bluuebunny/crossref_metadata_2025 huggingface dataset:
RNA associated with non‐histone chromosomal proteins in rat liver and in ascites hepatoma
Authors: Patel Nutan T. , Holoubek Viktor
Published: February 2007

The purpose of the experiments was to determine if changes in the post‐transcriptional processing of RNA in the hepatoma also affect the low molecular weight nuclear RNA which is transcribed from families of related genes and associated with non‐histone chromosomal proteins. Separation of non‐histone chromosomal proteins on Sephadex G‐200 into three fractions separated the low molecular weight RNA associated with these proteins into metabolically stable RNA firmly bound to the first eluted fractions of high molecular weight non‐histone chromosomal proteins, and into a metabolically active RNA which is eluted with the third protein fraction and can be separated from the low molecular weight non‐histone chromosomal proteins by chromatography on DEAE‐Sephadex A 25 (fraction III RNA). In liver as well as in hepatoma, this fraction III RNA represents about 50% of the RNA associated with the non‐histone chromosomal proteins. Fraction III RNA from both tissues has an approximate molecular weight of 13,000, is rich in guanylic acid, is lacking dihydropyrimidines and is copied from the repetitive sequences of DNA. The content of uridylic acid is much higher in fraction III RNA isolated from hepatoma than in the same RNA isolated from liver, and competitive hybridization has shown that hepatoma fraction III RNA contains not only new base sequences which are not present in liver fraction III RNA, but also lacks some sequences which are present in the liver RNA. The technique of RNA/DNA hybridization in the presence of competing RNA has shown that, in hepatoma, the cytoplasmic RNA competes with more than 60% of the fraction III RNA for the hybridization sites on repetitive DNA. No competition was found when liver cytoplasmic RNA was used. The low ratio of competing hepatoma cytoplasmic RNA or of liver or hepatoma nuclear RNA which is required to displace fraction III RNA from its hybridization with DNA indicates that this RNA is synthesized and in hepatoma is also released into the cytoplasm as a part of larger RNA molecules. The detection of the nucleotide sequences found in liver associated with non‐histone chromosomal proteins in the cytoplasm of hepatoma cells is evidence for extensive disruption of the post‐transcriptional control in hepatoma.
Study of the mechanism of Corynebacterium Parvum anti‐tumour activity. I. Protective effect on the growth of two syngeneic tumours
Authors: Mazurek Cypka , Chalvet Huguette , Stiffel Claude , Biozzi Guido
Published: February 2007

The protective effect of C. parvum against two different tumours—a lymphosarcoma and a mammary carcinoma—has been demonstrated. In the case of lymphosarcoma, a significant protective effect was obtained when both C. parvum and tumour cells were injected IV. In contrast in C3H mice the best protection was obtained when both C. parvum and mammary carcinoma cells were injected IP. Thus both C. parvum and tumour cells must be inoculated by the same route which, however, varies for different tumours. A very small dose of C. parvum still inhibitied the growth of the two tumours. Splenectomy performed before C. parvum treatment did not interfere with the antitumour activity of C. parvum on the tumours. However, when splenectomy was performed after C. parvum injection, the protective effect of C. parvum still persisted against XVII lymphosarcoma but not against C3H carcinoma.
Tumorigenicity of Epstein‐barr virus (EBV)‐transformed lymphoid line cells in autologous squirrel monkeys
Authors: Leibold Wolfgang , Flanagan Tom D. , Andersson Maria , Dalens Maurice , Klein George , Huldt Gunnel , Wright Dennis H. , Voller Alister
Published: February 2007

Eight squirrel monkeys (Saimiri sciureus) challenged with EBV or EBV‐transformed SLCL were naturally or experimentally infected with Plasmodium knowlesi or Pl. brasilianum. Most of the animals had been splenectomized and unilaterally nephrectomized. Three of these monkeys received one dose of 6 to 12 × 108 autologous SLCL. These lines were derived from saimiri lymphoid cells permanently transformed by B‐EBV in vitro. All three animals developed multiple undifferentiated malignant lymphomas and died 8 to 10 days post inoculation. Necropsy tumor specimens were EBNA‐positive and contained 7 to 21 EBV genome equivalents per cell. EBNA‐ and EA‐positive SLCL were established in vitro from four tumor explants of two monkeys. These results demonstrate that in vitro EBV‐transformed SLCL are able to cause tumor formation in autologous squirrel monkeys. Five monkeys received high transforming doses of B‐EBV or S‐EBV, derived from one of the tumorigenic SLCL. None of the animals developed any sign of tumor formation during an observation period of up to 130 days. Three of these monkeys showed no detectable EBV‐related seroconversion while the sera of two monkeys had become anti‐EBNA‐positive when tested at days 28 and 130 respectively post inoculation. Two additional monkeys received neither EBV nor SLCL. They showed no clinical evidence of tumor development or spontaneous seroconversion over a period of more than 1 year.
Tumour angiogenesis factor (TAF) in human and animal tumours
Authors: Phillips Paul , Steward James K. , Kumar Shant
Published: February 2007

Extracts were made from Walker 256 carcinoma, spontaneous rat mammary adenocarcinoma, Wilms' tumour, human neuroblastoma and human haemangioma. Chromatography of the extracts on Sephadex G‐100 yielded four fractions, A, B, C and D. Injection of fractions B and C resulted in the growth of new capillaries in the subcutaneous fascia of rats. Controls, e.g. similar extracts of rat liver or human kidney, did not induce neovascularisation. The endothelium of newly‐formed blood vessels contained many mitotic figures. A limitation of this method is that it is qualitative only. In order to develop a quantitative in vitro assay for a tumour angiogenesis factor (TAF), short‐term primary cultures were initiated from adult rat brain white matter, as cells from such cultures were shown to be vascular in origin. Addition of fractions containing TAF (B and C) which were active in vivo failed to stimulate thymidine uptake by the cells. The possible reasons for this failure and the therapeutic potential of TAF in cancer control are discussed.
Ability of delayed‐type hypersensitivity reactions to distinguish tumor‐associated antigens and histocompatibility antigens in soluble extracts from murine fibrosarcomas
Authors: Kon Neal D. , Forbes James T. , Klein Paul A.
Published: February 2007

The footpad swelling (FPS) test for delayed‐type hypersensitivity in the mouse was evaluated for its ability to measure both tumor‐associated antigens (TAA) and histocompatibility (H) antigens solubilized from methylcholanthrene (MCA) induced fibrosarcomas of C57Bl/6 (B6) mice. Tests for TAA were performed in mice immune to syngeneic tumors while H‐antigens were assayed in mice immunized with skin allografts. FPS was most intense in B6 mice challenged with TAA from the immunizing B6 tumor, but also occurred in response to cross‐reactive TAA solubilized from another B6 fibrosarcoma. Tests for tumor‐associated H‐antigens in allograft immune mice were strongly positive in response to donor/recipient H‐antigen differences and proved sensitive to shared third‐party H‐antigen differences. Comparison of soluble antigens from the same tumor maintained in vitro and in vivo revealed that, while both TAA and H‐antigens could be detected in preparations from the in vivo tumor line, only TAA and not H‐antigens could be detected by FPS in extracts prepared from the in vitro tumor line. These experiments have demonstrated that the mouse FPS test can distinguish both TAA and H‐antigen specificities present in the same complex mixture of tumor‐cell antigens.
Interaction of antibody and cell surface localized antigen
Authors: Yefenof E. , Witz I. P. , Klein E.
Published: February 2007

The changes occurring in the expression of a membrane‐associated antigen following binding of specific antibodies and the fate of the bound antibodies were investigated. Daudi cells, carrying membrane 7S IgM molecules, were coated with radio‐labelled anti‐IgM antibodies and incubated under culture conditions at 37°C. Within 10 h, more than 80% of the cell‐bound radioactivity was shed from the cells into the culture medium. Concomitantly, IgM molecules were lost, as the cells had a diminished ability to bind a new aliquot of antibody. This phenomenon occurred also when the antibody was used at a low concentration, i.e. did not saturate the cell‐surface antigens. The precipitability of the antibody released from the cells with 10% TCA and 40% saturated ammonium sulphate was lower than that of native antibody, indicating some degradation. Also, shed antibody could rebind to fresh Daudi cells less efficiently than native antibody. The presence of immune complexes in the culture supernatants was indicated by the following results: (1) some of the shed radioactivity could bind to IgM‐negative but Fc receptor‐bearing cells; and (2) immune precipitates of sheep anti‐IgM shed from 3H‐leucine labelled Daudi cells and of rabbit anti‐sheep IgG antibodies contained 3H activity.
Detection of Epstein‐Barr virus DNA in American Burkitt's lymphoma
Authors: Ziegler John L. , Andersson Maria , Klein George , Henle Werner
Published: February 2007

Twenty American patients with Burkitt's lymphoma (BL) were studied serologically and biochemically to detect an association with Epstein‐Barr virus (EBV). A wide range of antibody reactivities was encountered. Five patients had serorogical profiles similar to those of African patients with BL: one and possibly two of these patients harbored EBV‐DNA in their tumors. Fifteen patients had low or absent antibody to EBV: tumors from 10 of these patients lacked evidence of EBV‐DNA. An unexplained association between elevated antibody (≥1:80) to EBV virus capsid antigen (VCA) and a favorable prognosis was noted in this series; this prognostic observation requires further substantiation. Thus, it appears that EBV‐associated BL is inversely proportional to tumor endemicity. An etiological role for EBV in BL remains speculative.
Somatic cell hybrids between human lymphoma lines. II. Spontaneous and induced patterns of the Epstein‐Barr virus (EBV) cycle
Authors: Klein George , Westman Anita , Clements Geoffrey , Zeuthen Jesper
Published: February 2007

The regulation of spontaneous, IUDR‐induced and P3HR‐1 virus‐induced EA and VCA production patterns was studied in two new somatic hybrids between human lymphoma lines. The hybrid 8A was derived from the crossing of the non‐producer Raji with the spontaneous producer Daudi line. The second hybrid, 83, was produced by the fusion of Raji with the EBV‐genome‐negative B‐lymphoma line, BJAB. The studies suggest the following EBV regulation patterns: (1) the spontaneous production of EA and VCA appears to be regulated by controls that differ from the regulators ofP3HR‐1 virus‐induced or IUDR‐induced EA synthesis. While spontaneous producer status was dominant over non‐producer status, the level of EA inducibility was set by one of the parental cells, Raji ATG, and could either raise (in the previously studied Raji/Namalwa hybrid, cf Nyormoi et al., 1973) or depress (in Raji/Daudi) the level of relative EA inducibility found in the partner cell. (2) Although EA production is a prerequisite for VCA synthesis, the latter is under its own restriction mechanisms, quite independent of those that regulate the level of EA synthesis. (3) Inducibility of EA synthesis by P3HR‐1 virus and by IUDR appear to be under the influence of at least partially identical controls. (4) EBV‐negative lymphoma cells, exemplified by BJAB, may exert a “complementation” effect on the EA inducibility of their EBV‐positive fusion partner, in spite of their own restrictivity against virus‐induced EA synthesis. In more general terms, it is obvious that the EBV cycle is under the influence of multiple regulatory mechanisms in the human lymphoid cell. Depending on the parental cell and viral genomes that are allowed to interact, somatic cell hybrids may display a variety of patterns. At this time, cell hybridization is one of the few pathways that permit an approach to this complex and completely unknown world.
Humoral reactions in syngeneic hosts against tumor cell surface incomplete saccharide moieties
Authors: Tanino Takae , Egawa Kohji
Published: February 2007

Components on the surface of MM2 ascites mammary carcinoma cells induce agglutination factors in the serum of syngeneic host C3H/He mice, and bind the factors in vitro. These components have been classified into three groups: MM2‐specific substances, mammary tumor virus (MTV)‐associated substances and tumor‐associated embryonic materials. The substances contained saccharide moieties and their terminal sugar residues were essential for the binding of the serum factors. These terminal saccharides were exposed during cell proliferation, but masked in stationary cells, at least partly, due to elongation of the saccharide moieties. The terminal structures of these polysaccharide moieties of growing and stationary cells were studied by semiquantitative tumor cell agglutination using the agglutinating activities against MM2 cells of MM2‐regressor serum and of FM3A/R‐ and Ehrlich‐regressor sera which had partial cross‐agglutination activities. Agglutination by phytohemagglutinins, inhibition of the agglutination by saccharides or with isolated cell surface components and treatment of the cells with glycosidases were also used for this purpose.
Host immune potentiation of drug responses to a murine mammary adenocarcinoma
Authors: Radov L. A. , Haskill J. S. , Korn J. H.
Published: February 2007

The role of host immunity in the response to chemotherapy of a mouse mammary adenocarcinoma (T1699) was investigated. Suppression of the host response by previous irradiation or ALS (antilymphocyte serum) treatment considerably decreased the therapeutic effect of both cyclophosphamide and melphalan. The timing of drug administration to normal tumor‐bearing mice was critical as the response depended on the development of an anti‐tumor immune response by the host and not solely on the size of the tumor. Although the majority of tumor‐bearing mice with demonstrable anti‐tumor immunity showed complete tumor regression when treated with cyclophosphamide or melphalan, animals that failed to respond to melphalan initially, as well as responder animals whose tumor recurred, did not respond to a second dose of drug. Neither melphalan nor cyclophosphamide suppressed the ability of the host effector cells found within the tumor mass to kill target tumor cells in the colony inhibition assay.
Epstein‐Barr virus: Experimental infection of Callithrix Jacchus marmosets
Authors: Falk Lawrence , Deinhardt Friedrich , Wolfe Lauren , Johnson Donald , Hilgers Jo , De‐Thé Guy
Published: February 2007

Eight common marmoset monkeys (Callithrix jacchus) were inoculated with about 104 transforming units of B95‐8 virus; seven of the marmosets died 50‐111 days post inoculation and all seven showed microscopic and/or macroscopic lesions compatible with a diagnosis of lymphoproliferative disease. Low levels of anti‐VCA antibodies were detected in plasma from six marmosets. Attempts failed to establish continuous EBV‐carrying lymphoblastoid cell cultures by cultivation in vitro of circulating lymphocytes or minced lymphoid tissues obtained at necropsy.
Tube leukocyte (monocyte) adherence inhibition assay for the detection of anti‐tumour immunity. III. “Blockade” of monocyte reactivity by excess free antigen and immune complexes in advanced cancer patients
Authors: Grosser N. , Thomson D. M. P.
Published: February 2007

Leukocytes from patients with limited cancer display LAI reactivity whereas leukocytes from patients with metastatic cancer frequently demonstrate no reactivity in the tube LAI assay. The leukocytes (monocytes) of reactive patients react with tumour antigen through specific cytophilic anti‐tumour IgG antibody bound to the monocyte's Fc cell surface receptors. The non‐reactive monocytes from patients with advanced cancer lacked the ability to bind free cytophilic anti‐tumour antibody. Moreover, the serum of the non‐reactive patient contained no free cytophilic anti‐tumour antibody capable of “arming” normal leukocytes. The serum of patients with large tumour burdens contained free tumour antigenic determinants capable of absorbing free cytophilic anti‐tumour antibody from the serum of reactive patients or when preincubated with reactive leukocytes abrogating their LAI responsiveness immunologically specifically. Blocking was immunologically specific; therefore, the specificity must reside in the tumour antigenic determinant since immune complexes are bound non‐specifically. The tumour antigen coat was removed by gentle trypsinization of the monocyte's surface. This restored the monocyte's capacity to react with the sensitizing tumour antigen and to bind free cytophilic antibody from the microenvironment. Non‐reactivity in the tube LAI assay of patients with metastatic cancer was not the result of a numerical deficit of circulating monocytes but was mediated by an excess of tumour antigen in the microenvironment of the sensitized monocyte.
Production of lymphoid tumors in hamsters by direct implantation of normal human peripheral and umbilical cord leukocytes
Authors: Miyoshi I. , Kubonishi I. , Uchida H. , Hiraki S. , Matsuda Y. , Tanaka T. , Hiraki K. , Masuji H.
Published: February 2007

Peripheral leukocytes from Epstein‐Barr virus (EBV)‐seropositive or seronegative normal adults, or human umbilical cord leukocytes infected or not infected with EBV, were directly transplanted into 50 newborn hamsters treated with anti‐lymphocyte serum. Lymphoid tumors were produced after a latent period of 10–25 days in 39 animals: 8 of 14 recipients of seropositive donor leukocytes, 2 of 2 recipients of seronegative donor leukocytes, 13 of 15 recipients of EBV‐infected cord leukocytes, and 16 of 19 recipients of non‐infected cord leukocytes. EBV‐determined nuclear antigen‐positive human lymphoblastoid cell lines were established in vitro from tumors produced with seropositive donor leukocytes or EBV‐infected cord leukocytes but not from tumors produced with seronegative donor leukocytes or non‐infected cord leukocytes. The results indicate that EBV is not a prerequisite for in vivo production of tumors but necessary for in vitro establishment of lymphoblastoid cell lines from such tumors.
Serum dependence of expression of the transformed phenotype: Experiments with subline of mouse L fibroblasts adapted to growth in serum‐free medium
Authors: Bershadsky A. D. , Guelstein V. I. , Vasiliev J. M. , Gelfand V. I. , Gelfand I. M.
Published: February 2007

Characteristics of LSF cells grown in serum‐containing and serum‐free medium were compared. LSF is a subline of the L‐strain of mouse transformed fibroblasts adapted to continuous growth in serum‐free medium. Proliferation of LSF cells in monolayer on solid substratum was almost similar in serum‐containing and in serum‐free media. However, several other characters were found to be altered by the addition of serum to the serum‐free medium: ability of cells to form colonies in semi‐solid medium increased considerably; agglutinability of cells by Concanavalin A increased; uptake of 2‐deoxy‐D‐glucose by the cells increased considerably; ability of cells to metabolize benzo (a)pyrene was inhibited; cell morphology was altered and, in particular, the cells became less spread on the substratum and density of microvilli on the cell surface increased. All these changes induced by serum were reversed by transfer of the cells back into serum‐free medium. Thus, addition of serum increased the expression of a number of cellular traits characteristic of transformed phenotype, while in serum‐free medium partial phenotypic reversion of transformation was observed. A possible role of serum in the expression of the transformed phenotype is discussed. It is pointed out that cell lines adapted to growth in serum‐free medium provide an experimental system convenient for analysis of the effects of different serum components on the cell phenotype.
Selective suppression of t‐cell activity in tumor‐bearing mice and its improvement by lentinan, a potent anti‐tumor polysaccharide
Authors: Haba Seiji , Hamaoka Toshiyuki , Takatsu Kiyoshi , Kitagawa Masayasu
Published: February 2007

The cellular site of immunosuppression in Ehrlich tumor‐bearing mice was analysed with particular reference to the T‐ and B‐cell activities. The B‐cell activity as measured by the anti‐dinitrophenyl (DNP) antibody responses to DNP‐thymus‐independent carriers (TID) was not impaired in tumor‐bearing mice as compared with normal mice, whereas the anti‐DNP antibody responses to DNP‐thymus‐dependent carriers (TD) and the development of helper T‐cell activity to TD were markedly suppressed in tumor‐bearing animals or mice pretreated with cell‐free cancerous ascitic fluid. The selective suppression of T‐cell response was not mediated by the generation of suppressor cell activity toward TD, which may depress the manifestation of developed helper T‐cell activity. A marked suppression of T‐cell response was observed when the animals were inoculated with tumor cells or injected with cancerous ascitic fluid prior to antigenic stimulation, but not when the animals were rendered tumor‐bearing by such treatments after the immunization. The suppression of T‐cell activity in both sarcoma 180 tumor‐bearing mice and cell‐free Ehrlich cancerous ascitic fluid‐treated mice was prevented by treatment with lentinan, a potent anti‐tumor polysaccharide. The applicability of this experimental system to the search for immunopotentiators relevant to tumor immunotherapy is discussed in the light of the preventive effect of lentinan on the suppression of T‐cell response in tumor‐bearing animals.
Tumor bound immunoglobulins: The relationship between the in vivo coating of tumor cells by potentially cytotoxic anti‐tumor antibodies, and the expression of immune complex receptors
Authors: Braslawsky Gary , Ran Maya , Witz Isaac P.
Published: February 2007

In this study we investigated the relationship between binding of anti‐tumor antibodies by polyoma‐virus‐induced SEYF‐a tumor cells and the expression of immune‐complex receptors on these cells. It was shown that in vivo propagated cells became progressively coated with IgG. The increase in the IgG coating of SEYF‐a cells, occurring during the second week of propagation, was directly correlated with an increase in the coating of cells with potentially cytotoxic anti‐tumor antibodies. The activity of these antibodies was demonstrated by cell lysis following addition of exogenous complement. Cell populations propagated in vivo for longer periods (3 weeks or more) became less sensitive to exogenous complement although their IgG coating remained high, and although higher titers of anti‐tumor antibodies could be eluted from them. This indicated that antibodies coating young tumor cell populations have the capacity to activate complement whereas those coating older tumor cell populations are incapable of complement activation. Previous findings that SEYF‐a cell populations are able to bind unrelated immune complexes were confirmed in the present study. We also found that the capacity of these populations to bind such unrelated complexes decreased with propagation time in vivo. The involvement of anti‐tumor antibodies in this phenomenon was indicated by the finding that such antibodies inhibited binding of unrelated immune complexes by young cells but not by old cells. Furthermore, treatments causing dissociation of Ig from the cell surface restored, to some extent, the capacity of anti‐tumor antibodies to inhibit immune complex binding by old SEYF‐a populations.
Impaired general cell‐mediated immune functions in vivo and in vitro in patients with nasopharyngeal carcinoma
Authors: Chan S. H. , Chew T. S. , Goh E. H. , Simons M. J. , Shanmugaratnam K.
Published: February 2007

General cell‐mediated immune (CMI) functions in NPC patients were investigated by the in vitro Mantoux and in vitro lymphocyte response to PHA assays. Thirty‐eight (50%) of 76 untreated NPC patients were hyporesponsive in the Mantoux assay compared to 27 (25%) of 110 control patients. Forty‐three (65.2%) of 66 untreated NPC patients also showed lymphocyte hyporesponsiveness to PHA compared to 15 (15.5%) of 97 control patients. Combined deficiencies were observed in 35 (42.2%) of 83 NPC patients compared to only 2 (3.3%) of 61 control patients. No difference in the frequency of immuno‐deficiency was observed between “early” and “late” disease patients. CMI functions of treated “remission” NPC patients were found to be impaired to the same extent as those of untreated NPC patients.
Cryopreservation of human lymphocyte function as measured by in vitro assays
Authors: Oldham R. K. , Dean J. H. , Cannon G. B. , Ortaldo J. R. , Dunston G. , Applebaum F. , McCoy J. L. , Djeu J. , Herberman R. B.
Published: February 2007

Methods are described by which cryopreserved cells can be utilized in a number of in vivo assays. On a per cell basis, nearly total recovery of function can be demonstrated for lymphocyte transformation (mitogens, antigens and MLC) and rosette‐forming cells. Excellent recovery of mononuclear cell production of leukocyte migration inhibitory factor was also observed. Highly reproducible activity was recovered on a per lymphocyte basis in lymphocyte cytotoxicity but with a definite decrement in the percentage recovery. Both for longitudinal studies of immune function and for standardization of these assays in one or more laboratories such cryopreserved cells are of immense value and should be widely utilized.
Isolation from human gastric juice of an antigen closely related to the carcinoembryonic antigen
Authors: Vuento Matti , Engvall Eva , Seppälä Markku , Ruoslahti Erkki
Published: February 2007

A carcinoembryonic antigen‐like antigen(s) (CELIA) was isolated from normal human gastric juice by immunoadsorbents and gel chromatography. The isolated CELIA reacted identically to CEA in immunodiffusion tests against anti‐CEA and anti‐CELIA. Other experiments suggested subtle differences between CELIA and CEA. Two out of six CELIA preparations tested in immunodiffusion did not react in a completely identical manner with CEA. In gel filtration, CELIA eluted slightly after CEA. Absorption of anti‐CEA with CELIA resulted in antisera with greatly reduced reactivity to CELIA, but retained anti‐CEA activity. Such antisera may be helpful in attempts to increase the cancer specificity of the CEA test.
Interactions of murine leukemia virus (MuLV) with isolated lymphocytes. III. Alterations of splenic B and T cells in friend virus‐infected mice
Authors: Cerny Jan , Essex Myron , Thomas D. Brian
Published: February 2007

Lymphoid tissues of mice infected with murine leukemia virus (Friend) (MuLV‐F) were examined for the presence of cellular markers of MuLV‐F infection. The Friend virus‐associated cell membrane antigen (FVMA) and the virus group‐specific antigen (GSA) were detectable on cells from the spleen and, to a lesser degree, on cells from the bone‐marrow. In contrast, neither FVMA nor GSA was found in cells from the thymus. Alterations in the B‐cell and T‐cell spleen populations of MuLV‐F‐infected mice were then studied. The proportion of Ig‐positive cells declined from the initial 45% (in non‐infected controls) to about 10% after 2 weeks of infection. A similar decline of theta‐positive cells was noted. However, complement‐receptor‐bearing cells (EAC rosettes) declined even more rapidly and became undetectable in the second week after infection. The treatment of spleen cells from MuLV‐F‐infected mice with anti‐FVMA serum plus complement in vitro reduced the number of detectable Ig‐positive cells, specifically, whereas the number of theta‐positive cells remained unchanged. Furthermore, B and T cells from spleens of infected mice were separated on an affinity column with anti‐Ig antibody‐coated beads. The initial cell suspension contained about 45% FVMA‐positive cells, about 40% Ig‐positive cells and about 40% theta‐positive cells. Ig+ cells were retained on the column. The theta‐positive cell fraction was collected in the eluate and contained very few FVMA‐positive cells with some “null” cells. Most of the FVMA‐positive cells were retained on the column, which strongly suggested that they were B cells. These results confirm the previous experiments which showed the selective infections of purified splenic B cells by MuLV‐F in cultu.
Augmented immunogenicity of tumor cell membranes produced by surface budding viruses: Parameters of optimal immunization
Authors: Gillette Ronald W. , Boone Charles W.
Published: February 2007

Membranes prepared from tumor cells infected with surface budding viruses are much more immunogenic than membranes from uninfected tumor cells. Factors affecting immunization with membranes from virusinfected tumor cells were studied. Preparations made with influenza virus were clearly superior to those prepared with vesicular stomatitis virus (VSV). Membranes infected with VSV were maximally immunogenic at a dose equivalent to a 10% cell pack whereas influenza‐virus‐infected membranes were immunogenic at 1/100th of this dose. Subcutaneous inoculation was better than other routes of administration. Maximum protection against challenge with viable tumor cells was afforded by two inoculations of VSV‐infected membranes spaced 3 days apart or a single inoculation with influenza‐virus‐infected membranes. Administration of membranes in complete Freund's adjuvant either had no effect or induced a slight degree of tumor enhancement. Immunization with influenza‐virus‐infected membranes significantly reduced tumor size and incidence even at a challenge dose of tumor cells which was 50 times the LD100.
Design of experiments using the microcytotoxicity assay
Authors: Brown Joseph P. , Van Belle Gerald , Hellström Ingegerd
Published: February 2007

Examination of data from the microcytotoxicity assay revealed that the number of surviving target cells varies systematically both between microtest plates and within plates. If the layout of treatments on the plate is not planned carefully, these effects decrease precision and introduce bias. It is recommended that treatments which are to be compared be placed close together on the plate; for example, a plate with 96 wells might be considered as 24 blocks of 4 wells, with the treatments placed within these blocks. Data can be analyzed by means of paired t‐tests or randomized block analysis of variance. These design changes remove the effect of systematic variation and increase the precision of the assay.
Murine neuroblastoma clones with varying degrees of C‐type virus expression
Authors: Wivel Nelson A. , Yang Stringner S.
Published: February 2007

Three tissue culture clones of neuroblastoma cells derived from the C‐1300 tumor in strain A/J mice were found to contain type‐C virus‐specific gs antigen. None of the clones spontaneously released mousetropic type‐C viruses although one clone, N‐4, spontaneously released a xenotropic virus. Two clones, NB‐2A and N‐4, could be induced by treatment with 5‐iododeoxyuridine and dexamethasone phosphate to produce B‐tropic type‐C virus, but clone N‐18 failed to release either ecotropic or xenotropic virus under several different induction conditions. Karyotype analysis did not reveal specific chromosome deletions in clone N‐18.
Serologically detectable specific and cross‐reactive antigens on the membrane of a polyoma virus‐induced murine tumor
Authors: Witz Isaac P. , Lee Nora , Klein George
Published: February 2007

With the aid of an assay measuring complement dependent cytotoxicity mediated by syngeneic antibodies, we performed a serological analysis of surface antigens of a polyoma‐virus‐induced murine tumor (SEYF‐a). In vivo propagated SEYF‐a ascites tumor cells expressed a specific membrane antigen in addition to various other cross‐reacting antigens. Among these we could identify at least four separate specificities. Two of these were present on Mu LV‐induced lymphoma cells, the first on Moloney‐virus‐induced YAC cells and the second on Gross‐virus‐induced GHA cells. The third cross‐reacting antigen was detected on EL‐4 cells. At least one additional specificity was present on two methylcholanthreneinduced murine sarcomas. Normal syngeneic lymphoid cells were insensitive to cytotoxicity mediated by the anti‐tumor antisera. Quantitative and perhaps also qualitative differences between the antigenic expression of in vivo propagated and cultured SEYF‐a cells were indicated. These studies show that hyperimmune sera produced in syngeneic mice against transplanted tumors may contain a considerable number of antibody specificities, only some of which are specific for the tumor. Furthermore the results also suggest that polyoma‐virus‐induced tumors may possess individually distinct antigenic specificities, over and above the known cross‐reacting TSTA or TSSA type antigen.
The distribution and fate of blood‐borne 125 iudr‐labelled tumour cells in immune syngeneic rats
Authors: Proctor J. W. , Auclair B. G. , Rudenstam C. M.
Published: February 2007

Radiolabelled sarcoma cells injected into the tail veins of normal rats were held up almost exclusively in the lung, and were not observed to pass through into the systemic circulation. Intramuscularly injected tumour cells were retained at the site of injection. Radioactivity was lost from both sites though more rapidly from the lung than from muscular tissue and was probably the result of tumour‐cell death. Alveolar macrophages did not take part in the destruction of tumour cells in the lung. There was an increased rate of radiolabel loss from the lungs of hyperimmune, post excision and tumour‐bearing rats, as compared with normal rats. The destruction was immunologically specific; it was detected earlier, was more comprehensive in the hyperimmune and post‐excision animals than in tumour‐bearing animals, and correlated with the ability of the hyperimmune and post‐excision animals to reject larger numbers of intravenous unlabelled tumour cells, than the tumour‐bearing rats.
Leukocyte migration inhibition by cancer patients' sera
Authors: Cochran A. J. , Mackie R. M. , Ross C. E. , Ogg L. J. , Jackson A. M.
Published: February 2007

Sera from 38 of 89 melanoma patients, 4 of 15 patients with other cancers and 3 of 43 control donors inhibited the migration of autologous leukocytes. Sera from patients with clinically detectable metastatic disease and from the recipients of BCG were most frequently inhibitory. Autologous sera from 31 of 71 melanoma patients and 3 of 31 control donors increased the leukocyte migration inhibition induced by formalinized melanoma cells. This activity occurred in sera from patients at all stages of malignancy, whether bearing detectable tumour or not and whether receiving BCG or not. Abrogation of tumour‐cell‐induced leukocyte migration inhibition by serum was less frequent, occurring with 8 of 71 melanoma patients (6 Stage III, 1 Stage I and 1 Stage II) and no control sera. Preincubation of formalinized tumour cells had no effect on their activity in the leukocyte migration assay but the preincubation of melanoma leukocytes with either autologous serum or foetal calf serum inhibited leukocyte reactivity in around 50% of tests. However, this was also seen with control leukocytes and the effect appears to be immunologically non‐specific.
Search for anti‐tumor response in a bone tumor patient with a long clinical history
Authors: Vánky F. , Klein E. , Cornain S. , Bakács T. , Stjernswärd J. , Nilsonne U.
Published: February 2007

Immunological studies are presented on a patient with a long clinical history suggesting the existence of a tumor‐specific immune response. His tumor, first considered benign, progressed to a highly malignant osteosarcoma. Cell‐mediated immune reactivity against biopsy cells and against tumor extract was detected in vitro by the autologous tumor stimulation test (ATS) and in vitro by the skin test. In one ATS‐test with tumor extract, blastogenesis of T‐cells was demonstrated. The amount of Ig(s) in consecutive biopsies increased. Biopsies taken in the later period of the disease stimulated only after trypsin treatment. This stimulation was inhibited by autologous serum or acid eluate of the biopsy. The inhibitory factor in the serum was not intact immunoglobulin. Blood lymphocytes did not show a discriminatory or disease‐related cytotoxicity, either directly or after co‐cultivation with the tumor material. Lymphocytes isolated from one biopsy were non‐reactive in both the ATS and the cytotoxicity test.
An examination of the immunology of cancer patients
Authors: Cochran Alistair J. , Mackie Rona M. , Grant Robert M. , Ross Catherine E. , Connell Margaret D. , Sandilands Gavin , Whaley Keith , Hoyle Deirdre E. , Jackson Alan M.
Published: February 2007

We have examined 111 cancer patients and 111 control individuals for general immunocompetence (haematological values, “recall” antigen skin tests, PHA and PPD induced lymphocyte transformation, serum Ig levels and lymphocyte subpopulations), for evidence of sensitisation to tumour‐associated anti‐tigens (leucocyte migration test, serum inhibition of autologous leucocyte migration, lymphocytotoxicity, membrane immunofluorescence and immune adherence) and for evidence of continuing immune reactions (alterations of complement components and anti‐complementary activity). Major differences between the cancer patients and controls were demonstrated by several tests of sensitisation and these also detected differences between patients with and without metastases. The only differences detected between cancer patients and controls by the tests of general immunocompetence were in serum IgG and IgA (higher in the cancer patients) and lymphocyte subpopulations (“active” T, autorosetting lymphocytes and lymphocytes forming “super‐rosettes” increased in cancer patients). In a comparison of cancer patients with and without metastases, patients with metastases were less often reactive to the Candida DHS and streptokinase‐streptodornase antigens and had raised circulating Fc positive cells. Abnormalities of the individual components of complement occurred in about half the cancer patients, but were equally common in those with and without metastases. Serum anti‐complementary activity was very rarely detected. The tests of specific sensitisation correlated reasonably well but correlations of tests of general immunocompetence were infrequent.
Importance of progesterone in DNA synthesis of pregnancy‐dependent mammary tumors in mice
Authors: Yanai Reiko , Nagasawa Hiroshi
Published: February 2007

Hormone responsiveness of pregnancy‐independent mammary tumors in SHN mice and pregnancy‐dependent tumors in GR/A mice and in F1‐hybrids between these strains was studied. Force‐bred female mice with palpable mammary tumors were given subcutaneous injections of several hormones singly or in combination twice daily from 1 day before to 1 day after parturition. One group received a graft of three pituitary glands under the kidney capsule (3AP) during days 12–14 of pregnancy. One day after parturition, the in vitro incorporation of 3H‐thymidine into DNA of normal and neoplastic mammary glands was determined as the index of DNA synthesis. Plasma prolactin in some groups of GR/A mice was assayed by radioimmunoassay. In GR/A mice, estradiol benzoate (EB: 0.5 μg × 2/day) or 3AP had no effect on either normal glands or tumors, despite an increase in plasma prolactin level. Progesterone (P: 100 or 1,000 μg × 2/day) significantly increased DNA synthesis of both normal and neoplastic glands when compared to the controls, while the plasma prolactin level in this group was low. The administration of human placental lactogen (HPL: 100 μg × 2/day) stimulated DNA synthesis of normal glands only. P plus HPL promoted DNA synthesis of tumors more than P alone, but not P plus EB. While DNA synthesis of the tumors of SHN was never affected by these hormone treatments, the hormone responsiveness of tumors of F1‐hybrids was almost the same as that of GR/A mice; the effect of P was prominent. Correlation of DNA synthesis between pregnancy‐dependent mammary tumors and normal glands was significant only in groups treated with P alone or in combination with other hormones.
Oncogenicity of k‐region epoxides of benzo(a)pyrene and 7,12‐dimethylbenz(a)anthracene
Authors: Flesher James W. , Harvey Ronald G. , Sydnor Katherine L.
Published: February 2007

Female Sprague‐Dawley rats were given a subcutaneous injection of the parent hydrocarbon or its K‐region epoxide in 0.1 ml sesame oil on alternate days to a total of 30 doses and observed for sarcoma at the site of injection for 275 days. The parent compounds, benzo(a)pyrene (0.2 μmole/dose) and 7,12‐dimethylbenz(a)anthracene (0.2 μmole/dose), induced sarcoma in 100% of the animals with an average latent period of 101 and 95 days, respectively, whereas five of 12 rats (42%) injected with the K‐region epoxide of B(a)P (1.0 μmole/dose), developed sarcoma in 151±22 days, and the K‐region epoxide of DMBA (0.4 μmole/dose) failed to elicit tumors. Under these experimental conditions, these K‐region epoxides are, at best, only weak carcinogens.
Demonstration of tumor‐associated immunity with a leukocyte adherence inhibition (LAI) assay
Authors: Hellström Ingegerd , Hellström Karl Erik , Shantz Geraldine
Published: February 2007

A modification of the leukocyte adherence inhibition (LAI) assay of Halliday was used to search for immune reactions against tumor‐associated antigens of mouse tumors as well as against embryonic antigens in such neoplasms. Soluble antigen extracts were prepared from transplanted (BALB/c) methylcholanthrene‐induced sarcomas and carcinomas, from normal BALB/c embryos taken at 14–18 days' gestation and from kidneys and livers of adult BALB/c mice. Peritoneal cells (PC) from mice immunized against syngeneic tumors gave leukocyte adherence inhibition more commonly when exposed to antigens prepared from the same tumor than did PC from normal (untreated) mice or from mice immunized against a different tumor. However, different tumor antigen preparations varied vastly in their ability to give specific adherence inhibition; some preparations consistently gave a high tumor‐specific inhibition, while others did not. This may explain why the degree of reactivity observed was low and its tumor specificity not absolute when data obtained with all different antigen extracts were pooled. PC from multiparous mice gave adherence inhibition when exposed to antigenic extracts from syngeneic mouse embryos or from tumors, as compared to PC from virgin mice exposed to the same extracts. Furthermore, PC from tumor‐immunized mice reacted more commonly against antigen extracts from mouse embryos than did peritoneal cells from normal untreated mice. Adherence inhibition was not observed when PC from tumor‐immunized or multiparous mice were exposed to antigen extracts from adult syngeneic livers or kidneys.
Specific anti‐fibroblast cytotoxicity of antibodies to fibroblast surface antigen
Authors: Ruoslahti Erkki , Sjögren Hans O.
Published: February 2007

An antiserum to SF antigen was shown to be selectively cytotoxic to two human fibroblast lines, while two tumor cell lines (one melanoma and one Hela cell line) were resistant. The selective cytotoxicity was also demonstrable in mixtures of fibroblasts and tumor cells. The cytotoxic effect was abrogated by admixture of human serum containing SFA.
Immunosuppression in burkitt's lymphoma. II. Peripheral blood lymphocyte populations related to clinical status
Authors: Magrath I. T. , Simon R. M.
Published: February 2007

We have studied peripheral blood lymphocyte populations, defined in terms of their E and EAC' rosetteforming capacity in patients with Burkitt's lymphoma and controls. Total lymphocyte counts were reduced in patients compared to controls (p<0.005), and correlated with clinical stage and disease status. Presenting patients with Stage D tumours had the lowest levels, while patients in remission for at least 18 months had total lymphocyte counts simitar to those of controls. Absolute numbers of both E and EAC' rosette‐forming cells (RFC) were reduced, compared to controls, in tumour‐bearing patients (p < 0.0005 for both E and EAC' RFC) and also, to a lesser extent, in patients in remission (p < 0.025 and < 0.05 for E and EAC' RFC respectively). In the case of E RFC a significant reduction was present even when patients in remission for over 18 months were considered alone (p < 0.05). Non‐RFC were present in similar numbers in patients and controls, so that the reduction in total lymphocyte count can be accounted for entirely by the reduced numbers of RFC. As anticipated by this, percentages of RFC were also reduced in patients compared to controls, EAC' RFC to a lesser extent than E RFC. Non‐RFC percentages were correspondingly increased. Tumour‐bearing patients had significantly impaired PHA responses and cutaneous reactivity, which correlated significantly with very low levels of RFC. One possible explanation for these results is that immunoreactive lymphocytes are sequestered within the tumour. This is consistent with the immunosuppression observed in tumour‐bearing patients, and would also result in difficulty in detecting even a powerful tumour‐specific immune reaction by means of an assay dependent upon the participation of peripheral blood lymphocytes.
Cancer incidence in alaska natives
Authors: Lanier Anne P. , Bender Thomas R. , Blot William J. , Fraumeni Joseph F. , Hurlburt Ward B.
Published: February 2007

A survey of cancer incidence among Alaska Natives for the 5‐year period 1969–73 revealed fewer cancer cases overall than expected in relation to US rates, but significantly increased risk for certain cancer sites: the nasopharynx in both sexes (with excesses over 15‐fold), the liver in males, and the salivary glands, gallbladder, kidney and thyroid in females. Compared with earlier reports, the observations suggest marked changes in cancer incidence among Alaska Natives over the past two decades, with declines in esophageal and invasive cervical cancers, and increases in cancers of the lung, colon and rectum.
Fc receptor‐bearing cells as a reliable marker for quantitation of host lymphoreticular infiltration of progressively growing solid tumors
Authors: Kerbel R. S. , Pross H. F.
Published: February 2007

Disaggregated cell suspensions made from transplanted solid tumors, either chemically‐induced fibrosarcomas, or spontaneous mammary carcinomas, can contain very high numbers of Fc receptor‐bearing cells which are of host origin. Because most types of lymphoreticular cells have Fc receptors, and because T cells—most of which are Fc receptor‐negative—appear to infiltrate such tumors only to a very limited degree, the possibility that Fc receptor cells could serve as a reliable and simple marker for host lymphoreticular cell infiltration of solid tumors was tested. This was accomplished by comparing the ratios of Fc rosetting cells to serologically detectable host cells in H2d or H2k haplotype tumor cell suspensions grown in (H2d × H2k) F1 hybrid mice, where host cells could be distinguished from tumor cells by treatment with the appropriate anti‐H2 serum. Ratios of 0.8 to 1.08 were obtained for four different tumors including the SaD/2 fibrosarcoma, a CBA spontaneous fibrosarcoma, and the T1699 and CaD/2 mammary carcinomas. Analysis of the results showed that enumeration of Fc rosettes was a reliable host cell marker for at least three of the four tumors tested. The mean non‐malignant host cell content of the various tumors, as assessed by anti‐H2 cytotoxicity tests, ranged from 23% to 41%.