gebhart/patrepeval huggingface dataset:
Heparin-Associated Thrombocytopenia: The Effects of Various Intravenous lgG Preparations on Antibody Mediated Platelet Activation - A Possible New Indication for High Dose i.v. IgG (1994)

The immunologic type of heparin-associated thrombocytopenia (HAT) is caused by antibodies which activate platelets via the Fc-receptor in the presence of polysulfated oligosaccharides. The antigen is formed by a releasable platelet protein (in many cases PF4) complexed to heparin. Since the role of GP IIb/IIIa in platelet activation by HAT antibodies is controversial, we investigated platelet activation by antibodies related to HAT. We used normal platelets and platelets from a patient with Glanzmann's thrombasthenia (GT) lacking GP IIb/IIIa. Heparin and sera from patients with HAT stimulated GT platelets in the same manner as determined by 14C-serotonin release and the changes in phosphorylation of p20 and p47. Platelet activation could be inhibited by an anti FcRII monoclonal antibody (IV. 3, Fab-fragments), and by Fc-fragments, but not by F(ab')2-fragments of human IgG. The effect of four different, commercially available preparations of intact i.v. IgG on the platelet activation by six HAT sera was investigated by 14C-serotonin release. The inhibitory effect was strongly dependent upon the manufacturing process. At a concentration of 20 mg/ml only IgG that had been subjected to low pH and traces of pepsin sufficiently inhibited platelet activation. IgG treated with polyethylenglycol or sulfitolysis was less effective, whereas beta-propiolactone-treated IgG almost completely lost the ability to inhibit platelet activation by antibodies related to HAT. We conclude that inhibition of GP IIb/IIIa-fibrinogen interaction is insufficient for preventing platelet activation in HAT.(ABSTRACT TRUNCATED AT 250 WORDS)
Interleukin (IL)-23 p19 expression induced by IL-1 in human fibroblast-like synoviocytes with rheumatoid arthritis via active nuclear factor- B and AP-1 dependent pathway (2007)

Our results demonstrate that IL-23, produced by mononuclear cells in synovial fluid with RA and HFLS-RA, promotes inflammatory responses in RA by inducing IL-8 and IL-6 production from HFLS. IL-1beta regulates IL-23 p19 expression via NF-kappaB and AP-1 pathways. This report also demonstrates that IL-23 could promote inflammatory responses in HFLS-RA by stimulating IL-8 and IL-6 production.
Epithelial Cells Are Sensitive Detectors of Bacterial Pore-forming Toxins (2006)

Epithelial cells act as an interface between human mucosal surfaces and the surrounding environment. As a result, they are responsible for the initiation of local immune responses, which may be crucial for prevention of invasive infection. Here we show that epithelial cells detect the presence of bacterial pore-forming toxins (including pneumolysin from Streptococcus pneumoniae, alpha-hemolysin from Staphylococcus aureus, streptolysin O from Streptococcus pyogenes, and anthrolysin O from Bacillus anthracis) at nanomolar concentrations, far below those required to cause cytolysis. Phosphorylation of p38 MAPK appears to be a conserved response of epithelial cells to subcytolytic concentrations of bacterial poreforming toxins, and this activity is inhibited by the addition of high molecular weight osmolytes to the extracellular medium. By sensing osmotic stress caused by the insertion of a sublethal number of pores into their membranes, epithelial cells may act as an early warning system to commence an immune response, while the local density of toxin-producing bacteria remains low. Osmosensing may thus represent a novel innate immune response to a common bacterial virulence strategy.
Stabilization of Vascular Endothelial Growth Factor mRNA by Hypoxia and Hypoglycemia and Coregulation with Other Ischemia-Induced Genes (1995)

Expression of vascular endothelial growth factor (VEGF), an endothelial cell-specific mitogen and a potent angiogenic factor, is upregulated in response to a hypoxic or hypoglycemic stress. Here we show that the increase in steady-state levels of VEGF mRNA is partly due to transcriptional activation but mostly due to increase in mRNA stability. Both oxygen and glucose deficiencies result in extension of the VEGF mRNA half-life in a protein synthesis-dependent manner. Viewing VEGF as a stress-induced gene, we compared its mode of regulation with that of other stress-induced genes. Results showed that under nonstressed conditions, VEGF shares with the glucose transporter GLUT-1 a relatively short half-life (0.64 and 0.52 h, respectively), which is extended fourfold and more than eightfold, respectively, when cells are deprived of either oxygen or glucose. In contrast, the mRNAs of another hypoxia-inducible and hypoglycemia-inducible gene, grp78, as well as that of HSP70, were not stabilized by these metabolic insults. To show that VEGF and GLUT-1 are coinduced in differentially stressed microenvironments, multicell spheroids representing a clonal population of glioma cells in which each cell layer is differentially stressed were analyzed by in situ hybridization. Cellular microenvironments conducive to induction of VEGF and GLUT-1 were completely coincidental. These findings show that two different consequences of tissue ischemia, namely, hypoxia and glucose deprivation, induce VEGF and GLUT-1 expression by similar mechanisms. These proteins function, in turn, to satisfy the tissue needs through expanding its vasculature and improving its glucose utilization, respectively.
Analysis of Schottky gate electron tunneling in polarization induced AlGaN/GaN high electron mobility transistors (1999)

( gate=nickel)/(barrier=GaN/Al (y) Ga (1−y) N)/(buffer=GaN)/(substrate=SiC ) polarizationinduced high electron mobility transistors (PI-HEMTs) show promise for ultrahigh power microwave amplification. The polarization fields in these Ga-face, wurtzite structures are used to engineer the conduction band profile in the absence of any doping. One important attribute of these PI-HEMTs is their ability to withstand electric fields up to 3 MV/cm without avalanche breakdown. The combination of high electric field under the gate necessary to pinch off the channel, and the high electric field fringing to the gate from the large drain–source bias voltage, makes it possible for electron tunneling from the gate into and through the GaN/Al(y)Ga(1−y)N barrier into the GaN channel. A one-dimensional theoretical analysis of the tunneling current at pinchoff as a function of the aluminum fraction (0.05&amp;lt;y&amp;lt;0.45) in the barrier, the operating temperature of the gate metal at 300 and 573 K, and a uniform additional electric field of −1 and −2 MV/cm from drain bias reveals the potential for these GaN based devices to impose negligible current loading by the gate on a microwave driver. Unlike GaAs, avalanche breakdown induced by gate leakage is unimportant in these GaN based power devices.
Transcriptional activation of a conserved sequence element by ras requires a nuclear factor distinct from c-fos or c-jun. (1990)

The expression of transforming growth factor beta type 1 mRNA was increased by conditional expression of ras. A 31-base-pair sequence found approximately 420 base pairs upstream of the gene encoding human transforming growth factor beta 1 acted as a ras-responsive enhancer element in transient transfection assays. The human sequence contains the element TGACTCT that also is found in a murine ras-responsive enhancer. Analysis of nuclear factors present in cells stably transformed by ras indicated that both human and murine sequences were recognized by the same nuclear factor. The role of fos and jun in ras transcriptional activation was analyzed in transfection assays using murine elements that contained either TGACTCT or TGAGTAA. These experiments showed that while both elements are activated by fos/jun expression to nearly the same event, only the former element responded to ras. In addition, activation of reporters containing TGACTCT is 6-fold higher by ras than by fos/jun. Gel retention experiments revealed that the nuclear factor present in cells transformed by ras exhibited the same sequence preference as demonstrated in the transient transfection assays. UV-crosslinking experiments identify a protein of apparent molecular mass 120 kDa that recognizes the ras-responsive element. This work identifies a persistent signal transduction pathway that links ras to nuclear transcription and indicates that a 120-kDa protein is a target of this pathway.
Edar is a downstream target of beta-catenin and drives collagen accumulation in the mouse prostate (2019)

Beta-catenin (CTNNB1) directs ectodermal appendage spacing by activating ectodysplasin A receptor (EDAR) transcription, but whether CTNNB1 acts by a similar mechanism in the prostate, an endoderm-derived tissue, is unclear. Here we examined the expression, function, and CTNNB1 dependence of the EDAR pathway during prostate development. <i>In situ</i> hybridization studies reveal EDAR pathway components including <i>Wnt10b</i> in the developing prostate and localize these factors to prostatic bud epithelium where CTNNB1 target genes are co-expressed. We used a genetic approach to ectopically activate CTNNB1 in developing mouse prostate and observed focal increases in <i>Edar</i> and <i>Wnt10b</i> mRNAs. We also used a genetic approach to test the prostatic consequences of activating or inhibiting <i>Edar</i> expression. <i>Edar</i> overexpression does not visibly alter prostatic bud formation or branching morphogenesis, and <i>Edar</i> expression is not necessary for either of these events. However, <i>Edar</i> overexpression is associated with an abnormally thick and collagen-rich stroma in adult mouse prostates. These results support CTNNB1 as a transcriptional activator of <i>Edar</i> and <i>Wnt10b</i> in the developing prostate and demonstrate <i>Edar</i> is not only important for ectodermal appendage patterning but also influences collagen organization in adult prostates.This article has an associated First Person interview with the first author of the paper.
Hair follicles serve as local reservoirs of skin mast cell precursors (2003)

Several leukocyte populations normally reside in mouse skin, including Langerhans cells and gammadelta T cells in the epidermis and macrophage and mast cells in the dermis. Interestingly, these skin resident leukocytes are frequently identified within or around hair follicles (HFs), which are known to contain stem cell populations that can generate the epidermal architecture or give rise to the melanocyte lineage. Thus, we reasoned that HFs might serve as a local reservoir of the resident leukocyte populations in the skin. When vibrissal follicles of adult mice were cultured in the presence of stem cell factor (SCF), interleukin 3 (IL-3), IL-7, granulocyte-macrophage colony-stimulating factor, and Flt3 ligand, CD45+/lineage-/c-kit+/FcepsilonRI+ cells became detectable on the outgrowing fibroblasts in 10 days and expanded progressively thereafter. These HF-derived leukocytes showed characteristic features of connective tissue-type mast cells, including proliferative responsiveness to SCF, metachromatic granules, mRNA expression for mast cell proteases-1, -4, -5, and -6, and histamine release on ligation of surface IgE or stimulation with substance P or compound 48/80. These results, together with our findings that HFs contain c-kit+ cells and produce SCF mRNA and protein, suggest that HFs provide a unique microenvironment for local development of mast cells.
Proinflammatory interleukin-1 cytokines increase mesangial cell hexokinase activity and hexokinase II isoform abundance (2004)

Mesangial cell hexokinase (HK) activity is increased by a diverse array of factors that share both an association with pathological conditions and a common requirement for classic MAPK pathway activation. To better understand the relationship between glucose (Glc) metabolism and injury and to indirectly test the hypothesis that these changes constitute a general adaptive response to insult, we have sought to identify and characterize injury-associated factors that couple to mesangial cell HK regulation. Proinflammatory interleukin-1 (IL-1) cytokines activate the MAPK pathway and have known salutary effects in this cell type. We therefore examined their ability to influence mesangial cell HK activity, Glc utilization, MAPK pathway activation, and individual HK isoform abundance. IL-1beta increased HK activity in both a time- and concentration-dependent manner: activity increased maximally by approximately 50% between 12 and 24 h with an apparent EC(50) of 3 pM. IL-1alpha mimicked, but did not augment, the effects of IL-1beta. Specific IL-1 receptor antagonism and selective MAPK/ERK kinase or upstream Ras inhibition prevented these increases, whereas PKC inhibition did not. Changes in HK activity were associated with both increased Glc metabolism and selective increases in HKII isoform abundance. We conclude that IL-1 cytokines can regulate cellular Glc phosphorylating capacity via an IL-1 receptor-, Ras-, and classic MAPK pathway-mediated increase in HKII abundance. These findings suggest a novel, previously undescribed mechanism whereby metabolism may be coupled to inflammation and injury.
Additive effects of bovine serum albumin, dithiothreitol and glycerolon PCR (1998)

The effects of bovine serum albumin, dithiothreitol, and glycerol on PCR were studied. PCR under standard conditions failed the amplification of an enterohemorrhagic E. coli DNA fragment when the boiled bacterial cell lysate was used as the template. The addition of either one of bovine serum albumin, dithiothreitol, or glycerol in the reaction mixture allowed the specific fragment amplification; and the optimum concentrations were as follows: bovine serum albumin, 1 mg/ml; dithiothreitol, 10 mM; and glycerol, 5%. In addition, when all of the three agents were included at the above concentrations, the PCR yield was further increased. The effect of the three-agent mixture was not the template specific. Furthermore, the mixture enabled long PCR over 20 kb when Taq DNA polymerase with 3'-5' exonuclease activity was used for the amplification. Our simple PCR method allows robust PCR independent of template purity or amplification length.
Abstract 3483: Modeling circulating tumor cells in the peripheral blood and CSF of breast cancer patients. (2013)

Abstract The enumeration of circulating tumor cells (CTCs) using the CellSearch system (Veridex LLC) is a valuable prognostic clinical tool in several epithelial malignancies. Surveillance methods for metastatic disease involving the central nervous system (CNS) lack adequate sensitivity, specificity, and reproducibility in the clinic. We previously reported a method to enumerate CTCs in the cerebrospinal fluid (CSF) of breast cancer patients with metastases involving the CNS. The enumeration of CTCs in CSF by this method is highly sensitive, accurate, reproducible, and correlates with disease burden by several measures. Here, we concomitantly monitor CTCs in the peripheral blood and CSF of five patients with neoplastic meningitis receiving intrathecal (IT) chemotherapy. In each patient, CTC counts have been more sensitive than conventional cytology, and have predicted the course of symptoms and overall survival more precisely than conventional cytology. We observed a striking inverse relationship between CTC counts in the peripheral blood and CSF. This observation generated the hypothesis that CTCs migrate from the blood to the CSF and the converse as sanctuary sites during compartmentalized therapy to result in systemic disease recurrence. To test this hypothesis we created mouse models of these clinical phenomena including injection of triple-negative breast cancer into the peripheral blood or intracranially. Injection of luciferase-infected MDA-MB-231 or MDA-MB-468 human triple-negative breast cancer cells into the brain of athymic nude mice resulted in primary tumors at the site of injection. The MDA-MB-231, unlike the MDA-MB-468, generated detectable tumor cell dissemination into the CSF of inoculated mice that correlated with a significantly declined survival. CSF collected from the cisterna magna of inoculated mice corroborated these observations. Current studies are examining the impact of compartmentalized therapy on the migration of these tumor cells as well as profiling unique genetic drivers of the subset of tumors cells that disseminate into the CSF. The intercompartmental cycling of tumor cells may represent an important mechanism for disease persistence and recurrence, and suggests that concurrent systemic and CNS-directed therapy may be warranted. Citation Format: Joshua E. Allen, Akshal S. Patel, David T. Dicker, Jonas M. Sheehan, Michael Glantz, Wafik S. El-Deiry. Modeling circulating tumor cells in the peripheral blood and CSF of breast cancer patients. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3483. doi:10.1158/1538-7445.AM2013-3483
Cloning of DNA complementary to rat liver NADPH-cytochrome c (P-450) oxidoreductase and cytochrome P-450b mRNAs. Evidence that phenobarbital augments transcription of specific genes. (1982)

NADPH-cytochrome c oxidoreductase and cytochrome P-450b mRNAs were enriched from tightly membrane-bound polysomes isolated from the livers of rats administered phenobarbital.This was accomplished by polysome immunoadsorption with monospecific I g G directed toward the oxidoreductase and cytochrome P-450b in conjunction with Staphylococcus aureus ghosts and oligo(dT)-cellulose chromatography.Double-stranded cDNA, synthesized from a preparation of poly(A)-RNA specifically enriched in both mRNAs, was inserted into the ampicillin resistance gene of pBR322 by use of oligo(dG)-oligo(dC) tailing.Clones containing DNA complementary to either oxidoreductase or cytochrome P-450b mRNA were selected by differential colony hybridization with [32P] cDNA synthesized from nonenriched, oxidoreductase mRNA-enriched, and cytochrome P-45Ob-mRNA-enriched poly(A)-RNA.Plasmid DNAs isolated from clones which specifically annealed with either oxidoreductase-enriched cDNA or cytochrome P-450b cDNA were each verified by both a solution hybrid-arrest assay and a filter hybrid-selection assay.Restriction endonuclease maps were generated from oxidoreductase and cytochrome P-450b cDNA plasmids that contained inserts of 1870 and 1830 base pairs, respectively.Agarose gel electrophoresis and blot-filter hybridization with nick-translated 32P inserts were utilized to determine that oxidoreductase mRNA is 2800 f 150 nucleotides in length while cytochrome P-450b mRNA contains 2150 A 100 nucleotides.Recombinant plasmid DNAs were used in a hybridization assay which clearly demonstrated that phenobarbital induced the mRNAs coding for NADPH-cytochrome c oxidoreductase and cytochrome P-450b 3-and 14-fold, respectively, 4 h after administration of the drug.This induction process was accompanied by an increase in several distinct high molecular weight intranuclear RNAs that represent precursors to cytochrome P-450b mRNA.These data suggest that phenobarbital increases specific mRNA levels by augmenting transcription.Chronic administration of phenobarbital to rats results in an elevation of several enzymes associated with the hepatic microsomal mixed function oxidase system.Among these are
Atomic Layer Deposition of Ruthenium Thin Films from Ru(thd)3 and Oxygen (2004)

Abstract Ruthenium thin films were grown by atomic layer deposition (ALD) from tris(2,2,6,6‐tetramethyl‐3,5‐heptanedionato)ruthenium [Ru(thd) 3 ] and oxygen, at temperatures between 325 °C and 450 °C. All the films were polycrystalline metallic ruthenium as analyzed by X‐ray diffraction (XRD). Impurity contents of the films (&lt; 2.9 at.‐% H, &lt; 1.9 at.‐% C, and &lt; 5.5 at.‐% O) were nearly independent of the Ru(thd) 3 pulse time as analyzed by time of flight elastic recoil detection analysis (TOF‐ERDA). The films had resistivities below 20 μΩ cm and they adhered well to a thin Al 2 O 3 film on glass. Growth rates of 0.36 Å per cycle were obtained at a deposition temperature of 350 °C. The gaseous reaction by‐products were analyzed in situ by quadrupole mass spectrometry (QMS).
Anaphylactic Challenge Causes Eosinophil Accumulation in Bronchoalveolar Lavage Fluid of Guinea Pigs: Modulation by Betamethasone, Phenidone, Indomethacin, WEB 2086, and a Novel Antiallergy Agent, SCH 37224 (1990)

Eosinophil infiltration into bronchoalveolar areas of the lung has been assessed in guinea pigs sensitized to ovalbumin (OA) and then challenged with the aerosolized antigen. Cell content, histamine, and guinea pig albumin (GPA) have been measured in bronchoalveolar lavage (BAL) fluid from these animals. Extensive eosinophil accumulation resulted from sensitization followed by OA challenge; monocytes that initially accounted for greater than 80% of the BAL cells remained essentially constant, and neutrophils comprised less than 3% of the population throughout. Eosinophils were elevated at 3 h, peaked with a fivefold increase at 24 h, and remained elevated for at least 7 days. Histopathologic changes observed in lungs taken from sensitized guinea pigs 24 h after OA challenge confirm this eosinophilia. Increased histamine and GPA were detected only at 5 min. Oral treatment with betamethasone (ED50 = 0.4 mg/kg), phenidone (ED50 = 15 mg/kg), Sch 37224 (ED50 = 0.5 mg/kg), and WEB 2086 (ED50 = 4 mg/kg) decreased eosinophil accumulation in the BAL fluid, indicating roles for 5-lipoxygenase products and PAF in this multimediator-dependent model of allergic inflammation. On the other hand, 4 mg/kg of indomethacin increased total cells with no effect on eosinophils, precluding a major role for cyclooxygenase products. Sch 37224, an antileukotriene agent and an orally active novel antiallergy agent in sheep, guinea pigs, and humans, is as potent as betamethasone at blocking eosinophil infiltration, suggesting that it may also suppress human pulmonary inflammation.
Catalytic nitrene transfer from an imidoiron(iii) complex to form carbodiimides and isocyanates (2009)

The metastable iron(III) imido species LtBuFeNAd catalyzes transfer of the nitrene fragment NAd from an organic azide to isocyanides or CO, forming unsymmetrical carbodiimides or isocyanates.
Identification of the binding site for activated protein C on the light chain of factors V and VIII. (1990)

Activated protein C has been observed to bind to the light chains of factor Va and factor VIII. Fragments of the factor VIII light chain were produced by recombinant DNA techniques and expressed in Escherichia coli. Three fragments of the light chain were studied; L4 (residues 1974-2332), L3.2 (residues 1560-1829 and 2046-2332), and L3.3 (residues 1560-2052). Two fragments, L4 and L3.3, which overlapped sequences between residues 1974-2052, inhibited the anticoagulant activity of activated protein C. Comparison of the sequences of factors V and VIII in this region revealed that residues 2005-2018 in the factor VIII sequence were homologous with residues 1861-1874 in the factor V sequence. The peptides Arg-Ala-Gly-Met-Gln-Thr-Phe-Leu-Ile (RAGMQTPFLI; residues 1865-1874) from the factor V sequence and His-Ala-Gly-Met-Ser-Thr-Leu-Phe-Ile-Val (HAGMSTLFIV; residues 2009-2018) from the factor VIII sequence were synthesized. Both peptides were observed to inhibit the anticoagulant activity of activated protein C and its inactivation of factors Va and VIII. Furthermore RAGMQTPFLI quenched the fluorescence of the dansyl-Glu-Gly-Arg-modified protease. Polyclonal antibodies against RAGMQTPFLI bound to factor Va and inhibited the anticoagulant activity of activated protein C and the inactivation of factor Va. These results indicate that a portion of the binding sites for activated protein C on the light chains of factors V and VIII are contained in the sequences RAGMQTPFLI or HAGMSTLFIV, respectively.