bluuebunny/crossref_metadata_2025 huggingface dataset:
Patterns of gastro‐intestinal cancer in european migrants to Australia: The role of dietary change
Authors: McMichael A. J. , McCall M. G. , Hartshore J. M. , Woodings T. L.
Published: February 2007

Cancers of the stomach, pancreas, colon and rectum are increasingly regarded as being diet‐influenced. Migrants to Australia from England, Scotland, Ireland, Poland, Yugoslavia, Greece, and Italy have come from countries with varied dietary backgrounds and gastrointestinal cancer risks. Age‐standardized cancer death rates in migrants, by country of origin, sex, age, and duration of residence in Australia (≤16 years and >16 years), have been calculated for 1962–76, and compared with those of the Australian‐born population. All seven migrant source countries, in 1970, had higher rates of stomach cancer than Australia, and the corresponding migrants groups, which initially reflected those higher rates, experienced an approximately 25% risk reduction with increased duration of residence. For cancer of the pancreas, migrants initially had rates well above their “native” rates; with longer stay, the risks generally converged upon that of the Australian‐born population. The four “continental” (European) migrant groups, whose native risk of colon cancer is about half that of the Australian population, showed an increased risk with increasing duration of stay. The increase was greater in men than in women, perhaps reflecting their greater dietary acculturation. By contrast, Scottish migrants, with an initially high risk of colon cancer, experienced a subsequent reduction in risk. Rectal cancer continental migrants showed even larger increases than colon cancer, while in British migrants there was a marked decline towards the “Australian‐born” risk. These various changes in cancer risk are discussed with reference to inter‐country dietary differences.
The plate‐implant as a bioassay for the neoplastic potential of cultured cells
Authors: Sanford Katherine K. , Boone Charles W. , Merwin Ruth M. , Jones Gary M. , Garrison Carlton U.
Published: February 2007

One objective of this study was to test the plate implant as an in vivo bioassay for the neoplastic state with pairs of cell lines that were non‐tumorigenic and tumorigenic when inoculated in suspension at various sites. Each pair originated from a common cell pool or from one cell derived from normal rat or mouse embryonic tissue. The implantation of cells attached to polycarbonate plates was compared with the subcutaneous injection of comparable numbers of cells in suspension or the intraocular injection of 105 cells. In addtiion, some implants of glass helices with attached cells were made into syngeneic mice and compared with injection of comparable cell numbers intramuscularly into X‐irradiated hosts. A total of 10 lines or clones were tested on plates. Of four lines that were non‐tumorigenic when inoculated in suspension either subcutaneously or intraocularly, two were tumorigenic when implanted subcutaneously attached to plastic plates. The remaining two are the first permanent rodent lines that have not been tumorigenic on plastic plates. Of the remaining six lines, all were tumorigenic on plates and two produced sarcomas at a higher frequency on plates than in suspension. Cytologic diagnoses of the cells implanted on plates, subcutaneously and intraocularly, correlated best with the results from plate implants. Of three mouse lines implanted on helices, two were equally tumorigenic in suspension and on helices, whereas the third was tumorigenic on helices only. The plate implant was more satisfactory technically than the helices and proved to be one of the most sensitive bioassays for the neoplastic state of cultured cells.
Lymphoma development from transplanted murine leukemia virus infected organ cultured thymuses: Inhibitory effect of in vitro interferon treatment
Authors: Riesenfeld Inger , Tufveson Gunnar , Alm Gunnar V.
Published: February 2007

Thymuses of 14‐day‐old AKR mouse embryos were infected with Gross murine leukemia virus (MuLV) and then maintained in organ culture for 3 weeks. When they were transplanted to 3‐week‐old (AKR X C3H)F1 mice, approximately 50% of these developed T lymphomas within 3–4 months. Most (22/23) tumors were of host, F1‐hybrid, origin while only one was of donor AKR type. No clear evidence for in vitro MuLV‐induced lymphoma cells was therefore obtained. Exposure of MuLV‐infected embryonic thymuses to interferon during the organ culture period significantly reduced the incidence of lymphomas in mice receiving such thymus transplants. Interferon also prevented the appearance of detectable numbers of MuLV antigen‐containing lymphocytes in infected organ‐cultured thymuses. In contrast, despite the use of very high interferon concentrations, no effects were seen on the number of viable thymic lymphocytes, their proliferation or responsiveness to the polyclonal T‐cell mitogens concanavalin A (Con A) and leukoagglutinin (LA). Thus interferon, presumably through an antiviral effect, can limit the MuLV infection in the thymus and its consequence, i.e.development of a lymphoma.
Characterization of the presumptive sarcoma cells in primary MSV tumors
Authors: Becker Sanne , Haskill Stephen
Published: February 2007

Presumptive sarcoma cells have been isolated from primary MSV tumors induced in normal, immunosuppressed (ALG) and athymic nude mice. These cells were atypical in appearance, induced tumors in secondary hosts and expressed the viral antigens gp70, p30 and p12. In vitro growth characteristics of the MSV cells were tested in a variety of assays defining cell transformation. None of these indicated that the virus‐positive cells were transformed. Sex chromosome marker studies were carried out to determine if secondary tumor arose solely from proliferation of donor cells or through infection of host tissue. Tumors from female irradiated mice induced by injections of tumor cells derived from male mice contained a high proportion of metaphases of non‐donor origin, indicating that infection is an important but not the sole mechanism involved in tumor transfer. These data also demonstrated that many of the sarcoma cells are damaged as a result of infection as shown by the presence of chromosome breaks and aneuploid metaphases. Histologic sections of both regressor and progressor tumors showed that the virus‐positive cells were scattered as single cells surrounded by inflammatory cells, rather than as masses of dividing virus‐positive cells found in the MSV‐induced transplanted tumor. Collectively, these data support the contention that the MSV tumor is the manifestation of a response to a highly noxious virus infection rather than a tumor of dividing, transformed malignant cells.
Inhibition of rous sarcoma‐virus‐induced transformation by proteins involved in blood coagulation
Authors: de Petro G. , Brega A. , Mignatti P. , Barlati S.
Published: February 2007

Plasma, serum and the main proteins involved in the final steps of blood coagulation, fibrinogen, thrombin and plasma transglutaminase, have been tested for their ability to inhibit cell transformation and/or to induce reversion of the transformed to the normal phenotype in RSV‐infected chicken embryo fibroblasts. The results obtained show that plasma, and not serum, fibrinogen, when converted to fibrin by thrombin, and activated transglutaminase alone prevent focus appearance and cause reversion of transformed to normal cell morphology.
Potential pre‐screening for therapeutic agents that induce differentiation in human myeloid leukemia cells
Authors: Lothm Joseph , Sachs Leo
Published: February 2007

A cultured line of human myeloid leukemic cells has been used, to test for the ability of compounds used in chemotherapy to induce partial or complete differentiation of these leukemic cells. The compounds differed in their ability to induce specific differentiation‐associated properties. Effectiveness of induction of Fc and C3 rosettes was of the order actinomycin‐D > cytosine arabinoside > mitomycin‐C > adriamycin > bromodeoxyuridine > hydroxyurea. Induction of rosettes by actinomycin‐D required a 8212‐fold lower concentration than induction by hydroxyurea. All these compounds, except bromodeoxyuridine, induced the synthesis and secretion of lysozyme with the same order of effectiveness as for rosettes, but only actinomycin‐D and to a lesser extent bromodeoxyuridine induced the formation of mature granulocytes. Vincristine induced only a small increase in lysozyme. The results indicate that actinomycin‐D was the most potent inducer of differentiation in these human myeloid leukemic cells. It is suggested that pre‐screening of individual patients for the most effective compounds that can induce differentiation of their myeloid leukemic cells in culture, may prove beneficial for treatment in a from of chemotherapy based on the induction of normal differentiation in leukemic cells.
Modulation of target cell susceptibility to human natural killer cells by interferon
Authors: Moore M. , White Wendy J. , Potter M. R.
Published: February 2007

The spontaneous cytolytic activity of human peripheral blood lymphocytes in a short‐term 51chromium release assay was markedly enhanced by pretreatment with partially purified “Namalva” lymphoblastoid (type I)interferon (IF), provided that the target cells, five lymphoblastoid cell lines of variable natural killer (NK) sensitivity (K562, Molt 4, CCRF/CEM, Raji and Bri8), were not similarly treated with IF. When the targets were pre‐exposed to comparable concentrations of IF, their susceptibility to lysis by IF‐stimulated or unstimulated effectors was diminished, while exposure of both effectors and targets to IF for the duration of the cytotoxicity assay produced levels of cytotoxicity intermediate between those obtained when either effectors or targets were pretreated. The results indicate that, depending on the experimental design, IF is capable of exerting a protective effect on certain targets, a conclusion supported by competition assays Wherein IF‐treated cold K562 cells competed less successfully than untreated cold K562 cells for lysis of their radiolabelled counterparts by both IF‐stimulated and unstimulated effectors. The data suggest that certain lymphoblastoid targets, in common with effector lymphocytes, possess receptors for IF. Some possible biological implications of the protective interaction of IF with tumour targets, which is antagonistic to that on effector cells, are discussed.
Natural killer activity of lymphoid cells isolated from human ascitic ovarian tumors
Authors: Mantovani Alberto , Allavena Paola , Sessa Cristiana , Bolis Giorgio , Mangioni Costantino
Published: February 2007

Lymphocytes and tumor cells were isolated from the carcinomatous ascites of 24 patients with epithelial ovarian tumors by stepwise application of density and velocity sedimentation on discontinuous Ficoll‐lsopaque gradients and fetal bovine serum. Tumor‐associated lymphocytes showed a lower percentage of cells with receptors for sheep erythrocytes (E) or for complement than did peripheral blood lymphocytes from the same patients. NK activity was measured, 51Cr‐labelled K562 cells being used as targets in a 20‐h assay. Tumor‐associated lymphocytes showed significant NK activity. Cytotoxicity levels were lower than for peripheral blood effector cells from the same patients, and these in turn showed significantly lower cytotoxic capacity than peripheral blood lymphocytes from 64 control subjects. Similar results were obtained when lysis was measured after 4 h of incubation. Tumor‐associated lymphocytes forming E rosettes were at least as effective as the unseparated population. When tumor‐associated lymphocytes were mixed with normal effector cells, in three of six preparations with low NK activity tested, significant inhibition of normal lymphocyte NK activity was observed. Adherent macrophages from carcinomatous ascites, which contained lymphocytes that had suppressive activity, showed no inhibitory activity. Interferon (IF) boosted the NK activity against K562 of tumor‐associated lymphocytes. Purified ovarian carcinoma cells were relatively resistant to lysis by normal lymphocytes. However, they inhibited lysis of K 562 cells in cold target competition assays, though less efficiently than K 562 itself, and were consistently lysed when effector cells were stimulated with IF. It is therefore suggested that ovarian carcinoma cells express NK‐relevant recognition structures, but are relatively resistant to cytolysis by unstimulated effector cells.
Divergent effects of macrophage toxins on growth of primary tumors and lung metastases in mice
Authors: Mantovani Alberto , Giavazzi Raffaella , Polentarutti Nadia , Spreafico Federico , Garattini Silvio
Published: February 2007

The effects of silica and carrageenan on primary tumor growth and metastases were evaluated in C57BL/6 and BALB/c mice transplanted with the poorly immunogenic Lewis lung (3LL) carcinoma, mFS6 sarcoma and Madison 109 carcinoma spontaneously metastasizing to the lungs. Silica and carrageenan significantly enhanced lung metastases and decreased primary tumor weight in all three experimental models. A similar augmentation of lung secondaries was found after i.v. inoculation of 3LL tumor cells. The effects of carrageenan on primary 3LL tumor growth and metastases were observed also in thymus‐deprived animals. The effect of macrophage toxins was studied also in C57BL/6 mice transplanted with the M5076/73A ovarian carcinoma. This tumor spontaneously metastasizes to various abdominal organs, but not to the lung. After treatment with carrageenan, lung metastases were observed, but no effect on secondaries at other anatomical sites or on the primary tumor was detectable. It is suggested that host defense mechanisms impaired by silica and carrageenan may have divergent effects in the regulation of growth of some primary tumors and spontaneous lung metastases.
Tumorigenicity and in vitro characteristics of rat liver epithelial cells and their adenovirus‐transformed derivatives
Authors: Paraskeva Christos , Gallimore Phillip H.
Published: February 2007

Cloned and uncloned epithelial cultures were established from the liver of a 3‐week‐old AS rat. These epithelial cultures were neither tumorigenic nor did they display anchorage‐independent growth. One of the clones was cytogenetically normal after 53 in vitro passages (approximately 200 population doublings after cloning). Eight transformed lines were isolated from the liver epithelial cells after infection with adenovirus type 12 (Ad‐12). Five of these produced typical Ad‐12 T‐antigen, whereas three appeared to be T‐antigen‐negative. All were tumorigenic in newborn syngeneic rats. The T‐antigen‐positive transformed lines produced anaplastic‐epithelial tumors, whereas the T‐antigen‐negative transformed lines produced adenocarcinomas. Although all the transformed lines were tumorigenic, some were fibronectin‐positive while others produced no detectable fibronectin. The normal (untransformed) epithelial cells produced fibronectin. These results are interesting for two reasons: (1) there are relatively few reports of fibronectin on epithelial cells and (2) they emphasize the view that there is no absolute correlation between reduced fibronectin and tumorigenicity in transformed cells. The transformed lines displayed in vitro characteristics similar to those of transformants derived from embryonic and fibroblastic cell strains, notably, increased saturation density and changes in cellular morphology. Some of the transformed cell lines, but not all, displayed anchorage‐independent growth. All the transformed cell lines were picked from multi‐layered foci so that morphological criteria (i.e. piling‐up focus) for isolating transformants from the epithelial cultures were similar as in embryonic and fibroblastic transforming cell systems. With the new cell system we have developed we can, using the same epithelial cell line (clone C3), study both virus transformation and virus mutagenesis.
Oncogenicity of gibbon type‐C myelogenous leukemia virus
Authors: Kawakami Thomas G. , Kollias George V. , Holmberg Charles
Published: February 2007

Young gibbons that were experimentally inoculated with cell‐free gibbon ape leukemia virus (GaLV) and developed peristent viremia subsequently developed chronic granulocytic leukemia (CGL) with associated multifocal bone lesions and metastases. An 8‐month‐old gibbon inoculated with 105 tissue culture infectious virus (TCIV) developed acute myeloproliferative disease with associated bone lesions after a latency of 5 months, while a 9‐month‐old gibbon inoculated with 103 TCIV developed CGL after an II‐month latency. The clinical symptoms associated with the onset of leukemia were an increased number of leukocytes which were predominantly mature granulocytes, development of anemia, and multifocal bone lesions. Terminally, the animals had elevated immature granulocytes in the blood, cellular bone marrow with a predominant number of immature granulocytes, and hepatosplenomegaly. The gibbon with CGL had metastatic growth in the spleen and lung. Two 14‐month‐old gibbons that were inoculated with 103 TCIV and developed persistent neutralizing antibody to the virus infection remained free of hematopoietic disease, as did uninoculated animals. The fact that only animals with persistent viremia developed leukemia supports the oncogenicity of GaLV in gibbons.
Effect of horse antibody to rat alpha‐fetoprotein upon the growth of AH‐66 in donryu rats
Authors: Wepsic H. T. , Tsukada Y. , Takeichi N. , Nishi S. , Hirai H.
Published: February 2007

Studies were undertaken to evaluate whether the intraperitoneal administration of horse antibody to rat alpha‐fetoprotein (HabRatAFP) would inhibit or prevent the growth of AH‐66 tumor cells inoculated into Donryu male rats. In animals inoculated with tumor subcutaneously there was 100% tumor growth in uninjected control animals and the administration of HabRatAFP prevented tumor growth in 7/24 (29%) of the animals. When animals were inoculated with tumor intraperitoneally, the inhibition of tumor growth by Hab‐RatAFP only occurred at tumor‐cell doses of 50,000, 10,000, and 5,000. In these three groups, 15/35 (43%) of those animals treated with Hab‐RatAFP did not develop tumor whereas 1/36 (3%) of the normal horse‐serum treated animals did not develop tumor. The majority of those animals which were cured of their tumors by Hab RatAFP treatment resisted tumor rechallenge. Studies were done to elucidate the mechanisms responsible for the anti‐tumor effect of HabRatAFP. AH‐66 tumor cells which were placed into millipore chambers, implanted intraperitoneally, were killed by the intraperitoneal administration of HabRatAFP. Studies were conducted to see if treatment with HabRatAFP to rat AFP might increase the immunogenicity of an inoculum of X‐irradiated tumor cells. In one experiment, no animals which received only X‐irradiated tumor cells resisted tumor rechallenge with 5 × 106 tumor cells whereas 6/11 (54.5%) of those animals which received X‐irradiated tumor cells and treatment with HabRatAFP resisted tumor rechallenge.
Detection of bovine leukemia virus antigen in urine from naturally infected cattle
Authors: Gupta Phalguni , Ferrer Jorge F.
Published: February 2007

A competitive radioimmunoassay was used to detect the major internal protein (p25) of bovine leukemia virus (BLV) in urine from infected cattle. Whole urine samples from six out of seven infected cattle were found to contain the BLV p25 antigen. Analysis of different fractions of urine indicated that p25 was present in a soluble form as well as in the high‐speed pellet, but not in the low‐speed pellet. Similar results were obtained with urine samples collected from a BLV‐infected cow by catheterization of the bladder.
Incidence of childhood leukemia in shanghai
Authors: Li Frederick P. , Jin Fan , Tu Chi‐Tao , Gao Yu‐Tang
Published: February 2007

Data of the Shanghai Tumor Registry were examined for incidence rates of leukemia among children, ages 0–14 years. Between 1972 and 1978, leukemia developed in 344 children; 175 (52%) had acute lymphocytic leukemia. The incidence rates were 4.5 per 100,000 boys and 3.3 per 100,000 girls. The incidence of leukemia peaked between 2 and 7 years of age.
Establishment and characterization of a new leukaemic T‐cell line (Peer) with an unusual phenotype
Authors: Ravid Zohar , Goldblum Natan , Zaizov Rina , Schlesinger Michael , Kertes Tamar , Minowada Jun , Verbi Winston , Greaves Melvyn
Published: February 2007

We report the isolation and establishment in continuous culture of a human lymphoid cell line (Peer) from a case of T‐leukemia. The Peer cell line lacks some typical cell‐surface properties of T cells, namely sheep erythrocyte rosette formation and reactivity with two anti‐T‐cell sera, but has focal acid phosphatase and does express two other T‐cell antigens, one defined by a monoclonal antibody, the other related to a T‐cell subset (TH2). The cells are negative for B‐cell markers (Smlg or cytoplasmic μ Fcγ and C3 receptors, mouse erythrocyte rosettes) and EBV (EBNA). In addition, the Peer cell does not possess the typical phenotypic markers of “non‐B, non‐T” leukemia: cALL and la‐like antigens, and the cytoplasmic hexosaminidase isoenzyme I, but is positive for terminal deoxynucleotidyl transferase by enzymatic and immunofluorescent criteria. The cell line requires exogenous L‐asparagine for adequate growth in culture, a property known to be characteristic of certain T cells but not of B cells. The Peer cell line appears to have a maturation arrest at a developmental stage intermediate between the cortical thymocyte and a mature T‐cell subset and to have lost some T‐cell differentiation features.
Surface immunoglobulins on Burkitt's lymphoma biopsy cells from 91 patients
Authors: Gunvén Peter , Klein George , Klein Eva , Norin Torsten , Singh Surjit
Published: February 2007

One hundred and fourteen biopsies from 91 cases of African Burkitt's lymphoma were examined by immunofluorescence methods for the presence of surface‐associated mu, gamma, delta, kappa and lambda chains, as well as for the Fc region of gamma chains and for βic. Only 5% of the biopsies were surface‐Ig‐negative; 18% were negative for mu chains and 61% for gamma chains. Delta chain staining was absent, or borderline in a few tumors. Mu chains, gamma chains in a few highly reactive tumors and, in many cases, the predominant light chain seemed to be clonal markers. They gave no convincing evidence of more than one cell clone, either within single tumors or within syn‐ or metachronous tumors in one individual. Gamma chains in moderately stained tumors, Fc and βic correlated with each other and the first two reactivities decreased after incubation at low pH, indicating that their presence resulted from outside coating of the cells. The results indicated that one clone of B cells is involved in Burkitt's lymphoma in the large majority of cases. This clone is in a state of differentiation at which surface delta chains are not expressed. No prognostic information resulted from the analysis of the markers studied.
A prospective study on the development of hepatocellular carcinoma from liver cirrhosis with persistent hepatitis B virus infection
Authors: Obata Hiroshi , Hayashi Naoaki , Motoike Yoji , Hisamitsu Toju , Okuda Hiroaki , Kobayashi Seiichiro , Nishioka Kusuya
Published: February 2007

We made a prospective study on the development of hepatocellular carcinoma (HCC) in patients with liver cirrhosis with hepatitis B virus infection from April, 1973 to December, 1977. Seven out of 30 patients (23%) with hepatitis B surface antigen (HBsAg)‐positive cirrhosis developed HCC. On the other hand, only 5.9% of the patients with HBsAg‐negative liver cirrhosis developed HCC. These patients were classified into three groups according to their anti‐HB core (anti‐HBc) titers. When the anti‐HBc titer, expressed as a dilution of serum, was 210 or more (Group I),20‐24 % of the liver cirrhosis patients developed HCC either with or without a detectable amount of HBs Ag present in the sera. When the anti‐HBc titer was 29 or less (Group II), only 0–5.7% developed HCC. There was no significant difference between this and the anti‐HBc and HBsAg‐negative group (Group III), which was 4.4%. In five individual cases from group I, HBsAg was detected in serum, and in biopsies of liver cells, before HCC could be detected by angiography and/or rising levels of alphafetoprotein (AFP).In all of these cases, the anti‐HBc titer was higher than 210 throughout the observation period, even before the development of HCC. These findings indicate that active virus proliferation in chronic hepatitis B virus infection precedes the development of HCC as indicated by a higher anti‐HBc titer. Therefore we have prepared these studies to show the pathogenic role of hepatitis B virus in the development of hepatocellular carcinoma.
Restricted expression of endogenous N‐Tropic XC‐positive leukemia virus in hybrids between G and AKR mice: An effect of the Fv‐4r gene
Authors: Odaka Takeshi , Ikeda Hidetoshi , Akatsuka Toshitaka
Published: February 2007

G mice carrying the Fv‐4r gene are resistant to exogenous infections of various strains of ecotropic MuLVs (Suzuki, 1975). The expression of endogenous N‐tropic XC‐positive virus was studied in the progency of a cross between G and AKR mice. In the F1, mice, the virus expression was almost completely supressed, and no leukemia developed during I year of observation. Results of successive backcrossings with AKR mice indicated that a single dominant gene, the Fv‐4r, suffices for supression. It can be concluded that the extensive growth of N‐tropic XC‐positive virus is a prerequisite for leukemia development in AKR mice.
Separation of different molecular forms of macrophage‐ and granulocyte‐inducing proteins for normal and leukemic myeloid cells
Authors: Lotem Joseph , Lipton Jeffrey H. , Sachs Leo
Published: February 2007

It is shown that serum of mice treated with endotoxin (ES) contains three separable and functionally distinct forms of macrophage‐ and granulocyte‐inducing (MGI) proteins. One form (MGI‐IM) induced the formation of macrophage colonies from normal bone‐marrow cells and showed on gel filtration an apparent molecular weight of 300,000; a second form (MGI‐IG) induced the formation of granulocyte colonies from normal bonemarrow cells and had an apparent molecular weight of 45–100.000; and the third form (MGI‐2) induced the normal differentiation of MGI+D+ myeloid leukemic cells to macrophages and granulocytes and had an apparent molecular weight of 28,000. Studies on the time course of the decrease of these three activities in ES have indicated that MGI‐2 was more readily inactivated in vivo than MGI‐IM and MGI‐IG. The MGI‐IM in ES isolated after gel filtration was completely neutralized by an antiserum to MGI‐I from mouse L‐cells, whereas the isolated MGI‐IG and MGI‐2 were not affected by this antiserum. Gel filtration under dissociating conditions (6 M guanidinium chloride) resulted in a reduction of the apparent molecular weights of MGI‐IM from 300,000 to 42,000, and of MGI‐IG from 45–100,000 to 28,000, while it produced no change in the 28,000 apparent molecular weight of MGI‐2. Similar studies with conditioned medium produced in vitro from mouse lung and peritoneal macrophages showed that in these conditioned media, MGI‐I (both G and M) in the native form had an apparent molecular weight of 41,000 and MGI‐2 of 24,000, and that both MGI‐I and 2 had an apparent molecular weight of 24,000 under dissociating conditions. The results indicate that MGI‐I exists in serum in vivo and in these conditioned media as aggregated proteins, whereas MGI‐2 does not, and that macrophages and lung tissue are not the only source of the MGI proteins found in ES. It is suggested that all three forms of MGI activity are derived from one precursor protein; that only the MGI‐2 form assayed on leukemic cells should be used for treatment based on the induction of normal cell differentiation in myeloid leukemia; and that MGI‐2 may serve as a survey mechanism for inducing differentiation in myeloid leukemic cells that have lost their responsiveness to the MGI‐I molecules that control the viability, proliferation and differentiation of normal myeloblasts.
Quantitation of extracts containing tumour angiogenesis factor (TAF) by radioimmunometric and radioimmunoassays
Authors: Schor Ana M. , Kumar S. , Phillips P. J.
Published: February 2007

An antiserum which is able to inhibit TAF‐induced neovascularization in vivo(TAF antiserum) was used to develop two quantitative assays for TAF‐containing tumour extracts (tumor TAF).I) Radioimmunometric assay (RIMA): the IgG of the TAF antiserum was labelled with 125I. An excess of 125I‐IgG was incubated with increasing concentrations of tumour TAF and the antigen‐bound fraction was precipitated by addition of Clq. 2) Radioimmunoassay (RIA): an excess of iodinated antigen (tumour TAF) was incubated with TAF antiserum diluted so that binding in the absence of unlabelled antigen represented 70–40% of the maximum binding. When tumour TAF was added, competition between labelled and unlabelled antigen for the TAF antibody binding sites resulted in displacement of the former by increasing concentrations of the latter. A second antibody was used to precipitate the bound labelled antigen. Of the two assays, the RIMA was the more sensitive and, due to the lack of a purified antigen, allowed standardization of the results in a more accurate manner. Our data show that there was a good correlation between the ability of tumour TAF to induce angiogenesis in vivo and the degree of antiserum binding detected in vitro by both assays. Preparations containing TAF, whatever the source (i.e. human or animal tumours or tissue culture) shared common antigenic determinants. It is suggested that the quantitative assays should prove valuable in determining the clinical relevance of TAF as a tumour marker.
Tumor metastases and cell‐mediated immunity in a model system in DBA/2 mice X. Immunoselection of tumor variants differing in tumor antigen expression and metastatic capacity
Authors: Schirrmacher V. , Bosslet K.
Published: February 2007

We previously described morphological, functional and antigenic differences between a chemically‐induced DBA/2 lymphoma, Eb, and a spontaneous variant, ESb, which arose in 1968 and had highly increased metastatic capacity. Now we present evidence that the two cell lines, in spite of the differences observed, are still related. (I) Shifts from Eb to ESb can be reproduced after II years. They occur during routine i.p. transplantation, especially when high cell numbers are passaged. (2) ESb variant cells can be recovered from Eb tumor populations after immunoselection in vivowith specific anti‐Eb cytolytic T lymphocytes (CTL).(3) Parental‐type Eb cells can be isolated from ESb tumor populations after immunoselection in vitro with specific anti‐ESb CTL Ten ESb cells mixed with 106Eb cells and inoculated s.c. caused a shift in the mortality curve suggesting that a possible contamination of the Eb population with preexisting ESb variant cells was less than I in 100,000.
Cytogenetic studies on abelson‐virus‐induced mouse leukemias
Authors: Klein George , Ohno Shinsuke , Rosenberg Naomi , Wiener Francis , Spira Jack , Baltimore David
Published: February 2007

The karyotype of Abelson‐virus‐induced murine leukemias was studied by G‐banding. In contrast to the regular trisomy of chromosome 15 in most murine T‐cell leukemias, Abelson leukemias were purely diploid, and remained diploid for up to seven consecutive passages in vivo. The hypothesis is advanced that integration into the recipient cell of the DNA copy of the large cellular insert, carried by the Abelson virus, may perform a function similar to the effects of gene duplication by trisomy in the more slowly developing murine leukemias.
In vivo splenic irradiation eradicates suppressor T‐cells causing the regression and inhibition of established tumor
Authors: Enker Warren E. , Jacobitz Janet L.
Published: February 2007

Splenic irradiation has been employed in tumor‐bearing animals to eradicate non‐specific, spleen‐seeking suppressor T cells, and to inhibit established tumor growth. MC1315 tumor‐bearing BALB/c mice were treated with 400 R splenic irradiation. Untreated mice or mice receiving 400 R splenic irradiation plus reconstitution with syngeneic spleen cells served as controls. Statistically significant inhibition of tumor growth, regression of established lethal tumor, and the disappearance of suppressor cell activity from the spleens of tumor‐regressed mice were observed. Tumor growth inhibition was statistically significant at the p < 0.001 level. We postulate that non‐specific, spleen‐seeking, radiation‐sensitive suppressor T cells are in a large measure responsible for mediating progressive tumor growth. By taking advantage of their radiosensitivity and by exploiting their spleen‐seeking nature, we have achieved significant regression of established tumor in up to 50% of the animals treated. These findings lend further support to the role of suppressor cells in abrogating anti‐tumor immunity, and suggest that their manipulation may have potential implications for the design of human adjuvant therapy.
Changes in the expression of two Epstein‐Barr virus‐associated antigens, EBNA and RANA, during the cell cycle of transformed human B lymphoblasts
Authors: Slovin Susan F. , Vaughan John H. , Carson Dennis A.
Published: February 2007

Two methods of cell synchronization, density‐dependent arrest and double thymidine block, were used to assign two Epstein‐Barr virus‐associated antigens to different parts of the growth cycle of the human B lymphoblastoid cell lines, WI‐L2 and Raji. The Epstein‐Barr nuclear antigen (EBNA), as detected by anti‐complement immunofluorescence, was maximally expressed during early S phase, decreased during the G2 and M phases, and was absent in early G1. In contrast, the rheumatoid arthritis nuclear antigen (RANA), as detected by anti‐immunoglobulin immunofluorescence with a prototype serum from a patient with rheumatoid arthritis, was maximally expressed during early G1 phase, progressively decreased during S and early G2, and reappeared during late G2/M.
Lymphocytes that mediate systemic resistance to in vivo growth of a carcinogen‐induced syngeneic tumor
Authors: Crum E. D.
Published: February 2007

Wistar rats immunized with irradiated syngeneic methylcholanthrene‐induced sarcoma, Mc7, are able to suppress a subsequent challenge of this tumor. Cells obtained from thoracic‐duct lymph of these tumor‐immunized animals and infused intravenously into normal syngeneic rats transfer specific tumor resistance to the recipients. These mediators of tumor resistance have the characteristics of T lymphocytes that are in a non‐proliferating state and have an effective life span of at least 2 weeks in normal recipient rats.
Induction of transplantation immunity to rat colon carcinoma isografts by implantation of intact fetal colon tissue
Authors: Hedlund G. , Sjögren H. O.
Published: February 2007

The objective of this study was to demonstrate whether intact fetal colon tissue can induce immunity to large‐bowel cancer isografts. Adult rats were immunized against fetal antigens by implantation of mitomycin‐C‐treated intact fetal colon tissue beneath the renal capsule. Control animals received implants of pieces of intact adult colon tissue. Kidneys containing the implants were removed after 3 or 5 weeks and the rats were challenged with isografts of a 1,2‐dimethylhydrazin (DMH)‐induced colon carcinoma. Significant inhibition of tumor growth was observed in immunized groups compared to controls. The present results indicate that some embryo‐fetal antigens expressed in intact colon tissue of 13 to 15‐day‐old fetuses are also expressed in colon carcinoma cells and can act as transplantation antigens.
Development of carcinogen‐induced skin tumors in mice with varied states of immune capacity
Authors: Outzen Henry C.
Published: February 2007

The incidence of tumor formation in MCA‐treated skin grafted onto maximally immunosuppressed mice that had been restored to varying extents with normal spleen cells was significantly greater in the mice with intermediate immune capacities than in those that had either minimal or maximal capacities. A similar biphasic tumor incidence curve was observed when MCA‐treated skin was grafted onto mice of varying immune capacities, produced by thymectomy and varying doses of whole‐body irradiation. Significantly more tumors occurred in the mice given moderate doses of irradiation than in those given higher or lower doses. That both of these procedures were actually able to induce discrete levels of immunocompetence was demonstrated by measuring skin allograft rejection times. The immunomodulated mice were observed to have skin graft rejection times which strongly correlated with the number of immunologically competent spleen cells transferred into them. The outgrowth potential of syngeneic normal mammary epithelial cells grafted into cleared mammary fat pads was similar in both immunologically altered and normal control mice, showing that immunoaltered and normal control mice were equally able to support the growth of transplanted normal tissues. These results, which conform with the predictions of the immunostimulation hypothesis, suggest that the immune response is able to stimulate as well as inhibit oncogenesis.
Human lymphocyte/human erythrocyte rosettes. I. Blood “H” rosettes are high‐affinity E‐rosette‐forming T lymphocytes occurring in high frequency
Authors: Gallinger Lucy A. , Pross H. F. , Baines M. G.
Published: February 2007

Human lymphocytes will rosette with human red blood cells under certain conditions (H rosettes). The work presented in this paper documents the following: (1) a reproducible short‐term assay for the detection of H rosettes in proportions similar to those reported recently in the literature (25–30%); (2) technical improvements on the basic assay system demonstrating that, in fact, 40–65% of human lymphocytes form H rosettes; (3) the fact that, in normal donors, auto and allo H rosettes are formed by identical lymphocyte subpopulations; (4) that H rosettes are formed independently of the ABH, Rh and Thomsen‐Freidenreich (TF) red‐cell antigens on the indicator red cells; and (5) that H rosette‐forming cells consist almost entirely of T lymphocytes having high‐affinity receptors for sheep erythrocytes. The large difference in size between sheep and human RBC made it possible to do double rosette assays in which high‐and low‐affinity E‐rosette‐forming T cells could be visualized on the same slide. As with T lymphocytes in general, a large proportion of HRFC was found to have Fc‐IgM receptors while a smaller proportion has Fc‐IgG receptors. Studies done on a small group of leukemic patients supported the T‐cell nature of the H rosette‐forming cell.
Epstein‐Barr virus‐related serology in marrow transplant recipients
Authors: Lange Beverly , Henle Werner , Meyers Joel D. , Yang Lily C. , August Charles , Koch Penelope , Arbeter Allan , Henle Gertrude
Published: February 2007

Serial sera from 50 marrow transplant recipients were examined for their spectra and titers of antibodies to EBV‐specific antigens. Immediately before or after transplant, blood products passively transferred antibodies to EB viral capsid antigen (VCA) and EBV nuclear antigen (EBNA). In most recipients, passively‐transferred antibodies were replaced by endogenous antibodies regardless of whether donor or recipient had EBV antibodies before transplantation. Commencement or resumption of endogenous EBV antibody production was not associated with signs of infectious mononucleosis or heterophil antibody responses. Antibodies to VCA rose to abnormally high titers, followed successively by antibody to early antigens (EA), and disproportionately low levels of anti‐EBNA. Unusually high anti‐VCA and anti‐EA levels persisted when tests of immune function returned to normal. Antibodies to other herpes group viruses showed no consistent changes. We conclude that (1) EBV does not cause significant clinical problems in marrow transplant recipients; (2) persistent EBV infection can become established or reestablished in the presence of antibodies to EBV; (3) marrow transplant recipients show the same exaggerated immune response to EBV as other immunodeficient patients; and (4) the pattern of EBV‐specific antibodies may be a more sensitive measure of defective cell‐mediated immunity than most conventional tests of immune function.
Difficulties encountered in the application of clark classification and the Breslow thickness measurement in cutaneous malignant melanoma
Authors: Prade M. , Sancho‐Garnier H. , Cesarini J. P. , Cochran A.
Published: February 2007

The purpose of this study was to analyse the reproducibility of Clark's classification and Breslow's measure of tumor thickness to determine if there is general agreement among pathologists regarding these parameters and whether these pathologists reach consistent conclusions concerning each slide. Three successive workshops including a panel of pathologists were held at Amsterdam, in May 1977; at Villejuif in June 1977, followed by circulation of slides and at Villejuif again, in June 1978, followed by slide projection. This was necessary because of the great divergencies of opinion noted at the first meeting at Amsterdam. These sessions gave a better understanding of the divergencies and finally indicated that general agreement could only be reached by slide presentation followed by discussion. Regarding histogenesis, agreement between pathologists was improved after discussion from 6/11 cases to 11/13 cases. Regarding the level, no initial agreement was reached (Amsterdam). At the second meeting an agreement was obtained in 4/13 cases and finally in 11/13 cases (Villejuif). Clark's classification is more difficult to use than Breslow's because it depends on a discontinuous variable, the choice of the infiltration level. Breslow's classification, on the other hand, is based on a continuous variable. Because of frequent discrepancies, the classification of patients into various therapeutic groups according to Clark's level and Breslow's thickness necessitates that all cases included in therapeutic trials be reviewed by a panel of pathologists.
Establishment and characterization of a human acute monocytic leukemia cell line (THP‐1)
Authors: Tsuchiya Shigeru , Yamabe Michiko , Yamaguchi Yoshiko , Kobayashi Yasuko , Konno Tasuke , Tada Keiya
Published: February 2007

A human leukemic cell line (THP‐1) cultured from the blood of a boy with acute monocytic leukemia is described. This cell line had Fc and C3b receptors, but no surface or cytoplasmic immunoglobulins. HLA haplotypes of THP‐1 were HLA‐A2, ‐A9, ‐B5, ‐DRW1 and ‐DRW2. The monocytic nature of the cell line was characterized by: (1) the presence of α‐naphthyl butyrate esterase activities which could be inhibited by NaF; (2) lysozyme production; (3) the phagocytosis of latex particles and sensitized sheep erythrocytes; and (4) the ability to restore T‐lymphocyte response to Con A. The cells did not possess Epstein‐Barr virus‐associated nuclear antigen. These results indicate that THP‐1 is a leukemic cell line with distinct monocytic markers. During culture, THP‐1 maintained these monocytic characteristics for over 14 months.
Use of the macrophage migration inhibition test to evaluate antigenic differences in golden hamster transplantable melanomas
Authors: Kozlowska Krystyna , Zurawska‐Czupa Barbara , Mierzewski Piotr , Kostulak Alicja
Published: February 2007

Macrophage migration inhibition test in the presence of melanotic and amelanotic melanoma cells was analyzed by means of signal detection theory reasoning. The cellular immune response as measured by MMI test was stronger in hamsters grafted with amelanotic melanoma. A statistical analysis indicated that the amelanotic melanoma antigenic strength was greater than that of its melanotic counterpart.
Some effects of products from necrotic regions of tumours on the in vitro migration of cancer and peritoneal exudate cells
Authors: Turner Graham A. , Weiss Leonard
Published: February 2007

The invasion of normal tissues by cancer cells and the infiltration of tumours by macrophages to some degree involves active translatory movements by these cells. As necrosis is a common occurrence in solid tumours, we have studied the interactions of saline extracts from the necrotic regions of rat Walker‐256 tumours and mouse Gardner lymphosarcomas on the transmembrane, in vitro migration of Walker and Gardner cancer cells, and rat and mouse peritoneal macrophages. Necrotic extracts enhanced cell migration independently of chemotactic activity, an effect which was partially reduced by Trasylol, an inhibitor of neutral proteases. Rat liver lysosomal preparations which contain lower levels of neutral proteases than necrotic extract, inhibited or had no effects on cell migration, and the lysosomal stabilizer hydrocortisone did not inhibit the action of necrotic extracts. The results indicate that necrosis may enhance the migration of cancer cells out of tumours and the migration of macrophages into them. The extracts act partially through their neutral protease content. In contrast to the enhancement of cell detachment by necrotic extracts, which previous work has shown to be partially mediated by their indirect effect in causing lysosomal labilization and which is partially inhibited by hydrocortisone, this indirect mechanism is not demonstrable in the enhancement of cell migration. The results indicate that the consequences of necrosis are worthy of consideration in attempts at understanding the biology of solid tumours.
Evolution of cultured leukemic cell lines monitored by chromosomal and immunologic analysis
Authors: Hozier John , Lindquist Leanna , Hurwitz Richard , Lebien Tucker , Kersey John
Published: February 2007

We have investigated the karyotypes and markers of B lymphocyte differentiation in two leukemic cell lines, NALM‐6‐B and NALM‐6‐MI, both derived from a patient with non‐T, non‐B acute lymphoblastic leukemia. Both possess characteristics of thymus‐independent, bursalequivalent (B) lymphocytes. By means of immuno‐fluorescence techniques, NALM‐6‐B was shown to possess 47% surface membrane immunoglobulin‐positive (Slg+) cells, while NALM‐6‐MI is surface membrane imunoglobulin‐negative (Slg−), but does possess cytoplasmic immunoglobulin M (ClgM+) in more than 90% of the cells. The Slg− ClgM+ phenotype, coupled with morphologic features, is consistent with NALM‐6‐MI being arrested at a stage early in B‐lymphocyte differentiation (a “pre‐B” cell). The predominant banded chromosome karyotype of NALM‐6‐B is pseudodiploid with a translocation of chromosomal material from the long arm of a chromosome 5 to the short arm of a chromosome 12 (5q−/12p+) and a marker Y chromosome. NALM‐6‐MI possesses the same marker Y chromosome and a deletion of the long arm of chromosome 5 (5q−) since in most cells material missing from chromosome 5 does not appear on the short arm of chromosome 12. Within the limits of resolution available with the banding technique, no other karyotypic differences are observed in the two cell lines. The history of the two cell lines, the karyotypic analysis, and the pattern of immunoglobulin markers indicate the possible clonal evolution of NALM‐6‐MI from NALM‐6‐B and implicate a portion of the long arm of chromosome 5 in lymphoid differentiation of these leukemic cell lines.