1,720,984 research outputs found

    Effects of Immune Cells on 13762NF Mammary Adenocarcinoma Cell Attachment to Basement Membrane Components

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    ix, 61 p.13762NF mammary adenocarcinoma cell clones MTF7 and MTF7(Tl1.2) (Fl1.2) were allowed to adhere to extracellular matrix components. Polymorphonuclear leukocytes (PMN's) were then introduced in various concentrations using several methods to examine the effect of these immune cells on attachment of malignant cells to the basement membrane (BM). Simultaneous PMN and tumor cell addition to matrices and addition after coincubation at several physiological temperatures showed no effect on tumor cell adhesion. PMN's also had no effect on adhesion of MTF7 cells to endothelium. Matrix pretreatment with PMN's followed by a saline wash prior to the addition of malignant cells, however, was shown to have a significant effect on attachment, as the enzymatic action of PMN's facilitated partial liberation of the matrix. It was therefore concluded that PMN's are not involved in the step of the metastatic process involving attachment, but are associated with BM degradation. In addition, studies to determine the cytolytic activity of PMN's and natural killer (NK) cells on tumor cell lines of varying metastatic potential (MTF7, MTF7(Tl1.2), MTC, and MTLn3) were performed, and it was determined that PMN's and NK's do not effectively lyse malignant cells in vitro.Upjohn Company, Kalamazoo, M

    Analysis of Drug Resistance Patterns in 13762NF Rat Mammary Adenocarcinoma Cell Lines

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    v, 33 p.To study the effects of cellular subpopulation interactions on metastatic stability in polyclonal populations of 13762NF rat mammary adenocarcinoma cell lines, the restriction of clonal diversity was required. This clonal restriction was achieved through drug exposure and selection of drug resistant cell lines (Adr-, DAP-, Oua-, TG- and Vcr-resistant) to act as cell markers. The objective of this research was to identify the patterns of drug resistance of these selected MTF7(T35).3 parent and drug-resistant cell lines using clonogenic colony formation assays to assess survival after 7 d of continuous drug exposure. Dose-response curves were constructed from average percent survival data, 90% lethal dose (LD90) levels were calculated from these dose-response curves, and levels of drug resistance were determined from these values. All cell lines were resistant to their respective selecting agents except the Qua resistant cell line, but the level of resistance varied when compared to the parental F35.3 cell line. Crossresistance was observed primarily for the Vincristine sulfate resistant cell line but to a lesser degree for other cell lines. Individual resistance patterns of the cell lines did not change in coculture indicating no cooperativity between cell lines. These cell lines will be useful for future experiments designed to study the stability of metastatic potential.Upjohn Company, Kalamazoo, Michigan

    A Study of Immune Cell Supernatant-Induced Transient Characteristics of MTF7 and MTF7(T11).2 Mammary Adenocarcinoma Cells

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    vii, 54 p.13762NF mammary adenocarcinoma cell clone MTF7 and MTF7(Tl1).2 were grown in various media ( 10%, and 0.125% Fetal Bovine Serum (FBS), Macrophage-Conditioned Media (MCM), and Neurtophil-Conditioned Media (PCM)) for 48 hours prior to interveinous injection into synergeic rats. The rats were then sacrificed 23 days later, the lungs were removed and the metastases were counted and measured. No significant difference was observed between the various treatments. The actin arrangement in the cells, and the in vitro doubling time were also unchanged. The tumor cell morphology, however, was changed. In addition, the in vitro saturation density and the ftbronectin staining patterns were also altered by various media. The MCM and the PCM both caused the cells to become cytostatic

    Effect of Polymorphonuclear Cells on Invasive and Metastatic Potentials of 13762NF Rat Mammary Adenocarcinoma Cells

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    vii, 34 p.The number of circulating activated polymorphonuclear leukocytes (PMNs) increases in tumor-bearing rats in a manner corresponding to the metastatic propensity of the tumor cell inoculated. Because secretion of basement membrane degrading proteinases was also enhanced, it was proposed that activated PMNs may play a role in tumor metastasis, particularly tumor cell extravasation. To test this hypothesis, we measured the effects of normal PMNs and circulating PMNs isolated from peripheral blood of tumor bearing rats on the experimental metastatic and invasive potentials of 13762NF rat mammary adenocarcinoma cell clones. Circulating PMNs isolated from MTLn3 tumor-bearing rats increased the invasion potentials of 13762NF rat mammary adenocarcinoma clones in vitro when tested in the Membrane Invasion Culture System (MICS) using reconstituted basement membrane as a barrier, and experimental metastatic potentials in vivo in a dose dependent manner. In contrast, 'normal' PMNs isolated from peripheral blood, or proteose peptone-stimulated peritoneal exudate did not alter these malignant characteristics. When rats received intravenous co-injections of tumor-elicited PMNs and tumor cells at an effector:target (E:T) ratio of 50:1 the mean number of experimental lung metastases rose 23. 2-fold for weakly metastatic MTLn2, 1.6-fold for moderately metastatic, highly invasive MTF7 clone, and 3.0-fold for the highly metastatic MTLn3 clone. In vitro invasive potentials were measured in MICS with varying E:T ratios (up to 30:1) of tumor-elicited PMNs and tumor cells. Invasive potential increased up to 25.5-fold for MTLn2, 36.7-fold for MTF7, and 53.7-fold for MTLn3. These results indicate that PMNs isolated from MTLn3 tumor-bearing rats have properties that can contribute to the metastatic potentials of other 13762NF rat mammary adenocarcinoma clones by assisting their invasion through a reconstituted basement membrane.Glaxo, Inc. Research Triangle Park, North Carolina

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Mitochondrial haplotype affects histone modification profiles in MNX mice

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    Cancer is a growing problem. In the US, cancer is roughly tied with cardiac disease as the leading cause of death. Intriguingly, compared to the proportion of deaths attributable to primary tumors, roughly 90% of all cancer patient morbidity and mortality are a direct result of metastatic disease perturbing normal organ and system function. Research has shown that the propensity to form both spontaneous tumors and metastatic growths is a function of both the nuclear and mitochondrial genomes present within an organism. Specifically, studies have also shown that, when the nuclear background is held constant and the mitochondrial haplotype is varied, there are marked discrepancies in both tumor latency and the average number of metastatic growths observed. To further study the effects of varying the mitochondrial haplotype on cancer progression and metastasis, a unique in vivo model—known as Mitochondrial-Nuclear Exchange (MNX) mice—has been developed. Experiments using this model system further support the notion that mitochondrial haplotype can contribute significantly to tumor latency and the overall of metastatic growths. As an initial line of inquiry, the question was asked as to whether or not differences in gene expression could be present upon changing the mitochondrial haplotype. Given that clear differences in genome-wide expression profiles between wildtype and MNX mice were indeed observed, the next line of inquiry sought to determine whether or not DNA methylation profiles could be regulating the differences in expression. Likewise, significant differences in DNA methylation patterns were established. As a corollary to these findings, the subsequent line of inquiry sought to elucidate whether or not mitochondrial haplotype could influence other potential epigenetic mechanisms responsible for the differences in gene expression profiles. Specifically, given the known link between metabolism and epigenetics, the logical hypothesis of the experiment was simply that the mitochondrial haplotype could potentially able to directly influence the epigenetic process of post-translationally modifying the N-terminal tails of histones in order to affect chromatin state dynamics in the cell. To address this hypothesis, following rigorous antibody validation, a ChIP-Seq experiment comparing wildtype and MNX mice using antibodies against four known histone modifications (H3K4me1, H3K4me3, H3K27me3, and H3K27ac) was conducted. Post-sequencing analysis indicated a selective difference in the overall profile of differentially-bound, post-translationally modified histones, thus supporting the hypothesis that mitochondrial haplotype does directly contribute to overall histone modification profiles. As a next logical step, future work will involve integrating previously generated RNA-Seq, Methyl-Seq, and ChIP-Seq experiments (in combination with extensive metabolome data) to develop hypotheses as to possible causal mechanisms involved in driving the observed differences in tumor latency and metastatic growth. Furthermore, another direction could involve expanding the ChIP-Seq study to include newly characterized acylation (propionylation, butyrylation, succinylation, malonylation, etc.) post-translational modifications which functionally are thought to overlap with acetylation and may more closely link metabolism to overall chromatin state. The results of this research not only contribute to our understanding of how mitochondria participate in influencing the DNA packaging mechanisms involved in regulating chromatin dynamics, but, as our research is not limited to any single form of cancer, has the potential to benefit to all cancer patients

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods
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