity response in mice with progressively growing tumors: Stimulation followed by specific suppression
Authors: Paranjpe Meera S. , Boone Charles W.
Published: February 2007

At various times during the progressive growth of transplanted SV40 and methylcholanthrene fibrosarcomas in mice the delayed hypersensitivity (DH) response to tumor cells was determined using a quantitative radioisotopic foot‐pad assay. For the first 7 days a close correlation was found between tumor size and the degree of DH reactivity. After this time, as the tumor grew larger, the DH response declined to non‐detectable levels. Following excision of the tumors the DH response returned to a high level. This suppression, or “eclipse”, of the anti‐tumor cellular immune response in animals bearing tumors beyond a certain size was specific for the types of tumor used. The spleen lymphocytes from unresponsive tumor‐bearing mice still supported a positive DH reaction when mixed with tumor cells and injected into the foot‐pads of normal mice.
Oncornavirus‐like particles in HeLa cells. II. Immunological characterization of the virus
Authors: Bauer Heinz , Daams Johan Hendrik , Watson Kenneth F. , Mölling Karin , Gelderblom Hans , Schäfer Werner
Published: February 2007

An oncornavirus‐like agent has been described in HeLa cells of human origin (Gelderblom et al., 1974). The investigation of its protein constituents revealed a pattern similar to but different from that of known oncornaviruses. Six polypeptides with molecular weights (mw) between 12,000 d and 28,000 d, and two glycopolypeptides of about 60,000 d and 80,000 d mw were detected by SDS‐polyacrylamide gel electrophoresis. No serological cross‐reaction was found between the HeLa virus and B‐ and C‐type oncornaviruses. Essentially, none of two interspecies‐specific antigenic determinants described in mammalian C‐type viruses has been detected in the HeLa virus. However a distinct serological relationship was found between the HeLa virus and the Mason‐Pfizer monkey virus in that these viruses share at least two antigens in the mw range of 16,000 d and 28,000 d, respectively. These results confirm the electron microscopic data described before (Gelderblom et al., 1974) and extend the evidence for a new group of oncornavirus‐like particles.
The importance of dose and proliferation of sv40‐transformed cells with different oncogenic potentials to the level of tumor immunity
Authors: Stillström J.
Published: February 2007

The immunizing effects of syngeneic SV40‐transformed mouse embryo cells derived from a cloned line, ME1 C9, were studied. The number of initially inoculated cells was of decisive importance for immunization when both irradiated and non‐irradiated (proliferative) cells were used. The 50% immunizing dose (ImD50) of highly oncogenic ME1 C9‐V15 cells against a weak challenge 3 weeks after immunization was found to be 104.1 irradiated or 102.7 non‐irradiated cells. Doses just below the ImD50 suppressed immunity; 104 irradiated cells had a tumor‐enhancing effect 3 weeks after but not 10 weeks after inoculation and 102 non‐irradiated cells did not significantly immunize until 6 weeks after inoculation, in spite of growing tumors. An immune state was reached more rapidly after resection of tumors induced by 102 cells, even when resections were performed at a time when the animals were still non‐immune. The immune suppression induced by a low dose of non‐irradiated (proliferating) cells seemed to be perpetuated and 10 weeks after inoculation there was still an immune deficit in comparison with the state of immunity in animals which had had their tumors resected. A second inoculation of a regularly non‐immunizing dose of 101‐102 cells 3 weeks after inoculation of 102 ME1 C9‐V15 cells enhanced the tumor incidence of the first inoculated cells. After inoculation of 105 irradiated or non‐irradiated ME1 C9‐V15 cells a one thousand‐fold increase in tumor resistance was obtained within 3 weeks. Before reaching a size of 12 mm the tumor mass did not affect the level of immunity in animals inoculated with ME1 C9‐V15 cells. Tumor resections 3 weeks after inoculation of 105 cells preserved the otherwise declining immunity. The ImD50s of weakly oncogenic (TPD50 > 105) and highly oncogenic (TPD50 < 104) non‐irradiated cells in irradiated animals against a weak challenge 10 weeks after immunization were 102.6 and 101.5 cells, respectively, measured in tumor‐free animals. Immunization doses of 101‐102 weakly oncogenic cells, i.e. below the ImD50, enhanced challenge tumor takes. Non‐tumor‐bearing animals inoculated with weakly oncogenic cells were less immune than non‐tumor‐bearing animals inoculated with highly oncogenic cells, when animals inoculated with equal numbers of cells or animals inoculated with greater than immunizing doses were compared. Animals with tumors induced by weakly oncogenic cells were less immune than animals with tumors of comparable size induced by highly oncogenic cells. The critical tumor size at which immunity against 105 ME1 C9‐V15 cells was broken was 11–12 mm for highly oncogenic and less than 4 mm for weakly oncogenic cells.
Malignant transformation in vitro of mouse fibroblasts by 7, 12‐dimethylbenz(A)anthracene and 7‐hydroxymethylbenz(A)anthracene and by their K‐region derivatives
Authors: Marquardt H. , Sodergren J. E. , Sims P. , Grover P. L.
Published: February 2007

K‐region epoxides derived from 7, 12‐dimethylbenz(a)anthracene and from 7‐hydroxymethlybenz(a)anthracene were tested for their ability to induce malignant transformation of the M2 clone of fibroblasts derived from C3H mouse prostate. The parent hydrocarbons, the corresponding K‐region dihydrodiols and a phenol were also tested with these cells. The K‐region epoxides induced transformation but were somewhat less active than the hydrocarbons; the ring‐hydroxylated derivatives were inactive. In other experiments, the addition of α‐naphthoflavone was found to inhibit the formation of water‐soluble metabolites from and the toxicity of 7, 12‐dimethylbenz(a)anthracene without affecting malignant transformation. The results are discussed in relation to current theories regarding the metabolic activation of polycyclic hydrocarbons.
EB virus‐associated antibodies in caucasian patients with carcinoma OE the nasopharynx and in long‐term survivors after treatment
Authors: de Schryver André , Klein George , Henle Werner , Henle Gertrude
Published: February 2007

Sera from 30 Swedish patients with nasopharyngeal carcinoma (NPC) collected before or shortly after commencement of therapy and from 24 long‐term survivors (LTS) were tested for antibodies to Epstein‐Barr virus (EBV) capsid antigens (VCA), to the O and R components of the EBV‐induced early antigen (EA) complex, and to EBV‐determined cell membrane antigens (MA). In the tumor‐bearing patients, all serologic reactivities increased overall from stage I to later stages of the disease: that is, with an increase in total tumor burden. In the LTS, who had remained apparently tumor‐free for 3 to 29 years, all reactivities were substantially lower than in the tumor‐bearing patients. While the data agreed in principle with those reported previously for Chinese NPC patients, there were considerable differences with respect to the incidence and titres of antibodies to the D component which, as discussed, might reflect a reduced responsiveness of Caucasian NPC patients or a difference in the distribution of various types of the disease among ethnic groups.
Cell‐mediated mutagenesis of mammalian cells with chemical carcinogens
Authors: Huberman Eliezer , Sachs Leo
Published: February 2007

Chemically non‐reactive carcinogens, such as polycyclic hydrocarbons, have to be metabolized by cellular enzymes in order to exert their biological effects including mutagenicity. Chinese hamster V79 cells can be efficiently mutated from 8‐azaguanine susceptibility to resistance by N‐methyl‐N‐nitro‐N‐nitrosoguanidine. But these cells do not metabolize polycyclic hydrocarbons and were therefore not mutated by these compounds. A system of cell‐mediated mutagenesis with carcinogenic hydrocarbons has been developed, by co‐cultivating V79 cells with lethally irradiated rodent cells that can metabolize the carcinogens. The number of mutations was dependent on the number of metabolizing cells and the carcinogens were not mutagenic when V79 cells were co‐cultivated with non‐metabolizing cells. Inhibition of the hydrocarbon metabolizing enzymes by 7,8‐benzoflavone, inhibited mutagenicity. Cell‐mediated mutagenicity was obtained with the carcinogenic hydrocarbons 7,12‐dimethylbenz (a)anthracene, benzo(a)pyrene and 3‐methylcholanthrene and there was no mutagenicity with the non‐carcinogenic hydrocarbon benz(a)anthracene. The degree of mutagenicity was related to the degree of carcinogenicity and the method detected mutagenicity with 0.1μg/ml. It is suggested that cell‐mediated mutagenesis with human cells should provide a useful system to test for environmental chemicals hazardous to humans that have to be metabolically activated.
Comparison of EBV neutralization tests based on abortive infection or transformation of lymphoid cells and their relation to membrane reactive antibodies (anti‐MA)
Authors: de Schryver André , Klein George , Hewetson John , Rocchi Giovanni , Henle Werner , Henle Gertrude , Moss Denis J. , Pope John H.
Published: February 2007

Epstein‐Barr virus (EBV)‐neutralizing (N) antibodies were determined in human sera by three techniques based on (1) early antigen (EA) synthesis in lymphoblasts (NEA); (2) inhibition of colony formation by lymphoblasts (NICF); and (3) cordblood lymphocyte transformation (NLT). A good correlation was noted between the NEA and NICF titres of 41 sera so tested (r = 0.73). The correlation between NEA or NICF and NLT titres was less pronounced (r = 0.54 and 0.56), possibly because only 22 sera were tested by the last method. Limited to concordant sera, i.e. sera with either both high or both low titres of antibodies to EB viral capsid antigens (VCA) and to EBV‐determined cell membrane antigens (MA), the N titres determined by the three methods showed a good correlation with anti‐MA titres (r = 0.83, 0.80 and 0.68, respectively) as did the few discordant sera with high anti‐MA but low anti‐VCA titres. However, some discordant sera with low anti‐MA and high anti‐VCA titres also showed substantial N titres. The mean anti‐VCA titres were equal in the concordant and discordant groups (553), the anti‐MA (BT) titres were 25 and ⩽ 1.4, respectively, whereas the neutralization titres were 209 (NEA), 204 (NICF) and 523 (NLT) in the concordant, as compared to 128, 74 and 99 in the discordant group. These findings support the view that lymphoblast transformation and EA induction and inhibition of lymphoblast colony formation are induced by the same type of viral particle.
Epstein‐barr virus: Transformation of non‐human primate lymphocytes in vitro
Authors: Falk Lawrence , Wolfe Lauren , Deinhardt Friedrich , Paciga June , Dombos Laszlo , Klein George , Henle Werner , Henle Gertrude
Published: February 2007

Continuous lymphoblastoid cell cultures were established from marmoset (Saguinus sp.), squirrel (Saimiri sciureus), owl (Aotus trivirgatus) and cebus (Cebus apella) monkeys after culturing their peripheral lymphocytes with lethally X‐irradiated cells carrying Epstein‐Barr virus (EBV). Transformation also was achieved by exposing simian lymphocytes to infectious, cell‐free EBV derived from the simian lymphoblastoid cell cultures. Simian lymphocytes were not transformed after exposure to cell‐free EBV derived from HR‐1 cells. The simian cell cultures were similar to cell cultures derived from Burkitt's lymphoma or infectious mononucleosis patients. EBV‐induced early, viral capsid and membrane antigens, intranuclear inclusion bodies and herpesvirus virions were demonstrable in most cultures. Seven cultures were insusceptible to superinfection with EBV and treatment of the cultures with halogenated pyrimidines was relatively ineffective for inducing synthesis of early or viral capsid antigens. All cell cultures had B‐cell characteristics: they produced immunoglobulins but did not form spontaneous rosettes with sheep erythrocytes. Four of six marmoset monkeys, inoculated with EBV‐transformed marmoset lymphocytes, developed antibodies to EB viral capsid antigens and one marmoset inoculated with autochthonous transformed cells also developed heterophile antibodies. Seven marmosets, inoculated with cell‐free EBV derived from HR‐1 cell cultures, developed no detectable levels of antibodies to EBV‐specified antigens or heterophile antibodies. No overt clinical abnormalities were detected in any of the marmosets inoculated with HR‐1 or Kaplan EBV but one of five marmosets inoculated with B95hyphen;8 EBV developed a lymphoma.
Characteristics of murine C‐type viruses. IV. The virus produced by ehrlich tumor cells and its hybrids with mouse L cells
Authors: Grundner Gertrud , Fenyö Eva Maria , Klein Eva
Published: February 2007

The infectious properties of viruses produced by Ehrlich tumor cells (E), the A9 subline of mouse L cells (L), their hybrids (EL0 and EL) and high‐malignant sublines of the low‐malignant hybrid line (ELm) were investigated. The infectivity assays were antigen induction on JLS‐V9 cells, antigenic conversion and focus induction on S + L ‐ cells (D56 subline) and focus formation on BALB/3T3 cells. The E and L viruses, produced by the parental cells, were detected in the JLS‐V9 test but were distinguished in S + L ‐ and BALB/3T3 cells. The L virus was focus‐positive, the E virus focus‐negative (BALB/3T3). For antigenic conversion, the L virus was negative and the E virus positive (D56). The hybrid cell line, tested on several occasions after the hydridization event, produced viruses with characteristics similar to both E and L viruses, regardless of the complete or reduced chromosome numbers. The malignant sublines selected from the hybrid showed preferential loss of the A9 parent‐derived biarmed chromosomes. One of these lines produced virus (ELm) with infective properties similar to those of the E virus. This suggests that the virus produced by a particular cell line is determined by the cell genome. Another malignant subline was found to be negative for production of infectious virus in all three indicator systems.