gebhart/patrepeval huggingface dataset:
Ramiprilate Inhibits Functional Matrix Metalloproteinase Activity in Crohn’s Disease Fistulas (2011)

Increased expression of matrix metalloproteinase (MMP)-2, -3 and -9 has been demonstrated in Crohn's disease fistulas, but it is unknown whether these enzymes are biologically active and represent a therapeutic target. Therefore, we investigated the proteolytic activity of MMPs in fistula tissue and examined the effect of inhibitors, including clinically available drugs that beside their main action also suppress MMPs. Fistula specimens were obtained by surgical excision from 22 patients with Crohn's disease and from 10 patients with fistulas resulting from other causes. Colonic endoscopic biopsies from six controls were also included. Total functional MMP activity was measured by a high-pressure liquid chromatography (HPLC)-based, fluorogenic MMP-substrate cleavage assay, and the specific activity of MMP-2, -3 and -9 by the MMP Biotrak Activity Assay. The MMP inhibitors comprised ethylene-diamine-tetraacetic acid (EDTA), the synthetic broad-spectrum inhibitor, GM6001, the angiotensin-converting enzyme (ACE) inhibitor, ramiprilate, and the tetracycline, doxycycline. In Crohn's disease fistulas, about 50% of the total protease activity was attributable to MMP activity. The average total MMP activity was significantly higher (about 3.5-times) in Crohn's fistulas (471 FU/μg protein, range 49-2661) compared with non-Crohn's fistulas [134 FU/μg protein, range 0-495, (p < 0.05)] and normal colon [153 FU/μg protein, range 77-243, (p < 0.01)]. MMP-3 activity was increased in Crohn's fistulas (1.4 ng/ml, range 0-9.83) compared with non-Crohn's fistulas, [0.32 ng/ml, range 0-2.66, (p < 0.02)]. The same applied to MMP-9 activity [0.64 ng/ml, range 0-5.66 and 0.17 ng/ml, range 0-1.1, respectively (p < 0.04)]. Ramiprilate significantly decreased the average total MMP activity level by 42% and suppressed the specific MMP-3 activity by 72%, which is comparable to the effect of GM6001 (87%). Moreover, MMP-9 activity was completely blunted by ramiprilate. Doxycycline had no effect on MMP activity. Increased functional MMP activity, notably MMP-3 and -9, is present in Crohn's fistulas and may be inhibited by ramiprilate, a widely available ACE inhibitor.
Editorial (2000)

ADVERTISEMENT RETURN TO ISSUEPREVEditorialNEXTEditorialTrevor LairdView Author Information Editor Cite this: Org. Process Res. Dev. 2000, 4, 5, 370–371Publication Date (Web):August 24, 2000Publication History Published online24 August 2000Published inissue 1 September 2000https://pubs.acs.org/doi/10.1021/op000090shttps://doi.org/10.1021/op000090seditorialACS PublicationsCopyright © 2000 American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views730Altmetric-Citations8LEARN 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 PDF (18 KB) Get e-AlertscloseSUBJECTS:Crystallization,Pharmaceuticals,Quality management,Salts,Solvents Get e-Alerts
Color image compression for single-chip cameras (1991)

A review of the basic concepts of CFA (color filter array) pattern design and color interpolation is given, and conventional compression methods are discussed. New compression methods that are applied to the image data before color interpolation are presented. The idea is to separate the raw sensor data into the three color groups. Then the compression is performed individually on each group of data. This approach either eliminates or reduces most discontinuities in the raw data. Simulation results show good compression performance with good image quality and relatively low artifacts. This approach is also appropriate for real-time implementation in single-chip cameras.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Deformability based cell margination—A simple microfluidic design for malaria-infected erythrocyte separation (2010)

In blood vessels with luminal diameter less than 300 µm, red blood cells (RBCs) which are smaller in size and more deformable than leukocytes, migrate to the axial centre of the vessel due to flow velocity gradient within the vessels. This phenomenon displaces the leukocytes to the vessel wall and is aptly termed as margination. Here, we demonstrate using microfluidics that stiffer malaria-infected RBCs (iRBCs) behave similar to leukocytes and undergo margination towards the sidewalls. This provides better understanding of the hemodynamic effects of iRBCs in microcirculation and its contribution to pathophysiological outcome relating to cytoadherence to endothelium. In this work, cell margination is mimicked for the separation of iRBCs from whole blood based on their reduced deformability. The malaria infected sample was tested in a simple long straight channel microfluidic device fabricated in polydimethylsiloxane. In this microchannel, cell margination was directed along the channel width with the iRBCs aligning near each sidewall and then subsequently removed using a 3-outlet system, thus achieving separation. Tests were conducted using ring stage and late trophozoite/schizont stage iRBCs. Device performance was quantified by analyzing the distribution of these iRBCs across the microchannel width at the outlet and also conducting flow cytometry analysis. Results indicate recovery of approximately 75% for early stage iRBCs and >90% for late stage iRBCs at the side outlets. The simple and passive system operation makes this technique ideal for on-site iRBCs enrichment in resource-limited settings, and can be applied to other blood cell diseases, e.g. sickle cell anemia and leukemia, characterized by changes in cell stiffness.
Evidence for increased in vivo mutation and somatic recombination in Bloom's syndrome. (1989)

The glycophorin A assay was used to estimate the frequency of mutations that accumulate in vivo in somatic cells of persons with Bloom's syndrome (BS). This assay measures the frequency in persons of blood type MN of variant erythrocytes that lack the expression of one allelic form of glycophorin A, presumably due to mutational or recombinational events in erythroid precursor cells. Samples of blood from persons with BS showed dramatic 50- to 100-fold increases in the frequency of variants of three types, those with a hemizygous phenotype, those with a homozygous phenotype, and those with what appears to be partial loss of the expression of one locus. The high frequency of homozygous variants, genetic evidence for altered allelic segregation of a specific biochemical locus, provides evidence for increased somatic crossing-over in vivo in BS. An increased generation of functional hemizygosity and homozygosity in their somatic cells may play an important role in the extreme cancer risk of persons with BS.
Improved molecular imaging contrast agent for detection of human thrombus (2003)

Molecular imaging of microthrombus within fissures of unstable atherosclerotic plaques requires sensitive detection with a thrombus-specific agent. Effective molecular imaging has been previously demonstrated with fibrin-targeted Gd-DTPA-bis-oleate (BOA) nanoparticles. In this study, the relaxivity of an improved fibrin-targeted paramagnetic formulation, Gd-DTPA-phosphatidylethanolamine (PE), was compared with Gd-DTPA-BOA at 0.05-4.7 T. Ion- and particle-based r(1) relaxivities (1.5 T) for Gd-DTPA-PE (33.7 (s*mM)(-1) and 2.48 x 10(6) (s*mM)(-1), respectively) were about twofold higher than for Gd-DTPA-BOA, perhaps due to faster water exchange with surface gadolinium. Gd-DTPA-PE nanoparticles bound to thrombus surfaces via anti-fibrin antibodies (1H10) induced 72% +/- 5% higher change in R(1) values at 1.5 T (deltaR(1) = 0.77 +/- 0.02 1/s) relative to Gd-DTPA-BOA (deltaR(1) = 0.45 +/- 0.02 1/s). These studies demonstrate marked improvement in a fibrin-specific molecular imaging agent that might allow sensitive, early detection of vascular microthrombi, the antecedent to stroke and heart attack.
PPOs, HMOs, IPAs--understanding their concepts. (1985)

Over the past ten years, hospitals, physicians and health care administrators have been inundated with changes in health care reimbursement policies. Many administrators have dealt with changes in the way hospitals and physicians are reimbursed and, as employees, have had to make choices in their own personal health care coverage. The purpose of this paper is to examine several organizational structures that have been developed in response to reimbursement changes. We will look at the structure, and the advantages and disadvantages of PPOs, HMOs and IPAs.
Nucleic acid vaccination of sheep: Use in combination with a conventional adjuvanted vaccine against Taenia ovis (1997)

This report describes the use of a nucleic acid vaccine in a large outbred animal species both alone and in combination with a conventionally adjuvanted vaccine. The gene encoding a host-protective antigen (45W) from the sheep parasite Taenia ovis was cloned into the expression vector pcDNA3 and the resultant plasmid termed pcDNA3-45W. Eleven of 15 sheep injected either intramuscularly or intradermally with pcDNA3-45W mounted a serum antibody response to 45W which for both routes of injection was predominantly IgG1. However, the level of antibody elicited by the nucleic acid vaccine was low and repeated vaccinations did not boost the response. Injection of pcDNA3-45W into animals in which an immune response had previously been generated by vaccination with recombinant 45W using Quil A as adjuvant (rec45W vaccine), did not result in enhanced antibody levels. Initial vaccination with pcDNA3-45W and subsequently with the rec45W vaccine resulted in antibody levels significantly higher (P < 0.05) than those obtained in sheep which had only received the rec45W vaccine. This enhanced antibody response was predominantly of the IgG1 subclass (IgG1 : IgG2, 5 : 1) in animals injected with the nucleic acid vaccine by the i.m. route. Surprisingly, a second rec45W vaccination of these animals led to little or no increase in IgG1 levels and a 10-fold increase in IgG2 resulting in a predominance of 45W-specific IgG2 (IgG1 : IgG2, 0.25 1). These studies revealed that nucleic acid vaccination has efficacy, albeit limited, in the sheep and supports previous investigations which showed that antibody responses elicited by immunization are determined by both the route and mode of antigen delivery.
Systematic Review of the Association Between Respiratory Diseases and Oral Health (2006)

1) There is fair evidence (II-2, grade B recommendation) of an association of pneumonia with oral health (odds ratio [OR]=1.2 to 9.6 depending on oral health indicators). 2) There is poor evidence of a weak association (OR<2.0) between COPD and oral health (II-2/3, grade C recommendation). 3) There is good evidence (I, grade A recommendation) that improved oral hygiene and frequent professional oral health care reduces the progression or occurrence of respiratory diseases among high-risk elderly adults living in nursing homes and especially those in intensive care units (ICUs) (number needed to treat [NNT]=2 to 16; relative risk reduction [RRR]=34% to 83%).
Dual Inactivation of Akt and ERK by TIC10 Signals Foxo3a Nuclear Translocation, TRAIL Gene Induction, and Potent Antitumor Effects (2013)

Recombinant tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an antitumor protein that is in clinical trials as a potential anticancer therapy but suffers from drug properties that may limit efficacy such as short serum half-life, stability, cost, and biodistribution, particularly with respect to the brain. To overcome such limitations, we identified TRAIL-inducing compound 10 (TIC10), a potent, orally active, and stable small molecule that transcriptionally induces TRAIL in a p53-independent manner and crosses the blood-brain barrier. TIC10 induces a sustained up-regulation of TRAIL in tumors and normal cells that may contribute to the demonstrable antitumor activity of TIC10. TIC10 inactivates kinases Akt and extracellular signal-regulated kinase (ERK), leading to the translocation of Foxo3a into the nucleus, where it binds to the TRAIL promoter to up-regulate gene transcription. TIC10 is an efficacious antitumor therapeutic agent that acts on tumor cells and their microenvironment to enhance the concentrations of the endogenous tumor suppressor TRAIL.
Purification of the 110-kilodalton glycoprotein receptor for mouse hepatitis virus (MHV)-A59 from mouse liver and identification of a nonfunctional, homologous protein in MHV-resistant SJL/J mice (1990)

The receptor for mouse hepatitis virus strain A59 (MHV-A59) is a 110- to 120-kilodalton (kDa) glycoprotein which is expressed in MHV-susceptible mouse strains on the membranes of hepatocytes, intestinal epithelial cells, and macrophages. SJL/J mice, which are highly resistant to MHV-A59, were previously shown to lack detectable levels of receptor by using either solid-phase virus receptor assays or binding of a monoclonal anti-receptor antibody (MAb) which blocks infection of MHV-susceptible mouse cells. This MAb was used for affinity purification of the receptor glycoprotein from livers of MHV-susceptible Swiss Webster mice. The MHV receptor and an antigenically related protein of 48 to 58 kDa were copurified and then separated by preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The first 15 amino acids of the receptor were sequenced, and a synthetic peptide of this amino acid sequence was prepared. Rabbit antiserum made against this peptide bound to the MHV receptor glycoprotein and the 48- to 58-kDa protein from livers of MHV-susceptible BALB/c mice and Swiss Webster mice and from the intestinal brush border of BALB/c mice. In immunoblots of intestinal brush border and hepatocyte membranes of MHV-resistant SJL/J mice, the antibody against the amino terminus of the receptor identified proteins that are 5 to 10 kDa smaller than the MHV receptor and the 48- to 58-kDa related protein from Swiss Webster or BALB/c mice. Thus, SJL/J mice express a protein which shares some sequence homology with the MHV receptor but which lacks virus-binding activity and is not recognized by the blocking anti-receptor MAb. These results suggest that resistance of SJL/J mice to MHV-A59 may be due to absence or mutation of the virus-binding domain in the nonfunctional receptor homolog in SJL/J mice.
Treatment of diffuse intrinsic brainstem gliomas: failed approaches and future strategies (2009)

Diffuse intrinsic pontine gliomas constitute ~ 60-75% of tumors found within the pediatric brainstem. These malignant lesions present with rapidly progressive symptoms such as cranial nerve, long tract, or cerebellar dysfunctions. Magnetic resonance imaging is usually sufficient to establish the diagnosis and obviates the need for surgical biopsy in most cases. The prognosis of the disease is dismal, and the median survival is < 12 months. Resection is not a viable option. Standard therapy involves radiotherapy, which produces transient neurological improvement with a progression-free survival benefit, but provides no improvement in overall survival. Clinical trials have been conducted to assess the efficacy of chemotherapeutic and biological agents in the treatment of diffuse pontine gliomas. In this review, the authors discuss recent studies in which systemic therapy was administered prior to, concomitantly with, or after radiotherapy. For future perspective, the discussion includes a rationale for stereotactic biopsies as well as possible therapeutic options of local chemotherapy in these lesions.
Mechanisms of DNA double-strand break repair and their potential to induce chromosomal aberrations (2000)

DNA double-strand breaks (DSB) are considered to be critical primary lesions in the formation of chromosomal aberrations. DSB may be induced by exogenous agents, such as ionizing radiation, but also occur spontaneously during cellular processes at quite significant frequencies. To repair this potentially lethal damage, eukaryotic cells have evolved a variety of repair pathways related to homologous and illegitimate recombination, also called non-homologous DNA end joining, which may induce small scale mutations and chromosomal aberrations. In this paper we review the major cellular sources of spontaneous DSB and the different homologous and illegitimate recombination repair pathways, with particular focus on their potential to induce chromosomal aberrations.
Change in the ratio of interleukin-6 to interleukin-10 predicts a poor outcome in patients with systemic inflammatory response syndrome (1999)

In nonsurvivors, IL-6 concentrations did not decrease, IL-10 concentration decreased, and the ratio of IL-6 to IL-10 increased. An increase in the ratio of IL-6 to IL-10 indicated a correlation with a poor outcome.
Arid5a controls IL-6 mRNA stability, which contributes to elevation of IL-6 level in vivo (2013)

Posttranscriptional regulation of IL-6 has been largely uncharacterized, with the exception of the ribonuclease Regnase-1, which prevents autoimmunity by destabilizing IL-6 mRNA. Here, we identified AT-rich interactive domain-containing protein 5A (Arid5a) as a unique RNA binding protein, which stabilizes IL-6 but not TNF-α mRNA through binding to the 3′ untranslated region of IL-6 mRNA. Arid5a was enhanced in macrophages in response to LPS, IL-1β, and IL-6. Arid5a deficiency inhibited elevation of IL-6 serum level in LPS-treated mice and suppressed IL-6 levels and the development of T H 17 cells in experimental autoimmune encephalomyelitis. Importantly, Arid5a inhibited the destabilizing effect of Regnase-1 on IL-6 mRNA. These results indicate that Arid5a plays an important role in promotion of inflammatory processes and autoimmune diseases.
Basis for the Design of Anticandidal Agents from Studies of Peptide Utilization in Candida albicans (1976)

The growth of Candida albicans WD 18-4, a methionine and lysine double auxotroph, on a variety of methionine- and lysine-containing peptides was determined. This yeast does not excrete extracellular peptidases. Thus, the growth response to peptides containing the required amino acid is a measure of peptide transport. A variety of methionine-containing peptides such as Met-Met, Met-Met-Met, and Met-Met-Met-Met-Met are transported. Acylation of the N-terminus of transported peptides does not affect their transport, but derivitization of the C-terminus prevents peptide uptake. In contrast, all lysine-containing peptides tested, except Lys-Gly, were not growth substrates. The inability of a peptide to substitute for the requisite amino acid was not due to the absence of cellular peptidases or to toxicity of the nonutilized peptides. Several potentially toxic amino acids were carried into Candida as a component of transported peptides. This establishes the peptide transport system as a possible tool for the design of antibiotics for Candida albicans.
Ultrasensitive online SERS detection of structural isomers separated by capillary zone electrophoresis (2014)

A mixture of structural isomers was separated and identified at nanomolar concentrations (∼100,000 molecules) by incorporating capillary zone electrophoresis (CZE) with a sheath flow surface-enhanced Raman scattering (SERS) detector. Baseline resolution was obtained from three structural isomers of rhodamine using a planar silver SERS substrate, demonstrating the utility of this approach for trace chemical analysis.
Stem and Precursor Cells in the Nervous System (2004)

The early-formed neural tube consists of proliferating, morphologically homogeneous cells, termed "neuroepithelial (NEP) stem cells" which generate neurons, astrocytes, and oligodenrocytes through a series of intermediate precursor cells. In addition to NEP cells, a second class of stem cells-the neurosphere-forming cell-can be isolated at later stages of development. NEP cells can differentiate into neural crest stem cells, which in turn generate PNS derivatives. NEP cells and neurosphereforming stem cells and more restricted precursors express a characteristic spectrum of markers that can be used to characterize them. Each of these cell types can be isolated from embryonic stem (ES) cell cultures, and their behavior appears similar to cells isolated at later developmental ages. The relative advantages and disadvantages of these cells for cell replacement therapy are discussed.
Stimulation of Fibrotic Processes by the Infrapatellar Fat Pad in Cultured Synoviocytes From Patients With Osteoarthritis: A Possible Role for Prostaglandin F2α (2013)

These results indicate that the IPFP can contribute to the development of synovial fibrosis in the knee joint by increasing collagen production, PLOD2 expression, cell proliferation, and cell migration. In addition, whereas the findings showed that TGFβ is not involved, the more recently discovered profibrotic factor PGF2α appears to be partially involved in the regulation of profibrotic changes.
Self‐assembling peptide nanofibers and skeletal myoblast transplantation in infarcted myocardium (2008)

Cell transplantation is currently limited by poor graft retention and survival in the postinfarction scar. Because this issue could potentially be addressed by embedding cells in bioinjectable scaffolds and boosting cell survival pathways, we induced a myocardial infarction in 72 rats to assess the effects of different self-assembling peptides with or without platelet-derived growth factor (PDGF-BB) on survival of transplanted skeletal myoblasts. Two weeks after coronary artery ligation, rats were randomized to receive in-scar injections of culture medium (controls, n = 11), self-assembling peptide (RAD16-I) nanofibers (NF, n = 9), skeletal myoblasts (n = 12), or skeletal myoblasts in combination with NF (n = 8). In separate experiments with different self-assembling peptides (RAD16-II), rats received in-scar injections of culture medium (controls, n = 6), skeletal myoblasts (n = 10), PDGF-loaded peptides (n = 7), or skeletal myoblasts (5 x 10(6)) in combination with PDGF-loaded peptides (n = 9). After 1 month, left ventricular function, as assessed by echocardiography, was not improved in either of the experimental groups compared with controls. This correlated with the failure of RAD16-I peptides or PDGF-loaded RAD16-II peptides to improve myoblast survival despite a greater angiogenesis. In vitro experiments confirmed that the number of myoblasts decreased over time when seeded on nanofiber gels. These data suggest that the optimal use of biomaterial scaffolds for survival of transplanted cells will require specific tailoring of the biomaterial to the cell type.