1,720,961 research outputs found
ADOPTIVE TRANSFER OF LYMPHOKINE-ACTIVATED KILLER-CELLS LOADED WITH 4'-DEOXY-4'-IODODOXORUBICIN - THERAPEUTIC EFFECT IN MICE BEARING LUNG METASTASES
Full text linkWe studied the potential use of lymphokine-activated killer (LAK) cells loaded with 4'-deoxy-4'-iododoxorubicin (IDX) in adoptive immunotherapy experiments. Because LAK cells preferentially locate in the lung, we evaluated the therapeutic effect of IDX-loaded LAK cells in mice bearing lung metastases induced by B16F1 tumor cell injection. In vitro studies showed that LAK cells rapidly incorporated IDX, with maximum uptake at 15 min, followed by a plateau; drug efflux was initially rapid and then continued at a much slower rate. Evaluation of LAK cell cytotoxic activity against relevant target cells showed a 30% decrease after IDX treatment that progressed with time over the next 6 h. P388 tumor cell growth was inhibited by coculture with IDX-loaded LAK cells, thus demonstrating that the released IDX maintained its pharmacological activity. Finally, high performance liquid chromatography analysis of tissue IDX concentration revealed a considerably higher and long-lasting concentration in the lungs of mice receiving IDX-loaded LAK cells, compared to mice given injections of a comparable amount of free drug. Moreover, adoptive transfer of IDX-loaded LAK cells into tumor-bearing mice caused a significant reduction in the number of lung metastases versus control mice given injections of even higher doses of free drug
4'-Iodo-4'-deoxydoxorubicin disrupts the fibrillar structure of transthyretin amyloid
No full textTransthyretin (TTR) is a tetrameric protein synthesized mainly by the liver and the choroid plexus, from where it is secreted into the plasma and the cerebrospinal fluid, respectively. Some forms of polyneuropathy, vitreopathy, and cardiomyopathy are caused by the deposition of normal and/or mutant TTR molecules in the form of amyloid fibrils. Familial amyloidotic polyneuropathy is the most common form of TTR amyloidosis related to the V30M variant. It is still unclear the process by which soluble proteins deposit as amyloid. The treatment of amyloid-related disorders might attempt the stabilization of the soluble protein precursor to retard or inhibit its deposition as amyloid; or aim at the resorption of the deposited amyloid. The anthracycline 4'-iodo-4'-deoxydoxorubicin (I-DOX) has been shown to reduce the amyloid load in immunoglobulin light-chain amyloidosis. We investigated 1) whether I-DOX has affinity for TTR amyloid in tissues, 2) determined the I-DOX binding constants to TTR synthetic fibrils, and 3) determined the nature of the effect of I-DOX on TTR fibrils. We report that 1) I-DOX co-localizes with amyloid deposits in tissue sections of patients with familial amyloidotic polyneuropathy; 2) I-DOX strongly interacts with TTR amyloid fibrils and presents two binding sites with k(d) of 1.5 x 10(-11) mol/L and 5.6 x 10(-10) mol/L, respectively; and 3) I-DOX disrupts the fibrillar structure of TTR amyloid into amorphous material, as assessed by electron microscopy but does not solubilize the fibrils as confirmed by filter assays. These data support the hypothesis that I-DOX and less toxic derivatives can prove efficient in the treatment of TTR-related amyloidosis
Delivery of methoxymorpholinyl doxorubicin by interleukin 2-activated NK cells: effect in mice bearing hepatic metastases
Full text linkThe possibility of using interleukin 2 (IL-2)-activated natural killer cells
(A-NK) to carry methoxymorpholinyl doxorubicin (MMDX; PNU 152243) to
liver-infiltrating tumours was explored in mice bearing 2-day established M5076
reticulum cell sarcoma hepatic metastases. In vitro, MMDX was 5.5-fold more
potent than doxorubicin against M5076 tumour cells. MMDX uptake by A-NK cells
correlated linearly with drug concentration in the incubation medium [correlation
coefficient (r) = 0.999]; furthermore, as MMDX incorporation was readily
reproducible in different experiments, the amount of drug delivered by A-NK cells
could be modulated. In vivo experiments showed that intravenous (i.v.) injection
of MMDX-loaded A-NK cells exerted a greater therapeutic effect than equivalent or
even higher doses of free drug. The increase in lifespan (ILS) following A-NK
cell delivery of 53 microg kg(-1) MMDX, a dosage that is ineffective when
administered in free form, was similar to that observed in response to 92 microg
kg(-1) free drug, a dosage close to the 10% lethal dose (ILS 42% vs. 38%
respectively). These results correlated with pharmacokinetic studies showing that
MMDX encapsulation in A-NK cells strongly modifies its organ distribution and
targets it to tissues in which IL-2 activated lymphocytes are preferentially
entrapped after i.v. injection
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Full text linkWe 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
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe 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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