gebhart/patrepeval huggingface dataset:
Inhibitory effects of anti-rheumatic drugs on vascular endothelial growth factor in cultured rheumatoid synovial cells (1999)

Vascular endothelial growth factor (VEGF) is a potent inducer of angiogenesis and is constitutively expressed in the synovium of rheumatoid arthritis (RA). Over-expression of VEGF may play an important role in pathogenic vascularization and synovial hyperplasia of RA. In the present study, we examined whether disease-modifying anti-rheumatic drugs (DMARDs), including bucillamine (BUC), gold sodium thiomalate (GST), methotrexate (MTX) and salazosulfapiridine (SASP), act by inhibiting the production of VEGF by cultured synovial cells of patients with RA. Treatment of cultured synoviocytes with lipopolysaccharide (LPS) significantly increased VEGF production by cultured synovial cells. BUC significantly inhibited LPS-induced VEGF production, while GST tended to inhibit the production of VEGF. The inhibitory effects on VEGF production were dose-dependent. In contrast, MTX and SASP did not affect VEGF production. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis showed that BUC also inhibited LPS-induced VEGF mRNA expression in RA synovial cells. The present study provides the first evidence that BUC inhibits VEGF production and the expression of its mRNA in synovial cells of RA patients. Our results indicate that the anti-rheumatic effects of BUC are mediated by suppression of angiogenesis and synovial proliferation in the RA synovium through the inhibition of VEGF production by synovial cells.
Severity of articular cartilage abnormality in patients with osteoarthritis: evaluation with fast spin-echo MR vs arthroscopy. (1994)

Our results suggest that fat-presaturated fast spin-echo MR imaging depicts the severity of articular cartilage abnormalities in osteoarthritis with reasonable accuracy, as compared with arthroscopic evaluation as the standard of reference.
Separation of isomeric lysophospholipids by reverse phase HPLC (1985)

A reverse-phase high performance liquid chromatography (HPLC) method was developed which resolved isomers of lysophosphatidylcholine (LPC) differing in the location of the aliphatic chain (sn-1 or sn-2 position) and the position (delta 6 or delta 9) or geometric configuration (cis or trans) of the olefin group in monounsaturated species. LPC isomers containing an acyl substituent at the sn-2 position eluted before their 1-acyl-sn-glycero-3-phosphocholine (1-acyl LPC) counterparts. The retention times of both the sn-1 and sn-2 isomers of monounsaturated species increased in the order delta 9-cis less than delta 9-trans less than delta 6-cis. The integrated ultraviolet absorbance (203 nm) in binary mixtures of the delta 9-cis and delta 6-cis 2-acyl lysophospholipid isomers correlated with the lipid phosphorus content of corresponding column eluates (r = 0.994). Thus, the present method will facilitate synthesis of isomerically pure diradylphospholipids by providing homogeneous lysophospholipid precursors and help simplify the quantitative analysis of unsaturated lysophospholipid species.
Water Shut Off in Gas Wells: Is there Scope for a Chemical Treatment? (2001)

Abstract Water producing gas wells may suffer from liquid loading and get killed or their water production may exceed the capacity of the water handling facilities. Just closing off the water producing zone may be unacceptable if they have a large contribution to the gas production. A near well bore chemical treatment using a polymer solution is an option to reduce the water production and maintain the gas production. Once adsorbed to reservoir rock, the polymer may significantly reduce the relative permeability to water in the near well bore area. Hundreds of gas wells of the Nederlandse Aardolie Maatschappij (The Netherlands) suffer from water production. A simulation study using a radial single well model was carried out to look after the feasibility of a treatment. The study shows that a treatment based on reduction of the water relative permeability causes a choke effect: both the water and gas flow rates are reduced instead of only the water rate. Moreover, the benefits of a treatment are tempered because of a clean-up effect after injection of the chemicals. A reduction in the water/gas ratio by a factor 2 requires a reduction in the water relative permeability by at least a factor 10. A well which was killed due to liquid loading at a high water/gas ratio and with a high contribution to the gas production by the water producing interval is a suitable candidate for treatment. A treatment may also be considered for a well of which the water production exceeds the capacity of the water handling facilities. Provided that the flowing tubing head pressure can be significantly lowered, the loss of gas production from the water producing zone can be compensated by increased gas production from the other intervals.
Revised diagnostic criteria for neuromyelitis optica (2006)

The authors propose revised diagnostic criteria for definite neuromyelitis optica (NMO) that require optic neuritis, myelitis, and at least two of three supportive criteria: MRI evidence of a contiguous spinal cord lesion 3 or more segments in length, onset brain MRI nondiagnostic for multiple sclerosis, or NMO-IgG seropositivity. CNS involvement beyond the optic nerves and spinal cord is compatible with NMO.
Current Status of Oral Carbapenem Development (2002)

Since the discovery of thienamycin (1) in 1976, many studies on the synthesis and structure-activity relationships of parenteral-use drugs have been done and several carbapenems, imipenem (2), panipenem (3), and meropenem (7), have been marketed. The development of oral carbapenems, however, is a fairly slow process because carbapenems are considered unstable in the stomach and intestine. Recently, several orally active carbapenems without stability problems have been developed as prodrug esters or prodrug peptides, including GV-118819 (12), CS-834 (13), L-084 (14), DZ-2640 (15), and peptidic derivatives of CL 191,121 (16). The active forms (35), (41), (44), (45), (16) of these prodrugs exhibited potent and well balanced antibacterial activities as well as resistance to renal dehydropeptidase-I. The pharmacokinetic parameters of compounds (12), (13), (14), and (15) after oral administration to healthy volunteers were reported. The half-life (t1 / 2) of GV-118819 (12) was longer than that of the other compounds, while the Cmax, AUC and urinary excretion rate of L-084 (14) were higher than those of the others. In this review, the synthesis, chemical and biological properties, and pharmacokinetics of these oral carbapenems are described. Keywords: Carbapenem Development, Thienamycin, Imipenem, Panipenem, Meropenem, Synthsis, Beta-Methlazetidin-2-one
Salmonella -Type Heptaacylated Lipid A Is Inactive and Acts as an Antagonist of Lipopolysaccharide Action on Human Line Cells (2000)

The stimulation of both THP-1 and U937 human-derived cells by Salmonella lipid A preparations from various strains, as assessed by TNF-alpha induction and NF-kappaB activation, was found to be very low (almost inactive) compared with Escherichia coli lipid A, but all of the lipid As exerted strong activity on mouse cells and on Limulus gelation activity. Experiments using chemically synthesized E. coli-type hexaacylated lipid A (506) and Salmonella-type heptaacylated lipid A (516) yielded clearer results. Both lipid A preparations strongly induced TNF-alpha release and activated NF-kappaB in mouse peritoneal macrophages and mouse macrophage-like cell line J774-1 and induced Limulus gelation activity, although the activity of the latter was slightly weaker than that of the former. However, 516 was completely inactive on both THP-1 and U937 cells in terms of both induction of TNF-alpha and NF-kappaB activation, whereas 506 displayed strong activity on both cells, the same as natural E. coli LPS. In contrast to the action of the lipid A preparations, all the Salmonella LPSs also exhibited full activity on human cells. However, the polysaccharide portion of the LPS neither exhibited TNF-alpha induction activity on the cells when administered alone or together with lipid A nor inhibited the activity of the LPS. These results suggest that the mechanism of activation by LPS or the recognition of lipid A structure by human and mouse cells may differ. In addition, both 516 and lipid A from Salmonella were found to antagonize the 506 and E. coli LPS action that induced TNF-alpha release and NF-kappaB activation in THP-1 cells.
Interaction of the RAGE Cytoplasmic Domain with Diaphanous-1 Is Required for Ligand-stimulated Cellular Migration through Activation of Rac1 and Cdc42 (2008)

Cellular migration is a fundamental process linked to diverse pathological states such as diabetes and its complications, atherosclerosis, inflammation, and cancer. The receptor for advanced glycation end products (RAGE) is a multiligand cell surface macromolecule which binds distinct ligands that accumulate in these settings. RAGE-ligand interaction evokes central changes in key biological properties of cells, including proliferation, generation of inflammatory mediators, and migration. Although RAGE-dependent signal transduction is critically dependent on its short cytoplasmic domain, to date the proximate mechanism by which this RAGE domain engages and stimulates cytoplasmic signaling pathways has yet to be identified. Here we show that the RAGE cytoplasmic domain interacts with Diaphanous-1 (Dia-1) both in vitro and in vivo. We employed the human RAGE cytoplasmic domain as "bait" in the yeast two-hybrid assay and identified the formin homology (FH1) domain of Dia-1 as a potential binding partner of this RAGE domain. Immunoprecipitation studies revealed that the RAGE cytoplasmic domain interacts with the FH1 domain of Dia-1. Down-regulation of Dia-1 expression by RNA interference blocks RAGE-mediated activation of Rac-1 and Cdc42 and, in parallel, RAGE ligand-stimulated cellular migration. Taken together, these findings indicate that the interaction of the RAGE cytoplasmic domain with Dia-1 is required to transduce extracellular environmental cues evoked by binding of RAGE ligands to their cell surface receptor, a chief consequence of which is Rac-1 and Cdc42 activation and cellular migration. Because RAGE and Dia-1 are implicated in the regulation of inflammatory, vascular, and transformed cell migration, these findings highlight this interaction as a novel target for therapeutic intervention in inflammation, atherosclerosis, diabetes, and cancer.
Netrins: beyond the brain (2007)

Named after the Sanskrit word netr, which means 'one who guides', the netrin family of secreted proteins provides migrational cues in the developing central nervous system. Recently, netrins have also been shown to regulate diverse processes (such as cell adhesion, motility, proliferation, differentiation and, ultimately, cell survival) in a number of non-neuronal tissues. In some cases, netrins affect these functions through non-classic netrin receptors, prompting a renewed interest in these factors in and beyond the nervous system.
Analbuminemia: three cases resulting from different point mutations in the albumin gene. (1994)

Analbuminemia is a very rare recessive disorder in which subjects have little or no circulating albumin, although albumin is normally the most abundant plasma protein and has many functions. Analbuminemia is caused by a variety of mutations in the albumin gene and is exhibited only by subjects homozygous for the defect. Previously the mutation had been identified at the molecular level in only two human cases; in one case it resulted from an exon-splicing defect, and in the other case it was caused by a nucleotide insertion that caused a frameshift and premature stop codon. In this investigation we identified the mutations in three unrelated subjects from different countries. In each instance a single-nucleotide mutation produced a stop codon, but the mutations occurred at three different sites: (i) in an Italian male a C-->T transition at nt 2368 in the genomic sequence of albumin, (ii) a C-->T transition at nt 4446 for an American female, and (iii) a G-->A transition at nt 7708 in a Canadian male. The size of the albumin fragment that might have been produced for the three cases varied from 31- to 213-amino acid residues, but no evidence for a circulating albumin fragment was obtained. The paradox is that analbuminemia is extremely rare (frequency < 1 x 10(6)); yet the virtual absence of albumin is tolerable despite its multiple functions.
M-LCELP speech coding at 4 kbps (2002)

This paper presents the M-LCELP (multi-mode learned code excited LPC) speech coder, which has been developed for the North American half-rate digital cellular systems. M-LCELP develops the following techniques to achieve high-quality synthetic speech at 4 kbps: (1) Multimode and multi-codebook coding, (2) Pitch lag differential coding with pitch tracking, (3) A two-stage joint design regular-pulse codebook with common phase structure in voiced frames, (4) An efficient vector quantization for LSP parameters, (5) An adaptive MA type comb filter to suppress excitation signal inter-harmonic noise. The MOS subjective test shows that 4.075 kbps M-LCELP synthetic speech quality is high, and that its quality is mostly equivalent to that for an 8 kbps North American full-rate VSELP coder.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Branched-chain amino acids increase arterial blood ammonia in spite of enhanced intrinsic muscle ammonia metabolism in patients with cirrhosis and healthy subjects (2011)

Branched-chain amino acids (BCAA) are used in attempts to reduce blood ammonia in patients with cirrhosis and intermittent hepatic encephalopathy based on the hypothesis that BCAA stimulate muscle ammonia detoxification. We studied the effects of an oral dose of BCAA on the skeletal muscle metabolism of ammonia and amino acids in 14 patients with cirrhosis and in 7 healthy subjects by combining [(13)N]ammonia positron emission tomography (PET) of the thigh muscle with measurements of blood flow and arteriovenous (A-V) concentrations of ammonia and amino acids. PET was used to measure the metabolism of blood-supplied ammonia and the A-V measurements were used to measure the total ammonia metabolism across the thigh muscle. After intake of BCAA, blood ammonia increased more than 30% in both groups of subjects (both P < 0.05). Muscle clearance of blood-supplied ammonia (PET) was unaffected (P = 0.75), but the metabolic removal rate (PET) increased significantly because of increased blood ammonia in both groups (all P < 0.05). The total ammonia clearance across the leg muscle (A-V) increased by more than 50% in both groups, and the flux (A-V) of ammonia increased by more than 45% (all P < 0.05). BCAA intake led to a massive glutamine release from the muscle (cirrhotic patients, P < 0.05; healthy subjects, P = 0.12). In conclusion, BCAA enhanced the intrinsic muscle metabolism of ammonia but not the metabolism of blood-supplied ammonia in both the patients with cirrhosis and in the healthy subjects.
A Survey of Defense Mechanisms Against Distributed Denial of Service (DDoS) Flooding Attacks (2013)

Distributed Denial of Service (DDoS) flooding attacks are one of the biggest concerns for security professionals. DDoS flooding attacks are typically explicit attempts to disrupt legitimate users' access to services. Attackers usually gain access to a large number of computers by exploiting their vulnerabilities to set up attack armies (i.e., Botnets). Once an attack army has been set up, an attacker can invoke a coordinated, large-scale attack against one or more targets. Developing a comprehensive defense mechanism against identified and anticipated DDoS flooding attacks is a desired goal of the intrusion detection and prevention research community. However, the development of such a mechanism requires a comprehensive understanding of the problem and the techniques that have been used thus far in preventing, detecting, and responding to various DDoS flooding attacks. In this paper, we explore the scope of the DDoS flooding attack problem and attempts to combat it. We categorize the DDoS flooding attacks and classify existing countermeasures based on where and when they prevent, detect, and respond to the DDoS flooding attacks. Moreover, we highlight the need for a comprehensive distributed and collaborative defense approach. Our primary intention for this work is to stimulate the research community into developing creative, effective, efficient, and comprehensive prevention, detection, and response mechanisms that address the DDoS flooding problem before, during and after an actual attack.
A rapid, quantitative assay for direct detection of microRNAs and other small RNAs using splinted ligation (2007)

The discovery and characterization of microRNAs (miRNAs) and other families of short RNAs has led to a rapid expansion of research directed at elucidating their expression patterns and regulatory functions. Here, we describe a convenient, sensitive, and straightforward method to detect and quantitate specific miRNA levels in unfractionated total RNA samples. The method, based on splinted ligation, does not require specialized equipment or any amplification step, and is significantly faster and more sensitive than Northern blotting. We demonstrate that the method can be used to detect various classes of small regulatory RNAs from different organisms.
Conscious Neuromodulation of the Bladder before Clinical Use (2015)

No AccessJournal of UrologyEditorial1 Jul 2015Conscious Neuromodulation of the Bladder before Clinical Use Craig V. Comiter Craig V. ComiterCraig V. Comiter Financial interest and/or other relationship with Coloplast. More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.04.015AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Conscious Neuromodulation of the Bladder before Clinical Use." The Journal of Urology, 194(1), pp. 16–17 References 1 : Urinary bladder contraction and relaxation: physiology and pathophysiology. Physiol Rev2004; 84: 935. Google Scholar 2 : Comparison of low-dose ketamine to midazolam for sedation during pediatric urodynamic study. Pediatr Anesth2013; 23: 425. Google Scholar 3 : Rodent models for urodynamic investigation. Neurourol Urodyn2011; 30: 636. Google Scholar 4 : Effects of various drugs on bladder function in conscious restrained-denervated rats placed in a restraining cage and produced by transection of the hypogastric nerve. Jpn J Pharmacol1990; 52: 405. Google Scholar 5 : Lower urinary tract phenotype of experimental autoimmune cystitis in mouse: a potential animal model for interstitial cystitis. BJU Int2008; 102: 1724. Google Scholar 6 : Urodynamic changes in mice with experimental autoimmune encephalomyelitis correlate with neurological impairment. Neurourol Urodyn2015; . Epub ahead of print. Google Scholar 7 : A chronic, conscious large animal platform to quantify therapeutic effects of sacral neuromodulation on bladder function. J Urol2015; 194: 252. Link, Google Scholar 8 : Urethral pudendal afferent-evoked bladder and sphincter reflexes in decerebrate and acute spinal cats. Neurosci Lett1998; 244: 137. Google Scholar 9 : Bladder activation by selective stimulation of pudendal nerve afferents in the cat. Exp Neurol2008; 212: 218. Google Scholar 10 : Conventional, continuous, and telemetric monitoring of urodynamic parameters in hon-human primates: a comparative study. Neurourol Urodyn1996; 15: 203. Google Scholar 11 : Telemetric monitoring of bladder function in female Gottingen minipigs. BJU Int2015; . Epub ahead of print. Google Scholar © 2015FiguresReferencesRelatedDetails Volume 194Issue 1July 2015Page: 16-17 Advertisement Copyright & Permissions© 2015MetricsAuthor Information Craig V. Comiter Financial interest and/or other relationship with Coloplast. More articles by this author Expand All Advertisement PDF downloadLoading ...
Activation of Th1 and Tc1 cell adenosine A2A receptors directly inhibits IL-2 secretion in vitro and IL-2-driven expansion in vivo (2005)

To evaluate the direct effect of adenosine on cytokine-polarized effector T cells, murine type 1 helper T cells (Th1) and type 1 cytotoxic T lymphocytes (Tc1) and Th2/Tc2 cells were generated using an antigen-presenting cell (APC)-free method. Tc1 and Tc2 cells had similar adenosine signaling, as measured by intracellular cyclic AMP (cAMP) increase upon adenosine A(2A) receptor agonism by CGS21680 (CGS). CGS greatly reduced Tc1 and Tc2 cell interleukin 2 (IL-2) and tumor necrosis factor alpha (TNF-alpha) secretion, with nominal effect on interferon gamma (IFN-gamma) secretion. Tc2 cell IL-4 and IL-5 secretion was not reduced by CGS, and IL-10 secretion was moderately reduced. Agonist-mediated inhibition of IL-2 and TNF-alpha secretion occurred via A(2A) receptors, with no involvement of A(1), A(2B), or A(3) receptors. Adenosine agonist concentrations that abrogated cytokine secretion did not inhibit Tc1 or Tc2 cell cytolytic function. Adenosine modulated effector T cells in vivo, as CGS administration reduced CD4(+)Th1 and CD8(+)Tc1 cell expansion to alloantigen and, in a separate model, reduced antigen-specific CD4(+) Th1 cell numbers. Remarkably, agonist-mediated T-cell inhibition was abrogated by in vivo IL-2 therapy. Adenosine receptor activation therefore preferentially inhibits type I cytokine secretion, most notably IL-2. Modulation of adenosine receptors may thus represent a suitable target primarily for inflammatory conditions mediated by Th1 and Tc1 cells.
Murine embryonic stem cells without pig-a gene activity are competent for hematopoiesis with the PNH phenotype but not for clonal expansion. (1997)

Paroxysmal nocturnal hemoglobinuria (PNH) develops in patients who have had a somatic mutation in the X-linked PIG-A gene in a hematopoietic stem cell; as a result, a proportion of blood cells are deficient in all glycosyl phosphatidylinositol (GPI)-anchored proteins. Although the PIG-A mutation explains the phenotype of PNH cells, the mechanism enabling the PNH stem cell to expand is not clear. To examine this growth behavior, and to investigate the role of GPI-linked proteins in hematopoietic differentiation, we have inactivated the pig-a gene by homologous recombination in mouse embryonic stem (ES) cells. In mouse chimeras, pig-a- ES cells were able to contribute to hematopoiesis and to differentiate into mature red cells, granulocytes, and lymphocytes with the PNH phenotype. The proportion of PNH red cells was substantial in the fetus, but decreased rapidly after birth. Likewise, PNH granulocytes could only be demonstrated in the young mouse. In contrast, the percentage of lymphocytes deficient in GPI-linked proteins was more stable. In vitro, pig-a- ES cells were able to form pig-a- embryoid bodies and to undergo hematopoietic (erythroid and myeloid) differentiation. The number and the percentage of pig-a- embryoid bodies with hematopoietic differentiation, however, were significantly lower when compared with wild-type embryoid bodies. Our findings demonstrate that murine ES cells with a nonfunctional pig-a gene are competent for hematopoiesis, and give rise to blood cells with the PNH phenotype. pig-a inactivation on its own, however, does not confer a proliferative advantage to the hematopoietic stem cell. This provides direct evidence for the notion that some additional factor(s) are needed for the expansion of the mutant clone in patients with PNH.