bluuebunny/crossref_metadata_2025 huggingface dataset:
Cell interactions in adoptive immune rejection of a syngeneic tumor
Authors: Howell Stephen B. , Dean Jack H. , Esber Elaine C. , Law Lloyd W.
Published: February 2007

Studies of adoptive tumor neutralization (the Winn test) in BALB/c mice rendered immune to the Simian Virus 40‐induced tumor mKSA indicate that: a) the reaction is extremely specific; b) there is a very close correlation between immunity detected by the Winn test and the ability of the intact animal to reject tumor; and c) immunity reflected by the 51chromium lymphocytotoxicity assay (CRA) and microcytotoxicity test (MCI) correlate poorly with in vivo resistance to tumor challenge and the Winn test. Investigation of the contribution of the immune donor lymphocytes to the reaction demonstrated that immune thymus‐dependent lymphocytes (T cells) were essential, but other donor cell populations were not. Proliferation of immune donor cells was not required. Recipient T cells do not participate in the reaction. We propose that donor T cells do not attack the tumor directly, but must interact with recipient cells to generate an effector response. Some of the parameters of the postulated cooperative interaction are discussed.
Observations on the type of infection by epstein‐barr virus in peripheral lymphoid cells of patients with infectious mononucleosis
Authors: Rickinson A. B. , Jarvis J. E. , Crawford D. H. , Epstein M. A.
Published: February 2007

Transformation to continuous cell lines has been studied in cultures of peripheral leukocytes from infectious mononucleosis (IM) patients and in co‐cultures of IM leukocytes and foetal cord blood leukocytes of opposite sex. The transformed cells in the co‐cultures were of mixed origin with foetal cells usually predominating. Neutralizing antisera to EB virus markedly reduced or abolished the incidence of transformation in IM leukocyte cultures. This effect was not due to cytotoxicity and followed the pattern seen with cultures where transformation was known to depend on the intercellular transfer of infectious EB virus. The findings suggest that EB virus is harboured in peripheral lymphocytes of IM patients as a non‐productive unexpressed infection which is activated to produce virus in vitro, the particles released then infecting neighbouring cells to give transformed lines. The differences between this mechanism and the one whereby lines arise in culture from the malignant cells of Burkitt's lymphoma are considered, and their significance is discussed.
Increased polyamine concentrations in the cerebrospinal fluid of patients with brain tumors
Authors: Marton Laurence J. , Heby Olle , Wilson Charles B.
Published: February 2007

An automated method for the quantitative analysis of the polyamines putrescine, spermidine and spermine in cerebrospinal fluid (CSF) was used to analyze CSF samples from 37 patients with central nervous system (CNS) tumors and from 13p atients without tumors. The putrescine and spermidine concentrations in the CSF of most patients with tumors, particularly those with glioblastomas or medulloblastomas, were elevated when compared with those of non‐tumor‐bearing patients.
Requirement for cell replication in the fixation and expression of the transformed state in mouse cells treated with 4‐nitroquinoline‐1‐oxide
Authors: Kakunaga Takeo
Published: February 2007

A31‐714 cells, a subclone derived from BALB/3T3, did not produce transformed foci when kept under culture conditions of density‐dependent inhibition after treatment with 4NQO in either the growing or the non‐growing state. The transformation frequency increased to nearly maximum level only when the cells had undergone more than four cell generations after 4NQO‐treatment. Cells which were first kept in a non‐growing state after 4NQO‐treatment, rapidly lost the ability to exhibit transformation even when they were subsequently returned to a growing state. On the other hand, the cells which were allowed one cell replication soon after 4NQO‐treatment retained their ability to produce transformed foci even after being kept in the non‐growing state for as long as 6 days thereafter. These results suggest that one cell generation is required for the fixation of transformation, and more than four cell generations are required for the expression of the transformed state.
Distribution of concanavalin A receptors on normal rat liver cells and zajdela ascites hepatoma cells
Authors: Roth J.
Published: February 2007

The distribution of Concanavalin A receptors in cultures of normal rat liver cells and of Zajdela ascites hepatoma cells of the rat was investigated by the Con A‐po technique (Bernhard and Avrameas, 1971). Con A‐po labelling of the cell surface showed a patchy distribution of Concanavalin A receptors in ascites hepatoma cells, whereas continuous Con A‐po labelling was seen at the surface of normal rat liver cells. The different distribution of Concanavalin A receptors was caused by rapid internalization of Con A‐po labelled material and not by a simple rearrangement of the receptors. The significance of this process is discussed with respect to Concanavalin A receptor mobility and membrane stability after cell transformation.
Neuraminidase‐mediated augmentation of in vitro immune response of patients with solid tumors
Authors: Watkins Elton , Gray Bruce N. , Anderson Leonard L. , Baralt Oscar L. , Nebril Lourdes R. , Waters Margaret F. , Connery Cheryl K.
Published: February 2007

Host blood lymphocytes undergo accentuated blastic transformation when cultured with tumor cells pretreated with neuraminidase. The effect has been observed in 38 patients with such common solid tumors as bronchus carcinoma, skin melanoma, hypernephroma, or adenocarcinoma of the breast, lung, colon, or rectum. Individual response varied but often exceeded response to allogeneic cells. Three patients with glioblastoma of the brain did not respond. Lymphoblastic transformation was not observed in three of four cultures containing benign tumor or in any cultures containing normal tissue analogues of the malignant tumors.

A factor in host blood serum inhibiting lymphoblastic transformation correlated to abnormal elevation of serum‐bound sialic acid. This blocking factor differed in specificity from enhancing antibody or serum blocking complexes described by other investigators. Blocking effects were observed when the tumor‐cell type of a serum donor differed from the cell type of the culture test tumor. Serum with abnormal elevation of bound sialate from a cancerfree human also non‐specifically blocked host response to tumor. The blocking effect could be eliminated by partial enzymatic removal of bound sialic acid from serum glycoproteins.
Cell‐mediated immunity to moloney sarcoma virus in mice. I. Analysis of antigens responsible for lymphocyte stimulation in regressor mice
Authors: Knight R. A. , Gorczynski R. M.
Published: February 2007

Purified viruses, viral antigens, and cell extracts have been tested for their ability to stimulate protein synthesis by MSV‐M1 regressor spleen cells from BALB/c mice. Immune, but not normal cells, responded to MSV‐M, but not to MSV‐G virus1, and to the type‐specific viral envelope glycoprotein from MSV‐M, virus. Extracts of mouse embryo fibroblasts transformed by either MSV‐M or MSV‐G, however, specifically stimulated MSV‐M regressor spleen cells. Cells stimulated by different antigens, and by phytohaemagglutinin, had the same sedimentation profile and were identified as T‐lymphocytes.
Activation of carcinogenic polycyclic hydrocarbons in polyoma‐virus‐transformed cells as a prerequisite for polyoma virus induction
Authors: Huberman Eliezer , Fogel Marian
Published: February 2007

Polyoma‐virus (PV)‐transformed cell clones, which are inducible for virus synthesis by various physical and chemical agents, metabolize the chemically non‐reactive carcinogen benzo (a)pyrene (BP) into water‐soluble products. In cultures of such clones, which metabolize BP to a level of 30–60% of that of normal cells, up to 10.4% of the cells were induced for PV synthesis by BP, 20‐methylcholanthrene (MCA) and 7,12‐dimethylbenz (a) anthracene (DMBA). No PV induction was observed with the non‐carcinogenic polycyclic hydrocarbons pyrene chrysene and benz (a)‐anthracene. A proportion of subclones, isolated from a PV‐inducible clone, which metabolized 0.1 μg or less BP per 106 cells, proved non‐inducible by any of the carcinogenic polycyclic hydrocarbons BP, MCA and DMBA. However, subclones which metabolized more than 0.3 μg BP per 106 cells were all inducible for PV synthesis by these carcinogens. Subclones isolated from an inducible clone pretreated with BP were shown to metabolize less than 0.1 μg BP per 106 cells and were resistant to virus induction by the carcinogenic polycyclic hydrocarbons. Benzoflavone, which inhibited the metabolism of BP in clones metabolizing high levels of this carcinogen, also prevented the induction of PV antigen and infectious virus synthesis in these clones. The data indicate a relationship between the carcinogenicity of polycyclic hydrocarbons and their ability to induce virus in the PV‐transformed cells and suggest that virus induction depends on metabolic conversion of these hydrocarbons into similar reactive compounds that are responsible for malignant transformation and mutagenesis.
Refractoriness of lymph‐node cells from tumour‐bearing animals
Authors: Burk Martyn W. , Yu Samuel , Ristow Sandra S. , McKhann Charles F.
Published: February 2007

In vitro lymphocyte stimulation by mitomycin‐C‐blocked tumor cells has been used to demonstrate tumor‐specific antigens in syngeneic murine systems and to follow the evolution of tumor immunity with the tumor‐bearing state. Mitomycin‐blocked tumor cells stimulated syngeneic lymphocytes from normal mice, from those bearing small tumors (less than 1 cm in diameter) and from tumor‐immune mice, sensitized by tumor‐cell inoculation and subsequent tumor removal, to undergo increased DNA synthesis as measured by the incorporation of tritiated thymidine. However, lymphnode cells from mice bearing tumors over 1 cm in diameter appeared to be maximally stimulated in vivo and incapable of further stimulation by the same tumor cells in vitro. This was reflected by the progressively increasing background levels of nucleic acid synthesis with the length of tumor‐bearing and the size of the tumor. Although lymphnode cells from mice with large tumors did not respond to the same tumor cells in vitro, they did have normal responses to PHA. Within 7–14 days of surgical removal of the tumor, specific lymphocyte responsiveness and background activity returned to previous normal levels, but reinoculation with 106 tumor cells resulted in progressive tumor growth and loss of specific in vitro responsiveness when the second tumor had reached the critical size of 1 cm in diameter. Brief exposure of tumor‐immune lymph‐node cells to a soluble antigen extract of the same tumor resulted in a marked increase in DNA synthetic activity compared to that obtained after exposure to an extract of a different tumor or an extract of normal muscle tissue. Normally responsive tumor‐immune lymph‐node cells, after brief exposure to a different tumor extract, muscle extract or medium alone underwent stimulation when cultured with mitomycin‐blocked tumor cells. However, normally responsive tumor‐immune lymph‐node cells, after brief exposure to a soluble antigen extract of the same tumor, initially underwent increased DNA synthesis, but were incapable of further stimulation by mitomycinblocked tumor cells. Tumor antigen, alone or complexed with antibody, was also demonstrated in the sera of mice bearing large tumors and is thought to be responsible for the refractoriness of lymph‐node cells from these mice to further stimulation in vitro. These experiments demonstrate that tumor size and the consequent antigen load to which the tumor‐bearing animals is subjected have a profound effect on tumor‐specific lymphocyte responsiveness.
Serologic evidence for cross‐reacting antigens in two carcinogen‐induced murine sarcomas
Authors: Fritze D. , Kern D. H. , Waldman S. R. , Pilch Y. H.
Published: February 2007

Serological evidence is presented that two chemically‐induced (by methylcholanthrene and 3,4‐benz (a)pyrene) sarcomas of C3Hf mice contain cross‐reacting tumor‐associated cell‐surface antigens. Xenogeneic and syngeneic antitumor antisera against the two sarcomas were studied with an isotopic, complement‐dependent, antibody‐mediated microcytotoxicity assay and an isotopic antiglobulin test for the detection of antibodies to tumor‐associated antigens, in vitro. Absorptions with various tissues were performed which consistently revealed that the specific activity of the antitumor antisera could be removed by absorption with cells from either chemically‐induced tumor, while absorption with syngeneic normal adult tissues, normal fetal tissues, or cells from a histogenetically unrelated tumor (spontaneous mammary carcinoma) failed to remove any specific activity. In view of the individual character of carcinogen‐induced tumor antigens as detected by tumor transplantation techniques, our results suggest that chemically‐induced murine sarcomas (even when induced by different carcinogens) contain both private and common cell‐surface antigens, the latter detectable by serological methods. These common tumor‐associated antigens may be related to a viral genome involved in the malignant transformation of carcinogen‐induced murine sarcomas.
Demonstration of oncogenic potential of mammalian cells transformed by dna‐containing viruses following photodynamic inactivation
Authors: Li Jui‐Lien H. , Jerkofsky Mary Ann , Rapp Fred
Published: February 2007

The oncogenic properties of hamster embryo cells transformed by herpes simplex virus type 1 (HSV‐1) and type 2 (HSV‐2) and SV40 virus following photodynamic inactivation using neutral red were determined by subcutaneous inoculation into newborn Syrian hamsters. Cells transformed by all three viruses produced palpable tumors after different latent periods. Histopathological examination showed that HSV‐2 tumors were fibrosarcomas and metastases were often seen in the lungs. HSV‐2 primary tumors were reinoculated subcutaneously into weanling hamsters; they developed palpable tumors within 2 weeks. HSV‐specific antigens were detected in the cytoplasm and/or on the surface of both the HSV‐1 and HSV‐2 tumor‐cell cultures by the indirect immunofluorescence technique. The same method revealed SV40 tumor antigen in the nuclei of the SV40 tumor cells. Sera from HSV or SV40 tumor‐bearing hamsters gave positive reactions when tested against HSV‐infected hamster cells or SV40‐infected monkey cells, respectively. These results demonstrate that herpes simplex virus and SV40, whose infectivity was lost following photodynamic inactivation, retained the virus genetic information necessary for transformation of normal cells to an oncogenic phenotype.
Quantitative estimation of mouse mammary tumor virus (MTV) antigens by radioimmunoassay
Authors: Verstraeten A. A. , Van Nie R. , Kwa H. G. , Hageman Ph. C.
Published: February 2007

A radioimmunoassay for the antigens of the mouse mammary tumour virus has been developed. 125Iodine‐labelling of intact virus [derived from mammary tumours of (C3H × 020) F1 mice] followed by ether extraction and separation of the ether and water layers resulted in a separation of the labelled material into two main groups of antigenic components. The intact labelled material from each group was separated from viral debris and other possible contaminants by affinity chromatography. The antigens of the ether phase were proved to belong mainly to the viral nucleoid whereas the water phase contained mainly envelope antigens. No type‐specific antigens could be demonstrated in either of the phases. Radioimmunological assessment of plasma revealed that in the plasma of MTV‐S‐ and MTV‐P‐positive animals viral antigens were only measurable when palpable mammary tumours were present, whereas in MTV‐L‐positive tumour‐bearing animals some negative samples were found. In milk of individual nontumour‐bearing mice a close correlation was found between the expression of viral antigens and the generally accepted presence of virus in the strain of mice. In milk, viral antigen levels tend to increase with parity with a possible decrease after a finite number of pregnancies. In a pilot study the presence of MTV antigens could also be demonstrated in epididymis extracts of male GRS/A mice. Genetical analysis of the low‐virulent MTV‐L by radioimmunoassay of milk is in progress.
Influence of administration route and dosage schedule on tumor response to nitrosoheptamethyleneimine in rats
Authors: Taylor H. W. , Nettesheim P.
Published: February 2007

Nitrosoheptamethyleneimine (NHMI) was tested for carcinogenicity in Fischer‐344 and Sprague‐Dawley rats by intragastric administration and subcutaneous injection. Cumulative doses ranged from 5.5 to 1,200 mg/kg, and dosage schedules ranged from 40 serial administrations to one single injection. No difference in response was seen between sexes or strains of rats. Following the highest carcinogen doses by intragasritc administration, a high incidence of squamous‐cell tumors occurred in the lung. The highest incidence of squamous‐cell tumors occurred in the nasal cavity, trachea and esophagus. Following subcutaneous injection, tumors induced in the lungs were all alveologenic adenomas and adenocarcinomas. The upper respiratory and gastrointestinal tracts were again the most commonly affected sites, with tumors similar to those of the first group. Intragastric administration was more effective in producing tumors than was subcutaneous injection, and administration of multiple small doses was more efficient than single large doses. The results demonstrated that the route and schedule of administration markedly influenced the tumor response to NHMI, both quantitatively and qualitatively.
Classification and biological nature of established human hematopoietic cell lines
Authors: Nilsson Kenneth , Pontén Jan
Published: February 2007

Over 200 established human hematopoietic cell lines of normal and malignant origin have been investigated by morphological and functional parameters. Employing morphology as the overriding parameter four types of lines were identified. (1) Lymphoblastoid cell lines, derived from normal and neoplastic hematopoietic tissue, were characterized by the wide morphologic flexibility of individual lymphoblastoid cells, constant association with Epstein‐Barr virus (EBV), polyclonal derivation, differentiation for immunoglobulin production (secretion) and their diploids. (2) Lymphoma cell lines. This type of line was established at a high frequency from Burkitt's lymphoma and rarely from other types of lymphoma, but never from patients without malignancy or with non‐lymphoma malignancies. Important characteristics were morphologic stereotypia within each line, monoclonal derivation, common but not obligatory association with EBV, variability in the expression of Ig synthesis (no production, or membrane bound Ig, or secretion) and aneuploidy. (3) Myeloma cell lines could only rarely be obtained from patients with myeloma. The basis for classification of these lines is their production of Ig identical to the myeloma protein in vitro. Other important distinguishing features were: plasma cell morphology, absence of EBV and aneuploidy. (4) The leukemia cell line (MOLT 4) was the only line with T‐cell characteristics and was easily distinguished from the other types. Important characteristics were a typical surface ultrastructure, absence of EBV and absence of immunoglobulin production. Individual lymphoblastoid lines were in principle identical whereas each line of the other three types had its own characteristic profile. The phenotypic characteristics of the lymphoblastoid lines were very stable during prolonged serial cultivation. Only in a few cases were secondary chromosomal, functional or morphologic alterations noted. We conclude that EBV‐carrying lymphoblastoid lines can be obtained from non‐neoplastic precursor cells from healthy as well as from diseased individuals. Lymphoma, myeloma and leukemia lines are only obtained from the respective neoplastic tissue but generally at a low frequency. With the exception of Burkitt's lymphoma, malignant hematopoietic tissue and leukemia frequently give rise to established cell lines in vitro of the lymphoblastoid type rather than lines derived from the neoplastic cells.
Lymphoblastoid transformation and kinetics of appearance of viral nuclear antigen (EBNA) in cord‐blood lymphocytes infected by epstein‐barr virus (EBV)
Authors: Yata J. , Desgranges C. , Nakagawa T. , Favre M. C. , De‐Thé G.
Published: February 2007

Human cord‐blood lymphocytes were infected with B95.8 Epstein‐Barr virus (EBV) before and after separation into B‐ and T‐cell populations. Lymphoblastoid cells exhibiting B‐cell characteristics appeared after 2 to 3 days of culture in the total population and in the separated B‐cell subpopulation but not in the T‐cell subpopulation. EBV nuclear antigen (EBNA) was detected concurrently with the appearance of lymphoblastoid cells. The proportion of EBNA‐positive cells corresponded to that of lymphoblastoid cells, and reached 50% after 4 days. EBNA was present only in cells with B‐cell markers. These observations indicate that only B‐cells are susceptible to EBV infection, that the transformation occurs within a few days and that EBNA is a valid early marker for susceptibility to EBV transformation.
Studies on a gross‐virus‐induced lymphoma in the rat. II. The role of cell‐membrane‐associated and serum p30 antigen in the antibody and cell‐mediated response
Authors: Knight R. A. , Mitchison N. A. , Shellam G. R.
Published: February 2007

The internal viral protein, p301, has been identified by cytotoxicity tests using xenogeneic sera, on MuLV‐G‐induced rat lymphoma cells. In this system internal virion antigens, and in particular p30, are cytotoxic target antigens for syngeneic antibody and cell‐mediated cytotoxicity; p30 is also present in the serum of rats with progressively growing lymphomas, and is the principal antigen responsible for the inhibition of cell‐mediated cytotoxicity produced by these sera.
Cellular basis for the immune response to methylcholanthrene‐induced tumors in mice. Heterogeneity of effector cells
Authors: Kearney R. , Basten A. , Nelson D. S.
Published: February 2007

Immune resistance to methylcholanthrene‐induced tumors has two phases, an early specific and a late non‐specific phase. Both phases were found to be T‐cell‐dependent in vivo. Thus, adult thymectomized, irradiated, bone‐marrow‐protected mice bearing H‐1 tumor isografts showed impaired resistance to challenge with homologous (H‐I) and heterologous (H‐3) tumor cells. In each case resistance was restored by injection of thymus cells. In vitro analysis of the cellular basis of resistance revealed that different mechanisms were involved in the two phases. The cytotoxic effect of immune spleen cells taken during the early specific phase was inhibited by pretreatment with anti‐θ serum and complement and by removal of macrophages. Neither procedure, however, interfered with the cytotoxic potential of immune spleen cells taken during the late non‐specific phase of immunity. Passage of immune spleen cells through rabbit‐IgG anti‐mouse immunoglobulin‐coated columns (which yielded a T‐cell‐enriched, B‐cell‐depleted population) resulted in abrogation of cytotoxicity whether the cells were obtained during the early or the late phase of resistance. The inability of late‐phase spleen cells to kill was explicable in terms of B‐cell removal since T‐cells and macrophages had been shown to be ineffective at that time. In contrast, the failure of column‐treated cells from the early phase to kill was found to be due to removal of adherent cells rather than B‐cells since cytotoxicity (1) was abrogated by passage through control columns coated with rabbit‐IgG anti‐sheep red blood cell antibody which did not retain B‐cells and (2) could be restored by addition of immune macrophages (from anti‐θ serumtreated spleens). Taken together, these results indicate that the cellular basis of immune resistance to methylcholanthrene‐induced tumors is heterogeneous. The early specific phase seems to be mediated by an interaction between T‐cells and macrophages; the late non‐specific phase, although T‐cell dependent in its induction, depends on a different effector mechanism, possibly involving a cell or its products of the B lineage.
Effect of cordycepin on the replication of type‐c rna tumor viruses
Authors: Richardson L. S. , Ting R. C. , Gallo R. C. , Wu A. M.
Published: February 2007

Cordycepin (3′‐deoxyadenosine) was previously shown to inhibit virus production induced by iododeoxyuridine from murine fibroblasts (Wu et al., 1972). We now report that the inhibitory effect of cordycepin results in a reduction of the number of cells producing virus as measured by the infectious center assay and fluorescent antibody technique. Cordycepin has a much greater inhibitory effect on viral replication than on transformation of normal rat kidney cells by murine sarcoma virus since viral production was greatly reduced (seven‐ to 35‐fold) with 5–10 μg/ml of cordycepin while viral transformation was only slightly inhibited (two‐fold reduction in focus‐forming units) with the same concentration of cordycepin. Inhibition of viral production is most effective if the compound is present during the first 24 h after infection.
Distinction between tumor‐specific transplantation antigen and virion antigens in solubilized products from membranes of virus‐induced leukemic cells
Authors: Chang Kenneth S. S. , Law Lloyd W. , Appella Ettore
Published: February 2007

A membrane antigen from RBL‐5 leukemic cells that was solubilized and partially purified is further characterized in this study. This soluble antigen is capable of immunizing syngeneic hosts to reject neoplastic cells and thus resembles TSTA. It also induces cytotoxic antibody in syngeneic hosts capable of specifically lysing RBL‐5 cells in vitro. RBL‐5, however, releases infectious virus (RLV); it was necessary therefore to rule out virus or structural virion antigens as the effective immunogen. Infectious virus was not detectable in our initial crude membrane (CM) material, nor in the papain‐solubilized CS or the G‐150 Sephadex‐chromatographed fraction. Virus‐neutralizing antibody was not detected, under stringent assay conditions, in the syngeneic anti‐CM sera. Antigen preparations CM, CS and the chromatographed fractions F1, F2 and F3 were assayed in a complement‐fixation test against broad‐reacting antisera capable of detecting virus envelope antigen and gs antigen and against syngeneic antisera. Although our antigen preparations were positive for virion antigens. CS and F2 contained an antigen that reacted only with syngeneic antiserum. These same fractions were those reactive as immunogens. On the basis of these data, it is postulated that a cellular membrane component, other than viral, functions as TSTA.
Activation of c‐type viruses during skin graft rejection in the mouse. Interrelationships between immunostimulation and immunosuppression
Authors: Hirsch Martin S. , Ellis David A. , Kelly Ann P. , Proffitt Max R. , Black Paul H. , Monaco Anthony P. , Wood Mary L.
Published: February 2007

Both mouse‐tropic and zenotropic C‐type RNA viruses were activated in BALB/c mice during rejection reactions against skin grafts from mice differing at the major histocompatibility locus (A/J) or sharing this locus (DBA/2). Animals that maintained their skin grafts following immunosuppression with antilymphocyte serum (ALS) or cyclophosphamide had a much higher incidence of virus‐positivity than animals that did not receive ALS or cyclophosphamide, or that rejected their skin grafts despite immunosuppressive therapy. ALS itself activated type‐C viruses from a small proportion of BALB/c mice whereas cyclophosphamide alone did not. Type‐C viruses were detected in spleens and regional nodes draining skin‐graft sites between 1 and 2 weeks following transplantation; thereafter they reached maximum titers in spleens. Viruses were not detected at skin‐graft sites, in tails or in thymuses of grafted animals. Virus activation was associated with splenic histological changes consisting of germinal center formation, diffuse hyperplasia of reticulum cells, depletion of periarteriolar lymphocytes and hyperplasia of red pulp hematopoietic elements.
Eb virus‐associated nuclear antigen production and cell proliferation in adult peripheral blood leukocytes inoculated with the qimr‐wil strain of eb virus
Authors: Moss D. J. , Pope J. H.
Published: February 2007

A nuclear antigen, apparently the Epstein‐Barr virus (EBV)‐associated nuclear antigen (EBNA), was detected by anticomplement immunofluorescence (ACIF) tests in adult human peripheral blood leukocytes infected with the QIMR‐WIL strain of EBV. EBNA was not detectable at 24 h but appeared in about 11% of the cells by 3 days, and by 5 days up to 64% of the cells were positive. Proliferation of EBNA‐positive cells at this stage was confirmed by autoradiography. There was a good correlation between the concentration of virus and the number of EBNA‐positive cells in the first 5–7 days. The subsequent course of events was found to be influenced by the initial cell concentration and the time of subculture. EBNA production was delayed in cells infected with higher dilutions of virus but subsequently appeared in a high proportion of cells. Indirect immunofluorescence failed to detect viral capsid antigen (VCA) or early antigen (EA) by 10 days. The results show that EBV infection was abortive and that the critical events of viral transformation occurred within the first few days.
Helper specificity for retrieval of defective friend virus
Authors: Howard Fieldsteel A. , Kurahara Carole , Dawson Peter J.
Published: February 2007

A Friend virus‐induced reticulum‐cell sarcoma from BALB/c mice has been cultivated in vitro in our laboratory for more than 11 years and contains no detectable evidence of virus. However, Friend virus could be retrieved readily from the tissue cultures by any of several lymphatic leukemia viruses belonging to the Friend‐Moloney‐Rauscher (FMR) group, as long as the helper viruses were actively replicating in a culture. Helper activity appeared to be highly specific and limited to the FMR group including the B‐tropic Tennant leukemia virus which produced a B‐tropic Friend virus pseudotype. The naturally occurring type AKR murine leukemia viruses and the related Gross passage A virus failed both in vivo and in vitro to retrieve the Friend virus genome from the virus‐free tumor cells.
Transplantable murine tumors release mouse‐tropic and xenotropic type‐c viruses
Authors: Lieber Michael M. , Sherr Charles J. , Todaro George J.
Published: February 2007

Transplantable mouse tumors used in many areas of cancer research generally produce several host‐range classes of infectious type‐C virus. The release of virus from such tumors should be considered in the design and evaluation of experiments in which they are used.
Competition radioimmunoassay for mason‐pfizer monkey virus: Comparison with recent isolates
Authors: Yeh Jen , Ahmed Mumtaz , Lyles Joan , Larson David , Mayyasi Sami A.
Published: February 2007

The major core protein of Mason‐Pfizer monkey virus was purified by DEAE ion exchange column chromatography and shown to be 27,000 daltons (p27). Following the characterization of monospecific antisera prepared against p27, a radioimmunoassay was developed with these reagents and competition experiments were done with some of the recent M‐PMV‐like isolates as well as with other oncornaviruses. Results suggest that three of the viruses tested, AO, X‐381 and FTP‐1, are similar to M‐PMV while J‐96 virus is related, but not identical, to M‐PMV. It is also shown that competition RIA can be used successfully to detect the presence of viral proteins in tissue homogenates and cell extracts.
Cancer of asians in kenya
Authors: Chopra S. A. , Linsell C. A. , Peers F. G. , Chopra F. S.
Published: February 2007

The frequency of various cancers among Indian immigrants in Kenya was compared to corresponding data among native Africans and Indians in the regions of India from which most of the studied population originally migrated. The Kenyan Indians do not have the cancer pattern of their home country nor do they have the cancer pattern of indigenous Africans. They have instead, like Europeans and North Americans, a higher risk of cancer of the lung, breast and the large intestine. It is suggested that this is related to environmental factors and variations in living habits.
Prostaglandin synthesis inhibition: Effect on bone changes and sarcoma tumor induction in balb/c mice
Authors: Strausser Helen R. , Humes John L.
Published: February 2007

An increase in prostaglandins (PGs) of the E series has been demonstrated in Moloney sarcoma virus (MSV)‐induced leg tumors of 6‐week‐old BALB/c male mice. The level of the hormone has been shown to increase with the tumor diameter and decrease with tumor regression. At the peak of tumor size the tibial bones of the mice were considerably deformed, suggesting osteoclastic activity. The systemic calcium level was not elevated, indicating possible release of calcium into the local tumorous area. In mice treated with indomethacin the tumors failed to develop and PG levels were markedly lower. Tibial bones of treated mice were similar in appearance to those of control, non‐tumorous mice. PG levels of DBA/1J mice bearing extensive Cloudman S91 melanomas were not elevated and no bone deformation was seen. When contrasted with studies of immuno‐depressed mice the results suggest that indomethacin acted in conjunction with and possibly to restore the PG‐induced depression of the immune system in preventing tumor development. It is also hypothesized that indomethacin, by suppressing the PG‐mediated calcium release from bone, could be operative in inhibiting tumor growth.
Establishment of a continuous tumor‐cell line (PANC‐1) from a human carcinoma of the exocrine pancreas
Authors: Lieber Michael , Mazzetta Joann , Nelson‐Rees Walter , Kaplan Michael , Todaro George
Published: February 2007

An epithelioid cell line, started from a human pancreatic carcinoma of ductal cell origin, has been maintained in culture for over 2 years and has been subcultured more than 40 times. The PANC‐1 cell line has a doubling time of 52 h and G6PD activity of the slow mobility or B type. Chromosome studies show a modal number of 63 with three distinct marker chromosomes and a small ring chromosome. The malignant nature of the PANC‐1 cell line was verified by: (1) the ready growth of PANC‐1 cells in soft agar and on top of a fibroblast monolayer; and (2) the formation of a progressively growing anaplastic carcinoma after injection of a nude‐athymic mouse with PANC‐1 cells.
Epstein‐Barr virus‐induced cap formation in human lymphoblastoid cells
Authors: Hinuma Yorio , Suzuki Masahiro , Sairenji Takeshi
Published: February 2007

Redistribution and consequent cap formation of Epstein‐Barr virus adsorbed to human lymphoblastoid cells were studied by indirect membrane immunofluorescence carried out at 0° C. When EBV was adsorbed on cells at 0° C, the cell sur face fluorescence had a mostly ring‐like pattern. However, the ring cells could be transformed into cap cells when warmed at 37° C. This cap formation could be induced by EBV alone without participation of antibodies involved in the immunofluorescence procedure. The cap formation was temperature‐ and pH‐dependent, and was reversibly inhibited by sodium azide or some sugars. Thus the EBV‐induced cap formation was analogous to that induced by antibodies or ligands on other lymphoid cells.
Murine sarcoma virus related nucleic acid sequences in a non‐transforming virus derived from an interspecies pseudotype sarcoma virus
Authors: Okabe Hiromi , Gilden Raymond V. , Hatanaka Masakazu
Published: February 2007

A number of sarcomagenic viruses recovered from hamster tumors induced originally by Moloney sarcoma virus or several of its mouse pseudotypes appear to be interspecies pseudotypes with structural proteins of hamster type‐C viruses and nucleic acid sequences of both mouse and hamster specificity. A non‐transforming virus (GLOH−) recovered from a sarcomagenic virus preparation obtained from a tumor induced by the Gross pseudotype of Moloney sarcoma virus was previously shown to retain mouse sequences. The ability to discriminate readily between Gross and Moloney viruses by molecular hybridization, especially with regard to thermal stability of inter‐strain hybrid molecules, and the stability of Moloney virus sequences in a rat‐mouse interspecies pseudotype, made it possible to specify that the mouse virus‐specific sequences in GLOH− are derived from Moloney virus and not Gross. Thus, even though GLOH− is non‐transforming in vitro or in vivo, it still retains sequences highly related to Moloney sarcoma virus. The lack of transforming ability is thus probably based on loss or change of specific sequences necessary for transformation at some point in the history of this virus.
Tumour inhibition mediated by BCG in immunosuppressed rats
Authors: Moore Michael , Lawrence Nicola , Nisbet Norman W.
Published: February 2007

Two rat sarcomas (CC5 and P7) which grow progressively on transplantation into normal syngeneic hosts failed to develop when injected in admixture with the Glaxo strain of Bacillus Calmette‐Guérin (BCG). Under comparable conditions, the local development of a third neoplasm (P8) was temporarily inhibited and the number of pulmonary metastases significantly reduced. Experiments were undertaken to determine the extent to which the anti‐tumour action of BCG required an immunocompetent host. Rats were immunosuppressed by sub‐lethal whole‐body irradiation (450 R), with or without prior thymectomy and challenged with inocula of mixed BCG and tumour cells when their capacity to respond to bacterial, tumour and unrelated antigens was maximally depressed. In non‐sensitized immunosuppressed rats, the ability of BCG to limit tumour outgrowth was abrogated only in the case of sarcoma CC5. For this neoplasm, immunogenic in syngeneic hosts by conventional criteria, there was a statistically significant difference in the number of tumours in immunosuppressed rats (51%) compared with non‐sensitized immunocompetent controls (6%). Presensitization to either bacterial or tumour antigens, prior to thymectomy and/or irradiation, fully restored the tumour‐inhibitory capacity of BCG. By contrast, sarcoma P7 was not significantly less susceptible to BCG‐induced regression in non‐sensitized immunosuppressed rats than in non‐sensitized normal rats; and sarcoma P8 similarly failed to reveal any significant differences in susceptibility to BCG affecting primary or secondary tumour development. It is concluded that tumours may vary widely in their sensitivity to host reactions aroused by BCG. Certain neoplasms, exemplified by sarcoma CC5, require participation of an immune reaction of delayed hypersensitivity type for optimal destruction at BCG sites, while for others (e.g. sarcoma P7) an immunoreactive component of this type is not essential. By contrast, a third category of tumour (e.g. sarcoma P8) is relatively resistant to host reactions induced by the mycobacteria. An important component of BCG‐mediated tumour inhibition is not dependent on an immunologically intact host.
Genetic variation of in vitro cytolytic activity and in vivo rejection potential of non‐immunized semi‐syngeneic mice against a mouse lymphoma line
Authors: Kiessling Rolf , Petranyi Gyözö , Klein George , Wigzell Hans
Published: February 2007

Spleens of normal young mice of certain genotypes contain lymphocytes that can kill strain A‐derived YAC‐1 and some other in vitro‐grown Moloney lymphoma lines in a 51Cr‐release cytotoxic test. We have previously shown that mouse strains can be classified as high or low reactors in this test. F1 hybrids between low‐ and high‐reactive strains are high‐reactive. In the present study, strain‐A mice and eight different A F1 hybrids were tested in parallel for their spleen‐cell‐mediated killing effect in vitro and their ability to reject graded numbers of YAC ascites or in vitro cultivated cells in vivo. There was a clear correlation between in vitro cytotoxicity and in vivo rejection in all tested genotypes. In segregating (A × C57Bl) × A backcross mice, in vivo rejection of YAC cells was H‐2 linked. This is in line with the earlier backcross analysis of the in vitro cytotoxicity, suggesting a polygenic control with at least one H‐2 linked factor.
Influence of interferon on the synthesis of virus particles in oncornavirus carrier cell lines. III. Survey of effects on A‐, B‐ and C‐type oncornaviruses
Authors: Billiau A. , Edy V. G. , DeClercq E. , Heremans H. , DeSomer P.
Published: February 2007

The effect of interferon on the synthesis and release of A‐, B‐ and C‐type viruses by oncornavirus carrier lines was studied. Murine cell lines were selected which carry either of these viruses and are sensitive to the antiviral effect of interferon, as measured by inhibition of vesicular stomatitis virus. Release of C‐type virus was found to be highly sensitive. Release of B‐type virus, on the contrary, was only marginally inhibited. Synthesis of intracisternal A‐type particles was finally not inhibited by interferon pretreatment. These differences between infectious C‐type and non‐infectious A‐ and B‐type viruses may reflect fundamental differences in the synthesis of these viruses.
Resistance of certain leukaemic myeloblasts to immunological attack
Authors: Maclennan I. C. M. , Gale D. G. L. , Wood J.
Published: February 2007

Leukaemic cells from four out of 19 patients with acute myeloblastic leukaemia are shown to be resistant to lysis by rat anti‐human‐myeloblast antibody in the presence of complement. To a lesser degree this is reflected in lack of immunogenicity of these myeloblasts. It is suggested that these findings may be relevant in planning immunotherapy in this disease and evaluating the benefit of this type of treatment. Finally data are presented to show that loss of immunogenicity of myeloblasts after irradiation with 10,000 R, as is practised in certain immunotherapy schedules, is small compared with differences in immunogenicity between non‐irradiated myeloblasts from different individuals.
Lymphoproliferative disease in a cotton‐top marmoset after inoculation with infectious mononucleosis‐derived Epstein‐Barr virus
Authors: Werner Jürgen , Wolf Hans , Apodaca Jesus , Hausen Harald Zur
Published: February 2007

Injection of concentrated EBV derived from cells of the Kaplan line of infectious mononucleosis (IM) origin resulted in malignant lymphoproliferation in one out of three cotton‐top marmosets 6 weeks after inoculation. Two additional animals receiving the same isolate after incubation with an antibody‐containing human serum did not develop tumors. Inoculation of concentrated virus derived from the P3HR‐1 line of Burkitt origin did not lead to lymphoproliferation in five marmosets. Three of these received non‐neutralized, and two received neutralized P3HR‐1 virus. The tumor obtained with the Kaplan isolate revealed characteristics of a lymphosarcoma. It contained EBV‐specific DNA. In addition, EBV‐synthesizing lymphoblastoid lines were established from a tumorous lymph‐node, as well as from the spleen of the diseased marmoset. Virus recovered from these lines transformed lymphocytes derived from spleens of healthy marmosets. The tumor‐bearing animal developed low levels of anti‐VCA antibodies during the course of tumor growth. These data demonstrate the oncogenic potential of EBV directly derived from cells of IM origin.
Spleen‐cell cytotoxicity for cytomegalovirustransformed cells. II. Inhibition by cytomegalovirus antiserum
Authors: Murasko Donna M. , Lausch Robert N.
Published: February 2007

Serum from hamsters immunized repeatedly with cytomegalovirus (CMV) was able to block spleen‐cell cytotoxicity for CMV‐infected and CMV‐transformed cells. Inhibition was observed regardless of whether spleen cells were obtained from hamsters sensitized to the virus or to isografts of the transformed cells (designated Cx‐90‐3B, T‐2). Such serum did not significantly block effector cell response against transformed cells expressing herpes simplex virus or SV40‐associated membrane antigens. The mechanism of blocking was investigated. It was found that the blocking activity could be absorbed out with Cx‐90‐3B, T‐2 cells but not by untransformed hamster embryo fibroblasts. Cx‐90‐3B, T‐2 target cells treated with serum, and then washed, remained resistant to effector cell attack. On the other hand, if serum‐treated attacker cells were washed their cytotoxic activity was not significantly impaired. These results suggest that the blocking factor in the serum is antibody‐directed against cytomegalovirus‐related membrane antigen. This conclusion is supported by the finding that the serum contained antibody specifically reactive with the transformed cell surface in isotopic antiglobulin tests.
Distinctive banded marker chromosomes of human tumor cell lines
Authors: Nelson‐Rees Walter A. , Flandermeyer Robert R. , Hawthorne Paula K.
Published: February 2007

Nine human tumor cell lines (five breast carcinomas and four sarcomas) have been studied and each revealed groups of distinctive banded marker chromosomes which can serve to identify them and aid in monitoring cell line specificity. This was possible neither by conventional karyology in terms of numbers and morphology of chromosomes nor by glucose‐6‐phosphate‐dehydrogenase mobility which was type B for all cultures. The significance of the clonal nature of the cell lines is discussed.
Human tumor—lymphocyte interaction in vitro: Blastogenesis correlated to detectable immunoglobulin in the biopsy
Authors: Vánky F. , Trempe G. , Klein E. , Stjernswärd J.
Published: February 2007

Binding of radioiodinated anti‐immunoglobulin (Ig) reagent assayed by acid elutable radioactivity was shown in 18 of 44 cell suspensions (41%) prepared from surgical specimens of human tumors. Aliquots of these biopsies were admixed to autologous lymphocytes and in 13 cases they induced stimulation of DNA synthesis. In only one of these 13 cases was the anti‐Ig reagent bound, while among the 26 biopsies with low or no binding capacity 12 (46%) were stimulatory, indicating that immunoglobulin‐containing biopsies are not stimulatory. Experiments on 32 lymphocyte preparations from different lymphoid organs suggest that the immunoglobulin detected in the tumor‐cell suspension is not derived from the infiltrating lymphoid cells.
Production by EBV infection of an EBNA‐positive subline from an EBNA‐negative human lymphoma cell line without detectable EBV DNA
Authors: Clements G. B. , Klein G. , Povey S.
Published: February 2007

A continuous lymphoma cell line, BJAB, derived from the tumour of an exceptional African case of Burkitt's lymphoma, has previously been described. Unlike 97% of African BL cases studied, neither the original tumour cells nor the cell line contained detectable amounts of EBV (Epstein‐Barr virus) DNA, nor did they express the EBV‐determined nuclear antigen EBNA. The cells of the established line had the characteristics of B‐type lymphocytes and they carried receptors for EBV. EBNA was induced in the majority of BJAB cells after EBV infection. Usually the cells died within 10 days of infection, but it was possible to establish a permanent EBNA‐positive variant (GC‐BJAB) of BJAB. The patient from whose tumour the original BJAB line was established was seropositive for EBV antigens, indicating previous exposure to and continuing presence of the virus; yet the tumour had not become infected by EBV. This evidence shows that EBV is not readily “picked up” by the lymphoma.