gebhart/patrepeval huggingface dataset:
The “Nonamyloidogenic” p3 Fragment (Amyloid β17-42) Is a Major Constituent of Down's Syndrome Cerebellar Preamyloid (1996)

Down's syndrome (DS) patients show accelerated Alzheimer's disease (AD) neuropathology, which consists of preamyloid lesions followed by the development of neuritic plaques and neurofibrillary tangles. The major constituents of preamyloid and neuritic plaques are amyloid beta (Abeta) peptides. Preamyloid lesions are defined as being Abeta immunoreactive lesions, which unlike neuritic plaque amyloid are Congo red-negative and largely nonfibrillar ultrastructurally. DS patients can develop extensive preamyloid deposits in the cerebellum, without neuritic plaques; hence, DS cerebellums are a source of relatively pure preamyloid. We biochemically characterized the composition of DS preamyloid and compared it to amyloid in the neuritic plaques and leptomeninges in the same patients. We found that Abeta17-42 or p3 is a major Abeta peptide of DS cerebellar preamyloid. This 26-residue peptide is also present in low quantities in neuritic plaques. We suggest that preamyloid can now be defined biochemically as lesions in which a major Abeta peptide is p3.
Vascular Endothelial Growth Factor/Vascular Permeability Factor Enhances Vascular Permeability Via Nitric Oxide and Prostacyclin (1998)

These results implicate NO and prostacyclin produced by the interaction of VEGF/VPF with its Flk-1/KDR/VEGF-R2 receptor as mediators of VEGF/VPF-induced vascular permeability. Moreover, this property appears unique to VEGF/VPF among angiogenic cytokines.
The IDO1 selective inhibitor epacadostat enhances dendritic cell immunogenicity and lytic ability of tumor antigen-specific T cells (2016)

Epacadostat is a novel inhibitor of indoleamine-2,3-dioxygenase-1 (IDO1) that suppresses systemic tryptophan catabolism and is currently being evaluated in ongoing clinical trials. We investigated the effects of epacadostat on (a) human dendritic cells (DCs) with respect to maturation and ability to activate human tumor antigen-specific cytotoxic T-cell (CTL) lines, and subsequent T-cell lysis of tumor cells, (b) human regulatory T cells (Tregs), and (c) human peripheral blood mononuclear cells (PBMCs) in vitro. Simultaneous treatment with epacadostat and IFN-γ plus lipopolysaccharide (LPS) did not change the phenotype of matured human DCs, and as expected decreased the tryptophan breakdown and kynurenine production. Peptide-specific T-cell lines stimulated with DCs pulsed with peptide produced significantly more IFN-γ, TNFα, GM-CSF and IL-8 if the DCs were treated with epacadostat. These T cells also displayed higher levels of tumor cell lysis on a per cell basis. Epacadostat also significantly decreased Treg proliferation induced by IDO production from IFN-γ plus LPS matured human DCs, although the Treg phenotype did not change. Multicolor flow cytometry was performed on human PBMCs treated with epacadostat; analysis of 123 discrete immune cell subsets revealed no changes in major immune cell types, an increase in activated CD83+ conventional DCs, and a decrease in immature activated Tim3+ NK cells. These studies show for the first time several effects of epacadostat on human DCs, and subsequent effects on CTL and Tregs, and provide a rationale as to how epacadostat could potentially increase the efficacy of immunotherapeutics, including cancer vaccines.
Fabrication of drug‐loaded electrospun aligned fibrous threads for suture applications (2008)

In this work, drug-loaded fibers and threads were successfully fabricated by combining electrospinning with aligned fibers collection. Two different electrospinning processes, that is, blend and coaxial electrospinning, to incorporate a model drug tetracycline hydrochloride (TCH) into poly(L-lactic acid) (PLLA) fibers have been used and compared with each other. The resulting composite ultrafine fibers and threads were characterized through scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, differential scanning calorimetry, and tensile testing. It has been shown that average diameters of the fibers made from the same polymer concentration depended on the processing method. The blend TCH/PLLA fibers showed the smallest fiber diameter, whereas neat PLLA fibers and core-shell TCH-PLLA fibers showed a larger proximal average diameter. Higher rotating speed of a wheel collector is helpful for obtaining better-aligned fibers. Both the polymer and the drug in the electrospun fibers have poor crystalline property. In vitro release study indicated that threads made from the core-shell fibers could suppress the initial burst release and provide a sustained drug release useful for the release of growth factor or other therapeutic drugs. On the other hand, the threads from the blend fibers produced a large initial burst release that may be used to prevent bacteria infection. A combination of these results suggests that electrospinning technique provides a novel way to fabricate medical agents-loaded fibrous threads for tissue suturing and tissue regeneration applications.
Role of Drp1, a Key Mitochondrial Fission Protein, in Neuropathic Pain (2011)

While oxidative stress has been implicated in small-fiber painful peripheral neuropathies, antioxidants are only partially effective to treat patients. We have tested the hypothesis that Drp1 (dynamin-related protein 1), a GTPase that catalyzes the process of mitochondrial fission, which is a mechanism central for the effect and production of reactive oxygen species (ROS), plays a central role in these neuropathic pain syndromes. Intrathecal administration of oligodeoxynucleotide antisense against Drp1 produced a decrease in its expression in peripheral nerve and markedly attenuated neuropathic mechanical hyperalgesia caused by HIV/AIDS antiretroviral [ddC (2',3'-dideoxycytidine)] and anticancer (oxaliplatin) chemotherapy in male Sprague Dawley rats. To confirm the role of Drp1 in these models of neuropathic pain, as well as to demonstrate its contribution at the site of sensory transduction, we injected a highly selective Drp1 inhibitor, mdivi-1, at the site of nociceptive testing on the dorsum of the rat's hindpaw. mdivi-1 attenuated both forms of neuropathic pain. To evaluate the role of Drp1 in hyperalgesia induced by ROS, we demonstrated that intradermal hydrogen peroxide produced dose-dependent hyperalgesia that was inhibited by mdivi-1. Finally, mechanical hyperalgesia induced by diverse pronociceptive mediators involved in inflammatory and neuropathic pain-tumor necrosis factor α, glial-derived neurotrophic factor, and nitric oxide-was also inhibited by mdivi-1. These studies provide support for a substantial role of mitochondrial fission in preclinical models of inflammatory and neuropathic pain.
Laser scanning third-harmonic-generation microscopy in biology (1999)

A laser scanning microscope using third-harmonic generation as a probe is shown to produce high-resolution images of transparent biological specimens. Third harmonic light is generated by a tightly focused short-pulse laser beam and collected point-by-point to form a digital image. Demonstrations with two biological samples are presented. Live neurons in a cell culture are imaged with clear and detailed images, including organelles at the threshold of optical resolution. Internal organelles of yeast cells are also imaged, demonstrating the ability of the technique for cellular and intracellular imaging.
Separation of complementry strands of plasmid DNA using the biotin-avidin system and its application to heteroduplex formation and RNA/DNA hybridizations in electron microscopy (1985)

A method for the separation of complementary strands with the help of the biotin-avidin system is described. Restriction fragments were terminally labeled at both ends with biotinylated nucleotides. The DNA was cut by a second restriction enzyme, and the fragments were bound to an avidin agarose column. The non-biotinylated strands were eluted with 0.1 M NaOH, and the biotin-labeled strands were subsequently released from the column by elution with 50% guanidine isothiocyanate/formamide. Contamination of the separated strands by complementary single strands was less than 4%.-Separated linear single strands of the vector pEMBL were prepared. On annealing with recombinant circular DNA a substitution loop is formed which provides position and orientation markers for the unambiguous electron microscopic analysis of heteroduplexes or hybrids formed with the inserted sequences. -The terminal biotin label was visualized by complex formation with a streptavidin-ferritin conjugate.
Grb2 Forms an Inducible Protein Complex with CD28 through a Src Homology 3 Domain-Proline Interaction (1998)

CD28 provides a costimulatory signal that results in optimal activation of T cells. The signal transduction pathways necessary for CD28-mediated costimulation are presently unknown. Engagement of CD28 leads to its tyrosine phosphorylation and subsequent binding to Src homology 2 (SH2)-containing proteins including the p85 subunit of phosphatidylinositol 3′-kinase (PI3K); however, the contribution of PI3K to CD28-dependent costimulation remains controversial. Here we show that CD28 is capable of binding the Src homology 3 (SH3) domains of several proteins, including Grb2. The interaction between Grb2 and CD28 is mediated by the binding of Grb2-SH3 domains to the C-terminal diproline motif present in the cytoplasmic domain of CD28. While the affinity of the C-terminal SH3 domain of Grb2 for CD28 is greater than that of the N-terminal SH3 domain, optimal binding requires both SH3 domains. Ligation of CD28, but not tyrosine-phosphorylation, is required for the SH3-mediated binding of Grb2 to CD28. We propose a model whereby the association of Grb2 with CD28 occurs via an inducible SH3-mediated interaction and leads to the recruitment of tyrosine-phosphorylated proteins such as p52<sup>shc</sup> bound to the SH2 domain of Grb2. The inducible interaction of Grb2 to the C-terminal region of CD28 may form the basis for PI3K-independent signaling through CD28.
A Missense Mutation in the Gene Results in Total Absence of α3-Fucosylation of Human α1-Acid Glycoprotein (1996)

The major alpha3-fucosyltransferase activity in human plasma is encoded by the gene for fucosyltransferase VI (FUT6). A missense mutation (Gly-739 --> Ala) in this gene is responsible for deficiency of enzyme activity in plasma. To examine whether this fucosyltransferase is the sole enzyme responsible for the alpha3-fucosylation of serum glycoproteins in the liver, we studied the fucosylation of three glycoproteins in sera of individuals with or without inactivated FUT3 and/or FUT6 gene(s) but with a functional FUT5 gene. alpha1-Acid glycoprotein was used as the principal reporter protein for liver alpha3-fucosyltransferase activity, because of its high fucose content. In all individuals with the FUT6 missense mutation Gly-739 --> Ala in double dose, no fucosylation of alpha1-acid glycoprotein was found. This alpha1-acid glycoprotein was not intrinsically resistant to fucosylation, since it was susceptible to in vitro fucosylation using an alpha3/4-fucosyltransferase isolated from human milk. The same result was found for alpha1-antichymotrypsin and alpha1-protease inhibitor. On the other hand in all individuals with alpha3-fucosyltransferase activity in plasma, alpha3-fucosylated glycoforms of the glycoproteins studied were found. The degree of fucosylation of alpha1-acid glycoprotein was correlated with alpha3-fucosyltransferase activity (Rs = 0.82). These data indicate that the product of FUT6, but not of FUT3 or of FUT5, is responsible for the alpha3-fucosylation of glycoproteins produced in liver and suggest that this organ is a major source of alpha3-fucosyltransferase activity in plasma.
Disposable Polydimethylsioxane Package for 'Bio~Microfluidic System' (2005)

A disposable polydimethylsioxane package is developed for ‘Bio-Microfluidic System’. Disposable Bio-Microfluidic system avoids the contamination of the system after each use and this requires the use of low cost materials. Polydimethylsioxane (PDMS) is an attractive low cost material for making substrates of the micro-fluidic package. The disposable PDMS Package consists of PDMS substrates, which are fabricated by soft-lithography. The PDMS substrates are bonded together to form the disposable package with the use of a thin-film, coated both side with adhesive material. The adhesive material is selected by chemical soaking test, peel test and bio-analysis. The tests reveal that the adhesive material can handle all chemical reagents without causing blockage or discoloration to the package. The disposable PDMS package uses a plug-in concept as the macro-micro fluidic interconnects that allows easy detachment of package from the external fluidic system. The developed disposable PDMS package has demonstrated a fluidic leak-proof package that handles up to 100kPa pressure with flow-rate of 200µl/min. The package has also demonstrated that it can filter out Viral Ribonucleic Acids (RNA) from spiked blood sample. This micro fluidic package forms an integral part of the bio micro fluidic system.
The Baculovirus p35 Protein Inhibits Fas- and Tumor Necrosis Factor-induced Apoptosis (1995)

The baculovirus p35 gene product inhibits virally induced apoptosis, developmental cell death in Caenorhabditis elegans and Drosophila, and neuronal cell death in mammalian systems. Therefore, p35 likely inhibits a component of the death machinery that is both ubiquitous and highly conserved in evolution. We now show for the first time that p35 also inhibits Fas- and tumor necrosis factor (TNF)-induced apoptosis. Additionally, p35 blocks TNF- and Fas-induced proteolytic cleavage of the death substrate poly(ADP-ribose) polymerase from its native 116-kDa form to the characteristic 85-kDa form. This cleavage is thought to be catalyzed by an aspartate-specific protease of the interleukin 1 beta-converting enzyme family designated prICE (Lazebnik, Y. A., Kaufmann, S. H., Desnoyers, S., Poirier, G. G., and Earnshaw, W. C. (1994) Nature 371, 346-347). Our data suggest that p35 must directly or indirectly inhibit prICE. Given that p35 inhibits both TNF and Fas killing, along with previous reports of its ability to block developmental, viral, and x-irradiation-induced cell death, the present results indicate that TNF- and Fas-mediated apoptotic pathways must have components in common with these highly conserved death programs.
Rhabdovirus-Based Vectors with Human Immunodeficiency Virus Type 1 (HIV-1) Envelopes Display HIV-1-Like Tropism and Target Human Dendritic Cells (2002)

We describe replication-competent, vaccine strain-based rabies viruses (RVs) that lack their own single glycoprotein and express, instead, a chimeric RV-human immunodeficiency virus type 1 (HIV-1) envelope protein composed of the ectodomain and transmembrane domains of HIV-1 gp160 and the cytoplasmic domain of RV G. The envelope proteins from both X4 (NL4-3)- and R5X4 (89.6)-tropic HIV-1 strains were utilized. These recombinant viruses very closely mimicked an HIV-1- like tropism, as indicated by blocking experiments. Infection was inhibited by SDF-1 on cells expressing CD4 and CXCR4 for both viruses, whereas RANTES abolished infection of cells expressing CCR5 in addition to CD4 in studies of the RV expressing HIV-1(89.6) Env. In addition, preincubation with soluble CD4 or monoclonal antibodies directed against HIV-1 gp160 blocked the infectivity of both G-deficient viruses but did not affect the G-containing RVs. Our results also indicated that the G-deficient viruses expressing HIV-1 envelope protein, in contrast to wild-type RV but similar to HIV-1, enter cells by a pH-independent pathway. As observed for HIV-1, the surrogate viruses were able to target human peripheral blood mononuclear cells, macrophages, and immature and mature human dendritic cells (DC). Moreover, G-containing RV-based vectors also infected mature human DC, indicating that infection of these cells is also supported by RV G. The ability of RV-based vectors to infect professional antigen-presenting cells efficiently further emphasizes the potential use of recombinant RVs as vaccines.
Human factor VIII from heparinized plasma (1988)

Human factor VIII was purified from heparinized blood by cryoprecipitation, poly(ethyleneglycol) precipitation, Affi-Gel blue, aminohexyl, polyelectrolyte E5 and immunoaffinity chromatography. A purification of 280,000-fold over plasma with a specific activity over 5300 units/mg was achieved. Analyses of factor VIII using HPLC indicated a molecular mass of 280-340 kDa. Variation in the native mass may reflect heterogeneity of the protein due to associated lipid since structural analysis confirmed that factor VIII contained variable amounts of free fatty acids and diglycerides and triglycerides, but no phospholipids. Additional characterization by denaturing polyacrylamide gel electrophoresis under reducing conditions, followed by silver staining, showed a major single-chain polypeptide of factor VIII with a mass of approximately 260 kDa. To determine whether proteolyzed forms of factor VIII were present during fractionation, we analysed earlier steps in purification. This revealed additional species of factor VIII eluting faster than the single-chain form during chromatography on polyelectrolyte E5. Gel electrophoresis showed that these species of factor VIII consisted of multiple polypeptide chains, and partial peptide mapping using Staphylococcus aureus V8 protease indicated that they were structurally related. Monoclonal and hemophilic antibodies were used in immunoadsorption experiments to demonstrate that the purified factor VIII was composed predominantly of the 260-kDa factor VIII chain.
Prolonged binding of a radiolabeled monoclonal antibody (B72.3) used for the in situ radioimmunodetection of human colon carcinoma xenografts. (1984)

Monoclonal antibody B72.3 binds to a glycoprotein complex with a molecular weight of 220,000 to 400,000. B72.3 reacts with approximately 50% of human mammary carcinomas and to 80% of the colon carcinomas tested but does not react appreciably with normal mammary tissue, with normal colon, or to a variety of normal adult human tissues tested using immunohistochemical techniques. B72.3 immunoglobulin G was purified and radiolabeled with 125I without significant loss in its reactivity to tumor extracts. The radiolabeled B72.3 immunoglobulin G was shown to efficiently localize human colon carcinoma xenografts in athymic mice. Tumor:tissue ratios of the localized antibody rose over the 7-day period studied, with tumor:liver, tumor:spleen, or tumor:kidney ratios of approximately 18:1 at Day 7 and a tumor:blood ratio of approximately 5:1 at Day 7. Tumor:muscle or tumor:brain ratios rose to over 100:1. The amount of radioactivity in the tumor increased for the first 2 days postinoculation of antibody and stayed constant over a 19-day period of study. Thus, there was no appreciable loss of radioiodine from the tumor over the study interval. No localization was seen in mice bearing a B72.3 antigen-negative human melanoma xenograft or with an isotype-identical control immunoglobulin G in mice bearing colon tumor xenografts. Gamma camera imaging with a pinhole collimator confirmed the ability of the radiolabeled antibody to detect the presence of colon carcinoma xenografts less than 0.5 cm in diameter over a 19-day period. The potential use of this system as a model for radioimmunotherapy will be discussed.
Chemosensor Ensemble with Selectivity for Inositol-Trisphosphate (1998)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTChemosensor Ensemble with Selectivity for Inositol-TrisphosphateKenichi Niikura, Axel Metzger, and Eric V. AnslynView Author Information The Department of Chemistry and Biochemistry The University of Texas at Austin Austin, Texas 78712 Cite this: J. Am. Chem. Soc. 1998, 120, 33, 8533–8534Publication Date (Web):August 7, 1998Publication History Received24 March 1998Published online7 August 1998Published inissue 1 August 1998https://pubs.acs.org/doi/10.1021/ja980990chttps://doi.org/10.1021/ja980990crapid-communicationACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views1245Altmetric-Citations212LEARN 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 SUBJECTS:Alcohols,Assays,Fluorescence,Guanidine,Receptors Get e-Alerts
Abstract A112: Combined targeting of HER2 and HER3 inhibits tumor growth in both trastuzumab-sensitive and trastuzumab-resistant breast cancer models. (2013)

Abstract HER3 (ERBB3) is a tumor driver in divergent cancer types with high HRG levels or heightened EGFR or HER2 kinase activity via growth signal coupling to the PI3K-AKT pathway. HER3 lacks intrinsic tyrosine kinase activity but is capable of signaling after heterodimerizing with tyrosine kinase ERBB family members EGFR or HER2. Heterodimer formation is driven either by the binding of heregulin (NRG1/HRG) to HER3 (ligand dependent - LD), or alternatively, by overexpression of EGFR or HER2 (ligand-independent - LI). Preclinical evaluation of MEDI3379, a human IgG1 modified monoclonal anti-HER3 antibody that antagonizes both LD and LI signaling, demonstrated tumor growth inhibition in the HER2-expressing MDA-MB-361 breast cancer xenograft model. Anti-tumor activity of MEDI3379 in this model was increased in combination with the HER2-targeting drug trastuzumab to a greater extent than MEDI3379 when combined with either lapatinib or pertuzumab. Combined inhibition of HER2 and HER3 led to strong reduction in pHER3. Unexpectedly, co-administration of MEDI3379 together with trastuzumab in MDA-MB-361 tumor-bearing mice but not in naïve mice resulted in reduced serum levels of trastuzumab. A control antibody combined with trastuzumab in MDA-MB-361 tumor bearing mice did not have this effect. Furthermore, in the trastuzumab-resistant JIMT-1 breast cancer xenograft model which has high HRG and pHER3 levels MEDI3379 but not pertuzumab resensitized JIMT-1 tumors to trastuzumab resulting in synergistic anti-tumor activity and a reduction of pHER3. In vivo resistance to this regimen appeared with prolonged treatment of JIMT-1 tumors and was accompanied by a decrease in homogenous expression of HER2. In conclusion, the use of MEDI3379 in combination with trastuzumab in HER2-amplifed breast cancer cell lines has demonstrated additional tumor growth inhibition over single agent trastuzumab and overcoming trastuzumab-resistance mechanisms. This combination warrants further evaluation in preclinical and clinical studies. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A112. Citation Format: Philipp Steiner, Leslie Wetzel, Kevin Schifferli, Raymond Rothstein, Ravinder Tammali, Marlon Rebelatto, Zhan Xiao, Andrew Pierce, Robert Hollingsworth. Combined targeting of HER2 and HER3 inhibits tumor growth in both trastuzumab-sensitive and trastuzumab-resistant breast cancer models. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A112.