bluuebunny/crossref_metadata_2025 huggingface dataset:
Tumor‐specific and tumor‐associated membrane antigens of rous sarcoma virus transformed hamster fibroblasts
Authors: Comoglio Paolo M. , Bertini Marilena , Prat Maria
Published: February 2007

Hamster fibroblasts transformed by an env− strain of Rous sarcoma virus (RSV) express at their surface tumor‐associated antigens of unknown origin and a tumor‐specific antigen (VCSA) which is not expressed by hamster fibroblasts transformed by unrelated DNA or RNA oncogenic viruses. This antigen was detectable by rabbit antibodies and a complement‐dependent 51Cr‐release cytotoxicity assay and is common to RSV‐transformed cells of different animal species. By comparing the anti‐VCSA serum with antisera directed against purified gp85, gs‐proteins, reverse transcriptase or detergentlysed virus particles, it was shown that VCSA is not a known virion structural protein. Moreover, VCSA expression does not correlate with viral replication since it is not detectable in chick embryo fibroblasts productively infected with the transformation‐defective virus RAV‐1 which shares virus structural genes with RSV. Finally, in hamster cells transformed by an RSV mutant, temperature‐sensitive for the ability to transform the host cell, VCSA expression at the cell surface correlates with the expression of the transforming gene.
A prospective evaluation of the leukocyte adherence inhibition test in colorectal cancer and its correlation with carcinoembryonic antigen levels
Authors: Shani Adi , Ritts R. E. , Thynne G. S. , Weiland Louis H. , Silvers Abraham , Moertel Charles G. , Go V. L. W.
Published: February 2007

Fifty‐four patients from the surgical gastroenterology service and 22 healthy controls have been prospectively evaluated in a single‐blind protocol by the LAI tube method. The LAI correctly identified 25 of 33 early colorectal patients staged as Dukes' B and C at surgery but none of the Dukes' D patients. An inverse relationship was seen between the results of the non‐adherence index (NAI) and CEA levels which was most pronounced in those with advanced colorectal cancer. The majority of Dukes' B and C patients having a “false negative” LAI had a CEA level greater than 2.5 ng/ml, suggesting that more advanced disease than that seen at surgery may be present. Two of 22 normal controls gave a borderline positive NAI. Some technical problems, including the relatively short life of the tumor extracts, are discussed.
Antibody‐dependent cellular cytotoxicity against epstein‐barr virus‐associated antigens in african patients with nasopharyngeal carcinoma
Authors: Pearson Gary R. , Johansson Bo , Klein George
Published: February 2007

Antibody‐dependent cellular cytotoxicity (ADCC) was performed on serum samples from African patients with nasopharyngeal carcinoma (NPC) to determine whether antibody titers determined by this assay might be of prognostic value in this disease. The serum donors were divided into two groups: (1) those individuals who died within 2 years following diagnosis of NPC; and (2) individuals who responded well to therapy and survived for more than 2 years following diagnosis. The ADCC GMT for the survivor group was significantly higher than the GMT for non‐survivors (5,410 versus 615). Interestingly, there were a number of discordant sera in the non‐survivor group that had very low ADCC titers (<240) at diagnosis in the presence of high VCA titers. When ADCC titers were compared with anti‐EA or IgA antibody titers to VCA, a statistically significant inverse correlation was noted. These data suggest that ADCC titers might be of prognostic importance in African NPC.
Antibody patterns to herpesviruses in Kaposi's sarcoma. II. Serological association of american Kaposi's sarcoma with cytomegalovirus
Authors: Giraldo G. , Beth E. , Henle W. , Henle G. , Miká V. , Safai B. , Huraux J. M. , McHardy J. , De‐Thá G.
Published: February 2007

The prominent finding of this extended serologic analysis on American and African Kaposi's sarcoma (KS) patients and appropriately matched control groups is the detection of a specific serologic association of cytomegalovirus (CMV) with American KS patients. All American KS sera contained CMV antibodies and their geometric mean titers (GMT) were significantly higher than those in sera of melanoma patients (GMT ratio k = 5.3 to 7.7 by complement fixation [CF], k = 8.9 by indirect hemagglutination [IHA]) or in sera of age‐ and sex‐matched healthy controls (k = 12.6 to 16.0 by CF, k = 12.6 by IHA). The result is strongly reminiscent of the data obtained previously for European KS. Although the GMT to CMV of African KS patients were similar to the GMT of the American KS groups, their significance cannot be demonstrated due to the high background of CMV infections in the control groups. Complex mechanisms are hypothesized, by analogy with the Epstein‐Barr virus (EBV) involvement in Burkitt's lymphoma (BL), for a CMV involvement in the development of KS.
Antibody production by spleen cells of mice bearing MCA‐induced tumours: Search for suppressor cells
Authors: Yagello Micaël , Lespinats G. , Fridman W. H.
Published: February 2007

The antibody response to sheep red blood cells of spleen cells from mice bearing a methylcholanthrene (MCA)‐induced tumour was measured with the local hemolysis technique, after in vivo or in vitro immunization. The in vivo data varied according to the stage of tumour growth and were related to the splenomegaly developing during the tumour growth process. During the first 10–15 days after tumour grafting, the total number of plaque‐forming cells in the spleen increased in proportion to the spleen growth and thereafter remained relatively constant although the splenomegaly still progressed. Experiments performed in vitro were used to test the antibody response of mixtures of cells from normal mice and syngeneic tumour‐bearing animals. In most cases, no suppression of antibody production, due to cells from tumour‐bearing hosts, could be detected. The results suggest that those cells, which suppress cell‐mediated immune reactions, previously found in the spleen of animals bearing the MCA‐induced tumour, do not suppress antibody production.
Inhibition of mitogen and immune blastogenesis by two distinct populations of suppressor cells present in the spleens of fibrosarcoma‐bearing mice: Adoptive transfer of suppression
Authors: Farrar William L. , Elgert Klaus D.
Published: February 2007

Mitogen and immune blastogenic responses were progressively impaired in the spleens of mice with transplanted fibrosarcomas. Spleen cells from tumour‐bearing BALB/c mice were shown to suppress in vitro phytohemagglutinin (PHA) and immune blastogenesis of normal syngeneic spleen cells. Nylon wool column and other depletion techniques were utilized to characterize the cellular source of suppressive activity in tumour‐bearing host (TBH) spleens. Evidence is presented for two distinct suppressor cell systems operating in the spleens, but not lymph nodes, of TBH BALB/c mice. Both normal and TBH splenic macrophages were shown to suppress in vitro PHA and immune blastogenesis at high in vitro concentrations. No functional difference was detected between normal and TBH splenic macrophages. Suppressor T cells, detected in a macrophage‐depleted culture system, significantly suppressed normal spleen cell blastogenesis at low in vitro concentrations. Anti‐Thy 1 serum‐sensitive suppressor T cells elaborated an immunosuppressive material that could also mediate inhibition of blastogenesis. Tumour‐bearing host thymocytes also elaborated such a material. No soluble inhibitor(s) was released by macrophages or TBH lymph‐node cells. The suppressor T cell was tentatively defined as a spleen‐seeking, mildly nylon‐wool‐adherent, and anti‐Thy 1 serum and hydrocortisone succinate‐sensitive T lymphocyte. Adoptive transfer studies revealed that both macrophages (normal or TBH) and suppressor T cells were inhibitory. The data suggest that suppressor T cells may significantly affect blastogenesis at low in vitro and in vivo concentrations, whereas macrophage‐mediated suppression requires higher concentrations.
Heterogeneity of epstein‐barr virus. IV. Induction of a specific antigen by EBV from two transformed marmoset cell lines in ramos cells
Authors: Fresen K.‐O. , Cho M.‐S. , Hausen H. Zur
Published: February 2007

Infection of cells of the EBV‐genome‐negative human B‐lymphoma Ramos line with viral isolates obtained from two EBV‐transformed marmoset cell lines (B95/8; Nyevu) resulted in the induction of a nuclear antigen (RAM‐ag) apparently different from other EBV‐associated antigen complexes. This antigen is revealed by indirect immunofluorescence and shows no detectable cross‐antigenicity with EBNA or any other known EBV‐associated antigen. EBV‐isolates from P3HR‐1 cells fail to induce a similar antigen in Ramos cells although they induce EBNA. No RAM‐ag was expressed, either after infection of cells of another EBV‐genome‐negative human B‐lymphoma line BJAB with B95‐8 EBV or in a series of EBV‐harbouring cell lines. Thus the antigen appears to be cell‐line‐specific for Ramos cells. It is also induced upon infection of either B95‐8 or P3HR‐1 converted Ramos sublines with EBV from B95‐8 cells. All human sera with RAM‐ag‐reactivity revealed antibodies against VCA. However, sera from patients with acute infectious mononucleosis containing high anti‐VCA‐antibodies did not react with RAM‐ag. Seroconversion for this antigen apparently more closely coincides with the appearance of EBNA‐directed antibodies.
Inhibition by lymphoblastoid interferon of growth of cells derived from the human breast
Authors: Balkwill F. , Watling D. , Taylor‐Papadimitriou J.
Published: February 2007

Human lymphoblastoid interferon inhibited the growth in vitro of fibroblasts and epithelial cells from normal, hyperplastic and neoplastic human breast tissue. At an interferon concentration of 103 international units (IU) per ml, the inhibitory effects on monolayer growth were completely reversible but the growth potential of cells at lower density in colony‐forming cultures was not completely recovered. Studies on the cell cycle distribution of interferon‐treated cells demonstrated that the growth‐inhibitory effect was not due to an effect on one specific phase of the cell cycle, but to a lengthening of all phases.
Reaction of 7,12‐dimethylbenz(a)anthracene with DNA of fetal and maternal rat tissues in vivo
Authors: Doerjer Gerhard , Diessner Helga , Bücheler Joachim , Kleihues Paul
Published: February 2007

Pregnant BD‐IX rats (21st day of gestation) received a single IV injection (15 mg/kg) of tritiated 7,12‐dimethylbenz(a)anthracene (DMBA), a dose known to induce a high incidence of nervous‐system tumors in the offspring. The animals were killed 12 h later and hydrocarbon‐deoxyribonucleoside products from DNA of maternal and fetal tissues were separated on Sephadex LH‐20 columns eluted with a 20–100% methanol gradient. Concentrations of the major DMBA‐DNA adduct varied considerably, with highest values in maternal intestine, liver and lung, followed by spleen, kidney and brain. In fetal intestine and liver, concentrations were 34% and 16% lower than in the respective maternal organs whereas the reaction with cerebral DNA was 2 1/2 times higher in fetuses than in the pregnant mother. This indicates that there is no significant placental barrier to DMBA or DMBA metabolites involved in DNA binding and that rat fetuses participate in the metabolic formation of the ultimate carcinogen.
Specific cytotoxic lymphocytes against syngeneic tumors are generated in culture in the presence of syngeneic, but not xenogeneic, serum
Authors: Fogel Mina , Segal Shraga , Gorelik Eliezer , Feldman Michael
Published: February 2007

Experiments were performed to test the effect of xenogeneic (fetal calf) serum (FCS), as compared to syngeneic mouse serum (SMS) on the generation in culture of specific cytotoxic lymphocytes (CL) against syngeneic tumors. Sensitization in FCS against 3LL tumor cells resulted in CL cross‐reacting with B‐16 tumor cells and vice versa. Anti‐syngeneic fibroblast CL also cross‐reacted with 3LL. Such cross‐reactivities were shown to be derived from CL directed against FCS determinants. In contrast, sensitization in the presence of SMS resulted in CL directed against tumor‐specific antigens. Anti‐3LL generated in SMS lysed 3LL targets but not B‐16, and anti‐B‐16 lysed B‐16 but not 3LL. The two types of CL had two distinct reactivities in vivo. Anti‐3LL CL generated in FCS enhanced tumor growth in vivo, whereas anti‐3LL CL generated in SMS had an inhibiting effect on the growth of tumor cells. These results indicate that the application of syngeneic serum during in vitro sensitization against syngeneic tumors may open up new possibilities for the analysis of tumor‐specific antigens and for eliciting specific immune reactions against such antigens.
Ultrastructural detection of alpha1‐fetoprotein in hepatomas by use of peroxidase‐labelled antibodies
Authors: Kuhlmann W. D.
Published: February 2007

Hepatomas were induced in rats by feeding N‐nitrosomorpholine. Nodules from an alpha1‐fetoprotein (AFP)‐producing hepatoma were taken and subcutaneously injected into syngeneic hosts. From the first generation, the hepatoma producing most AFP was selected for further transfers. Four weeks after transplantation, the AFP concentration in the host rats was in the range of 0.8 to 1.5 mg AFP/ml serum. Transplanted hepatomas of the 14th to 19th generations were used for ultrastructural localization of AFP. Various methods of tissue processing were examined under the light and electron microscopes for intracellular detection of AFP by use of specific anti‐AFP antibodies conjugated with peroxidase. AFP was localized in the perinuclear space, the rough‐surfaced endoplasmic reticulum and the Golgi apparatus. Non‐membrane‐bound ribosomes did not stain for AFP. Fixation with 6% formaldehyde for 5 h followed by 6% formaldehyde plus 0.25–0.5% glutaraldehyde for 60–90 min proved best both for satisfactory ultrastructural conservation of the organs and for immunocytochemical localization of AFP. Concentrations of glutaraldehyde which exceeded 0.5% led to a significant decrease in immunocytochemical AFP reactions. On the other hand, weak aldehyde fixation poorly preserved ultrastructural detail and leakage of insufficiently fixed material caused staining artifacts. Under our conditions, thick frozen sections from well‐fixed hepatomas gave consistently reproducible results in that intracellular penetration of antibody‐peroxidase conjugates was superior to hand‐cut small tissue fragments. Tissue fixation and sampling were most important above all for other experimental steps.
Demonstration of specific cell‐mediated anti‐tumor immunity in lung cancer to autologous tissue extracts
Authors: Dean J. H. , Jerrells T. R. , Cannon G. B. , Kibrite A. , Baumgardner B. , Weese J. L. , Silva J. , Herberman R. B.
Published: February 2007

Cell‐mediated immunity (CMI) of lung cancer patients to autologous tumor antigens was assessed by mixed lymphocyte tumor interactions (MLTI) as measured in a microculture (200 μl) lymphocyte proliferation (LP) assay. Positive lymphoproliferative responses were observed with cryopreserved intact mitomycin‐C‐treated autologous tumor cells (8/12 or 67% patients reactive) and with hypotonic membrane extracts (HMP) of tumor cells (28/40 or 70%). Good correlation was found between reactivity to tumor cells and extracts in parallel testing. In contrast, HMP of autologous normal lung tissue elicited very little LP reactivity, with only one patient giving a weak response by the SI criterion and low level of n cpm. Upon repeat testing, many patients gave reproducibly positive LP responses to tumor HMP. Patients at all clinical stages of disease and with different histologic tumor types had a similar proportion of HMP reactivity. Most reactive patients responded to a broad range of protein concentrations of tumor HMP, and LP responses were frequently elicited with 1 μg or less of HMP. Thus, HMP appear to afford a convenient source of reactive tumor antigen for assessing anti‐tumor immunity.
Recovery of transforming EBV from non‐producer cells after superinfection with non‐transforming P3HR‐1 EBV
Authors: Fresen K.‐O. , Cho M.‐S. , Hausen H. Zur
Published: February 2007

Cells of the Raji and NC37 lines can be induced by chemical inducers, such as BrdUrd and IdUrd, or the tumor‐promoter TPA to EA‐expression only, but do not reveal any VCA synthesis. After super‐infection by nontransforming P3HR‐1 EBV, however, a varying percentage of the cell population shows VCA synthesis and releases infectious viral particles. The recovered virus differs biologically from P3HR‐1 EBV since it transforms human umbilical cord blood lymphocytes into EBNA‐positive lymphoblastoid cell lines. Cells of these established lines are susceptible to renewed infection by P3HR‐1 EBV which results in EA induction and VCA synthesis. Only cells of one line, NC37‐R1, spontaneously produce VCA and EBV particles, which reveal transforming properties and do not induce EA upon superinfection of Raji cells. Infection of P3HR‐1 EBV‐converted BJA‐B cells also leads to EA and VCA induction and the release of viral particles. In contrast to particles recovered from Raji and NC37 cells, no transforming activity was detectable in these virus preparations. According to these data, we propose that viral genomes persisting within Raji and NC37 cells are defective and become complemented by the superinfecting P3HR‐1 virus.
Secretion of plasminogen activator by normal, reactive and neoplastic human tissues cultured in vitro
Authors: Wilson Elaine Lynette , Dowdle Eugene
Published: February 2007

Plasminogen activator secretion by 39 primary or early‐passage cultures of malignant human neoplasms has been compared with that of 16 similar cultures of benign neoplasms and 39 cultures of normal or reactive tissue. While normal cells of mesenchymal or neural origin secreted considerably less plasminogen activator than did cells from frankly malignant tissues, elevated levels of enzyme secretion were also encountered in cultures of benign neoplastic or reactive cells. In the case of epithelial tissue, no consistent relationship between plasminogen activator secretion and neoplasia could be documented. Our failure to observe, for any particular cell type, a reproducible correlation between malignancy and plasminogen activator secretion may be attributable to the artificial conditions of in vitro culture, where normal in vivo regulatory mechanisms do not obtain.
Delayed hypersensitivity reactions of cancer patients to antigens on lymphoid cell lines
Authors: Levine P. H. , Ho J. H. C. , Nkrumah F. , Periman P. , Mourali N. , Cannon G. , Middleton M. B. , Perkins I. V. , Herberman R.
Published: February 2007

Four‐hundred and fifty niné cancer patients were skin tested with extracts from five lymphoid cell lines. More than 50% of patients with lymphoma had positive skin tests with the extracts prepared from the cell line derived from Burkitt's lymphoma (BL) and more than 50% of nasopharyngeal carcinoma (NPC) patients reacted to the NPC‐derived cell line extracts. Although the significant association between patient diagnosis and origin of cell lines suggested that tumor‐associated antigens were responsible for the pattern of delayed hyper‐sensitivity, problems in standardization of antigen potency and non‐specificity need to be resolved before this in vivo assay achieves its full potential.
Nonspecific activation of complement by leukemic cells
Authors: Shimbo Toshikazu , Yata Junichi , Okada Hidechika
Published: February 2007

Non‐specific activation of complement (NAC) on cell membranes via the alternative pathway was studied by using leukemic cells and cells from a generalized reticulohistiocytosis. The cells were treated with normal human serum in veronal‐buffered saline containing ethyleneglycoltetra‐acetate and Mg++. Since human erythrocytes (HuE) are known to adhere to complement‐reacted cell membranes in an immune adherence reaction, complement activation on the cell membrane was confirmed by the rosette formation of HuE which is due to the generation of C3b molecules on the cell membrane. Only cells from Schilling‐type acute monocytic leukemias and cells from a generalized reticulohistiocytosis possessed NAC ability. All other leukemic cells tested, as well as normal hematopoietic and lymphoreticular cells, were NAC‐negative. Furthermore, none of the mitogens tested generated NAC ability on normal peripheral blood lymphocytes.
Immunological characterization of the low‐molecular‐weight dna binding protein of mouse mammary tumor virus
Authors: Arthur L. O. , Long C. W. , Smith G. H. , Fine D. L.
Published: February 2007

P14, a low‐molecular‐weight MMTV protein previously identified as having DNA‐binding properties and encoded by the gag region of the MMTV genome, was purified by affinity chromatography on DNA‐sepharose. Immunological characterization of the purified protein showed that MMTV p14 shares no cross‐reactivity with gp52, gp36 and p10, antigens associated with the MMTV envelope, nor with p27 antigen found in the virion core. Purified MMTV p14 did show cross‐reactivity with purified intracytoplasmic A particles, supporting the concept that A particles are morphological precursors to MMTV cores. In addition, shared antigenic determinants between intracytoplasmic A particles and MMTV p27, p20 and p10 were demonstrated. MMTV p14 did not cross‐react with the low‐molecular‐weight DNA‐binding proteins of MuLV or of type‐C or ‐D viruses of higher mammals.
Neoplastic transformation of canine embryo cells in vitro by N‐methyl‐N′‐nitro‐N‐nitrosoguanidine
Authors: Rhim Johng S. , Park Dai K. , Arnstein Paul , Nelson‐Rees Walter A.
Published: February 2007

A cell line derived from a normal beagle embryo was treated in vitro with various levels of N‐methyl‐N′‐nitro‐N‐nitrosoguanidine or dimethyl sulfoxide (control). Cells treated only with the carcinogen underwent morphologic alteration in vitro, and one of these altered cell lines produced tumors sub‐cutaneously when injected into NIH nude mice. The tumorigenic transformed line formed larger cell aggregates and grew in this aggregate form when suspended in liquid growth medium above an agar base.
Chromosome changes (trisomy 15) in murine T‐cell leukemia induced by 7,12‐dimethylbenz(a)anthracene (DMBA)
Authors: Wiener Francis , Spira Jack , Ohno Shinsuke , Haran‐Ghera Nechama , Klein Georges
Published: February 2007

The banding pattern of DMBA‐induced leukemias in C57BL/6 mice revealed a very constant chromosome pattern: the presence of trisomy 15 in almost all leukemic cells. This finding strongly suggests that chromosome 15 trisomy is the first detectable specific chromosome change associated with the development of DMBA‐induced T‐cell lymphomas. A similar association was previously shown with regard to development of radiation‐leukemia‐virus‐induced T‐cell lymphoma. It is conceivable that in tumors of diverse etiologies common cytogenetic changes may appear in the same common target‐cell precursor, by a process of the “convergent microevolution” type.
Neoplastic behavior of chromosomally abnormal clones in New Zealand black mice
Authors: Friedman J. M. , Fialkow Philip J. , Bryant Jean , Reddy A. L. , Salo Armi C.
Published: February 2007

Old New Zealand Black (NZB) mice frequently develop reticulum‐cell sarcoma and clones of aneuploid cells in their spleens. In order to define the relationship between neoplasms and chromosomal abnormalities, the pattern of distribution of aneuploid cells was studied to see if it corresponds to that expected of the malignancy, and chromosomally aberrant or normal spleen cells were transplanted into syngeneic newborn recipients. The results indicate that aneuploid cells arise focally but may disseminate widely in an affected mouse. A strong association was found between spleen‐cell aneuploidy in a transplantation donor and both aneuploidy and histological evidence of reticulum‐cell sarcoma in young recipients. Chromosomal aberrations in young recipients were always of donor origin. On the basis of these data, it seems likely that aneuploid clones which arise in the spleens of old NZB mice usually are at least potentially neoplastic.
An immunoregulatory factor associated with spleen cells from tumor‐bearing animals. II. Characterization of the cell populations involved in its production and release
Authors: Hollander Nurit , Isakov Noah , Segal Shraga , Feldman Michael
Published: February 2007

Culture supernatants of spleen cells from tumor‐bearing mice (TBM) have been found to enhance tumor growth, when injected together with tumor cells, and to augment the generation of antibody‐producing cells (APC), when injected into mice together with sheep erythrocytes (SRBC). In an attempt to characterize the cellular entity in the spleen‐cell population which is involved in release of the enhancing factor (EF), “B”, adult‐thymectomized, and nude mice were inoculated with 3LL tumor cells, and their spleen‐cell supernatants were tested. We found that spleen‐cell supernatants from the three different categories of 3LL tumor‐bearing mice were highly effective in augmenting anti‐SRBC APC production and in accelerating tumor growth. In a second line of experiments, T or B lymphocytes were eliminated from spleens of TBM before the cells were incubated in vitro. Culture supernatants of TBM spleen cells adherent to nylon wool colums, which were enriched mainly for B lymphocytes and macrophages, manifested higher EF activity than supernatants of eluted spleen cells which were enriched for T lymphocytes. Supernatants of TBM spleen cells, which were pretreated with anti‐Thy 1,2 serum in the presence of complement before culturing, were found to be highly effective in potentiation of APC generation and in enhancement of tumor growth. These results suggest that EF is not released by lymphoid cells that possess characteristics of mature T lymphocytes. EF was produced in culture by 3LL tumor cells; 90 min after injection of 3LL supernatant, the recipient spleen cells were capable of releasing EF in vitro. Trypsin treatment did not affect EF production by tumor cells but stopped its release from spleen cells of TBM. It therefore appears that EF is produced by the tumor cells and is then adsorbed onto spleen cells.
Oncogenicity of friend‐virus‐infected cells: Determination of origin of spleen colonies by the H‐2 antigens as genetic markers
Authors: Wendling F. , Tambourin P. E.
Published: February 2007

Spleen cells from mice infected with Friend leukemia virus (FLV) inoculated by the intravenous route give rise to macroscopically visible colonies in the spleens of normal F1 histocompatible hybrid hosts. A study of H‐2 antigens as generic markers for identification of strains of origin of cells constituting the spleen colonies was undertaken. The standard cytotoxic test was demonstrated to be suitable for characterizing the H‐2 antigens present on the surface of spleen cells from normal or FLV‐leukemic parents or F1 hybrid mice. Individual colonies dissected out of the spleen of (C3H × C57BL/6) F1 recipients (H‐2k/H‐2b), 10 days after the intravenous graft of FLV‐infected spleen cells of C3H origin (H‐2k), were all sensitive to anti‐C57BL/6 antibodies. In the same way, colonies obtained from the spleens of (DBA/2 × C57BL/10) F1 recipients (H‐2d/H‐2b) grafted with DBA/2 leukemic spleen cells (H‐2d) were all sensitive to both anti‐H‐2b and anti‐H‐2d antibodies. These results directly prove that the main cell population constituing a spleen colony arises from the recipient. The authors conclude that the spleen colonies do not result from the neoplastic proliferation of injected donor cells but rather from the multiplication of host cells transformed by Friend virus produced by the grafted cells.
The covalent binding of polycyclic hydrocarbons to DNA in the skin of mice of different strains
Authors: Phillips David H. , Grover Philip L. , Sims Peter
Published: February 2007

The binding of three tritium‐labelled carcinogenic polycyclic hydrocarbons, 7,12‐dimethylbenz (a) anthracene (DMBA), benzo (a) pyrene (BP) and 3‐methylcholanthrene (MCA) to DNA in mouse skin has been studied in C57BL, DBA/2 and Swiss mice following topical application of the hydrocarbons. DNA isolated from the treated areas was hydrolysed to deoxyribonucleosides and chromatographed on Sephadex LH20 columns. The levels of binding of hydrocarbon to DNA were determined from the amount of radioactivity eluted from Sephadex LH20 columns in those fractions containing hydrocarbon‐DNA adducts and the radioactivity shown, by rechromatography on AG5OWX4 columns, to be due to tritium incorporation into normal deoxyribonucleosides was not included. C57BL mice were treated with doses of DMBA ranging from 0.025 μmol to 1 μmol/mouse and the levels of hydrocarbon bound to DNA 19 h after treatment were determined; there was no evidence for a threshold dose below which no binding to DNA occurs, and the same hydrocarbon‐DNA product peaks were obtained at all doses. The levels of binding of DMBA (1 μmol/mouse) to DNA in skin were compared in C57BL, DBA/2 and Swiss mice at times varying from 6 h to 8 days after treatment. DMBA became bound to similar extents in Swiss and C57BL mice and to a slightly greater extent in DBA/2 mice; the rate of disappearance of bound DMBA from DNA was similar in all three strains. DMBA (0.1 μmol/mouse) was bound to DNA in C57BL and DBA/2 mice to similar extents 19 h after treatment and to a slightly lesser extent in Swiss mice. The ratios of the sizes of the hydrocarbon‐DNA product peaks varied with the time after treatment, but were similar at any given time for the three strains. Both BP (1 μmol/mouse) and MCA (1 μmol/mouse) were bound to DNA to similar extents 19 h and 48 h after treatment in all three strains. BP (0.1 μmol/mouse) was bound to DNA in the order DBA/2>C57BL> Swiss 19 h after treatment. The levels of binding for all three hydrocarbons in the different strains do not show a correlation with the reported susceptibilities of the three strains to polycylic hydrocarbon carcinogenesis.
Developmental changes in carbohydrate moiety of human alpha‐fetoprotein
Authors: Ruoslahti Erkki , Engvall Eva , Pekkala Aulikki , Seppälä Markku
Published: February 2007

Human AFP purified from fetal serum and amniotic fluid was separated into three different variants by chromatography on concanavalin A insolubilized on Sepharose (Con A—Sepharose). The three variants were indistinguishable in immunodiffusion and radioimmunoassay. Sera from patients with yolk‐sac tumor and amniotic fluid from early pregnancy were found to contain a high proportion (15–45%) of AFP which does not bind to Con A, while AFP in fetal and newborn sera, and in amniotic fluid from late pregnancy, contained less (2–6%) of this variant. The use of a large excess of Con A—Sepharose and the fact that the non‐bound AFP consistently eluted as non‐bound in rechromatography showed that this AFP is non‐reactive with Con A. Fractionation of radiolabelled AFP from cord serum in a mixture with amniotic fluid verified the difference in the amount of the Con‐A non‐reactive variant in AFP from these two sources. These results suggest that AFP synthesized by the yolk‐sac tissue and by the liver are glycosylated differently. The variant may prove to be diagnostically useful.
Immunotherapy with an intralesionally administered synthetic cord factor analogue
Authors: Yarkoni Eliyahu , Rapp Herbert J. , Polonsky Judith , Lederer Edgar
Published: February 2007

Injection of emulsified 6,6′‐di‐O‐2‐tetradecyl‐3‐hydroxyoctadecanoyl‐α,α trehalose designated C76, a synthetic analogue of the mycobacterial glycolipid trehalose‐6,6′‐dimycolate (TDM), into transplants of an established, syngeneic murine fibrosarcoma induced complete regression of tumor in a number of animals. The number of animals in which tumor regressed completely depended on the amount of oil in the emulsion. On a weight basis, C76 was at least as active as TDM. Intralesional injection of an emulsified mixture of C76 and endotoxin (ET) or of TDM and ET caused regression of an established transplant of a guinea‐pig hepatoma in syngeneic animals. In mice, intravenously administered emulsions of C76 were less toxic and less granulomagenic than those made with TDM.
Induction of a tumor with greatly increased metastatic growth potential by injection of cells from a low‐metastatic H‐2 heterozygous tumor cell line into an H‐2 incompatible parental strain
Authors: Kerbel R. S. , Twiddy R. R. , Robertson D. M.
Published: February 2007

An H‐2 heterozygous sarcoma, MDAY, originally induced with methylcholanthrene in an (A × DBA/2)F1 (H‐2a × H‐2d) hybrid host was selected for growth in the H‐2d homozygous parental DBA/2 strain by serial intraperitoneal transplantation of ascites tumor cells. An apparent variant, designated MDAY‐D2, was obtained which showed the expected loss of the private and public H‐2Kk haplotype antigens normally associated with the A strain parent and the original MDAY tumor. Comparison of the original and variant lines revealed a wide variety of cell surface antigen and receptor differences. Both tumors were found to be highly anaplastic and histologically unclassifiable. Examination of the two tumor lines growing in vivo revealed a remarkable difference in their metastatic growth potential. The original MDAY line showed little propensity to spread to any organ site, with the occasional exception of liver, after subcutaneous inoculation of (A × DBA/2)F1 mice. In striking contrast, there was a rapid and massive spread of MDAY‐D2 to liver, spleen, lungs and kidneys within 12–16 days: liver and spleen could be totally replaced by tumor within 2–3 weeks. These characteristics were observed in both (A × DBA/2)F1 and DBA/2 mice. The tendency to metastasize, as well as loss of the H‐2Kk haplotype, appeared stable and irreversible. Although the precise origin of MDAY‐D2 is not clear, its metastasizing properties are unique, making it a useful and desirable model to study the biology of metastasis.
Enhancement of thermal killing by polyamines. II. Uptake and metabolism of exogenous polyamines in hyperthermic chinese hamster cells
Authors: Ben‐Hur Ehud , Riklis Emanuel
Published: February 2007

The uptake and metabolism of the polyamines spermine, spermidine, cadaverine and putrescine, previously shown to potentiate heat sensitivity, were studied in cultured Chinese hamster cells. Heat (42°C) causes enhanced uptake of exogenously supplied polyamines into the acid‐soluble fraction of the cells. Putrescine is taken up exceptionally fast at 37°C, about 10 times faster than its homologue, cadaverine. This uptake is slower at 42°C. The polyamines taken up were metabolized to some extent and the metabolites were similar at 37°C and 42°C except in the case of putrescine. These results suggest that potentiation of heat‐sensitivity is probably mediated by the polyamines as such and not by their metabolites. Polyamines slightly protect the cells against the inhibitory effect of heat on RNA and protein synthesis. It is suggested that exogenous polyamines interact with nucleic acids inside the cell, and this interaction may underlie their synergism with heat. The exact nature of this interaction and the way it leads to enhanced thermal sensitivity are still obscure.
Biochemical studies on RNA tumor virus information and its transmission in B16 murine melanoma
Authors: Hehlmann R. , Erfle V.
Published: February 2007

The mouse melanoma B16 contains particles encapsulating a high molecular weight RNA of 60–70S size associated with a reverse transcriptase. The particles possess a density of 1.14–1.18 g/cm3. The RNA shares sequences with the 70S RNAs of several mammalian C‐type RNA tumor viruses. The nuclear DNA of the mouse melanoma B16 possesses particle‐related sequences not present in the genome of normal C57BI mice.
Expression of human mammary epithelial (HME) antigens in primary cultures of normal and abnormal breast tissue
Authors: Peterson Jerry A. , Buehring Gertrude Case , Taylor‐Papadimitriou Joyce , Ceriani Roberto L.
Published: February 2007

The expression of human mammary epithelial (HME) antigens was studied in primary cell cultures of normal and abnormal breast tissue and of tissues from other organs. By indirect immunofluorescence it was shown that heterologous anti‐HME bound to the cell surface of both suspension and monolayer cultures of human breast epithelial cells from normal breast tissue, normal breast fluid, non‐malignant atypical lesions of the female breast, gynecomastia in the male breast, breast carcinomas, and peritoneal and pleural effusions of patients with breast carcinomas. The fibroblast‐like cells cultured from either normal, non‐malignant atypical, or malignant breast tissue never bound anti‐HME, nor did histiocyte‐like cells from breast fluid or a sarcoid granuloma of the breast. From a Paget tumor of the breast, two distinguishable epithelial‐like colonies appeared in the cultures, only one of which expressed HME‐antigens. Anti‐HME did not bind to cells cultured from tissues of other organs, whether epithelial‐like or fibroblast‐like; these organs included thyroid, ovary, endometrium, and skin.
Long‐term T‐cell‐mediated immunity to epstein‐barr virus in man. I. Complete regression of virus‐induced transformation in cultures of seropositive donor leukocytes
Authors: Moss D. J. , Rickinson A. B. , Pope J. H.
Published: February 2007

Peripheral blood mononuclear cells from donors of known serological status with respect to EB virus were exposed to the virus in vitro and then cultured at various cell concentrations. All cultures from nine seronegative adult and 12 foetal donors gave rise to cell lines following subculture 4 weeks post infection. In contrast, seropositive donor cultures seeded at the higher cell concentrations developed foci of proliferating EBNA‐positive cells within the first 1–2 weeks but thereafter regressed completely and subcultures made after 4 weeks never gave rise to cell lines. Out of 18 seropositive donors tested, 15 showed regression in all cultures seeded at 106 cells/ml and above, and with the other three donors a proportion of replicate cultures regressed. T‐cell depletion and reconstitution experiments showed that the effect was absolutely dependent upon the presence in the cultures of T cells from these seropositive donors. The results strongly suggest that the regression phenomenon is an in vitro expression of long‐term T‐cell‐mediated immunity to EB virus which the large majority, if not all, infected individuals possess.
Abnormalites in evening plasma prolactin levels in nulliparous women with benign or malignant breast disease
Authors: Tarquini A. , di Martino L. , Malloci A. , Kwa H. G. , van der Gugten A. A. , Bulbrook R. D. , Wang D. Y.
Published: February 2007

In the present study the assay results of prolactin concentrations in serial samples of blood obtained from premenopausal women with benign or malignant disease of the breast are compared with—and discussed in relation to—findings reported in earlier studies based on single samples of blood taken at various times from a large and ostensibly normal population of women. The finding of an abnormality in nycthemeral prolactin levels in the established disease is considered to strengthen the concept that the same abnormality found in high‐risk groups is of aetiological importance.
Heteroantiserum against acute lymphocytic leukemia raised to the lymphoblastoid cell line NALM‐1
Authors: Billing Ronald , Clark Bill , Guidera Kathy , Minowada Jun
Published: February 2007

Antisera have been raised in rabbits to the lymphoblastoid cell line NALM 1 precoated with antilymphocyte serum (ALS). Following absorption with chronic lymphocytic leukemia cells (CLL) the antisera reacted mainly with acute lymphocytic leukemia (ALL) cells, and were very similar in specificity to antisera raised to ALL cells precoated with ALS. Leukemia cells from the following numbers of patients were positive for the anti‐NALM 1 sera in a complement‐dependent cytotoxicity test; 11/14 ALL, 3/15 acute myelocytic leukemia (AML), 1/5 chronic myelocytic leukemia (CML) and 0/8 CLL. Normal B and T peripheral blood lymphocytes were negative. The titer of the anti‐NALM 1 sera against positive cells was 1:64 to 1:256 whereas the undiluted sera did not react with negative cells. Ten out of 11 of the positive ALL cells were of the non‐B non‐T type. However, cells from 1/4 T ALL patients and a cultured T ALL line 8402 were also positive. Six of 12 cultured lymphoblastoid cell lines were positive, all of which were of malignant origin. The molecular weight of the ALL antigen detected by anti‐NALM‐1 serum was determined by immunoprecipitation and sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis (PAGE) to be approximately 98,000 daltons.
Antigenic characterization of a new gibbon ape leukemia virus isolate: Seroepidemiologic assessment of an outbreak of gibbon leukemia
Authors: Krakower Jeffery M. , Tronick Steven R. , Gallagher Robert E. , Gallo Robert C. , Aaronson Stuart A.
Published: February 2007

A type‐C virus recently isolated from a leukemic gibbon in a colony located on Hall's Island, Bermuda, was characterized with respect to the antigenic properties of its gag and env gene‐coded proteins. This virus, designated GaLV‐H, was found to be closely related immunologically to type‐C viruses previously isolated from gibbons (GaLV‐SF, GaLV‐SEATO, GaLV‐Br) and from woolly monkey (SSAV). However, GaLV‐H was readily differentiated from these isolates in a radioimmunoassay for its env gene product, gp70. Seroepidemiology established that GaLV‐H was horizontally transmitted among gibbons within the colony. There was no evidence of exposure leading to an immune response to the virus or viral antigenemia in humans working in association with these animals.
The effect of fibre size on the in vitro biological activity of three types of amphibole asbestos
Authors: Brown R. C. , Chamberlain M. , Griffiths D. M. , Timbrell V.
Published: February 2007

Three standard (UICC) samples of amphibole asbestos were subjected to ball‐milling; the main effect of this procedure was to reduce the length of the fibres present in each sample. The numbers of fibres in unit masses, and the distribution of fibre sizes in all the samples, both parent and milled, were estimated from electron micrographs. The ability of all the samples to reduce the plating efficiency of V79‐4 cells is compared, on the basis of mass, fibre number and fibre number above various length thresholds. This biological activity of all the samples correlated best with the number of fibres above a threshold length of 6.5 μm. This is compared with the sizes of fibre previously reported to induce mesotheliomata when implanted into the pleural cavities of rats.
Naturally occurring humoral immunity to murine mammary tumor virus (MuMTV) and MuMTV GP52 in mice with low mammary tumor incidence
Authors: Arthur L. O. , Fine D. L.
Published: February 2007

Antibodies to murine mammary tumor virus (MuMTV) were found in sera from male and female mice by means of a radiolabelled intact MuMTV precipitation assay. These antibodies were demonstrated both in strains of mice that have a high incidence of mammary tumors and transmit the highly oncogenic MuMTV via the milk (C3H) and in mice that have been foster‐nursed to remove the highly oncogenic milk‐borne MuMTV (C3Hf) and subsequently have a decreased mammary tumor incidence. Antibodies to MuMTV were readily demonstrated in C3H mice at 6 weeks of age, whereas only marginal antibody activity was detected in C3Hf mice of less than 15 weeks of age. Antibody levels increased with age in both strains, but in C3Hf mice the immune response was also accelerated by pregnancy. Several feral and BALB/c NIV mouse sera with high (125I)MMTV precipitating titers also precipitated the major MuMTV envelope glycoprotein (gp52). Maximum precipitation of the (125I)gp52 was >50% with a 20% endpoint binding titer of 1:40, whereas the same sera precipitated >80% of (125I)MMTV with a titer of >1:2560. These naturally occurring antibodies were specific for gp52 since only MuMTV and purified MuMTV gp52 competed for binding of radiolabelled antigens by limiting dilutions of mouse sera. MuMTV gp52 was found in both C3H and C3Hf mice, predominantly in organs which had secretory functions, such as submaxillary glands and mammary tissue of females and submaxillary, coagulating, and vesicular glands and vas deferens of males. Extracts of other tissues were negative for MuMTV gp52. Neither gp52 nor naturally occurring antibodies for MuMTV were found in BALB/c or C57BL/6 mice.
Identification of murine endogenous xenotropic retrovirus in cultured multicellular tumour spheroids from nude‐mouse‐passaged nasopharyngeal carcinoma
Authors: Crawford D. H. , Achono B. G. , Teich N. M. , Finerty S. , Thompson J. L. , Epstein M. A. , Giovanella B. C.
Published: February 2007

After nude‐mouse‐passage, a carcinoma of the nasopharynx was found to contain a few scattered C‐t/pe retrovirus particles. Culture of this nude‐mouse‐grown material over solid agar allowed the human tumour cells to grow as multicellular spheroids which increased in number by budding and could be subcultured for up to 6 months. Within the spheroids the human tumour cells expressed increased retrovirus replication and large numbers of C‐type particles were observed. Treatment with a halogenated pyrimidine further enhanced the virus production. This tissue culture system provided sufficient virus production for the identification of the retrovirus as an endogenous xenotropic murine leukaemia virus and not a human agent.
Cytolytic activity of circulating human monocytes on transformed and untransformed human fibroblasts
Authors: Mantovani Alberto , Tagliabue Aldo , Dean Jack H. , Jerrells Thomas R. , Herberman Ronald B.
Published: February 2007

Monocytes from the peripheral blood of 10 normal adult human donors were tested for their cytolytic activity on untransformed or SV40‐transformed, early passage, human fibroblasts. Two pairs of human fibroblast lines (2303 and SV40–2303, 2931 and SV40–2931) were used and lysis was assessed in terms of release of [3H]thymidine from prelabelled target cells over a 72‐h incubation period. High levels of cytolytic activity were consistently observed on transformed fibroblasts at attacker to target cell (A:T) ratios ranging from 5:1 to 40:1. Low, but significant, lysis of untransformed cells was observed only with two donors at the highest (40:1) A:T ratio tested. With all donors, the cytolytic activity on transformed lines was significantly greater than on untransformed fibroblasts. Thus natural human monocyte‐mediated cytotoxicity is preferentially expressed on transformed, as compared to untransformed, cells although sparing of the latter is not absolute.
Correlated expression of a B‐lymphocyte‐specific glycoprotein (gp27/35) and the EBV receptor/c3 receptor complex in sublines from the same Burkitt lymphoma
Authors: Klein George , Hyman Robert , Trowbridge Ian
Published: February 2007

A series of virus‐producer and non‐producer sublines, derived from the Burkitt lymphoma line Jijoye and its P3HR‐1 clone, were previously found to differ in the expression of EBV receptors and, in parallel, C3 receptors. The differences could be related to an “internal selection” caused by the cytopathic P3HR‐1 virus variant, favouring the growth of receptor‐negative cells. We have now analyzed the same lines for the expression of a B‐lymphocyte‐specific glycoprotein (gp27/35). A close parallellism was found between the expression of the EBV receptor‐complement receptor complex and the glycoprotein, measured by quantitative absorption. The results favour a relationship between gp27/35 and EBV/C3 receptor expression.