gebhart/patrepeval huggingface dataset:
DCC protein expression in hematopoietic cell populations and its relation to leukemogenesis. (1996)

Using flow cytometry and immunoprecipitation (IP), we have investigated the deleted in colon cancer (DCC) protein expression on the bone marrow (BM) and peripheral blood (PB) cells of 16 normal subjects, 17 myelodysplastic syndrome (MDS) patients, and 10 acute myelogenous leukemia (AML) patients. With regard to the BM mononuclear cells (BM-MNCs) of normal subjects, the DCC protein expression ranged from 6.6 to 57.0%. Two-color flow cytometry revealed that among the IBM-MNCs the DCC protein was clearly expressed on the CD14+, CD13+, and factor 8+ cells, whereas it was low on the CD19+ and CD7+ cells and did not express on the CD34+, CD8+, and the glycophorin A+ cells. Further, the DCC protein expression was not seen on the PB CD11b+ and CD13+ cells. The IP results revealed that the 180-kD DCC protein was detected on the MNCs of both the BM and PB cells by the antibodies AF5, specific for the DCC extracellular domain, and G97-449, specific for the cytoplasmic domain. In contrast, flow cytometry did not detect the DCC protein on any BM-MNC MDS lineages (0.1-1.5%) or on AML leukemic cells (0.1-0.9%). The IP results indicated that the AF5 antibody did not detect the DCC protein on BM-MNCs of three of five MDS patients and four of five AML patients; however, the G97-449 antibody detected the 180-kD DCC protein in two MDS patients in whom AF5 had detected greatly reduced DCC band. These findings suggest that the DCC protein presence appears to be associated with normal hematopoiesis, and that its absence on the surfaces of the BM-MNCs and AML cells may contribute to the MDS and AML pathogenesis.
Genetics of Candida albicans (1990)

Candida albicans is among the most common fungal pathogens. Infections caused by C. albicans and other Candida species can be life threatening in individuals with impaired immune function. Genetic analysis of C. albicans pathogenesis is complicated by the diploid nature of the species and the absence of a known sexual cycle. Through a combination of parasexual techniques and molecular approaches, an effective genetic system has been developed. The close relationship of C. albicans to the more extensively studied Saccharomyces cerevisiae has been of great utility in the isolation of Candida genes and development of the C. albicans DNA transformation system. Molecular methods have been used for clarification of taxonomic relationships and more precise epidemiologic investigations. Analysis of the physical and genetic maps of C. albicans and the closely related Candida stellatoidea has provided much information on the highly fluid nature of the Candida genome. The genetic system is seeing increased application to biological questions such as drug resistance, virulence determinants, and the phenomenon of phenotypic variation. Although most molecular analysis to data has been with C. albicans, the same methodologies are proving highly effective with other Candida species.
Molecular mediators of hepatic steatosis and liver injury (2004)

Obesity and its associated comorbidities are among the most prevalent and challenging conditions confronting the medical profession in the 21st century. A major metabolic consequence of obesity is insulin resistance, which is strongly associated with the deposition of triglycerides in the liver. Hepatic steatosis can either be a benign, noninflammatory condition that appears to have no adverse sequelae or can be associated with steatohepatitis: a condition that can result in end-stage liver disease, accounting for up to 14% of liver transplants in the US. Here we highlight recent advances in our understanding of the molecular events contributing to hepatic steatosis and nonalcoholic steatohepatitis.
Lentivector immunization induces tumor antigen‐specific B and T cell responses in vivo (2008)

Expression of the cancer/germ-line antigen NY-ESO-1 by tumors elicits spontaneous humoral and cellular immune responses in some cancer patients. Development of vaccines capable of stimulating such comprehensive immune responses is desirable. We have produced recombinant lentivectors directing the intracellular synthesis of NY-ESO-1 (rLV/ESO) and have analyzed the in vivo immune response elicited by this vector. Single injection of rLV/ESO into HLA-A2-transgenic mice elicited long-lasting B and T cell responses against NY-ESO-1. CD8+ T cells against the HLA-A2-restricted peptide NY-ESO-1(157-165) were readily detectable ex vivo and showed restricted TCR Vbeta usage. Moreover, rLV/ESO elicited a far greater anti-NY-ESO-1(157-165) CD8+ T cell response than peptide- or protein-based vaccines. Anti-NY-ESO-1 antibodies were rapidly induced after immunization and their detection preceded that of the antigen-specific CD8+ T cells. The rLV/ESO also induced CD4+ T cells. These cells played an essential role as their depletion completely abrogated B cell and CD8+ T cell responses against NY-ESO-1. The induced CD4+ T cells were primarily directed against a single NY-ESO-1 epitope spanning amino acids 81-100. Altogether, our study shows that rLV/ESO induces potent and comprehensive immune responses in vivo.
Fosfomycin in Osteomyelitis (1976)

Fosfomycin was exclusively used as antibiotic treatment in 37 patients suffering from osteomyelitis, out ot which 23 were operated for sequestrectomy or fistulectomy, whereas the remaining 14 did not undergo any surgery during fosfomycin treatment. Fosfomycin was adminsitered parenterally, alone or combined with oral administration, and in some cases only orally. The dosage varied from 4 to 8 g/day for an average period of 3 weeks. After one or two treatments the results were 29 definitive cures (78%), 2 failures and 6 relapses (22%).
Suppression of Ovarian Follicle Activation in Mice by the Transcription Factor Foxo3a (2003)

Foxo transcription factors have been implicated in diverse biological processes, including metabolism, cellular stress responses, and aging. Here, we show that Foxo3a-/- female mice exhibit a distinctive ovarian phenotype of global follicular activation leading to oocyte death, early depletion of functional ovarian follicles, and secondary infertility. Foxo3a thus functions at the earliest stages of follicular growth as a suppressor of follicular activation. In addition to providing a molecular entry point for studying the regulation of follicular growth, these results raise the possibility that accelerated follicular initiation plays a role in premature ovarian failure, a common cause of infertility and premature aging in women.
3-NP-induced neurodegeneration studies in experimental models of Huntington's disease. (2005)

This thesis investigates the possible role of apoptosis, or programmed cell death, in Huntington's disease (HD). HD is caused by an expanded CAG repeat in the N-terminal region of the huntingtin protein leading to specific neostriatal neurodegeneration. The sequence of events that leads to this selective neuronal death is unknown, but inappropriate activation of apoptosis may be involved. To study mechanisms of apoptotic cell death in HD, we developed animal models using the mitochondrial toxin 3-nitropropionic acid (3-NP) that induces specific neuronal death in the striatum and resembles the characteristic HD neuropathology in a wide spectrum. Apoptotic features at various time points of the process were studied in the 3-NP in vivo model, in 3-NP-exposed organotypic slice cultures and in brains of HD patients. We found an increased expression of several regulatory proteins (such as Bax, Bcl-2, caspase-3 and PARP) that are involved in the apoptotic cascade combined with typical TUNEL labeling. These findings do provide evidence for activation of apoptosis in both the 3-NP models of HD and in human HD. In addition, we examined neuroprotective effects of the bioenergetic compound creatine in the 3-NP in vitro model. Our findings suggest that creatine can prevent 3-NP-induced neurodegeneration in the cortex, while in striatal cells it may lead to accelerated and increased execution of apoptotic cell death in order to prevent further necrosis-related damage in this region. Although, the in vivo and in vitro 3-NP models used in this thesis represent one aspect of human HD, they are suited to perform different types of studies. The 3-NP slice culture system may be useful for screening new therapeutic agents, whereas the 3-NP in vivo model may be used neuropathologically for further elucidating apoptotic processes and pathways that are involved in the selective striatal neurodegeneration.
T Cell Activation Modulates Retrovirus-Mediated Gene Expression (1998)

Important considerations for T lymphocyte-based gene therapy include efficient gene delivery and expression in primary, human T cells. In this study, retrovirus-mediated gene transfer and the fate of proviral gene expression were evaluated in human T cells activated using (1) immobilized anti-CD3 monoclonal antibody (MAb) plus interleukin 2, or (2) cis costimulation using beads carrying coimmobilized anti-CD3 and anti-CD28 MAbs. By cross-linking the CD3 and CD28 receptors, these MAbs mimic in vivo signaling events, leading to cytokine production and proliferation. A modified human interleukin 1beta (IL-1beta) cDNA inserted into the MFG retroviral vector served as an indicator gene. Retroviral transduction frequencies were similar for T lymphocytes activated by the respective methods. However, early after MAb stimulation and virus exposure, proviral gene expression was greater at the RNA and protein levels in optimized anti-CD3/anti-CD28 bead-activated T cells, corresponding with augmented endogenous cytokine responses and mitogenesis. Proviral gene expression was not regulated by extrinsic cell factors present in activated T cell supernatants. Regardless of the MAb stimulation method, proviral IL-1beta expression declined in later T cell cultures concomitant with a decrease in cellular cytokines. Restimulation by either method reinduced both T cell activity and vector expression. Our finding that proviral gene regulation is downmodulated in the absence of T cell signaling events has implications for clinical strategies using retrovirus-modified T cells.
Reported adverse reactions to and consumption of nonsteroidal anti-inflammatory drugs in Denmark over a 17-year period. (1988)

Over the 17-year period 1969-1985, 2,721 reports of 3,521 suspected adverse drug reactions (ADRs) associated with non-steroidal anti-inflammatory drugs (NSAIDs) were submitted to the Danish Committee on ADRs. The results are presented together with the consumption of each drug during the same period. The total sale of NSAIDs showed a four-fold increase during the 17 years, the average corresponding to a permanent intake by 2.2% of the population. The number of reported ADRs per defined daily dose (DDD) sold was markedly lower for "older" drugs like the butazones, indomethacin, ibuprofen, naproxen, ketoprofen, and fenoprofen than for the drugs marketed during the last decade. These differences could not be accounted for by the well-known biases attached to spontaneous ADR reporting. Of 67 fatal reactions, 25 were due to bleeding or perforation of a gastric ulcer, mostly during treatment with indomethacin and naproxen, and in elderly people, and 27 were caused by bone marrow depression or leukaemia, begun mostly during treatment with butazones, but some with indomethacin and naproxen as well. It is pointed out that all reports on fatal bone marrow depression associated with butazones were submitted before 1976 and that the fact that none have been received since that time could be a result of better understanding of the proper dosage of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)
Nucleic Acid Enzymes (Ribozymes and Deoxyribozymes): In Vitro Selection and Application (2008)

Abstract Natural catalysts composed of RNA were discovered in the early 1980s. After this advance, it was logical to consider that artificial nucleic acid enzymes made from either RNA or DNA could be developed by recapitulating the basic evolutionary principles in the laboratory. In subsequent years, many artificial ribozymes and deoxyribozymes have indeed been identified by in vitro selection, and the scope of nucleic acid catalysis now encompasses a much wider range of chemical reactions than is found in nature. The study of artificial ribozymes and deoxyribozymes can provide fundamental insight into the functioning of natural catalytic nucleic acids. In addition, artificial nucleic acid enzymes are increasingly used in practical applications ranging from analytical chemistry to biology.
Induction of a Pea Cell-Wall Invertase Gene by Wounding and Its Localized Expression in Phloem (1996)

A full-length cell-wall invertase cDNA obtained from pea (Pisum sativum L.) seedlings was cloned previously. The gene exhibits tissue-specific expression, and both its transcript and enzyme activities are abundant only in root tissues. Mechanical wounding dramatically induced the accumulation of the cell-wall invertase mRNA in detached or intact leaves, stems, and roots. In both detached and intact tissues mRNA started to accumulate 3 h after wounding and in detached tissues (except root tissues) was much stronger and lasted longer compared with that in intact pea plants. The induction of cell-wall invertase by wounding was not systemic, since no significant increase of transcript was found in the unwounded tissues remote from the site of wounding. Accumulation of this cell-wall invertase was induced by abscisic or jasmonic acid, and in situ hybridization studies show that this invertase mRNA is differentially localized in wounded plant tissue, being most abundant in the phloem. mRNA accumulation was limited mainly to the wounded area; no significant increase was detected in the unwounded portions of the wounded stem segments. The results suggest that, as part of the wounding response, this cell-wall invertase may provide energy through hexose availability to companion cells in the phloem.
Simvastatin attenuates vascular leak and inflammation in murine inflammatory lung injury (2005)

Therapies to limit the life-threatening vascular leak observed in patients with acute lung injury (ALI) are currently lacking. We explored the effect of simvastatin, a 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitor that mediates endothelial cell barrier protection in vitro, in a murine inflammatory model of ALI. C57BL/6J mice were treated with simvastatin (5 or 20 mg/kg body wt via intraperitoneal injection) 24 h before and again concomitantly with intratracheally administered LPS (2 microg/g body wt). Inflammatory indexes [bronchoalveolar lavage (BAL) myeloperoxidase activity and total neutrophil counts assessed at 24 h with histological confirmation] were markedly increased after LPS alone but significantly reduced in mice that also received simvastatin (20 mg/kg; approximately 35-60% reduction). Simvastatin also decreased BAL albumin (approximately 50% reduction) and Evans blue albumin dye extravasation into lung tissue (100%) consistent with barrier protection. Finally, the sustained nature of simvastatin-mediated lung protection was assessed by analysis of simvastatin-induced gene expression (Affymetrix platform). LPS-mediated lung gene expression was significantly modulated by simvastatin within a number of gene ontologies (e.g., inflammation and immune response, NF-kappaB regulation) and with respect to individual genes implicated in the development or severity of ALI (e.g., IL-6, Toll-like receptor 4). Together, these findings confirm significant protection by simvastatin on LPS-induced lung vascular leak and inflammation and implicate a potential role for statins in the management of ALI.
Absence of the mdr1a P-Glycoprotein in mice affects tissue distribution and pharmacokinetics of dexamethasone, digoxin, and cyclosporin A. (1995)

We have previously shown that absence of the mouse mdr1a (also called mdr3) P-glycoprotein in mdr1a (-/-) "knockout" mice has a profound effect on the tissue distribution and elimination of vinblastine and ivermectin, and hence on the toxicity of these compounds. We show here that the mouse mdr1a and the human MDR1 P-glycoprotein actively transport ivermectin, dexamethasone, digoxin, and cyclosporin A and, to a lesser extent, morphine across a polarized kidney epithelial cell layer in vitro. Injection of these radio-labeled drugs in mdr1a (-/-) and wild-type mice resulted in markedly (20- to 50-fold) higher levels of radioactivity in mdr1a (-/-) brain for digoxin and cyclosporin A, with more moderate effects for dexamethasone (2- to 3-fold) and morphine (1.7-fold). Digoxin and cyclosporin A were also more slowly eliminated from mdr1a (-/-) mice. Our findings show that P-glycoprotein can be a major determinant for the pharmacology of several medically important drugs other than anti-cancer agents, especially in the blood-brain barrier. These results may explain a range of pharmacological interactions observed between various drugs in patients.
Review article: mechanisms of action and therapeutic applications of ursodeoxycholic acid in chronic liver diseases (1999)

Ursodeoxycholic acid (ursodiol) is a non-toxic, hydrophilic bile acid used to treat predominantly cholestatic liver disorders. Better understanding of the cellular and molecular mechanisms of action of ursodeoxycholic acid has helped to elucidate its cytoprotective, anti-apoptotic, immunomodulatory and choleretic effects. Ursodeoxycholic acid prolongs survival in primary biliary cirrhosis and it improves biochemical parameters of cholestasis in various other cholestatic disorders including primary sclerosing cholangitis, intrahepatic cholestasis of pregnancy, cystic fibrosis and total parenteral nutrition-induced cholestasis. However, a positive effect on survival remains to be established in these diseases. Ursodeoxycholic acid is of unproven efficacy in non-cholestatic disorders such as acute rejection after liver transplantation, non-alcoholic steatohepatitis, alcoholic liver disease and chronic viral hepatitis. This review outlines the present knowledge of the modes of action of ursodeoxycholic acid, and presents data from clinical trials on its use in chronic liver diseases.
Design and implementation of fingerprinting-based broadcasting content identification system (2014)

The existing fingerprinting technologies are not appropriate for broadcasting content identification services which identify broadcasting content in real-time because of the low fingerprint extraction speed and long DB update time. Thus, to apply fingerprinting to the second screen service, it needs a fingerprinting technology which can extract fingerprint while playing the content and update fingerprint DB in real-time. In this paper, we propose a fingerprint-based second screen framework which can identify broadcasting content in real time by on-time content identifier. We define this fingerprint as on-time identifier, and content identification system using on-time identifier as the identification system.
Assessment of optical coatings for 193-nm lithography (1998)

We present an assessment of antireflective coatings for 193-nm lithography. Coatings from nine suppliers were exposed in a nitrogen ambient for up to 1.5 billion pulses at 15 mJ/cm<SUP>2</SUP>/pulse at 400 Hz. Sensitive metrology, developed for this study, included reflectance/transmittance measurements, in-situ ratiometric transmission measurements, and interferometric calorimetry for absorption measurements. The coatings from at least two suppliers withstood greater than 1 billion pulses with no observable degradation. Catastrophic damage observed on some samples included blistering and a dramatic transmission drop. Such damage occurred rather early (less than 100 million pulses).
Historical contexts: Britain and Europe (2008)

Edmund Spenser lived at a time when the charged relation between the two 'contexts' of this chapter, Britain and Europe, was changing drastically, and, as we will see, his own relation to these shifting contexts was often equivocal. Inserting Spenser into historical contexts can be problematic, and, certainly, no amount of 'context' can finally decide the meaning of Spenser's life or work. In the several books of The Faerie Queene and elsewhere, we find an ongoing mediation on historical contexts that is an index both of Spenser's own uncertain placement within them and his indeterminate effect on them. Sometimes this dialectic can be traced quite clearly: not only can Spenser's work be set 'within' these historical contexts, but these contexts themselves are, to an extent, being defined by him as he writes. In the later years of the sixteenth century, for instance, one of our contexts, that of 'Britain', was not yet assembled as an effective political union. Strictly speaking, 'Great Britain' would not come into existence until 1801. But Spenser invested in the imagining of such a polity throughout his career, and some of our conception of 'Britain' as a splendid fusion of disparate nations we owe to him. 'How brutish is it not to vnderstand', cries Arthur in the second book of The Faerie Queene, looking up from a chronicle titled Briton moniments, 'How much to [Britain] we owe, that all vs gaue, / That gaue vnto vs all, what euer good we haue' (II, x, 69). In other places, however, the dialectic between Spenser and his contexts is less easy to discern.
The Anti-Inflammatory and Anti-Angiogenic Role of Mesenchymal Stem Cells in Corneal Wound Healing Following Chemical Injury (2008)

To investigate the anti-inflammatory and anti-angiogenic effects of mesenchymal stem cells (MSC) in the chemically burned corneas, we mechanically removed the corneal epithelium of rats after 100% alcohol instillation. The rats were then randomized into four groups: fresh media, conditioned media derived from the MSC culture (MSC-CM), MSC applied topically to the damaged corneas for 2 hours immediately after the injury or MSC-CM applied either once or 3 times per day for 3 consecutive days. Corneal surface was evaluated every week. After 3 weeks, the corneas were stained with the hematoxylin-eosin, and the expression of interleukin (IL)-2, interferon (IFN)-gamma, IL-6, IL-10, transforming growth factor (TGF)-beta1, thrombospondin-1 (TSP-1), matrix metalloproteinase-2 (MMP-2), and vascular endothelial growth factor (VEGF) were analyzed. CD4+ cells were assessed in the corneas. We found that both MSC and three-time applied MSC-CM (1) reduced corneal inflammation and neovascularization, (2) decreased IL-2 and IFN-gamma, although increased IL-10 and TGF-beta1 as well as IL-6, (3) reduced the infiltration of CD4+ cells, and (4) upregulated the expression of TSP-1, although downregulated that of MMP-2. Interestingly, whereas three-time application of MSC-CM was partially effective, transplantation of MSC achieved a better outcome in suppressing corneal inflammation. The results of this study suggest that the anti-inflammatory and anti-angiogenic action of MSC in the chemically burned corneas might be mediated in part through paracrine pathways involving soluble factors such as IL-10, TGF-beta1, IL-6 and TSP-1.