gebhart/patrepeval huggingface dataset:
Oxygen toxicity, oxygen radicals, transition metals and disease (1984)

Research Article| April 01 1984 Oxygen toxicity, oxygen radicals, transition metals and disease B Halliwell; B Halliwell Search for other works by this author on: This Site PubMed Google Scholar J M C Gutteridge J M C Gutteridge Search for other works by this author on: This Site PubMed Google Scholar Biochem J (1984) 219 (1): 1–14. https://doi.org/10.1042/bj2190001 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share MailTo Twitter LinkedIn Cite Icon Cite Get Permissions Citation B Halliwell, J M C Gutteridge; Oxygen toxicity, oxygen radicals, transition metals and disease. Biochem J 1 April 1984; 219 (1): 1–14. doi: https://doi.org/10.1042/bj2190001 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 Journal Search Advanced Search This content is only available as a PDF. © 1984 London: The Biochemical Society1984 Article PDF first page preview Close Modal You do not currently have access to this content.
Macroporous p-Type Silicon Fabry−Perot Layers. Fabrication, Characterization, and Applications in Biosensing (1998)

We present in this paper that porous silicon can be used as a large surface area matrix as well as the transducer of biomolecular interactions. We report the fabrication of heavily doped p-type porous silicon with pore diameters that can be tuned, depending on the etching condition, from approximately 5 to 1200 nm. The structure and porosity of the matrixes were characterized by scanning force microscopy (SFM) and scanning electron microscopy (SEM), Brunnauer−Emmett−Teller nitrogen adsorption isotherms, and reflectance interference spectroscopy. The thin porous silicon layers are transparent to the visible region of the reflectance spectra due to their high porosity (80−90%) and are smooth enough to produce Fabry−Perot fringe patterns upon white light illumination. Porous silicon matrixes were modified by ozone oxidation, functionalized in the presence of (2-pyridyldithiopropionamidobutyl)dimethylmethoxysilane, reduced to unmask the sulfhydryl functionalities, and coupled to biotin through a disulfide-bond-forming reaction. Such functionalized matrixes display considerable stability against oxidation and corrosion in aqueous media and were used to evaluate the utility of porous silicon in biosensing. The streptavidin−biotin interactions on the surface of porous silicon could be monitored by the changes in the effective optical thickness calculated from the observed shifts in the Fabry−Perot fringe pattern caused by the change in the refractive index of the medium upon protein−ligand binding. Porous silicon thus combines the properties of a mechanically and chemically stable high surface area matrix with the function of an optical transducer and as such may find utility in the fabrication of biosensor devices.
The pathology of Rift Valley fever. II. Lesions occurring in field cases in adult cattle, calves and aborted foetuses. (1982)

Since the original description of Rift Valley fever in sheep, cattle and man in the Rift Valley in Kenya in 1931, very little has been published on the disease in cattle. This report deals with the macroscopic and microscopic pathology of field cases of Rift Valley fever in 22 adult cattle, 8 calves and 8 aborted foetuses. The microscopic liver lesions in 13 adult cattle were characterized by marked centri- and midzonal eosinophilic necrosis, involving almost 2/3 of the lobules, and accompanied by sparsely distributed primary foci of necrosis. In 3 animals, however, the hepatic lesions were more focal in nature, while a massive hepatic necrosis was evident in 6 others. In calves, the lesions in the liver ranged from cases showing numerous haphazardly scattered primary foci of necrosis to cases where the latter were accompanied by eosinophilic necrosis of the remaining hepatocytes in the lobules. Vascular lesions, thrombosis and sinusoidal fibrin deposits were sometimes seen in the livers of both calves and adult cattle. Although the aborted foetuses were in a fairly advanced state of autolysis, it was still possible to make a diagnosis of Rift Valley fever from the characteristic lesions which were similar to those reported for new-born lambs. Other noteworthy lesions in adult cattle and calves included pyknosis and karyorrhexis of lymphocytes in the spleen and lymph nodes, widespread serosal and visceral haemorrhages which were sometimes accompanied by copious free blood in the gastrointestinal tract, and a nephrosis.
Nucleophilic Catalysis of Semicarbazone Formation by Anilines (1962)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNucleophilic Catalysis of Semicarbazone Formation by AnilinesEugene H. Cordes and William P. JencksCite this: J. Am. Chem. Soc. 1962, 84, 5, 826–831Publication Date (Print):March 1, 1962Publication History Published online1 May 2002Published inissue 1 March 1962https://pubs.acs.org/doi/10.1021/ja00864a030https://doi.org/10.1021/ja00864a030research-articleACS PublicationsRequest reuse permissionsArticle Views2237Altmetric-Citations178LEARN 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
Isolation and Sequence Comparison of a Maize Calmodulin cDNA (1994)

CaM is a key re@atory protein involved in the ca2+
Myosin Phosphatase-Rho Interacting Protein (2003)

Regulation of vascular smooth muscle cell contractile state is critical for the maintenance of blood vessel tone. Abnormal vascular smooth muscle cell contractility plays an important role in the pathogenesis of hypertension, blood vessel spasm, and atherosclerosis. Myosin phosphatase, the key enzyme controlling myosin light chain dephosphorylation, regulates smooth muscle cell contraction. Vasoconstrictor and vasodilator pathways inhibit and activate myosin phosphatase, respectively. G-protein-coupled receptor agonists can inhibit myosin phosphatase and cause smooth muscle cell contraction by activating RhoA/Rho kinase, whereas NO/cGMP can activate myosin phosphatase and cause smooth muscle cell relaxation by activation of cGMP-dependent protein kinase. We have used yeast two-hybrid screening to identify a 116-kDa human protein that interacts with both myosin phosphatase and RhoA. This myosin phosphatase-RhoA interacting protein, or M-RIP, is highly homologous to murine p116RIP3, is expressed in vascular smooth muscle, and is localized to actin myofilaments. M-RIP binds directly to the myosin binding subunit of myosin phosphatase in vivo in vascular smooth muscle cells by an interaction between coiled-coil and leucine zipper domains in the two proteins. An adjacent domain of M-RIP directly binds RhoA in a nucleotide-independent manner. M-RIP copurifies with RhoA and Rho kinase, colocalizes on actin stress fibers with RhoA and MBS, and is associated with Rho kinase activity in vascular smooth muscle cells. M-RIP can assemble a complex containing both RhoA and MBS, suggesting that M-RIP may play a role in myosin phosphatase regulation by RhoA.
G Protein Subunit Gα 13 Binds to Integrin α IIb β 3 and Mediates Integrin “Outside-In” Signaling (2010)

Integrins mediate cell adhesion to the extracellular matrix and transmit signals within the cell that stimulate cell spreading, retraction, migration, and proliferation. The mechanism of integrin outside-in signaling has been unclear. We found that the heterotrimeric guanine nucleotide-binding protein (G protein) Galpha13 directly bound to the integrin beta3 cytoplasmic domain and that Galpha13-integrin interaction was promoted by ligand binding to the integrin alphaIIbbeta3 and by guanosine triphosphate (GTP) loading of Galpha13. Interference of Galpha13 expression or a myristoylated fragment of Galpha13 that inhibited interaction of alphaIIbbeta3 with Galpha13 diminished activation of protein kinase c-Src and stimulated the small guanosine triphosphatase RhoA, consequently inhibiting cell spreading and accelerating cell retraction. We conclude that integrins are noncanonical Galpha13-coupled receptors that provide a mechanism for dynamic regulation of RhoA.
Modulation of the CD40–CD40 ligand interaction using human anti‐CD40 single‐chain antibody fragments obtained from the n‐CoDeR phage display library (2002)

CD40 plays a central regulatory role in the immune system and antibodies able to modulate CD40 signalling may consequently have a potential in immunotherapy, in particular for treatment of lymphomas and autoimmune disease like multiple sclerosis. As a first step to achieve this goal, we describe the selection and characterization of a novel set of fully human anti-CD40 antibody fragments (scFv) from a phage display library (n-CoDeR). In order to determine their biological potential, these antibody fragments have been analysed for their ability to promote B-cell activation, rescue from apoptosis and to block the CD40-CD40 ligand (CD40L) interaction. The selected cohort of human scFv could be subcategorized, each expressing a distinct functional signature. Thus scFv were generated that induced B-cell proliferation, rescued B cells from apoptosis and blocked the CD40-CD40L interaction to different extents. In particular, one of the scFv clones (F33) had the ability to abrogate completely this interaction. The epitope recognition patterns as well as individual rate constants were also determined and the affinity was shown to vary from low to high nanomolar range. In conclusion, this panel of human anti-CD40 scFv fragments displays a number of distinct properties, which may constitute a valuable source when evaluating candidates for in vivo trials.
Prospective Investigation of Autonomic Nervous System Function and the Development of Type 2 Diabetes (2003)

These findings suggest that ANS dysfunction may be associated with the development of diabetes in healthy adults.
Combinatorial drug screening identifies synergistic co-targeting of Bruton’s tyrosine kinase and the proteasome in mantle cell lymphoma (2013)

Combinatorial drug screening identifies synergistic co-targeting of Bruton’s tyrosine kinase and the proteasome in mantle cell lymphoma
TH17 Cells in Autoimmunity and Immunodeficiency: Protective or Pathogenic? (2012)

In 2005 a newly discovered T helper cell subset that secreted interleukin (IL)-17 became the center of attention in immunology. Initial studies painted Th17 cells as the culprit for destruction in many different autoimmune and auto-inflammatory diseases. Subsequently, the discovery of patients with primary immunodeficiencies in the IL-17 pathway taught us that Th17 cells have a critical role in defense against certain fungal and bacterial infections. Moreover, the paradoxical exacerbation of Crohn's disease in the clinical trials of a Secukinumab (AIN457), a fully human neutralizing antibody to IL-17A, has cast into doubt a universal pro-inflammatory and harmful role for Th17 cells. Evidence now suggests that depending on the environment Th17 cells can alter their differentiation program, ultimately giving rise to either protective or pro-inflammatory cells. In this review we will summarize the evidence from patients with immunodeficiencies, autoimmune, or auto-inflammatory diseases that teaches us how the pro-inflammatory versus protective function of Th17 cells varies within the context of different human diseases.
Detection of the human papilloma virus type 16 mRNA‐transcripts in cytological abnormal scrapings (1992)

The RNA-polymerase chain reaction (PCR) was carried out on cervical scrapings to detect and analyze transcripts from the E6-E7 open reading frames (ORF) of human papilloma virus type 16 (HPV16). The method, described previously for cervical squamous carcinomas and cervical intraepithelial neoplasias, was adapted to cervical scrapings. A primer set and two different probes specific for the E6-E7 ORFs were selected. One of the probes was able to detect the amplification products from the full length, the major, and the minor transcripts whereas the other was specific for the major transcript only. To check the quality of the mRNA in the cervical scrapings, a primer set and a probe specific for the human keratin mRNA were selected. A group of 17 abnormal cytological cervical scrapes, which were positive for HPV16 DNA, was analyzed. In this group the human papilloma virus was not always transcriptionally active, as HPV16 mRNA transcripts were detected only in about one-half (8/17) of the samples. These findings suggest that the RNA-PCR method on cervical scrapings may be very useful for epidemiological studies on the role of transcriptionally active/inactive HPV16 genes in the pathogenesis of an HPV16 infected lesion.
Autocrine and Juxtacrine Effects of Amphiregulin on the Proliferative, Invasive, and Migratory Properties of Normal and Neoplastic Human Mammary Epithelial Cells (2006)

Amphiregulin (AR) autocrine loops have been associated with several types of cancer. We demonstrate that SUM149 breast cancer cells have a self-sustaining AR autocrine loop. SUM149 cells are epidermal growth factor (EGF)-independent for growth, and they overexpress AR mRNA, AR membrane precursor protein, and secreted AR relative to the EGF-dependent human mammary epithelial cell line MCF10A. MCF10A cells made to overexpress AR (MCF10A AR) are also EGF-independent for growth. Treatment with the pan-ErbB inhibitor CI1033 and the anti-EGF receptor (EGFR) antibody C225 demonstrated that ligand-mediated activation of EGFR is required for SUM149 cell proliferation. AR-neutralizing antibody significantly reduced both SUM149 EGFR activity and cell proliferation, confirming that an AR autocrine loop is required for mitogenesis in SUM149 cells. EGFR tyrosine phosphorylation was dramatically decreased in both SUM149 and MCF10A AR cells after inhibition of AR cleavage with the broad spectrum metalloprotease inhibitor GM6001, indicating that an AR autocrine loop is strictly dependent on AR cleavage in culture. However, a juxtacrine assay where fixed SUM149 cells and MCF10A AR cells were overlaid on top of EGF-deprived MCF10A cells showed that the AR membrane precursor can activate EGFR. SUM149 cells, MCF10A AR cells, and MCF10A cells growing in exogenous AR were all considerably more invasive and motile than MCF10A cells grown in EGF. Moreover, AR up-regulates a number of genes involved in cell motility and invasion in MCF10A cells, suggesting that an AR autocrine loop contributes to the aggressive breast cancer phenotype.
Suturing Versus Immobilization of a Muscle Laceration (1999)

Muscle laceration remains a difficult problem for orthopaedic surgeons. Despite many studies related to the muscle's ability to regenerate after muscle degeneration, very few reports are available regarding structural and functional recovery after skeletal muscle laceration. We developed an animal model of muscle laceration in mice, where the gastrocnemius muscles were reproducibly transected. We compared the effect of a surgical repair versus a short period of immobilization (5 days) on the muscle healing. The natural course of muscle recovery was monitored at several points after injury using histologic, immunohistochemical, and functional testing. In the injured muscle, we observed a high number of regenerating myofibers and development of fibrotic scar tissue. Suturing the lacerated muscle immediately after injury promoted better healing of the injured muscle and prevented the development of deep scar tissue in the lacerated muscle; conversely, immobilization resulted in slower muscle regeneration and the development of a large area of scar tissue. Tetanus strength 1 month after injury was 81% of control muscles for the sutured muscles, 35% for the lacerated muscles with no treatment, and 18% for the immobilized muscles. Based on this study, suturing a muscle laceration with a modified Kessler stitch results in the best morphologic and functional healing.
Bevacizumab plus Ipilimumab in Patients with Metastatic Melanoma (2014)

Ipilimumab improves survival in advanced melanoma and can induce immune-mediated tumor vasculopathy. Besides promoting angiogenesis, vascular endothelial growth factor (VEGF) suppresses dendritic cell maturation and modulates lymphocyte endothelial trafficking. This study investigated the combination of CTLA4 blockade with ipilimumab and VEGF inhibition with bevacizumab. Patients with metastatic melanoma were treated in four dosing cohorts of ipilimumab (3 or 10 mg/kg) with four doses at 3-week intervals and then every 12 weeks, and bevacizumab (7.5 or 15 mg/kg) every 3 weeks. Forty-six patients were treated. Inflammatory events included giant cell arteritis (n = 1), hepatitis (n = 2), and uveitis (n = 2). On-treatment tumor biopsies revealed activated vessel endothelium with extensive CD8(+) and macrophage cell infiltration. Peripheral blood analyses demonstrated increases in CCR7(+/-)/CD45RO(+) cells and anti-galectin antibodies. Best overall response included 8 partial responses, 22 instances of stable disease, and a disease-control rate of 67.4%. Median survival was 25.1 months. Bevacizumab influences changes in tumor vasculature and immune responses with ipilimumab administration. The combination of bevacizumab and ipilimumab can be safely administered and reveals VEGF-A blockade influences on inflammation, lymphocyte trafficking, and immune regulation. These findings provide a basis for further investigating the dual roles of angiogenic factors in blood vessel formation and immune regulation, as well as future combinations of antiangiogenesis agents and immune checkpoint blockade.
Production of a Novel Pyranose 2-Oxidase by Basidiomycete Trametes multicolor (1998)

During a screening for the enzyme pyranose 2-oxidase (P2O) which has a great potential as a biocatalyst for carbohydrate transformations, Trametes multicolor was identified as a promising, not-yet-described producer of this particular enzyme activity. Furthermore, it was found in this screening that the enzyme frequently occurs in basidiomycetes. Intracellular P2O was produced in a growth-associated manner by T. multicolor during growth on various substrates, including mono-, oligo-, and polysaccharides. Highest levels of this enzyme activity were formed when lactose or whey were used as substrates. Peptones from casein and other casein hydrolysates were found to be the most favorable nitrogen sources for the formation of P2O. By applying an appropriate feeding strategy for the substrate lactose, which ensured an elevated concentration of the carbon source during the entire cultivation, levels of P2O activity obtained in laboratory fermentations, as well as the productivity of these bioprocess experiments, could be enhanced more than 2.5-fold.
Telomestatin, a Potent Telomerase Inhibitor That Interacts Quite Specifically with the Human Telomeric Intramolecular G-Quadruplex (2002)

Telomestatin is a natural product isolated from Streptomyces anulatus 3533-SV4 and has been shown to be a very potent telomerase inhibitor. The structural similarity between telomestatin and a G-tetrad suggested to us that the telomerase inhibition might be due to its ability either to facilitate the formation of or trap out preformed G-quadruplex structures, and thereby sequester single-stranded d[T(2)AG(3)](n) primer molecules required for telomerase activity. Significantly, telomestatin appears to be a more potent inhibitor of telomerase (5 nM) than any of the previously described G-quadruplex-interactive molecules. In this communication we provide the first experimental evidence that telomestatin selectively facilitates the formation of or stabilizes intramolecular G-quadruplexes, in particular, that produced from the human telomeric sequence d[T(2)AG(3)](4). A simulated annealing (SA) docking approach was used to study the binding interactions of telomestatin with the intramolecular antiparallel G-quadruplex structure. Each intramolecular G-quadruplex molecule was found to bind two telomestatin molecules (unpublished results). A 2:1 model for the telomestatin bound in the external stacking mode in an energy minimized complex with the human telomeric basket-type G-quadruplex was constructed. Our observation that a G-quadruplex-interactive molecule without significant groove interactions is able to reorient in a G-quadruplex structure proints to the importance of core interaction with an asymmetric G-quadruplex structure in producing selective binding. Furthermore, the G-quadruplex interactions of telomestatin are more selective for the intramolecular structure in contrast to other G-quadruplex-interactive agents, such as TMPyP4.
Novel Derivatives of 2-Pyridinemethylamine as Selective, Potent, and Orally Active Agonists at 5-HT1A Receptors (1999)

The aim of this work was to improve the oral bioavailability of a recently discovered, novel structural class of 5-HT1A receptor agonists: aryl-{[4-(6-R-pyridin-2-ylmethyl)-amino]-methyl}-piperidin-1 -yl-metha none. Incorporation of a fluorine atom in the beta-position to the amino function in the side chain led to analogues that exhibited, in general, enhanced and long-lasting 5-HT1A agonist activity in rats after oral administration. Location of the fluorine atom at the C-4 position of the piperidine ring was the most favorable, and among the various substituents tested, the ability of the fluorine was unique in improving the oral activity of this family of ligands. Thus, the derivatives 39, 46, and 61 bound with higher affinity and selectivity to 5-HT1A receptors (versus dopaminergic D2 and adrenergic alpha1 receptors) and displayed more potent 5-HT1A agonist activity in vitro and in vivo than their C-4 desfluoro analogues. To examine the relationship between the conformation of the pharmacophore and the level of agonistic activity of this type of ligand, we synthesized a series of 3-chloro-4-fluorophenyl-(4-fluoro-4{[(5-(H or CH3)-6-R-pyridin-2-ylmethyl)-amino]-methyl}-piperidin-1-yl-+ ++methanone derivatives and found that the combination of a 5-methyl and a 6-methylamino substituent on the pyridine ring synergistically affected their 5-HT1A agonist properties. Thus, the 3-chloro-4-fluorophenyl-(4-fluoro-4{[(5-methyl-6-methylamino-pyridin- 2-ylmethyl)-amino]-methyl}-piperidin-1-yl-methanone 40 behaved as a more potent 5-HT1A receptor agonist in vitro and in vivo than its 5-unsubstituted analogue 38. The antidepressant potential of the lead compounds 40, 45, and 54 was examined by means of the forced swimming test (FST) in rats. The results indicated that, after a single oral administration, these compounds inhibited immobility in the FST more potently and more extensively than the clinically used antidepressant imipramine. Thus, 40, 45, and 54 are potent, orally active 5-HT1A receptor agonists with marked antidepressant potential.