gebhart/patrepeval huggingface dataset:
A critical role for IL‐15 in TLR‐mediated innate antiviral immunity against genital HSV‐2 infection (2011)

Innate antiviral immunity, particularly at mucosal surfaces, has a critical role in early control of viral infections. Both type I interferons (IFNs) and interleukin-15 (IL-15) are essential components of innate antiviral immunity. It has been shown that toll-like receptor (TLR) ligand-induced innate antiviral immunity requires IFN-α/β and -λ receptor signaling. However, it is not known if IL-15 has a role in TLR ligand-mediated antiviral responses. Here, we report that ligands for TLR-3 and TLR-9 cannot confer protection against genital herpes simplex virus-2 (HSV-2) in the absence of IL-15 in vivo. Interestingly, wild-type mice depleted of natural killer (NK) cells and treated with TLR ligands are protected upon HSV-2 challenge, suggesting that the critical role of IL-15 is independent of NK cell-mediated activity. To examine the cytokine response in the absence of IL-15, we investigated TLR ligand-induced IFN-β and -λ production in the vaginal washes, but found no impairment in IL-15(-/-) mice. Finally, we report no impairment in the expression of the IFN-stimulated genes in IL-15(-/-) mice. Collectively, the data suggest that TLR ligands induce an IFN-mediated response in the vaginal tract of both wild-type and IL-15(-/-) mice, but its induction is insufficient for providing protection against HSV-2 in the absence of IL-15.
Oxyntomodulin ameliorates glucose intolerance in mice fed a high-fat diet (2007)

We evaluated the acute effects of OXM on glucose metabolism in diet-induced insulin-resistant male C57Bl/6 mice. To determine the effects on glucose tolerance, mice were intraperitoneally injected with OXM (0.75, 2.5, or 7.5 nmol) or vehicle prior to an ip glucose tolerance test. OXM (0.75 nmol/h) or vehicle was infused during a hyperinsulinemic euglycemic clamp to quantify insulin action on glucose production and disposal. OXM dose-dependently improved glucose tolerance as estimated by AUC for glucose (OXM: 7.5 nmol, 1,564 +/- 460, P < 0.01; 2.5 nmol, 1,828 +/- 684, P < 0.01; 0.75 nmol, 2,322 +/- 303, P < 0.05; control: 2,790 +/- 222 mmol.l(-1).120 min). Insulin levels in response to glucose administration were higher in 7.5 nmol OXM-treated animals compared with controls. In basal clamp conditions, OXM increased EGP (82.2 +/- 14.7 vs. 39.9 +/- 5.7 micromol.min(-1).kg(-1), P < 0.001). During insulin infusion, insulin levels were twice as high in OXM-treated mice compared with controls (10.6 +/- 2.8 vs. 4.4 +/- 2.2 ng/ml, P < 0.01). Consequently, glucose infusion rate (118.6 +/- 30.8 vs. 38.8 +/- 26.4 microl/h, P < 0.001) and glucose disposal (88.1 +/- 13.0 vs. 45.2 +/- 6.9 micromol.min(-1).kg(-1), P < 0.001) were enhanced in mice that received OXM. In addition, glucose production was more suppressed during OXM infusion (35.7 +/- 15.5 vs. 15.8 +/- 11.4% inhibition, P < 0.05). However, if these data were expressed per unit concentration of circulating insulin, OXM did not affect insulin action on glucose disposal and production. These results indicate that OXM beneficially affects glucose metabolism in diet-induced insulin-resistant C57Bl/6 mice. It ameliorates glucose intolerance, most likely because it elevates glucose-induced plasma insulin concentrations. OXM does not appear to impact on insulin action.
Impact of Flavophospholipol and Vancomycin on Conjugational Transfer of Vancomycin Resistance Plasmids (2000)

The influence of vancomycin and flavophospholipol (FPL) on the transfer rate of conjugative plasmids harboring the vancomycin resistance operon vanA was determined in several clinical and animal isolates of Enterococcus faecium. FPL significantly inhibited the frequency of transfer of conjugative VanA plasmids up to 70-fold. Vancomycin had no significant effect on the transfer rate of VanA plasmids.
Do the Physical and Histologic Features and Time Course in Acute Generalized Exanthematous Pustulosis Reflect a Pattern of Cytokine Dysregulation? (2003)

Background: Acute generalized exanthematous pustulosis (AGEP) is characterized by fever and an indurated erythematous eruption early, with the development of nonfollicular pinhead sterile pustules on an erythematous background. The eruption progresses and resolves relatively rapidly. Although drugs are believed to be the major etiologic agents, other immune modulators, including infections, heavy metals, and radiation, have been implicated. Objective: The purpose of this study was to document underlying diseases in patients with AGEP and to determine if this data and the histologic features suggested an underlying pattern of immune dysregulation. Methods: Twenty-one patients with new or recurrent episodes of AGEP were questioned concerning underlying diseases. The histopathologic features seen in the biopsy sections and the approximate time of biopsy during the course of their eruptions were recorded. Results: Two patients had a history of psoriasis and one patient had a family history of psoriasis, two patients had diagnoses of sarcoid, two patients had inflammatory bowel disease, one had autoimmune thyroiditis, and one patient had multiple sclerosis. Biopsies done at the onset of the eruption showed marked to moderate papillary dermal edema and a mixed dermal inflammatory infiltrate. Shortly thereafter, biopsies showed spongiform pustules within the epidermis and occasional dyskeratotic cells with residual perivascular dermal edema. Although no definitive vasculitis was seen, there was leukocytoclasis within the dermal infiltrate in the majority of biopsy specimens performed more than 48 hours after the onset of the eruption. Conclusion: The histologic features seen in AGEP and the disease associations suggest that patients who develop this eruption may have an underlying tendency for development of a pattern of immune dysregulation characterized by a T helper-1 cytokine pattern.
Identification of neovasculature using nestin in colorectal cancer (2007)

CD34 is commonly used as an endothelial cell marker of tumor vessels. However, this marker detects not only newly formed, but also pre-existing large blood vessels. Nestin, a class VI intermediate filament protein, has recently received attention as a marker for detecting newly formed endothelial cells. In this study, whether nestin is a novel angiogenesis marker in colorectal cancer was examined. HCT-15, a human colon cancer cell line, was subcutaneously implanted into the dorsum of nude mice. After the tumor grew, the mice were perfused with fluorescent beads (Fluospheres). Then, the tumor tissues were used for immunofluorescence staining using nestin and the CD34 antibody. Immunohistochemistry was performed with nestin and CD34 on 101 human colorectal cancer tissue samples. Proliferating endothelial cells were detected immunohistochemically by a proliferating cell nuclear antigen (PCNA) antibody. Clinicopathological factors and prognosis were compared between two groups: that with a microvessel density (MVD) higher than the median MVD and that with MVD lower than the median MVD, as detected by nestin and CD34 labellings. Nestin was localized in endothelial cells in small blood vessels (median, 9.06 microm), whereas CD34 was localized in large blood vessels (median, 9.67 microm) in nude mice. The diameter of nestin-positive vessels was smaller than that of CD34-positive vessels in human colorectal cancer. The number ratio of PCNA-positive cells to nestin-positive vascular endothelial cells was higher than that of PCNA-positive to CD34-positive cells (p=0.002). There were no correlations between nestin-positive blood vessels and clinicopathological factors, but the prognosis was worse in the highly nestin-positive MVD group (p=0.071). Nestin is considered a novel angiogenesis marker of proliferating endothelial cells in colorectal cancer tissue.
Eptifibatide-induced thrombocytopenia and thrombosis in humans require FcγRIIa and the integrin β3 cytoplasmic domain (2009)

Thrombocytopenia and thrombosis following treatment with the integrin alphaIIbbeta3 antagonist eptifibatide are rare complications caused by patient antibodies specific for ligand-occupied alphaIIbbeta3. Whether such antibodies induce platelet clearance by simple opsonization, by inducing mild platelet activation, or both is poorly understood. To gain insight into the mechanism by which eptifibatide-dependent antibodies initiate platelet clearance, we incubated normal human platelets with patient serum containing an alphaIIbbeta3-specific, eptifibatide-dependent antibody. We observed that in the presence of eptifibatide, patient IgG induced platelet secretion and aggregation as well as tyrosine phosphorylation of the integrin beta3 cytoplasmic domain, the platelet FcgammaRIIa Fc receptor, the protein-tyrosine kinase Syk, and phospholipase Cgamma2. Each activation event was inhibited by preincubation of the platelets with Fab fragments of the FcgammaRIIa-specific mAb IV.3 or with the Src family kinase inhibitor PP2. Patient serum plus eptifibatide did not, however, activate platelets from a patient with a variant form of Glanzmann thrombasthenia that expressed normal levels of FcgammaRIIa and the alphaIIbbeta3 complex but lacked most of the beta3 cytoplasmic domain. Taken together, these data suggest a novel mechanism whereby eptifibatide-dependent antibodies engage the integrin beta3 subunit such that FcgammaRIIa and its downstream signaling components become activated, resulting in thrombocytopenia and a predisposition to thrombosis.
Glycobiology: “Towards Understanding the Function of Sugars” (1995)

Conference Article| February 01 1995 Glycobiology: "Towards Understanding the Function of Sugars" R. A. Dwek R. A. Dwek 1The Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, U.K. Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1995) 23 (1): 1–25. https://doi.org/10.1042/bst0230001 Article history Received: September 05 1994 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation R. A. Dwek; Glycobiology: "Towards Understanding the Function of Sugars". Biochem Soc Trans 1 February 1995; 23 (1): 1–25. doi: https://doi.org/10.1042/bst0230001 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search Keywords: AEC, anion-exchange chromatography, CHO, Chinese hamster ovary, CIA, collagen-induced arthritis, CRD, carbohydrate-recognition domain, CTL, cytotoxic T-cell response, 3D, three-dimensional, GC, gas chromatography, GlcNAc, N-acetyl glucosamine, Gnt, GlcNAc transferase, GPC, gel permeation chromatography This content is only available as a PDF. © 1995 Biochemical Society1995 Article PDF first page preview Close Modal You do not currently have access to this content.
Single-electron tunneling at room temperature in cobalt nanoparticles (2002)

We report on the observation of the Coulomb blockade with Coulomb staircases at room temperature in cobalt nanoparticles, with sizes ranging between 1 and 4 nm. A monolayer of these particles is supported by a thin 1–2 nm thick Al2O3 film, deposited on a smooth Au(111) surface. The local electrical transport on isolated Co clusters was investigated with a scanning tunneling microscope (STM). The tunnel contact of the STM tip allowed us to observe single-electron tunneling in the double barrier system STM-tip/Co/Al2O3/Au. Very high values of the Coulomb blockade of up to 1.0 V were reproducibly measured at room temperature on different particles with this setup. The current–voltage characteristics fit well by simulations based on the orthodox theory of single-electron tunneling.
HCI(Human Computer Interaction) Using Multi-touch Tabletop Display (2007)

In this paper, we describe the development of multi-touch tabletop display system and the classification of hand gesture commands for interacting with our system. And also, we analyze the suitability for interactive tabletop in light of the respective input and output degrees of freedom, as well as the precision and completeness provided by each. Our system is based on FTIR (frustrated total internal reflection) principle and hand gestures for necessary instructions are predefined using position sensing and tracking of multi-touch points and the number of fingertips. The system consists of two beam-projectors, diffuser film, infrared cameras and large acrylic screen that attached infrared LED. In recognition process, gesture commands are analyzed by comparing with predefined gesture instructions according to the number of contacted fingertips, Euclidean distance and angles between two bright spots. In this paper, vision based tabletop display system that we proposed provides much advantages understanding human and computer interaction. Also the efficiency of proposed method can be proved through controlling Google-earth.
Domain mapping of the Rad51 paralog protein complexes (2004)

The five human Rad51 paralogs are suggested to play an important role in the maintenance of genome stability through their function in DNA double-strand break repair. These proteins have been found to form two distinct complexes in vivo, Rad51B-Rad51C-Rad51D-Xrcc2 (BCDX2) and Rad51C-Xrcc3 (CX3). Based on the recent Pyrococcus furiosus Rad51 structure, we have used homology modeling to design deletion mutants of the Rad51 paralogs. The models of the human Rad51B, Rad51C, Xrcc3 and murine Rad51D (mRad51D) proteins reveal distinct N-terminal and C-terminal domains connected by a linker region. Using yeast two-hybrid and co-immunoprecipitation techniques, we have demonstrated that a fragment of Rad51B containing amino acid residues 1-75 interacts with the C-terminus and linker of Rad51C, residues 79-376, and this region of Rad51C also interacts with mRad51D and Xrcc3. We have also determined that the N-terminal domain of mRad51D, residues 4-77, binds to Xrcc2 while the C-terminal domain of mRad51D, residues 77-328, binds Rad51C. By this, we have identified the binding domains of the BCDX2 and CX3 complexes to further characterize the interaction of these proteins and propose a scheme for the three-dimensional architecture of the BCDX2 and CX3 paralog complexes.
Neurochemical characterization of excitotoxin lesions in the cerebral cortex (1991)

Neuronal degeneration that occurs in both ischemia and degenerative neurologic illnesses may involve excitotoxic mechanisms. In the present study, we examined whether cortical lesions with agonists acting at subtypes of glutamate receptors result in selective patterns of neuronal death. Injections of quinolinic acid, NMDA, homocysteic acid, kainic acid (KA), and alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) were made at 2 sites in the dorsolateral frontoparietal cortex in rats. After 1 week, the cerebral cortex was either dissected for neurochemical studies, or animals were perfused for histologic evaluation. Concentrations of somatostatin (SS), neuropeptide Y (NPY), substance P (SP), cholecystokinin (CCK), and vasoactive intestinal polypeptide (VIP) were measured by radioimmunoassay, while amino acids and catecholamines were measured by high-performance liquid chromatography (HPLC) with electrochemical detection. NMDA agonists (quinolinic acid, homocysteic acid, and NMDA itself) resulted in dose-dependent reductions in glutamate and GABA, while SS, NPY, SP, CCK, and VIP were either unchanged or significantly increased in concentration. KA and AMPA at doses that resulted in comparable GABA depletions caused significant reductions in SS concentrations. Markers of cortical afferents were spared. All excitotoxins resulted in dose-dependent marked increases in uric acid concentrations. Histologic examination verified that lesions with NMDA agonists produced relative sparing of NADPH-diaphorase, SS, VIP, and CCK neurons. These results show that NMDA excitotoxin lesions result in a pattern of selective neuronal damage in the cerebral cortex that is similar to that which occurs in both ischemia and Huntington's disease.
Tocilizumab (Anti-IL6-Receptor) Therapy For Donor-Specific Antibody (DSA+) Antibody Mediated Rejection (ABMR+) Resistant To IVIG + Rituxan Treatment. (2014)

Introduction: ABMR is a serious and significant complication of transplantation after desensitization (DES) in highly-HLA sensitized patients (HS). Therapies for treatment of ABMR usually include IVIG + Rituximab (I+R) and/or PLEX + I + R. Despite these treatments, many ABMR+ patients experience irreversible allograft injury and progress to ESRD with return to dialysis. The personal and economic costs of allograft failure are enormous. Recent data suggests an important role for IL-6 in mediation of ABMR. Data from animal models show a significant modification of allo-antibody responses and chronic ABMR, a reduction in CD138+ plasma cells and induction of Tregs using anti-IL-6R therapy. Here, we examined the utility of a novel agent (Tocilizumab {TCZ} {anti-IL-6R}, {Genentech-Roche}) for treatment of ABMR+/DSA+ patients resistant to treatment with I + R or PLEX + I + R. Patients & Methods: From 4/2011-10/2013, we identified 11 patients who developed ABMR+ including patients with chronic TG and DSA+. Detailed characteristic of each patient is shown in figure 1. Briefly, patients received TCZ @ 8mg/kg, monthly X 3-9M. Patients were monitored for DSA levels and renal function. Results: All patients had significant pathologic findings of ABMR, usually with elevated DSA levels at time of treatment. After TCZ treatment, DSA levels decreased in 6/11 patients (55%) while 3/11 (27%) remained stable over the 12M observation period. One patient experienced CMV and PCP infection and recovered, otherwise, no SAEs were observed. Renal function was stable in 10/11 patients (91%) while one patient lost the allograft due to unremitting ABMR+.One patient with nephrogenic systemic fibrosis showed significant improvement in skin softening and ROM of L hand post-TCZ.Table: No Caption available.Conclusions: From this small case series, we are cautiously optimistic that TCZ may offer a new option for dealing with severe PLEX + I + R resistant ABMR+ patients. Potential benefits of TCZ therapy include inhibition of B-cell activation, reduction in plasma cell Ig production and induction of Tregs. DISCLOSURE:Jordan, S.: Grant/Research Support, Genentech-Roche, CSL Behring.
Volume-sensitive chloride current in pigmented ciliary epithelial cells: role of phospholipases (1997)

The whole cell recording technique was used to examine an outwardly rectifying chloride current activated by hypotonic shock in bovine pigmented ciliary epithelial (PCE) cells. Removal of internal and external Ca2+ did not affect the activation of these currents, but they were abolished by the phospholipase C inhibitor neomycin. The current was blocked by 5-nitro-2-(3-phenylpropylamino)benzoic acid, 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid, and 4,4'-disothiocyanostilbene-2,2'-disulfonic acid (DIDS) in a voltage-dependent manner, but tamoxifen, dideoxyforskolin, and quinidine did not affect it. This blocking profile differs from that of the volume-sensitive chloride channel in neighboring nonpigmented ciliary epithelial cells (Wu, J., J. J. Zhang, H. Koppel, and T. J. C. Jacob, J. Physiol, Lond. 491: 743-755, 1996), and this difference implies that the volume responses of the two cell types are mediated by different chloride channels (Jacob, T. J. C., and J. J. Zhang. J. Physiol. Lond. In press). Intracellular administration of guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) to PCE cells induced a transient, time-independent, outwardly rectifying chloride current that closely resembled the current activated by hypotonic shock. DIDS produced a voltage-dependent block of the GTP gamma S-activated current similar to the block of the hypotonically activated current. Intracellular neomycin completely prevented activation of this current as did incubation of the cells in calphostin C. and inhibitor of protein kinase C (PKC). Removal of Ca2+ did not affect activation of the current by GTP gamma S but extended the duration of the response. Inhibition of phospholipase A2 (PLA2) with p-bromophenacyl bromide prevented the activation of the hypotonically induced current and also inhibited the current once activated by hypotonic solution. The findings imply that the hypotonic response in PCE cells is mediated by both phospholipase C (PLC) and PLA2. Both phospholipases generate arachidonic acid, and, in addition, the PLC pathway regulates the PLA2 pathway via a PKC-dependent phosphorylation of PLA2.
Thymosin-like peptides as potential immunostimulants. Synthesis via the polymeric-reagent method (1990)

This paper reports our attempt at designing new immunostimulating peptides which are chemically related to the bioactive peptides thymosin alpha 1 and thymopentin. Three peptides were synthesized, Asp-Leu-Lys-Glu-Arg-Lys-Asp-Val-Tyr (3), Arg-Lys-Asp-Val-Tyr-Glu-Glu-Ala-Glu-Asn (2), and Asp-Leu-Lys-Glu-Arg-Lys-Asp-Val-Tyr-Glu-Glu-Ala-Glu-Asn (1), each of which contains the thymopentin sequence and portions of the bioactive sequence of thymosin alpha 1. Peptides 1-3 were assembled from selected blocked fragments that were synthesized by the polymeric-reagent method, using PHBT (polystyrene-bound 1-hydroxybenzotriazole) as the activating polymer. The ability of peptides 1-3 to enhance the activation (RNA synthesis) and proliferation (DNA synthesis) of human T lymphocytes was determined. In comparison to thymosin alpha 1, thymosin alpha 1 (15-28), and thymopentin, peptides 1-3 did not show significant enhancement of these processes.
Spaciotemporal Association and Bone Morphogenetic Protein Regulation of Sclerostin and Osterix Expression during Embryonic Osteogenesis (2004)

Sclerostin (SOST), a member of the cystine-knot superfamily, is essential for proper skeletogenesis because a loss-of-function mutation in the SOST gene results in sclerosteosis featured with massive bone growth in humans. To understand the function of SOST in developmental skeletal tissue formation, we examined SOST gene expression in embryonic osteogenesis in vitro and in vivo. During osteoblastic differentiation in primary calvarial cells, the levels of SOST expression were increased along with those of alkaline phosphatase activity and nodule formation. In situ hybridization study revealed that SOST mRNA expression was observed in the digits in embryonic 13-d limb buds, and SOST expression was observed in osteogenic front in embryonic 16.5-d postcoitus embryonic calvariae, and this expression persisted in the peripheral area of cranial bone in the later developmental stage (embryonic 18.5-d post coitum). These temporal and spacial expression patterns in vivo and in vitro were in parallel to those of osterix (Osx), which is a critical transcriptional factor for bone formation. Similar coexpression of SOST and Osx mRNA was observed when the primary osteoblastic calvarial cells were cultured in the presence of bone morphogenetic protein (BMP)2 in vitro. Moreover, endogenous expression of SOST and Osx mRNA was inhibited by infection of noggin-expression adenovirus into the primary osteoblastic calvarial cells, suggesting that endogenous BMPs are required for these cells to express SOST and Osx mRNA. Thus, expression and regulation of SOST under the control of BMP were closely associated with those of Osx in vivo and in vitro.