gebhart/patrepeval huggingface dataset:
Penicillamine, Captopril, and Hypoglycemia (1985)

Letters and Corrections1 October 1985Penicillamine, Captopril, and HypoglycemiaPREBEN ELLING, M.D., HANNE ELLINGPREBEN ELLING, M.D.Search for more papers by this author, HANNE ELLINGSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-103-4-644 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: D-Penicillamine is a useful anti-rheumatoid arthritis drug with many side effects, but to date no effect of this drug on carbohydrate metabolism has been reported. We have recently seen two cases of unexplained hypoglycemia in insulin-dependent diabetics when penicillamine was used with their usual insulin dosage.A 60-year-old man had been treated for nearly 30 years with a stable dose of insulin (Insulin Retard [NPH], 40 units/d). He had never had any hypoglycemic reactions, but 8 weeks after receiving penicillamine, 250 mg/d, for a seropositive erosive rheumatoid arthritis, he had severe attacks of typical hypoglycemic symptoms including...References1. FERRIERELACHKARRICHARDBRINGERORSETTIMIROUZE MHJJAJ. Captopril and insulin sensitivity. Ann Intern Med. 1985;102:134-5. LinkGoogle Scholar2. JAFFE I. The effects of penicillamine on laboratory parametres in rheumatoid arthritis. Arthritis Rheum. 1965;8:1064-79. CrossrefMedlineGoogle Scholar3. ANDERSON O. Clinical significance of antiinsulin-antibodies. Acta Endocrinol (Copenh). 1971;205(suppl):231-8. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Viborg City Hospital 8800 Viborg Denmark PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byPenicillamineGLUCOCORTICOIDS AND DISEASE – MODIFYING ANTIRHEUMATIC DRUGSENDOCRINE AND METABOLIC ADVERSE EFFECTS OF NON-HORMONAL AND NON-METABOLIC DRUGSPenicillamineBasistherapeutika und ImmunsuppressivaBasistherapeutika und ImmunsuppressivaTherapeutic challenges in the obese diabetic patient with hypertensionHypertension in Diabetics with Renal DiseaseMetal antagonistsPenicillamine-Induced Insulin AntibodiesRICHARD C. BECKER, M.D., RAQUEL G. MARTIN, D.O.Basistherapeutika und Immunsuppressiva 1 October 1985Volume 103, Issue 4Page: 644-645KeywordsAdverse reactionsArthritisCarbohydrate metabolismDrug metabolismHypoglycemiaHypoglycemicsInsulinRheumatoid arthritis ePublished: 1 December 2008 Issue Published: 1 October 1985 PDF downloadLoading ...
Characterization of regions of herpes simplex virus type 1 glycoprotein E involved in binding the Fc domain of monomeric IgG and in forming a complex with glycoprotein I. (1995)

Glycoprotein E (gE) and glycoprotein I (gI) of herpes simplex virus type 1 form a molecular complex that binds the Fc domain of monomeric IgG. Two approaches were used to define regions of gE-1 involved in monomeric IgG binding and complex formation with gI-1. First, we constructed 22 in-frame gE-1 linker-insertion mutants and, in cotransfection experiments with gI-1, assayed each mutant for IgG monomer binding and the ability to complex with gI-1. Nine mutants with insertions between gE-1 amino acids 235 and 380 failed to bind IgG monomers, whereas mutants outside this region retained binding activity. Each mutant reacted with several gE-1 mAbs, was detected at the cell surface, and was fully processed. Only two gE-1 mutants with insertions at residues 235 and 264 lost the ability to co-immunoprecipitate with gI-1, which defines a region of gE-1 that complexes with gI-1. As an additional approach, we assayed 8 gE-1/gD-1 fusion proteins containing large overlapping gE-1 peptides inserted within the ectodomain of gD-1 for binding of IgG monomers and complex formation with gI-1. Three fusion proteins containing gE-1 peptides that overlap at residues 183-402 bound monomeric IgG. This region of gE-1 includes the Fc binding region defined by linker insertion mutagenesis. Five fusion proteins containing gE-1 peptides that overlap at residues 183-288 were co-immunoprecipitated with gI-1, confirming results of gE-1 linker insertion mutagenesis. These studies define two regions on gE-1 involved in Fc binding activity, one that interacts with gI-1, and another that binds IgG.
Silybin and Silymarin - New and Emerging Applications in Medicine (2007)

This review critically surveys the literature published mainly within this millennium on the new and emerging applications of silybin (pure, chemically defined substance) and silymarin (flavonoid complex from Silybum marianum - milk thistle seeds). These compounds used so far mostly as hepatoprotectants were shown to have other interesting activities, e.g. anticancer and canceroprotective and also hypocholesterolemic activity. These effects were demonstrated in a large variety of illnesses of different organs, e.g. prostate, lungs, CNS, kidneys, pancreas and also in the skin protection. Besides the cytoprotective activity of silybin mediated by its antioxidative and radical-scavenging properties also new functions based on the specific receptor interaction were discovered. These were studied on the molecular level and modulation of various cell-signaling pathways with silybin was disclosed--e.g. NF-kappaB, inhibition of EGFR-MAPK/ERK1/2 signaling, activity upon Rb and E2F proteins, IGF-receptor signaling. Proapoptotic activity of silybin in pre- and/or cancerogenic cells and anti-angiogenic activity of silybin are other important findings that bring silymarin preparations closer to respective application in the cancer treatment. Discovery of the inhibition and modulation of drug transporters, P-glycoproteins, estrogenic receptors, nuclear receptors by silybin and some of its new derivatives contribute further to the better understanding of silybin activity on the molecular level. Silymarin application in veterinary medicine is reviewed as well. Recent works using optically pure silybin diastereomers clearly indicate extreme importance of the use of optically active silybin namely in the receptor studies. Significance of silymarin and its components in the medicine is clearly indicated by an exponential growth of publications on this topic--over 800 papers in the last 5 years.
Potent Inhibition of Grb2 SH2 Domain Binding by Non-Phosphate-Containing Ligands (1998)

Development of Grb2 Src homology 2 (SH2) domain binding inhibitors has important implications for treatment of a variety of diseases, including several cancers. In cellular studies, inhibitors of Grb2 SH2 domain binding have to date been large, highly charged peptides which relied on special transport devices for cell membrane penetration. Work presented in the current study examines a variety of pTyr mimetics in the context of a high-affinity Grb2 binding platform. Among the analogues studied are new non-phosphorus-containing pTyr mimetics 23a and 23b which, when incorporated into tripeptide structures 18f and 20f, are able to inhibit Grb2 SH2 domain binding with affinities among the best yet reported for non-phosphorus-containing SH2 domain inhibitors (IC50 values of 6.7 and 1.3 microM, respectively). The present study has also demonstrated the usefulness of the Nalpha-oxalyl group as an auxiliary which enhances the binding potency of both phosphorus- and non-phosphorus-containing pTyr mimetics. When combined with the (phosphonomethyl)phenylalanine (Pmp) residue to give analogues such as L-20d, potent inhibition of Grb2 SH2 domain binding can be achieved both in extracellular assays using isolated Grb2 SH2 domain protein and in intracellular systems measuring the association of endogenous Grb2 with its cognate p185erbB-2 ligand. These latter effects can be achieved at micromolar to submicromolar concentrations without prodrug derivatization. The oxalyl-containing pTyr mimetics presented in this study should be of general usefulness for the development of other Grb2 SH2 domain antagonists, independent of the beta-bend-mimicking platform utilized for their display.
Graphene-based biosensors for detection of bacteria and their metabolic activities (2011)

Graphene, which is a recently discovered single-atom-thick planar sheet of carbon atoms perfectly arranged in a honeycomb lattice, has great potential in biosensing owing to its extraordinary electrical, physical, and optical properties. In this work, we demonstrate a graphene based biosensor to electrically detect E. coli bacteria with high sensitivity and specificity. The large-sized graphene film was grown by chemical vapor deposition and functionalized with anti-E. coliantibodies and passivation layer. Significant conductance increase of the graphene device was observed after exposure to E. coli bacteria at a concentration as low as 10 cfu/mL, while no significant response was triggered by high concentration of the another bacterial strain. In addition, this biosensor was employed to detect the glucose induced metabolic activities of the bound E. coli bacteria in real time. This simple, fast, sensitive, and label-free nanoelectronic biosensor, in principle, could serve as a high throughput platform for detection of any pathogenic bacteria, and for functional studies or screening of antibacterial drugs.
Deaths: final data for 1998. (2000)

The overall improvements in general mortality and life expectancy in 1998 continue the long-term downward trend in U.S. mortality. Although unchanged from 1997, the trend in U.S. infant mortality is of steady declines over the past four decades.
Energetically efficient electrochemically tunable affinity separation using multicomponent polymeric nanostructures for water treatment (2018)

We describe a water treatment strategy, electrochemically tunable affinity separation (ETAS), which, unlike other previously developed electrochemical processes, targets uncharged organic pollutants in water.
In vivo estimates of division and death rates of human T lymphocytes. (1995)

We present data on the decay, after radiotherapy, of naive and memory human T lymphocytes with stable chromosome damage. These data are analyzed in conjunction with existing data on the decay of naive and memory T lymphocytes with unstable chromosome damage and older data on unsorted lymphocytes. The analyses yield in vivo estimates for some life-history parameters of human T lymphocytes. Best estimates of proliferation rates have naive lymphocytes dividing once every 3.5 years and memory lymphocytes dividing once every 22 weeks. It appears that memory lymphocytes can revert to the naive phenotype, but only, on average, after 3.5 years in the memory class. The lymphocytes with stable chromosome damage decay very slowly, yielding surprisingly low estimates of their death rate. The estimated parameters are used in a simple mathematical model of the population dynamics of undamaged naive and memory lymphocytes. We use this model to illustrate that it is possible for the unprimed subset of a constantly stimulated clone to stay small, even when there is a large population of specific primed cells reverting to the unprimed state.
Silica Nanostructures Templated by Oriented Block Copolymer Thin Films Using Pore-Filling and Selective-Mineralization Routes (2005)

Poly(styrene-block-methyl methacrylate) thin films with cylindrical microdomains oriented normal to the surface were used as templates for nanoscopic silica structures. Silicon oxide was synthesized using vapor-phase and liquid-phase sol−gel reactions of tetraethoxysilane (TEOS). The vapor-phase reaction selectively formed silicon oxide within the poly(methyl methacrylate) (PMMA) domains. The use of liquid sols led to reconstruction of the film by selective solvation of the PMMA chains, followed by mineralization of silicon oxide. In addition, the vapor-phase and liquid-phase reactions were used to deposit silica in porous polystyrene (PS) films made by selective etching of the PMMA cylinders. Removal of polymer by calcination in air at 500 °C resulted in ordered arrays of silica nanostructures. Dynamic wettability measurements were made on nanostructured surfaces after functionalization with hydrophobic organosilanes.
In Vitro Investigation of the Antibacterial Effect of Ketamine (2008)

Ketamine with higher doses showed antibacterial activity. We thought that it will be proper to use ketamine hesitantly in experimental animal studies like sepsis and translocation.
Characteristics of D-Leucine Uptake by Mouse Ehrlich Ascites Tumor Cells (1979)

In a previous paper, we reported that various D-amino acids were taken up several times more effectively than the corresponding L-isomers into several tumors tested in vivo. In order to investigate this further, the in vitro uptake of D-[14C]leucine by Ehrlich ascites tumor cells was investigated in comparison with that of L-[14C]leucine. The distribution ratio, the effects of amino acids and pH, and an approximately linear Lineweaver-Burk plot indicated that D-leucine was transported by an active transport system for L-leucine. Vmax and ku, the first-order rate constant for the unsaturable component, for the uptake of D- and L-leucines decreased with a fall in temperature. The activation energies for Vmax and ku were in the range of 5-10 and 18-21 kcal/mol, respectively. The values for L-leucine were greater than those for D-leucine. Km for D-leucine transport increased with decreasing temperature, whereas Km for L-leucine decreased. This difference suggests that the large alkyl chains of D- and L-leucines bind to different portions of a carrier protein.
Avoiding multipath to revive inbuilding WiFi localization (2013)

Despite of several years of innovative research, indoor localization is still not mainstream. Existing techniques either employ cumbersome fingerprinting, or rely upon the deployment of additional infrastructure. Towards a solution that is easier to adopt, we propose CUPID, which is free from these restrictions, yet is comparable in accuracy. While existing WiFi based solutions are highly susceptible to indoor multipath, CUPID utilizes physical layer (PHY) information to extract the signal strength and the angle of only the direct path, successfully avoiding the effect of multipath reflections. Our main observation is that natural human mobility, when combined with PHY layer information, can help in accurately estimating the angle and distance of a mobile device from an wireless access point (AP). Real-world indoor experiments using off-the-shelf wireless chipsets confirm the feasibility of CUPID. In addition, while previous approaches rely on multiple APs, CUPID is able to localize a device when only a single AP is present. When a few more APs are available, CUPID can improve the median localization error to 2.7m, which is comparable to schemes that rely on expensive fingerprinting or additional infrastructure.
ChemInform Abstract: PHOSPHORYLATION OF INDOLES BY AMIDOPHOSPHITES (1980)

Abstract Die Phosphorylierung des Indols (I) mit den Phosphorverbindungen (II) liefert das in 1‐Stellung substituierte Derivat (III).
Invasion and replication of Salmonella typhimurium in animal cells (1990)

A total of 81 avirulent Tn10 insertion mutants of Salmonella typhimurium have previously been described. These mutants were selected for the inability to survive in murine macrophages. We have characterized the abilities of the most avirulent of these mutants to adhere to, invade, and replicate in both macrophages and nonphagocytic epithelial cells. The results suggest that most mutants contain a defect that is specific to survival within professional phagocytes. These mutants invaded and replicated normally within nonphagocytic human colon adenocarcinoma cells (Caco-2) but did not survive in the macrophage cell line J774. One mutant invaded both macrophages and epithelial cells much less efficiently than the parental strain. The defect associated with this mutant appears to be a result of decreased adherence to animal cells.
Thalidomide-derived immunomodulatory drugs as therapeutic agents (2004)

Thalidomide, a drug originally used to treat morning sickness, was removed from the market place in the early 1960s after it was found to cause serious congenital birth defects. However, thalidomide has recently been investigated in a new light following its activity in a number of chronic diseases. Moreover, like thalidomide itself, its second-generation immunomodulatory drug (IMiD) analogues have been shown to act as powerful anticancer agents and are clearly active in the treatment of patients with relapsed multiple myeloma. These new drugs, in particular the second-generation IMiDs, lenalidomide (CC-5013, REVLIMID; Celgene Corp., NJ, USA) and CC-4047 (ACTIMID; Celgene Corp.), offer improvements over thalidomide (a first-generation IMiD) in terms of efficacy and safety in human studies. The key to the therapeutic potential of IMiDs lies in the fact that the drugs have multiple mechanisms of action, which may produce both anti-inflammatory and antitumour effects. These effects are probably contextual, depending both on the cell type and the stimulus involved. Mechanisms associated with IMiD activity include TNF-alpha-inhibitory, T cell costimulatory and antiangiogenic activities. Studies of the mechanisms of action of these drugs are ongoing and will facilitate the continued development of this class of compound in a number of diseases.
Factors affecting HLA expression: A review (2019)

The detection and semiquantitative measurement of circulating human leucocyte antigen (HLA)-specific antibodies is essential for the management of patients before and after transplantation. In addition, the pretransplant cross-match to assess the reactivity of recipient HLA antibody against donor lymphocytes has long been the gold standard to prevent hyperacute rejection. Whilst both of these tests assume that recipient HLA-specific antibody is the only variable in the assessment of transplant risk, this is not the case. Transplant immunologists recognize that some HLA antigens are expressed at levels a magnitude lower than others (e.g., HLA-C, HLA-DQ), but within loci, and between different cell types there are many factors that influence HLA expression in both resting and activated cells. HLA is not usually expressed without the specific promoter proteins NLRC5, for HLA class I, and CIITA, for class II. The quantity of HLA protein production is then affected by factors including promoter region polymorphisms, alternative exon splice sites, methylation and microRNA-directed degradation. Different loci are influenced by multiple combinations of these control mechanisms making prediction of HLA regulation difficult, but an ability to measure the cellular expression of each HLA antigen, in conjunction with knowledge of circulating HLA-specific antibody, would lead to a more informed algorithm to assess transplant risk.
Bioisosterism: A Useful Strategy for Molecular Modification and Drug Design (2005)

This review aim to demonstrate the role of bioisosterism in rational drug design as well as in the molecular modification and optimization process aiming to improve pharmacodynamic and pharmacokinetic properties of lead compounds. Keywords: lead compound, isosterism, antagonist, pharmacodynamic, pharmacokinetic, hplc, prostaglandin-h synthase-2 (pghs-
Of Extracellular Matrix, Scaffolds, and Signaling: Tissue Architecture Regulates Development, Homeostasis, and Cancer (2006)

The microenvironment influences gene expression so that the behavior of a cell is largely determined by its interactions with the extracellular matrix, neighboring cells, and soluble local and systemic cues. We describe the essential roles of context and organ structure in directing mammary gland development and differentiated function and in determining the response to oncogenic insults, including mutations. We expand on the concept of "dynamic reciprocity" to present an integrated view of development, cancer, and aging and posit that genes are like the keys on a piano: Although they are essential, it is the context that makes the music.
Platelet Derived Growth Factor (Pdgf), Androgens and Inflammation: Possible Etiologic Factors in the Development of Prostatic Hyperplasia (1993)

Benign prostatic hyperplasia (BPH) is characterized by varying degrees of epithelial and stromal hyperplasia in association with inflammation. Although androgens are known to be important for the growth and function of the prostate, their role in the development of BPH is unclear. The release of platelet-derived growth factor (PDGF) in response to inflammation suggests that PDGF may participate in the development of BPH. Cultured prostate cells derived from patients with BPH were examined for the presence of functional PDGF and androgen receptors. The cells expressed PDGF receptors and responded to PDGF stimulation by the activation of the PDGF signal transduction pathway and a dose-dependent stimulation of cell proliferation. Even though the cells expressed androgen receptors, dihydrotestosterone failed to elicit a mitogenic response. While the role of androgens in BPH remains unclear, these results suggest that inflammation and, specifically, PDGF may be important etiologic factors in the development of BPH.
Enzymatic Amplification of β-Globin Genomic Sequences and Restriction Site Analysis for Diagnosis of Sickle Cell Anemia (1985)

Two new methods were used to establish a rapid and highly sensitive prenatal diagnostic test for sickle cell anemia. The first involves the primer-mediated enzymatic amplification of specific beta-globin target sequences in genomic DNA, resulting in the exponential increase (220,000 times) of target DNA copies. In the second technique, the presence of the beta A and beta S alleles is determined by restriction endonuclease digestion of an end-labeled oligonucleotide probe hybridized in solution to the amplified beta-globin sequences. The beta-globin genotype can be determined in less than 1 day on samples containing significantly less than 1 microgram of genomic DNA.
Interleukin-36 (IL-36) Ligands Require Processing for Full Agonist (IL-36α, IL-36β, and IL-36γ) or Antagonist (IL-36Ra) Activity (2011)

IL-36α, IL-36β, and IL-36γ (formerly IL-1F6, IL-1F8, and IL-1F9) are IL-1 family members that signal through the IL-1 receptor family members IL-1Rrp2 (IL-1RL2) and IL-1RAcP. IL-36Ra (formerly IL-1F5) has been reported to antagonize IL-36γ. However, our previous attempts to demonstrate IL-36Ra antagonism were unsuccessful. Here, we demonstrate that IL-36Ra antagonist activity is dependent upon removal of its N-terminal methionine. IL-36Ra starting at Val-2 is fully active and capable of inhibiting not only IL-36γ but also IL-36α and IL-36β. Val-2 of IL-36Ra lies 9 amino acids N-terminal to an A-X-Asp motif conserved in all IL-1 family members. In further experiments, we show that truncation of IL-36α, IL-36β, and IL-36γ to this same point increased their specific activity by ∼10(3)-10(4)-fold (from EC(50) 1 μg/ml to EC(50) 1 ng/ml). Inhibition of truncated IL-36β activity required ∼10(2)-10(3)-fold excess IL-36Ra, similar to the ratio required for IL-1Ra to inhibit IL-1β. Chimeric receptor experiments demonstrated that the extracellular (but not cytoplasmic) domain of IL-1Rrp2 or IL-1R1 is required for inhibition by their respective natural antagonists. IL-36Ra bound to IL-1Rrp2, and pretreatment of IL-1Rrp2-expressing cells with IL-36Ra prevented IL-36β-mediated co-immunoprecipitation of IL-1Rrp2 with IL-1RAcP. Taken together, these results suggest that the mechanism of IL-36Ra antagonism is analogous to that of IL-1Ra, such that IL-36Ra binds to IL-1Rrp2 and prevents IL-1RAcP recruitment and the formation of a functional signaling complex. In addition, truncation of IL-36α, IL-36β, and IL-36γ dramatically enhances their activity, suggesting that post-translational processing is required for full activity.