bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and persistence of cytolytic T lymphocytes in regressing or progressing moloney sarcomas
Authors: Gillespie G. Yancey , Russell Stephen W.
Published: February 2007

Intratumoral T lymphocytes were recovered sequentially after induction of regressing or progressing Moloney sarcomas in BALB/c mice and were assayed quantitatively for their ability to kill specifically the tumor (MSC) cells used for induction. The cytolytic activities of the two lymphocyte populations described two distinct biphasic kinetic profiles that were similar in amplitude and duration but separated from each other by 4‐6 days. In progressing neoplasm, there was a rapidly occurring accumulation of T lymphocytes highly cytolytic for MSC cells. This response, however, was not sustained and disappeared in association with the onset of unchecked tumor growth. In contrast, T lymphocyte cytolytic activity developed more slowly in regressing sarcomas and attained peak levels coincident with the beginning of tumor regression. Similar changes in cytolytic activity characterized T lymphocytes in lymph nodes draining tumors. When cultured in vitro for 4 days, non‐cytotoxic T lymphocytes from regional lymph nodes draining progressing sarcomas regained very high levels of cytolytic activity. Such restitution was diminished, however, if MSC cell lysates, macrophages or macro‐phages fed MSC cell lysates were present during the culture period. These experiments provided presumptive evidence that T lymphocyte‐mediated cytolytic activity was lost in progressively growing Moloney sarcomas as a consequence of suppression in vivo of the genesis and/or functional expression of cytolytic T lymphocytes, perhaps by macrophages and/or soluble tumor antigen.
Genetic analysis of in vitro leukemogenesis induced by thymus epithelial reticulum cells transmitting murine leukemia viruses
Authors: Haas Martin
Published: February 2007

Lymphatic leukemia developed in C57BL/6 mice following inoculation of normal thymocytes that had been co‐cultured on leukemic thymus epithelial reticulum monolayer cells. Using thymocytes genetically marked in Ly membrane antigens, we showed that the thymomas which developed were produced by the co‐cultured thymocytes rather than by leukemic cells derived from the monolayer. Thus, leukemogenic conversion of normal thymocytes took place in vitro. Inoculation of cultured leukemic thymus epithelial reticulum monolayer cells (LTER) gave rise mainly to reticulum cell sarcomas and myeloid leukemias, rather than to lymphatic leukemias (which developed following inoculation of thymocytes that had been cultured on the LTER monolayers). Thus LTER cells may themselves be tumor cells capable of producing RCNA (reticulum cell neoplasm type A) or myeloid tumors in addition to their ability to convert normal thymocytes into leukemic cells.
Isolation of a sulfated glycopeptidic antigen from human gastric tumors: Its localization in normal and cancerous gastrointestinal tissues
Authors: Bara Jacques , Paul‐Gardais Annick , Loisillier Felix , Burtin Pierre
Published: February 2007

A sulfated glycopeptidic antigen (SGA) was purified from papain‐digested cancerous human gastric mucosa. The amino acid composition of this antigen was characterized by a high percentage of threonine and proline. Serine was present in small quantities and aromatic amino acids were absent. The amount of sulfate present was evaluated at 7.5%. Fucose, galactose, N‐acetyl glucosamine, N‐acetyl galactosamine and sialic acid were found to be present in the molar ratio 1:4.6:3.0:6.2:5.0. With immunofluorescence techniques, a rabbit antiserum against the sulfated glycopeptide stained adult gastric mucosa when this tissue had intestinal metaplasia and stained the goblet cells of the intestinal tract (small and large intestines). About 50% of colonic carcinomas and some gastric carcinomas contained SGA. This sulfated antigen was present in well‐differentiated tumors and there was a good correlation between tumoral acid mucous secretory activity and the SGA positivity.
A new aspect of the urinary excretion of tryptophan metabolites in patients with cancer of the bladder
Authors: Teulings F. A. G. , Peters H. A. , Hop W. C. J. , Fokkens W. , Haije W. G. , Portengen H. , van der Werf‐Messing B.
Published: February 2007

Metabolites of the amino acid tryptophan have been suspected of being involved in the genesis of human urinary bladder cancer. It was suggested that a neoplastic change could result from increased urinary excretion of tryptophan metabolites. From studies in which the excretion of metabolites was assessed after loading the patients with L‐tryptophan it was concluded that abnormalities in tryptophan metabolism are causing the elevation of metabolite excretion. The present study however, which measured basal excretion of metabolites, demonstrates that the presence of tumor in the urinary tract must be considered as causative for elevations of metabolite excretion. An improved method for determining the spontaneous metabolite excretion is described. The metabolites kynurenine, kynurenic acid, 3‐hydroxykynurenine, xanthurenic acid and 3‐hydroxyanthranilic acid were determined in 165 urine samples obtained from bladder cancer patients, renal cancer patients, patients cured of bladder cancer and control subjects. Thirty six percent of the bladder cancer patients and 67% of the renal carcinoma patients excreted abnormally high amounts of at least one of the metabolites. It was observed that in bladder cancer an elevated excretion of metabolites occurred principally in patients with obstruction to the outflow of urine from the kidneys. Ureteral obstruction, probably a direct consequence of the presence of tumor in the urinary tract, causes an alteration in renal function which is reflected in urea and creatinine retention. The high incidence of abnormal excretion of tryptophan metabolites in renal cancer also points to alterations in renal function caused by the presence of tumor.
Two E‐rosette‐forming lymphoid cell lines
Authors: Morikawa Shigeru , Tatsumi Eiji , Baba Mitsuo , Harada Takayuki , Yasuhira Kimio
Published: February 2007

Two E‐rosette (spontaneous rosette with sheep red blood cells)‐forming lymphoid cell lines were established. One (HPB‐ALL) was derived from a young male Japanese patient with acute lympho‐blastic leukemia (ALL), and the other (HPB‐MLT) was from a 62‐year‐old female Japanese patient with a leukemic T‐lymphoid malignancy. Formation of E rosettes, absence of any immunoglobulin determinants, absence of EBNA (Epstein‐Barr virus associated nuclear antigen) and very limited stimulating ability in mixed lymphocyte culture, were characteristics mostly identical with those of so far established T‐cell‐derived lymphoid cell lines, MOLT, CCRF‐CEM, CCRF‐HS‐B2, RPMI‐8402 and JM. Only HPB‐MLT, however, has been derived from an aged patient with T‐lymphoid malignancy.
Adoptive immunochemotherapy of a transplantable AKR leukemia (K36)
Authors: Putman Donald L. , Kind Phyllis D. , Goldin Abraham , Kende Meir
Published: February 2007

Adoptive immunotherapy of a transplantable AKR leukemia (K36) was carried out as an adjunct to cytoxan chemotherapy using normal allogeneic H‐2‐incompatible spleen cells as well as sensitized H‐2‐matched allogeneic spleen cells. A significant therapeutic effect was obtained with cytoxan and allogeneic C57BL/6 splenocytes, demonstrating the potential use of the graft‐versus‐host reaction. Utilizing specific adoptive immunochemotherapy, a maximum effect was found with splenocytes from allogeneic but H‐2‐compatible CBA/J mice immunized against an allogeneic Gross‐virus‐induced lymphoma (EoG2). This therapeutic effect was most likely the result of prior sensitization of donor lymphocytes to common virus‐associated tumor antigens.
Synthesis and accumulation of polyamines in rat liver during chemical carcinogenesis
Authors: Scalabrino G. , Pösö H. , Hölttä E. , Hannonen P. , Kallio A. , Jänne J.
Published: February 2007

The activities of L‐ornithine decarboxylase (EC 4.1.1.17) and S‐adenosyl‐L‐methionine decarboxylase (EC 4.1.1.50) exhibited marked fluctuations in the livers of rats fed 4‐dimethylaminoazobenzene. After 1 month of dye feeding the activity of ornithine decarboxylase rose to a level about six times higher than that of controls and the activity of adenosyl‐methionine decarboxylase was more than twice the initial control level. These elevations were transient, and returned to near normal values within the next 2 months. Four months after the commencement of the azo‐dye diet, ornithine and adenosylmethionine decarboxylase activities showed a second distinct stimulation and appeared to remain high until liver tumors appeared. In contrast, the activity of tyrosine aminotransferase (EC 2.6.1.5) initially decreased but increased after 3 to 6 months to levels slightly exceeding the control values. The biphasic response of the two decarboxylases to the carcinogen appeared to be specific for the liver since both enzyme activities showed a sharp decrease in the kidney during the first 3 months of dye feeding followed by a transient increase 1 month later. The concentration of putrescine in the liver roughly followed the fluctuations of ornithine decarboxylase activity, being about twice the control level in carcinogentreated rats. Spermidine and spermine concentrations were normal although the activities of spermidine synthase (EC 2.5.1.16) and spermine synthase appeared to be lower in animals fed the carcinogenic diet than in normal controls. The response of liver ornithine decarboxylase, adenosylmethionine decarboxylase and tyrosine aminotransferase to growth hormone, glucagon and hydrocortisone was measured several times during the course of the azo‐dye diet. There were only small changes, if any, in the stimulation of tyrosine aminotransferase by growth hormone or hydrocortisone whereas the stimulation by glucagon was totally lost. The striking response of ornithine decarboxylase to porcine growth hormone was markedly reduced, and the moderate stimulation elicited by glucagon completely disappeared during the carcinogenic diet. The response of adenosylmethionine decarboxylase to growth hormone remained unchanged, while the marginal stimulation evoked by either glucagon or hydrocortisone in normal rats totally disappeared after 4 months of dye feeding. Elevated activities of ornithine decarboxylase and adenosylmethionine decarboxylase, together with a distinctly reduced response of these enzymes to hormonal stimulations, thus appear to be characteristics of rat liver undergoing chemical carcinogenesis.
Separation of the tumor rejection antigen (TSTA) from the major viral structural proteins associated with the membrane of an R‐MuLV‐induced leukemia
Authors: Rogers Michael J. , Law Lloyd W. , Prat Maria , Oroszlan Stephen , Appella Ettore
Published: February 2007

A tumor rejection antigen (TSTA) has been solubilized by DOC 1 from purified plasma membranes of an R‐MuLV‐induced leukemia, RBL‐5. Gel filtration chromatography resulted in the separation of high molecular weight fractions containing TSTA from lower molecular weight fractions containing the viral structural proteins, gp70 and p30. Furthermore, the antigen reacting with a syngeneic serum from mice immunized with RBL‐5 membranes was also separated from TSTA and evidence is presented that the antigen recognized by this serum is the viral envelope protein p15E. The implications of these results for the host anti‐tumor immune response are discussed.
Unique and common tumor‐specific transplantation antigens of chemically induced mouse sarcomas
Authors: Hellström Karl Erik , Hellström Ingegerd , Brown Joseph P.
Published: February 2007

Methylcholanthrene‐induced sarcomas of BALB/c mice express unique tumor specific transplantation antigens (TSTA), and weaker, common TSTA. Antigens of endogenous murine leukemia virus (MuLV) expressed by some of these tumors cannot completely account for these common TSTA. However, MuLV antigens on the immunizing tumor appear to increase the immunogenicity of the common TSTA.
The frequency of occurrence of feline leukaemia virus subgroups in cats
Authors: Jarrett Oswald , Hardy William D. , Golder Matthew C. , Hay David
Published: February 2007

Feline leukaemia viruses (FeLV) were isolated from cats in Glasgow and New York with lympho‐sarcoma and from apparently healthy carrier cats. The subgroup composition of each isolate was determined. All isolates contained FeLV of subgroup A (FeLV‐A) and a high proportion also contained subgroup B virus (FeLV‐B). Virus of subgroup C (FeLV‐C) was rare and occurred in association with FeLV‐A and, in some isolates, with FeLV‐B as well. The same pattern was observed in isolates from British and American cats. The frequency of FeLV subgroups was different in cats with lymphosarcoma and in healthy carrier cats. In cats with lymphosarcoma, 42% had FeLV‐A and 58% had FeLV‐AB; there was no obvious correlation between virus subgroup and type of disease. In FeLV‐positive healthy cats, 65% had FeLV‐A and 33% had FeLV‐AB. FeLV‐C was isolated only from cats with disease. The healthy carrier cats were from multiple‐cat households (MCH). Two distinct types of FeLV‐infected MCH were found: MCH‐A in which the carrier cats yielded only FeLV‐A, and MCH‐AB in which cats with either FeLV‐A or FeLV‐AB were present. In MCH‐AB half of the cats had FeLV‐A and half had FeLV‐AB. Overall, the proportion of cats in MCH which were viraemic with FeLV was 42%. However, there was a marked difference in the prevalence of carrier cats in each type of MCH: in MCH‐A, 28% were FeLV‐positive while in MCH‐AB, 53% were viraemic.
Growth characteristics in vitro of hybrids between normal and transformed cell lines
Authors: le Borgne de Kaouël C. , Billard C. , Macieira‐Coelho A.
Published: February 2007

Sensitivity to the inhibition of division during cell crowding in vitro was determined for hybrids between normal and tumor cell populations of human and mouse origin. Interspecies hybrids were more sensitive to cell crowding than intraspecies hybrids. The results suggest that the inhibition of cell division due to crowding was more dependent upon the species of origin rather than on the normal or transformed character of the parental cell lines of the hybrid cell populations.
Solubilized tumour‐associated antigens of methyl‐cholanthrene‐induced mouse sarcomas. Comparative studies by in vitro sensitization of lymph‐node cells, macrophage electrophoretic mobility assay and transplantation tests
Authors: Bubeník J. , Indrová M. , Nemečková Š. , Malkovský M. , von Broen B. , Pálek V. , Anderlíková J.
Published: February 2007

Cell‐mediated immune response to tumour‐associated antigens (taa) extracted from syngeneic methylcholanthrene (mc)‐induced mouse sarcomas with 3 m kci was simultaneously examined by in vitro sensitization of lymph‐node cells (lnc), macrophage electrophoretic mobility (mem) assay and transplantation tests. the solubilized taa elicited in vivo both primary and secondary immune responses as judged from induction of transplantation resistance. the resistance to transplantation of the corresponding sarcoma cells was tumour‐specific and relative in nature, i.e., only partial and weaker than that induced by immunization with irradiated tumour tissue. treatment of mice with solubilized taa prior to immunization with irradiated tumour tissue inhibited the induction of transplantation resistance by irradiated tumour cells. the interaction of the solubilized taa preparations in vitro, either with lnc from animals immunized against the corresponding tumour or with lnc from tumour‐bearing animals, gave rise to a macrophage‐slowing factor detectable by the mem test. taa detected by the mem assay in kci extracts of individual mc‐induced sarcomas were found to be non‐cross‐reacting, individually distinct, like those detected by transplantation tests. individual specificity of taa present in the mc‐induced sarcomas was also demonstrated in vitro by sensitization of normal syngeneic lnc on monolayers of irradiated sarcoma cells followed by detection of the generated cytotoxic lnc in a cytotoxicity assay utilizing the inhibition of [3h]thymidine incorporation. whereas sensitization of lnc on layers of irradiated sarcoma cells gave rise to lymphocytes cytotoxic for cells of the sensitizing tumour, sensitization of lnc with solubilized taa isolated from the same sarcoma has thus far given negative results.
In vitro and in vivo indications of the carcinogenicity and toxicity of food dyes
Authors: Price Paul J. , Suk William A. , Freeman Aaron E. , Lane William T. , Peters Robert L. , Vernon Mina Lee , Huebner Robert J.
Published: February 2007

Eight food dyes or commercial color mixtures certified for use in the United States were tested for their ability to transform in vitro a serial line of Fischer rat embryo cells previously reported to be a sensitive indicator of chemicals having carcinogenic potential. Malignant cell transformation was induced by a commercial mixture (G2024) of two of these dyes (Blue 1 and Yellow 5) and by Blue 2, Green 3 (one of two experiments) and Red 4. Food dyes Blue 1, Red 3, Yellow 5 and Yellow 6 did not induce cell transformation. One to 1.5 mg of each dye was injected into suckling LVG or Graffi hamsters which were monitored for tumor induction and/or death over a 330‐day period. None of the non‐transforming dyes (Blue 1, Red 3, Yellow 5, Yellow 6) or Green 3 induced a significant increase in tumor (mostly lymphoma) incidence or animal mortality. Three of the transforming dyes (Blue 2, Green 2024, Red 4) did increase tumor incidence and/or mortality in at least one strain of hamster. We conclude that the in vitro assay suggested that certain food dyes were carcinogens and that in vivo studies in hamsters supported this interpretation.
Localization of ALPHA1‐fetoprotein and DNA‐synthesis in liver cell populations during experimental hepatocarcinogenesis in rats
Authors: Kuhlmann W. D.
Published: February 2007

Six‐, 12‐ and 20‐week‐old rats were fed N‐nitrosomorpholine (NNM) at low concentrations (6 mg/kg/day) or high concentrations (20 mg/kg/day) for 6 or 12 weeks. Irrespective of the age of the rats, both NNM schedules resulted in development of hepatomas and during the early stages of hepatoma induction, liver histotoxic patterns depended only on the dose of carcinogen employed. Necrosis of hepatocytes and proliferation of small, oval‐shaped cells occurred when high doses of NNM were applied. Parallel to the proliferation of oval‐shaped cells, resurgence of alpha1‐fetoprotein (AFP) in rat sera was observed and production of this protein was confined to the oval‐shaped cells as shown by immunoperoxidase staining. During proliferation of bile duct epithelium, induced by galactosamine injections, those cells could also stain for AFP, and proliferation of oval‐shaped cells concomitant with intracellular AFP staining resulted from restitution of heavily damaged liver. In pulse‐chase labelling experiments with 3H‐thymidine, oval‐shaped cells were seen in continuous development towards hepatocytes, and distinct areas of hyperplastic appearance occurred. Normal hepatocytes and hyperplastic areas did not stain for AFP. Upon low‐dose feeding of NNM, no cellular AFP and no serum AFP were detected unless hepatoma cells had developed. At the stage of malignant conversion, distinct AFP‐staining nodules were localized which consisted of neoplastic hepatocytes. AFP‐staining and non‐AFP‐staining nodules were seen concomitantly in the same animal. AFP was localized only in neoplastic hepatocytes. Pulse‐labelling experiments with [3H]thymidine showed the proliferative character of hepatoma cells from which the AFP‐staining population in particular was involved. No correlation was found between the presence of AFP and histological grading of hepatomas. The wide range of both serum AFP levels and their rising rates in individual rats indicated the highly heterogeneous character of the induced hepatomas with respect to AFP production.
Colonies of ebna‐positive cells in soft agar from peripheral leukocytes of infectious mononucleosis patients
Authors: Hinuma Yorio , Katsuki Takato
Published: February 2007

Epstein‐Barr virus (EBV)‐associated nuclear antigen (EBNA)‐positive lymphoblastoid cells grew as colonies in soft agar after seeding of leukocytes from the peripheral blood of four patients with infectious mononucleosis serologically determined to be caused by EBV. In individual cases more colonies were obtained from blood specimens during the acute phase of the disease than during the convalescent phase. Incorporation of human umbilical cord serum, which contained neutralizing antibody to EBV, into the agar medium did not reduce the number of colonies developing. Our observations indicate that colony‐forming cells were originally present in the blood samples, and that they were not infected and subsequently transformed in vitro. Cells from less than 20% of the EBNA‐positive colonies grew to form lymphoblastoid cell lines, which were EBNA‐positive and had B lymphocyte surface markers. However, the majority (over 80%) of the EBNA‐positive colonies failed to form immortalized cell lines. No colonies were obtained from 91 blood samples from healthy young adults and from five patients with an IM‐like disease unrelated to EBV infections. The present results strongly suggest that already transformed cells or cells very easily transformed by EBV are present in the blood of IM patients.
Risk factors of breast cancer in burma
Authors: Thein‐Hlaing  , Thein‐Maung‐Myint
Published: February 2007

A hospital‐based case‐control study of breast cancer was undertaken in Rangoon. The age‐standardized incidence rate, 25.1 per 100,000 woman‐years and the shape of the age‐incidence curve show that Rangoon women have an intermediate level of breast cancer risk compared to women of other countries in the world. The analysis is based on 193 cases and 400 controls. Breast cancer risk was found to be directly related to educational attainment. There was an increased risk associated with early menarche and late menopause. The most striking finding was the strong inverse relationship between risk and parity; women who had six or more children have only one‐third the breast cancer risk of married women who had less than four children. This association is not confounded by case‐control differences in age at birth of first child. The association of breast cancer risk with age at first birth was not striking; only women with a first birth after age 30 were at increased risk. Breast cancer risk was unrelated to lactation. Overall, the epidemiology of breast cancer in Burma is similar to that in most other countries. However, the possibility of an unusual relationship of risk to parity and age at first parturition warrants further exploration.
Melphalan‐induced chromosome damage in sensitive and resistant human melanoma cell lines
Authors: Parsons P. G. , Morrison Leanne
Published: February 2007

Twelve consecutive treatments of a human melanoma cell line (MM253) with melphalan gave a subline (MM253‐12M) which was five times more resistant to melphalan with respect to survival. In contrast to mustard‐resistant rodent cells, the MM253‐12M line had a higher stemline number than the parent line while growth rate and cell and colony morphology were unchanged. A further melphalan treatment following attempted mutagenesis with UV did not increase resistance. In a comparison of these two lines with two melanoma lines derived from other patients and the rat XC line, resistance was correlated with lower frequency of melphalan‐induced chromosome aberrations, determined 48 h after a 4‐h exposure to melphalan(3 μg/ml). In the two cell lines studied, aberration‐free metaphase cells from treated culture had fewer chromosomes than untreated cells. DNA synthesis studied in the 4‐ to 72‐h period after treatment was inhibited to the same extent in MM253 and MM253‐12M cells at 4 μg/ml but to a greater extent in the sensitive line at 0.1‐1.5 μg/ml. During the first hour of treatment at 0.1‐1.5 μg/ml, DNA synthesis in MM253 appeared to be enhanced.
Genetic transmission of mammary tumour virus in the DBAf mouse strain
Authors: Verstraeten A. A. , Van Nie R.
Published: February 2007

MTV antigens were demonstrable by radio‐immunoassay in milk samples from individual DBAf mice, and in samples from (♀B́LB/c × ♂DBAf) F1 mice. Although some samples collected during the first lactation periods of these mice were virus‐negative, all samples of later lactation periods were virus‐positive. From 75 mice of the [♀(♂BALB/c× ♂ BALB/c× DBAf)]Bc I population, milk samples were collected during one or more lactation periods and tested for the presence of viral antigens; the samples of 42 mice were virus‐positive. In the {([BALB/c ×(BALB/c × DBAf)]) × BALB/c}Bc II population two groups were distinguished. In the first group, the progeny of virus‐positive Bc I mothers, 37 out of 62 mice had detectable levels of viral antigen in the milk. None of the 43 samples from mice of the second group, derived from MTV‐negative Bc I females, were virus‐positive. These data suggest that the presence of viral antigens in the milk of DBAf mice is controlled by a single dominant gene; evidence for linkage of this gene and the albino locus was obtained (recombination percentage: 20).
Mammary leukaemia (ML) antigen isolated from L1210 leukaemia cells
Authors: Zak‐Nejmark Teresa , Steuden Jadwiga , Radzikowski Czesławs
Published: February 2007

Crude 3 M KCI extracts from L 1210 cells and purified ML antigen were characterized and the presence of ML antigens was verified by various anti‐ML sera, as well as by antisera to disrupted MMTV B particles. Selected ML‐positive fractions from preparative polyacrylamide electrophoresis and purified ML antigen isolated by affinity chromatography were analyzed by polyacrylamide disc electrophoresis. With both procedures the same sharp band was obtained. The molecular weight of both preparations was found to be 73,500 as estimated. The relationship between ML antigen, MMTV antigenic products and cell‐associated viral proteins is discussed.
Specificity of acquired clonal chromosome abnormalities in new zealand black mice
Authors: Fialkow Philip J. , Bryant Jean I. , Friedman Jan M.
Published: February 2007

New Zealand Black (NZB) mice, an inbred strain characterized by immunological dysfunction and lymphoreticular malignancy, also develop populations of aneuploid spleen cells. In detailed cytogenetic analyses performed on 10 NZBs, the chromosomally abnormal cells were found to be clonally related within each mouse. Moreover, the karyotypic changes observed were highly non‐random, usually involving the 15 (10/10 mice), 2 (8/10 mice), 16 or 17 (9/10 mice), and sex (6/10 mice) chromosomes. These observations suggest an important relationship between chromosomal alterations and tumorigenesis in NZB mice and emphasize the role of chromosome 15 in murine abnormal lymphoreticular proliferations.
Relationship between epstein‐barr virus (EBV)‐production and the loss of the ebv receptor/complement receptor complex in a series of sublines derived from the same original burkitt's lymphoma
Authors: Klein George , Yefeno Eitan , Falk Kerstin , Westman Anitha
Published: February 2007

Virus production, EBV (P3HR‐1 substrain) superinfectability, IdUrd inducibility, EBV receptor and complement (C3) receptor expression were assessed in two independently maintained Jijoye lines, the derived P3HR‐1 clone that releases a growth inhibitory and cytopathic, non‐transforming viral mutant, and in non‐producer sublines derived from the P3HR‐1 line by the spontaneous cessation of virus production. Both Jijoye lines were superinfectable, inducible, and carried EBV and C3 receptors. Virus‐producing P3HR‐1 cells and recently derived non‐producer sublines lacked EBV‐receptors and C3 receptors, could not be superinfected, but were IdUrd inducible. Two long‐passaged non‐producer sublines of P3HR‐1 reexpressed EBV and C3 receptors to an equal degree (different in the two sublines). EBV‐superinfectability became partially reestablished in the subline with the higher expression of EBV and C3 receptors. These findings support the hypothesis that the EBV‐receptor/C3 receptor negativity of the producer P3HR‐1 sublines and their recent non‐producer derivatives is due to negative selection by the growth‐inhibitory, cytopathic P3HR‐1 virus variant. The closely linked disappearance and reappearance of EBV‐receptors and complement receptors gives further support to the idea that these two receptors are either identical or closely linked constituents of the cell membrane.
Failure to relate the anti‐tumour action of cyclophosphamide with the immunogenicity of two murine fibrosarcomas
Authors: Evans R.
Published: February 2007

A single intraperitoneal injection of cyclophos‐phamide (CY) had a stronger anti‐tumour effect upon two syngeneic mouse fibrosarcomas when given within a few days of tumour implantation than when given 7‐20 days after. CY was more active against the fast‐growing, relatively non‐immunogenic CBA fibrosarcoma, FS13, inducing a higher proportion of permanent regressions, than the slower‐growing, highly immunogenic C57BL fibrosarcoma, FS6, at all comparable stages of tumour growth. Whole‐body irradiation, which suppressed concomitant immunity in FS6‐tumour‐bearing mice, had no effect on the anti‐tumour action of CY. A study of the cellular composition of the tumour masses over a 4‐day period immediately after CY injection showed that there was a decrease in total cell yields, involving mainly a decrease in neoplastic cells, although normal cells, Fc‐receptor‐positive and ‐negative, were also affected to a lesser degree. The overall findings indicated a lack of correlation between the anti‐tumour effects of CY and tumour immunogenicity. Moreover, it was apparent that the anti‐tumour action of CY was mediated by a direct effect of its metabolites on neoplastic cells rather than by host anti‐tumour effector mechanisms.
Genetic control of sensitivity to moloney‐virus‐induced leukemias in mice. I. Demonstration of multigenic control
Authors: Gisselbrecht S. , Pozo F. , Debré P. , Hurot M. A. , Lacombe M. J. , Levy J. P.
Published: February 2007

The appearance of hematopoietic malignancies and the level of viremia were studied in mice of different inbred strains and their F1 or F2 hybrids inoculated with the Moloney leukemia virus (MLV) The viremia was regularly measured in individual mice by radioimmunoassay of the major internal virion component p30. A complex genetic control was found. (1) The level of circulating virus was controlled by at least two genes. An H‐2 linked gene, tentatively called Rmv‐1, displayed a dominant sensitivity. Alleles for resistance existed in H‐2b and H‐2r haplotypes and alleles for sensitivity in H‐2a, H‐2d and H‐2f. Another gene with dominant resistance mapped outside the H‐2 complex and probably interacted with Rmv‐1. (2) A good correlation existed between viremia and the appearance of leukemias, the most viremic strains being also the most leukemic. (3) Nevertheless, additional genes which were not involved in the viremia control could be determinant in the induction of malignancies. One of them with a resistant allele in DBA/2 mice seemed to inhibit the appearance of leukemia despite a high level of viremia. Another gene controlled the spleen involvement resulting in generalized leukemias in sensitive lines contrasting with mainly thymus‐localized tumors in resistant animals.
Murine rous‐sarcoma‐specific immunity detected by leukocyte adherence inhibition: Inhibitory effect of normal serum
Authors: Wikstrand Carol J. , Proctor Jude O. , Hartsell Stephen C. , Haughton Geoffrey
Published: February 2007

The standard one‐stage lymphocyte adherence inhibition (LAI) assay was used to investigate cellular and humoral immune responses within the murine Rous sarcoma system. Significant specific cellular reactivity to Rous sarcoma antigen extracts was detected when the responder peritoneal exudate cells (PEC) were obtained from mice bearing or immunized against primary or transplanted Rous sarcomas; no cellular reactivity to control methylcholanthrene (MC)‐induced tumor antigen extracts was observed. Similarly, specific cell‐mediated recognition of MC tumor antigen extract was demonstrated. Initial experiments designed to assess the role of serum components in the LAI assay demonstrated that normal mouse serum of C57BL/10ScSn, B10.D2, or A/WySn origin, either fresh or frozen, obtained from old (over 7 months) or young (under 6 weeks) mice non‐specifically abrogated the specific loss of PEC adherence.
EBV antigens in lymphocytes of patients with exudative tonsillitis, infectious mononucleosis and hodgkin's disease
Authors: Veltri Robert W. , McClung James E. , Sprinkle Philip M.
Published: February 2007

A protocol utilizing isokinetic gradients to isolate human lymphocytes is combined with another that purifies the C3 receptor‐bearing B lymphocyte subpopulation, thus enriching the EB virus genome‐carrying population. Also, rabbit antisera were prepared to the Epstein‐Barr virus nuclear antigen (EBNA) and the early antigen (EA) and utilized in an indirect immunofluorescence test (IIT) to detect these antigens in human lymphocytes isolated from various disease states. Using these methods we demonstrated excellent correlation between standard methods previously employed to detect EB virus‐coded antigens and our IIT employing xenogenic antisera. Such tests were done on lymphoblastoid cell lines as well as lymphocytes isolated directly from patients with EB vims lymphoproliferative diseases. Human palatine tonsil‐derived lymphocytes from children with exudative tonsillitis and peripheral blood lymphocytes of infectious mononucleosis contained only EBNA in C3 receptor‐bearing B lymphocytes. However, patients with lymphoproliferative disorders, including Hodgkin's disease, harbored in their spleens and lymph nodes lymphocytes producing both EBNA and EA.
Initial tumor cell arrest in animals of defined coagulative status
Authors: Glaves D. , Weiss L.
Published: February 2007

Experiments were made to evaluate the potential role played by thrombogenic factors on the hematogenous arrest of circulating tumor cells in mice with demonstrable coagulopathies associated with the presence of a primary tumor, by administration of “therapeutic” doses of anticoagulants. The effects of warfarin, aspirin and heparin administration on the early arrest patterns of 125IdUrd‐labelled TA3 carcinoma and Gardner lympho‐sarcoma cells injected intravenously into tumor‐bearing mice were examined. Several hematologic parameters of carcinoma‐ and lymphosarcoma‐bearing animals were measured prior to anti‐coagulation experiments and the results indicated that mice had coagulopathies similar to those found in cancer patients with disseminated intra‐vascular coagulation syndrome, i.e., thrombocyto‐penia and elevated fibrinogen levels. Despite the presence of coagulation abnormalities and effective anticoagulation in recipient animals, all three agents were without effect on localization patterns of both tumor types. It was concluded that the proposed involvement of thrombogenesis in metastasis was probably not due to any role played by those clotting factors inhibited by aspirin, warfarin and heparin in early intravascular tumor cell arrest.
The specificity of neutralizing antibodies to feline leukaemia viruses
Authors: Russell Peter H. , Jarrett Oswald
Published: February 2007

Feline leukaemia viruses (FeLV) of subgroups A (FeLV‐A), B (FeLV‐B) and C (FeLV‐C) were examined by neutralization. The FeLV‐A isolates were monotypic. By contrast, there was antigenic variation within subgroups B and C. There was also considerable cross‐reactivity between subgroups. Thus, FeLV‐A viruses showed weak cross‐reactivity to the standard FeLV‐C isolate; four of the subgroup B viruses were identical and cross‐reacted with the standard FeLV‐C, but not with FeLV‐A or the fifth FeLV‐B, and this latter virus weakly cross‐reacted with FeLV‐A but not with the FeLV‐C; within subgroup C, one virus was indistinguishable from the standard FeLV‐C strain but the other two were very similar to FeLV‐A. Therefore, subgroup classification based on interference did not altogether correspond with neutralizing behaviour for subgroups B and C.
Effects of corynebacterium parvum and cortisone on the primary lewis tumour and its metastases
Authors: Jones P. D. E. , Sadler T. E. , Castro J. E.
Published: February 2007

The effects of Corynebacterinm parvum and cortisone acetate (CA) on the primary Lewis lung carcinoma and its pulmonary metastases were investigated. C. parvum given IV either on the same day or 7 days after tumour inoculation, reduced primary tumour growth, while 2.5 mg CA (high‐dose) given SC 4 and 11 days after tumour, alone or in combination with C. parvum, administered on day 0, reduced primary tumour growth to the same extent as C. parvum alone. High‐dose CA given on days 2 and 6 had no effect on primary tumour growth or the action of C. parvum, administered on day 7, while 0.05 mg CA (low‐dose) given on days 4 and 11 did not alter tumour growth or the action of C. parvum, given at the same time as tumour. High‐dose CA given 4 and 11 days after tumour caused a significant enhancement in metastases. C. parvum given to these mice on the same day as tumour significantly reduced the pulmonary nodules but only to the level found in control, saline‐treated mice. In mice given C. parvum alone, metastases were significantly reduced when compared with controls. Similarly, high‐dose CA given on days 2 and 6 significantly enhanced metastases, and C. parvum on day 7 reduced their level to that found in control mice. Low‐dose CA had no effect on the number of metastases or the antimetastatic action of C. parvum. The relevance of these results to the clinical situation is discussed.
Infectious mononucleosis and Hodgkin's disease
Authors: Muñoz N. , Davidson R. J. L. , Witthoff B. , Ericsson J. E. , De‐Thé G.
Published: February 2007

A cohort of 9,454 patients with infectious mono‐nucleosis, serologically confirmed, was followed up to determine their risk of developing lymphopro‐liferative diseases. A total of 1,759 patients was identified in Scotland from 1959 to 1971 and 7,695 in Sweden from 1952 to 1970. The cancer cases were identified by matching the list of patients with infectious mononucleosis against a list of patients with lymphoma, nasopharyngeal and colon carcinomas registered through 1972 in Sweden and through 1973 in Scotland. A four‐fold increase in risk was found for Hodgkin's disease based on 7 cases observed against 1.8 expected. Most of the excess cases of Hodgkin's disease occurred within three years of the diagnosis of infectious mononucleosis and among females. These results are similar to those of four other cohort studies and it is concluded that a positive association exists between infectious mononucleosis and Hodgkin's disease. Several explanations of this association were evaluated. Firstly, it may be that a very small proportion of persons who are in the course of developing Hodgkin's disease are temporarily misdiagnosed as having infectious mononucleosis. Secondly, infectious mononucleosis may increase the susceptibility to a factor which causes or promotes the development of Hodgkin's disease. Thirdly, infectious mononucleosis and Hodgkin's disease may share a common aetiology. Arguments in favour of, or against, each of these explanations are presented.
Chromosome 14 translocations in non‐burkitt lymphomas
Authors: Fukuhara Shirou , Rowley Janet D.
Published: February 2007

Chromosome studies were performed on malignant cells obtained from 27 patients with non‐Burkitt lymphomas. A marker chromosome affecting the long arm of No. 14 (14q+) was the single most frequent abnormality and was noted in 17 of these patients. The frequency of the 14q+ marker varied with the type of lymphoma. For patients with malignant lymphoma, histiocytic, the frequency was 5 of 8; for mixed‐cell type, 1 of 3; for poorly differentiated lymphocytic, 8 of 8; for well‐differentiated lymphocytic, 0 of 3; for lymphoblastic, 0 of 1; for Hodgkin's disease, 2 of 3; and for mycosis fungoides, 1 of 1. The donor chromosome involved in the 14q translocation was identified in 12 cases; certain chromosomes appeared to be affected more frequently than others. Although the break point was band 14q32 in most cases, the exact location of the receptor site on 14q was not always consistent. The distal part of 14q24 was also involved as a receptor site in at least one translocation. These findings suggest that, in some types of lymphoid malignancy, cells with a 14q translocation have a proliferative advantage over cells with other chromosome re‐arrangements. The presence of the 14q translocation may be important in the future for the distinction among morphologically different, but functionally comparable, subgroups of lymphoid malignancies.
Regional differences in tumor growth: Studies of the vascular system
Authors: Auerbach Robert , Morrissey Lawrence W. , Kubai Louis , Sidky Younan A.
Published: February 2007

We have previously shown that tumor cells inoculated into the thoracic region of the trunk grow much more rapidly and with a higher frequency than do an equivalent number of cells injected more posteriorly. We thought that these results might have been a reflection of an underlying difference in the vascular system supplying these regions of the trunk. The present experiments which were undertaken to characterize various aspects of the vascular system associated with the transplantation sites used in these studies include measurements of rates of diffusion of salt solutions, of protein clearance, and of the retention of radio‐labelled cells and cellular debris. We have examined local differences in temperatures and studied the effect of change of ambient temperature on those local differences as well as on tumor growth. More directly, we have measured blood flow to the capillaries by intracardiac administration of radioactive microspheres, and assessed the ability of inoculated tumor cells to induce angiogenesis. We have been unable to detect any major differences in the parameters of the vascular system that we have analyzed. Thus we cannot offer any satisfactory explanation for the observed four‐fold differences in tumor growth in anterior vs posterior inoculation sites. The results are discussed in terms of underlying developmental gradients which can be invoked to provide a basis for further experimentation.
A portion of the feline leukaemia virus genome is not endogenous in cat cells
Authors: Okabe H. , Dubuy J. , Gilden R. V. , Gardner M. B.
Published: February 2007

Although viral sequences closely related to feline leukaemia virus are represented in multiple copies in cellular DNA of all domestic cats, a specific fraction was present only in the virus‐infected cells. This fraction was detected by viral cDNA enriched by a prior absorption of a total complementary DNA (cDNA) transcript with normal cat liver DNA. The recycled cDNA hybridized well with the cellular DNA of virus‐infected cells, but to a lesser extent with DNA from uninfected cat cells. The probe was used to differentiate virus‐positive from virus‐negative tumour tissues of cats. The same approach with cDNA of another endogenous feline virus, RD114, failed to show any difference between a virus‐infected cell line and normal cells, including both virus‐inducible and non‐inducible lines.
Relationship of tumor‐specific transplantation antigens to the histocompatibility complex: Dissociation of in vitro alloantigen expression and in vivo alloimmunity from tumor‐specific transplantation antigen strength
Authors: Chauvenet P. H. , Smith R. T.
Published: February 2007

The studies reported here explore the relationship between tumor‐specific transplantation antigens (TSTA) and (1) the expression of serologically defined specificities, and (2) the immunogenicity of H‐2K‐ or H‐2D‐determined alloantigens on methylcholanthrene (MCA)‐induced murine fibro‐sarcomas. Expression of H‐2K and H‐2D serologically‐detected private specificities on groups of tumors raised in B10.A, B10.BR or B10.D2 strains varied greatly among tumors. No regular reciprocal or direct relationship to tumor TSTA strength was found. Each tumor, however, expressed H‐2K or H‐2D alloantigens stably as determined by direct cytotoxicity or absorption techniques. Even those tumors expressing little or no detectable alloantigen by serologic analysis were immunogenic in H‐2K or H‐2D incompatible congeneic hosts. This was assayed in terms of capacity to evoke primary or secondary tumor resistance, and to induce allo‐antibody toward private H‐2K or H‐2D end specificities. An exception was that B10.BR tumors failed to induce anti‐H‐2Dk antibody despite strong surface alloantigen expression. While TSTA strength did not correlate with serologically detected alloantigen expression, TSTA strength did tend to correlate inversely with capacity to resist primary growth in the H‐2K different host, and directly with resistance in the H‐2D different host.
Production et Analyse D'un Complexe Viral Dérivé D'un Virus des Radioleucoses de la Souris C57BL
Authors: Mamoun R. , Guillemain B. , Astier T. , Portail J. P. , Legrand E. , Duplan J. F.
Published: February 2007

Production and analysis of a viral complex derived from a radiation‐induced leukemia virus of the C57BL mouse

The MuLV isolate RadLV‐Rs derived from a radiation‐induced leukemia of a C57BL mouse was shown to induce preferentially lymphoreticulum cell neoplasms of spleen and lymph nodes rather than thymomas. Several cell lines were established in culture from spleen or lymph node tumors induced by RaLV‐Rs. These lines were originally composed of round shaped virus‐producing cells but their ability to produce virus disappeared progressively with serial passages and simultaneously they were growing as a monolayer of polygonal epithelial‐like cells. Several clones were derived from one of the tumor cell lines and the presence of round cells correlated positively with the viral release. Besides these morphological differences the karyotype of the clones chronically producing virus was strongly modified. Thus, cells of clone 13‐3C (producing a virus called 13C) contained 43 chromosomes, a large number of which were metacentrics or minutes. On the opposite, clone 13‐2D which had the same origin as 13–3C but did not produce virus had 70 acrocentric chromosomes. The in vitro produced virus 13C had the same pathogenic effects as the original RaLV‐Rs; on the basis of its biochemical and morphological properties it could be classified as a type‐C retrovirus and it also induced Gross type cell surface antigens. In contrast to most of the MuLV, 13C virus did not show any helper activity on the MSV integrated in S+L‐ mouse cells, however syncytia formation was readily observed after cocultivation of 13–3C and XC cells. The 13C virus was shown to be a complex composed of an ecotropic MuLV which preferentially infects B type mouse cells (MuLV‐B) and a xenotropic virus (MuLV‐X). The MuLV‐B had no helper activity for integrated MSV and did not induce XC syncytia formation. The MuLV‐X was a potent helper for MSV in S+L‐ mink cells but did not induce XC syncytia formation.
Epstein‐barr virus infection following bone‐marrow transplantation
Authors: Sullivan John L. , Wallen William C. , Johnson F. Leonard
Published: February 2007

A 12‐year‐old patient with acute lymphoblastic leukemia received a bone‐marrow transplant (BMT) from a matched sibling donor. Nine weeks prior to transplant the donor experienced Epstein‐Barr virus (EBV)‐induced infectious mononucleosis. The bone‐marrow recipient was EBV‐negative at the time of transplant; however, 4 weeks post transplant the recipient developed clinical symptoms of graft‐versus‐host disease (GVHD) coincident with serological evidence of acute EBV infection. In addition, a lymphoblastoid cell line positive for Epstein‐Barr nuclear antigen was established from a bone‐marrow sample obtained at the onset of symptoms compatible with GVHD. Sera obtained from the recipient over the ensuing 2 months showed the appearance of antibodies to specific EBV antigens consistent with a primary immune response to EBV infection. This association of acute EBV infection with symptoms of GVHD in a BMT recipient suggests a need for further investigation of the epidemiology of EBV infections in human bone‐marrow transplantation and the relationship between EBV infection and GVHD.