bluuebunny/crossref_metadata_2025 huggingface dataset:
Studies on epstein‐barr virus‐related antigens. III. Purification of the virus‐determined nuclear antigen (EBNA) from non‐producer raji cells
Authors: Matsuo T. , Hibi N. , Nishi S. , Hirai H. , Osato T.
Published: February 2007

The purification of Epstein‐Barr virus‐determined nuclear antigen (EBNA) was attempted on the basis of its biochemical and physicochemical properties and its immunological specificity, assayed by the indirect single radial immunodiffusion test and anti‐complement immunofluorescence absorption test. When non‐producer Raji cell extract was subjected to 20–60% saturated ammonium sulfate fractionation, followed by DNA‐cellulose chromatography and immunoadsorbent chromatography, EBNA was purified more than 3,000 times with a 8% yield. Such purified protein was composed of three polypeptides with molecular weights of 100,000 ± 5,000, 70,000 ± 5,000 and 50,000 daltons, respectively, on SDS‐polyacrylamide gel electrophoresis. Similar purification was achieved by heating the extract at 70° C for 10 min, instead of ammonium sulfate fractionation, followed by DNA‐cellulose chromatography and immunoadsorbent chromatography. This final preparation consisted almost exclusively of 100,000 ± 5,000 daltons polypeptide, 50,000 polypeptide, and the 70,000 ± 5,000 polypeptide passing through the adsorbent column. These findings suggest that EBNA is probably a molecular complex of three smaller subunits of heat‐stable 100,000 ± 5,000 and 50,000 daltons and heat‐labile 70,000 ± 5,000 daltons polypeptides, respectively.
Burkitt's lymphoma in Iraq. Clinical and pathological study of forty‐seven patients
Authors: Al‐Attar Adil , Al‐Mondhiry Hamid , Al‐Bahrani Zuhair , Al‐Saleem Tahseen
Published: February 2007

The clinical and pathological features of 47 patients with Burkitt's lymphoma seen at the University of Baghdad Teaching Hospital over the years 1969–1977 are described. There were 30 males and 17 females with a mean age of 7.5 years. All patients presented with advanced disease; 44 were in Stage III and 3 in Stage IV, (1 with central nervous system involvement; 1 with bone‐marrow involvement; 1 presented as acute leukaemia). The abdomen, with or without other sites, was involved in 42 patients. Thirty‐four patients died within 18 months, 11 in the immediate post‐operative period. Cyclophosphamide in variable dosages was administered to 29 patients with a good response in 15. The 3 patients with Stage IV disease died with poor response to therapy. Thus, in Iraq, a non‐endemic area for the disease, Burkitt's lymphoma seems to have somewhat different clinical and pathological features from the endemic (African), or the rare, sporadic disease reported eisewhere.
Cytolytic and cytostatic activity on tumor cells of circulating human monocytes
Authors: Mantovani Alberto , Jerrells Thomas R. , Dean Jack H. , Herberman Ronald B.
Published: February 2007

Monocytes from the peripheral blood of normal adult human donors were found to have appreciable levels of cytotoxic activity against murine and human tumor‐cell lines. Adherent cells ( > 90% monocytes) were obtained from the peripheral blood of 29 normal healthy volunteers either by adherence on plastic and scraping with a rubber policeman or by adherence on microexudate‐coated plastic and exposure to ethylene diamine tetra‐acetic acid. Cytolytic capacity was tested by incubating effector cells for 72 h with murine and human tumor cell lines prelabelled with tritiated thy‐midine. Cytostasis was evaluated by inhibition of [125I]iododeoxyuridine (125IdUrd) uptake. Tumor target cells employed were: a murine SV40‐trans‐formed kidney line (TU5), a murine chemically‐induced sarcoma (1023), a human breast‐cancer‐derived cell line (G11) and a human lung‐cancer‐derived cell line (CaLu). Monocyte preparations at attacker to target cell ratios of 1:1 to 40:1, showed significant cytolytic and cytostatic activity against tumor target cells. Tumor cells showed different susceptibility to cytolytic activity, whereas comparable levels of cytostasls were observed with the various targets: TU5 and G11 tumor cells were more susceptible than 1023 and CaLu target cells to the cytolytic capacity of human monocytes and TU5 was used in most subsequent experiments. Peak isotope release from prelabelled target cells was observed after 72 h of incubation, whereas peak inhibition of [125I]dUrd uptake occurred after 24 h of culture. The cytotoxic capacity of monocytes isolated by either of the two methods mentioned above was similar. The monocytes had higher cytotoxic activity than unseparated mononuclear cells, and non‐adherent cells showed minimal cytotoxic effects. Cytotoxicity by natural killer cells did not appear to have a major role in these assays, since adherent cells did not lyse K562 cells in a 4‐h 51Cr release assay. Treatment with anti‐human T‐cell serum and complement did not inhibit the cytotoxic capacity of the monocyte preparations, whereas exposure to silica particles significantly inhibited the cytotoxic activity. Monocyte‐mediated cytotoxicity on tumor cells was expressed in the presence of both fetal bovine serum and human AB serum.
Reactive antibodies in the bronchial washings of lung cancer patients
Authors: Paluch Edward , Ioachim Harry L.
Published: February 2007

Lung‐carcinoma‐reactive antibodies have been previously isolated from tumor tissues and pleural effusions. To explore the immunoglobulin (Ig) content of bronchial secretions, bronchial washings of patients with inflammatory and neoplastic lung diseases were studied with respect to Ig levels and specificity. Expressed as Ig/potassium ratios, statistically significant increases in Ig levels were found in inflammatory diseases and even higher increases in lung carcinomas. The isolation of Ig from bronchial washings was achieved by dissociation of immune complexes at low pH, neutralization and subsequent purification by anion exchange chromatography. The isolated immunoglobulins were tested in indirect immunofluorescence against lung cancer cells of various histologic types In tissue cultures and fresh suspensions. Positive cytoplasmic fluorescence was obtained with cells of adeno carcinomas and squamous‐cell carcinomas of the lung but not with cells of normal lung. The accessibility of bronchial washings makes the investigation of their lung‐cancer‐reactive Immunoglobulins relatively easy and raises the possibility of its eventual conversion into a screening test.
Carcinogenesis of hexachlorobenzene in mice
Authors: Cabral J. R. P. , Mollner T. , Raitano F. , Shubik P.
Published: February 2007

Hexachlorobenzene (HCB) is a fungicide and a by‐product in the manufacture of many chlorinated solvents and pesticides. In Turkey, between 1955 and 1959 HCB was the causative agent of an epidemic of toxic porphyria, which involved more than 3,000 people, predominantly children. HCB was studied in long‐term experiments for carcinogenicity in mice. Outbred Swiss mice were given HCB in the diet at dose levels of 50, 100 and 200 parts per million (ppm), for 101–120 weeks. Survival rates in females and males of group HCB 200 were markedly affected by deaths due to toxic manifestations of HCB. All survivors were killed at 120 weeks. Exposure to HCB resulted in an increased incidence of liver‐cell tumors in groups HCB 100 and HCB 200. No liver‐cell tumors were observed in the controls and in the group fed HCB 50. The incidence of mouse lympho‐mas was 35% in controls and 11% in HCB 200. The decrease reflects probably the shortest life‐span of HCB‐treated animals. The incidence of lung tumors was higher in controls than in the treated groups, but the multiplicity (nodule/mouse) was approximately the same in all groups. In a separate experiment 30 female and 30 male mice were administered 300 ppm HCB in the diet for only 15 weeks. Most of the males died early. The survival rate at 110 weeks of age was 10% and comparable to that of controls. Two mice in the HCB 300 group developed liver‐cell tumors. The proportion of tumor‐bearing animals and the incidence of lymphomas, lung adenomas and other tumor types in HCB 300 mice were similar to those reported in control animals. The present results indicate the carcinogenicity effect of HCB in mice.
Rigid plasma‐membrane‐derived vesicles, enriched in tumour‐associated surface antigens (MLr), occurring in the ascites fluid of a murine leukaemia (GRSL)
Authors: van Blitterswijk W. J. , Emmelot P. , Hilkmann H. A. M. , Hilgers J. , Feltkamp C. A.
Published: February 2007

Extracellular membraneous vesicles of GRSL leukaemia cells were isolated from the ascites fluid bathing the cells in vivo, and from cell washes. Mammary tumour virus‐induced antigens (MLr) expressed on the surface of the cells are enriched on these vesicles as compared to plasma membranes isolated from the cell homogenate. The lipid fluidity of the vesicles is much smaller than that of the plasma membranes, and the content of the pertinent lipid parameters, cholesterol and sphingomyelin, are accordingly greatly increased. The extracellular vesicles which are also enriched in sialic acid and 5‐nucleotidase are apparently derived from the plasma membrane, probably at least partly by exfoliation of selected parts or domains of the surface of living cells. An analogy between this shedding of vesicles, the formation of endocytotic vesicles and the budding of viruses is noted; all these processes select or assemble rigid lipid domains of the cell membrane. The possible participation of surface microvilli and sub‐lethal autolysis in the process of shedding is discussed.
Tumour angiogenesis factor (TAF) and its neutralisation by a xenogeneic antiserum
Authors: Phillips Paul , Kumar Shant
Published: February 2007

Tumour angiogenesis factor (TAF) has been extracted from a variety of animal and human tumours. Its ability to induce neovascularization in two bioassays, viz. rat air‐sac and chick chorio‐allantoic membrane, is demonstrated. Similar extracts from normal tissues fail to induce angiogenesis. TAF extracts have been used to raise a xenogeneic antiserum, the specificity of which was investigated using classical immunological methods. Its ability to neutralize the biological activity of TAF using the two in vivo assays, was also demonstrated.
Enhanced induction of growth of B lymphoblasts from fresh human blood by primate type‐C retroviruses (gibbon ape leukemia virus and simian sarcoma virus)
Authors: Markham P. D. , Ruscetti F. , Salahuddin S. Z. , Gallagher R. E. , Gallo R. C.
Published: February 2007

Cell lines were established from the fresh peripheral blood of over 50% (11 of 21) of Epstein‐Barr virus (EBV) seropositive human donors after exposure to viruses of the gibbon ape leukemia virus (GALV)—simian sarcoma virus/simian sarcoma‐associated virus (SiSV/SiSAV) group. The incidence of growth induction upon exposure to baboon endogenous virus (BaEV), feline leukemia virus (FeLV) or to uninfected monolayer cultures was lower than 10%. Leukocytes from the peripheral blood of leukemic patients gave similar results, but exposure of fresh peripheral blood from eight normal EBV seronegative donors to the same viruses did not result in induction of cell growth. The established cell lines were polyclonal B‐lympho‐blasts as determined by morphological cytochemlcal, immunological and functional properties. The cells expressed EBV nuclear antigen (EBNA test), formed rosettes with complement‐activated sheep or bovine erythrocytes (EAC‐rosette test), but not with untreated erythrocytes (E‐rosette test), and were positive for one or more surface‐bound immunoglobullns. They were also karyotypically normal as determined by standard chromosome analysis and by trypsin‐Giemsa banding techniques. However, unlike other reported newly‐established diploid B‐lymphoblast cell lines, cells from approximately 80% of the cultures tested grew as locally invasive tumors when inoculated into 1‐to 3‐week‐old athymic nude mice and formed colonies in semi‐solid medium. Lymphoblasts from nude mouse tumors were readily re‐established as suspension cultures which retained their lymphoblastic properties and remained karyotypically normal. These studies indicate that under certain conditions, type‐C retroviruses of the GALV‐SISV/ SISAV group directly or indirectly increase the incidence of transformation of human B lymphocytes.
Effects on in vitro tumor growth of macrophages isolated from human ascitic ovarian tumors
Authors: Mantovani Alberto , Peri Giuseppe , Polentarutti Nadia , Bolis Giorgio , Mangioni Costantino , Spreafico Federico
Published: February 2007

Macrophages were isolated from 22 human ascitic ovarian epithelial tumors and their growth‐inhibitory capacity was tested using as targets the following in vitro tumor cell lines: murlne TLX9 lymphoma and FS6 sarcoma; human myeloid K562 leukemia and human E cell line derived from an ovarian carcinoma. Macrophage preparations were heterogeneous in their interaction with tumor target cells, and assay conditions, such as the type of target cell, incubation time, and attacker to target cell (A:T) ratio critically affected the evaluation of the cytotoxic potential of tumor‐associated macrophages. At an A:T ratio of 7:1 no cytostatic activity on TLX9 and K562 cells was ever observed, but in the presence of specific antibody 8 out of 12 macrophage preparations tested showed significant antibody‐dependent cytotoxicity on TLX9 lymphoma cells. Macrophage preparations from two patients significantly inhibited growth of the FS6 sarcoma and a cytostatic activity on E cells was observed in five additional patients. Significant stimulation of the proliferative capacity of at least one of the target cell lines was observed in 11 subjects at an A:T ratio of 7:1. In 12 patients, macrophage cytostatic activity on E cells was also tested at an A:T ratio of 35:1; eight out of 12 preparations showed significant cytotoxicity under these conditions. When the same subject was repeatedly tested at short intervals the same pattern of inhibition or stimulation of tumor growth was observed.
A comparison of the prognostic value of antibody‐dependent lymphocyte cytotoxicity and other ebv antibody assays in Chinese patients with nasopharyngeal carcinoma
Authors: Chan S. H. , Levine P. H. , De‐Thé G. B. , Mulroney S. E. , Lavoue M. F. , Glen S. P. P. , Goh E. H. , Khor T. H. , Connelly R. R.
Published: February 2007

Antibody titres to EBV‐associated antigens in Chinese NPC patients were analysed according to length of survival after diagnosis and to disease stage. Geometric mean titres of ADLC antibody were highest in the long‐term survivors, whereas VCA, EA and EBNA antibody titres showed an inverse relationship to survival. High VCA, EA and EBNA titres were less frequent, and high ADLC titres were more frequent in long‐term survivors than in intermediate or short‐term survivors. The association of geometric mean titres of EBV antibodies with prognosis could not be entirely explained by stage of disease. A functional role for the ADLC antibody is suggested by the association of a high ADLC antibody titre with a good prognosis regardless of stage of disease.
Azathioprine‐induced lymphocytic neoplasms of NZB mice lack ecotropic murine leukaemia virus
Authors: Harvey Jennifer J. , East June , Katz Fay E.
Published: February 2007

NZB mice injected intramuscularly throughout a 6‐month period with the immunosuppressant azathioprine (Imuran) developed lymphocytic lymphomas 6–7 months after treatment was initiated. These malignancies were quite distinct from the reticulum‐cell neoplasia which occurs spontaneously in the strain, and were readily transplantable to NZB or histocompatible BALB/c recipients. Xenotropic, but not ecotropic murine leukaemia virus (MuLV) was detected in leukaemic tissues of some donor and recipient NZBs when tested in vitro by co‐cultivation with permissive cell lines, genome rescue, XC and viral polymerase assays. Virus filtrates prepared from donor leukaemic tissues were non‐pathogenic when injected into newborn C3H mice. These results are evidence against a mandatory ecotropic MuLV genome in lymphocytic neoplasia.
A quantitative assay for tumor antigen based on inhibition of cytotoxicity of sensitized lymphocytes
Authors: Huber Sally , Lucas Zoltan J.
Published: February 2007

Specific inhibition of cell‐mediated cytotoxicity can be used as a quantitative measure of soluble tumor antigen if highly cytolytic cells are obtained. In vitro secondary stimulation of spleen cells sensitized in vivo to the syngeneic 13762A mammary adenocarcinoma results in a lymphocyte population consistently more cytolytic than lymphocytes after primary stimulation. Maximal cytolysis requires removal of dead lymphocytes from the effector population. Soluble tumor antigen (STA) is detected only in supernatant: of 13762A mammary tumor cultures grown in the presence of the proteolytic enzyme inhibitor, ε‐amino caproic acid. Soluble MTM antigen preparations block lymphocytes immune to the mammary tumor but not lymphocytes immune to a second mammary adenocarcinoma (R3230) or to allogeneic spleen cells. Soluble antigen preparations from other tumors do not inhibit lymphocytes specifically cytolytic to the 13762A tumor. Additional evidence that the STA preparation contains tumor antigen is its ability to induce specific cytolytic lymphocytes and partial protection from challenge with live MTA tumor cells.
Interactions of murine leukemia virus (MuLV) with isolated lymphocytes. Iv. The role of mitogen‐induced cellular dna synthesis in virus infection and replication
Authors: Cerny Jan , Isaak Dale D.
Published: February 2007

The requirement for lymphocyte activation with mitogen during in vitro infection with murlne leukemia virus (MuLV) of Friend virus complex (FV) and the suppressive effects of MuLV on mitogen‐induced lymphocyte activation were studied in short‐term suspension cultures. Lymphocytes were infected with FV in vitro and then resuspended in culture medium with or without mitogens. Cells releasing infectious MuLV were enumerated as infectious centers (IC) on sarcoma virus+, leukemia virus‐fibroblasts. The accumulation of IC in cultures followed a Diphasic curve characterized by a plateau between days 1 and 4 and by a 10‐fold increase in IC between days 5 and 7. Stimulation with a B‐cell mitogen, bacterial lipopolysaccharide (LPS), following infection increased the number of IC 10‐to 40‐fold. On the other hand, stimulation with concanavalin A (Con A), a T‐cell mitogen, did not appreciably increase the number of 1C detected on day 5 post infection. Further studies on the role of LPS‐induced DNA synthesis in the enhancement of MuLV replication revealed two points: (1) a comparable enhancement of 1C was observed In cultures stimulated with LPS 2 days prior to or immediately after FV infection and in those which were not stimulated until 2 days after infection; (2) treatment of FV‐infected, LPS‐stimulated lymphocytes with 5,6‐bromodeoxyuridine (BrdUrd) and visible light at 2 days abolished cellular DNA and RNA synthesis but did not diminish subsequent MuLV replication; however, cellular DNA and RNA synthesis as well as MuLV replication were inhibited in LPS‐stimulated cells treated with BrdUrd and light prior to infection with FV. The uptake of both [3H]thymidine and [14C]uridine by LPS‐stimulated lymphocytes was inhibited by about 50% in the presence of infectious FV whereas uptake in Con‐A‐stimulated lymphocytes was not inhibited. Kinetic studies showed that the inhibition of LPS stimulation was not detectable until 24 h and later; the uptake of [3H] thymidine during the first 12 h after infection and mitogen activation was the same in infected and non‐infected cultures. Collectively, the results indicate that MuLV‐Friend infects normal B cells but that the subsequent virus replication and secondary infection remain low unless the cells are activated with a mitogen. Virus replication, however, eventually become independent of cellular DNA synthesis and the virus itself inhibits the cellular nucleic acid synthesis at a later stage in the infection.
Effector and suppressor lymphoid cells in tumor‐bearing guinea‐pigs
Authors: Berczi I. , Sehon A. H.
Published: February 2007

The immune reaction of guinea‐pigs against their growing tumors was studied. Strain 13 guinea‐pigs were killed 2 weeks after SC implantation of the transplantable methylcholanthrene‐induced sarcoma (MC‐D), when the tumor was 2–3 cm In diameter. Spleen, lymph‐node, bone‐marrow and peripheral blood leukocytes (PBL), and subsets of spleen cells and PBL were mixed with lethal doses (105) of tumor cells and inoculated SC into normal recipients. Spleen, lymph‐node and bone‐marrow cells either enhanced or did not influence tumor growth, while PBL exerted a strong inhibitory effect. Normal spleen and normal PBL did not affect tumor growth. The spleen cells of tumor‐bearing animals were separated on nylon wool columns: the first fraction containing T cells was responsible for tumor enhancement, the second fraction containing predominantly non‐T (Ia+) cells inhibited tumor growth. Adherent cells had no effect. Similarly, after removal of T cells from the spleens with a specific rabbit antiserum or of non‐T cells plus a minor portion of T cells with an anti‐la serum (produced in strain 2 guinea‐pigs), the remaining cell population had, respectively, an inhibitory or an enhancing effect on tumor growth. By contrast, removal of either T or la+ cells from PBL eliminated their anti‐tumor effect. The major portion of splenic T cells formed EA rosettes. EA rosette‐positive cells were restricted to a minor portion of peripheral T lymphocytes. Thus, splenic and peripheral T cells from tumor‐bearing animals were different both functionally and according to their surface markers. It is hypothesized that Fc+ T cells are suppressors which are triggered by immune complexes.
Uninhibited growth and metastases of herpes simplex virus‐transformed cells in virus‐sensitized hosts
Authors: Hay Kathleen A. , Lausch Robert N.
Published: February 2007

Four established tumour lines of hamster cells transformed by herpes simplex virus (HSV) but not shedding the virus were examined for continued expression of virus‐associated antigens. Hamster or rabbits, appropriately immunized to the tumour cells, produced virus‐neutralizing antibody. The serum titres were invariably low, suggesting that only small quantities of virion antigen were present in the cells. Hamsters sensitized to HSV and resistant to virulent virus challenge did not reject low numbers of tumour cells, nor was the incidence of lung metastases significantly reduced. Virus‐sensitized lymph‐node cells, readily cytotoxic for HSV‐infected hamster embryo fibroblasts, did not lyse any of three transformed lines tested in an 18‐h 51chromium release test. Animals that had their tumour excised demonstrated no or only modest resistance to tumour rechallenge. Thus, virus‐specific transplantation rejection antigen could not be detected in the HSV tumour lines although low levels of virus structural antigens were present.
Dissociation of anti‐tumor immune responses in rats immunized with solubilized tumor‐associated antigens from a methylcholanthrene‐induced fibrosarcoma
Authors: Minami Akio , Mizushima Yutaka , Takeichi Noritoshi , Hosokawa Masuo , Kobayashi Hiroshi
Published: February 2007

Soluble tumor antigens were prepared from chemically‐induced rat fibrosarcoma KMT‐17 cells by various methods [Na‐deoxycholate (DOC), 3 M‐KCI extraction, and crude membrane preparations by mechanical disruption]. Soluble tumor antigens prepared by DOC extraction (DOC‐STA) could be detected by a radioisotopic footpad assay (FPA) and they showed the strongest antigenic activity in KMT‐17 immune rats. Anti‐tumor immune responses in rats previously immunized with DOC‐STA were measured by FPA, Winn assay, and transplantation resistance. Significant responses detected by the FPA and Winn assay were demonstrated in rats immunized with DOC‐STA. However, rats previously immunized with DOC‐STA showed a significant enhancement of tumor growth when challenged with KMT‐17 cells. This enhancement was specific for the tumor line used. Normal rats which received adoptive transfer of thymus and spleen cells from rats immunized with DOC‐STA produced specific enhancement of tumor growth as compared with non‐treated rats. Administration of cyclophosphamide before immunization with DOC‐STA abrogated the enhanced tumor growth in the host. These results suggest that immunization with soluble tumor antigens specifically enhanced tumor growth by the induction of immunosuppressor cells. Dissociation between the anti‐tumor immunity detected by the FPA and Winn assay and the enhanced tumor growth detected by transplantation resistance in rats immunized with DOC‐STA is discussed.
Age as a modifying factor of 7, 12‐dimethylbenz(a)‐anthracene‐induced mammary carcinogenesis in the lewis rat
Authors: Haslam Sandra Z.
Published: February 2007

The influence of age at DMBA administration on (1) susceptibility to mammary tumor development, (2) the proportion of tumors which are ovary‐dependent, and (3) the frequency of spontaneous tumor regression was examined in female Lewis rats between 25 and 200 days of age. Tumor development was monitored for a 12‐month period after carcinogen administration. Age at carcinogen administration affected (1) the number of tumors induced, (2) the latent period of tumor development, and (3) the number of tumors which regressed spontaneously. More tumors developed in young rats; however, a large fraction of these tumors regressed spontaneously. The frequency of spontaneous tumor regression was strongly age‐related, being highest in rats treated up to 70 or after 150 days of age. Mean latent period of development of tumors which regressed spontaneously (SRT) was significantly shorter than that of tumors which grew progressively (PGT). Furthermore, mean latent period of SRT development was significantly shorter in rats treated at 25 or 50 days of age. In contrast, all age‐groups were equally susceptible to the development of progressively growing tumors (PGT). PGT incidence, mean latent period of PGT development, mean numbers of PGT per PGT‐bearing rat and the relative proportion of PGT which were ovary‐dependent were similar for all age‐groups at the end of 12 months. These results indicate that, in the Lewis rat strain, age does not confer significant or permanent refractoriness. Furthermore, spontaneous tumor regression is a frequent and strongly age‐related phenomenon.
Influence of the mouse hepatitis virus (MHV) infection on the growth of human tumors in the athymic mouse
Authors: Kyriazis Andreas P. , Dipersio Linda , Michael J. Gabriel , Pesce Amadeo J.
Published: February 2007

The growth characteristics and histological appearance of tumors resulting from transplantation of the tumor lines HEp‐2 and SW480 into pathogen‐free and mouse hepatitis virus infected athymic mice were studied. Subcutaneous or intra‐peritoneal implantation 1 × 106 neoplastic cells into pathogen‐free animals resulted in tumor growth. Subcutaneous transplants grew locally, surrounded by a capsule of connective tissue. The fibrovascular stroma supporting the neoplastic tissue was minimal and infiltration of tumor capsule was observed. Intraperitoneal tumors grew in a multifocal pattern, were not encapsulated, showed marked invasiveness and metastasized. The same number of neoplastic cells (1×106) transplanted into hepatitis‐positive animals failed to develop into grossly visible tumors. When the number of transplanted cells was increased to 2×107, tumors appeared in a few animals. All tumors, regardless of the site of transplantation, were characterized by the presence of severe fibrohistiocytic reaction at the site of implantation that possibly influenced the tumor growth. No evidence supporting T‐cell‐mediated tumor rejection was observed. It is concluded that the state of health of the athymic mice is critical for the growth of human tumors and may account for the variations in reporting successful transplantation of such tumors in nude mice.
Neutralization of pseudotypes of vesicular stomatitis virus by sera from avian retrovirus‐infected hosts
Authors: Mandeville Rosemonde , Rohan Peter , Wainberg Mark A.
Published: February 2007

We investigated the capacity of lymphocytes and sera from chickens bearing tumors induced by avian sarcoma viruses (ASV) to interact with phenotypically mixed particles of vesicular stomatitis virus (VSV) and ASV. Immune chicken sera were able to specifically neutralize such VSV pseudotypes. This ability could be absorbed out, however, on purified preparations of avian retro‐viruses, suggesting that reactivity was primarily against avian retrovirus envelope components. Supernatant fluids containing phenotypically mixed particles were unable to stimulate division of lymphocytes of tumor‐bearing hosts, an ability possessed by culture fluids containing native ASV particles. Polyacrylamide gel analysis was unable to resolve any distinct pseudotype protein, which was not present in either of the parental virus types. Treatment with crude preparations of ultraviolet (UV)‐irradiated VSV pseudotype material did not afford immunity against subsequent challenge with live ASV.
A new virion precipitation test for oncovirus envelope antigens which detects common antigenic determinants in mammalian type‐C viruses and mason‐pfizer monkey virus
Authors: Altstein A. D. , Zakharova L. G. , Zhdanov V. M.
Published: February 2007

A method for the study of oncovirus envelope antigens was developed, based on the precipitation of intact virions by a double antibody technique. The amount of precipitated virus was then measured as reverse transcriptase activity. The method was designated the virion precipitation test (VPT). It has been used for titration of antibodies to envelope antigens of oncoviruses. The study of envelop antigens of 11 different oncoviruses permitted their differentiation into the following groups: (1) murine type‐C viruses: (2) feline type‐C viruses; (3) simian type‐C viruses; (4) the RD‐114/BEV group; (5) Mason‐Pfizer monkey virus (M‐PMV); (6) bovine leukemia virus; (7) avian type‐C viruses; (8) mouse mammary tumor virus. No common antigenic determinants were detected in the last three groups. Mammalian type‐C viruses (RD‐114, NIH‐MuLV, G‐MuLV) had common antigenic determinants in the envelope, as demonstrated with an anti‐RD‐114 serum. Mammalian type‐C viruses also shared antigenic determinants with M‐PMV. The relationship of type‐C viruses to M‐PMV decreased in the follwoing order: RD‐114—NIH‐MuLV—G‐MuLV. It was also shown that the endogenous xenotropic feline RD‐114 virus was more closely related to xenotropic NIH‐MuLV than to ecotropic G‐MuLV. The nature of the common antigenic determinants, as demonstrated by VPT on the surface of mammalian type‐C viruses and M‐PMV, and their significance for the concept of oncovirus evolution are discussed.
Cell surface glycoprotein changes in Epstein‐Barr virus‐positive and ‐negative human hematopoietic cell lines
Authors: Van Beek Wim P. , Nilsson Kenneth , Klein George , Emmelot Peter
Published: February 2007

It has previously been shown that differential fucose labelling of many normal and homologous tumor cells, followed by proteolytic release and degradation, yields glycopeptides which upon gel filtration shown an increase in fast‐eluting glycopeptides for the tumor cells. This technique has now been applied to cell‐surface glycoproteins of different human hematopoietic cell lines. These lines included Epstein‐Barr virus (EBV)‐carrying lymphoblastoid cell lines of presumed non‐neoplastic origin, and malignant EBV‐genome‐positive Burkitt lymphoma and EBV‐negative non‐Burkitt lymphoma, leukemia and myeloma lines. As compared with normal peripheral lymphocytes, both the lymphoblastoid type of cell lines and the different types of lines of proven malignant ancestry contained the fast‐eluting glycopeptides on their cell surface with very few exceptions. It is therefore concluded that (I) malignant conversion of human lymphoid cells in vivo is commonly, but not obligatorily, associated with a specific change in the composition of the fucosyl glycopeptides, and (2) EBV infection of B lymphocytes does not lead only to the well‐documented immortalization in vitro but also, as a rule, to the same type of alteration in fucosyl glycopeptides as was demonstrated for the neoplastic cell lines. It proved possible to distinguish several categories of hematopoietic cell lines due to the effect that pretreatment of the glycopeptides with neuraminidase or mild acid exerted on their subsequent chromatographic behavior.
Moloney lymphoma cells express a polyprotein contanining the GAG gene‐coded p15 and the moloney leukemia virus‐induced cell surface antigen (MCSA)
Authors: Karande Anjali , Yefenof Eitan , Fenyö Eva Maria , Klein George
Published: February 2007

The relationship between MCSA and the viral structural proteins in YAC Moloney lymphoma cells was further investigated by using membrane immunofluorescence and immunoadsorbent columns. As previously observed, MCSA showed only minimal capping and thereby differed In behaviour from gp70, p30 and p12 virion antigens. Whereas antibody‐induced capping of gp70 did not change the membrane distribution of MCSA, co‐capping was observed between MCSA and p30 and p12 gag protein antigens. This indicated that, whereas MCSA is distinct from gp70, it is linked to p30 and p12 on the membrane of living cells. It was then attempted to isolate MCSA on anti‐p30 and anti‐pIS immunoadsorbent columns from solubilized YAC cells. Contrary to what was expected, no MCSA was bound to the anti‐p30 column. On the other hand, a part (10–15%) of the MCSA was bound to the anti‐pIS column, indicating that MCSA is linked to the gag p15.
Expression of Fv‐4r allele in hematopoietic cells from g mice resistant to friend leukemia virus
Authors: Ikeda Hidetoshi , Odaka Takeshi
Published: February 2007

G mice carrying the Fv‐4 resistant allele supported virus growth neither at an early nor a later (Kai et al., 1976) stage of infection with NB‐tropic FLV. This resistance could not be abolished by treatment of G mice with cyclophosphamide or cortisone acetate. By bone‐marrow or spleen‐cell transplantation into irradiated mice, the resistance of G mice could be transferred to Fv‐4‐susceptible mice. Conversely, transfer of bone‐marrow or spleen cells of Fv‐4‐susceptible mice rendered G mice susceptible. It could be concluded that, as assessed by the virus content in the spleen, helper LLV grows mainly in radiosensitive, bone‐marrow‐derived cells, and the Fv‐4 gene is expressed in these cells.
Antiserum to murine leukemia virus recognizes novel cell surface molecules associated with growth control and transformation
Authors: Rieber Manuel , Rieber Mary , Alonso Mina
Published: February 2007

Antiserum directed against murine leukemia virus also reacts with several external proteins present in rat cells transformed by a temperature‐sensitive Rous sarcoma virus. Reaction of iodinated cell extracts with anti‐MLV (murine leukemia virus) serum revealed the presence of a 200,000 dalton iodinated component detectable also by metabolic labelling with glucosamine only in serum‐starved cultures restricted in the expression of transformation. A similar assay with iodinated cells that express the transformed phenotype revealed the preferential recognition of two components with an approximate molecular weight of 100,000 daltons as well as an additional 65,000‐dalton external component. Growth of the transformed non‐producer NT3‐KR cells in the presence of inducers of C‐type viruses leads to an increased synthesis of a 100,000‐dalton glycoprotein (gp100) recognized by the anti‐MLV serum, which is also recognized by the antiserum in NRK‐MSV‐MLV transformed producer cells, in addition to a virus‐like glycoprotein of 71,000 dalton (gp71). Absorption of the anti‐MLV serum with monolayers of NT3‐KR cells eliminated the ability of the serum to recognize the gplOO but not the gp71 from NRK‐MSV‐MLV‐transformed producer cells. The mediation of post‐translational changes in growth control is suggested by the transformation‐dependent alteration in the molecular weight of the non‐virion surface proteins recognized by anti‐MLV serum in the rat cells used in this study.
Cell‐mediated reactivity to antigens shared by moloney‐virus‐induced lymphomas (LSTRA) and certain 3‐methylcholanthrene‐induced mouse sarcomas
Authors: Hellstrom I. , Hellstrom K. E. , Zeidman L. , Bernstein I. D. , Brown J. P.
Published: February 2007

Spleen cells (SC) both from BALB/c mice whose primary Moloney sarcoma virus (MSV)‐induced sarcomas had spontaneously regressed and from normal, untreated BALB/c mice, were co‐cultivated for 5 days with mitomycin‐C‐treated LSTRA cells; LSTRA is a BALB/c Moloney lymphoma which shares cell surface antigens with MSV‐induced sarcomas. These SC, referred to as CMR and CU cells, respectively, were shown to be cytotoxic to LSTRA cells in 3 h 51Cr‐release assays; CMR cells showed, in most cases, the greatest lytic activity against LSTRA targets. The same SC were also reactive, in 20‐h microcytotoxicity and 51Cr‐assays, against target cells from a variety of transplanted sarcomas induced by 3‐methylcholanthrene (MCA) in BALB/c mice. The highest reactivity was seen when CMR or CU cells were tested against target cells from sarcoma lines that expressed an NB‐ecotropic MuLV cross‐reacting serologically with Moloney virus. Reactivity against isotope‐labelled tumor cells expressing MuLV‐associated cell surface antigens could be competitively inhibited by adding unlabelled tumor cells expressing such antigens. Finally, Winn assays were performed in which CMR cells strongly inhibited the outgrowth of cells from three sarcoma lines that express the NB‐ecotropic MuLV. There was less but significant inhibition of cells from some other MCA sarcomas, either negative for the expression of MuLV‐associated antigens or expressing the N‐ecotropic endogenous BALB/c MuLV. CU cells enhanced tumor outgrowth in Winn assays at least as often as they inhibited it.
Low natural killer‐cell activity and immunoglobulin levels associated with smoking in human subjects
Authors: Ferson M. , Edwards Anne , Lind Anne , Milton G. W. , Hersey P.
Published: February 2007

Previous studies have shown that smoking is associated with a high incidence of certain malignancies and a high incidence of metastatic spread of melanoma. The purpose of the present study was to examine whether this high incidence of malignancy could be associated with certain aspects of immune function believed to be important in restricting tumour growth. Age‐and sex‐matched smoking and non‐smoking normal subjects and male, smoking and non‐smoking melanoma patients, were studied for the natural killing (NK) activity of their blood leukocytes against cultured melanoma and Chang cells. The levels of the various immunoglobulin classes in their sera and the E rosette levels of the normal subjects were also assessed. The results indicate that the NK activity of blood leukocytes from both normal subjects and melanoma patients who smoked was significantly lower against cultured melanoma cells than that of non‐smokers. Smokers were also shown to have lower IgG and IgA Immunoglobulin levels in their sera compared to non‐smokers but no differences in the percentage of E‐rosetting (T) cells was detected. Recent studies provide some basis for the belief that the low NK activity and immunoglobulin levels in smokers may be related. These results further suggest that a closer examination of the effects of this environmental hazard on the immune system and its relation to malignancy is needed.
Isolation and characterization of lymphocytes and macrophages from solid, malignant human tumours
Authors: Svennevig Jan‐L. , Lövik Martinus , Svaar Helge
Published: February 2007

In mechanically prepared cell suspensions from 17 solid, malignant human tumours, 0.5–5.0% (mean 2.0%) lymphocytes and 1.0–28.0% (mean 7.4%) macrophages were found. Mononuclear cells (MC) were isolated using the Böyum technique. From each biopsy weighing 1–4 g, on average, 1.3×106 lymphocytes and 0.8×106 macrophages were reco vered. The tumour‐infiltrating lymphocytes (TIL) were characterized with regard to T and B markers. The proportion of TIL‐forming rosettes with SRBC (T cells) was 43%, which was significantly less than for peripheral blood lymphocytes (PBL) from cancer patients (58%), or normal controls (80%), On average, 15% of the TIL were B cells, whereas 42% had no T‐or B‐cell markers. Macrophages (TIM) were identified by non‐specific esterase staining and phagocytosis. In four cases the tumour cells were also stained with a‐naphthyl butyrate. Corresponding findings were made on esterase‐stained cryostat sections from four tumours. Macrophages were found within and around the tumour tissues, occasionally localized to necrotic areas, but in most cases with no sign of necrosis of the surrounding cells. In some tumour cell suspensions typical clusters of lymphocytes and macrophages were seen. Total lymphocyte and T‐cell counts were markedly reduced in the peripheral blood of cancer patients, whereas total monocyte counts were within the normal range.
A 14q+ chromosome in a B‐cell acute lymphocytic leukemia and in a leukemic non‐endemic Burkitt lymphoma
Authors: Slater R. M. , Philip P. , Badsberg E. , Behrendt H. , Hansen N. E. , Van Heerde P.
Published: February 2007

Chromosome analysis using banding staining techniques was carried out on cells from a B‐cell acute lymphocytic leukemia (ALL) of the Burkitt type and a case of non‐endemic Burkitt lymphoma presenting as ALL. In both patients a marker chomo‐some 14q+ was found which was morphologically identical to those reported for endemic and non‐endemic Burkitt lymphoma and a few other B‐cell malignancies. However, the origin of the translocated segment could not be identified in either case. In addition, both patients had a 13q+ chromosome with a breakpoint in the 13q3 region but involving different material of unknown origin. Other marker chromosomes in the B‐cell ALL included rearrangements of chromosome arms 1q and 6q. Serial studies showed that cells with a partial duplication of the long arm of chromosome No. 1, in addition to the 14q+ chromosome, were important in the karyotype evolution of the malignant cell population. In this patient the 14q + chromosome had a brightly fluorescing satellite region indicating the probable monoclonal development of the leukemic cell population. From this and other reports it appears that the B‐cell type of ALL is characterized by a 14q+ chromosome. Because of the pathological and cytogenetic similarities between certain types of B‐cell ALL and Burkitt lymphoma it is suggested that they may be different manifestations of the same disorder.
The role of the macrophage in Marek's disease: In vitro and in vivo studies
Authors: Haffer Keith , Sevoian Martin , Wilder Martin
Published: February 2007

Macrophages from Sand K‐strain Leghorn chickens, susceptible and resistant to Marek's disease (MD) respectively, were studied to determine the macrophage contribution to the dynamics of MD infection, tumorigenesis and genetic resistance to this disease. In vitro studies demonstrated that macrophages from both strains were similar in their responses toward JM strain of Marek's disease virus (MDV) and JM‐1 tumor cells. Macrophages were observed to phagocytize JM virus, but the interiorized virus was not seen to replicate within the macrophage or induce antigenic changes of the cell membrane. Clearance of JM‐1 tumor cells was by both cytolytic and phagocytic mechanisms. In vivo selective suppression of macrophage functions by antimacrophage serum or trypan blue inoculations resulted in significantly elevated viral titers and increased tumorigenesis, as compared to infected, non‐suppressed or non‐infected control groups. Results from this study indicate that genetic susceptibility or resistance to MD, as exhibited by Sand K‐strain chickens, respectively, is not controlled at the macrophage level. The role of the macrophage in MD infection appears to be specifically surveillance.
Enhancement of host cell reactivation of ultraviolet‐irradiated herpes simplex virus by caffeine, hydroxyurea and 5‐bromodeoxyuridine
Authors: Fogel Marian , Yamanishi Koichi , Rapp Fred
Published: February 2007

Enhancement of host cell reactivation (HCR) of ultraviolet (UV)‐irradiated herpes simplex virus (HSV) was demonstrated in cell cultures pretreated with caffeine, hydroxyurea, or 5‐bromodeoxyuridine (Brd Urd). The effect of caffeine on HCR was shown to depend on the time of drug treatment with respect to infection. In cultures treated with caffeine during the course of virus replication, the infectivity of irradiated HSV was reduced about nine‐fold, while cultures pretreated with the drug before infection showed an increase in infectivity. The extent of HCR enhancement depended on the time interval between treatment with caffeine and infection, drug concentration, and the UV irradiation dose to which HSV was exposed. Magnitude of enhancement of HCR by caffeine differed in various cell species. The results suggest that enhanced HCR of UV‐irradiated HSV by DNA antimetabolites is associated with DNA repair activated in consequence of cell DNA damage.
Immune suppression in BALB/c mice bearing the plasmacytoma TEPC‐183: Evidence for normal lymphocyte but defective macrophage function
Authors: Joshua D. E. , Brown G. , MacLennan I. C. M.
Published: February 2007

This paper analyses impairment of the primary immune response of mice bearing the plasmacytoma TEPC‐183. Healthy animals and mice bearing the reported non‐immunosuppressive tumour MOPC‐104E were used as controls. The defect was shown to affect both primary IgG and IgM responses to chicken cells (CRBC) and to be related to tumour size. However, the primary immune depression could be overcome either by increasing the antigen dose or by using Freund's complete adjuvant together with antigen. Secondary responses were also depressed. This depression was more pronounced if the animals was primed after, rather than before, tumour implantation. Further studies involved the measurement of primary immune responses of immunologically deprived syngeneic mice, after they had been reconstituted with cells from normal or tumour‐bearing mice. Lymphocyte reconstitution experiments were carried out in mice which had been irradiated with 950R. Various lymphoid preparations from TEPC‐183‐bearing mice were as effective as those from healthy controls in reconstituting primary immune responses. When mice were deprived of macrophage function by the method of Gorczynsky et al. (1971) using large doses of horse red cells macrophage preparations from normal mice were able to partially restore primary immune responsiveness. However, macrophages from TEPC‐183‐bearing mice were unable to bring about such restoration. It is concluded that the impairment of the primary immune response of mice bearing the plasmacytoma TEPC‐183 is due to a macrophage, rather than a lymphocyte, abnormality. However, none of these transfer studies suggested that positive suppression of primary immune responses was being mediated by cells from TEPC‐183‐bearing mice.
Methylation of DNA in target and non‐target organs of the rat with methylbenzylnitrosamine and dimethylnitrosamine
Authors: Fong Louise Y. Y. , Lin Hsiang Ju , Lee Clara Lai Hing
Published: February 2007

The sites of labelling of DNA with [14C]methyl groups from methylbenzylnitrosamine and dimethylnitrosamine were studied in rat oeso‐phageal epithelium and liver. All four combinations of tissue and carcinogen were studied. Tissues were labelled in vitro and the DNA contained therein purified and hydrolysed (pH 1, 37° C) to free purines and apurinic acid. Quantitative analysis was performed with the aid of thin‐layer chromatography. The apurinic acid and 7‐methylguanine fractions were found to be extensively labelled. Smaller amounts of radioactivity were found in O6‐methyl‐guanine and some of the methylated adenines. The same carcinogen produced different patterns of labelling in oesophageal and liver DNA. The proportion of O6‐methylguanine to 7‐methylguanine was higher when the methylating agent was a carcinogen specific for the organ.