bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of human cells transformed in vitro by n‐methyl‐n'‐nitro‐n‐nitrosoguanidine
Authors: Rhim Johng S. , Putman Donald L. , Arnstein Paul , Huebner Robert J. , McAllister Robert M.
Published: February 2007

Human osteosarcoma (HOS) clonal cells transformed in vitro by N‐methyl‐N'‐nitro‐N‐nitroso‐guanidine (MNNG) were characterized, and compared to non‐producer HOS cells transformed by Kirsten murine sarcoma virus (Ki‐MSV). The MNNG‐ and virus‐transformed cells grew in the aggregate form above an agar base, grew in soft agar, and had a high fibrinolytic activity. When inoculated into nude mice, all the chemically or virally altered cells produced tumors or tumor nodules. When transplanted into ATS‐treated hamsters, the cells transformed by MNNG (0.01 μg/ml) and Ki‐MSV produced tumors but MNNG (0.1 μg/ml) transformed cells did not produce tumors. The control HOS cells did not grow in the aggregate form but formed colonies in soft agar, and had low fibrinolytic activity and no capacity to form tumors in nude mice and ATS‐treated hamsters. However, one of the control clonal lines had a high level of fibrinolytic activity. Cellular aggregation properties of human transformed cells did appear to correlate with tumorigenicity in nude mice.
Effect of bnu treatment on leukaemogenesis in lethally irradiated akr mice restored with bone‐marrow and spleen cells
Authors: Shisa H. , Legrand E. , Daculsi R.
Published: February 2007

The leukaemogenic effect of N‐butyl‐N‐nitrosourea (BNU) was studied in normal and thymectomized AKR mice which were lethally irradiated and restored with either bone‐marrow (BM) or spleen cells from (AKR × AKR/T1ALD)F1 donors. In some instances T1ALD thymic cells were added to the restorative inoculum. It was possible to determine the origin of the leukemic cells by the metacentric marker chromosomes of T1ALD. The T‐ or B‐cell characteristics were further ascertained by the cytotoxicity test for θ antigen and the EAC rosette test. All leukaemias whether thymic (TLS) or extra‐thymic (ETL), developed from donor bone‐marrow or spleen cells and never from the injected thymic cells. In non‐thymectomized animals BNU increased the percentage of TLS and shortened their latency. Most of TLS which occurred after BNU treatment of BM‐restored mice were θ‐negative whereas the majority of TLS which occurred in controls and in spleen‐restored animals were θ‐positive. This suggests that during their maturation process BM‐derived T precursors transit through a θ‐negative compartment. This compartment does not reach a similar size during the maturation process of the spleen‐derived precursors. Adding thymic cells to the restorative inoculum enhanced leukaemogenesis and suppressed θ‐negative TLS in BM‐restored mice. Thymectomized mice, restored either by BM or spleen, had a low incidence of ETL which was not significantly increased by BNU treatment except in the case of mice restored with spleen cells. The leukaemic cells of one ETL were θ‐positive whereas all the other leukaemias had no detectable T or B marker. The percentage of ETL was higher in thymectomized mice treated with BNU alone than in those previously subjected to irradiation and restoration. These results strongly suggest that a θ‐negative T precursor could be involved in extra‐thymic leukaemogenesis but the possible involvement of a B precursor cannot be ruled out unless experiments are carried out with specific markers of T‐ and B‐cell sub‐classes.
The presence of herpesvirus saimiri genomes in virus‐transformed cells
Authors: Fleckenstein Bernhard , Müller Ingrid , Werner Jürgen
Published: February 2007

Herpesvirus saimiri (H. saimiri) ‐transformed cells contain both types of viral DNA, unique L‐DNA and highly repetitive H‐DNA. DNA from spleen and lymph‐node autopsies of two tumor‐bearing marmoset monkeys contained 0.14–0.75 / viral L‐DNA and 0.115–1.08 / H‐DNA. This amount of H‐DNA would be equivalent to the presence of 14–130 M‐genomes per diploid tumor tissue cell. Six virus‐transformed lymphoid cell lines, two of them virus‐producing, contained 0.69–2.27 / H‐DNA and more than 0.72–1.95 / L‐DNA. These concentrations of H‐DNA sequences correspond to 83–274 M‐genome copies per lymphoid tissue culture cell. The majority of viral genomes in transformed non‐producer lymphoid cell lines appeared to be defective, since part of the L‐sequences present in virions were found to be deleted in the genome copies of transformed cells. There was a relative excess of repetitive H‐sequences in all transformed cells in regard to the ratio of H‐DNA/L‐DNA in M‐genomes of H. saimiri virions.
Augmentation of natural cytotoxic reactivity of mouse lymphoid cells against syngeneic and allogeneic target cells
Authors: Herberman Ronald B. , Nunn Myrtel E. , Holden Howard T. , Staal Steven , Djeu Julie Y.
Published: February 2007

The levels of natural cell‐mediated cytotoxicity against tumor cells in young BALB/c and BALB/c nude mice could be augmented by inoculation of a variety of mouse tumor cells or of mouse thymocytes. In older mice with low levels of spontaneous cytotoxic reactivity, inoculation of tumor cells led to rapid appearance of cytotoxicity. This augmented cytotoxicity reached a peak 3 days after inoculation, and then declined rapidly. The specificity of the augmented cytotoxicity appeared to be the same as that seen with natural cell‐mediated cytotoxicity. The detected antigens were restricted to mouse tumor cells and thymocytes, and were absent on cells from other species. The effector cells after boosting also had the same cell surface characteristics as the natural cytotoxic effector cells, being non‐adherent, non‐phagocytic, and only weakly sensitive to treatment with anti‐theta serum plus complement. In addition to this boosting by mouse tumor cells, marked increases in the levels of cytotoxicity were caused by a variety of murine viruses, including murine sarcoma virus and lymphocytic choriomeningitis virus. These effector cells also had the same properties as those seen with natural cytotoxic effector cells. The results indicate that the levels of natural cell‐mediated cytotoxicity in conventional and athymic BALB/c mice can be consistently and rapidly boosted by inoculation with tumor cells or viruses. This should provide a valuable tool for better understanding of the mechanisms responsible for the expression of natural cytotoxicity and its relevance to in vivo resistance to tumor growth.
Tumor cell locomotion—a factor in metastasis formation? influence of cytochalasin b on a tumor dissemination pattern
Authors: Hagmar B. , Ryd W.
Published: February 2007

The influence of Cytochalasin B (CB) on TA3 ascites tumor cells was studied in vivo in order to assess whether CB‐induced cell paralysis would affect the transplantation behavior of the cells and in particular tumor distribution after IV cell infusion (“experimental metastases”). Tumor cell pre‐treatment with CB (1 μg/ml) did not alter the SC or IV transplantability of TA3 cells. Pre‐treatment with 10 μg/ml CB, in contrast, consistently increased the incidence and number of extra‐pulmonary tumor takes from IV transfused cells. The amount of pulmonary tumors was not significantly altered. SC transplantability was not affected by 10 μg/ml CB. The importance of cell mobility and cell surface topography for tumor cell nidation in vessels is discussed.
Felv epidemiology in los angeles cats: Appraisal of detection methods
Authors: Gardner Murray B. , Brown John C. , Rongey Robert W. , Dworsky Ruth , Charman Howard P. , Gilden Raymond V. , Stephenson John R. , Huebner Robert J. , Hauser Duane E. , Diegmann Frank , Howard Edwin
Published: February 2007

We investigated the reliability of the fixed cell indirect fluorescent antibody (IFA) peripheral blood smear test as an index of systemic infection with FeLV. Positive results with this test were found to correlate well with detectable FeLV p30 antigen in bone‐marrow smears by IFA, in serum and tissue by competition immunoassays, and with type‐C particles in bone marrow or spleen by electron microscopy. Most cats with lymphoma, anemia or infectious peritonitis were positive for FeLV and showed a poor or absent antibody response to FeLV p30, gp70, and FOCMA antigens. Most older cats with lymphoma, carcinoma, or sarcoma were negative for FeLV expression and also lacked these FeLV‐related antibodies. Detectable immunologic response to FeLV p30 and gp70 proteins and a high‐titered FOCMA antibody response were generally restricted to certain healthy cats exposed to FeLV. Antibody to endogenous RD‐114 viral p30 and gp70 was not detected in any of a large number of feline sera tested. The prevalence of FeLV‐related diseases and immunologic responses to FeLV in healthy cats was directly correlated with the degree of FeLV exposure. By using the IFA blood smear and FOCMA antibody tests one can monitor the horizontal spread of FeLV in multi‐cat households and accurately predict the FeLV disease susceptibility or resistance of individual cats in such environments.
Epidemiology of Hodgkin's disease in the young
Authors: Gutensohn Nancy , Cole Philip
Published: February 2007

Many features of Hodgkin's disease (HD) among adolescents and young adults suggest that it has an infectious etiology. However, the proposal that HD is a contagious disease which can be transmitted by patients or their close contacts has not been substantiated. An alternative infectious disease model is suggested by analogy with paralytic poliomyelitis (PP). For both diseases, the peak age of incidence is delayed as living conditions improve. For both, increased risk is associated with higher social class and small family size. Like PP, HD may be a rare manifestation of a common infection with the probability of disease development increasing as age at infection is delayed. This analogy is supported by the report that the risk of HD is higher for persons who had a low frequency of childhood infectious diseases. If this model is valid, HD patients represent no hazard to their contacts. However, the incidence of HD among young adults may increase in the coming decade because of the current high standard of living and small family size.
A comparative study of the localization of CEA and NCA2 in cancerous and normal gastrointestinal tissues
Authors: Burtin P. , Sabine M. C. , Chavanel G.
Published: February 2007

The histological localization of CEA in gastrointestinal tissues was re‐evaluated after absorption of anti‐CEA antiserum with NCA2, another normal antigen cross‐reacting with CEA. This absorbed antiserum showed clearly the presence of CEA in colonic tumors and some non‐cancerous colonic mucosae, obtained even from non‐cancerous patients. In contrast, some of the gastric adeno‐carcinomas we studied were stained very weakly by absorbed anti‐CEA antiserum, althouth non‐absorbed antiserum (or serum absorbed with NCA alone) labelled them strongly. The same difference in reactivity between both antisera was observed in intestinal metaplasia. The localization of NCA2 was studied with a specific antiserum, previously absorbed with CEA and NCA. NCA2 was found to be a noromal cytoplasmic and mucus‐associated antigen of gastrointestinal tissues. It was present also in fetal stomach and colon. Sections of gastric and colonic tumors as well as intestinal metaplasia of gastric mucosae always reacted brilliantly with absorbed anti‐NCA2 antiserum.
Cell kinetics and immunogenicity of lymphoma cells treated with 5‐(3,3‐dimethyl‐1‐triazeno) imidazole‐4‐carboxamide (DIC) in vivo
Authors: Silvestrini R. , Testorelli C. , Goldin A. , Nicolin A.
Published: February 2007

A cycle of treatment with antineoplastic compounds may alter the immunologic properties of experimental tumors leading to an increased survival of syngeneic hosts as compared to that observed with the original parental tumors. However, a loss of growth potential in drug‐treated tumors might account for this preferential rejection by syngeneic or by allogeneic animals. In the present study the cell cycle kinetics of parental (L1210 and L5178Y) and DIC‐altered leukemic cells (L1210/DIC; L5178Y/DIC) has been evaluated by the establishment of labelled mitosis curves. The in vitro DNA synthesis and cell loss were also investigated. The experimental results indicate that no significant differences in the above properties were present for parental and corresponding drug‐treated leukemic sublines. Immunodepressed allogeneic mice were more resistant to lymphoma challenge when inoculated with the DIC‐sublines than with the parental lines. On adoptive transfer of immune lymphocytes there was increased survival of allogeneic animals challenged with DIC cells, attributable to an additional immune response to DIC‐induced antigens. Thus, parental or DIC‐tumors showed similar tumorigenic characteristics, and the increased allogeneic host survival to DIC‐cell challenge may be attributed to an additional immune response of the animal against DIC‐induced antigens.
Rate‐limiting step in the progression of mouse breast tumors
Authors: Prehn Richmond T.
Published: February 2007

Age‐specific incidence curves of mouse breast cancer suggest a rate‐limiting step in tumor progression one step prior to overt cancer and the withdrawal prior to middle life of a critical etiological condition (hormonal?) for one or more of the earlier steps in the oncogenic sequence.
Immune response of athymic nude mice to papovavirus SV40 tumor‐associated antigens
Authors: Tevethia Satvir S. , Waneck Gerald , Tevethia Mary J.
Published: February 2007

The requirement of T cell functions in the induction of immune response to SV40‐specific transplantation rejection antigen and intranuclear tumor antigen was studied using athymic nude mice. The results obtained indicated that virus‐immunized athymic nude mice were unable to reject SV40 tumor cell challenge, and sensitized lymphocytes capable of inhibiting tumor growth in vivo could not be demonstrated in the spleens of virus‐immunized mice. Athymic nude mice bearing tumors induced by virus‐free SV40‐transformed BALB/c cells failed to develop antibodies to intranuclear T antigen. Athymic nude mice also failed to respond to viral antigens. Thus it can be concluded that T cell functions are required in the induction of cellular immune response to SV40‐specific transplantation rejection antigen and in humoral immune response to SV40‐specific T antigen and virion antigen.
Immunologic responses to a murine mammary adenocarcinoma. II. Monocyte effector activation by humoral factors
Authors: Yamamura Yasuhiro
Published: February 2007

Sera from DBA/2 mice bearing a syngeneic T1699 mammary adenocarcinoma not only induced specific antibody‐dependent cellular cytotoxicity (ADCC) mediated by monocytes (and/or macrophages) but also armed (activated) such effector cells into specific killer cells in vitro. Removal of specific anti‐tumor antibody (IgG2a subclass) by absorption with T1699 cells abolished the ADCC activity at the level of target cell coating but did not alter the level of effector‐arming activity. Fractionation on Sephadex G‐20 indicated more than one factor capable of inducing specific monocyte‐mediated lysis of target cells in vitro, including immune complexes, free IgG2a 7S antibody (ADCC), and another factor(s) with a molecular weight very close to that of 7S immunoglobulins.
Loss of specific natural cell‐mediated cytotoxicity with absorption of natural antibodies from serum
Authors: Akira D. , Takasugi M.
Published: February 2007

When effector cells from most individuals are tested directly against a number of target cells for cell‐mediated cytotoxicity, most of the reactivity is non‐selective. This apparent non‐selectiveness is a result of specific activity against multiple antigens on target cells by each effector suspension. The specific reactions can be demonstrated through competitive inhibition of natural cell‐mediated cytotoxicity. The specific inhibition of cytotoxicity by competitor cells directed our attention toward the determination of specificity to the effector cell surface. Natural cell‐mediated cytotoxicity was decreased when effector cells were treated with proteolytic enzymes or low pH and regained when these cells were incubated in serum, suggesting an antibody on cell surfaces of the effector cell. Reconstitution of trypsinized effector cells with absorbed serum resulted in selective loss of cytotoxicity against the absorbing cell. To determine the role of the effector cell and the role of antibodies in natural cell‐mediated cytotoxicity, effector cells from two different persons were reconstituted in the same absorbed sera. The selective pattern achieved was similar. When effector cells from the same individual were reconstituted with two different sera absorbed in the same way, the selective pattern achieved showed greater differences. We concluded that natural antibodies loosely attached to effector cells provided the specificity of natural cell‐mediated cytotoxicity.
Differential induction of Epstein‐Barr virus‐related antigens in heterokaryon cultures
Authors: Yamamoto K. , Osato T.
Published: February 2007

Different patterns of induction of Epstein‐Barr virus (EBV)‐related antigens were observed in heterokaryons produced by Sendai virus‐mediated fusion of producer and non‐producer human lymphoblastoid cells with various other cell types. EBV‐related early antigens (EA) and viral capsid antigen (VCA) could obviously be induced in heterokaryons between producer cells (P3HR‐1 and QIMR‐WIL), normally expressing these antigens at very low frequency, and human FL or HeLa cells. Positive cells were detected as early as 3 h after fusion and there often followed a rapid increase in positive cells. In contrast, in heterokaryons between non‐producer cells (Raji and NC‐37) and FL or HeLa cells, only EA but not VCA was induced. EA induction was also evident in fusion of human lymphoblastoid cells with monkey cells (Vero) but with mouse cells (L‐M (TK−) C11D and MCB‐2) no EBV induction occurred. The EBV induction in heterokaryons was significantly enhanced by 5‐iododeoxyuridine treatment.
ESTROGEN AND PROGESTOGEN CYTOSOL RECEPTORS IN HUMAN BREAST CARCINOMA
Authors: May‐Levin F. , Guerinot F. , Contesso G. , Delarue J. C. , Bohuon C.
Published: February 2007

The authors have studied Estrogen (RE) and Progestin (RP) cytosol receptors in 379 human breast carcinomas: 281 tumors suitable for surgery, 26 pseudo‐inflammatory tumors, 52 metastases and 20 recurrences. They have used an exchange technique with estradiol for RE and a synthetic compound, R 5020, for RP. The results point out that high rates of RE correlate with post‐menopausal women and high rates of RP with pre‐menopausal women. Tumours are considered receptor‐positive when the binding sites concentration exceeds 100 fmoles/g tissue. Using this as a base 32% of the tumors are RE and RP negative. Considering only the positive tumors, 54% contain both receptors, 31% only RE and 15% only RP. The percentages are also given in terms of the hormonal state of the patients. The results are discussed in terms of Mc Guire's hypothesis that both receptors are necessary to obtain a positive response to hormonal therapy. Correlation between histology and receptors is also discussed.
Intra‐tumour host cells of transplanted rat neoplasms of different immunogenicity
Authors: Moore Keith , Moore Michael
Published: February 2007

The nature of host‐derived cells present in serial transplants of five tumours of variable immunogenicity in syngeneic NW rats was investigated. Single‐cell suspensions obtained by tumour disaggregation in papain‐collagenase‐DNase (PCD) mixture were quantitatively analysed for cells with Fc receptors by formation of erythrocyte‐antibody (EA) rosettes; for cells with receptors for the third component of complement (C3) by formation of erythrocyte‐antibody‐complement (EAC) rosettes; for macrophages by the uptake of polystyrene particles and/or phagocytosis of membrane‐bound EA rosettes and for T cells by means of rabbit anti‐rat thymocyte serum (ATS). In addition, the total host cell content of two neoplasms (MC40A and SP22) was determined by immunofluorescence analysis of tumours grown in (NWxPVG/c) F1 hybrids, using NW anti‐PVG/c antiserum. There was close correspondence between the host cell content of these tumours as determined by immunofluorescence and summation of total EA‐RFC and T lymphocytes, indicating the probability that EA‐RFC were of host, rather than tumour, origin. This latter population consisted of macrophages and non‐phagocytic Fc+ cells and these, together with T cells, constituted the major infiltrative components. Host cells were most evident in the two neoplasms (MC40A, MC57) which were immunogenic, where macrophages, non‐phagocytic Fc+ cells and T lymphocytes were present in approximately equivalent proportions. (Total host cells: 42% and 45% respectively.) For the nonimmunogenic tumours (AAF 57, SP1 and SP22) host cells accounted for ± 15% of the enzyme‐dispersed suspension. However, analysis of cellular infiltration as a function of time after injection of cultured tumour cells revealed that the macrophage content of MC40A, AAF 57 and SP22 was greatest when the tumours first became clinically manifest and thereafter rapidly declined to the levels observed in serial transplants. EA‐RFC were represented almost wholly by macrophages in AAF 57 and SP22, whereas in MC40A the declining macrophage population was replaced by non‐phagocytic Fc+ cells, the precise identity of which was not established. The results indicate that cellular infiltration of established neoplasms correlates with their immunogenicity; that this host cell component comprises non‐phagocytic Fc+ cells and T cells as well as macrophages; but that the macrophage content is significantly greater when tumours are first palpable than at later stages of development, even in neoplasms which evoke no transplantation immunity.
Bovine leukemia virus specific antibodies among French cattle. I. Comparison of complement fixation and hematological tests
Authors: Levy D. , Deshayes L. , Guillemain B. , Parodi A.‐L.
Published: February 2007

Complement fixation (CF) and hematological studies were performed on 517 cows living in normal conditions in different geographical areas of France. The animals belonged to three different categories: (1) multiple or single case herds, in which lymphosarcomas had been detected in the past five years. (2) Leukemia free herds of high risk regions. (3) Leukemia free and apparently unexposed herds. Positive animals were found with both methods in the first two categories but not in the third. Persistent lymphocytosis and CF antibodies were more frequent in leukemia than in exposed but leukemia free herds. Approximately 2 times more animals were found positive by serologic than by hematologic tests. The mean geometrical titer of CF antibodies was higher in lymphocytotic than in normal animals and highest in lymphosarcomatous cows. Persistent lymphocytosis was first detected in 3‐years‐old animals whereas 22% of younger cows were positive in the CF test.
The metabolic activation of 7‐methylbenz(a)anthracene: The induction of malignant transformation and mutation in mammalian cells by non‐K‐region dihydrodiols
Authors: Marquardt H. , Baker S. , Tierney B. , Grover P. L. , Sims P.
Published: February 2007

Four different dihydrodiols derived from 7‐methylbenz(a)anthracene have been tested, together with the parent hydrocarbon, for their ability to induce the in vitro malignant transformation of mouse M2 fibroblasts and mutations in V79 Chinese hamster cells. In the transformation tests with the non‐K‐region dihydrodiols, the 3,4‐diol was the most active dihydrodiol tested and the 8,9‐diol was also more active than 7‐methylbenz(a)anthracene itself; the 1,2‐diol showed only slight activity. The K‐region dihydrodiol, the 5,6‐diol, which cannot be directly metabolized to a vicinal diol‐epoxide, was inactive. These differences in biological activity were similar to those apparent in the results from the mutagenicity tests. The data support the general hypothesis that non‐K‐region dihydrodiols, which can be metabolized to vicinal diol‐epoxides, are important in the metabolic activation of the carcinogenic polycyclic hydrocarbons and, when taken together with other results, indicate that 3,4‐dihydro‐3,4‐dihydroxy‐7‐methylbenz(a)anthracene is most probably involved in the metabolic activation of 7‐methylbenz(a)anthracene presumably following conversion into the related diol‐epoxide, 3,4‐dihydro‐3,4‐dihydroxy‐7‐methylbenz(a)anthracene 1,2‐oxide.
Immunologic studies of the low molecular weight DNA binding protein of murine oncornaviruses
Authors: Long Cedric W. , Berzinski Richard , Gilden Raymond V.
Published: February 2007

A low molecular weight, highly basic DNA‐binding protein was purified from several oncornaviruses by the sequential procedures of gel filtration in guanidine‐hydrochloride, DEAE‐cellulose chromatography and affinity chromatography on single‐stranded DNA sepharose. The binding protein from Rauscher and woolly monkey type‐C viruses was the fastest migrating of the virion proteins in SDS‐polyacrylamide gels and thus is designated p10 according to previous convention although our estimates of molecular weight were 8–9,000 daltons. The binding protein from these two viruses was resolved into two bands by acid‐urea electrophoresis although only a single NH2 terminal amino acid was detected (S. Oroszlan, personal communication), thus indicating charge heterogeneity. Antibody to Rauscher virus p10 species‐specific in gel diffusion and complement‐fixation tests and did not exhibit cross‐reactivity with other virion proteins. A DNA‐binding protein was also detected in preparations of mouse mammary tumor virus. This purified protein had an apparent molecular weight of 12,500, was the second fastest migrating component in the virus preparations, and was antigenically unrelated to the mouse type‐C virus p10.
Drug sensitivity studies on clonal cell lines isolated from heteroploid tumour cell populations. I. Dose response of clones growing in monolayer cultures
Authors: Pályi I. , Oláh Edit , Sugár J.
Published: February 2007

Drug sensitivity of a heteroploid tumour cell line and three clones isolated from it was studied in tissue culture. Cells of the parent line, P0, and of clone P1 were fibroblast‐like and pseudo‐ and hypodiploid. Clones P3 and P4 consisted mostly of epithelial and round cells, respectively, and were hypotetraploid. In dose‐response experiments, P1 and P4 clones were more sensitive to dianhydro‐dulcitol than P0 or P3 clones. Adriamycin was more toxic to P3 than to the other three cell lines. P3 and P4 clones were more sensitive to vincristine than P0 or P1 clones. N‐formyl‐leurosine, a new derivative of the Vinca alkaloids, was least toxic to P4 cells, and the other three cell lines were equally sensitive. It was concluded that relative sensitivity of the clones depended on the particular drug. Presence of clones of lower sensitivity in heteroploid cell populations may have some bearing on regrowth of tumours after chemotherapy.
Sequential evaluation of cutaneous delayed hypersensitivity responses to recall and to lymphoid cell line antigens in Burkitt's lymphoma
Authors: Nkrumah F. K. , Herberman R. , Biggar R. , Perkins I. V.
Published: February 2007

Delayed cutaneous hypersensitivity reactions to standard recall antigens (candidin, mumps and PPD), to crude membrane extracts of a cell line derived from Burkitt's lymphoma (Raji) and to a cell line derived from normal lymphocytes (F265) were sequentially evaluated in 44 patients with Burkitt's lymphoma. Sixteen patients (36%) manifested delayed hypersensitivity responses to the standard antigens and seven (16%) to the Raji membrane extract at presentation. Following successful chemotherapy, there was prompt and significant improvement of reactivity to both the standard and Raji antigens (p>0.001), suggesting that the initial impairment of delayed hypersensitivity was most likely related to tumor burden. By 9 months after treatment, all patients in sustained remission expressed reactivity to Raji and 21 of 22 to the standard antigens. None of the patients skin‐tested with the F265 extract at presentation gave a positive response and only one subsequently expressed reactivity after remission was induced. On relapse, reactivity to the standard antigens was more readily lost (4 of 11) than reactivity to the Raji extract (1 of 7). Pretreatment delayed hypersensitivity to the standard antigens also correlated better with long‐term survival than to pretreatment responses to Raji. It remains to be determined whether the antigens expressed in the Raji extract are indeed tumor‐specific or related to Epstein‐Barr virus.
An abnormal luteal‐phase evening peak of plasma prolactin in women with a family history of breast cancer
Authors: Kwa H. G. , Wang D. Y.
Published: February 2007

In an earlier study an abnormally high luteal‐phase evening peak of plasma prolactin in women with a family history of breast cancer was first noted, but there were few observations. The current study confirms the original findings. Other groups, e.g. nulliparous women and tall and heavy women also appear to show the same abnormality. Further work is required to establish this finding. However, the abnormally high luteal‐phase evening peak of plasma prolactin in the family history group is still present when such women are disregarded. The possible relevance of the restriction of elevated prolactin levels, in enhanced‐risk women, to the luteal phase, when both oestradiol and progesterone levels are also elevated, is discussed briefly as is the question why a minor peak at 19.00 h is important when plasma prolactin levels show a massive increase between 03.00 and 09.00 h.
Antigenic differences between primary methylcholanthrene‐induced rat sarcomas and post‐surgical recurrences
Authors: Pimm M. V. , Baldwin R. W.
Published: February 2007

The immunogenicities of in vivo lines established from primary MCA‐induced rat sarcomas have been compared with those of lines initiated from tumour recurrences at the site of the primaries' surgical excisions. Lines from two of four primary sarcomas showed little or no immunogenicity, as assessed by protection against challenge afforded by graft excision or implantation of irradiated tissue. In contrast, lines from all four recurrences were immunogenic, giving protection against up to 5 × 106 tumour cells. Most importantly, with all four tumours, lines established from recurrences were antigenically distinct from lines derived from their original primary sarcomas, so that immunization with regrowth lines gave no protection against the lines from the primaries, and vice versa. These studies demonstrate that primary MCA‐induced sarcomas are antigenically distinct from recurrent tumours arising after surgical removal of the primaries, implying that these tumours arose by clonal amplification of separate populations of transformed cells. This may reflect proliferation of dormant neoplastic cells or the further induction of transformed cells by residual carcinogen. These findings are relevant to the multifocal origin of tumours and for the design of active immunotherapy for the treatment of recurrences or metastatic deposits.
SV40 tumor rejection induced by vesicular stomatitis virus bearing SV40 tumor‐specific transplantation antigen (SV40‐TSTA). II. Association of sv40‐tsta activity with liposomes containing vsv glycolipids
Authors: Huet Christian , Ansel Sandra
Published: February 2007

Highly purified vesicular stomatitis virus (VSV) was obtained from VSV‐infected SV40‐transformed and from “normal” hamster cell lines. A glycolipid extract was prepared from these VSV preparations according to the Folch partition procedure. These glycolipids were rendered immunogenic to the Syrian hamsters when incorporated within liposomal membranes composed of lecithin/sphingomyelin/cholesterol (1/1/2 by weight). When the glycolipids were extracted from VSV grown on cell lines (TSV5‐cl2 and EHSVi‐cl1) which contained the SV40 tumor‐specific transplantation antigen (SV40‐TSTA), it was possible either to induce a tumor rejection or at least to slow the growth of the tumor in Syrian hamsters challenged with TSV3‐cl2 cells. No protection was obtained in animals treated with liposomes containing glycolipids extracted from purified VSV grown on SV40‐TSTA‐negative cells (EHB). The SV40‐TSTA could be a glycolipid of the transformed cell membrane which is incorporated within the VSV envelope.
Experimental yolk‐sac tumors produced by fetectomy without virus infection in rats
Authors: Sakashita Shigeo , Tsukada Yutaka , Nakamura Kyoji , Tsuji Ichiro , Hirai Hidematsu
Published: February 2007

Pregnant WKA rats were laparotomized on the 12th day of gestation, and all fetuses were removed from the uteri, leaving the fetal membranes attached to placentas in situ, protruding into the peritoneal cavity. After 5 to 6 months, extrauterine tumors were observed in 80% of the operated rats, and elevated serum α‐fetoprotein levels were detected in 80% of the tumor‐bearing rats. The tumors in AFP‐positive rats always contained yolk‐sac tumor elements. In transplantable tumor lines established in the ascites form, numerous free‐floating embryoid bodies were observed. The experiments demonstrate that yolk‐sac tumors (endodermal sinus tumors) can be induced by simple fetectomy without infection by exogenous tumor virus.
Studies of bone and soft‐tissue tumours induced in rats with radioactive cerium chloride
Authors: Klein B. , Pals S. , Masse R. , Lafuma J. , Morin M. , Binart N. , Jasmin J. R. , Jasmin C.
Published: February 2007

A colloidal suspension of radioactive cerium chloride was inoculated into the hind legs of Sprague Dawley rats. Bone and soft‐tissue tumours were induced at the site of inoculation in 77% of the animals. All bone tumours were osteogenic osteo‐sarcomas. Soft tissue tumours were mostly malignant and were of various histological types, predominantly fibrosarcomas, haemangiopericytomas, angiosarcomas and rhabdomyosarcomas. A kinetic study showed that the doubling time (DT) of tumours was closely correlated with the anatomical site of tumour development: bone tumours had a DT of 17.4±4.3 days and malignant tumours which developed in soft tissues had a DT ranging from 7.4 to 8.4 days with the exception of two haeman‐giosarcomas which had a long DT of 17±0.6 days. Pulmonary metastases were frequent for osteo‐sarcomas and tumours of vascular origin. This model of induction of bone and soft‐tissue tumours in rats by injection of a colloidal suspension of radioactive cerium chloride offers the possibility of more comprehensive physiopathological and kinetic studies of these tumours and may constitute a good model for their human counterparts.
A proliferation gradient in three‐dimensional colonies of cultured human glioma cells
Authors: Carlsson Jörgen
Published: February 2007

The growth of colonies of human glioma cells cultured in agarose has been studied. The mitotic activity and the fraction of cells which incorporated tritiated thymidine decreased nearly exponentially with the depth in the colonies, the shape and inclination of the proliferation gradient being independent of the colony diameter. This explains why the volume doubling times were rather similar for colonies of different sizes. It is also shown that the stability of the gradient during growth gave rise to nearly exponential growth, although a large part of the centrally situated cells were out of the cell cycle or had a reduced proliferative rate. The incorporation of tritiated thymidine into labelled cells was similar in the peripheral and the central regions as evaluated from grain counting. This indicated that the length of the S‐phase was constant.
Identification and solubilization of iodinated cell surface human melanoma associated antigens
Authors: Bystryn Jean‐Claude , Smalley James R.
Published: February 2007

To identify soluble cell surface melanoma‐associated antigens (MAA), human melanoma cells in culture were radioiodinated by the lactoper‐oxidase technique and solubilized in non‐ionic detergent (NP‐40). Labelled MAA were identified by a quantitative double‐antibody antigen binding assay and unrelated labelled macromolecules by trichloroacetic acid precipitation. Detergent solubilized 95% of the macromolecule‐associated radioactivity. Approximately 8%, presumably MAA, was bound specifically by anti‐melanoma serum. In contrast, anti‐melanoma serum bound specifically only 0.5 to 1.5% of the acid precipitable radioactivity in control cells iodinated in a similar manner. Specificity was further studied by quantitative serum absorption. Two different melanoma lines were equally effective in inhibiting specific binding of iodinated melanoma lysate, whereas 50‐100 times more normal fresh lymphocytes, liver and spleen cells, cultured HeLa or colon adenocarcinoma cells, and 8 times more cultured fetal cells were required to produce similar reductions in specific binding. These studies demonstrate that cell surface human melanoma antigens that differ qualitatively and/or quantitatively from those on normal or malignant allogeneic tissues can be solubilized and identified. These antigens are shared with other melanomas, and some are also present on fetal cells.
Cellular cytotoxicity in vitro in transitional cell carcinoma of the human urinary bladder: 51Cr‐release assay
Authors: Troye Marita , Perlmann P. , Larsson Å. , Blomgren H. , Johansson B.
Published: February 2007

The cytotoxicity in vitro of peripheral blood lymphocytes from 54 patients with transitional cell carcinoma of the urinary bladder (TCC‐bladder) against a small panel of allogeneic target cells was studied by the 51Cr‐release assay. Lymphocytes from 20 patients with other neoplastic diseases, mainly urogenital cancers, were used as controls. Also included were lymphocytes from 24 healthy donors. Lymphocytes from individual donors of all three groups were frequently cytotoxic to any one of the target cell types on the panel and occasionally this cytotoxicity was high. However, lymphocytes from TCC‐bladder patients who were untreated for their disease had an elevated mean cytotoxicity against cells from two different cell lines of TCC‐bladder origin as compared with that against other target cells, derived either from normal bladder epithelium, from colon carcinoma or from malignant melanoma. The cytotoxicity against TCC‐bladder targets of lymphocytes from the clinical controls (who were untreated for their cancer) was not significantly elevated over that against the other targets. The same was true for the healthy donors. Lymphocytes from TCC‐bladder patients treated with radiotherapy from 1‐12 years before testing also had an elevated mean cytotoxicity against TCC‐bladder targets. This group (31 patients) was heterogeneous, comprising patients with a generally reduced cytotoxicity and others whose lymphocytes were strongly cytotoxic to TCC‐targets. However, while no correlations between cytotoxicity to TCC‐bladder targets and targets of other origin were seen for the untreated patients, the treated TCC‐bladder patients showed a positive correlation between cytotoxicity to TCC‐bladder targets and “normal” bladder targets. Taken together, the results indicate that lymphocytes of most (but not all) donors was selective, i.e. individual donors' lymphocytes were cytotoxic for some target cell types but not for others. Inspection of cytotoxicity profiles suggests that these selective reactions reflect multifactorial immune responses against a variety of antigens. In addition, in TCC‐bladder patients there exists a superimposed cytotoxicity, probably reflecting reactions against one or several tumor‐associated antigens. In treated patients this may be masked by a higher incidence of cross‐reactions, or by a generally suppressed reactivity. Finally, the results also emphasize the importance of using age‐ and sex‐matched controls for assessing the relative cytotoxicity of different groups of lymphocyte donors.
Terminal deoxynucleotidyl transferase activity and cell surface antigens of two unique cell lines (nalm‐1 and balm‐2) of human leukemic origin
Authors: Srivastava B. I. Sahai , Minowada J.
Published: February 2007

Two unique cell lines, NALM‐1 and BALM‐2 derived from lymphoblast‐like cells of chronic myelogenous leukemia and rare B cell acute lymphoblastic leukemia patients, respectively, were compared with fresh parent cells from the patients and with a Philadelphia chromosome positive K‐562 cell line previously established from a chronic myelogenous leukemia patient in blastic phase. NALM‐1 resembled the parent cells in the presence of Philadelphia chromosome, non‐T/non‐B acute lymphoblastic leukemia specific antigens and lack of T or B cell markers, whereas BALM‐2, like the parent cells, had two chromosome markers and bore x, δ and μ immunoglobulins. NALM‐1 lacked Epstein‐Barr virus genome, whereas BALM‐2 showed the presence of Epstein‐Barr virus genome. K‐562 cells lacked all the antigen markers examined. All cells had high DNA polymerase α activity and low DNA polymerase γ activity. NALM‐1, like the parent cells and unlike K‐562 cells, had high terminal deoxynucleotidyl transferase activity of about 200 μ/mg DNA, whereas BALM‐2, like its parent cells, had terminal deoxynucleotidyl transferase activity of 1‐2 μ/mg DNA (1 u = 1 nmole Mn++‐dGTP/h on dA12‐18, initiator). Terminal deoxynucleotidyl transferase was characterized by its chromatographic and sedimentation behavior, thermal sensitivity and specific inhibition by streptolydigin and terminal deoxynucleotidyl transferase antisera. These results indicate that NALM‐1 and K‐562 may represent different phenotypes of cells in CML blastic crisis. Moreover, NALM‐1 and BALM‐2 seem to have retained the characteristics of original leukemic cells from which they may have been derived.
Transformation of lymphocytes by herpesvirus papio
Authors: Falk Lawrence A. , Henle Gertrude , Henle Werner , Deinhardt Friedrich , Schudel Alex
Published: February 2007

Cotton‐topped (CT) or white‐lipped (WL) marmoset lymphocytes were transformed in vitro with herpesvirus papio (HVP) into permanently growing lymphoblastoid cell lines (LCL). Five of 9 HVP‐transformed CT cell lines contained cells with antigens reacting with antibodies to Epstein‐Barr virus (EBV) capsid antigen (VCA) and/or to EBV‐induced early antigens (EA). None of 12 WL LCL revealed such antigen‐producing cells. Cells from both groups of cultures failed to react with antibodies to the EBV‐specified nuclear antigen (EBNA). Exposure of baboon circulating lymphocytes to X‐irradiated HVP or EBV‐carrying cells, or to suspensions of EBV resulted in establishment of LCL which all contained VCA and/or EA‐positive, but no EBNA‐positive cells. Nuclear antigens were undetectable also with anti‐VCA‐positive sera from baboons, chimpanzees, or other non‐human primates. DNA‐complementary RNA (cRNA) filter hybridization with EBV cRNA showed that with one exception transformed CT or WL marmoset cells contained at least 1‐2 virus genome equivalents per cell, while at least 12‐25 virus genome equivalents per cell were detected in transformed baboon cells. These data need confirmation by DNA‐DNA reassociation kinetics.
Enhancing lymphocytes in spleens of tumor‐bearing mice: affinity chromatography on insolubilized histamine
Authors: Schechter B. , Segal S. , Feldman M.
Published: February 2007

Spleen cells from C57BL mice carrying the metastatic Lewis lung carcinoma (3LL) developed a transient cytotoxic response towards the tumor shortly after tumor transplantation. Later on, the cytotoxic activity was lost and enhancing lymphocytes could be demonstrated in the spleens of the tumor‐bearing mice (TBM). Spleen cells that were transferred together with tumor cells into syngeneic recipients enhanced tumor growth. The enhancing activity could be eliminated by the removal of a cell population that bound to histamine/rabbit serum albumin/Sepharose (HRS). The adherent population was enriched for enhancing lymphocytes, since it enhanced tumor growth more than the unfractionated population. The non‐adherent cells, on the other hand, lost their enhancing activity in vivo and were sometimes protective against tumor growth. In addition, these cells manifested in vitro cytotoxi‐city against tumor cells. Hence the suppresssion of the cytotoxic expression in TBM is, at least in part, due to suppressor lymphocytes that bind to unsolubilized histamine. These cells seem to enhance tumor growth by suppressing host reactivity. Thus the enhancing lymphocyte populations can be separated into two subpopulations, of which one is enriched while the other is depleted of suppressor cells.
A mouse leukemia cell mutant resistant to blasticidin s
Authors: Kuwano Michihiko , Matsui Katsuko , Takenaka Kenji , Akiyama Shin‐Ichi , Endo Hideya
Published: February 2007

After nitrosoguanidine mutagenesis we isolated from mouse leukemia L5178Y cells a mutant cell (Bla‐R) resistant to blasticidin S, an inhibitor of protein synthesis. Neither growth nor leucine incorporation into hot‐acid insoluble fraction of Bla‐R cell was inhibited by 5 to 20 μg/ml blasticidin S, which almost completely blocked protein synthesis as well as growth of the parental L5178Y cells. However, other inhibitors such as fusidic acid, cycloheximide, ricin D or L‐asparaginase blocked protein synthesis in Bla‐R cells to the same extent as in L5178Y cells. Protein synthesis in vitro using S‐30 extracts from the parental cell line L5178Y was almost completely blocked in the presence of the antibiotic, while no inhibition by blasticidin S occurred when S‐30 extracts from Bla‐R mutant cells were used. Protein synthesis assays were made by using the S100 fraction from rat liver together with ribosomes from either L5178Y cells or Bla‐R cells. Blasticidin S inhibited protein synthesis when ribosomes were derived from L5178Y cells, but not from Bla‐R mutant.
Comparative studies on immunity to EBV‐associated antigens in NPC patients in North America, Tunisia, France and Hong Kong
Authors: Levine Paul H. , Wallen William C. , Ablashi Dharam V. , Granlund David J. , Connelly Roger
Published: February 2007

This study compared the relative antibody titers to EBV‐related antigens in patients with naso‐pharyngeal carcinoma (NPC) and controls from a high‐incidence (Hong Kong), an intermediate incidence (Tunisia), and two low‐incidence (France, North America) areas to determine which of several EBV antibodies best differentiated NPC patients from controls. Antibodies measured include anti‐virus capsid antigen (VCA), anti‐early antigen (EA), anti‐soluble antigen by complement‐fixation (CF) and antibody‐dependent lymphocyte cytotoxicity (ADLC). A matched pair analysis showed that significantly more NPC patients had higher VCA and EA but not CF or ADLC antibody titers than their matched cancer controls. The comparison of geometric mean titers between NPC cases and controls was more than seven‐fold (816 vs 11.5) for EA antibody and more than three‐fold (359.7 vs 95.4) for VCA antibody (p<0.01). A two‐fold difference was seen for CF antibody to soluble antigens (27.3 vs 12.9, p<0.01) and a three‐fold difference (2657.7 vs 870.9, p<0.05) was observed for ADLC. Our finding of significant differences between NPC patients from four countries and their matched controls suggest that if EBV is the etiological agent of NPC in Chinese, it is quite likely to cause the majority of NPC cases in other ethnic groups living in other countries as well.