bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytocidal activity and proliferative ability of macrophages infiltrating the EMT6 tumor
Authors: Stewart Carleton C. , Beetham Karen L.
Published: February 2007

The EMT6 mouse tumor was selected for use in the study of cytocidal activity and proliferative ability of infiltrating macrophages because of its high plating efficiency when explanted to culture. The plating efficiency for cells directly plated in culture from the tumor was 28±9.3%, irrespective of the size of the tumor. Of the adherent cells derived from the tumor, the fraction that was macrophages increased from 27% at 7 days to 47% at 28 days after initial injection. Time‐lapse cinemicrography was used to directly observe adherent cells derived from the tumor, and macrophages were found to be cytocidal. When grown in the presence of L‐cell conditioned medium no macrophage colonies were found when cultures were established from untreated mice even though most tumor cell colonies contained macrophages. When mice were first treated with 0.8 mg BCNU prior to establishment of the cultures, in order to reduce the frequency of colony‐forming tumor cells, approximately half the colonies found contained only macrophages. These results show that macrophages in this tumor are cytocidal and capable of proliferation.
Surface expression of murine leukemia virus structural polypeptides on host cell and the virion
Authors: Schneider Josef , Hunsmann Gerhard
Published: February 2007

The expression of murine leukemia virus structural polypeptides on the surface of cells producing exogenous Friend leukemia virus, endogenous ecotropic AKR and xenotropic BALB/c virus was investigated. Antisera to Friend virus gp71, p30, p15E, p12 and p10 were employed in a complement‐dependent chromium release assay and to immuno‐precipitate lactoperoxidase iodinated surface polypeptides prior to analysis in polyacrylamide gel electrophoresis. With the latter technique gag‐gene encoded proteins and their precursors were not discovered on the viral and cellular surface membranes. Only env‐gene encoded polypeptides gp85, gp71 and p15E were detectable. p15E is embedded into the lipid membrane. gp85 is formed by disulfide linkage of p15E to surface‐exposed gp71. The ratio of gp71 to gp85 is variable and apparently determined by the host cell. Antibodies of strong cytotoxicity are those against type‐ and group‐specific epitopes of gp71 as well as type‐specific epitopes of p12.
Genetic dissociation of different cellular effects of interferon on myeloid leukemic cells
Authors: Lotem Joseph , Sachs Leo
Published: February 2007

Mutant clones of mouse myeloid leukemic cells have been used to study the effect of mouse interferon on the expression of different cellular genes. The cell mutants, MGI+D+, MGI+D− and MGI−D−, differed in their competence to be induced to undergo cell differentiation by the normal macrophage and granulocyte protein inducer MGI or the steroid hormone dexamethasone. The growth of all the clones tested was inhibited by interferon, but there was a 20‐fold difference in sensitivity to growth inhibition in different clones. This difference was not associated with the same difference in susceptibility to the cytotoxic effect of cytosine arabinoside and actinomycin D, or with cell competence for the induction of differentiation. The variation in cytotoxic effect of interferon on different malignant cell populations should, therefore, be taken into consideration in the possible clinical use of interferon as an anti‐tumor agent. Some MGI+D+ clones, but none of the MGI+D− or MGI−D− clones, showed, in addition to a high sensitivity to growth inhibition by interferon, a 14‐ and 2‐fold enhancement of the induction of lysozyme by dexamethasone and MGI, respectively, and a slight induction of Fc rosettes with dexamethasone. But interferon had no effect on induction of C3 rosettes, immune phagocytosis and differentiation to mature macrophages or granulocytes. The enhancing effect on lysozyme induction by interferon was also obtained with cordycepin, vinblastine, or 2‐deoxy‐D‐glucose, although neither interferon nor any of these other compounds alone induced any of the differentiation‐associated properties. A MGI+D− mutant, derived from an MGI+D+ clone with an enhancement of lysozyme induction by interferon, showed the same high sensitivity to growth inhibition by interferon as its parental MGI+D+ clone, but there was no enhancement of the induction of lysozyme by MGI or dexamethasone. The results indicate that interferon can exert a selective enhancing effect on the expression of some genes involved in differentiation in clones with the appropriate genotype and that, by using appropriate cell mutants, it is possible to genetically dissociate different cellular effects of interferon.
Primary epstein‐barr virus infections in African infants. II. Clinical and serological observations during seroconversion
Authors: Biggar Robert J. , Henle Gertrude , Böcker Jörg , Lennette Evelyne T. , Fleisher Gary , Henle Werner
Published: February 2007

Of 27 Ghanaian infants examined monthly for the first 15 months of life and once more at 21 months, 12 acquired primary Epstein‐Barr virus (EBV) infections by the age of 1 year and 9 others seroconverted during the subsequent period of observation. The seroconversions were not accompanied by significant clinical or physical signs of illness and in none of the infants was a diagnosis of infectious mononucleosis (IM) suspected on the basis of hematologic observations. The 12 early seroconverters, providing the most extensive follow‐up data, showed transient IgM antibody responses to EB viral capsid antigen (VCA) which in some cases initially exceeded the corresponding IgG antibodies in titer. Peak VCA‐specific IgG titers were noted 2 months after seroconversion and were comparable to those seen in IM. Most of the infants developed antibodies to the EBV‐induced early antigen complex which were directed, however, against the R (restricted) component, as observed in Burkitt's lymphoma, and not against the D (diffuse) component, as noted in IM. Low titers of VCA‐specific IgA antibodies emerged in five of the cases. Usually, EBV‐neutralizing antibodies were already present in the first anti‐VCA‐positive serum but antibodies to the EBV‐associated nuclear antigen (EBNA) and antibody‐dependent cell‐mediated cytolysis (ADCC) became detectable only months after seroconversion. No heterophil antibody responses, or at most barely significant ones, were recorded. Attempts to demonstrate EBV in throat swab specimens met with limited success, suggesting a low degree of viral excretion during silent seroconversions. Possible explanations for the differences between clinical, hematologic and serologic responses to primary EBV infections in infancy and later in life are discussed.
Interaction of the B95‐8 and P3HR‐1 substrains of epstein‐barr virus (EBV) with peripheral human lymphocytes
Authors: Steinitz Michael , Bakács Tibor , Klein George
Published: February 2007

Two substrains of the Epstein‐Barr virus derived from the B95‐8 and P3HR‐1 cell lines were studied for their interaction with human peripheral lymphocytes. It has been previously shown that B95‐8 virus has and P3HR‐1 virus lacks lymphocyte‐transforming (“immortalizing”) properties. DNA stimulation induced by B95‐8 virus showed a good correlation with the number of surface Ig‐positive cells. P3HR‐1 virus added before B95‐8 virus completely abolished the stimulation of DNA synthesis. It also prevented EBNA induction by B95‐8 virus. P3HR‐1 virus added after B95‐8 virus diminished DNA stimulation by the latter in a time‐dependent fashion. P3HR‐1 virus did not inhibit DNA stimulation by phytohaemagglutinin but was inhibitory if added before a B‐cell mitogen (Staphylococcus Aureus). The origin of P3HR‐1 virus and its relationship to the transformation process are discussed.
Presence of EBNA in nasopharyngeal carcinoma and control patient tissues related to ebv serology
Authors: Huang D. P. , Ho H. C. , Henle W. , Henle G. , Saw D. , Lui M.
Published: February 2007

A search was made for Epstein‐BARR virus (EBV) associated nuclear antigen (EBNA) in touch preparations of fresh biopsy material from 26 carcinomas of the nasopharynx, 39 other tumours of the head and neck, the nasopharyngeal mucosa of 32 patients in whom nasopharyngeal neoplasm had been excluded, and the mucosa from enlarged but non‐neoplastic tonsils removed from 12 patients. EBNA‐positive cells were uniformly detected in the preparations from the undifferentiated and poorly differentiated squamous‐cell carcinomas of the nasopharynx, provided they contained tumour‐cell aggregates. Such cells were not detected in the preparations from the single case of well‐differentiated papillary adenocarcinoma in the nasopharyngeal carcinoma group. There were no moderately or well‐differentiated squamous‐cell carcinomas among the nasopharyngeal carcinoma group. Among other tumours of the head and neck, only three undifferentiated carcinomas of the nasal fossa were found to contain EBNA‐positive cells. None of the nasopharyngeal or tonsillar mucosal preparations contained such cells. These findings confirm the unique regular association of EBNA with nasopharyngeal carcinoma of undifferentiated and poorly differentiated squamous‐cell types (NPC). The EBV‐related serological findings support the value of tests for IgG and IgA antibodies to VCA and EA(D) in the exclusion of NPC in patients with suspicious symptoms and the differentiation between NPC and other tumours of the head and neck. Examination of biopsy specimens for the presence of EBNA‐positive cells or EBV‐DNA is essential, however, for confirmation of the diagnosis.
Failure of selective screning for breast cancer by combining risk factors
Authors: Soini Irma , Hakama Matti
Published: February 2007

The possibilities of selective screening to reduce the costs of screening programmes for breast cancer were considered. Discriminant function analysis was used in an effort to describe a high‐risk group of breast cancer, which will be subjected to screening. The high‐risk group consisted of females with a combination of reproductive and hormone use characteristics. One‐fifth of the breast cancer cases remained in the low‐risk group, when the high‐risk group was small enough (two‐thirds of the population) to yield a meaningful reduction in costs. Selective screening for breast cancer seems to have only limited applicability and is not effective enough for application in public health work.
Activation of complement by spontaneous leukemic cells of AKR mice
Authors: Okada Noriko , Okada Hidechika
Published: February 2007

Complement activation via the alternative pathway by tumor cells was tested by rosette formation of human erythrocytes (HuE). Test cells were treated with C4‐deficient guinea‐pig serum (C4DS) in the presence of Mg++ and absence of Ca++, following which 10–30% of lymphoma cells and 10–17% of thymoma cells of spontaneous leukemia in AKR mice formed rosettes. The incidence of rosette formation did not change significantly after transplantation of these cells to other non‐leukemic AKR mice or after in vitro cultivation. Following treatment with fresh C4DS, however, normal AKR mouse thymocytes as well as lymph‐node cells contained only 3–4% HuE‐positive cells. These findings suggest that the ability of non‐specific activation of complement (NAC) may be increased when normal AKR mouse cells become transformed into leukemic cells and/or that the leukemic cells arise from thymus cells which possess NAC ability. This interpretation was further confirmed by the finding that a higher proportion of leukemic cells than of normal thymocytes were lysed by mouse complement in Mg++‐EGTA. The fact that NAC‐positive AKR thymoma cells were lysed effectively by homologous C3H/He plasma agrees with earlier findings that in leukemic AKR mice supplemented with C5 a temporary regression of leukemia occurs.
Effect of light on the hydrocarbon‐DNA adducts formed in hamster embryo cells
Authors: Baird William M.
Published: February 2007

Polycyclic aromatic hydrocarbons are metabolically activated and bind to DNA in hamster embryo cell cultures. The effect of light exposure on the DNA adducts formed from two hydrocarbons of different photosensitivities was investigated by exposing cells to light during hydrocarbon treatment and by exposing DNA to light after isolation from cells treated with hydrocarbon in darkness. The total hydrocarbon‐DNA adducts formed per mg DNA in cells treated with the highly photosensitive hydrocarbon 7,12‐dimethylbenz(a)anthracene (DMBA) in the presence of light was less than in cells treated in darkness. No appreciable amounts of hydrocarbon‐DNA adducts were formed in cells treated with a major photo‐oxidation product of DMBA, the 7,12‐endoperoxide, in either the presence or absence of light. DMBA‐deoxyribonucleoside adducts were analyzed by chromatography on Sephadex LH20 columns. Exposure to light of the DMBA‐deoxyribonucleoside adducts obtained by enzymatic degradation of DNA isolated from cells treated with DMBA in darkness converted more than half to photoproducts. DNA that was exposed to light prior to degradation contained less than half as many photoproducts and had an elution profile similar to that obtained from DNA isolated from cells treated with DMBA in the presence of light. With the less photosensitive hydrocarbon benzo(a)pyrene, benzo(a)pyrene‐DNA adducts were identical for DNA from cells treated with benzo(a)pyrene in darkness, DNA from cells treated in the presence of light, and DNA exposed to light after isolation. These results indicate that exposure to light does not alter the mechanism of binding of hydrocarbons to DNA in hamster embryo cells, but does affect the DNA adducts of the photosensitive hydrocarbon DMBA in a similar manner in cells and in isolated DNA.
Effects of carcinogen dose on the characteristics of the tracheal tumor response induced by N‐nitroso‐N‐methylurea in hamsters
Authors: Yarita Tsutomu , Nettesheim Paul
Published: February 2007

Tracheal tumors were induced by repeated intratracheal exposures to the carcinogen N‐nitroso‐N‐methylurea (NMU), using a catheter system previously described. Carcinogen concentrations of 0.25, 0.50 and 1.0% were employed in 20 or 30 twice‐weekly exposures. Most of the tumors developed in the mid‐portion of the tracheas. Virtually all tumors developed after the end of the 10‐ to 15‐week exposure period. Tumor incidence ranged from 20–94% with mean tumor induction times of 13–46 weeks, depending on NMU concentration and frequency of exposure (i.e., dose). At lower doses, mostly non‐invasive tumors were induced; at higher doses, mostly invasive carcinomas of various histological types (epidermoid, adeno‐, epidermoid‐adeno, and anaplastic large‐ and small‐cell carcinomas) were induced. Adenocarcinomas were most frequent at low NMU concentrations. The possible mechanisms of the carcinogen dose effects are discussed.
Inhibition of morphological transformation induced with N‐methyl‐N′‐nitro‐N‐nitrosoguanidine in cultures of hamster embryo cells by 5′‐bromo‐2′‐deoxyuridine‐photolysis
Authors: Mironescu Stefan G. D.
Published: February 2007

The present study was performed in order to determine whether type III transformed foci induced by N‐methyl‐N′‐nitro‐N‐nitrosoguanidine originate from the small subpopulation of cells stimulated by the carcinogen to enter DNA synthesis. During the last 30 min of variable treatment periods using different doses of N‐methyl‐N′‐nitro‐N‐nitrosoguanidine, administered alone or in association with the thymidine analogue, 5′‐bromo‐2′‐deoxyuridine (0.98 × 10−5 M), the density‐inhibited monolayers of hamster embryo cells were exposed to fluorescent light and then assayed for abnormal growth patterns by the focus formation method. Mock‐irradiated cultures as well as monolayers whose medium lacked N‐methyl‐N′‐nitro‐N‐nitro‐soguanidine, 5′‐bromo‐2′‐deoxyuridine, or both, served as controls. The cytotoxicity of 5′‐bromo‐2′‐deoxyuridine + N‐methyl‐N′‐nitro‐N‐nitrosoguanidine + photolysis (BMP) protocol on confluent as well as logarithmically growing hamster embryo cells was estimated in single‐cell survival experiments. Plating efficiency determinations have demonstrated that, unlike their actively growing counterparts, confluent hamster embryo cell mono‐layers are extremely resistant to the cytotoxic effects of the BMP protocol. The quantitative transformation assays indicated that: (1) in non‐illuminated cultures addition of 5′‐bromo‐2′‐deoxyuridine to carcinogen‐containing medium does affect transformation frequency of hamster embryo cells in the sense that the incidence of type III foci did not subside at later intervals during the post‐carcinogen administration period as it did in the absence of the analogue; (2) irradiation of N‐methyl‐N′‐nitro‐N‐nitrosoguanidine and halogenated pyrimidine analogue‐treated cultures with fluorescent light practically suppressed transformation; (3) analogueadded and analogue‐removed experiments pointed out that the event(s) on which 5′‐bromo‐2′‐deoxy‐uridine fluorescent light sensitization of morphological transformation largely depends, takes place between 5 and 15 h after N‐methyl‐N′‐nitro‐N‐nitrosoguanidine administration, i.e., during the period of maximal carcinogen‐stimulated DNA synthesis; and (4) neither fluorescent light nor 5′‐bromo‐2′‐deoxyuridine, singly or in combination, were able to transform cultures of hamster embryo cells. These findings are strong indirect arguments for the concept that carcinogen‐induced DNA synthesis and the initiation of transformed clones are causally related.
Differences in the capacity of simian virus 40 (SV40) tumor antigens on cells, membranes and in soluble form to induce transplantation immunity in hamsters and mice
Authors: Law Lloyd W. , Takemoto Kenneth K. , Rogers Michael J. , Henriksen Ole , Ting Robert C.
Published: February 2007

The immunogenicity of the SV40 tumor‐specific transplantation antigen (TSTA) on cells, cell particulates and solubilized membranes was studied in mice and in Syrian hamsters. Immunizations were done with various concentrations of tissue‐culture‐passaged, non‐virus‐releasing transformed cells, purified cell membranes and in some cases purified nuclei and papain‐solubilized membranes obtained from several species, including the mouse, hamster, man, and sheep. All transformed cell lines were T‐antigen‐positive. The immunosensitive mKSA line of BALB/c mice and the immunosensitive SV34 cell line of the hamster were used for tumor challenge. All materials, regardless of source and of type of preparation, were strikingly immunogenic in the mouse but only SV40 virus and SV34 (hamster) cells provided protection against tumor cell challenge in the hamster. Also, in a limited study, BKV‐transformed hamster cells and purified cell membranes and JCV‐transformed hamster cells were found to be immunogenic by the tumor rejection assay in the mouse but not in the hamster. SV40 immunization did not protect the hamster against BKV‐ and JCV‐transformed hamster cells. These results are discussed in terms of possible different specificities resident on the TSTA molecule.
Virus‐induced papillomas of the alimentary tract of cattle
Authors: Jarrett W. F. H. , Murphy J. , O'Neil B. W. , Laird Helen M.
Published: February 2007

An abattoir survey was carried out to determine the incidence and aetiology of squamous papillomas of the alimentary tract of cattle in Scotland and North England as they were suspected of being involved in the genesis of alimentary carcinoma in certain localized geographical areas. A total of 7,746 cattle of a wide age range was examined. Various subsets of this number were subjected to analyses of certain specific factors. The calculated overall incidence was 19% and the detailed site incidence and tumour multiplicity are given. The sites at which papillomas were found were identical with those at which carcinoma had been noted in animals from a high‐cancer area. The number of sites affected by papilloma and the tumour multiplicity were much lower in the general population than in the high‐cancer area. Inclusion bodies, identified by electronmicroscopy as virus, were found in tumour cell nuclei and a typical papilloma virus was purified from the tumours. The structure of the tumours is described and the possible plurality of bovine papilloma‐viruses is discussed in the light of recent findings in the human viruses. The general interest of a naturally occurring and geographically localized oncogenic system, in which an environmental carcinogen and a virus might be involved, is extended.
The occurrence of feline leukaemia virus neutralizing antibodies in cats
Authors: Russell Peter H. , Jarrett Oswald
Published: February 2007

The prevalence of feline leukaemia virus (FeLV)‐neutralizing antibodies to subgroups A (FeLV‐A), B (FeLV‐B) and C (FeLV‐C) was determined in four populations: specific pathogen‐free (SPF) cats; urban and suburban free‐range cats; cats from FeLV‐infected multiple cat households (MCHs); and cats with leukaemia. The prevalence of anti‐FeLV‐A antibodies was closely related to the frequency of isolation of FeLV‐A in each population, except in leukaemic cats. Thus, antibody was found in none of the SPF cats, in 4% of free‐range cats and in 42% of the cats in MCHs. In individual cats in MCHs there was a strong correlation between the presence of antibodies to FeLV‐A and the absence of an active FeLV viraemia. Anti‐FeLV‐B antibodies were encountered less frequently although FeLV‐B was present in about half of the FeLV isolates. It is likely that this was due to the restricted growth of FeLV‐B in cats. Surprisingly, in view of the very rare isolation of FeLV‐C, the prevalence of anti‐FeLV‐C antibodies was high: 11% in free‐range, 51% in MCH and 40% in leukaemic cats. None were found in SPF cats. The occurrence of these, unlike antibodies to FeLV‐A, was not related to whether or not a cat was viraemic. The relationship between the development of neutralizing antibodies and persistent viraemia was studied in experimental infections of cats with FeLV by inoculation or contact. The outcome of the infection was determined soon after infection. All of the classes of cats which were found in the epidemiological survey were observed in these experiments.
Aryl hydrocarbon hydroxylase in persons with lung or laryngeal cancer
Authors: Ward Elizabeth , Paigen Beverly , Steenland Kyle , Vincent Ronald , Minowada Jun , Gurtoo Hira L. , Sartori Pam , Havens Mary Bohne
Published: February 2007

To test whether the distribution of AHH inducibility is shifted toward the high end of the range in patients who had lung and laryngeal cancer, we measured this trait in 59 patients (32 lung and 27 laryngeal) who had resectable tumors and had been disease‐free for a period of time. The advantage of selecting patients who were free of clinical disease was that measurement of their AHH inducibility should not have been affected by the disease state. Patient and control populations showed no difference in basal and induced AHH activity or AHH inducibility. The mean AHH inducibility in patients who had lung cancer was 3.20±0.20; in patients who had laryngeal cancer 2.96±0.18, and for all controls 3.29±0.04 (no significant difference at p = 0 05). Further analysis of the distribution of AHH inducibility in the patient group compared to controls showed no suggestion of a shift toward the higher end of the range in patients who had lung and laryngeal cancer.
Interferon and spontaneous cytotoxicity in man. I. Enhancement of the spontaneous cytotoxicity of peripheral lymphocytes by human leukocyte interferon
Authors: Einhorn Stefan , Blomgren Henric , Strander Hans
Published: February 2007

A purified preparation of human leukocyte interferon used at this hospital in the treatment of malignant diseases was tested for its ability to modify the spontaneous cytotoxicity of peripheral lymphocytes from healthy donors. The inhibitory effect of allogeneic lymphocytes on the [3H]thymidine incorporation of a lymphoblastoid cell line, Raji, was augmented by the presence of interferon or by pretreatment of the lymphocytes with interferon. This form of pretreatment also increased lymphocytes' capacity for reducing the number of surface‐adherent tumor cells in a microassay. Moreover, lymphocytes treated with interferon exhibited an enhanced cytotoxic capacity for target cells on incubation with such cells labelled with 51Cr.
The circulating alpha subunit of human chorionic gonadotrophin in gynacologic tumours
Authors: Rutanen Eeva‐Marja
Published: February 2007

The circulating levels of the immunoreactive alpha subunit of glycoprotein hormones were measured by the hCG alpha subunit radioimmunoassay in 101 patients with non‐trophoblastic gynaecological cancer and in 164 serum samples obtained from 10 patients with choriocarcinoma and five patients with hydatidiform mole. Serum samples from six patients with choriocarcinoma and four with hydatidiform mole were further examined for the existence of free alpha by chromatography on a calibrated Sephadex G‐100 column. In patients with non‐trophoblastic cancer the immunoreactive alpha subunit levels were not different from those of controls in the corresponding age groups. In trophoblastic disease all hCG‐positive samples showed also alpha subunit immunoreactivity when tested by radioimmunoassay, but no isolated alpha elevation was found. Chromatographic analyses revealed free alpha subunits in three out of six patients with choriocarcinoma and two out of four patients with hydatidiform mole. A patient who eventually died of choriocarcinoma was carefully followed for the free alpha secretion, and no alpha elevation was found in any of the 16 serum samples taken at various phases of disease. The present study shows that, unlike pancreatic islet cell tumours in vivo and HeLa cells in vitro, non‐trophoblastic gynaecologic cancer in vivo does not appear to have any significant alpha secretion. In trophoblastic disease free alpha subunits may coexist with native hCG more frequently than it was originally assumed, but no isolated alpha secretion could be demonstrated. The intriguing disparity between the alpha secretion by normal and abnormal trophoblasts was confirmed in this study, but the biological basis and significance of this phenomenon remain obscure.
BCG treatment of transplanted rat tumours of spontaneous origin
Authors: Pimm M. V. , Cook A. J. , Hopper D. G. , Dickinson A. M. , Baldwin R. W.
Published: February 2007

Six transplanted rat tumours (three mammary carcinomas and three fibrosarcomas), all of spontaneous origin and of limited immunogenicity, have been examined for susceptibility to immunotherapy with BCG (Glaxo). Growth of limited numbers of cells from five tumours was suppressed when cells were injected subcutaneously in admixture with BCG organisms. There was no clear correlation between the immunogenicity of tumour lines and their susceptibility to regionally applied BCG. Active specific immunotherapy, using vaccines of viable or radiation‐attenuated tumour cells in admixture with BCG, was reproducibly successful with only one tumour, the mammary carcinoma Sp4, this being the most immunogenic of the tumours examined. These studies indicate that naturally arising tumours are less susceptible to BCG‐mediated suppression than carcinogen‐induced tumours widely used for experimental immunotherapy, but indicate that local application of BCG may give the best therapeutic response.
Longitudinal studies of chromosomal abnomalities and reticulum cell proliferation in new zealand black mice
Authors: Friedman J. M. , Fialkow Philip J. , East June , Bryant Jean I. , Salo Armi C.
Published: February 2007

A longitudinal study of 40 New Zealand Black (NZB) mice and 20 BALB/c control animals was performed. A significant association was observed between the presence of acquired spleen‐cell aneuploidy at some time during life and development of histological evidence of reticulum‐cell neoplasia in individual animals. This finding is compatible with the hypothesis that aneuploid clones which arise in the spleens of aging NZBs are at least potentially neoplastic. However, no relationship between histologically neoplastic reticulum cell proliferation and aneuploidy was apparent in single splenic specimens obtained from NZB mice of various ages. This lack of association indicates that failure to detect chromosomal abnormalities on direct study of cells from a tumor cannot be taken as evidence that the neoplastic cells themselves lack such abnormalities.
An immunoregulatory factor associated with spleen cells from tumor‐bearing animals. I. Effect on tumor growth and antibody production
Authors: Isakov Noah , Segal Shraga , Hollander Nurit , Feldman Michael
Published: February 2007

An immunopotentiating factor associated with spleen cells of C57BL/6J mice bearing the 3LL tumor is described. Supernatants of cultured spleen cells from tumor‐bearing mice (TBM) augmented the generation of both 19S and 7S antibody‐producing cells, when injected with sheep erythrocytes into syngeneic C57BL/6J mice. The enhancing supernatant acted both as a polyclonal activator, when injected in the absence of antigen, and as a potentiator of specific antigen‐dependent humoral immune responses, when injected in the presence of antigen. It was found to augment induction of specific memory, but not memory expression. Concomitantly with their influence on humoral immune responses, TBM spleen cell supernatants enhanced tumor growth when injected, mixed with 3LL tumor cells, into syngeneic recipients. The secretion of a factor which augments antibody production was not confined to the 3LL tumor system. Spleen supernatants of C47BL mice carrying the B16 melanoma and those of C3H mice carrying the KHT sarcoma had a similar effect on antibody production. These findings suggest that an immunoregulatory factor(s) appears in spleen cells of TBM as a result of their interaction with the neoplastic tissue. This factor can potentiate production of antibodies, possibly also against tumor‐associated antigens. The relevance of the immunopotentiating effects of such factor(s) to tumor growth is discussed.
The early appearance and subsequent distribution of murine leukaemia virus in NZB embryos
Authors: East June , Tilly Rita J. , Tuffrey Mauren , Harvey Jennifer J.
Published: February 2007

Information concerning both spontaneous autoimmune haemolytic disease and a uniquely high expression of solely xenotropic murine leukaemia virus (MuLV) is transmitted genetically in New Zealand Black (NZB) mice. The actual production, location, and dissemination of MuLV has now been monitored in NZB embryos by electronmicroscopy, which is the most suitable method for detecting such virus very early in prenatal life i.e. in eggs before they become implanted approximately 4 1/2 days after mating. A systematic search was made for intracisternal type‐A and type‐C virus particles in NZB embryos from the one‐cell stage to the 14th day of gestation. AKR, Balb/c, and F1 (BALB/cx NZB) eggs were included for comparison of preimplantation phases, and five combinations of blastocysts fused in vitro as 6‐ to 8‐celI eggs were also examined. Four variants of type‐A particles were distinguished, characteristically associated with the cisternae of the endoplasmic reticulum. All replicated at some stage of preimplantation development in NZB and AKR eggs, as well as in fused AKRAKR and BALB/c↔BALB/c blastocysts, and three of them were still to be found in 8‐ or 14‐day NZB embryos. Moreover, the smallest type‐A variant also appeared in one‐cell unfertilized NZB eggs, indicating that its production did not depend on the stimulus of fertilization. No type‐A virus was identified in normal BALB/c and F1 (BALB/cx NZB) blastocysts, or in NZBB́LB c, CBA/H‐T6CBA/H‐T6, and AKRCBA/H‐T6 combinants. By comparison, immature type‐C virus was first seen in 5‐day NZB implants. But it was not possible to decide whether implantation or a particular stage of differentiation determined its emergence, or whether it had only then reached detectable levels. Thereafter, immature C and type‐A particles coexisted and replicated until at least the 14th day of gestation, but mature C virus was not evident at this age. Both ecotropic and xenotropic MuLV can be represented morphologically as type‐C particles. The known lack of infectivity of the type‐A particles, coupled with our evidence of their genetic transmission and of their ubiquity in NZB embryos which do not harbour ecotropic Mulv, could indicate that they, too, are xenotropic. Coincidentally, huge numbers of immature and mature type‐C MuLV were found distending the uterine glands of pregnant NZB females carrying 5‐ or 7‐day implants. But a similarly extravagant picture was seen in agematched NZB virgins. These findings are to be investigated further.
Leukocyte migration inhibition responses in canine lymphosarcoma
Authors: Onions D. E. , Owen L. N. , Bostock D. E.
Published: February 2007

The leukocyte migration inhibition (LMI) responses of 16 cases of canine lymphosarcoma were assessed at several stages of a combined chemotherapy immunotherapy regime. Pooled allogeneic lymphosarcoma cells used in treatment together with other allogeneic lymphosarcoma cells and autochthonous tumour cells were employed as antigens. Positive inhibitions were detected at all stages of treatment when medium controls were used but were not detected in five normal dogs with the same control. There was no association between relapse and remission and LMI response. When a normal lymph‐node cell control was used only four dogs produced positive responses, all of which occurred after allogeneic cell administration. These positive responses could not be completely accounted for by sensitization to histocompatibility antigens but as they occurred both in remission and in relapse, including very advanced cases necessitating euthanasia, they were of no value in determining prognoses.
Study of epstein‐barr virus‐determined nuclear antigen (EBNA) by chromatography on fixed cell nuclei
Authors: Hirsch Ivan , Suchánková Alena , Závadová Hana , Vonka Vladimír
Published: February 2007

Low ionic strength (50 to 100 mM NaCl) and pH 6.0 were found to be optimal conditions for in vitro conversion of Epstein‐Barr virus (EBV)‐determined nuclear antigen (EBNA)‐negative nuclei to EBNA‐positive nuclei by addition of the complement‐fixing (CF) antigen extracted from Raji cells. In vitro conversion of nuclei to EBNA‐positivity was sensitive to DNase but not to RNase treatment. This suggests that nuclear DNA is a specific target substance to which EBV‐CF antigen binds. If nuclei were fixed with methanol/acetic acid and subsequently treated with 0.6 M NaCl, EBNA could be eluted from in vitro‐converted Ramos nuclei with 0.3 and 0.4 M NaCl. The same conditions were also found to be optimal for the adsorption and elution of EBV‐CF antigen in DNA‐cellulose chromato‐graphy. This indicates that the DNA‐binding properties of EBNA antigen can be studied by “chro‐matography” on fixed nuclei followed by the ACIF test. The obvious advantages of this method over chromatography on DNA‐cellulose are its simplicity, the possibility of testing many samples in one experiment and, especially, the use of minimal amounts of material. Significant differences in elution patterns for EBNA were found when nuclei derived from different cell lines (Ramos, Raji, and P3HR‐1) were converted in vitro to EBNA‐positivity. EBNA is eluted from in vitro‐converted nuclei of EBV genome‐positive P3HR‐1 cells at an almost 0.1 M higher concentration of NaCl than is necessary for a similar degree of elution from nuclei of EBV genome‐negative Ramos cells.
Studies of effector cell, antibody, and target cell interactions in natural cell‐mediated cytotoxicity
Authors: Koide Yukio , Kwok Rose , Takasugi Mitsuo
Published: February 2007

IgG antibodies bound to effector cells through Fc receptors were observed to determine the specificity of natural cell‐mediated cytotoxicity (NCMC) against cultured target cells. When effector lymphocytes were isolated from the peripheral blood of most individuals, they already possessed natural antibodies specific for antigens on cultured cells. Since they lacked IgG antibodies specific for antigens on sheep red blood cell (SRBC) targets, natural cytotoxicity against SRBC was almost non‐existent. Effector cells incubated in IgG anti‐SRBC became specifically cytotoxic to SRBC. In the process, NCMC and antibody‐dependent cell‐mediated cytotoxicity was diminished, indicating that arming with anti‐SRBC replaced natural antibodies and occupied Fc receptors on effector cells. Thus, treating effector cells with serum may result in increased or decreased cytotoxicity depending upon the specificity of antibodies within the serum. This type of modulation of NCMC occurs at the interaction between antibody Fc and Fc receptors and can explain blocking and unblocking.
Effect of ricin and abrin on survival of L1210 leukemic mice and on leukemic and normal bone‐marrow cells
Authors: Fodstad øystein , Pihl Alexander
Published: February 2007

The effect of ricin and abrin on the survival of mice treated with L1210 leukemic cells intraperitoneally or intravenously was studied. In mice given 1 × 105 L1210 leukemia cells intraperitoneally a single dose of ricin (2.1 μg/kg) intraperitoneally gave the best results, an increased life span (ILS) of 59%. Abrin also increased the life span of such animals although to a lesser extent. The effect of ricin was superior to that of 5‐fluorouracil, but inferior to that of adriamycin, which gave a maximum ILS of 280%. In mice given L1210 cells intravenously no increase in life span was obtained with ricin, abrin or adriamycin, whereas 5‐fluorouracil gave an ILS of 40–50%. In spleen colony assays the differential effect of ricin and abrin on the proliferative capacity of normal hematopoietic and leukemic colony‐forming cells in bone marrow was studied. The differential effect of ricin was as good as that of adriamycin and considerably better than that of 5‐fluorouracil. Abrin had a much smaller effect than ricin on both normal and leukemic cells. The effect of abrin on the leukemic cells was too small to be of therapeutic value. The results warrant exploration of the use of ricin in the treatment of human leukemia.
Cytotoxic activity of guinea‐pig lymph‐node cells stimulated in vitro
Authors: Altman Amnon , Rapp Herbert J.
Published: February 2007

Guinea‐pig lymph‐node cells (LNC) cultured for 5 days in medium containing fetal calf serum (FCS) were cytotoxic to various target cells. LNC cultured in medium supplemented with fresh, autologous guinea‐pig serum (GPS) instead of FCS were not detectably cytotoxic unless agents that stimulate lymphocyte proliferation were added to the culture medium. The stimulating agents we studied were 2‐mercaptoethanol (2‐ME), syngeneic tumor cells, allogeneic peritoneal exudate cells (PEC) and the T‐cell mitogens concanavalin A (Con A) and phytohemagglutinin (PHA). LNC cultured in the presence of these agents were cytotoxic to normal syngeneic fibroblasts and to syngeneic, allogeneic or xenogeneic tumor cells but not to PHA‐induced lymphoblasts. Potentiation of cytotoxicity in vitro was accompanied by a marked proliferation of the cultured LNC; the combination of several stimulatory agents had an additive effect on the generation of cytotoxicity in culture.
Enhancement of thermal killing by polyamines. I. Survival of chinese hamster cells
Authors: Ben‐Hur E. , Prager A. , Riklis E.
Published: February 2007

Exposure of Chinese hamster cells to polyamines at an elevated temperature (42°C) results in synergistic cell killing. The effectiveness of polyamines in potentiating thermal killing decreases in the following order: spermine>spermidine> cadaverine>putrescine. The magnitude of the synergism increases with exposure time. The survival curves, when plotted as a function of polyamine concentration, display a shoulder during 1 h exposure at 42°C, followed by exponential cell killing. Longer exposure times eliminate the shoulder and result in steeper slopes of the survival curves. The effect is maximal when exposure to polyamines and heat is simultaneous. Separation in time between the two treatments causes a rapid disappearance of the synergism. The order of application is of only minor importance in this regard. The results suggest that the intracellular level of spermine may be a major factor in determining heat sensitivity of Chinese hamster cells.
Cancer and „cancer related”︁ colorectal lesions in São Paulo, Brazil
Authors: Marigo Carlos , Correa Pelayo , Haenszel William
Published: February 2007

A series of 832 necropsy specimens were studied grossly with a magnifying lens and all lesions identified were studied microscopically. The age and sex‐specific prevalence of adenomatous and hyperplastic polyps is reported and results are compared with those of other populations. A correlation was made between polyps and cancer of the colon and rectum (407 cases). The data suggest that São Paulo is a community in a transitional stage between intermediate and high risk of cancer of the colon. The epidemiologic characteristics of lower rectum cancer are peculiar to some populations and appear unrelated to colon cancer. The black population of São Paulo has a higher prevalence than that reported for African negroes. The data also implicate adenomatous polyps, diverticulosis and hemorrhoids as being probably related diseases.
Somatic cell hybrids between human lymphoma cell lines. V. IdUrd inducibility and P3HR‐1 superinfectability of Daudi/HeLa (DAD) and Daudi/P3HR‐1 (DIP‐1) cell lines
Authors: Moar M. H. , Ber R. , Klein G. , Westman A. , Eriksson I.
Published: February 2007

We have studied two types of somatic cell hybrid with regard to expression of the Epstein‐Barr virus (EBV) cycle and its regulation. The first, DIP‐1, a hybrid formed between two human lymphoma EBV producers (Daudi and P3HR‐1), contained EBV DNA, expressed the virus‐determined nuclear antigen (EBNA), and was a producer of the EBV‐associated antigens EA (early antigen) and VCA (viral capsid antigen). The second, DAD, a hybrid series of clones formed between Daudi and a HeLa cell derivative (D98), differed with regard to the expression of EBNA, EA, VCA and the content of EBV DNA. EA was regularly induced in the EBV DNA‐containing hybrids following treatment with iododeoxyuridine (IdUrd). This induction was greater in lines spontaneously expressing EA. In two hybrids, DIP‐1 and DAD10, VCA and virus DNA synthesis were also induced in the presence of IdUrd, the latter being detected by in situ hybridization with P3HR‐1 EBV complementary RNA. Finally, while DIP‐1 was superinfectable by the P3HR‐1 EBV strain, the DAD series of hybrids were refractory to P3HR‐1 superinfection and lacked EBV receptors.
Malignant lymphoma in four of five siblings
Authors: Nagel G. A. , Nagel‐Studer E. , Seiler W. , Hofer H. O.
Published: February 2007

In one family four out of five siblings were affected with malignant lymphoma and HD has been diagnosed in two other relatives. HLA‐haplotypes were identical for the three diseased siblings who were so studied, whereas for the unaffected one they were different.
Sister chromatid exchanges and chromosomes in chronic myelogenous leukemia and cancer families
Authors: Cheng Wind‐Show , Mulvihill John J. , Greene Mark H. , Pickle Linda W. , Tsai Shien , Whang‐Peng Jacqueline
Published: February 2007

Spontaneouas sister chromatid exchanges and banded karyotypes were studied in blood lymphocytes from 96 individuals: seven patients with chronic myelogenous leukemia, 15 normal controls, and five “cancer families” comprising 12 cancer patients, 40 tumor‐free blood relatives and 22 spouses. The families had: malignant melanoma; Epstein‐Barr virus‐associated malignancies and a birth defect syndrome; non‐Hodgkin lymphoma and diverse carcinomas; Hodgkin's lymphoma and adenocarcinomas; and acute myelogenous leukemia. In addition to the Philadelphia chromosome in chronic myelogenous leukemia patients, karyotypic abnormalities, especially breaks and fragments, were found in 29% of cancer family members, but were inconsistent and usually attributable to radiotherapy. Mean sister chromatid exchange values were normal in chronic myelogenous leukemia, but low (by t‐test) in tumor patients and their blood relatives in cancer‐prone families. In tumor patients, mean sister chromatid exchange levels fell as age increased. After adjusting for this age effect, no significant differences remained among groups. In patients at high risk of cancer (because they have chronic myelogenous leukemia or a strong family history of cancer), spontaneous sister chromatid exchange rates were not a marker of cancer risk.
14q+ marker chromosome in an EBV‐genome‐negative lymph node without signs of malignancy in a patient with EBV‐genome‐positive nasopharyngeal carcinoma
Authors: Mitelman F. , Klein G. , Andersson‐Anvret M. , Forsby N. , Johansson B.
Published: February 2007

In a patient with an EBV‐genome‐positive naso‐pharyngeal carcinoma, an EBV‐genome‐negative inguinal lymph node without histological evidence of malignant lymphoma or metastatic carcinoma growth was found to contain a 14q+ marker chromosome, identified as an 8;14 translocation, in all cells analyzed. This observation Indicates that chromosome aberrations may precede histological signs of malignancy. The possible implication of this finding in relation to the postulated role of the 14q + marker and lymphoma development is discussed.
Cell‐density‐dependence for growth in agarose of two human lymphoma lines and its decrease after epstein‐barr virus conversion
Authors: Montaonier L. , Gruest J.
Published: February 2007

We have compared the growth in agarose medium of two EBV‐negative Burkitt lymphoma lines, BJAB and Ramos, and that of their EBV‐converted derivatives. Optimal conditions for growth in agarose medium are described. The original EBV‐negative lines can grow in agarose to a high efficiency, provided a critical level of cell concentration is attained. Below this level, there is no growth at all. EBV‐converted sublines form colonies at a much lower cell concentration, and their maximal plating efficiency is higher. These differences may be related to a super‐transformation state induced in these cells by EBV.
Immunogenic properties of a soluble tumor rejection antigen (TSTA) from a simian virus 40‐induced sarcoma
Authors: Rogers Michael J. , Law Lloyd W.
Published: February 2007

Tumor rejection antigen (TSTA) has been prepared in soluble form and in good yield from the tissue‐culture‐adapted SV40‐induced sarcoma, mKSA, without resorting to the usual extraction procedures of proteolysis, 3 M KCI extraction or treatment with detergents. Chromatography on a Biogel A.5m column of the high‐speed supernatant material yielded a fraction, fraction 5, that contained the most active TSTA (and T antigen). This activity was purified in relation to the tumor‐rejection activity of the cell‐bound TSTA on intact cells or on membranes; a single immunization in the 1 μg to 10 μg protein range strikingly inhibited the growth of the syngeneic neoplasm, mKSA, in tumor‐cell challenges at 5×10″ (500×TD50), The soluble TSTA was immunologically specific and extremely stable. Inhibition of growth was not achieved against Meth A, another BALB/c syngeneic sarcoma, and preparations frozen for 6 months at −20°C maintained their strong specific immunogenicity. The immune deviations of the host that have been reported following inoculations of solubilized (extracted) tumor antigens or crude extracts were not observed in this study using our soluble TSTA. We found no evidence of antigen “overloading;” i.e. an optimal protective effect in a restricted dose range of antigen or with a particular size of tumor‐cell challenge; nor did we observe facilitated tumor growth or inhibition of cell‐mediated immune responses under a variety of conditions.