bluuebunny/crossref_metadata_2025 huggingface dataset:
Social class risk factors among children with Hodgkin's disease
Authors: Gutensohn Nancy M. , Shapiro Daniel S.
Published: February 2007

We compared the social class characteristics of 66 families with children diagnosed with Hodgkin's disease (HD) from 1959 through 1977 in a defined population with that of 182 “control families” identified by a random process from the population base. The 14 youngest cases (<10 years at diagnosis) were from somewhat lower social‐class backgrounds than their 37 controls as evidenced by the distribution of median income, single‐unit housing, and poverty level of their census tract of residence, as well as by the occupational class of head‐of‐household. In contrast, the social class characteristics of the 52 older children with HD (10–14 years) were quite similar to that of their 145 controls. This apparent shift from lower to average social class between younger and older children with HD Hodgkin's disease may reflect a shift in their age of exposure to common infections. If true, these findings are consistent with the hypothesis that HD may develop as a rare consequence of a common infection. However, these findings are based on small numbers of cases and on indirect measures of social class.
Induction of avidin in chickens infected with the acute leukemia virus OK 10
Authors: Korpela Jukka , Kulomaa Markku , Tuohimaa Pentti , Vaheri Antti
Published: February 2007

The presence of avidin, a progesterone‐dependent oviductal glycoprotein, was studied in viral tumors. Newborn chickens were infected with the acute leukemia virus OK 10, and the first tumors occurred within 2–3 weeks. Avidin was assayed using a [14]biotin‐binding method and radioimmunoassay. In the control chickens, avidin concentrations were <0.3 μg/g in the plasma and <1.5 μg/g in various tissues including the immature oviduct. In the OK 10 virus‐infected chickens, no significant induction was observed during the acute infection or any time thereafter if no tumors were seen. In chickens that developed tumors, avidin concentrations were significantly increased in tumorous tissue only located in the mesenterium and occasionally in the oviduct. In tumors occurring elsewhere (kidney, ovary, muscle, testis, liver, colon) avidin concentrations were not elevated. Tumor‐associated avidin had extraordinary biotin‐binding capacity after treatment at +90° C similar to the progesterone‐dependent avidin, whereas antibody‐binding properties suggested that tumor‐associated avidin may have a some‐what altered antigenic structure.
Anti‐tumor activity of daunorubicin linked to poly‐L‐aspartic acid
Authors: Zunino Franco , Giuliani Fernando , Savi Giuseppina , Dasdia Teresa , Gambetta Romolo
Published: February 2007

Daunorubicin was bound to poly‐l‐aspartic acid via the methylketone side chain of the drug to avoid reaction of the sugar amino group believed to be essential for optimal drug activity. Attachment of the drug to the poly‐amino acid by an ester linkage was achieved by nucleophylic substitution reaction of 14‐bromo‐daunorubicin. Compared with free daunorubicin, the polymeric derivative was less cytotoxic to HeLa cells in vitro, but more effective against all tumor models tested (P388 leukemia, Gross leukemia, MS‐2 sarcoma). The binding to the poly‐peptide markedly reduced drug toxicity but only slightly decreased drug potency. The daunorubicin‐poly‐L‐aspartic acid conjugate demonstrated antitumor activity comparable to that of doxorubicin in leukemia models, but superior to that of doxorubicin in a solid tumor model (MS‐2 sarcoma).
Non‐random duplication of chromosome 15 in T‐cell leukemias induced in mice heterozygous for reciprocal and robertsonian translocations
Authors: Wiener Francis , Spira Jack , Babonits Magda , Klein George
Published: February 2007

Two translocation – carrying stocks of mice, T(7;15)9H and Rb(4;15) were resistant to chemical leukemogenesis by 7,12‐dimethylbenz(a)‐anthracene (DMBA) or methyl‐nitroso‐ N‐urea (MNU). Lymphomas were induced in F1 hybrids derived from crossing these two stocks with various susceptible strains. In T‐cell leukemias originating from F1 hybrids with Rb(4;15) as one parent and strain CBA or ASW as the other, the translocation chromosome was present in two copies. In trisomic tumors derived from Rb(4;15) X AKR F1 cross, the AKR‐derived chromosome 15 was duplicated regularly. In contrast, all trisomic lymphomas of the T(7;15)9H F1 outcrosses showed duplication of the non‐translocated chromosome 15 and not of the (7;15) translocation chromosome. It is suggested that the resistance of the T(7;15)9H stock to chemical induction of T‐cell leukemia may be related to the position of the translocation on chromosome 15 (band D2). Our previous studies (reviewed by Klein, 1981) have indicated that this area may contain an oncogene that needs to be activated and subsequently undergo duplication in the course of leukemia development. In our previous studies on trisomic leukemias induced in heterozygotes (Wiener et al., 1979, 1980b), we have found that duplication was nonrandom in all investigated crosses, unless the normal and the translocation marker carrying chromosomes were derived from the same inbred strain. A “duplication preference” scale could be established between chromosomes No. 15 derived from different strains. This suggested that the likelihood of leukemia development was different, depending on the genetic origin of chromosome 15. In the present study, we have found that the duplication of chromosome 15 occurred at random in the CBAT6T6 × C3H F1 cross. This is attributed to the close genetic relationship between the two strains, as indicated by their shared isoenzyme and other markers.
Epstein‐Barr virus induction by a serum factor: IV. Ubiquitous occurrence of the factor within vertebrates and its interaction with defined lymphoid cell lines
Authors: Wittmann Peter , Höfler Petra , Bauer Georg
Published: February 2007

We have recently reported the existence of a serum factor that induces Epstein‐Barr virus antigens in Raji cells (Bauer et al., 1982b, c). Here we demonstrate the ubiquitous presence of this factor in sera of vertebrates of all five classes. Furthermore, we tested 48 EBV‐genomepositive lymphoid cell lines of different origins for responsiveness to the serum factor. Only cells from lines of two groups, i.e. Burkitt's lymphoma and EBV‐transformed marmoset lines, responded to the factor, whereas human lymphoblastoid cell lines were not induced by the serum factor.
Tumor localization of CEA‐containing human tumors in nude mice by means of monoclonal anti‐CEA antibodies
Authors: Hedin Anders , Wahren Britta , Hammarström Sten
Published: February 2007

Three different monoclonal antibodies (mabs) directed against conformation‐dependent protein determinants in carcinoembryonic antigen (CEA) were evaluated for tumorimmunolocalization of CEA‐containing human tumors grown in nude mice. The antibodies were of high affinity and of the IgG1 subclass. They did not react with non‐specific cross‐reacting antigen (NCA), biliary glyco‐protein 1 (BGP 1) or orosomucoid. 10–20 μCi(1–2 μg) of 131I‐labelled mab was injected intraperitoneally into mice bearing heterografts of the CEA‐containing human tumor cell lines LS 174T, Detroit 562 or HT‐29 or into mice bearing grafts of the non‐CEA‐containing human tumor cell line RD. The concentration of radiolabelled mab in the tumor compared with the mean concentration in the mouse increased up to day 4 after injection. In contrast, the concentration ratios of radioactivity in the other tissues decreased with time. Excellent tumor localization was obtained with mab 38SI in mice bearing LS 174T tumors. The concentration of radioactivity (cpm/g) tissue wet weight) was 24–390 times higher in the tumor than in the muscle. The difference between tumor and liver and between tumor and blood was 4–89 times and 2–25 times, respectively. A mean value of 40% of the total radioactivity in the mouse at day 4 was localized to the tumor. Mab 38SI also showed positive tumor localization in mice carrying Detroit and HT‐29 tumors. Means of 22% and 18% of the total radioactivity in the mouse at day 4 were found in these tumors, respectively. Mab 38SI was, however, not enriched in the tumor of mice bearing the non‐CEA‐containing sarcoma RD. Furthermore, when LS 174T tumor‐bearing mice were injected with normal mouse IgG, no enrichment of radioactivity in the tumor was seen. Positive tumor localization with mab 48 was obtained while mab 9 was not enriched in the tumor. Scanning pictures of LS 174T‐grafted mice on day 4 after injection of 131I‐mab 38SI showed a definite radioactive spot corresponding to the tumor and in addition a spot corresponding to the liver or the heart.
Antibody responses to epstein‐barr virus‐specific DNase in relation to the prognosis of juvenile patients with nasopharyngeal carcinoma
Authors: Tan Reng‐Seng , Cheng Yung‐Chi , Naegele Robert F. , Henle Werner , Glaser Ronald , Champion John
Published: February 2007

We have examined serial sera from 17 juvenile patients with nasopharyngeal carcinoma (NPC) for their capacity to neutralize the activity of Epstein‐Barr virus (EBV)‐specific DNase. The results revealed that NPC patients who became long‐term survivors (LTS) without evidence of the disease either never possessed significant levels of antibodies to the enzyme or showed a gradual decline in the number of EBV DNase units neutralized from an elevated level at diagnosis to an insignificant figure several years later. All the 10 LTS neutralized less than 4, and some neutralized less than 2 units of the enzyme 3 or more years after the initial diagnosis. In contrast, serial sera from juvenile patients who died of NPC neutralized over 10 and as many as 25 units of EBV DNase either persistently until death occurred or with transient declines during unmaintained remissions. Rises and declines in the neutralizing activity were, with few exceptions, accompanied by corresponding changes in the titers of IgA and IgG antibodies to EB viral capsid antigen and to the diffuse component of the early antigens. Although the number of juvenile NPC cases available for study was small, the observations suggest that the EBV DNase neutralization test may serve to provide information on the prognosis of the patients.
Hybridization between a human epithelial line, infectable by Epstein‐Barr virus, and burkitt lymphoma lines: Membrane properties, superinfectability, inducibility and tumorigenicity
Authors: Mitrani‐Rosenbaum Stella , Ber Rosalie , Goldblum Natan , Povey Susan , Gamliel Haim , Ben‐Bassat Hannah
Published: February 2007

The human epithelial line U, which is partially infectable with EBV, was hybridized with the EBV‐genome carrying Burkitt lymphoma lines P3HR‐1 and Daudi. Authenticity of the hybrids U‐Put and U‐Dut was established by isoenzyme studies. Although the two hybrids carried the EBV genome derived from the lymphoma parent, being 100% positive for Epstein‐Barr‐virus‐associated nuclear antigen (EBNA), they resembled the U parent in many respects: they were deficient for membrane immunoglobulins and Fc receptors, and had a lower concentration of EBV‐C1 receptors than either parent. Unlike the P3HR‐1 parent, U‐Put hybrid was nonpermissive for both the EBV cycle antigens, early antigen (EA) and viral capsid antigen (VCA). The inducing agent 12‐O‐tetra‐decanoyl‐phorbol‐13‐acetate (TPA) caused distinct viral early antigen synthesis (EA) in U‐Put, lower, however, than that of the parental P3HR‐1. U‐Dut was completely nonpermissive and noninducible for early and viral capsis antigens. Thus, even an epithelial parent infectable by EBV restricted, although not completely, expression of EBV antigens, with the exception of EBNA. It has been suggested that EBNA is an autonomous function of the viral genome, independent of host cell control; the latter regulates expression of antigens related to viral cycle. The hybrids U‐Put and U‐Dut resembled the U parent also in regard to growth in soft agar and tumorigenicity in nude mice, although in this respect the lymphoma parental properties were not completely eclipsed.
Interferon treatment of murine meth‐a sarcoma cells: Effects on the malignant phenotype and expression of tumor‐specific and H‐2 antigens
Authors: Wivel Nelson A. , Pitha Paula M.
Published: February 2007

A virus‐free methycholanthrene‐induced sarcoma (Meth‐A) in BALB/c mice was grown in culture and treated with purified mouse interferon (α and β mixture) prior to testing for oncogenicity in the host animal. Use of interferon in vitro caused growth inhibition, but not cytotoxic effects; such effects were fully reversible upon interferon removal from the system. There was a significant decrease in tumor incidence in mice challenged with interferon‐treated cells, but this could be overcome by sufficiently increasing the number of cells in the inoculating dose. By transplanting these BALB/c sarcoma cells into Sprague‐Dawley nude mice, the effects of interferon could be negated. Since these mice have an unaltered activity of NK cells, the results suggest that NK cells do not play a major role in rejection of the Meth‐A tumor, but that the reduction in tumor incidence is dependent on the presence of functional T cells. Interferon caused a detectable reduction in the expression of the tumor‐specific transplantation antigen (TSTA) associated with Meth‐A cells, but increased the expression of H‐2 antigens. It has recently been shown that H‐2 antigens play a role in host recognition of the TSTA of methylcholanthrene‐induced sarcomas. It is suggested that the increased expression of H‐2 antigens on interferon‐treated Meth‐A cells could lead to an increased frequency of recognition by T‐cells.
Acquisition of sensitivity to exogenous fibronectin by friend leukemia cells correlates with reduction of their tumorigenic potential
Authors: Benedetto A. , Amici C. , Djaczenko W. , Zaniratti S. , Elia G.
Published: February 2007

Strongly adhesive, highly flattened clones (FF clones) can be selected from Friend leukemia cells (FLC) cultivated on top of monolayers of human embryonic fibro‐blasts (HEF). The flattened phenotype of FF clones is stable during cell replication either in soft agar or in vivo. With the number of passages of FLC on HEF the fibronectin (FN) sensitivity of FF clones increases with a proportional reduction of their tumorigenicity. The FN‐sensitivity was defined as the ability of a certain dose of FN to flatten 50% of cells of a given FF clone. Tumorigenicity was defined as the number of FF cells able to give palpable tumors, in 50% of inoculated mice. Exogenous FN does not modify the duplication time of FF clones but strongly influences their growth behavior. In the presence of FN, the growth rate of FF cells is controlled by the size of the growth area available. Highly FN‐sensitive FF cells grown on FN‐coated substrata die at confluency while FF cells not adherent to substrata escape cell death and grow in suspension. We conclude that the high intrinsic FN‐sensitivity of FF cells and FN availability at the site of tumor inoculation could be responsible for the reduced tumorigenicity of highly flattened FF clones.
Inhibitory effects of phenolics, teas and saliva on the formation of mutagenic nitrosation products of salted fish
Authors: Stich Hans F. , Chan Peter K. L. , Rosin Miriam P.
Published: February 2007

The objectives of this study were to simulate in vitro some of the conditions that may prevail in man during the ingestion of a meal and to quantitate the inhibitory effect of phenolics and phenolic‐containing beverages on the formation of mutagenic nitrosation products. The test system consisted of nitrosating (pH 2, 1 h, 37°C) an aqueous fraction of a salt‐preserved Chinese fish (Pak Wik) with or without the inhibitors to be tested and estimating the frequency of his+ revertants per survivor of Salmonella typhimurium (strain TA1535). The phenolics and teas were added to the nitrosation mixture. Catechin, chlorogenic acid, gallic acid, pyrogallol and tannic acid suppressed the formation of mutagenic nitrosation products. The inhibitory efficiency was comparable to that of ascorbic acid. A Japanese, a Chinese and a Ceylonese tea also prevented the formation of mutagenic nitrosated fish products at doses which are usually consumed by man. Moreover, saliva exerted an inhibitory effect. The inhibitory effect was not additive when the phenolics or saliva were added concurrently to the nitrosation mixture. The possibility that phenolics are involved in the apparent chemopreventive effect of fruits and vegetables is discussed.
A monoclonal antibody marker of human primitive endoderm
Authors: Williams L. K. , Sullivan A. , McIlhinney R. A. J. , Neville A. M.
Published: February 2007

Monoclonal antibodies were raised against the human germ‐cell tumor line, LICR LON HT39/7. The cells of this human embryonal carcinoma cell line were first fixed in formol saline and then dehydrated prior to immunization so that antibodies were produced which reacted with antigens surviving conventional histological processing. Eleven hybrid clones secreted antibody that reacted with both formol saline‐fixed and living cells of the immunogen. One of these antibodies, LICR LON FC 10.2, has been found to react with a membrane glycoprotein of molecular weight 200,000 restricted in distribution to the surfaces of undifferentiated teratoma‐derived cell lines, the luminal surface of human fetal intestine and bronchus and areas of putative endodermal differentiation within germcell neoplasms.
Cell‐mediated immunity to Epstein‐Barr virus (EBV) and natural killer (NK)‐cell activity in the X‐linked lymphoproliferative syndrome
Authors: Harada Shinji , Bechtold Thomas , Seeley Janet K. , Purtilo David T.
Published: February 2007

The activity of T‐cell‐mediated immunity to Epstein‐Barr virus (EBV) was assessed by an assay of regression of the outgrowth of EBV‐infected autologous B cells. Regression and natural killer (NK)‐cell activities were compared for patients and their mothers from five families with X‐linked lymphoproliferative syndrome (XLP) and three control groups. Seven of the 10 patients with XLP exhibited weak T‐cell activity against autologous EBV‐infected lymphoblastoid cell lines (LCL) comparable to EBV‐seronegative controls. In contrast, 8 of 10 obligate carrier females of XLP had unusually strong activity, which was comparable to anti‐early‐antigen (EA) positive controls. The results of the regression assays correlated with their EBV serology: mothers showed high titers, and their affected sons showed low‐titer EBV‐specific antibody responses. Defective NK‐cell activity was found only in the patients with XLP. NK and regression activities did not correlate. Our findings explain, in part, the vulnerability to EBV of males with XLP and why their mothers are protected from life‐threatening phenotypes of XLP.
Characterization of stable spontaneous metastatic variant lines of RSV‐transformed mouse fibroblasts
Authors: Renzo Maria Flavia Di , Bretti Sergio
Published: February 2007

The correlation between metastatic potential and a series of biological properties was investigated in two mouse fibrosarcoma lines (SR‐BALB and B77–3T3), transformed by different strains of Rous sarcoma virus (RSV). In the absence of selective pressure the metastatic potential was different in the two lines. The SR‐BALB sarcoma did produce both spontaneous metastases from s.c. site and i.v. lung colonization with a high incidence (respectively in 60% and 80% of treated animals). Conversely, the metastatic incidence of the B77–3T3 sarcoma was much lower. Differences in lung implantation between the two lines turned out to be even greater when the number of colonies growing in the lung was evaluated. Organ distribution of cells after i.v. injection, tumorigenicity, growth rate in vivo and in vitro, plating efficiency in liquid medium and cloning efficiency in semi‐solid agar medium were evaluated in the two lines. A strict correlation was found only between the metastatic potential and the capability of growth in 0.6% (“hard”) agar. Such a correlation was supported by the isolation in “hard” agar of highly metastasizing subclones of the low‐metastasizing B77–3T3 line.
Embryo‐derived teratocarcinoma. IV. The role of immune factors in the regulation of teratocarcinogenesis
Authors: Damjanov Ivan , Bagasra Omar , Dominis Mara , Solter Davor
Published: February 2007

Seven‐day‐old mouse embryos were transplanted under the kidney capsule of adult syngeneic recipients which were either X‐irradiated, treated with cyclophosphamide, splenectomized or immunized with teratocarcinoma cell lines prior to embryonic transplantation. The yield of malignant tumors was decreased in preirradiated, as well as in cyclophosphamide‐pretreated animals, as compared with untreated hosts. The effect of the pre‐treatment could be fully abrogated by allowing animals to spontaneously recover for 4 weeks or by adoptive transfer of thymus cells from untreated animals. Partial recovery was obtained by the adoptive transfer of spleen cells. Splenectomy at the time of embryonic transplantation did not affect the embryo‐derived teratocarcinogenesis in C3H mice but reduced the yield of malignancy and the weight of tumors produced in C57BL/6 mice. Immunization of hosts with teratocarcinoma cells did not influence the subsequent embryo‐derived teratocarcinogenesis. These data indicate that embryo‐derived teratocarcinogenesis is regulated by X‐ray and cyclophosphamide‐sensitive cells residing in the thymus and the spleen. The permissiveness to teratocarcinogenesis seems to be a function of the total number of these regulatory cells in the host.
Altered adhesiveness of tumor cell surface variants with reduced metastasizing capacity – reduced adhesiveness to vascular wall components in culture
Authors: Tao Tien‐Wen , Johnson Lorin K.
Published: February 2007

Heterotypic adhesiveness of surface variant clones of B‐16 melanoma cells exibiting different metastasizing capacity was studied with respect to components of the vascular wall in culture including endothelial (E) and smooth muscle (SM) cells from adult bovine aorta, and the extracellular matrices laid down by them. The ricinresistant cells (ricinR) and the wheat‐germ agglutininresistant (WGAR) cells, both of which showed reduced hematogenous metastases in vivo, showed reduced adhesiveness specifically to endothelial cells and extracellular matrices. This reduced heterotypic adhesiveness is in contrast to the homotypic adhesive properties in which respect the ricinR cells had similar values to the parental cells, while the WGAR cells had much higher values than the latter. There appeared to be a positive correlation between metastasizing capacity and specific adhesiveness to E cells and the extracellular matrix surfaces.
Phytohemagglutinin inhibits phorbol diester promotion of UV‐irradiation initiated transformation in syrian hamster embryo cells
Authors: Dipaolo J. A. , Evans C. H. , Demarinis A. J. , Doniger J.
Published: February 2007

Phytohemagglutinin (PHA) or either of its isolectins, erythroagglutinin or leukoagglutinin, causes a dose‐dependent decrease in 12‐O‐tetradecanoylphorbol 13‐acetate (TPA)‐promoted transformation of Syrian hamster embryo cells, but has no effect on transformation induced by ultraviolet irradiation. The ineffectiveness of concanavalin A indicates that not every lectin inhibits TPA. Galactose, a dominant sugar in receptors for PHA binding, reverses the inhibition of TPA promotion caused by PHA but galactose does not inhibit TPA promotion itself. Therefore, the TPA and PHA binding sites are functionally discrete. The PHA inhibition of TPA‐promoted transformation is reversible because PHA is only effective if present with TPA, whereas lymphotoxin, an immunologic hormone, has a persistent anti‐carcinogenic effect, regardless of whether it is added before or after TPA. PHA in conjunction with lymphotoxin causes additional inhibition of TPA‐promoted transformation. PHA and lymphotoxin affect the biological activity of TPA by diverse mechanisms. Lymphotoxin alters the physiological state of the cell, causing a change in the cellular response to TPA. PHA may affect either the binding of TPA to a critical cellular receptor for promotion or a later step in promotion.
Effect of elicitation on peritoneal macrophage subpopulations: Size distributions, ectoenzyme phenotypes and antitumor activity
Authors: Morahan Page S. , Rozner Marc A. , Jessee Ellen J.
Published: February 2007

Resident (R), Brewer's thioglycollate broth (TG) and C. parvum (CP)‐elicited murine peritoneal cell populations were separated into subpopulations by centrifugation on discontinuous Ficoll gradients consisting of layers of 4, 6, 8 and 10% Ficoll. The resulting subpopulations were shown to be distinct on the basis of cell size, ectoenzyme phenotypes and antitumor activity. The cell size distributions were analyzed by means of a Coulter channelyzer and software developed for a computer. The 4–6% Ficoll interface fraction comprised the smallest macrophages, with most cells in this subpopulation appearing to range in cell volume from 150–275 μm3. The largest sized macrophages were found in the 10%‐pellet fraction, with most cells appearing to range in cell volume from 300–600 μm3. The ectoenzyme phenotypes of the R, TG and CP unseparated macrophage populations were significantly different. Moreover, the ectoenzyme phenotypes of the smallest, (4–6% Ficoll interface) subpopulation in the R and CP macrophages differed from the other subpopulations. Reduction in alkaline phosphodiesterase I (APD‐I) ectoenzyme activity (as compared with unseparated R macrophages) appeared to be a marker for acquisition of antitumor activity. The small CP macrophages (4–6% Ficoll interface) showed no antitumor activity while the unseparated CP macrophages and all other CP macrophages subpopulations exhibited antitumor activity. The CP macrophage unseparated population and the subpopulations with antitumor activity expressed reduced ADP‐I activity. Conversely, the R or TG macrophage unseparated populations and their subpopulations, along with the CP macrophage 4–6% subpopulation, lacked antitumor activity and failed to show a change in ADP‐I ectoenzyme activity.
Antitumor effects of interferon in mice injected with interferon‐sensitive and interferon‐resistant friend leukemia cells. I.
Authors: Belardelli F. , Gresser I. , Maury C. , Maunoury M.‐T.
Published: February 2007

Interferon‐sensitive (745) and interferon‐resistant (3Cl‐8) Friend leukemia cells (FLC) are highly tumorigenic for DBA/2 mice. The phenotype of interferon sensitivity or resistance does not change with in vivo passage. Daily administration of mouse interferon markedly enhanced the survival time of mice injected with either 745 or 3Cl‐8 cells. Use of quantitative methods for determining the number of FLC (colony formation in agarose and immunofluorescence) permitted us to show that potent, partially purified or highly purified mouse interferon (s.a. 0.5 to 1 × 109 u/mg protein) induced a 100‐ to 1,000‐fold decrease in the number of tumor cells in the peritoneal cavity in the days following inoculation of 745 or 3Cl‐8 cells. Interferon decreased the number of FLC even when treatment was initiated at a time when tumor cells were multiplying exponentially in the peritoneal cavity. There was no evidence that interferon acted as an inducer of FLC differentiation in vivo. The finding that interferon was equally effective in mice inoculated with interferonresistant cells as in mice inoculated with interferon‐sensitive cells suggests that in this experimental system interferon does not act directly on the tumor cells, but that the interferon‐induced antitumor activity is mediated by the host.
Activation of the EBV‐cycle and aggregation of human blood lymphocytes by the tumor promoters teleocidin, lyngbyatoxin a, aplysiatoxin and debromoaplysiatoxin
Authors: Eliasson L. , Kallin B. , Patarroyo M. , Klein G. , Fujiki H. , Sugimura T.
Published: February 2007

A variety of tumor promoters such as the phorbol esters were found to be capable of inducing the viral cycle in cell lines latently infected with Epstein‐Barr virus (EBV). We tested two classes of new tumor promoters; indole alkaloids and polyacetates, for their ability to induce the synthesis of the Epstein‐Barr virus determined early antigen (EA) complex. Teleocidin and lyngbyatoxin A are indole alkaloids. Aplysiatoxin and debromoaplysiatoxin are polyacetates. Of these four tumor promoters all but debromoaplysiatoxin induced the synthesis of the EA complex. However, in combination with 3 mM n‐butyrate, all four induced EA synthesis. The potent tumor promoters teleocidin, lyngbyatoxin A and aplysiatoxin induced maximal synthesis of EA at the concentration of 5 to 10 ng/ml, whereas the weak tumor promoter debromoaplysiatoxin required a concentration of 250 ng/ml to achieve maximal induction. Phorbol esters induce quick morphological changes and aggregation of human blood lymphocytes. The latter phenomenon has been interpreted as the expression of a “cell binding phenotype” (Patarroyo et al., in press). We showed that all four promoters induced aggregation of human lymphocytes at similar concentrations. The induction seemed to be a common effect which could be induced by both strong and weak tumor promoters.
Insensitivity to interferon of two subclones of human endometrial carcinoma cell line, HEC‐1
Authors: Morinaga Naoko , Yonehara Shin , Tomita Yoshimi , Kuwata Tsuguo
Published: February 2007

Two cloned cell lines, HEC‐IC and HEC‐ID, derived from the human endometrial adenocarcinoma cell line HEC‐I, were found to be as resistant to the antiviral and anticellular activities of interferon (IFN) as were the parental cells, and 2′‐5′ oligoadenylate (2‐5A) synthetase was not induced in these clones by IFN treatment. They were sensitive to the cytotoxicity of natural killer (NK) cells but their sensitivity was not changed by treatment of the cell lines with IFN. Binding of [3H]‐leucine‐labelled IFN‐a to HEC‐IC cells was examined, and Scatchard plot analysis showed that HEC‐IC cells did not have any high‐affinity binding sites for IFN‐a. The cells had hyperploid chromosomes. HEC‐IC had three copies of chromosome 21 while HEC‐ID had only one copy of chromosome 21. The results suggest that these clones may have the structural gene for the IFN receptor but that functional receptor sites may be absent.
Modulation of natural killer (NK) cell activity during FLV‐P virus infection of mice
Authors: Migliorati Graziella , Jezzi Teresa , Frati Luigi , Bonmassar Enzo , Rossi Giovanni B. , Garaci Enrico , Riccardi Carlo
Published: February 2007

We analyzed the effects of a polycythemic substrain of Friend leukemia virus, i.e. the FLV‐P virus, on splenic NK activity of DBA/2 susceptible mice. One day after virus injection a significant increase of NK activity was found, which persisted until day 10. On the other hand, 14‐21 days after virus injection a marked and significant depression of activity was measured. This depression was associated with the appearance of suppressor cells able to inhibit the lytic activity of untreated splenocytes when mixed in vitro in the 4 h 51Cr‐release assay. The suppressor cell population was insensitive to treatment with anti‐Thy 1.2 plus complement, was adherent to Sephadex G‐10 and nylon, but did not adhere to plastic, suggesting it is neither a T‐cell nor a typical macrophage. The possible relevance of NK activity modulation in relation to the induction of leukemia is discussed.
Distribution of the transferrin receptor in normal human fibroblasts and fibrosarcoma cells
Authors: Ekblom Peter , Thesleff Irma , Lehto Veli‐Pekka , Virtanen Ismo
Published: February 2007

Transferrin is required for proliferation of most cells in culture. This effect is presumably mediated by the binding of transferrin to its receptor, a surface glycoprotein which is preferentially expressed by actively growing cells. Here we show that normal human fibroblasts cultured in serum, and other media containing transferrin express transferrin receptors in a distinctly non‐random way: punctate foci of the receptor were seen only at the leading lamellae of the cells, whereas cells grown without serum, or in transferrin‐depleted serum showed a random distribution of the receptor. In contrast, malignant fibrosarcoma cells showed the receptor uniformly throughout the cell surface in all media tested, including those containing transferrin. The data suggest that the ligand causes a directional lateral movement of the receptor in normal but not in malignant cells. Application of the receptor antibody caused a rapid internalization of the receptor in both cell types.
Establishment and characterization of a human non‐secretory plasmacytoid cell line and its hybridization with human B cells
Authors: Ritts R. E. , Ruiz‐Argüelles Alejandro , Weyl Karin G. , Bradley Anne L. , Weihmeir Bernadette , Jacobsen Deborah J. , Strehlo Bonnie L.
Published: February 2007

A human non‐secretory plasmacytoid cell line has been established for 6 years in more than 170 passages. Over 300 passages have been made from several early and late passages. The cell line is karyotypically normal, easily grown and has the characteristic features of a non‐secretory plasmablast. Its characteristics suggest its use for hybridization by new methods as well as a study of its secretory defect. HPRT‐negative phenotypic mutants can be derived from this line and a single polyploid clone has also been isolated. Hybridization with the HPRT+ and HPRT‐ lines X human B cells is described.
Pregnancy‐associated alpha2 glycoprotein (α2PAG) synthesis by human breast cancer tissue and cultured cell lines
Authors: Sarcione Edward J. , Delluomo Daniel , Zloty Martin
Published: February 2007

Elevated α2PAG serum levels are found in pregnant women and patients with diverse types of neoplasms including breast cancer. Primary human breast cancer tissue, MCF‐7 and BT‐20 human breast cancer cultured cell lines were shown to synthesize α2PAG in vitro. BT‐20 breast cancer cells also released this pregnancy‐associated protein. Synthesis was demonstrated by l‐[14C]‐leucine incorporation into immunochemically isolated protein and confirmed by radioimmunodiffusion and radioimmuno‐electrophoresis. These data (1) provide direct evidence for α2PAG synthesis by well‐characterized human breast cancer cells per se;(2) strongly suggest that at least part of the α22PAG synthesis observed in primary human breast cancer tissue in vitro was due specifically to breast cancer cells rather than exclusively to monocytes/mac‐rophages known to infiltrate neoplastic tissues and to produce this protein during pregnancy; and (3) are consistent with the conclusion that serum α2PAG is a definite breast cancer “marker protein” which originates from and reflects breast cancer status. On the basis of the association of elevated serum α2PAG levels in breast cancer patients, its known immunosuppressive activity in vitro, and the direct evidence for α2PAG synthesis by human breast cancer cells perse, we postulate that this protein plays an important immunoregulatory role in vivo to prevent immune rejection and/or destruction of breast cancer cells.
Radioimmunoassay of prostatic acid phosphatase: Validation and clinical application
Authors: Franchimont P. , Bouffioux Ch. , Reuter A. , Rigo‐Betz Ch. , Vrindts‐Gevaert Y. , Jaspar J. M. , Lecomte‐Yerna M. J.
Published: February 2007

A radioimmunoassay for prostatic acid phosphatase (PAP) has been established, using a purified preparation extracted from human seminal plasma. To obtain immunologically intact 125I‐PAP as a tracer, the lactoperox‐idase technique was used followed by double chromatography on Sephadex G‐50 and G‐200. The assay was sensitive, accurate and reproducible. Only leukocyte acid phosphatase cross‐reacted completely whilst acid phosphatases from other tissues (skin, lymph nodes, lung, kidney, liver, testis, platelets) did not interfere in the assay. When this method was used, PAP levels in men over the age of 20 were greater than those of women and younger men. Patients with prostatitis, benign prostatic hypertrophy (BPH) and other prostatic disorders had normal levels in more than 95% of cases. Patients who had prostatectomy for BPH had levels significantly lower than those of normal controls and those with unoperated BPH. This provides indirect evidence for the specificity of the PAP radioimmunoassay. In prostatic cancer, PAP levels measured by radioimmunoassay were more frequently and more greatly elevated with progression of the disease: 25% atstages A and B, 75% at stage C and 100% at stage D. Further, PAP measurement provided a quantitative marker to follow therapeutic response as PAP levels varied in parallel with clinical, radiologic and scintigraphic progression. Under our experimental conditions, the PAP radioimmunoassay proved to be more sensitive (percentage of increased levels in the serum of patients with prostatic cancer) and more specific (percentage of normal levels in the serum of patients with prostatic disorders other than cancer) than the enzymatic assay of these enzymes.
Transformation‐enhancing activity in plasma of tumor patients: Relationship with fibronectin fragments
Authors: De Petro Giuseppina , Barlati Sergio , Vartio Tapio , Vaheri Antti
Published: February 2007

Human plasma cryoprecipitates (cryos) of tumor patients have been shown to contain transformation‐enhancing factors (TEF)4, able to promote morphological cell transformation in vitro. A similar activity is associated with proteolytic fibronectin fragments retaining the gelatin‐binding site. We have now studied whether similarities exist between TEF found in cryos and the fibronectin fragments. Of 14 TEF‐positive tumor cryos tested, 13 (including carcinomas, leukemias, lymphomas and myelomas) retained their activity in the gelatin‐binding fraction, and in one the activity was not recovered. In one case of myeloma, TEF activity was detected only in the gelatin‐binding fraction and not in the starting cryo. In contrast, none of the TEF‐negative control samples tested, obtained from healthy donors and patients affected by different non‐malignant diseases, showed any TEF activity in the gelatin‐binding or ‐nonbinding fractions. The TEF‐positive gelatin‐binding fractions of tumor cryos were active even at the concentration of ∼ 50 ng/ ml. The presence of fibronectin in human plasma cryos was detected using immunoblotting. In the gelatin‐binding fractions, fibronectin antigenicity was seen in the position of intact fibronectin subunits (Mr = 220,000) and different fragments (Mr = 50,000‐200,000). while the gelatin‐binding fractions contained a single antigenic polypeptide (Mr ∼94,000). The TEF activity of cryo, as well as that of plasminolytic digest of purified plasma fibronectin, could be inhibited by fibronectin antibodies. The data suggest that the' TEF activity present in tumor patient plasma cryoprecipitates is related to gelatin‐binding fragments of fibronectin.
Epstein‐barr virus‐specific antibodies in patients with adult T‐cell leukemia (ATL) and healthy ATL virus‐carriers
Authors: Imai Joko , Hinuma Yorio
Published: February 2007

Antibodies to Epstein‐Barr virus (EBV)‐capsid antigen (VCA), early antigen (EA) and EBV‐associated nuclear antigen (EBNA) in the sera of 103 patients with adult T‐cell leukemia (ATL) and the sera of 243 age‐ and sex‐matched healthy adults, namely 99 anti‐ATLA‐positive (antibodies to ATL virus‐associated antigen) and 144 anti‐ATLA‐negative individuals, were determined by indirect immunofluorescence. The anti‐VCA titers in the sera from ATL patients were within the range observed in healthy controls. Anti‐EA was found in 27% of the sera from ATL patients, but in only 8% of the sera from anti‐ATLA‐negative healthy controls. Antibodies to EBNA, which were present in almost all healthy adults, were not found in 30% of the sera from ATL patients. Of the sera of anti‐ATLA‐positive healthy adult donors 11% were negative for EBNA antibody. These results suggest that functional impairment of the T‐cell system in most ATL patients, and also to a lesser extent in anti‐ATLA‐positive adults who might be healthy ATLV‐carriers, may cause an unusual immune response of antibodies to EBV‐associated antigens.
Seasonal variation in the junctional component of pigmented naevi
Authors: Holman C. D. J. , Heenan P. J. , Caruso V. , Glancy R. J. , Armstrong B. K.
Published: February 2007

From an assessment of the presence of a junctional component in 8,380 pigmented naevi, and histological review of its extent and the presence of inflammation and regression in a sample of 216 junctional and compound naevi, it was determined that naevi excised in summer were more likely to have a junctional component and evidence of inflammatory response than those excised in winter. It is suggested that a short‐term promotional effect of sunlight on cells in the junctional zone of pigmented naevi may, in addition to increased case ascertainment in summer, explain reported seasonal variation in the incidence of malignant melanoma.
Immunodepression by the oncogen does not determine the relationship between tumor latency and immunogenicity
Authors: Prehn Richmond T. , Karcher Christine A.
Published: February 2007

Immunogenic and non‐immunogenic tumor implants were made at varying intervals after administration of an oncogenic dose of 3‐methylcholanthrene to mice. The length of the interval did not detectably influence the growth of the implants, suggesting that immunodepression by the oncogen is probably not the cause of the relationship between the latencies and the immunogenicities of hydrocarbon‐induced tumors.
Effects of several species of human leukocyte interferon on cytotoxic activity of NK cells and monocytes
Authors: Ortaldo John R. , Mantovani Alberto , Hobbs Donna , Rubinstein Menachem , Pestka Sidney , Herberman Ronald B.
Published: February 2007

Ten species of purified human leukocyte interferon were tested for their ability to modulate the cytolytic activity of natural killer (NK) cells and the cytolytic and cytostatic activities of monocytes. The interferon species were tested at several antiviral tilers and examined for quantitative differences in their ability to modulate immunological function. At the higher doses of interferon (i.e., >500 units) all of the interferon species demonstrated significant augmentation of cytolysis and cytostasis. However, when low levels (i.e., 10‐50 units) of interferon were emplpyed, appreciable differences between the various interferon species were seen. A similar pattern of relative potency among the various species of pure leukocyte interferon was seen for augmentation of cytolysis by monocytes and NK cells. In contrast, a different pattern of relative potency was observed for augmentation of cytostasis. These results demonstrated substantial quantitative differences (as much as 100‐fold) in the ability of the various species of human leukocyte inperferon to induce significant levels of augmentation of these cellmediated functions. Such results should have significant impact in choosing a specific interferon species for appropriate clinical trials.
Natural killer cell activity during mouse hepatitis virus infection: Response in the absence of interferon
Authors: Stohlman Stephen A. , Brayton Peter R. , Harmon Richard C. , Stevenson Douglas , Ganges Roland G. , Matsushima Glenn K.
Published: February 2007

The ability of the JHM3 strain of mouse hepatitis virus (MHV) to induce natural killer (NK) cells was examined. Infection of C57BU6 (86) mice with this virus resulted in the augmentation of natural cytotoxicity against YAC‐I target cells in the absence of a detectable interferon response. The cells responsible for this increased cytotoxicity were sensitive to complement‐mediated lysis with an anti‐Q‐5 reagent but not with a Thy 1.2 antiserum, indicating that they possess an NK‐like surface phenotype. Although variation in the NK response of individual B6 mice following JHM virus infection was found, even the animal with the most responsive NK cell population had no detectable interferon in the spleen. This finding contrasted with observations with an unrelated virus (lymphocytic choriomeningitis virus) and a serologically related strain of MHV. Infection with both of these viruses induced augmented NK cell activity and interferon responses. In addition, we found that neither the ability to mount an augmented NK cell response nor preferential lysis of virus‐infected targets correlated with resistance or susceptibility to JHM virus infection.
The presence of p53 transformation‐related protein in Ab‐MuLV transformed cells is required for their development into lethal tumors in mice
Authors: Rotter Varda , Abutbul Haya , Wolf David
Published: February 2007

p53, a cellular‐encoded protein, is synthesized at elevated levels in a wide range of tumor cells. Ab‐MuLV‐transformed cells expressing both the viral‐encoded p120 oncogene and the cellular‐encoded p53 display a lethal tumor phenotype in syngeneic mice. L12 is an exceptional Ab‐MuLV‐transformed cell line that expresses the p120 oncogene and lacks the p53 cellular protein. Injection of L12 cells into syngeneic mice is followed by the development of local tumors that are subsequently rejected. Prolonged treatment of L12 cells with TPA, a tumor cell promoter, gave rise to L12T cells that synthesize the p53 protein and exhibit a lethal tumor phenotype. Comparison of one‐dimensional proteolytic partial peptide map of p53 obtained from L12T to that obtained from other Ab‐MuLV‐transformed cell lines confirmed their identity. These results suggest a correlation between the cellular expression of p53 in Ab‐MuLV‐transformed cells and their capacity to develop into lethal tumors in syngeneic mice.
Genetic control of the organ specificity of lymphoproliferative disease virus (LPDV) of Turkeys
Authors: Gazit Arnona , Yantv Abraham , Ilani Aviva , Ianconescu Marius , Perk Kalman , Zimber Amatzia
Published: February 2007

In a previous study based on the kinetics of virus replication and tumor formation (Gazit et al., 1982), it was shown that the organotropism of lymphoproliferative disease virus (LPDV) is confined to lymphoid tissues. The present paper demonstrates that this organ specificity is controlled at the level of infection and integration, that is, the lymphoid organs, which are the only organs sustaining virus replication, and also the only organs in whose cells integrated LPDV proviruses are detectable. At the same time, the efficiency of virus replication within the various target organs is regulated both at the level of infection and integration and at the level of viral gene transcription.
The mechanism of augmentation of natural killer cell activity by syngeneic tumor cells: Role of macrophage‐derived factor in NK boosting
Authors: Kawase Ichiro , Urdal David L. , Newman Walter , Henney Christopher S.
Published: February 2007

The role of natural killer (NK) cells in controlling tumor growth was investigated using an NK‐susceptible (cl27v‐IC2) and an NK‐insusceptible (c127av) subline of the lymphoma L5178Y. Syngeneic DBA/2 mice inoculated intraperitoneally with c127v‐IC2 tumor cells survived significantly longer than did c127av‐bearing mice. Similarly, c127v‐IC2, but not c127av tumor cells, were found to augment NK activity of spleen and peritoneal exudate cells in both DBA/2 and BALB/c nu/numice when inoculated into the peritoneal cavity. C127v‐IC2 tumor cells incubated with either DBA/2 or BALB/c nu/nu spleen cells in vitro boosted NK activity and induced the production of gamma‐type interferon (IFN), whereas incubation with c127av tumor cells induced neither NK activity nor IFN. Two kinds of cells cooperated in the production of IFN in response to c127v‐IC2 tumor cells, namely, cells which were nonadherent, bore asialo‐GM1, NK‐1.2 and a low level of Thy‐1.2 antigen and thus closely resembled NK cells, and those which were adherent and phagocytic and lacked both asialo‐GM1, and NK‐1.2 markers, presumably macrophages. Further analysis strongly suggested that c127‐v‐IC2 tumor cells stimulate macrophages to produce factor(s) which can induce the production of IFN by NK cells. The induced IFN was shown to be of the gamma type by its lability at ph 2.0 and insusceptibility to anti‐IFNα,β serum. This suggests a novel pathway for NK cell activation, and strongly supports the importance of macrophages and NK cells in natural resistance against certain tumors.