bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of serum blocking factors against leukocyte‐dependent antibody in melanoma patients
Authors: Murray E. , Ruygrok S. , Hersey P. , Milton G. W.
Published: February 2007

Previous studies have shown that leukocyte‐dependent antibody activity against melanoma cells in the sera of melanoma patients is often completely blocked by factors in their sera. In the present study, characterization of these factors blocking melanoma LDA was carried out by a number of sequential separation procedures involving gel filtration on Sepharose 6B, affinity chromatography on concanavalin A (Con A) and electrophoresis in polyacrylamide gels in the presence of sodium dodecyl sulphate (PAGE‐SDS). The blocking factors were identified throughout the separation procedure by their blocking activity against melanoma LDA. It was found that blocking activity against melanoma LDA was located in small (<60,000) and large (approx. 300,000) molecular weight fractions obtained by gel filtration. Both of the latter fractions were found to have affinity for concanavalin A and were therefore glucose‐ and/or mannose‐containing glycoproteins. The blocking activity in both fractions was further resolved into a single fraction of 15,000 d by PAGE‐SDS. This small molecular weight fraction appeared to be melanoma antigen as shown by its removal by affinity chromatography on melanoma antibody bound to sepharose and by its blocking activity against melanoma LDA. A similar fraction was isolated by this separation procedure from supernatants and membranes of cultured melanoma cells. These results appear to provide a basis for the development of in vitro assays to monitor tumour growth in melanoma patients and for further characterization of the biological nature of melanoma antigens.
In vitro generation of cytotoxicity against autologous human tumour biopsy cells
Authors: Vose B. M. , Vánky F. , Klein Eva , Fopp M.
Published: February 2007

Blood lymphocytes from 22 cancer patients were examined for cytotoxicity against autologous tumour cells in a short‐term 51Cr release assay. Only three showed reactivity. In an attempt to increase cytotoxic potential in these and induce reactivity in non‐reactive cases, the lymphocytes were cultured alone or with autologous tumour cells for 6 days. Upon subsequent testing against frozen, stored targets, nine samples reacted, including two of those with primary reactivity. In seven cases augmented cytotoxicity was evident in mixed cultures compared with lymphocytes cultured alone. Two of 10 cases showed cytotoxicity against the K562 cell line after culture and, in two of 13 tests in which allogeneic tumour biopsy targets were used, weak reactivity was bound. Cytotoxicity for autologous tumour biopsy cells was uniformly accompanied by positive blastogenesis in MLTI assays. In four cases blastogenesis occurred without the induction of cytotoxicity.
Proteolytic release of antigenic fragments corresponding to normal fecal antigen and non‐specific cross‐reacting antigen from carcinoembryonic antigen
Authors: Matsuoka Y. , Koga Y. , Maruta H. , Yoshino M. , Tsuru E.
Published: February 2007

Three immunogenic parts have so far been identified in the carcinoembryonic antigen (CEA) molecule. These are: determinants cross‐reacting with the normal fecal antigen (NFA) (NFA determinant); determinants cross‐reacting with the non‐specific cross‐reacting antigen (NCA) (NCA determinant); and determinants which appear to be more cancer‐specific (cancer determinant). The chemical nature of these parts of the CEA molecule was investigated by digestion with proteolytic enzymes together with anti‐CEA preparations with which these three immunogenic parts of CEA molecule could be identified. The CEA digest obtained with pepsin did not react in immunodiffusion and radioimmunoassay, indicating that pepsin completely destroyed all the antigenic parts. Digestion by pronase E destroyed only the cancer determinant and liberated two antigenic fragments corresponding to the NFA determinant and the NCA determinant, respectively. These results suggest that the cancer determinant may reside in a protein or a peptide part of the molecule. The chemical nature of the NFA and NCA determinant remains to be clarified.
Induction of mammary tumors in C57BL/haag female mice by a low oncogenic mammary tumor virus
Authors: Vlahakis G. , Chopra H. C. , Sawdon M. R.
Published: February 2007

Mammary tumor virus (MuMTV)‐negative mouse substrain C57BL/Haag foster‐nursed by strain DD becomes a line with a moderately high incidence of mammary tumors occurring in the females at a late age. Electron microscopy revealed B particles in the tumors, providing additional evidence for the propagation and transmission of DD‐MuMTV in C57BL/HaagfDD. Since both albino strains DD and RIII originated in Europe, develop pregnancy‐dependent mammary tumors, carry black and agouti genes (cc, BB, AA), and therefore may be related, evidence is presented which suggests that the two naturally occurring MuMTVs from DD and RIII may also be related, and that they may share a common origin.
Transformation of marmoset lymphocytes in vitro with herpesvirus ateles
Authors: Falk Lawrence , Johnson Donald , Deinhardt Friedrich
Published: February 2007

Circulating lymphocytes from three species of marmoset monkeys were transformed in vitro with Herpesvirus ateles (HVA) either by co‐cultivation with lethally X‐irradiated HVA‐producing lymphoblastoid cells or by infection with cell‐free virus: 42 transformed lymphocyte cultures were obtained from 72 transformation attempts. Attempts to transform squirrel monkey lymphocytes were unsuccessful in 29 attempts. Association of HVA with each transformed culture was demonstrated by staining of antigen‐positive cells in indirect fluorescent antibody (FA) tests and recovery of HVA after co‐cultivation of the transformed cells with permissive monolayer cells. Cells of most transformed cultures possessed T lymphocyte properties: i.e. formation of E rosettes, reactivity with a specific anti‐marmoset T lymphocyte serum and lack of surface Ig.
Lysis of RSV‐transformed japanese quail cells by a factor from normal quail serum
Authors: Yoshikawa Yasuhiro , Yamanouchi Kazuya , Hishiyama Michiko , Kobune Kaoru
Published: February 2007

Normal sera of Japanese quails caused lysis of tumor cells from a Rous sarcoma virus (RSV)‐induced quail tumor (QT cells). Other tumor cell lines, including RSV‐transformed quail embryo cells and methylcholanthrene‐induced quail tumors, were not lysed. This naturally occurring cytolytic factor (NCLF) was sensitive to heating at 56° C, zymosan, and inulin, and it required magnesium but not calcium for the expression of its activity. These results suggested that NCLF activity was mediated by complement activated through an alternative pathway. This possible complement activation occurred in the absence of specific antibodies to the target cells.
Abnormalities of chromosome no. 1 in human solid malignant tumours
Authors: Kovacs G. Y.
Published: February 2007

Marker chromosomes involving chromosome No. 1 were studied with banding techniques in 10 primary solid tumours. Structural or numerical aberrations of chromosome No. 1 were found in nine of these. Two major types of rearrangement of chromosome No. 1 were observed: translocation of the long arm (partial trisomy) and an isochromosome of 1q. Earlier chromosome studies and the present cases suggest that regions near the centromere and q21 are vulnerable points on human chromosome No. 1, and that region q21–32 is important for development of certain tumour types.
Search for infective mammalian type‐C virus‐related genes in the dna of human sarcomas and leukemias
Authors: Nicolson M. O. , McAllister R. M. , Gilden R. V. , Charman H. , Rice N. , Heberling R.
Published: February 2007

DNA was extracted from two human sarcoma cell lines, TE‐32 and TE‐418, and the leukemic cells from five children with acute myelocytic leukemia, three children with acute lymphocytic leukemia and four adults with acute myelocytic leukemia. The DNAs, assayed for infectivity by transfection techniques, induced no measurable virus by methods which would detect known mammalian C‐type antigens or RNA‐directed DNA polymerase in TE‐32, D‐17 dog cells and other indicator cells, nor did they recombine with or rescue endogenous human or exogenous murine or baboon type‐C virus. Model systems used as controls were human sarcoma cells, TE‐32 and HT‐1080, and human lymphoma cells, TE‐543, experimentally infected with KiMuLV, GaLV or baboon type‐C virus, all of which released infectious virus and whose DNAs were infectious for TE‐32 and D‐17 dog cells. Other model systems included. two baboon placentas and one embryonic cell strain spontaneously releasing infectious endogenous baboon virus and yielding DNAs infectious for D‐17 dog cells but not for TE‐32 cells. Four other baboon embryonic tissues and two embryonic cell strains, releasing either low levels of virus or no virus, did not yield infectious DNA.
Somatic cell hybrids between human lymphoma lines. IV. Establishment and characterization of a p3HR‐1/daudi hybrid
Authors: Ber R. , Klein G. , Moar M. , Rosén A. , Westman A. , Yefenof E. , Povey S. , Zeuthen J.
Published: February 2007

A new human B‐lymphoma hybrid line designated DIP‐1 was derived from the fusion of the Burkitt lines Daudi and P3HR‐1. Cytogenetic analyses proved hybridity and showed that the hybrid was nearly complete from the chromosomal point of view. Hybridity was also confirmed by isozyme marker tests. The Daudi‐derived IgM‐kappa ring was fully exposed on DIP‐1, together with the P3HR‐1‐derived human beta‐2‐microglobulin. Expression of C3 receptors was intermediate between the two parents and EBV receptors were some what reduced in comparison with both. The spontaneous low‐level EBV antigen (EA and VCA) production of the parents was maintained and amplified in the hybrid. The hybrid, like its Daudi parent, was highly inducible with IdUrd. In P3HR‐1 virus super‐infection experiments, the Daudi parent was more permissive than the BU‐P3HR‐1 parent. The hybrid was intermediate, resembling the previously studied Raji/Daudi hybrid and contrasting with Raji/Namalwa and Raji/BJAB hybrids. Virus DNA replication patterns after P3HR‐1 virus superinfection resembled the antigen pattern. The implication of these findings for the understanding of virus‐host cell relationships and the regulation of the viral cycle is discussed The findings are meant to imply that genetically determined isozyme markers are autonomously expressed, as in other systems. Differentiation‐related markers and EBV‐cycle‐related characteristics are autonomously expressed in some cases (surface immunoglobulin, beta‐2‐microglobulin, spontaneous EBV‐production, IdUrd inducibility) and appear to be under a restrictive control in others (EA inducibility by P3HR‐1 virus superinfection, C3 and EBV receptors, viral DNA replication).
Chromosome 14q+ in a retinoblastoma
Authors: Hossfeld D. K.
Published: February 2007

A chromosome 14q+ was found in the tumor cells of a patient with sporadic, bilateral retino‐blastoma. Eighty‐six per cent of the metaphases contained the marker. Some metaphases showed a chromosome 6q— in addition. The question of the specificity of such markers in lymphoid malignancies is raised.
Activation of endogenous type‐C viral p30 antigen in chemically‐induced rat hepatocellular carcinomas
Authors: Becker Frederick F. , Sherr Charles J.
Published: February 2007

Chemically induced rat hepatocellular carcinomas were prospectively examined for expression of the major group‐specific antigen (p30) of genetically transmitted rat type‐C viruses. Ten primary tumors induced following oral administration of the carcinogen N‐2‐acetylaminofluorine did not express elevated levels of viral antigen as compared to antigen levels detected in normal liver tissue. By contrast, rapidly growing transplantable hepatocellular carcinomas (THCs) derived from primary tumors expressed increased quantities of viral antigen. The expression of antigen was marginally elevated after only one transplantation, increased to maximal levels after several transplant generations and, once achieved, was stably maintained throughout subsequent transplants. Studies with additional previously established THCs showed that poorly differentiated, rapidly proliferating tumors tended to express elevated levels of viral antigen, while more differentiated, slowly growing tumors did not. The results show that the expression of endogenous type‐C viral 30 antigen is a stable phenotypic property of many rat THC lines.
Rapidly progressing breast cancer (poussée Évolutive) in Tunisia: Studies on delayed hypersensitivity
Authors: Mourali Nejib , Levine Paul H. , Tabanne Francoise , Belhassen Slim , Bahi Jacqueline , Bennaceur Meri , Herberman Ronald B.
Published: February 2007

Delayed hypersensitivity reactions to a battery of antigens were measured in 145 Tunisian breast cancer patients to determine whether an immuno‐logic mechanism could be detected which might explain the high frequency (60%) of the rapidly progressing form in Tunisian breast cancer patients. Although a greater proportion (30%) of patients with rapidly progressing breast cancer reacted to extracts of a breast tumor antigen (2937) than patients without PEV (9%), no significant difference between PEV and non‐PEV patients could be found in reactivity to DNCB, standard microbial antigens, or extracts from tissue culture cell lines. Rapidly progressing breast cancer in Tunisia is not associated with an impairment of delayed hypersensitivity.
High terminal deoxynucleotidyl transferase activity in pediatric patients with acute lymphocytic and acute myelocytic leukemias
Authors: Srivastava B. I. Sahai , Khan Sohaib A. , Minowada Jun , Freeman Arnold
Published: February 2007

Specificity of TdT5 as a marker for ALL was evaluated by determining its activity in cells from normal control subjects and from 35 pediatric patients with ALL, AML, Hodgkin's disease and disseminated Burkitt's lymphoma. We evaluated the DNA polymerase activity, cell surface pheno‐types (E rosettes, EAC rosettes, SmIg and Ia‐like, HTLA and cALL antigens), and hematological and cytochemical characteristics in both the normal and patient groups. DNA polymerase α+β and DNA polymerase γ activity were indiscriminately high in all immature cells as found in ALL, AML, Burkitt's lymphoma and phytohemagglutinin‐stimulated normal lymphocytes, when compared to mature leukocytes found in normal individuals or in patients whose cancer was in remission. High TdT activity was found in 24 of 26 T and non‐T/non‐B ALL patients in active phase as well as in two of three AML patients one of whom had Auer rods. Thus, TdT, although valuable for monitoring ALL patients, may have limitations in separating AML from ALL.
Conditions required for induction of murine p30 by herpes simplex virus
Authors: Isom H. , Colberg A. , Reed C. , Rapp F.
Published: February 2007

Mouse cells (line N clA cl10) contain 1.2–2.5 ng murine leukaemia virus (MuLV) p30 antigen/mg of protein; this amount of antigen is measurable by competition radioimmunoassay (RIA) but is not detectable by indirect immunofluorescence (IF). Infection of N clA cl10 cells with herpes simplex virus type 2 (HSV‐2) induces expression of MuLV p30. Induction by HSV‐2 does not require either cell or virus DNA synthesis and is optimal 8 h post infection when cells at 50–70% confluence are infected at a multiplicity of infection (MOI) of 5–8 PFU/cell. At an MOI of 2.5, 70–80% of the cells express HSV antigens while none of the cells express p30; at an MOI of 5.0, 70–80% of the cells express HSV antigens but 55% of the cells express p30. Using the conditions reported in this paper for preparation of competing antigen, induction of p30 by HSV‐2 (strain 333) infection is not measurable by competition RIA.
Stimulatory effect of cigarette smoke on the metabolism and covalent binding of benzo(a)pyrene in the trachea of the rat
Authors: Simberg Niklas , Uotila Pekka
Published: February 2007

The activity of aryl hydrocarbon hydroxylase (substrate: benzo(a)pyrene) was increased in the tracheas of rats exposed to cigarette smoke for 1 h daily for either 1 or 10 days. However the degree of increase in activity was lower in the trachea than in the lung. After a single exposure, activity in the trachea was at its highest level 12 h following exposure (3.2‐fold compared to the control), but had returned to the control level within 24 h. Also, the amounts of covalently bound metabolites of benzo(a)pyrene were increased (2‐fold) in nucleic acid and protein fractions of the trachea, when the rats were killed 12 h after a single cigarette smoke exposure. No significant changes in the activity of epoxide hydratase (substrate: styrene oxide) could be detected in the trachea. After repeated exposures the activity of UDP‐glucuronosyltransferase (substrate: methylumbelliferone) was increased (1.7‐fold) in the trachea.
Non‐phorbol mouse skin tumor promoters do not mimic phorbol myristate acetate in its effects on chick embryo fibroblasts
Authors: Driedger Paul E. , Blumberg Peter M.
Published: February 2007

Phorbol esters, the most potent class of tumor promoter for mouse skin, have been shown to cause loss of the large external transformation‐sensitive glycoprotein LETS1 from the surface of chicken embryo fibroblasts (CEF) and to cause an increase in the rate of deoxyglucose (DG) transport by these cells. Several compounds which promote mouse skin tumors but which are structurally unrelated to the phorbol esters were tested for their abilities to cause loss of LETS from CEF and to stimulate DG transport. Of the seven compounds tested, only oleic acid (at 140 μM) caused a decrease of more than 20% in LETS, as measured by lactoperoxidase‐catalyzed surface radioiodination. Phenol at 1 mM caused a 70% increase in LETS levels. Only three agents, anthralin, lauric acid and limonene, caused increases in DG transport. Iodo‐acetic acid and canthridin were inactive in both assays. None of the compounds affected CEF LETS levels or DG transport to the extent that the phorbol esters do. Palmitic and stearic acids, which are structurally similar to oleic acid but which do not promote mouse skin tumors, were inactive in both assays. The lack of correspondence between the effects on CEF of the phorbol esters and the non‐phorbol promoters suggests that these two groups may have different mechanisms of action.
Immunological characteristics of leukemia and lymphoma in allogeneic cell immunity: Growth of syngeneic tumors in rats immunized with allogeneic cells
Authors: Hosokawa Masuo , Yamashita Tetsuro , Gotohda Eiki , Takeichi Noritoshi , Kodama Takao , Kobayashi Hiroshi
Published: February 2007

The growth of transplanted tumors was strongly inhibited in syngeneic Wistar King Aptekman (WKA) rats immunized with allogeneic tumor cells from Donryu rats. This phenomenon of non‐specific immunity against tumors is referred to as “allogeneic cell immunity”. However, an exception to the “allogeneic cell immunity” was observed in leukemias and lymphomas. Four transplanted leukemia or lymphoma lines were not inhibited in syngeneic rats immunized with allogeneic tumor cells. Furthermore, immunization with allogeneic leukemic cells had only a relatively weak inhibitory effect upon a syngeneic fibrosarcoma and no inhibitory effect upon leukemias. In WKA rats immunized with allogeneic lymphoid cells from Donryu rats, the growth of fibrosarcoma, but not of lymphoma, was inhibited. Using transplantation experiments, both fibrosarcoma and lymphoma were defined as antigenic tumors in WKA rats. Transplantation of mixtures of syngeneic tumor cells and allogeneic tumor cells in WKA rats confirmed the above findings. These results revealed that leukemia and lymphoma differ from non‐leukemic tumors in regard to “allogeneic cell immunity”.
Identification and behavior of the precipitating BLV antibodies in sera of leukotic cattle
Authors: Matthaeus W. , Kaaden O. R. , Frenzel B. , Schlotterer E.
Published: February 2007

Precipitating bovine leukemia virus antibodies isolated from bovine leukemic sera by ion‐exchange chromatography, gel filtration and affinity chromatography were identified as immunoglobulins of the IgG1 subclass and IgA class. They proved to be different with regard to molecular size and electrical charge. Immunoglobulins IgG2 and IgM as well as low‐molecular components ranging in the micro‐globulin regions (<4S) failed to precipitate BLV antigens. Individual bovine leukemic sera showed differing precipitating activities against p24 and gp69 antigens. Precipitating monospecific gp69 antibodies represented exclusively the IgG1 subclass. Some unidentified antigens in disrupted BLV preparations showed serological relationship to p24 and gp69, respectively.
DNA damage in liver, colon, stomach, lung and kidney of BALB/c mice treated with 1,2‐dimethylhydrazine
Authors: Brambilla G. , Cavanna M. , Parodi S. , Sciabà L. , Pino A. , Robbiano L.
Published: February 2007

DNA single‐strand breaks induced in various organs of BALB/c mice by treatment with a single dose of 1,2‐dimethylhydrazine (DMH) were studied by means of the alkaline elution method modified in order to allow the evaluation of DNA damage in vivo with no need of radioactive prelabelling. DNA damage was detected in liver, lung, kidney, stomach and colon mucosa, with the liver showing the greatest amount of damage. Its degree was dependent on the dose and route of administration. A differential effect was evident in colon mucosa from Swiss and C57BL/6 mice which are respectively susceptible and resistant to the induction of bowel tumors by DMH. The higher degree of DNA damage found in liver in comparison with colon mucosa is consistent with the previously reported higher degree of DNA methylation, but does not correlate with the specificity of this carcinogen in inducing tumors of the large intestine in mice given repeated subcutaneous injections.
Cellular basis of induced α‐fetoprotein synthesis by hepatocytes of adult mouse after hepatotoxic injury and partial hepatectomy
Authors: Mohanty Mira , Das P. K. , Mittal Asha , Nayak N. C.
Published: February 2007

The dynamics of α‐fetoprotein (AFP) production by hepatocytes following different experimental manoeuvres that are known to induce regeneration of the liver was studied in young adult mice by simultaneous identification of dividing cells arrested during mitosis and of cells containing immuno‐histochemically detectable AFP. After 70% hepatectomy AFP was produced by a few, largely periportally located hepatocytes, following waves of brisk and active cell division. Carbon tetrachloride (CCl4)‐induced hepatic injury, on the other hand, led to participation of a relatively larger number of cells in early AFP synthesis preceding a less extensive cell proliferation. Initially, AFP‐producing cells were located in the peripheral part of the lobule but later they were more centrally placed, most often surrounding the zone of necrosis. Cells in mitosis often contained large amounts of AFP. CCl4 administration 48 h after 70% hepatectomy resulted in extensive AFP production by approximately a quarter of all surviving liver cells, although the concurrent rate of cell division was low. Intoxication with dimethylnitrosamine showed a pattern identical to that of hepatectomy but both cell division and AFP production were of comparatively lower magnitude. It is concluded that at least two distinct modes exist for augmented synthesis of AFP by hepatocytes of adult animals. In one, pre‐existent cells are stimulated to produce the protein before and irrespective of cell division while in the other, small amounts are synthesized by newly generated cells. Combination of the two mechanisms results in high levels of AFP production by stimulation of a large number of young hepatocytes.
Metabolism and DNA binding of polycyclic aromatic hydrocarbons by human diploid fibroblasts
Authors: Baird William M. , Diamond Leila
Published: February 2007

The metabolism of three carcinogenic polycyclic aromatic hydrocarbons was measured in mid‐(population doubling levels of 20–39) and late‐(population doubling levels > 55) passage cultures of WI‐38 human diploid fibroblasts. Cultures of mid‐and late‐passage cells metabolized these hydrocarbons to both water‐ and organic solvent‐soluble derivatives. In stationary cultures, the same amounts of benzo(a)pyrene (BP) and 3‐methyl‐cholanthrene were metabolized per cell, but late‐passage cells metabolized only one‐third as much 7,12‐dimethylbenz(a)anthracene per cell as mid‐passage cells. The DNA adducts formed from BP in WI‐38 cells were examined by chromatography of enzyme‐degraded DNA samples on Sephadex LH20 columns. On columns eluted with methanol‐water gradients, the [3H]BP‐deoxyribonucleoside adducts eluted in the same volume as the product peak isolated from DNA that had been reacted with 7,8‐dihydroxy‐9,10‐epoxy‐7,8,9,10‐tetrahydroBP. On columns eluted with borate‐containing methanol‐water gradients, 62% of the cellular products eluted in the same volume as the product peak isolated from DNA that had been reacted with (±) 7α,8β‐dihydroxy‐9β,10β‐epoxy‐7,8,9,10‐tetrahydroBP (the anti‐isomer) and 35% eluted in the same volume as a product peak isolated from DNA that had been reacted with (±) 7α,8β‐dihydroxy‐9α,10α‐epoxy‐7,8,9,10‐tetrahydroBP (the syn‐isomer). Thus, more than one type of DNA adduct is formed in these cells, possibly through the reacticn of different isomers of this BP‐diol‐epoxide with DNA.
Some mechanisms involved in cancer cell detachment by necrotic material
Authors: Weiss Leonard
Published: February 2007

Factors influencing cell detachment are thought to play a role in metastasis and invasion. Previous studies on cylinders punched from Walker 256 (W‐256) tumors growing in rats showed that detachment of viable cancer cells was facilitated by their proximity to necrotic regions and exposure to a necrotic extract. By the use of pure cultures of W‐256 cells, it is shown that necrotic extracts which are rich in lysosomal hydrolases act directly on W‐256 cells, facilitating their in vitro detachment. Lysosomal enzymes have previously been shown to facilitate cell detachment. The partial inhibition of this process by hydrocortisone suggests that the extracts also act by labilizing the W‐256 cell lysosomes; this enzyme release is also demonstrable by direct assay. Although secondary lysosomes could not be visualized in the W‐256 cells, both they and macrophages release lysosomal hydrolases on freeze‐thawing, and could both account for the high enzyme content of the necrotic regions, by a process of continuous secretion and/or cell input. Histologic examination of perinecrotic and peripheral regions of tumors showed a higher proportion of macrophages in the former, which is thought to be mainly due to differential trapping of the macrophages. The results emphasize the functional properties of necrotic regions of tumors and the necessity of referring to specific regions of the same tumor when referring to its metastatic and other properties.
Relevance of circulating immune complexes in childhood acute lymphoblastic leukaemia
Authors: Clague Roy B. , Kumar Shant , Hann Ian M. , Jones Patricia H. Morris , Holt P. J. Lennox
Published: February 2007

Circulating immune complexes have been measured using the (125I)C1q binding test in 216 sera from 135 children with acute lymphoblastic leukaemia. Increased circulating immune complexes were detectable in 10.7% of the sera and 10.4% of the children. There was no correlation between the presence of circulating immune complexes and prognosis, but a strong correlation with a history of recent infection.
Genetics of SV40 T‐antigen expression: Studies of twins, heritable syndromes and cancer families
Authors: Blattner W. A. , Lubiniecki A. S. , Mulvihill J. J. , Lalley P. , Fraumeni J. F.
Published: February 2007

Susceptibility of human skin fibroblasts to SV40 virus infection has been suggested as a marker of cancer risk. To evaluate the role of heritable factors in the regulation of SV40 T‐antigen, fibroblasts from 9 pairs of identical twins and 129 members of cancer‐prone families, including 16 with cancer, were tested in a 3‐day immunofluorescence assay. In the twin study, the variance of T‐antigen values was significantly less in identical than in fraternal or non‐twin sibs, suggesting a heritable component in the regulation of SV40 infection. In the families, T‐antigen values of parents and children were compared to models of Mendelian inheritance. At least three modes of inheritance—autosomal dominant, recessive, and X‐linked—were observed. The distribution of offspring values compared to those of their parents suggested that interaction of multiple genetic factors influences the T‐antigen value in individual patients. With the exception of Fanconi's anemia, the values for patients with cancer or predisposing syndromes were not uniformly elevated. The utility of this assay as a marker of cancer risk appears limited because of the complexity of factors that influence T‐antigen expression in individual cases.
Primary epstein‐barr virus infections in african infants. I. Decline of maternal antibodies and time of infection
Authors: Biggar Robert J. , Henle Werner , Fleisher Gary , Böcker Jörg , Lennette Evelyne T. , Henle Gertrude
Published: February 2007

Thirty‐one infants living in Accra, Ghana, an area endemic for Burkitt's lymphoma, were visited at monthly intervals for the first 15 months of life and once again at 21 months. Sera obtained at each visit were tested for antibodies to Epstein‐Barr virus (EBV) capsid antigen (VCA), EBV‐induced early antigens (EA) and EBV‐associated nuclear antigen (EBNA) by immunofluorescence techniques as well as for EBV‐neutralizing antibodies and antibody‐dependent cell‐mediated cytolysis. All infants had maternal antibodies to VCA at 1 month of age and the majority also antibodies detected by the other tests, except anti‐EA. The maternal anti‐VCA titers declined in subsequent months according to a half‐life of nearly 5 weeks. Depending on the initial titers, all infants became seronegative for all antibodies by 2–8 months of age, with anti‐VCA persisting longest. The earliest primary EBV infection occurred in the third month after maternal antibodies to VCA had become non‐detectable. By 12 months of age, 44% of the infants had seroconverted, by 15 months, 62% and by 21 months, 81%. There was no seasonal variation in the incidence of infections. Infants from families of the lowest socio‐economic level tended to become infected somewhat earlier than those from better situated families (p = 0.22) but no other factors, such as household size or crowding, seemed to be associated with enhanced risk of early infection.
Expression of oncofetal antigens on murine sarcomas characterized for expression of endogenous MuLV
Authors: Pollack Sylvia B.
Published: February 2007

A rabbit antiserum raised by repeated immunization with BALB/c fetuses obtained at 10–14 days of gestation was used to search for oncofetal antigens (OFA) in murine sarcomas which had previously been characterized for the expression of endogenous murine leukemia virus (MuLV). Iodinated protein A from staphylococcus aureus (IPA) was used to quantitate binding of the antiserum to cultured tumor or fetal cells or to saline extracts of tumors and fetuses. Use of the “antigen” extracts facilitated the assay: the extracts bound to plastic and served as targets for the binding assay, eliminating the need to establish tumors in culture. After absorbtion in vitro and in vivo with adult tissues the rabbit antiserum bound to day 10–14 fetal cells and extract but not to endogenous MuLV (BALB virus 1). The antiserum bound equally well to MuLV‐negative and MuLV‐positive sublines of MCA‐induced sarcomas 1420 and 1414 but not to Moloney sarcoma cells and MCA‐induced sarcoma 1386. Thus, the absorbed antiserum detects a class of common cross‐reacting antigens which are serologically distinct from MuLV‐associated antigens.
Longitudinal study of epstein‐barr virus antibody titers and excretion in pediatric patients with Hodgkin's disease
Authors: Lange Beverly , Arbeter Allan , Hewetson John , Henle Werner
Published: February 2007

Nineteen pediatric patients with Hodgkin's disease (HD) who had experienced primary Epstein‐Barr virus (EBV) before, or in one case after, diagnosis, were studied longitudinally for changes in the titers and spectra of EBV‐related antibodies, excretion of EBV into the oropharynx, the number of EBV‐carrying lymphoid cells in the peripheral blood, and clinical signs and symptoms suggestive of reactivation of the latent virus. The incidence and geometric mean titers of IgG antibodies to viral capsid antigen (VCA) in the HD patients at the time of diagnosis and in the controls were similar. The anti‐VCA titers of the patients rose above control levels during and after therapy and remained elevated for up to 7 years of observation. At no time were heterophil or VCA‐specific IgM antibodies detected. Antibodies to EBV‐induced early antigens were more common in patients (ultimately 80%) than in controls (9%). In contrast, antibody levels to EBV‐associated nuclear antigen were disproportionally low in the patients. Excretion of EBV was noted at increased frequency in the patients but the number of circulating, EBV‐carrying lymphoid cells was the same as in controls. No discrete clinical syndrome was associated with rising antibody titers or viral excretion. While these results are best explained by a presumed reactivation of the persistent EBV infection by immunosuppressive effects of HD or its therapy, they have not provided direct evidence for this suggestion.
Stimulation of human NK‐cell activity by cultured cells. I. Response of normals
Authors: Grohmann P. , Holmes W. , Porzsolt F. , Quirt I. , Miller R. G. , Phillips R. A.
Published: February 2007

Natural cell‐mediated cytotoxicity, observed on co‐cultivation of peripheral blood lymphocytes (PBL) with malignant melanoma tumor cells (M4), is described. The activity was inhibited when PBL were cultured in autologous serum. Studies using competitive inhibition with cold targets and stimulation of PBL with other tumor cell lines failed to detect specificity.
Frequent elevation of tissue polypeptide antigen in the sera of workers exposed to bladder carcinogens
Authors: Kumar Shant , Wilson Philip , Brenchley Paul , Taylor Geoffrey , Björklund Bertil , Eklund Gunnar
Published: February 2007

A group of 108 male workers previously exposed to bladder carcinogens and a group of 26 patients with carcinoma of the bladder differed significantly from a control group comprising 63 healthy male donors with respect to their levels of tissue polypeptide antigen (TPA). The risk group exhibited 4–6 times more frequent elevations of TPA than did the group of healthy donors.
Carcinogenesis of N‐nitrosodiethylamine (DENA) in chickens and domestic cats
Authors: Schmähl D. , Habs M. , Ivankovic S.
Published: February 2007

The environmental carcinogen N‐nitrosodiethyl‐amine (diethylnitrosamine, DENA) has been found to be carcinogenic in 18 animal species. In this study we demonstrate that, after intramuscular injection in chickens, it induces hepatocellular carcinomas of the liver and adenocarcinomas of the kidney. Oral administration in domestic cats causes malignant hepatomas and tumors of the esophagus and kidney. Since DENA is carcinogenic in all species in which it has been tested adequately it can be expected to be a human carcinogen, too.
Differentiation of mouse myeloid leukemia cells is inhibited by a factor from non‐differentiating leukemia cells
Authors: Okabe Junko , Hayashi Moriaki , Honma Yoshio , Hozumi Motoo
Published: February 2007

Mouse myeloid leukemia cells (MI) were induced to differentiate by a factor(s) (D‐factor) in ascitic fluid. An inhibitory activity (I‐activity) for the induction of differentiation was present in conditioned medium and lysate of MI cells resistant to the D‐factor. The I‐activity was non‐dialyzable, heat‐labile and protease‐sensitive. Most of the activity was recovered in the fraction precipitated with 30–50% saturated ammonium sulfate. The fraction inhibited induction of phagocytic activity, migrating activity and morphological changes in MI cells, which are typical properties of differentiated MI cells. Low levels of I‐activity were detected in conditioned medium or lysate of MI cells sensitive to the D‐factor. The resistant MI cells were sensitized to the D‐factor by treatment with a low concentration (5–10 ng/ml) of actinomycin D. The I‐activity in conditioned medium of actinomycin D‐treated resistant cells decreased with development of sensitivity to the D‐factor. These results suggest that production of the I‐activity in the resistant cells is closely associated with resistance of the MI cells to the D‐factor.
Circulating immune complexes in rats bearing chemically induced tumours. II. Characterization of sera from different stages of tumour growth
Authors: Höffken Klaus , Price Michael R. , Moore Valerie E. , Baldwin Robert W.
Published: February 2007

Sera from rats bearing intraperitoneal implants of an aminoazo dye‐induced hepatoma were fractionated by Sephadex G200 and DEAE‐cellulose ion exchange column chromatography. Isolated fractions were examined for their capacity to bind [125I]C1q as a measure of immune complex levels, and for their ability to bind soluble tumour‐specific antigen as well as to react with antigens expressed at the surface of viable hepatoma cells. Elevated levels of circulating immune complexes in unfractionated serum were directly detectable during early tumour development although, following serum fractionation, immune complexes were identified at both early and late stages of tumour growth. The present findings suggest that the detection of immune complexes in unfractionated samples of late tumour‐bearer serum using a C1q‐binding assay is masked by the increasing production of tumour‐specific antibodies and by a shift from complement fixing to non‐complement‐fixing tumour‐specific antibodies.
Surface membrane changes of T cells induced by syngeneic tumour cells. I. Formation and uptake of complexes of Ig and tumour antigens by T cells
Authors: Dular U. , Chow D. A. , Paraskevas F.
Published: February 2007

A large dose of tumour cells (107) from two different tumours produced a significant increase of Ig‐bearing spleen cells 6 h after intraperitoneal administration in syngeneic mice, like conventional antigens previously tested. Incubation of normal spleen cells in serum taken 6 h after administration of tumour cells reproduced in vitro the changes observed in the spleen cell population of the serum donors, demonstrating the presence of a cytophilic Ig, which was shown to be taken up by T cells. Serum collected 6 h after tumour cell inoculation contains also a 4S factor which can generate in vitro cytophilic Ig for T cells in the presence of a foreign soluble protein or tumour antigen. Extracts obtained from tumours cells, which were shown to contain tumour antigens, were labelled with 125I and mixed with the 4S factor and normal 7S Ig. Upon fractionation of the mixture, high molecular weight material containing radioactivity and 7S Ig were eluted in the void volume, well ahead of the position of both the tumour cell preparation and the 7S Ig. This material contained Ig cytophilic for splenic T cells and it is likely that it represents cytophilic complexes of Ig and tumour antigens. It is postulated that the cytophilic Ig detected in the serum of animals 6 h after injection of a large number of tumour cells represents cytophilic complexes of Ig and tumour antigens formed through the mediation of a soluble factor.
Surface membrane changes of T cells induced by syngeneic tumour cells. II. T‐cell defects induced by small tumour cell inocula or tumour cell antigens
Authors: Chow D. A. , Paraskevas F. , Dular U.
Published: February 2007

Injection of a large number of tumour cells, like other strong immunogenic challenges, is followed within 6 h by the uptake of cytophilic Ig (probably complexes) by a subpopulation of T cells. This phenomenon, known as the “6‐hour T‐cell response” is abrogated when small tumour cell inocula (102), or small amounts of a preparation from tumour cells, which contains tumour antigens, are injected prior to the immunogenic challenge Abrogation of the “6‐hour T‐cell response” resulted in a decrease in specific anti‐tumour cell immunity as tested in vitro by measuring growth inhibition (cytostasis). It has also resulted in loss of the amplifying function on antibody formation against sheep erythrocytes, normally detected in a T‐B cell co‐operative system when T cells are used 6 h after priming with sheep erythrocytes. It is postulated that this T‐cell defect may represent a mechanism by which tumour cells, in the early stages of their growth, interfere with inductive stages of the immune response for a sufficient period of time to allow the tumour to grow beyond immune control.
Human tumor‐lymphocyte interaction in vitro. III. T lymphocytes in autologous tumor stimulation (ATS)
Authors: Vánky F. , Klein Eva , Stjernswärd J. , Rodriguez L. , Péterffy Á. , Steiner L. , Nilsonne U.
Published: February 2007

The T‐cell nature of the responding cells in autologous tumor stimulation (ATS) was proven by (1) E‐rosette formation of lymphocytes attached to tumor cells during the early period of co‐cultivation; (2) blast‐transformed E‐rosetting cells detectable at the end of the test period (day 6) and (3) the reactivity of T‐enriched lymphocyte subset and unresponsiveness of T‐depleted fractions. Preparation of tumor suspensions devoid of lymphocytes made it possible to carry out cross‐tests between patients. Blastogenesis with allogeneic tumors was rare. The restricted autologous nature of the reaction is a strong indication for genuine tumor‐relatedness.
An abnormal early evening peak of plasma prolactin in nulliparous and obese post‐menopausal women
Authors: Kwa H. G. , Bulbrook R. D. , Cleton F. , Verstraeten A. A. , Hayward J. L. , Wang D. Y.
Published: February 2007

Plasma specimens were obtained in the afternoon (13.30 to 17.29 h) from 668 post‐menopausal women and in the evening (17.30 to 20.30 h) from 219 further women. The mean evening plasma prolactin level was significantly higher than that found in the afternoon (p<0.0007). Mean afternoon prolactin levels were not related to nulliparity and body weight. In nulliparous obese women the mean of the evening peak prolactin concentrations was double that of comparable women studied in the afternoon (p<0.003).
Oral contraceptives and breast disease in premenopausal northern albertan women
Authors: Lees Alan W. , Burns Patricia E. , Grace Michael
Published: February 2007

The results of a prospective study on oral contraceptive use and breast disease in northern Alberta are presented. The study groups comprised all women aged 30 to 49 examined in diagnostic breast clinics at the Cross Cancer Institute between 1971 and 1974. Three hundred and one patients had breast cancer, 692 had a subsequent biopsy for a benign breast condition, and 548 had no subsequent biopsy. A tendency for an increased relative risk (RR) of breast cancer in women taking oral contraceptives for periods of 1 to 5 years was evident, with relative risk decreased or unaffected in users of less than 12 months (RR = 0.6) or more than 5 years (RR = 1.0). A slightly increased risk was apparent in patients using oral contraceptives within a year prior to attendance at the clinic (recent users); this increase was emphasized when recent users with a prior biopsy for benign breast disease were analyzed alone (RR = 5.0). In women with a prior breast biopsy, use of oral contraceptives for more than 5 years increased risk of breast cancer nine‐fold. Former users who had taken oral contraceptives for less than a year showed a significant reduction in breast cancer risk (RR = 0.3). The risk of benign breast disease was also reduced in former users (RR = 0.6) as well as in long‐term users (RR = 0.5).
Antibodies to herpes simplex virus types 1 and 2 in patients with squamous‐cell carcinoma of uterine cervix in India
Authors: Seth Pradeep , Prakash S. S. , Ghosh D.
Published: February 2007

Antibody activity to Herpes simplex virus type‐1 (HSV‐1) and type‐2 (HSV‐2) was measured by the indirect hemagglutination (IHA) test in sera from 124 women with squamous‐cell carcinoma of the uterine cervix, 46 women with non‐cervical cancer and 116 matched normal women. The type‐specific antibodies were assayed by IHA inhibition test. The proportion of cervical cancer cases positive for HSV‐2 infection was significantly greater than that of non‐cervical cancer cases and matched control women. No difference was observed in the percentages positive for HSV‐1 infection among the three study groups. The mean titers of antibodies to HSV‐1 as well as HSV‐2 were significantly higher than the respective titers in the other two study groups. However, determination of type‐specific antibodies did not help in establishing evidence for past infection by HSV‐2 in patients with cervical cancer, as no type‐specific HSV‐2 antibodies were produced in 58% of the cases. The cervical cancer cases were also analysed according to clinical staging (Stages 0 to IV) and histological differentiation of squamous‐cell carcinoma. Neither the percentage of positives for HSV‐2 infection nor HSV‐antibody titers varied, either in clinical staging or in histological differentiation of cervical cancer. These findings suggest that HSV‐2 may be related to cervical cancer as an etiological agent but not as a passenger virus of carcinomatous tissue.
Mechanism of sensitivity of cultured pancreatic carcinoma to asparaginase
Authors: Wu Ming‐Chi , Arimura Grace K. , Yunis Adel A.
Published: February 2007

The effects of E. coli L‐asparaginase on cultured human pancreatic carcinoma (MIA PaCa‐2) have been studied. The enzyme (1 U/ml) inhibited growth and protein synthesis in both MIA PaCa‐2 and PANC‐1, another pancreatic carcinoma cell line, but had little or no effect on human breast carcinoma or melanoma cells. The inhibition of protein synthesis by E. coli L‐asparaginase was largely reversed by L‐glutamine but not by L‐asparagine. The growth of both MIA PaCa‐2 and PANC‐1 showed absolute dependence on L‐glutamine. These results indicate that the effect of E. coli L‐asparaginase on cultured pancreatic carcinoma cells is exerted at least in part through its L‐glutaminase activity. Although the addition of L‐glutamine to the culture appeared to prevent cell death caused by L‐asparaginase, it did not restore the ability of the cells to proliferate. Asparaginase derived from vibrio succinogenes, which is virtually free of L‐glutaminase activity, was equally inhibitory to MIA PaCa‐2 cell growth but did not affect protein synthesis. It is concluded that the inhibition of growth of cultured pancreatic carcinoma cells by E. coli asparaginase is a combined function of both its L‐asparaginase and L‐glutaminase activity.
Effects on in vitro tumor growth of murine macrophages isolated from sarcoma lines differing in immunogenicity and metastasizing capacity
Authors: Mantovani Alberto
Published: February 2007

Macrophages were isolated from the strongly immunogenic, non‐metastasizing FS6 sarcoma transplanted in syngeneic C57BL/6 mice and from a weakly immunogenic, spontaneously metastasizing line (mFS6) of the same tumor. Macrophages isolated from the FS6 sarcoma non‐specifically inhibited growth and DNA synthesis of tumor cells in vitro. After culture FS6 macrophages rapidly lost their cytotoxic activity and became capable of non‐specifically stimulating tumor growth in vitro. Macrophages obtained from the mFS6 tumor non‐specifically enhanced the proliferative activity of tumor target cells and this capacity was maintained when the macrophages were cultured.