gebhart/patrepeval huggingface dataset:
Surface Finish Mechanics Explain Different Clinical Survivorship of Cemented Femoral Stems for Total Hip Arthroplasty (2006)

The ability of bone cement to adhere to the implant surface is dependent on the surface finish. Stems with a rough surface finish require greater force to disrupt their interface with the cement than do stems with a smooth or polished surface. However, if micromotion occurs at the cement-metal interface, the fretting of a smoother surface implant results in less cement and metallic abrasion than an implant with a rough surface finish. Today, surgeons implant femoral stems with a wide variety of surface finish and textures that are supported by the previously mentioned contrasting philosophy of fixation. This article presents the micro and macro surface finish mechanics, history, and rationale for changes in surface finish, the clinical and operative implications of changes in surface finish, the retrieval analysis, and the clinical evidence that examine the consequences of changes in surface finish in the outcome of cemented femoral stems for total hip arthroplasty. Current data and our own experience support the use of cemented femoral stems with a smooth or polished surface finish.
Cloning of complete genome sets of six dsRNA viruses using an improved cloning method for large dsRNA genes (2002)

Cloning full-length large (>3 kb) dsRNA genome segments from small amounts of dsRNA has thus far remained problematic. Here, a single-primer amplification sequence-independent dsRNA cloning procedure was perfected for large genes and tailored for routine use to clone complete genome sets or individual genes. Nine complete viral genome sets were amplified by PCR, namely those of two human rotaviruses, two African horsesickness viruses (AHSV), two equine encephalosis viruses (EEV), one bluetongue virus (BTV), one reovirus and bacteriophage Phi12. Of these amplified genomes, six complete genome sets were cloned for viruses with genes ranging in size from 0.8 to 6.8 kb. Rotavirus dsRNA was extracted directly from stool samples. Co-expressed EEV VP3 and VP7 assembled into core-like particles that have typical orbivirus capsomeres. This work presents the first EEV sequence data and establishes that EEV genes have the same conserved termini (5' GUU and UAC 3') and coding assignment as AHSV and BTV. To clone complete genome sets, one-tube reactions were developed for oligo-ligation, cDNA synthesis and PCR amplification. The method is simple and efficient compared to other methods. Complete genomes can be cloned from as little as 1 ng dsRNA and a considerably reduced number of PCR cycles (22-30 cycles compared to 30-35 of other methods). This progress with cloning large dsRNA genes is important for recombinant vaccine development and determination of the role of terminal sequences for replication and gene expression.
Characterization of a Mobile Stat6 Activation Motif in the Human IL-4 Receptor (1998)

The IL-4R induces proliferation and gene expression through the use of conserved tyrosine residues located in growth and gene regulation domains, respectively. We demonstrate that residues surrounding these conserved tyrosines (juxtatyrosine residues) are essential for the proper activation of the signaling molecules IRS-2 and Stat6, as well as for IL-4-induced gene expression. Further, we found that the IL-4R gene regulation domain (amino acids 557-657) contains a tyrosine-based sequence (EAGYKAF) that can convey Stat6 DNA binding and gene expression activities to a minimally active IL-4R mutant, delta 557. Thus, this tyrosine-based sequence can function as a mobile Stat6 activation cassette. However, mutants bearing this sequence induced CD23 expression much less efficiently than did wild-type IL-4R, requiring 150-fold more IL-4 to reach maximal CD23 expression. Our results indicate the importance of juxtatyrosine residues in IL-4R signaling and argue for an essential role of extended domain structure in the recognition and function of juxtatyrosine sequences.
Ondansetron plus Dexamethasone Compared to the ‘Standard’ Metoclopramide Combination (1993)

This paper describes a multicentre, double-blind, parallel group study which compared ondansetron (0.15 mg/kg i.v. x 3) plus dexamethasone (20 mg i.v.) with metoclopramide (3 mg/kg i.v. x 2) plus dexamethasone (20 mg i.v.) and diphenhydramine (50 mg i.v.) for the prevention of cisplatin-induced emesis and nausea. Two hundred and eighty-nine consecutive patients receiving chemotherapy containing cisplatin at doses > or = 50 mg/m2 entered the study and 267 patients were evaluable for efficacy. The ondansetron regimen was significantly superior compared with the metoclopramide regimen in the control of acute emesis and nausea. Ondansetron plus dexamethasone provided complete protection against retching and vomiting in 79% of patients compared with 59% of patients given the metoclopramide combination (p < 0.002). Similarly ondansetron plus dexamethasone completely prevented nausea in 77% of patients, whereas the metoclopramide combination protected 66% of patients (p < 0.051). Success (no nausea and no emesis) was afforded to 69% of those patients given ondansetron plus dexamethasone as opposed to 50% of patients given the metoclopramide combination (p < 0.003). From day 2-4 all patients received the same anti-emetic regimen of oral metoclopramide and intramuscular dexamethasone. Significantly fewer patients who had received the ondansetron regimen on day 1 vomited on days 2 and 3 compared with those who had received the triple drug combination (84-86 and 68-71%, respectively, p < 0.006). Nausea was also better controlled in this group on day 2. On subsequent cisplatin cycles, the incidence of acute vomiting rose to 53% in those patients given the metoclopramide regimen, but remained low (26%) in the group treated with ondansetron plus dexamethasone. Patients receiving the metoclopramide regimen had significantly more sedation than patients receiving ondansetron plus dexamethasone (12 vs. 2%; p < 0.005). Extrapyramidal reactions were only observed in metoclopramide-treated patients (3%). The results of this study suggest that ondansetron plus dexamethasone is a more effective and better tolerated anti-emetic regimen compared with metoclopramide plus dexamethasone and diphenhydramine for the prevention of acute cisplatin-induced emesis.
Lack of evidence for aromatase in human prostatic tissues: effects of 4-hydroxyandrostenedione and other inhibitors on androgen metabolism. (1989)

The effects of 4-hydroxyandrostenedione (4-OHA) and other aromatase inhibitors, 10-propargylestr-4-ene-3,17-dione and imidazo[1,5-alpha]-3,4,5,6-tetrahydropyrin-6-yl-(4-benzonitrile), as well as 5 alpha-reductase inhibitors N,N-diethyl-4-methyl-3-oxo-4-aza-5 alpha-androstane-17 beta-carboxyamide and 4-methyl-3-oxo-4-aza-androsta-5-ene-17-ol were investigated in prostatic tissue from six patients with benign prostatic hypertrophy and seven patients with prostatic cancer, and from normal men at autopsy. We attempted to measure aromatase activity in the tissue incubations by quantitating 3H2O released from androstenedione or testosterone labeled at the C-1 position. High performance liquid chromatography and thin layer chromatography were used to isolate steroid products. Although the amount of 3H2O released was at least twice that of the heat-inactivated tissue samples, no estrone or estradiol was detected on high performance liquid chromatography. The 3H2O release was significantly inhibited by 4-OHA and N,N-diethyl-4-methyl-3-oxo-4-aza-5 alpha-androstane-17 beta-carboxyamide, but not by the other aromatase inhibitors. 4-OHA also inhibited 5 alpha-reductase in both benign prostatic hypertrophy and cancer tissue, although to a lesser extent than N,N-diethyl-4-methyl-3-oxo-4-aza-5 alpha-androstane-17 beta-carboxyamide. The other aromatase inhibitors were without effect on 5 alpha-reductase. Our results indicate that 3H2O released from [1 beta-3H]androstenedione and [1,2,6,7-3H]androstenedione does not correlate with estrogen formation and may be the result of other metabolic reactions. Although it appears that the prostate lacks aromatase, 4-OHA may be of benefit in patients with benign prostatic hypertrophy or prostatic cancer by inhibiting this enzyme in peripheral tissue.
Sacral Neuromodulation is an Effective Treatment for Interstitial Cystitis/Bladder Pain Syndrome: Con (2012)

No AccessJournal of UrologyOpposing View1 Dec 2012Sacral Neuromodulation is an Effective Treatment for Interstitial Cystitis/Bladder Pain Syndrome: Con Robert J. Evans Robert J. EvansRobert J. Evans More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.09.073AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Sacral Neuromodulation is an Effective Treatment for Interstitial Cystitis/Bladder Pain Syndrome: Con." The Journal of Urology, 188(6), pp. 2044–2045 References 1 : Sexual function and sexual distress in women with interstitial cystitis: a case controlled study. Urology2007; 70: 543. Google Scholar 2 : Using the International Continence Society's definition of painful bladder syndrome. Urology2006; 67: 1138. Google Scholar 3 : Sacral neuromodulation for the symptomatic treatment of refractory interstitial cystitis: a prospective study. J Urol2003; 160: 1369. Google Scholar 4 : Bilateral S3 stimulator in patients with interstitial cystitis. Urology2007; 69: 441. Google Scholar 5 : A prospective, single blind, randomized crossover trial of sacral vs pudendal nerve stimulation for interstitial cystitis. BJU Int2007; 100: 1369. Google Scholar Department of Urology, Wake Forest University, Winston-Salem, North Carolina© 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 188Issue 6December 2012Page: 2044-2045 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Robert J. Evans More articles by this author Expand All Advertisement PDF DownloadLoading ...
Epidermal Growth Factor Receptor: Association of Extracellular Domain Negatively Regulates Intracellular Kinase Activation in the Absence of Ligand (2003)

The epidermal growth factor receptor (EGFR) plays an important role in many types of human cancers. Receptor amplification, autocrine activation and/or deletion of exons 2-7 of EGFR gene have all been associated with tumor development. The traditional model of EGFR activation via ligand induced dimerization and consequential kinase activation does not provide full understanding of its tumorigenicity. The main function of the receptor extracellular domain (ECD) has been thought to be ligand recognition and binding. We report that the EGFR ECD, through its association also negatively regulates the activity of the intracellular kinase in the absence of ligand. Even in the absence of its ligands, the EGF receptor forms homodimers, however, the ECD prevents constitutive receptor kinase activation through its intrinsic ligand-independent interaction. The removal of this domain, either partial or total, results in constitutive activation of the receptor kinase as observed by its phosphorylation in intact cells. Furthermore, EGF receptors truncated in the ECD induce phosphorylation of the wild-type full-length receptor, indicating an inter-molecular inhibitory mechanism by the receptor ECD. The tumor associated delta2-7EGFR mutant also dimerizes with and phosphorylates the wild type EGFR in the absence of ligand. Thus, in addition to its role in ligand recognition, EGFR ECD interacts with each other, imposing an inhibitory effect on the activation of the intracellular kinase.
Antibiotics and prevention of microbial colonization of catheters (1995)

Slime-producing staphylococci frequently colonize catheters, and when they are embedded in biofilm, they become resistant to various antibiotics. In the study that is described, the comparative efficacies of vancomycin, clindamycin, novobiocin, and minocycline, alone or in combination with rifampin, were tested in an in vitro model of colonization. The model consisted of the modified Robbins device with antibiotic-impregnated cement filling the lumen of catheter segments. The synergistic combination of minocycline and rifampin was the most efficacious in preventing bacterial colonization of slime-producing strains of Staphylococcus epidermidis and Staphylococcus aureus to catheter surfaces. A similar trend was observed when the inhibitory activities of polyurethane catheters coated with minocycline and rifampin were compared with the inhibitory activities of catheters coated with other antimicrobial agents. The inhibitory activities of catheters coated with minocycline and rifampin against S. epidermidis, S. aureus, and Enterococcus faecalis strains, for example, were significantly better than those of catheters coated with vancomycin (P < 0.05). The inhibitory activities of catheters coated with minocycline and rifampin against gram-negative bacilli and Candida albicans were comparable to those of catheters coated with ceftazidime and amphotericin B, respectively. We found that the combination of minocycline and rifampin is unique and highly effective in preventing the colonization of catheters with slime-producing staphylococci and that it also displays a broad-spectrum inhibitory activity against gram-negative bacteria and yeast cells.
P2Y12 regulates platelet adhesion/activation, thrombus growth, and thrombus stability in injured arteries (2003)

The critical role for ADP in arterial thrombogenesis was established by the clinical success of P2Y12 antagonists, currently used at doses that block 40-50% of the P2Y12 on platelets. This study was designed to determine the role of P2Y12 in platelet thrombosis and how its complete absence affects the thrombotic process. P2Y12-null mice were generated by a gene-targeting strategy. Using an in vivo mesenteric artery injury model and real-time continuous analysis of the thrombotic process, we observed that the time for appearance of first thrombus was delayed and that only small, unstable thrombi formed in P2Y12-/- mice without reaching occlusive size, in the absence of aspirin. Platelet adhesion to vWF was impaired in P2Y12-/- platelets. While adhesion to fibrinogen and collagen appeared normal, the platelets in thrombi from P2Y12-/- mice on collagen were less dense and less activated than their WT counterparts. P2Y12-/- platelet activation was also reduced in response to ADP or a PAR-4-activating peptide. Thus, P2Y12 is involved in several key steps of thrombosis: platelet adhesion/activation, thrombus growth, and stability. The data suggest that more aggressive strategies of P2Y12 antagonism will be antithrombotic without the requirement of aspirin cotherapy and may provide benefits even to the aspirin-nonresponder population.
DNA sequence of mip, a Legionella pneumophila gene associated with macrophage infectivity (1989)

In a previous study, a 24-kilodalton (kDa) protein surface antigen of Legionella pneumophila was cloned into Escherichia coli and found to be expressed on the host cell surface. Subsequently, a site-directed mutation in this gene (designated mip) in L. pneumophila was found to impair the capacity of this bacterium to initiate intracellular infection in human macrophages. The work presented here indicates that the antigenic gene product is distinct from the 24- to 29-kDa major outer membrane protein of L. pneumophila. In addition, the antigen was identified as a highly basic protein on two-dimensional nonequilibrium polyacrylamide gels and on two-dimensional monoclonal antibody immunoblots. When the DNA fragment encoding this protein was sequenced, a long open reading frame of 699 base pairs was identified within a region to which antigen expression was previously mapped. mip mRNA isolated from both L. pneumophila and transformed E. coli had the same 5' end, as determined by primer extension analysis, indicating that the same promoter sequences are used in both species. A likely factor-independent transcriptional terminator was found 20 residues downstream of the stop codon, suggesting that mip is encoded on a monocistronic message. The inferred polypeptide began with a possible 20- to 24-residue signal sequence, and, as predicted by two-dimensional electrophoresis, had a molecular weight of 24,868 and was a potent polycation with an estimated pI of 9.8.
Inactivation of a T cell receptor-associated GTP-binding protein by antibody-induced modulation of the T cell receptor/CD3 complex. (1988)

TCR modulation induced by anti-TCR or anti-CD3 mAbs leads to a transient state of refractoriness of the T cell to all signals given via cell surface structures. To investigate the underlying mechanisms, we have used human CTL permeabilized with the alpha toxin of S. aureus. This method of permeabilization allows manipulation of the interior milieu of the cell, but maintains its functional and structural integrity. Introduction of the G protein activator GTP gamma S into permeabilized CTL leads to triggering of granule exocytosis. The G protein inactivator GDP beta S inhibited exocytosis induced by TCR triggering but not that induced by activation of protein kinase C. This indicates that the G protein that triggers exocytosis is localized after CD3 triggering but before formation of the polyphosphoinositol breakdown product diacylglycerol. In TCR-modulated CTL, GTP gamma S is no longer able to activate exocytosis. Such CTL, however, still respond to PKC activators. This demonstrates that a TCR-associated G protein has been functionally inactivated by TCR modulation.
A phase I study of bevacizumab in combination with niraparib in patients with platinum-sensitive epithelial ovarian cancer: The ENGOT-OV24/AVANOVA1 trial. (2016)

5555 Background: PARP-inhibitors and anti-angiogenic agents are active substances against ovarian cancer (OC). We investigated the safety, tolerability and Recommended Phase 2 Dose (RP2D) of the combination of niraparib, a PARP-inhibitor, and bevacizumab. NCT02354131 Methods: This single-arm study enrolled patients with platinum-sensitive high-grade serous/endometrioid OC. Any number of previous chemotherapy courses was permitted. In 3+3 design the patients received fixed dose bevacizumab (15mg/kg iv q 21 days) with dose escalation of niraparib (100, 200, 300mg oral, daily). Prior anti-angiogenic therapy was permitted. The primary objectives were to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of the bevacizumab-niraparib combination therapy and to decide the RP2D of this combination. Results: 12 patients (3+3+6) were enrolled to three dose levels. 3 patients had gBRCA2 mutation, while others were gBRCAwt. Common related toxicities at cycle 1 were hypertension (G3 = 5), anaemia (G3 = 3), thrombocytopenia (G3 = 1), fatigue (G2 = 1), constipation (G2 = 1), and nausea (G2 = 1). One DLT (Grade 3 thrombocytopenia that persisted for ≥ 5 days) was observed at the highest dose level (bevacizumab 15 mg/kg iv q 21 days; niraparib 300mg daily). The RP2D is bevacizumab 15 mg/kg iv q 21 days with niraparib 300mg daily. Niraparib dose reductions were needed in 4 pts (cohort 2 = 1; cohort 3 = 3), bevacizumab dose interruptions in 2 pts. First patient entered study on April 20, 2015. Median number of cycles delivered to date is 48. Ten patients are continuing treatment while 2 pts have ended treatment (1PD; 1 withdrawal of consent). Disease control rate is 91%, response rate 45% (1CR, 4PR). Conclusions: Bevacizumab-niraparib combination has hematologic DLT and manageable class toxicities. This combination has preliminary evidence of efficacy. A phase 2 randomized trial is on-going (AVANOVA2). Clinical trial information: NCT02354131.
Protein-solvent preferential interactions, protein hydration, and the modulation of biochemical reactions by solvent components (2002)

Solvent additives (cosolvents, osmolytes) modulate biochemical reactions if, during the course of the reaction, there is a change in preferential interactions of solvent components with the reacting system. Preferential interactions can be expressed in terms of preferential binding of the cosolvent or its preferential exclusion (preferential hydration). The driving force is the perturbation by the protein of the chemical potential of the cosolvent. It is shown that the measured change of the amount of water in contact with protein during the course of the reaction modulated by an osmolyte is a change in preferential hydration that is strictly a measure of the cosolvent chemical potential perturbation by the protein in the ternary water-protein-cosolvent system. It is not equal to the change in water of hydration, because water of hydration is a reflection strictly of protein-water forces in a binary system. There is no direct relation between water of preferential hydration and water of hydration.
Characterization of the Divergent sacBK and sacAR Operons, Involved in Sucrose Utilization by Lactococcus lactis (1999)

The divergently transcribed sacBK and sacAR operons, which are involved in the utilization of sucrose by Lactococcus lactis NZ9800, were examined by transcriptional and gene inactivation studies. Northern analyses of RNA isolated from cells grown at the expense of different carbon sources revealed three sucrose-inducible transcripts: one of 3.2 kb containing sacB and sacK, a second of 3.4 kb containing sacA and sacR, and a third of 1.8 kb containing only sacR. The inactivation of the sacR gene by replacement recombination resulted in the constitutive transcription of the sacBK and sacAR operons in the presence of different carbon sources, indicating that SacR acts as a repressor of transcription.
High-resolution photoacoustic imaging with focused laser and ultrasonic beams (2009)

We report a photoacoustic imager that utilizes a focused laser beam in combination with a 20 MHz ultrasound focusing transducer to obtain micron-resolution tissue images over a long working distance. The imager is based on a ring transducer that combines ultrasonic and laser beams collinearly and confocally in a monolithic element. The combination of focused laser beam and short pulse irradiation led to significant improvement in lateral and axial resolutions compared to the pulse-echo ultrasonic imaging technique or photoacoustic imaging with an unfocused laser. Potential applications include clinical examination of the eye and characterization of thin and superficial tissues.
Regulation and Identity of Florigen: FLOWERING LOCUS T Moves Center Stage (2008)

The transition from vegetative to reproductive growth is controlled by day length in many plant species. Day length is perceived in leaves and induces a systemic signal, called florigen, that moves through the phloem to the shoot apex. At the shoot apical meristem (SAM), florigen causes changes in gene expression that reprogram the SAM to form flowers instead of leaves. Analysis of flowering of Arabidopsis thaliana placed the CONSTANS/FLOWERING LOCUS T (CO/FT) module at the core of a pathway that promotes flowering in response to changes in day length. We describe progress in defining the molecular mechanisms that activate this module in response to changing day length and the increasing evidence that FT protein is a major component of florigen. Finally, we discuss conservation of FT function in other species and how variation in its regulation could generate different flowering behaviors.