tbuckley/cabot-search huggingface dataset:
Are unilateral and bilateral patellar tendinopathy distinguished by differences in anthropometry, body composition, or muscle strength in elite female basketball players?
Authors: J E Gaida, J L Cook, S L Bass, S Austen, Z S Kiss
Journal: British Journal of Sports Medicine (2004)

Background: Overuse injury to the patellar tendon (patellar tendinopathy) is a major reason for interrupted training and competition for elite athletes. In both sexes, the prevalence of unilateral and bilateral tendinopathy has been shown to differ. It has been proposed that bilateral pathology may have a different aetiology from unilateral pathology. Investigation of risk factors that may be unique to unilateral and bilateral patellar tendinopathy in female athletes may reveal insights into the aetiology of this condition. Objectives: To examine whether anthropometry, body composition, or muscle strength distinguished elite female basketball players with unilateral or bilateral patellar tendinopathy. Methods: Body composition, anthropometry, and muscle strength were compared in elite female basketball players with unilateral (n = 8), bilateral (n = 7), or no (n = 24) patellar tendinopathy. Body composition was analysed using a dual energy x ray absorptiometer. Anthropometric measures were assessed using standard techniques. Knee extensor strength was measured at 180°/s using an isokinetic dynamometer. z scores were calculated for the unilateral and bilateral groups (using the no tendinopathy group as controls). z scores were tested against zero. Results: The tibia length to stature ratio was approximately 1.3 (1.3) SDs above zero in both the affected and non-affected legs in the unilateral group (p&lt;0.05). The waist to hip ratio was 0.66 (0.78) SD above zero in the unilateral group (p&lt;0.05). In the unilateral group, leg lean to total lean ratio was 0.42 (0.55) SD above zero (p&lt;0.07), the trunk lean to total lean ratio was 0.63 (0.68) SD below zero (p&lt;0.05), and leg fat relative to total fat was 0.47 (0.65) SD below zero (p&lt;0.09). In the unilateral group, the leg with pathology was 0.78 (1.03) SD weaker during eccentric contractions (p&lt;0.07). Conclusions: Unilateral patellar tendinopathy has identifiable risk factors whereas bilateral patellar tendinopathy may not. This suggests that the aetiology of these conditions may be different. However, interpretation must respect the limitation of small subject numbers.
Intraoperative molecular sentinel lymph node analysis with OSNA: multicentre prospective UK evaluation.
Authors: MW Kissin, KL Snook, GT Layer, P Jackson, CS de Vries, S Shousha, HD Sinnett, H Singhal, E Nigar, G Cunnick, Y Chia
Journal: Cancer Research (2009)

Abstract Abstract #1003 Introduction: Rapid intraoperative molecular analysis of sentinel lymph nodes (SLNs) in breast cancer (BC) patients has the advantage of providing the surgeon with an immediate automated result, without the opinion of a consultant histopathologist, allowing axillary dissection to proceed in SLN positive patients. We undertook a multicentre, prospective evaluation of the OSNA system (One Step Nucleic Acid Amplification) for molecular analysis, to evaluate this new diagnostic technique's accuracy and feasibility for use in our hospital system. This abstract reports our 'Phase 2 - Intraoperative' experience.&amp;#x2028; Method: Four study centres, both district general and major teaching hospitals took part in the evaluation. SLNs from breast cancer patients were excised using standard surgical techniques. Fresh SLNs were defatted and cut into 4 x 1 or 2mm slices depending on size and weight. Alternate slices underwent lysate preparation and immediate OSNA molecular analysis (detection and amplification of CK19 mRNA); remaining slices were processed for permanent section - intensive haematoxylin &amp; eosin and immunohistochemistry (CK19 and AE1/AE3) examination (25μm multistep sections, 5 levels). OSNA results were correlated with final histopathology findings. Processing times were also recorded. No clinical decision was made based on the intraoperative OSNA result.&amp;#x2028; Results: 396 lymph node samples were included in the analysis. Concordance with histopathology was 96.2% overall with all sites reaching concordance &amp;gt;95%. Overall sensitivity was 91.5%, specificity 97.2%, positive predictive value 87.7%, negative predictive value 98.1%. Concordance of OSNA with histopathology for lobular carcinoma (34 SLN samples) was &amp;gt;95%. There were 14 cases of tissue allocation bias confirmed on repeated molecular and histology testing that were excluded from overall results. Minimum time to reach a result on a single node was 22 minutes.&amp;#x2028; Conclusion: The OSNA molecular system for SLN diagnosis provides an accurate and feasible intraoperative assessment of SLN status, achieving consistent results across multiple centres. This system may replace current histopathology-based techniques for intraoperative SLN analysis due to high concordance with histology and that it does not require input from a consultant pathologist. OSNA could allow more breast cancer patients in the UK access to one step axillary surgery. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1003.
Biorobotic simulations might offer some advantages over purely computational ones
Authors: Donald R Franceschetti
Journal: Behavioral and Brain Sciences (2001)

A slight modification of Webb's diagrammatic representation of the dimensions for describing models is proposed which extends it to cover a range of theoretical models as well as material models. It is also argued that beyond a certain level robotic simulations could offer a number of real advantages over computer simulations of organisms interacting with their environment.
Toll-like Receptor 9 Agonist IMO Cooperates with Cetuximab in <i>K</i>-<i>Ras</i> Mutant Colorectal and Pancreatic Cancers
Authors: Roberta Rosa, Davide Melisi, Vincenzo Damiano, Roberto Bianco, Sonia Garofalo, Teresa Gelardi, Sudhir Agrawal, Federica Di Nicolantonio, Aldo Scarpa, Alberto Bardelli, Giampaolo Tortora
Journal: Clinical Cancer Research (2011)

K-Ras somatic mutations are a strong predictive biomarker for resistance to epidermal growth factor receptor (EGFR) inhibitors in patients with colorectal and pancreatic cancer. We previously showed that the novel Toll-like receptor 9 (TLR9) agonist immunomodulatory oligonucleotide (IMO) has a strong in vivo activity in colorectal cancer models by interfering with EGFR-related signaling and synergizing with the anti-EGFR monoclonal antibody cetuximab.In the present study, we investigated, both in vitro and in vivo, the antitumor effect of IMO alone or in combination with cetuximab in subcutaneous colon and orthotopic pancreatic cancer models harboring K-Ras mutations and resistance to EGFR inhibitors.We showed that IMO was able to significantly restore the sensitivity of K-Ras mutant cancer cells to cetuximab, producing a marked inhibition of cell survival and a complete suppression of mitogen-activated protein kinase phosphorylation, when used in combination with cetuximab. IMO interfered with EGFR-dependent signaling, modulating the functional interaction between TLR9 and EGFR. In vivo, IMO plus cetuximab combination caused a potent and long-lasting cooperative antitumor activity in LS174T colorectal cancer and in orthotopic AsPC1 pancreatic cancer. The capability of IMO to restore cetuximab sensitivity was further confirmed by using K-Ras mutant colorectal cancer cell models obtained through homologous recombination technology.We showed that IMO markedly inhibits growth of K-Ras mutant colon and pancreatic cancers in vitro and in nude mice and cooperates with cetuximab via multiple mechanisms of action. Therefore, we propose IMO plus cetuximab as a therapeutic strategy for K-Ras wild-type as well for K-Ras mutant, cetuximab-resistant colorectal and pancreatic cancers.
Efficacy and safety of the peripheral kappa agonist fedotozine versus placebo in the treatment of functional dyspepsia
Authors: N W Read, J L Abitbol, K D Bardhan, P J Whorwell, B Fraitag
Journal: Gut (1997)

Background —Peripheral kappa receptor agonists may provide a new therapeutic approach for the treatment of functional dyspepsia. Aims —To evaluate, in a large multicentre trial, the use of the kappa receptor agonist fedotozine to improve symptoms associated with functional dyspepsia. Methods —Two or more of the following persistent symptoms were required for inclusion: epigastric pain, early satiety, epigastric fullness or distension, nausea, vomiting, and a feeling of slow digestion. On completing a two week placebo washout, 271 patients were randomised into two groups to receive 30 mg fedotozine three times daily or placebo for six weeks under double blind conditions. Results —The improvement in the overall intensity of dyspeptic symptoms (main efficacy criterion) was significantly more pronounced in the fedotozine group (p=0.002) compared with placebo, as was epigastric pain (p=0.004) and nausea (p=0.01); the improvement in postprandial fullness was nearly significant (p=0.052). Inability to finish a meal and slow digestion were unaffected. The patient global score, the average of the five individual symptoms, was notably ameliorated with fedotozine (p=0.021). The safety of fedotozine was excellent. Conclusions —Fedotozine at 30 mg three times daily is safe and more effective than placebo for the relief of key symptoms associated with functional dyspepsia.
Peptic ulcer bleeding: accessory risk factors and interactions with non-steroidal anti-inflammatory drugs
Authors: J Weil
Journal: Gut (2000)

<h3>AIMS</h3> To determine risk factors for peptic ulcer bleeding other than non-steroidal anti-inflammatory drugs (NSAIDs)<i>.</i> Methods—Data on possible antecedent risk factors obtained in a large case control study of 1121 patients admitted to hospitals in Glasgow, Newcastle, Nottingham, Oxford, and Portsmouth with bleeding peptic ulcers were compared with the same information obtained in 989 population controls. Data were analysed by logistic regression with the calculation of odds ratios (OR) and 95% confidence intervals (CI). <h3>RESULTS</h3> From a logistic regression model, oral anticoagulants (OR 7.8; 95% CI 2.8–21.5), previous peptic ulcer (3.8; 2.6–4.9), treatment for heart failure (5.9; 2.3–13.1), oral corticosteroid use (2.7; 1.3–4.5), treatment for diabetes (3.1; 1.2–4.3), and current smoking (1.6; 1.2–2.0) were all independent risk factors. No association was found with use of calcium channel antagonists. Odds ratios for concomitant NSAID usage were multiplicative with the exception of current smoking. <h3>CONCLUSIONS</h3> Some 45% of admissions for peptic ulcer bleeding in England and Wales in those aged 60 or more are calculated to be attributable to, or associated with, these accessory risk factors, which, together with those associated with aspirin or other NSAID use will account for over 80% of predisposing factors to ulcer bleeding.
Cyclophilin A Is a Secreted Growth Factor Induced by Oxidative Stress
Authors: Zheng-Gen Jin, Matthew G. Melaragno, Duan-Fang Liao, Chen Yan, Judith Haendeler, Young-Ah Suh, J. David Lambeth, Bradford C. Berk
Journal: Circulation Research (2000)

Abstract —Reactive oxygen species have been implicated in the pathogenesis of atherosclerosis, hypertension, and restenosis, in part by promoting vascular smooth muscle cell (VSMC) growth. Many VSMC growth factors are secreted by VSMC and act in an autocrine manner. Here we demonstrate that cyclophilin A (CyPA), a member of the immunophilin family, is secreted by VSMCs in response to oxidative stress and mediates extracellular signal–regulated kinase (ERK1/2) activation and VSMC growth by reactive oxygen species. Human recombinant CyPA can mimic the effects of secreted CyPA to stimulate ERK1/2 and cell growth. The peptidyl-prolyl isomerase activity is required for ERK1/2 activation by CyPA. In vivo, CyPA expression and secretion are increased by oxidative stress and vascular injury. These findings are the first to identify CyPA as a secreted redox-sensitive mediator, establish CyPA as a VSMC growth factor, and suggest an important role for CyPA and enzymes with peptidyl-prolyl isomerase activity in the pathogenesis of vascular diseases.
Chemokine Requirements for B Cell Entry to Lymph Nodes and Peyer's Patches
Authors: Takaharu Okada, Vu N. Ngo, Eric H. Ekland, Reinhold Förster, Martin Lipp, Dan R. Littman, Jason G. Cyster
Journal: The Journal of Experimental Medicine (2002)

B cell entry to lymph nodes and Peyer's patches depends on chemokine receptor signaling, but the principal chemokine involved has not been defined. Here we show that the homing of CXCR4−/− B cells is suppressed in CCL19 (ELC)- and CCL21 (SLC)-deficient paucity of lymph node T cells mice, but not in wild-type mice. We also find that CXCR4 can contribute to T cell homing. Using intravital microscopy, we find that B cell adhesion to high endothelial venules (HEVs) is disrupted when CCR7 and CXCR4 are predesensitized. In Peyer's patches, B cell entry is dependent on CXCR5 in addition to CCR7/CXCR4. CXCL12 (SDF1) is displayed broadly on HEVs, whereas CXCL13 (BLC) is found selectively on Peyer's patch follicular HEVs. These findings establish the principal chemokine and chemokine receptor requirements for B cell entry to lymph nodes and Peyer's patches.
Factor Xa Releases Matrix Metalloproteinase-2 (MMP-2) From Human Vascular Smooth Muscle Cells and Stimulates the Conversion of Pro–MMP-2 to MMP-2
Authors: Bernhard H. Rauch, Ellen Bretschneider, Marina Braun, Karsten Schrör
Journal: Circulation Research (2002)

Pro–matrix metalloproteinase-2 (pro–MMP-2) is expressed in vascular smooth muscle cells (SMCs). We report that activated coagulation factor X (FXa) induces the release of MMP-2 (65 kDa) from human SMCs. In addition, FXa cleaves pro–MMP-2 (72 kDa) into MMP-2. Pro–MMP-2 and MMP-2 were determined by gelatin zymography. MMP-2 was generated in conditioned medium containing pro–MMP-2 in a concentration-dependent fashion by FXa (3 to 100 nmol/L). FX at concentrations up to 300 nmol/L was ineffective. The conversion of pro–MMP-2 to MMP-2 was inhibited by a selective FXa inhibitor (DX-9065a) at 3 to 10 μmol/L. There was a concentration-dependent induction of an intermediate MMP-2 form (68 kDa) in lysates of FXa-treated cells. This indicates that cellular mechanisms are involved in FXa-induced conversion of pro–MMP-2. As a possible biological consequence of MMP-2 activation by FXa, DNA synthesis and matrix invasion of SMCs were determined. Both were stimulated by FXa and inhibited by the selective FXa inhibitor DX-9065a and the MMP inhibitor GM 6001 but not by hirudin or aprotinin. It is concluded that stimulation of SMCs by FXa increases the levels of MMP-2 in the extracellular space and that two different mechanisms are involved: release of active MMP-2 and cleavage of secreted pro–MMP-2. Both might contribute to the mitogenic potency of FXa and FXa-stimulated matrix invasion of SMCs.
Potentiation of TRAIL-induced apoptosis in primary effusion lymphoma through azidothymidine-mediated inhibition of NF-κB
Authors: Subrata K. Ghosh, Charles Wood, Lawrence H. Boise, Abdul M. Mian, Vadim V. Deyev, Gerold Feuer, Ngoc L. Toomey, Nicole C. Shank, Lisa Cabral, Glen N. Barber, William J. Harrington
Journal: Blood (2003)
Assessing potential health risks from microcystin toxins in blue-green algae dietary supplements.
Authors: D J Gilroy, K W Kauffman, R A Hall, X Huang, F S Chu
Journal: Environmental Health Perspectives (2000)

The presence of blue-green algae (BGA) toxins in surface waters used for drinking water sources and recreation is receiving increasing attention around the world as a public health concern. However, potential risks from exposure to these toxins in contaminated health food products that contain BGA have been largely ignored. BGA products are commonly consumed in the United States, Canada, and Europe for their putative beneficial effects, including increased energy and elevated mood. Many of these products contain Aphanizomenon flos-aquae, a BGA that is harvested from Upper Klamath Lake (UKL) in southern Oregon, where the growth of a toxic BGA, Microcystis aeruginosa, is a regular occurrence. M. aeruginosa produces compounds called microcystins, which are potent hepatotoxins and probable tumor promoters. Because M. aeruginosa coexists with A. flos-aquae, it can be collected inadvertently during the harvesting process, resulting in microcystin contamination of BGA products. In fall 1996, the Oregon Health Division learned that UKL was experiencing an extensive M. aeruginosa bloom, and an advisory was issued recommending against water contact. The advisory prompted calls from consumers of BGA products, who expressed concern about possible contamination of these products with microcystins. In response, the Oregon Health Division and the Oregon Department of Agriculture established a regulatory limit of 1 microg/g for microcystins in BGA-containing products and tested BGA products for the presence of microcystins. Microcystins were detected in 85 of 87 samples tested, with 63 samples (72%) containing concentrations > 1 microg/g. HPLC and ELISA tentatively identified microcystin-LR, the most toxic microcystin variant, as the predominant congener.
A Recessive Gene for Primary Vesicoureteral Reflux Maps to Chromosome 12p11-q13
Authors: Patricia L. Weng, Simone Sanna-Cherchi, Terry Hensle, Ellen Shapiro, Alan Werzberger, Gianluca Caridi, Claudia Izzi, Anita Konka, Adam C. Reese, Rong Cheng, Samuel Werzberger, Richard N. Schlussel, Robert D. Burk, Joseph H. Lee, Roberto Ravazzolo, Francesco Scolari, Gian Marco Ghiggeri, Kenneth Glassberg, Ali G. Gharavi
Journal: Journal of the American Society of Nephrology (2009)

Primary vesicoureteral reflux (pVUR) is one of the most common causes of pediatric kidney failure. Linkage scans suggest that pVUR is genetically heterogeneous with two loci on chromosomes 1p13 and 2q37 under autosomal dominant inheritance. Absence of pVUR in parents of affected individuals raises the possibility of a recessive contribution to pVUR. We performed a genome-wide linkage scan in 12 large families segregating pVUR, comprising 72 affected individuals. To avoid potential misspecification of the trait locus, we performed a parametric linkage analysis using both dominant and recessive models. Analysis under the dominant model yielded no signals across the entire genome. In contrast, we identified a unique linkage peak under the recessive model on chromosome 12p11-q13 (D12S1048), which we confirmed by fine mapping. This interval achieved a peak heterogeneity LOD score of 3.6 with 60% of families linked. This heterogeneity LOD score improved to 4.5 with exclusion of two high-density pedigrees that failed to link across the entire genome. The linkage signal on chromosome 12p11-q13 originated from pedigrees of varying ethnicity, suggesting that recessive inheritance of a high frequency risk allele occurs in pVUR kindreds from many different populations. In conclusion, this study identifies a major new locus for pVUR and suggests that in addition to genetic heterogeneity, recessive contributions should be considered in all pVUR genome scans.
Nonsteroidal anti-inflammatory drugs upregulate function of wild-type and mutant CFTR
Authors: J. Li, Y-Y. Xiang, L. Ye, L-C. Tsui, J. F. MacDonald, J. Hu, W-Y. Lu
Journal: European Respiratory Journal (2008)

Small-scale clinical trials show that treatment of cystic fibrosis (CF) patients with ibuprofen, a nonsteroidal anti-inflammatory drug, improves the symptoms of CF and slows down the decline of lung function. Paradoxically, ibuprofen inhibits ligand-stimulated CF transmembrance conductance regulator (CFTR) activity. The aim of the present study was to investigate the effects of ibuprofen on CFTR function under different conditions. Patch-clamp recordings were performed in two lines of human airway epithelial cells: IB3-8-3-7 cells, which express wild-type CFTR; and IB3-1 cells, which express the variant CFTR with deletion of phenylalanine 580 (ΔF580CFTR). Addition of ibuprofen to the extracellular solution caused a rapid inhibition of CFTR activity in IB3-8-3-7 cells in the presence of a high intracellular concentration of cAMP, whereas ibuprofen enhanced the CFTR conductance at low levels of cAMP. Introducing ibuprofen into the interior of cells occluded the enhancing effect of ibuprofen. Notably, the variant CFTR-mediated conductance was detected in IB3-1 cells treated with myoinositol and was enhanced by ibuprofen at endogenous levels of cAMP. In summary, nonsteroidal anti-inflammatory drugs increase the function of both wild-type cystic fibrosis transmembrane conductance regulator and the phenylalanine 580 deletion in cultured human airway epithelial cells at endogenous levels of cAMP.
CASES ILLUSTRATIVE OF THE TREATMENT OF SOME VARIETIES OF CHRONIC RHEUMATISM
Authors: C. H. Jones
Journal: BMJ (1853)

THE following cases of diseased action depending upon rheumatism seem of sufficient interest to be worth record- ing, if only as memoranda of well marked instances of dis- ease, and of the action of remedies.The brief way in which they are reported was unavoidable, as they all occurred in hospital out-patients, and time was of course wanting to make detaile inquiries.CAsE I. Jane F., aged 6, residing at Kensal Green, was admitted on Feb. 9th.She had a kind of fit, her mother stated, six weeks previously; but she did not lose her con- sciousness.At present, she was stupefied several times in the course of the day.She had pain in different parts of the head, which was not increased at night.The tongue was clean; the urine clear.She was living on the bank of a canal, in a damp place.The following medicine was ordered:PA Potassii iodidi 3 ss.Liquoris potasste 3 iss.Infusi calumbab 3ij.Al.Sumat 3ss.ter die.Feb. 16th.She was decidedly better this week than last; but made a groaning dismal noise in her sleep, much more some nights than others.The medicines were continued.Feb. 23rd.She was not free from fits, but had them cer- tainly less often.Her mother said that when she was affected, she could compare her " to nothing so much as to a tipsy man in his foolish talk".The bowels were properly open; the pulse weak.The head was tender; she could not bear to have it touched.A blister was ordered to be applied to the neck.Rg Ferri carbonatis gr.x. ter die.March 1st.She had had no fit since the blister; but had one sharp attack on the night on which it was applied.March 8th.She had no more fits, but rambled and talked during the night.The bowels were confined.