gebhart/patrepeval huggingface dataset:
Inhibition of fibroblast chemotaxis by recombinant human interferon γ and interferon α (1987)

Interferons have recently been recognized as potent mediators in inflammatory processes, exerting profound effects on fibroblasts. The influence of interferons gamma and alpha on the chemotactic movement of fibroblasts toward various attractants was, therefore, investigated. Normal human adult and embryonal dermal fibroblasts, fibrosarcoma-derived fibroblasts and SV40-transformed fibroblasts were tested against conditioned medium from fibroblasts, the chemotactic peptide C-140 of fibronectin, platelet-derived growth factor, and leukotriene B4 as attractants in the presence or absence of the interferons. Interferons gamma and alpha inhibited chemotaxis in a dose-dependent manner and at concentrations at least as low as 10(-2) ng/ml. Inhibition was noticeable when the cells were exposed to interferon for as short a period as 60 minutes, and the effect was not readily reversible. Inhibition occurred when the cells came from sparse or dense cultures, but when platelet-derived growth factor was the attractant and the cells had been grown at low density there was no inhibition. It is concluded that this is a specific effect, not to be wholly explained by overall increase in membrane rigidity. Inhibition of fibroblast chemotaxis by interferons may be an important regulatory mechanism during wound healing or fibrosis and metastatic spread of tumor cells.
Decreased Levels of Helper T Cells (1982)

DECREASED maternal immune responsiveness during pregnancy may partly explain the survival of the fetus as an allograft. It may also account for changes in disease activity and antibody production in several autoimmune diseases during pregnancy and in the post-partum period. Previous in vitro studies of cellular immunity in pregnant women have demonstrated decreased lymphocyte responses to phytohemagglutinin,1 to mixed lymphocyte culture,1 and to soluble antigens.2 An increased incidence and severity of certain viral infections has also been observed.1 , 3 An imbalance between helper and suppressor T cells has recently been demonstrated in several autoimmune diseases4 , 5 and in immunodeficiency states,4 in studies . . .
Variations in Affinities of Antibodies during the Immune Response* (1964)

ADVERTISEMENT RETURN TO ISSUEPREVArticleVariations in Affinities of Antibodies during the Immune Response*Herman N. Eisen and Gregory W. SiskindCite this: Biochemistry 1964, 3, 7, 996–1008Publication Date (Print):July 1, 1964Publication History Published online1 May 2002Published inissue 1 July 1964https://pubs.acs.org/doi/10.1021/bi00895a027https://doi.org/10.1021/bi00895a027research-articleACS PublicationsRequest reuse permissionsArticle Views1516Altmetric-Citations758LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
The Influence of Intensively Managed Rotational Grazing, Traditional Continuous Grazing, and Confinement Housing on Bulk Tank Milk Quality and Udder Health (1992)

Monthly bulk tank milk samples and veterinary records were analyzed for 1 yr on 15 Vermont dairy farms. Data were evaluated using ANOVA to compare effects of grazing management systems on milk quality and udder health. Systems evaluated were intensively managed rotational grazing, traditional continuous grazing, and confinement housing. Bulk tank samples were evaluated for standard plate count, bacterial type counts on tryptose-blood-esculin agar, and SCC. Veterinary records were evaluated for incidence of clinical mastitis, udder edema, and teat injuries. Within- and between-treatment group analyses were conducted by season, herd size, and udder sanitation systems. Mean standard plate counts were lower in rotationally grazed herds than counts of confined herds during the grazing season. Similarly, rotationally grazed herds with fewer than 60 cows had lower standard plate counts than confined herds of similar size. Mean bulk tank counts of streptococci other than Streptococcus agalactiae during the grazing season differed among treatments. The lowest counts occurred in rotationally grazed herds. Among herd using predip products recognized as efficacious, fewer streptococci other than S. agalactiae were isolated from bulk tank milk of rotationally grazed herds than confined herds. Rotationally grazed herds using postdips recognized as efficacious had lower SCC than those using unrecognized postdips. No udder health differences were observed among grazing treatments.
Spontaneous Transformation of Human Adult Nontumorigenic Stem Cells to Cancer Stem Cells Is Driven by Genomic Instability in a Human Model of Glioblastoma (2007)

The presence of a CD133+/nestin+ population in brain tumors suggests that a normal neural stem cell may be the cell of origin for gliomas. We have identified human CD133-positive NSCs from adult glioma tissue and established them as long-term in vitro cultures human neuroglial culture (HNGC)-1. Replicative senescence in HNGC-1 led to a high level of genomic instability and emergence of a spontaneously immortalized clone that developed into cell line HNGC-2 with features of cancer stem cells (CSCs), which include the ability for self-renewal and the capacity to form CD133-positive neurospheres and develop intracranial tumors. The data from our study specify an important role of genomic instability in initiation of transformed state as well as its progression into highly tumorigenic CSCs. The activated forms of Notch and Hes isoforms were expressed in both non-neoplastic neural stem cells and brain tumor stem cells derived from it. Importantly, a significant overexpression of these molecules was found in the brain tumor stem cells. These findings suggest that this model comprised of HNGC-1 and HNGC-2 cells would be a useful system for studying pathways involved in self-renewal of stem cells and their transformation to cancer stem cells. Disclosure of potential conflicts of interest is found at the end of this article.
The Siderocalin/Enterobactin Interaction: A Link between Mammalian Immunity and Bacterial Iron Transport1 (2008)

The siderophore enterobactin (Ent) is produced by enteric bacteria to mediate iron uptake. Ent scavenges iron and is taken up by the bacteria as the highly stable ferric complex [Fe (III)(Ent)] (3-). This complex is also a specific target of the mammalian innate immune system protein, Siderocalin (Scn), which acts as an antibacterial agent by specifically sequestering siderophores and their ferric complexes during infection. Recent literature suggesting that Scn may also be involved in cellular iron transport has increased the importance of understanding the mechanism of siderophore interception and clearance by Scn; Scn is observed to release iron in acidic endosomes and [Fe (III)(Ent)] (3-) is known to undergo a change from catecholate to salicylate coordination in acidic conditions, which is predicted to be sterically incompatible with the Scn binding pocket (also referred to as the calyx). To investigate the interactions between the ferric Ent complex and Scn at different pH values, two recombinant forms of Scn with mutations in three residues lining the calyx were prepared: Scn-W79A/R81A and Scn-Y106F. Binding studies and crystal structures of the Scn-W79A/R81A:[Fe (III)(Ent)] (3-) and Scn-Y106F:[Fe (III)(Ent)] (3-) complexes confirm that such mutations do not affect the overall conformation of the protein but do weaken significantly its affinity for [Fe (III)(Ent)] (3-). Fluorescence, UV-vis, and EXAFS spectroscopies were used to determine Scn/siderophore dissociation constants and to characterize the coordination mode of iron over a wide pH range, in the presence of both mutant proteins and synthetic salicylate analogues of Ent. While Scn binding hinders salicylate coordination transformation, strong acidification results in the release of iron and degraded siderophore. Iron release may therefore result from a combination of Ent degradation and coordination change.
A Strategy to Achieve Efficient Dual‐Mode Luminescence of Eu3+ in Lanthanides Doped Multifunctional NaGdF4 Nanocrystals (2010)

A strategy is proposed to fabricate dual-mode luminescent NaGdF4 nanocrystals that are composed of NaGdF4:Yb3+,Tm3+ core and NaGdF4:Eu3+ shell. Intense downconversion via the sensitization of Gd3+ and upconversion luminescence of Eu3+ that is one order of magnitude higher than the triply-doped core only counterparts have been achieved by employing the distinct core/shell nanostructures and double sensitizations of Yb3+ and Tm3+.
Prediction of Free PSA, PSA Density and PSA Density Transition Zone in the Outcome of Sextant Prostate Biopsies in Patients with Total PSA between 3 and 15 ng/ml (2004)

Objectives: This multicentric clinical study was initiated to check whether percent free PSA, PSA density (PSAD) and PSA density of the transition zone (TZ-PSAD) could enhance the specificity of total PSA alone without reducing its sensitivity in the diagnosis of clinical T1c prostate cancer by ultrasonically guided transrectal sextant biopsies in patients with a total PSA between 3 and 15 ng/ml. Patients and methods: A total of 306 patients were evaluated in seven different centres in the Netherlands and Belgium over a 2-year period. Patients with intermediate PSA levels (3.0–15 ng/ml) underwent measurement of prostate volume by transrectal ultrasound (TRUS) and sextant biopsy under TRUS guidance. The PSAD, TZ-PSAD and percent free PSA were determined for each patient, and their relationship to prostate cancer detection was examined. Results: Identical receiver operating characteristic (ROC) curves for PSAD and TZ-PSAD could be constructed. ROC analysis showed that percent free PSA was inferior to total PSA, PSAD and TZ-PSAD in the detection of prostate cancer. Conclusion: PSAD, TZ-PSAD and percent free PSA do not enhance the specificity of total PSA for cancer detection in men with PSA values between 3 and 15 ng/ml. Each centre has to use his preferential PSA-modification.
Leukemia inhibitory factor: A biological perspective (1991)

The notion that a single hormone may exert a broad range of effects has become well established. As such, leukemia inhibitory factor (LIF) is a prime example. LIF was initially described, purified, and genetically cloned on the basis of its ability to induce the differentiation and suppress the clonogenicity of the monocytic leukemia cell line, M1. Subsequently, it has become apparent that in vitro LIF inhibits the differentiation of pluripotential ES cells, stimulates the synthesis of hepatic acute-phase proteins, induces a switch in neurotransmitter phenotype from adrenergic to cholinergic, suppresses adipocyte lipoprotein lipase activity, and results in an increase in bone resorption. Moreover, elevation of LIF levels in vivo has a number of patho-physiological consequences, many of which parallel those effects observed in vitro. The challenge that lies ahead is to determine whether other sites of LIF action exist and to define more clearly the physiological role LIF plays in vivo. A major mechanism of cell-cell communication is by the production and secretion of polypeptide hormones by one cell type, which act either systemically or locally, via interaction with specific receptors on the surface of responsive cells. Recently, it has become apparent that hormones initially described and named, on the basis of a specific action, in many cases exert a spectrum of effects on a broad range of cell types. Moreover, the effects exerted are often mimicked closely by other hormones. Hormones that act in a pleiotropic manner are, for example, transforming growth factor-beta (TGF-beta), the various fibroblast growth factors (FGFs), interleukin-6 (IL-6), and leukemia inhibitory factor (LIF). This review will focus on the various biological effects ascribed to LIF.
Methy-Pipe: An Integrated Bioinformatics Pipeline for Whole Genome Bisulfite Sequencing Data Analysis (2014)

DNA methylation, one of the most important epigenetic modifications, plays a crucial role in various biological processes. The level of DNA methylation can be measured using whole-genome bisulfite sequencing at single base resolution. However, until now, there is a paucity of publicly available software for carrying out integrated methylation data analysis. In this study, we implemented Methy-Pipe, which not only fulfills the core data analysis requirements (e.g. sequence alignment, differential methylation analysis, etc.) but also provides useful tools for methylation data annotation and visualization. Specifically, it uses Burrow-Wheeler Transform (BWT) algorithm to directly align bisulfite sequencing reads to a reference genome and implements a novel sliding window based approach with statistical methods for the identification of differentially methylated regions (DMRs). The capability of processing data parallelly allows it to outperform a number of other bisulfite alignment software packages. To demonstrate its utility and performance, we applied it to both real and simulated bisulfite sequencing datasets. The results indicate that Methy-Pipe can accurately estimate methylation densities, identify DMRs and provide a variety of utility programs for downstream methylation data analysis. In summary, Methy-Pipe is a useful pipeline that can process whole genome bisulfite sequencing data in an efficient, accurate, and user-friendly manner. Software and test dataset are available at http://sunlab.lihs.cuhk.edu.hk/methy-pipe/.
Multifunctional Nanocarriers for diagnostics, drug delivery and targeted treatment across blood-brain barrier: perspectives on tracking and neuroimaging (2010)

Nanotechnology has brought a variety of new possibilities into biological discovery and clinical practice. In particular, nano-scaled carriers have revolutionalized drug delivery, allowing for therapeutic agents to be selectively targeted on an organ, tissue and cell specific level, also minimizing exposure of healthy tissue to drugs. In this review we discuss and analyze three issues, which are considered to be at the core of nano-scaled drug delivery systems, namely functionalization of nanocarriers, delivery to target organs and in vivo imaging. The latest developments on highly specific conjugation strategies that are used to attach biomolecules to the surface of nanoparticles (NP) are first reviewed. Besides drug carrying capabilities, the functionalization of nanocarriers also facilitate their transport to primary target organs. We highlight the leading advantage of nanocarriers, i.e. their ability to cross the blood-brain barrier (BBB), a tightly packed layer of endothelial cells surrounding the brain that prevents high-molecular weight molecules from entering the brain. The BBB has several transport molecules such as growth factors, insulin and transferrin that can potentially increase the efficiency and kinetics of brain-targeting nanocarriers. Potential treatments for common neurological disorders, such as stroke, tumours and Alzheimer's, are therefore a much sought-after application of nanomedicine. Likewise any other drug delivery system, a number of parameters need to be registered once functionalized NPs are administered, for instance their efficiency in organ-selective targeting, bioaccumulation and excretion. Finally, direct in vivo imaging of nanomaterials is an exciting recent field that can provide real-time tracking of those nanocarriers. We review a range of systems suitable for in vivo imaging and monitoring of drug delivery, with an emphasis on most recently introduced molecular imaging modalities based on optical and hybrid contrast, such as fluorescent protein tomography and multispectral optoacoustic tomography. Overall, great potential is foreseen for nanocarriers in medical diagnostics, therapeutics and molecular targeting. A proposed roadmap for ongoing and future research directions is therefore discussed in detail with emphasis on the development of novel approaches for functionalization, targeting and imaging of nano-based drug delivery systems, a cutting-edge technology poised to change the ways medicine is administered.
The long terminal repeat of an endogenous intracisternal A-particle gene functions as a promoter when introduced into eucaryotic cells by transfection. (1984)

We describe experiments designed to determine whether an endogenous intracisternal A-particle (IAP) gene randomly selected from a mouse embryo library has the potential to be transcriptionally active. Assays for IAP gene transcription were done with permanently transformed rat cells and transiently transfected monkey and mouse cells. The rat cells, which had integrated IAP gene copies, contained IAP RNA. A start site within the IAP 5' long terminal repeat (LTR) was localized by S1 mapping. The promoter activity of the IAP LTR was also measured in cells 48 h after the introduction of recombinant plasmids in which bacterial chloramphenicol acetyl transferase (CAT) encoding sequences were under the control of the LTR. The IAP LTR promoted CAT activity in mouse and monkey cells. In mouse L-cells, the levels of CAT activity were 10 to 25% of those promoted by an analogous recombinant containing the Moloney murine sarcoma virus LTR as the promoter. In contrast to the Moloney murine sarcoma virus LTR, the IAP LTR was five- to eightfold more active in monkey cells than in mouse cells. The 5' and 3' LTRs were equally active, and promoter activity was dependent on having the orientation of the LTRs with respect to the CAT gene the same as their orientation with respect to the IAP gene. A 5'-flanking sequence containing a member of the highly repetitive R-sequence family increased CAT activity in COS cells 11-fold when present along with the LTR. Our results indicate that the LTR of an endogenous mouse IAP gene can function as an efficient promoter in heterologous as well as homologous cells.
HDA1 and HDA3 Are Components of a Yeast Histone Deacetylase (HDA) Complex (1996)

Histone acetylation is maintained through the action of histone acetyltransferases and deacetylases and has been correlated with increased gene activity. To investigate the functional role of these enzymes in the regulation of transcription, we have purified from Saccharomyces cerevisiae two histone deacetylase activities, HDA and HDB, with molecular masses of approximately 350 and 600 kDa, respectively. In vitro, the HDA activity deacetylates all four core histones, has a preference for histone H3, and is strongly inhibited by trichostatin A (a specific inhibitor of histone deacetylases). HDB is considerably less sensitive to trichostatin A. We report the extensive purification of the HDA activity and the identification of peptides (p75, p73, p72, and p71) whose presence correlates with deacetylase activity on native polyacrylamide gels. An antibody to p75 immunoprecipitates peptides with molecular masses similar to those in the 350-kDa complex. Additionally, antibodies to p75 and p71 specifically precipitate histone deacetylase activity and co-immunoprecipitate each other. Gene disruptions of p75 (HDA1) or p71 (HDA3) cause the loss of the 350-kDa (but not the 600-kDa) activity from our chromatography profiles. These data argue strongly that HDA1 and HDA3 are subunits of the HDA complex, which is structurally distinct from the second, HDB complex.
Acute graft versus host disease: pathophysiology, risk factors, and prevention strategies. (2005)

Acute graft versus host disease (GVHD) remains the greatest complication of allogeneic bone marrow transplantation and a major cause of morbidity and mortality. This article summarizes the risk factors and prevention strategies for acute GVHD by considering them within the context of disease pathophysiology. Acute GVHD can be considered a 3-step process: 1) damage from chemotherapy/radiotherapy; 2) host antigen-presenting cell activation and amplification of donor T cells; and 3) target cell apoptosis via cellular and inflammatory mediators. This conceptual framework helps to explain the effectiveness of current prevention strategies and points to areas where new drugs and approaches may be of clinical benefit.
Hodgkin’s Lymphoma Reed Sternberg Cells over Express the T-Cell Inhibitory Carbohydrate-Binding Lectin, Galectin 1: Role of AP-1 and Likely Mechanism of Tumor Immune Escape. (2006)

Abstract Primary Hodgkin lymphomas (HL) contain small numbers of neoplastic Reed-Sternberg (RS) cells within an extensive host inflammatory infiltrate, which includes few cytotoxic T-cells. The lack of an effective host anti-tumor response prompts speculation regarding the mechanisms that HL RS cells use to evade immune surveillance. To identify novel HL-specific T-cell inhibitory molecules, we compared the gene expression profiles of a series of HL and diffuse large B-cell lymphoma (DLBCL) cell lines. The HL cell lines overexpressed galectin-1 (GAL1), a carbohydrate-binding lectin that selectively induces the apoptosis of cytotoxic T cells. GAL1 mRNA abundance was 5- to 33- fold higher in HL cell lines than in DLBCL lines. GAL1 protein expression was also uniformly high in HL cell lines and low or undectable in DLBCL lines by western blotting. Immunohistochemical staining of primary tumors revealed abundant GAL1 expression in HL RS cells whereas DLBCLs were uniformly negative. To elucidate the mechanisms responsible for GAL1 over expression in HL, we analyzed the GAL1 locus and identified a candidate AP1 enhancer element 1.5 kb downstream of the GAL1 transcription start site. The predicted enhancer element increased the expression of a reporter gene (luciferase) 5-fold in a HL cell line but had no effect in either a DLBCL or fibroblast cell line. In electrophoretic mobility studies, AP1 bound to the predicted GAL1 enhancer element in a cell-type specific manner. In addition, mutation of the AP1 binding site in the GAL1 enhancer abolished its activity. Since the AP1 components, cJUN and JUN-B, are known to be overexpressed in HL, we analyzed cJUN and JUN-B copy numbers and transcript abundance in the HL cell lines using 100K high-density SNP arrays and oligonucleotide RNA microarrays. We found increased copy numbers of cJUN and/or JUN-B in all HL cell lines tested and confirmed these findings using fluorescence in situ hybridization (FISH). Increased cJUN and JUN-B copy numbers were associated with significantly higher transcript abundance in the HL cell lines. In additional functional assays, we confirmed previous reports that recombinant GAL1 induced the apoptosis of CD3+ PHA-stimulated lymphoblasts in a dose- and time-dependent manner. Taken together, these studies indicate that HL RS cells selectively over express GAL1, at least in part, via AP1-mediated induction of the GAL1 enhancer. Given the profound effects of GAL1 on cytotoxic T cells, RS-specific expression of GAL1 likely inhibits the host anti-tumor response in HL.
Quantification and application of the placental epigenetic signature of the RASSF1A gene in maternal plasma (2010)

Hypermethylated RASSF1A gene may be considered as an epigenetic marker to detect the fetal DNA in maternal plasma and expands the clinical application of non-invasive prenatal diagnosis.