gebhart/patrepeval huggingface dataset:
Atriopeptin, sodium azide and cyclic GMP reduce secretion of aqueous humour and inhibit intracellular calcium release in bovine cultured ciliary epithelium (1999)

This study examined the involvement of cyclic GMP, protein kinase G and intracellular Ca2+ movements in the modulation of aqueous humour formation. Using the bovine arterially-perfused eye preparation, drug effects on intraocular pressure and aqueous humour formation rate were measured by manometry and fluorescein dilution, respectively. Drug effects on intracellular [Ca2+] were determined by fura-2 fluorescence ratio technique in nontransformed, cultured ciliary epithelium. Intra-arterial injection of atriopeptin (50 pmol) or sodium azide (10 nmol) produced significant reduction in aqueous humour formation (>38%). This was blocked by selective inhibition (KT-5823) of protein kinase G, but not by selective inhibition (KT-5720) of protein kinase A. Reductions of intraocular pressure produced by atriopeptin or azide were almost completely blocked by KT-5823. ATP (100 microM) caused rapid, transient increase in intracellular Ca2+ followed by a slow decline and prolonged plateau. This response showed concentration-dependent inhibition by atriopeptin, azide or 8-bromo cyclic GMP, and this inhibition of the rapid (peak) Ca2+ increase was enhanced by zaprinast (100 microM; phosphodiesterase inhibitor). KT-5823 blocked the suppression of the peak Ca2+ response but not suppression of the plateau. Arterial perfusion of ATP (0.1-100 microM) produced a concentration-dependent decrease in aqueous humour formation. Aqueous humour formation in the bovine eye can be manipulated through cyclic GMP, operating via protein kinase G. Close parallels appear when Ca2+ movements are modified by similar manipulations of cyclic GMP, suggesting that Ca2+ transients may play an important role in aqueous humour formation and that interplay occurs between cyclic GMP and Ca2+.
Washout of local anesthetic during arthroscopy (1988)

The recommended dose of lidocaine is often insufficient to obtain adequate local anesthesia when performing knee arthroscopy, particularly in bilateral procedures. A prospective study was conducted to identify the quantity of anesthetic washed out of the knee by irrigation solution. Fourteen patients had knee arthroscopy performed with local anesthetic, either for diagnosis or reparative surgery. Anesthesia was obtained using 20 ml of 0.5% lidocaine injected intraarticularly at the beginning of each procedure, augmented in four cases by an additional 20 ml of 0.5% lidocaine during the procedure. Each of three portals was also infiltrated with bupivacaine 0.25% with epinephrine. Analysis of the normal saline effluent from knee irrigation during the procedure revealed that washout of lidocaine was 50% by weight (range, 42-66%). This percentage did not vary with age, operative time, or quantity of irrigation. We conclude that: (a) safe local anesthesia can be obtained in the average patient with less than the maximum dose of lidocaine, and (b) because of the 50% washout, the safe dose of lidocaine can be increased substantially if needed.
Review: On TRAIL for malignant glioma therapy? (2010)

Glioblastoma (GBM) is a devastating cancer with a median survival of around 15 months. Significant advances in treatment have not been achieved yet, even with a host of new therapeutics under investigation. Therefore, the quest for a cure for GBM remains as intense as ever. Of particular interest for GBM therapy is the selective induction of apoptosis using the pro-apoptotic tumour necrosis factor-related apoptosis-inducing ligand (TRAIL). TRAIL signals apoptosis via its two agonistic receptors TRAIL-R1 and TRAIL-R2. TRAIL is normally present as homotrimeric transmembrane protein, but can also be processed into a soluble trimeric form (sTRAIL). Recombinant sTRAIL has strong tumouricidal activity towards GBM cells, with no or minimal toxicity towards normal human cells. Unfortunately, GBM is a very heterogeneous tumour, with multiple genetically aberrant clones within one tumour. Consequently, any single agent therapy is likely to be not effective enough. However, the anti-GBM activity of TRAIL can be synergistically enhanced by a variety of conventional and novel targeted therapies, making TRAIL an ideal candidate for combinatorial strategies. Here we will, after briefly detailing the biology of TRAIL/TRAIL receptor signalling, focus on the promises and pitfalls of recombinant TRAIL as a therapeutic agent alone and in combinatorial therapeutic approaches for GBM.
Tunable Flexible Pressure Sensors using Microstructured Elastomer Geometries for Intuitive Electronics (2014)

Pressure and touch sensitivity is crucial for intuitive human‐machine interfaces. Here, we investigate the use of different microstructured elastomers for use as dielectric material in capacitive pressure sensors. We use finite element modeling to simulate how different microstructures can reduce the effective mechanical modulus. We found that pyramidal structures are optimal shapes that reduce the effective mechanical modulus of the elastomer by an order of magnitude. We also investigate the dependence of spacing of the pyramidal microstructures and how it impacts mechanical sensitivity. We further demonstrate the use of these elastomeric microstructures as the dielectric material on a variety of flexible and stretchable substrates to capture touch information in order to enable large area human‐computer interfaces for next generation input devices, as well as continuous health‐monitoring sensors.
tRNA genes and pathogenicity islands: influence on virulence and metabolic properties of uropathogenic Escherichia coli (1995)

The uropathogenic Escherichia coli strain 536 (O6:K15:H31) carries two unstable DNA regions on its chromosome which were termed pathogenicity islands (Pais). Both pathogenicity islands, Pai I and Pai II, are incorporated into tRNA specific loci: Pai I is located in the tRNA gene for selenocysteine (selC), and Pai II is integrated in the leucine-specific tRNA locus leuX. Mutant strain 536-21 has lost the two pathogenicity islands together with the intact tRNA genes. While 536 is a virulent strain, 536-21 has lost a number of properties, including in vivo virulence. In previous publications we reported that the genes coding for two haemolysins (hly I, hly II) and P-related fimbria (prf) are located on the Pais. In this paper, we demonstrate that the expression of other gene products influencing metabolic properties in addition to in vivo virulence are strongly dependent on the intact tRNA loci selC and leuX. In order to determine the influence of the two tRNAs on the expression of these properties, the genes selC and leuX were cloned from the genome of strain 536 and then introduced into the mutant 536-21. Our results clearly show that the seleno-cysteine-specific tRNA (tRNA(Sec)) directly influences the ability of the bacteria to grow under anaerobic conditions, because selenocysteine is part of the enzyme formate dehydrogenase (FDH) which is involved in mixed acid fermentation. The rare leucine-specific tRNA5(Leu), encoded by leuX, influences a number if properties including type 1 fimbria production, flagellation and motility, production of enterobactin and serum resistance, and is also necessary for full in vivo virulence. While the tRNA(Sec) is directly involved in the production of FDHs, the leuX specific tRNA5(Leu) appears to influence the expression of various factors through specific transcriptional or translational control mechanisms.
Polyanhydride microspheres as drug carriers. II. Microencapsulation by solvent removal (1988)

Abstract A new method to prepare polyanhydride microspheres, namely via solvent removal, is presented. Polyanhydrides composed of the following diacids were used: sebacic acid (SA), bis ( p ‐carboxy‐phenoxy) propane (CPP), and dodecanedioic acid (DD). Polymers were characterized by infrared (IR) spectroscopy, X‐ray diffraction, viscosity, differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). Drug release was affected by polymer composition, physical properties of the microspheres, and type of drug. The potential for injectable microspheres (size range 1–300 μm) made of copolymer (CPP‐SA 50:50), as biodegradable polymer carriers for the controlled release of insulin in treating diabetes mellitus, was assessed. Both 5% and 10% w/w insulin‐loaded microspheres were prepared. The 10% loaded microspheres produced the best clinical response, demonstrating five days of urine glucose control and four days of serum glucose control in diabetic rats.
Synthesis, anticancer, and antibacterial activities of piplartine derivatives on cell cycle regulation and growth inhibition (2013)

A series of piplartine derivatives were synthesized via Baylis-Hillman reaction and evaluated for anticancer and antibacterial activities. The cytotoxicity of these compounds was examined in two different human tumor cell lines, IMR-32 and HeLa. The antibacterial activity was examined in Staphylococcus aureus and Pseudomonas aeruginosa. The results showed that compounds 2b, 2e, and 2j were found to be the most active compounds, which displayed line no cytotoxicity, but G2-M cell cycle arrest in tumor cells, and showed cytostatic effects in bacteria.
Phenylquinoxaline Polymers and Low Molar Mass Glasses as Electron-Transport Materials in Organic Light-Emitting Diodes (1998)

We present a new synthetic approach to both phenylquinoxaline polymers and low molar mass glasses. A palladium-catalyzed coupling of arylalkynes and bromobenzenes and subsequent oxidation of the triple bonds lead to the corresponding benziles. Reaction with diaminobenzidine yields poly(phenylquinoxalines) (PPQs), whereas the reaction with 1,2-diaminobenzenes leads to low molar mass bis(phenylquinoxalines) (BPQs) and tris(phenylquinoxalines) (TPQs). Both PPQs and TPQs carry tert-butyl or CF3− substituents and are fully soluble in chlorinated hydrocarbons. The starburst TPQs are able to form stable, low molar mass glasses. Cyclic voltammetry reveals that the TPQs have low-lying lowest unoccupied molecular orbitals levels at about −3.6 eV and are attractive as electron-transport materials in organic light-emitting diodes (LEDs). Two-layer LEDs with poly(phenylenevinylene) were fabricated that show a maximum brightness of 450 cd/m2.
Histone Deacetylase Inhibitor LAQ824 Augments Inflammatory Responses in Macrophages through Transcriptional Regulation of IL-10 (2011)

APCs are important in the initiation of productive Ag-specific T cell responses and the induction of T cell anergy. The inflammatory status of the APC at the time of encounter with Ag-specific T cells plays a central role in determining such divergent T cell outcomes. A better understanding of the regulation of proinflammatory and anti-inflammatory genes in its natural setting, the chromatin substrate, might provide novel insights to overcome anergic mechanisms mediated by APCs. In this study, we show for the first time, to our knowledge, that treatment of BALB/c murine macrophages with the histone deacetylase inhibitor LAQ824 induces chromatin changes at the level of the IL-10 gene promoter that lead to enhanced recruitment of the transcriptional repressors HDAC11 and PU.1. Such an effect is associated with diminished IL-10 production and induction of inflammatory cells able of priming naive Ag-specific T cells, but more importantly, capable of restoring the responsiveness of anergized Ag-specific CD4(+) T cells.
A new route to 2′,3′‐dideoxycytidine (1990)

Abstract 2‐Deoxy‐D‐ribose ( 1 ) was converted into its methyl glycofuranoside 2 , which was treated with 4‐biphenylcarbonyl chloride to give a separable mixture of 3 (26%) and 4 (40%). Compounds 3 and 4 were deoxygenated by Barton deoxygenation to give the corresponding 2,3‐dideoxyribose derivatives 7 and 8 in good yields as crystalline materials. Reaction of 7 and 8 with the silylated N 4 ‐isobutyrylcytosine 9 , using trimethylsilyl triflate as catalyst afforded a separable mixture of the protected 2′,3′‐dideoxynucleosides 10 (29%) and 11 (31%) which were deprotected with methanolic ammonia to give 2′,3′‐dideoxycytidine ( 12 ) and its α‐anomer 13 .
Textbook of Endocrine Physiology (2011)

The sixth edition of this highly popular text retains its comprehensive coverage of endocrine basics from previous editions while featuring entirely new chapters on several topics, including the assessment of endocrine function, sexual differentiation, growth regulation, the thyroid, the adrenals, and calcium homeostasis. Chapters have been updated and reorganized to make information easily accessible in concise form, and new figures and tables have been added to enhance the presentation of complex concepts. Fundamental principles of endocrine physiology are reinforced with illustrative examples from clinical observation and the limitations of current knowledge are properly identified. The ideal resource for students entering the field, the Textbook of Endocrine Physiology aims to provide for all a solid basis in fundamentals of endocrinology and for some, inspiration for the pursuit of advanced medical or graduate studies in the field.
Fidelity of the RNA-dependent DNA synthesis exhibited by the reverse transcriptases of human immunodeficiency virus types 1 and 2 and of murine leukemia virus: mispair extension frequencies (1992)

Human immunodeficiency viruses type 1 and 2 (HIV-1 and HIV-2, respectively) exhibit extensive genetic variations. It was postulated that much of this genetic variability stems from the low fidelity of the reverse transcription step. Both HIV reverse transcriptases (RTs) were shown to be particularly error-prone during the in vitro DNA-dependent DNA synthesis relative to other retroviral RTs. Extension of mismatched 3'-termini of the primer DNA was shown to be a major determinant in the infidelity of HIV RTs. However, reverse transcriptases generally exhibit dual template specificities. Therefore, we determined in the current study the fidelity of RNA-dependent DNA synthesis catalyzed in vitro by the RTs of HIV-1 and HIV-2 in comparison with that of murine leukemia virus (MLV) RT. Consequently, we examined the ability of these enzymes to extend preformed 3'-terminal A.A, A.C, and A.G mispairs by quantitating the amount and length of extended primers in a primer extension assay using ribosomal RNA as a template. The results demonstrate that the three RTs studied exhibited efficient extensions from 3'-terminal mispairs with a specificity of A.C greater than A.A greater than A.G. Nevertheless, the HIV RTs are qualitatively as well as quantitatively more error-prone than MLV RT. The mispair extension efficiency appears to be affected mainly by the increase of apparent Km values, rather than by the change in Vmax values.(ABSTRACT TRUNCATED AT 250 WORDS)
Epinephrine acts through erythroid signaling pathways to activate sickle cell adhesion to endothelium via LW-αvβ3 interactions (2004)

The possible role of physiologic stress hormones in enhancing adhesion of sickle erythrocytes (SS RBCs) to endothelial cells (ECs) in sickle cell disease (SCD) has not been previously explored. We have now found that up-regulation of intracellular cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) by epinephrine significantly increased sickle but not normal erythrocyte adhesion to both primary and immortalized ECs. Inhibition of serine/threonine phosphatases also enhanced sickle erythrocyte adhesion at least partially through a PKA-dependent mechanism. Adhesion was mediated through LW (intercellular adhesion molecule-4 [ICAM-4], CD242) blood group glycoprotein, and immunoprecipitation studies showed that LW on sickle but not on normal erythrocytes undergoes increased PKA-dependent serine phosphorylation as a result of activation. The major counter receptor for LW was identified as the alphavbeta3 integrin on ECs. These data suggest that adrenergic hormones such as epinephrine may initiate or exacerbate vaso-occlusion and thus contribute to the association of vaso-occlusive events with physiologic stress.
AXL Inhibitors in Cancer: A Medicinal Chemistry Perspective (2015)

Dysregulation of the AXL receptor tyrosine kinase has been associated with many types of cancer. It has not been until recently, however, that targeting AXL has come under the spotlight because of ever accumulating evidence of its strong correlation with poor prognosis and drug resistance. The entry of the first AXL-branded inhibitor in clinical trials in 2013 marked an important milestone for the clinical validation of AXL as an anticancer target. Nevertheless, to weigh the current contribution and potential future impact of AXL inhibition in the clinic, it is fundamental to recognize that several kinase inhibitors approved or in clinical development have AXL as either a prominent secondary or even the primary target. Through this review, the chemical and biological properties of the main inhibitors targeting AXL (either intentionally or unintentionally) will be discussed, along with the prospects and challenges to translate AXL inhibitors into a bona fide therapeutic option.
Suramin increases p53 protein levels but does not activate the p53-dependent G1 checkpoint. (1996)

Suramin is an antineoplastic agent which has a cytostatic effect on both normal and tumor-derived cells. We have investigated whether the induction of growth arrest by suramin requires the p53 protein, a tumor suppressor gene product involved in the initiation of growth arrest following DNA damage. Activation of the p53 protein by genotoxic agents causes increased p53 protein levels and p53-dependent transcription of the p21 gene. The p21 protein then inhibits cyclin-dependent kinases, initiating G1 arrest. Exposure of NIH-3T3 cells to suramin caused a rapid (1-2 h) increase in the level of p53-DNA-binding activity. Flow cytometric analysis indicated that suramin arrested NIH-3T3 cells in G0-G1. However, suramin did not increase the p53-dependent transcription of the p21 gene or inhibit cyclin-dependent kinase 2 kinase activity. If NIH-3T3 cells were exposed to radiation or suramin plus radiation, p21 mRNA levels were increased and cyclin-dependent kinase 2 kinase activity was inhibited, indicating that suramin does not block the cells' ability to increase p21 levels. To determine whether the G0-G1 arrest induced by suramin required p53, NIH-3T3 cells transfected with a dominant negative mutant p53 gene to eliminate wild-type p53 function (NMP cells) were exposed to suramin. NMP cells still exhibited G0-G1 arrest after suramin treatment. Suramin increases p53 protein levels, but fails to increase p21 mRNA levels or to activate the G1 checkpoint. These data suggest that suramin induces growth arrest in NIH-3T3 cells by a mechanism that is independent of cellular p53 status.
The Amino Acid Composition of Bombyx mori Silk Fibroin and of Tussah Silk Fibroin (1955)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Amino Acid Composition of Bombyx mori Silk Fibroin and of Tussah Silk FibroinW. A. Schroeder, Lois M. Kay, Barry Lewis, and Nancy MungerCite this: J. Am. Chem. Soc. 1955, 77, 14, 3908–3913Publication Date (Print):July 1, 1955Publication History Published online1 May 2002Published inissue 1 July 1955https://pubs.acs.org/doi/10.1021/ja01619a066https://doi.org/10.1021/ja01619a066research-articleACS PublicationsRequest reuse permissionsArticle Views940Altmetric-Citations51LEARN 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
N-Myristoylated c-Abl Tyrosine Kinase Localizes to the Endoplasmic Reticulum upon Binding to an Allosteric Inhibitor (2009)

Allosteric kinase inhibitors hold promise for revealing unique features of kinases that may not be apparent using conventional ATP-competitive inhibitors. Here we explore the activity of a previously reported allosteric inhibitor of BCR-Abl kinase, GNF-2, against two cellular isoforms of Abl tyrosine kinase: one that carries a myristate in the N terminus and the other that is deficient in N-myristoylation. Our results show that GNF-2 inhibits the kinase activity of non-myristoylated c-Abl more potently than that of myristoylated c-Abl by binding to the myristate-binding pocket in the C-lobe of the kinase domain. Unexpectedly, indirect immunofluorescence reveals a translocation of myristoylated c-Abl to the endoplasmic reticulum in GNF-2-treated cells, whereas GNF-2 has no detectable effect on the localization of non-myristoylated c-Abl. These results indicate that GNF-2 competes with the NH(2)-terminal myristate for binding to the c-Abl kinase myristate-binding pocket and that the exposed myristoyl group accounts for the localization to the endoplasmic reticulum. We also demonstrate that GNF-2 can inhibit enzymatic and cellular kinase activity of Arg, a kinase highly homologous to c-Abl, which is also likely to be regulated through intramolecular binding of an NH(2)-terminal myristate lipid. These results suggest that non-ATP-competitive inhibitors, such as GNF-2, can serve as chemical tools that can discriminate between c-Abl isoform-specific behaviors.
Amphiregulin Is a Novel Growth Factor Involved in Normal Bone Development and in the Cellular Response to Parathyroid Hormone Stimulation (2004)

Parathyroid hormone (PTH) is the major mediator of calcium homeostasis and bone remodeling and is now known to be an effective drug for osteoporosis treatment. Yet the mechanisms responsible for its functions in bone are largely unknown. Here we report that the expression of amphiregulin (AR), a member of the epidermal growth factor (EGF) family, is rapidly and highly up-regulated by PTH in several osteoblastic cell lines and bone tissues. Other osteotropic hormones (1alpha,25-dihydroxyvitamin D3 and prostaglandin E2) also strongly stimulate AR expression. We found all EGF-like ligands and their receptors are expressed in osteoblasts, but AR is the only member that is highly regulated by PTH. Functional studies demonstrated that although AR is a potent growth factor for preosteoblasts, it completely inhibits further differentiation. AR also strongly and quickly stimulated Akt and ERK phosphorylation and c-fos and c-jun expression in an EGF receptor-dependent manner. Moreover, AR null mice displayed significantly less tibial trabecular bone than wild-type mice. Taken together, we have identified a novel growth factor that is PTH-regulated and appears to have an important role in bone metabolism.
Multiplex Analysis of Serum Cytokines in Melanoma Patients Treated with Interferon-α2b (2007)

These data show that multiplexed analysis of serum biomarkers is useful for the evaluation of prognostic markers of clinical outcome and potential predictive markers of response to IFN-alpha2b in patients with high-risk operable melanoma.
Modification of the asthma quality of life questionnaire (standardised) for patients 12 years and older (2005)

The measurement properties of the AQLQ12+ are similar in adolescents and adults and therefore the instrument is valid for use in adult studies which include children 12 years and older.