bluuebunny/crossref_metadata_2025 huggingface dataset:
Interleukin‐10 production by a B‐cell line derived from human post‐transplant lymphoproliferative disease
Authors: Randhawa Parmjeet , Nalesnik Michael , Demetris Jake , Zeevi Adriana
Published: February 2007

Interleukin‐10 (IL‐10) is a cytokine known to regulate growth and differentiation in activated human B cells. We studied IL‐10 production in a B‐cell line derived from Epstein‐Barr virus associated post‐transplant lymphoproliferative disease (PTLD). Reverse transcriptase polymerase chain reaction (RTPCR) demonstrated IL‐10 mRNA within the cells. Transcripts of the virally encoded homologue BCRF‐1 were not detected. ELISA assays demonstrated translation of IL‐10 message into the corresponding cytokine, and its subsequent secretion into the culture medium. The rate of 3H‐thymidine incorporation by the PTLD cells was not affected by immunologic neutralization of the secreted cytokine, or, by addition of exogenous recombinant IL‐10 to the culture medium. Thus, IL‐10 does not have an autocrine growth regulatory role in this PTLD line.
IL6 and IL6 receptor expression in Burkitt's lymphoma and lymphoblastoid cell lines: Promotion of IL6 receptor expression by EBV
Authors: Klein S. C. , Jücker M. , Abts H. , Tesch H.
Published: February 2007

We have analysed a panel of different Burkitt's lymphoma (BL) and lymphoblastoid cell lines (LCLs) for the expression of IL6 and IL6 receptor (IL6R). Epstein‐Barr‐Virus (EBV) positive or negative BL cell lines and the corresponding lymphoblastoid cell lines (LCL), derived from EBV immortalized mononuclear cells of the BL patients, were tested for the expression of IL6 mRNA and protein by Northern blot experiments and ELISA, and for the expression of the IL6R mRNA and protein by Northern blot Reverse Transcriptase‐Polymerase Chain Reaction (RT‐PCR) and flow cytometry. Our results demonstrate that six out of 19 Burkitt's lymphoma cell lines produced IL6 constitutively. All three cell lines infected with the EBV substrain B95‐8 (B95‐8 convertants) produced IL6, in contrast to the original EBV negative lines and to the cell lines infected with the EBV substrain P3HR1 (P3HR1 convertants). The produced IL6 was biologically active as shown by proliferation of the IL6 dependent cell line TEPC 1033 C2. The two BL cell lines with the highest level of IL6 production (190 pg/ml and 550 pg/ml) expressed in addition IL6R molecules on the cell surface. Monoclonal antibodies directed against IL6 did not inhibit the growth of these two BL cell lines, thus excluding autocrine stimulation in these lines. IL6R expression could be further demonstrated in all LCLs analysed, in five out of seven EBV positive BLs and two out of three B95‐8 convertants, but only in one out of the six EBV negative BL cell lines. Our results suggest that EBV in immortalized B cells and in Burkitt's lymphoma cells can promote IL6 receptor expression.
Prognostic factors for primary gastrointestinal lymphoma
Authors: Liang Raymond , Todd David , Chan T. K. , Chiu Edmond , Lie Albert , Kwong Yok‐Lam , Choy Damon , Ho Faith C. S.
Published: February 2007

The gastrointestinal tract is a common primary extranodal site for non‐Hodgkin's lymphoma. There is however no uniform consensus on its pathological classification, clinical staging system and management. This paper reports the experience in the management of 425 Chinese patients with primary gastrointestinal lymphoma in Hong Kong from January 1975 to June 1993. There were 230 (54 per cent) males and 195 (46 per cent) females. Their median age was 53 years. The primary sites were: the esophagus in three (1 per cent), stomach in 238 (56 per cent), small intestine in 131 (31 per cent) and large intestine in 53 (12 per cent). According to the Working Formulation, there were 20 (4.7 per cent) small lymphocytic, 10 (2.4 per cent) follicular small cleaved cell, 15 (3.5 per cent) follicular mixed, five (1.2 per cent) follicular large cell, 40 (9.4 per cent) diffuse small cleaved cell, 50 (12 per cent) diffuse mixed, 181 (43 per cent) diffuse large cell, 30 (7.1 per cent) immunoblastic, five (1.2 per cent) lymphoblastic, 10 (2.4 per cent) diffuse small non‐cleaved cell and 50 (14 per cent) unclassifiable lymphoma. Immunophenotyping was performed in 199 (47 per cent) patients: 90 per cent B‐cell, 7 per cent T‐cell and 3 per cent uncertain. According to a Manchester system, 81 (19 per cent) patients had stage I disease, 44 (10 per cent) stage II, 85 (20 per cent) stage III and 215 (51 per cent) stage IV. B symptoms were present in 275 (65 per cent) patients and bulky disease in 104 (25 per cent). Surgery followed by chemotherapy was the mainstaly of treatment. Of the 408 patients treated, 63 per cent had a complete remission with relapse rate of 42 per cent. For those with complete remission, 47 per cent were free from disease at 5 years. The overall median survival of all patients was 45 per cent at 5 years. Multivariate analysis revealed that significant independent prognostic factors predicting better survival were young age of <60 years, low grade histology, stage I and II disease and absence of bulky tumour. For gastric lymphoma, aggressive surgery did not significantly improve their outcome. Chemotherapy appears to play an important role in the management of gastrointestinal lymphoma. Better classification of the primary gastrointestinal lymphoma and more refined stratification of the patients according to the prognostic variables my allow individualization of treatment. Prospective randomized studies are essential to define the relative roles of surgery, chemotherapy and radiotherapy.
Identification of chromosomal rearrangements in the human myeloid leukemia cell line GF‐D8 by dual‐colour fluorescence in situ hybridization
Authors: Doneda Luisa , Biondi Andrea , Rambaldi Alessandro , Larizza Lidia
Published: February 2007

Fluorescence In Situ Hybridization (FISH) studies with chromosome‐specific libraries and repetitive probes were performed on the human acute myeloid leukemia cell line GF‐D8 in order to define the complex chromosomal rearrangements observed by conventional cytogenetic analysis. Two‐colour FISH with whole chromosome painting probes 8 and 11 showed that the add(8) chromosome had an 11‐derived region inserted at q24, whereas the add(11) chromosome had an 8‐derived region translocated onto q23. It also demonstrated that no normal chromosome 11 is present in GF‐D8 cells, since a translocation involving chromosomes 11 and 17q was detected in addition to the add(11). The der(7) chromosome with extra material in its long arm, identified by QFQ and GTG banding, turned out to have a chromosome 15‐derived segment translocated to q22. The deletion of 7q was proved to be interstitial, as the 7q‐specific telomere as well as a tiny 7‐specific band were observed on an unknown chromosome. Fine mapping of the breakpoints involved in the multiple chromosomal rearrangements of the GF‐D8 cell line might provide insights into the mechanisms of myeloid leukaemogenesis.
Cell kinetic analysis of non‐Hodgkin's lymphomas using in vivo iododeoxyuridine incorporation and flow cytometry
Authors: Erlanson Martin , Lindh Jack , Zackrisson Björn , Landberg Göran , Roos Göran
Published: February 2007

The aim of this study was to analyse dynamic cell proliferation parameters in non‐Hodgkin's lymphomas. Sixty‐one patients with newly diagnosed or with recurrent disease were given iododeoxyuridine (IdUrd) intravenously near 4 h prior to tumour biopsy. After staining with an IdUrd reactive antibody and propidium iodide, S‐phase fraction (SPF), labelling index (LI), S‐phase duration time (Ts) and potential tumour doubling time (Tpot) were determined by flow cytometry. Thirty‐eight samples, 15 low grade (LGM) and 23 high grade (HGM) malignant lymphomas, were possible to evaluate. Twenty‐three cases were excluded due to aneuploidy, insufficient amount of material or technical problems.

Tpot values varied between 0.8–32.9 days (mean 7.0 days). HGM lymphomas had shorter mean Tpot times than LGM lymphomas (4.8 versus 10.4 days, p=0.05). For Ts the range was 4.2–20.1 h (mean 9.1 h), and a difference between the two histological groups was demonstrated with a longer mean Ts for HGM compared with LGM cases (10.0 versus 7.8 h, p=0.04). Tpot showed a negative correlation with SPF (P=0.003), and Ts demonstrated a positive correlation to SPF (p=0.02). The clinical significance of the dynamic cell proliferation parameters studied remains to be clarified, but the interelationships between Ts/SPF and Ts/morphologic subtype might be factors of interest for future prognostic studies in malignant lymphomas.
Temperature drop analysis of the thruster in a space cryogenic environment
Authors: Xiao Ze‐Juan , Cheng Hui‐Er , Zhou Hong‐Ling , Huang Rui‐Sheng
Published: February 2007

Based on the conservation of energy, a coupling heat‐transfer physical model and a set of mathematical equations are put forward to calculate the main components of the thruster, including the capillary injection tube, the aggregate organ, the injection plate, and the bracket when they are exposed to a space cryogenic environment. The typical temperature drop course of a 10N monopropellant thruster has been calculated by this computational model. The calculation results agree well with test data in a vacuum cryogenic simulation experiment performed on the ground. The temperature of the injection tube provides the thermal boundary conditions for the propellant temperature drop calculation while flowing through it. This provided the criterion to judge whether the propellant freezes or not. The upper stage has no air conditioning, so the injection tube is a weak link for the cryogenic reliability work of the thruster. This is considered one of the most important areas of the whole for reliability research. © 2007 Wiley Periodicals, Inc. Heat Trans Asian Res, 36(2): 85–95, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.20144
The impact of methamphetamine use on subjective well‐being in an Internet survey: preliminary findings
Authors: Looby Alison , Earleywine Mitch
Published: February 2007

Methamphetamine is one of the most widely used stimulants worldwide. Common reasons for use of the drug include efforts to improve or enhance one's life and to uplift one's mood. Nevertheless, acute effects of the drug lead to temporary improvements in mood followed by negative affect. The purpose of the present study was to expand on the current literature and examine other aspects of mood and satisfaction with life in methamphetamine users. Over 6000 adults completed an Internet survey and reported on depression, apathy, satisfaction with life, happiness, and subjective well‐being, in addition to measures of methamphetamine use. We compared those who had used methamphetamine at least once within the past year (N = 610) to those who had never used (N = 6063). Methamphetamine use accounted for significant variance in depression, apathy, satisfaction with life, happiness, and subjective well‐being even when alcohol and other drugs served as covariates. Methamphetamine use may decrease one's subjective well‐being instead of enhancing it, which is contradictory to the perceptions of many users. Increasing awareness about methamphetamine's negative impact on mood and life satisfaction might help decrease prevalence of the drug's use and associated troubles. Copyright © 2007 John Wiley & Sons, Ltd.
Biologic characterization of gross lymphoma homogenates concentrated by density gradient and differential centrifugation
Authors: Wahren Britta
Published: February 2007

Fractions of Gross lymphoma homogenates were prepared by density gradient centrifugation or by differential centrifugation. Primary lymphomas developed in 80% of newborn mice inoculated with pellets obtained after differential centrifugation and in 48% of mice inoculated with fractions of Gross lymphoma homogenate with a density of 1.16–1.18. Such fractions induced a relative transplantation resistance as measured by a decrease in the frequency of tumor takes and a prolonged latency period when isogenic Gross lymphoma cells were inoculated into immunized mice.

Sera obtained from mice immunized with fractions of density 1.16–1.18 from Gross lymphoma homogenate were shown to contain cytotoxic antibodies active against Gross lymphoma cells. The results indicate that viral particles are responsible for the induction of antibodies against the Gross lymphoma antigen, either directly by sharing antigenic properties with the surface of the lymphoma cells from which they are derived, or indirectly by infection and transformation of susceptible cells.
The covalent binding of metabolites of dimethylaminoazobenzene, β‐naphthylamine and aniline to nucleic acids in vivo
Authors: Roberts J. J. , Warwick G. P.
Published: February 2007

Following injection of dimethylaminoazobenzene‐3H labelled in the primed ring (150 mg/kg) into male albino rats and guinea‐pigs maintained on a diet containing 10% protein, radioactivity was covalently bound to r‐RNA, DNA, cytoplasmic protein and nuclear protein of liver and spleen.

For liver the maximum levels of binding (μM/g × 102) were r‐RNA 11.4, cytoplasmic protein 54, nuclear protein 39, DNA 1.4; for spleen: r‐RNA 1.0, DNA 0.5, cytoplasmic protein 89, and nuclear protein 39; and for guinea‐pig liver r‐RNA 3.4, DNA 2.2, cytoplasmic protein 55, nuclear protein 28, indicating a much higher ratio of protein binding to r‐RNA binding than in the rat (16 compared with 5). The difference in ratio was also large for the binding to two transplanted hepatomas in August and Hooded rats compared with albino rat liver (37 and 13).

For rat liver r‐RNA and protein the decay of radioactivity paralleled the rate of turnover of r‐RNA (as measured by orotic acid‐3H incorporation) and of protein. The level of DNA‐bound radioactivity remained constant for 290 hours.

The radioactivity associated with the nucleic acids and proteins remained bound after treatment with 0.3 N KOH which converts the nucleic acids to nucleotides, and with Crotalus adamanteus venom which converts them to purine and pyrimidine nucleosides. Treatment with N HCl for 1 hr at 100°C which forms purine bases and pyrimidine nucleotides and degrades proteins into peptides and amino acids, liberated the majority of the radioactivity so that it became extractable at various pH values.

The binding of β‐naphthylamine‐3H and aniline‐3H hydrochloride to rat liver, spleen and kidney were also studied. Binding occurred to DNA, ribosomal RNA and protein in each case. For β‐naphthylamine the levels of metabolite binding were similar to dimethylaminoazobenzene metabolite binding to guinea‐pig liver components. For aniline hydrochloride, binding to ribosomal RNA and protein was of a low order.

The possible relevance of these findings to the problem of carcinogenesis is discussed.
Anahormones of growth hormone, exophthalmic factor, melanophore‐stimulating hormone, adrenocorticotropin and gonadotropin in experimental and clinical endocrinology
Authors: Dilman V. M.
Published: February 2007

Data on the dissociation of some properties of protein hormones are summarized. Preparations have been made in which the hormonal effect has been lost whereas the antigenic specificity or ability to localize in the target tissue has been retained.

Hormone derivatives with these properties have been defined as “anahormones” by analogy with anatoxins. The anahormones can inhibit the activity of endogenous hormones.

The ability of modified hormones to inhibit hormone action was retained in the following inactivated hormones: human acetylated somatotropin, acetylated exophthalmic factor, and MSH and ACTH (melanophore activity) after treatment with Lithospermum officinale extract.

The retention of antigenic specificity was observed in the following inactivated hormones: iodinated chorionic gonadotropin, acetylated human somatotropin, acetylated thyrotropin and formalinized sheep gonadotropin.

It was also shown that immunization by gonadotropins inhibited to a considerable extent the growth of intrasplenic transplants of the ovary in rats.

The possibility of using anahormones to counteract the carcinogenic influence of an excess of endogenous hormones is discussed.
Cell contact and cell adhesion during tissue organization
Authors: Saxén Lauri , Wartiovaara Jorma
Published: February 2007

The morphogenesis of mouse metanephros has been studied in vitro both in whole organ rudiments and with the aid of experimental recombinations of the inductor and the responding tissue. Time‐lapse cinematography as well as light and electron microscopy were employed to explore cell movements and intercellular contacts during the early steps of tubulogenesis. The first detectable change in the responding mesenchyme is condensation of the induced cells into large aggregates. This is discernible as a cessation of the random motility of the cells, and as a gradual disappearance of the intercellular spaces. In both whole kidney rudiments and experimental recombinants, this stage is followed by secondary fragmentations of the primary aggregates. In whole kidney rudiments, this lobulation always takes place along the midline between two inductively active tips of the branching ureteric tree. Finally, the most central parts of these condensates are pinched off as ball‐shaped pretubular aggregates. Inside these pretubular condensates, cells tend to increase their mutual contact area and to become elongated and radially oriented. Subsequently, connecting membrane units are formed, cells become polarized, and the lumen develops in the centre of the mass. Before this stage, no polarization has been observed in electron micrographs. The subsequent development of the pretubular anlage into the typical S‐shaped body takes place in situ by a continuous partial pinching‐off of the different parts of the loop from the original tissue mass.

The observations are discussed in the light of a working hypothesis that an epigenetic inductive stimulus triggers a gradual increase in the mutual adhesiveness in the responding cells. This surface change may explain the primary aggregation and the subsequent lobulation of the condensate. Moreover, aggregation of the cells by reason of this increased adhesiveness may be a prerequisite for polarization inside a certain tissue mass where different parts become exposed to different environmental conditions.
Action of the fluorescent dye, acridine orange, on radiation‐induced leukocytosis in mice
Authors: Sukhatankar Jayashree V. , Korgaonkar K. S.
Published: February 2007

The action of the fluorescent dye acridine orange, which is known to bind selectively to nucleic acids in cells, was tested on radiation‐induced leukocytosis in 2‐month‐old female Strong “A” strain mice. The toxic effect of different doses of the dye for the animals was determined, as was the whole‐body X‐ray irradiation dose that induced leukocytosis in the animals. Irradiated animals developing this disease were injected with a single dose of acridine orange (0.3 μg/20 g body weight) 30 or 45 days after irradiation. In both cases the blood picture, extended life‐span of the animals and histological examination of the tissues after such treatment indicated a strong inhibitive action of acridine orange on this radiation‐induced disease.
A review: Applications of the laser beam in cancer biology
Authors: Goldman Leon
Published: February 2007

Experiments with lasers in the past three years have shown encouraging initial results in many fields of cancer research. Laser technology, still in its early phases of development, is a new discipline even for the radiation biologist. Those in cancer research who wish to work with the laser must have help and co‐operation from the laser physicist and laser engineer. The cancer investigator must be familiar with all types of lasers, especially the recent high‐output, continuous‐wave lasers: the hazards of laser radiation must be known and a definite program of area and personnel protection must be available before any work is started. The laser attached to the microscope is valuable accessory instrumentation for work in cancer cytology and cytogenetics. The laser microprobe can do spectroscopy of living cancer tissues without significant destruction of the specimen. Some of the various parameters of the laser reaction in tissue have been studied in cancer in animals, the most striking results being obtained with melanomas. More studies are needed in cancer immunobiology concerning laser treatment and the role of the laser in aiding or hindering the induction of tumors. Laser synergism with gamma radiation and cancer chemotherapy is also still in the very early stages.

Laser treatment of human cancer has been limited to accessible lesions or to those made accessible by the surgeon. The most important results have been obtained with melanoma; other lesions have included a variety of skin tumors, including nonpigmented and pigmented basal cell epitheliomas, squamous cell epitheliomas, malignant lymphomas and vascular tumors. The relatively few visceral lesions treated have been adenocarcinomas and brain tumors. Many of the clinical investigations in patients with multiple tumors have not been controlled with other modalities of surgery, especially electrosurgery. Laser technology, then, is a new field in which the cancer chemist, the cancer biologist, the cancer radiologist and especially the cancer surgeon must become interested so that the very necessary basic studies may be continued in all these fields.
Studies on allogeneic inhibition I. Differential behavior of mouse tumors transplanted to homozygous and F1 hybrid hosts
Authors: Hellström K. E.
Published: February 2007

Lymphomas, carcinomas and sarcomas originating in homozygous hosts grew better when transplanted into syngeneic mice than in F1 hybrids between the syngeneic and an allogeneic strain. The growth inhibition in F1 hybrids was called allogeneic inhibition. In order to demonstrate the phenomenon small inocula had to be used, as a rule below 106 cells. It was demonstrated with tumors originating in seven different mouse strains tested (A, A.SW, A.CA, A.BY, C57BL, C57L and C3H).

Allogeneic inhibition was also detected with isoantigenic variant sublines, selected from an (A × A.SW)F1 hybrid lymphoma for compatibility with the A or A.SW parental strains, the variants giving more tumors in the selective A or A.SW strains than in (A × A.SW)F1. The unselected (A × A.SW)F1 lymphoma from which the variants were derived grew as well in (A × A.SW)F1 as did the variants in their selective parental strains.
Studies on allogeneic inhibition II. Inhibition of mouse tumor cell growth by In vitro contact with cells containing foreign H‐2 antigens
Authors: Bergheden C. , Hellström K. E.
Published: February 2007

Mouse lymphoma cells were inoculated into preirradiated syngeneic hosts after incubation with lymph‐node, spleen, liver or lymphoma cells from different sources in the presence of phytohemagglutinin. Neutralization of tumor growth was detected after incubation of lymphoma target cells with added untreated or X‐irradiated normal lymphoid or liver cells or with X‐irradiated intact or ultrasonically disintegrated lymphoma cells in all cases where the added cells contained H‐2 isoantigens which were foreign to the targets.
Studies on the aetiology of bilharzial carcinoma of the urinary bladder V. Excretion of tryptophan metabolites in urine
Authors: Abdel‐Tawab G. A. , Kelada F. S. , Kelada N. L. , Abdel‐Daim M. H. , Makhyoun N.
Published: February 2007

The urinary excretion of certain metabolites of tryptophan by eight control subjects, six patients with active urinary bilharziasis, five pellagrins with active urinary bilharziasis and 11 patients with bilharzial cancer of the bladder, was investigated. Pellagrins infested with S. haematobium and bilharzial patients with cancer of the bladder excreted some metabolites in excess when compared to controls and to patients infested with S. haematobium alone. Pyridoxine supplementation to seven of the patients with bilharzial cancer of the bladder reduced the differences between metabolite excretion of these patients and of the controls.

This evidence suggests that bilharzial patients with or without bladder tumours and pellagrins infested with S. haematobium suffer from pyridoxine deficiency. Therefore, it is concluded that bilharziasis is not the only causal factor in the associated abnormality of tryptophan metabolism.
Évolution in vitro et cancérisation des cellules pulmonaires de souris
Authors: Barski Georges , Billardon Claude , Jullien Paule‐Marie , Carswell Elizabeth
Published: February 2007

A partir du 3e–4e mois in vitro, on observait parmi les cellules de toutes les souches P une accumulation progressive de caryotypes anormaux, à nombres chromosomiques largement dispersés entre 45 et 100 et au‐delà, qui remplaçait progressivement les cellules à caryotypes normaux. Cet étalement considérable de nombres chromosomiques persistait et on l'a constaté, pour toutes les souches P, entre le 27e et le 32e mois de culture. Des chromosomes marqueurs à deux bras, à centromère médian ou subterminal, sont apparus et se maintenaient dans certaines souches. Les épreuves de malignité, entreprises entre le 7e et le 12e mois de culture et comportant des inoculations sous‐cutanées de routine de 5 × 106 cellules aux jeunes adultes C57Bl, ou de 1 × 106 cellules aux nouveaunés, ont démontré le pouvoir de produire des tumeurs sarcomateuses, propre pour toutes les souches sauf la P6 et la P7. Cette dernière est devenue cancéreuse après 16 mois in vitro. La P6 est restée non cancéreuse jusqu'à la fin de la 3e année in vitro, malgré sa transformation caryologique radicale.

De règle, les modifications du caryotype précédaient l'apparition de la malignité. Morphologiquement, les cellules des souches P évoluaient de leur aspect mixte initial vers une plus grande homogénéité. Des différences de type cellulaire persistaient cependant entre les souches, ainsi que parfois à l'intérieur de la měme souche (P4bis). De měme, les souches P différaient entre elles dans le degré de malignité, évalué par la vitesse de croissance tumorale et le nombre minimum de cellules nécessaires pour obtenir une tumeur. Une certaine relation existait entre la malignité et la morphologie cellulaire. Les cellules des souches hautement malignes étaient de type fibroblastique prononcé et produisaient in vitro une croissance polystratifiée et enchevětrée; les souches moins malignes ou non malignes (P6) maintenaient l'arrangement monostratifié et pavimenteux, étant inhibées dans leur progression par contacts intercellulaires, měme dans les cultures ǎgées. Les différences entre les souches P se répercutaient dans l'aspect histologique des tumeurs respectives: p. ex. les cellules géantes de la P4bis apparaissaient in vivo ainsi que in vitro, et, d'autre part, la production massive de collagène était propre surtout aux tumeurs P3 et P4. Certaines souches P montraient au microscope électronique des particules virales de type C. Le rǒle possible d'infection virale dans la transformation “spontanée” des cellules de souris in vitro est prise en considération et discutée.
Prolonged survival of allogeneic skin from tumour‐bearing mice
Authors: Marchant June
Published: February 2007

The survival of simultaneous skin grafts from normal and syngeneic tumourbearing mice has been compared in both normal and tumour‐bearing recipients of a foreign strain. Allografts from tumour‐bearing donors survived longer in 22 out of 27 tumour‐bearing hosts and in 49 out of 58 normal hosts.

In allografts donated by animals with a variety of tumours induced in a number of different ways, prolonged survival occurred. Grafts from mice with primary tumours induced with chemical carcinogens generally showed a very modest prolongation of 1 or 2 days. Considerable prolongation of 4 to 7 days was obtained with grafts from 19 donors, 15 of which bore large transplanted tumours.
Further observations on in vitro cytopathic effects associated with murine leukemia virus infection
Authors: Tyndall R. L. , Teeter E. , Otten J. A. , Bowles N. D. , Vidrine J. G. , Upton A. C. , Walburg H. E.
Published: February 2007

The previously reported cytopathic effects (CPE) in an established cell culture chronically infected with the Rauscher murine leukemia virus have been investigated in more detail. Initiation of CPE and morphologic transformation was observed in newly infected cultures. Suppression of CPE and transformation by NCTC 109 medium containing 25% human serum was also found to be reproducible in newly infected cultures. Adult human serum, human cord serum, fetal calf serum and fetuin had a suppressive effect on the CPE and transformation. Serological tests to detect non‐leukemogenic mouse viruses in the transformed cells were negative. Infected, trans‐formed cells were highly tumorigenic when inoculated subcutaneously into BALB/c mice. The resultant tumors were classified as myxofibrosarcomas. Approximately 50% of such tumor‐bearing mice also developed leukemia. In contrast, control uninfected cells under similar conditions were less tumorigenic and produced spindle‐cell sarcomas. None of the mice injected with control uninfected cells developed leukemia. The tumori‐genicity of both the infected and uninfected cell cultures increased when the cells were cultured on 4 × BME medium containing 10% calf serum.
Bovine fibroblasts in long‐term tissue culture: Chromosome studies
Authors: Lithner Folke , Pontén Jan
Published: February 2007

Three fibroblastic strains of fetal calf lung origin have been grown in vitro in serial culture. Chromosome alterations were found in all three. In early passages the cells remained diploid without chromosome changes. After this period cells started to become hypodiploid until they were all abnormal. The decrease in the counts was caused by a process interpreted as a fusion or association of telocentric elements. In the process telocentric chromosomes were randomly joined two and two at the centromere forming single biarmed chromosomes. No loss of detectable chromatid material accompanied the apparent fusion. No cytological changes were observed in the cultures at this stage.

Around passage 70, additional abnormalities began to appear. Severe chromosome alterations were observed with aneuploidy, widely scattered counts dominated by hypotetraploid numbers, breaks, dicentric forms and various other rearrangements. This change was accompanied by a decreased growth rate and degenerative cytological changes in the cultures analogous to those described in human and hamster fibroblasts approaching the end of their finite life span in vitro.
Some characteristic features of the biotransport of the cytostatic agent 1,6‐dibromo‐1,6‐dideoxy‐dulcitol
Authors: Institóris László , Piroska Horváth I. , Pethes George
Published: February 2007

Aspects of the biological transport of cytostatically active 1,6‐dibromo‐1,6‐dideoxydulcitol (DBD) were studied using 82Br‐labelled material on dogs and Yoshida tumorbearing rats. Thirty‐five per cent of the DBD dose was excreted in the urine within 12 hours. Besides unchanged DBD, metabolites containing C‐Br bonds could also be detected in the urine. In vivo, the 50% decomposition time of the C‐Br bonds in DBD is about 5 to 6 hours. One hour after administration of DBD, more than 50% of the persisting dose had entered the cells. Accumulation of the drug in the tumor tissue could not be demonstrated. A fraction of the dose enters the enterohepatic circulation.
Further studies on the relationship of a rhabdomyosarcoma virus to muscle tissue
Authors: Perk K. , Moloney J. B. , Jenkins E. G.
Published: February 2007

The pathogenesis of a rhabdomyosarcoma virus isolate was studied in a total of 300 newborn BALB/c mice, 11 different routes of inoculation being used. The latent periods, or time in days to palpable tumor, varied over a wide range among the inoculated groups. The growth of the tumor was very rapid in the muscle tissue. Regardless of the route of inoculation, the neoplasms arose from the adjacent muscle tissue attaching to and proliferating into the different organs and from their surfaces. Secondary tumor nodules were also observed in different areas of muscle tissue demonstrating the affinity of this virus to muscle tissue. Exceptions were found in some of the intrasplenically and intramyocardially inoculated mice where primary tumor nodules were found within these organs. Histologically the tumor cells were less differentiated toward myocytes than those described in a previous study.

It is suggested that this host response is a reflection of the high initiating virus dose employed.

Increase in spleen and liver weights and decrease in hematocrit values correlated closely to the extent of tumor development.
Immune responses in preleukaemic and leukaemic AKR mice
Authors: Metcalf D. , Moulds R.
Published: February 2007

The proliferation of haemolytic plaque‐forming cells in the spleen of preleukaemic AKR mice following primary immunization with sheep red cells was slightly delayed and the peak response was not as high as in normal mice. In leukaemic AKR mice, although there were normal numbers of background plaque‐forming cells in the spleens of unimmunized animals, these cells failed to proliferate following antigenic stimulation and no detectable haemolysin antibody response occurred before the seventh day following immunization.

Haemagglutinin responses were normal in preleukaemic AKR mice but were depressed severely in mice with thymic lymphomata or generalized lymphoid leukaemia.

The present results do not support the concept that severe immunological deficiencies are a necessary prerequisite of the preleukaemic state.
Pituitary hormones and the metabolism of N‐hydroxy‐N‐2‐fluorenylacetamide in female rats
Authors: Shirasu Y. , Grantham P. H. , Weisburger J. H.
Published: February 2007

The transplantable functional pituitary tumor, Furth MtT/F4, enhances hepatoma formation by the carcinogen N‐hydroxy‐N‐2‐fluorenylacetamide (N‐OH‐FAA) in rats. Therefore the metabolism of a single intraperitoneal dose of N‐OH‐FAA‐9‐14C was followed in groups of female Fischer rats which were fed either N‐OH‐FAA‐containing or control diets for 8 weeks, with or without MtT implantation.

The MtT markedly increased rectal temperature, food and water intake, urinary volume and body, liver, and kidney weights. The carcinogen‐prefeeding alone did not affect the total percentage of radioactivity from labeled N‐OH‐FAA excreted in 24‐hour urine, but the proportion excreted as urinary glucosiduronic acids and as the glucuronide of N‐OH‐FAA was greater. MtT implantation had no significant effect on the urinary metabolites in the animals on a control diet. However, the combination of carcinogen‐prefeeding and MtT transplantation increased the urinary excretion of total radioactivity, the urinary glucosiduronic acids, and especially the glucuronide of N‐OH‐FAA. Maintenance of higher levels of N‐OH‐FAA, the altered endocrine situation and the increased metabolic rate may contribute to the enhancement of hepatoma formation in female rats implanted with MtT.
Pretreatment with croton oil, DNA synthesis. And carcinogenesis by carcinogen followed by croton oil
Authors: Shinozuka H. , Ritchie A. C.
Published: February 2007

In the mouse, the number of epidermal cells labelled by tritiated thydidine is reduced 12 hours after a single application of 5% croton oil in mineral oil, increases four‐fold 24 hours affterwards, and returns towards normal 72 hours afterwards. The yield of papillomata induced by a single application of 7,12‐dimethylbenz (α)anthracene followed by repeated applications of croton oil is increased by an application of croton oil given 23 hours before the administration of carcinogen, but not by croton oil given 72 hours beforhand. The yield of papillomata induced by a single injection of urethane followed by croton oil is also increased by an application of croton oil given 23 hours before the carcingogen. These findings are cokmpatible with the theory that the carcinogens tested act on epidermal cells synthesizing DNA.

It is also suggested that, following a single application, mineral oil may remain on the skin for at least 24 hours. If a carcinogen is applied within this period, it may be diluted, and so apparently reduced in potency.
The detection of intracellular adenovirus type 12 antigens by indirect immunoferritin technique
Authors: Levinthal J. D. , Cerottini J. C. , Ahmad‐Zadeh C. , Wicker R.
Published: February 2007

An indirect immunoferritin technique for the localization of intracellular antigens is described. By the use of a variety of specific hamster and rabbit sera followed by double‐labeled fluorescein‐ferritin antiglobulins, antigens induced by human adenovirus type 12 could be specifically marked by a reaction analogous to the indirect technique of immunofluorescence in infected and transformed hamster, human and monkey cells. The cellular plasma membrane was rendered permeable to antibody with a dilute solution of digitonin, and fixation in dilute formaldehyde, 0.5 %, preserved a reasonable degree of morphologic detail as well as antigenic activity. Whole cells were reacted in suspension with antibody followed by antiglobulin. The antigens “stained” by ferritin‐labeled antibody were then located in thin sections after post‐fixation and Epon embedding. It is concluded that use of the indirect technique should permit a more general utilization of ferritin‐labeled antibodies.
Immune reactivity prior to development of thymic lymphoma in C57BL mice
Authors: Doell Ruth G. , De Vaux Christiane , Cyr St. , Grabar Pierre
Published: February 2007

The immune response of C57BL mice was tested following treatment with either irradiation or methylcholanthrene. Response to a weak histocompatibility antigen difference (male to female skin grafts) was found to be depressed after both treatments as was the response to a strong (H2) antigen difference as measured by the Simonsen graft‐versus‐host reaction.

The potent immunodepressant drug 6‐mercaptopurine was found to be carcinogenic in this strain of mouse, inducing approximately 29 % thymic lymphomas when given to young mice.

Females of the high spontaneous lymphoma strain AKR were found to have a markeldly decreased ability to reject male skin grafts as compared with the C57BL strain.
Autoradiographic analysis of the proliferation in vitro of six murine cell lines of non‐malignant or malignant origin
Authors: Sawicki W. , Kieler J. , Briand P.
Published: February 2007

A high rate of cell growth in culture has often been thought to be indicative of malignancy. In the present work the generation time of six murine cell lines and the duration of their various mitotic and intermitotic phases were studied using thymidine‐6‐3H and autoradiography. No definite correlation could be established between the growth kinetics and the tumor‐producing capacity of these cells, but cultures which were more than one year old showed a slightly shorter generation time and a somewhat shorter phase of DNA synthesis (ts) than 6‐ to 8‐month‐old cultures.
Sequential electron microscopical study of experimental mouse skin carcinogenesis
Authors: Tarin D.
Published: February 2007

Electron microscopical study of experimentally induced skin tumours was undertaken. The investigation was designed to determine the sequence of morphological changes between first painting with a carcinogen (methylcholanthrene) and the development of invasive neoplasms. It was found that changes occurred in both the epidermis and the dermis but that the most profound disturbances affected the region of the dermoepidermal junction.

The epidermal changes corresponded to those described by previous investigators. Changes in dermal organization appeared by the end of the second week. These consisted mainly of a decrease in the size of collagen fibres and a relative increase in connective tissue ground substance. There was also an increase in the dermal cell population, many of the new arrivals being mast cells. Examination of the dermo‐epidermal junction revealed that the basement membrane was thickened and in several places had separated slightly from the basal epidermal cells.

After five to six weeks' painting, small gaps appeared in the basement membrane. These were accompanied by the accumulation of fragmented material, similar in consistency to the basement membrane, in the superficial dermis. Where this material lay close to mast cells it appeared to coalesce to form reduplicated basement membranes.

By the time papillomas appeared, reduplication of the basement membrane had ceased and basement membrane material was decreasing. The dermal aspects of the basal cells pushed out cytoplasmic projections into the connective tissue. These projections constricted and separated from the cell to produce free‐lying vesicles in the superficial dermis. Later the vesicles ruptured and the release of their contents was associated with destruction of small areas of surrounding connective tissue. These appearances suggested enzymatic destruction of dermis by epidermis.

The dermo‐epidermal junction of carcinomas showed similar but more pronounced changes of which complete absence of basement membrane, vesicular activity of basal cells and gross disorganization of surrounding connective tissue were the most characteristic features.

Preliminary studies indicated that similar changes occur in spontaneous and experimentally induced breast tumours.
Cereal consumption and gastric cancer
Authors: Hakama Matti , Saxén E. A.
Published: February 2007

An association between cereal consumption and stomach cancer mortality is proposed. The data consist of age‐sex adjusted mortality rates of stomach cancer and cereal consumption per capita in 16 countries. Both the cereal consumption and stomach cancer mortality, as also changes in each of the variables, are significantly correlated.
Enhancement of lung adenoma formation by neonatal thymectomy in mice treated with 7,12‐dimethylbenz(a)anthracene or urethan
Authors: Trainin Nathan , Linker‐Israeli Mariana , Small Myra , Boiato‐Chen Louise
Published: February 2007

The influence of neonatal thymectomy on lung adenoma formation in mice was investigated. SWR and Swiss mice thymectomized at 3 days of age and given a single dose of 7,12‐dimethylbenz (a) anthracene (DMBA) or urethan showed significantly higher incidences of tumors than did intact controls, when examined at various intervals after the carcinogenic treatment. These differences in the yield of tumors were manifested as early as 10 weeks after urethan administration. Levels of hemolysins and hemagglutinins in response to sheep erythrocytes were decreased in thymectomized mice as compared with normal animals.

The probable relationship between enhanced susceptibility to chemical carcinogens and immunological deficit of neonatally thymectomized mice is discussed.
Chronic ethanol ingestion and the hepatocarcinogenicity of N‐hydroxy‐N‐2‐fluorenylacetamide
Authors: Yamamoto R. S. , Korzis J. , Weisburger J. H.
Published: February 2007

The effect of long‐term administration of 10% and 20% ethanol solutions on the hepatocarcinogenicity of N‐hydroxy‐N‐2‐fluorenylacetamide in two strains of rats was investigated. In tests with ethanol and carcinogen, started with 4‐ to 6‐week‐old Fischer rats the size of the liver and the extent of tumor formation were slightly less with male rats, and slightly more with females, as compared to rats fed only carcinogen. Experiments beginning with 16‐week‐old males, or with ethanol following carcinogen, were without additional effect. In NIH black rats, less susceptible to carcinogen and with a longer experimental period of 64 weeks, the concurrent intake of 10% ethanol did not affect the liver tumor incidence, although in females there seemed to be fewer cholangiomas and more hepatomas.
Iron‐dextran carcinogenesis in rats: Influence of dose on the number and types of neoplasm induced
Authors: Roe F. J. C. , Carter R. L.
Published: February 2007

Groups of 16, 32, 64 and 128 male CB Wistar rats were given, respectively, 16, 8, 4 and 2 subcutaneous injections of 0.75 ml iron‐dextran (“Imferon”) at weekly intervals: 64 untreated rats served as controls. Injection site tumours arose in 8, 11, 7 and 8 rats, respectively, in the four groups treated with iron‐dextran. The average time of tumour induction was similar in the four test groups but the grade of malignancy of tumours was directly related to the total dose of iron‐dextran administered. The wider implications of this latter observation are briefly discussed. The incidence of tumours at locations distant from the injection site was higher in the 128 rats which received only two injections of iron‐dextran than in the 64 untreated controls. However, the risk of dying with a distant tumour was not statistically higher in the combined test groups than in the control group. Several of the distant neoplasms in the iron‐dextran treated animals were of unusual types but their relationship to treatment with iron‐dextran remains uncertain.
The effect of isonicotinic acid hydrazide on the development of tumors
Authors: Toth Bela , Rustja Marjan
Published: February 2007

Isonicotinic acid hydrazide (INH) was administered as a 0.1% solution in the drinking water for the life span of adult AKR inbred mice. The treatment resulted in no significant inhibitory effect on the development of malignant lymphomas which are characteristic of these animals, nor did it induce other tumors.

Similar administration of INH as 0.05 and 0.15% solutions to adult randomly bred Swiss mice enhanced the formation of pulmonary adenomas, while it had no apparent inhibitory influence on the progression of other types of tumors.

Single doses of 500, 400, 300, 250, 200 and 100 μg of INH were injected subcutane‐ously on the day of birth to Swiss mice, without significant tumorigenic effect.

The problem of tumor induction versus inhibition is discussed.
Selective chemotherapy in relation to the site of tumor transplantation
Authors: Donelli M. G. , Rosso R. , Garattini S.
Published: February 2007

Sarcoma 180 and Ehrlich carcinoma maintained in the ascitic form were transplanted subcutaneously, intraperitoneally and intracerebrally. The same tumor transplanted in different sites showed a different sensitivity to the same chemotherapeutic agent. Cyclophosphamide and sarcolysin were active on subcutaneous and intraperitoneal, but not on the intracerebral tumors. On the other hand, I‐methylnitrosourea was effective only on the tumors transplanted intracerebrally.
Two established in vitro cell lines from human mesenchymal tumours
Authors: Ponten Jan , Saksela Eero
Published: February 2007

The development and cultivation of two cell lines from human mesenchymal tumours is described. Lines 2T and 4T differed from normal human fibroblastic cell strains by showing cytological atypia (high nucleocytoplasmic ratio, hyperchromasia and pleo‐morphism), an altered “epithelial‐like” pavement growth pattern, a deficient inhibition of cell division in crowded cultures and a potential for “indefinite” multiplication in vitro. Both lines were chromosomally abnormal in all samples and differed karyo‐typically from any known continuous cell line as well as from each other. Line 2T has retained, at least for 3 months (passage 111–126), a fairly narrow chromosomal mode of 34–38 with two specific marker chromosomes. A high frequency of chromosome breakage was observed in line 2T and extensive chromosome fragmentation, “chromosome pulverization”, occurred. No viruses could, however, be detected in the cultures despite numerous attempts. A control cell strain (2S) was developed from uninvolved skin of one of the tumour patients. Its behaviour followed the general pattern of human diploid cell strains in culture. To our knowledge, the described cell lines are the first derived from human mesenchymal tumours where the availability of a control fibroblast strain will provide us with opportunities to compare autologous normal and neoplastic human mesenchymal cells under in vitro conditions.