tbuckley/cabot-search huggingface dataset:
Sex differences in force attenuation: a clinical assessment of single-leg hop performance on a portable force plate
Authors: A D Harrison, K R Ford, G D Myer, T E Hewett
Journal: British Journal of Sports Medicine (2009)

Objective Impaired biomechanics and neuromuscular control have been suggested as probable links to female sex bias in the onset of patellofemoral pain syndrome. There are limited objective, clinical measures for assessment of impaired biomechanics and neuromuscular control. The primary objective of this investigation was to examine sex differences in vertical ground reaction force (vGRF) and force loading rate in young athletes performing maximum, repeated vertical single-leg hops (RVSHs). The authors hypothesised that females would demonstrate greater vGRF and force loading rate than males and show interlimb differences in force attenuation. Design Cross-sectional study. Setting Paediatric sports medicine clinic. Participants 109 Healthy high school, soccer and basketball athletes. Assessment of risk factors Participants performed RVSHs for 15 seconds on a portable force plate with a sampling rate of 400 Hz (Accupower; AMTI, Watertown, Massachusetts, USA). Main outcome measurements Raw vGRF was filtered with a generalised cross-validation spline using a 50-Hz cutoff frequency and then normalised to potential energy. Force loading rate was calculated by dividing normalised vGRF by time-to-peak force. Group means were compared using analysis of variance. Results The females demonstrated significantly greater normalised vGRF (p&lt;0.001) and force loading rate (p&lt;0.001) during landing than their male counterparts. Neither sex demonstrated significant interlimb differences in force attenuation (p&gt;0.05). Conclusions The female athletes may have altered force attenuation capability during RVSHs as identified by increased vGRF and force loading rate compared with the male athletes. Portable force plates may be potential tools to identify altered force attenuation in clinical settings.
Reactive Oxygen Species Promote Caspase-12 Expression and Tubular Apoptosis in Diabetic Nephropathy
Authors: Marie-Luise Brezniceanu, Cara J. Lau, Nicolas Godin, Isabelle Chénier, Alain Duclos, Jean Éthier, Janos G. Filep, Julie R. Ingelfinger, Shao-Ling Zhang, John S.D. Chan
Journal: Journal of the American Society of Nephrology (2010)

Apoptosis of tubular epithelial cells contributes to the tubular atrophy that accompanies diabetic nephropathy. Reactive oxygen species (ROS) promote tubular apoptosis, but the mechanisms by which this occurs are incompletely understood. Here, we sought proapoptotic genes that ROS differentially upregulate in renal proximal tubular cells of diabetic (db/db) mice. We performed microarray analysis using total RNA from freshly isolated renal proximal tubules of nondiabetic, diabetic, and diabetic transgenic mice overexpressing catalase in the proximal tubule (thereby attenuating ROS). We observed greater expression of caspase-12 in the proximal tubules of the diabetic mice compared with the nondiabetic and diabetic transgenic mice. Quantitative PCR and immunohistochemistry confirmed the enhanced expression of caspase-12, as well as members of the endoplasmic reticulum stress-induced apoptotic pathway. Ex vivo, albumin induced caspase-12 activity and expression (protein and mRNA) and mRNA expression of the CCAT/enhancer-binding protein homologous protein in freshly isolated wild-type proximal tubules but not in catalase-overexpressing proximal tubules. In vitro, albumin stimulated activity of both caspase-12 and caspase-3 as well as expression of caspase-12 and CCAT/enhancer-binding protein homologous protein in a human proximal tubule cell line (HK-2). The free radical scavenger tiron inhibited these effects. Furthermore, knockdown of caspase-12 with small interfering RNA reduced albumin-induced apoptosis in HK-2 cells. Taken together, these studies demonstrate that albuminuria may induce tubular apoptosis through generation of ROS and the subsequent expression and activation of endoplasmic reticulum stress genes in the diabetic kidney.
The pro-angiogenic factor CCN1 enhances the re-endothelialization of biological vascularized matrices in vitro
Authors: A. Bar, S. E. Dorfman, P. Fischer, D. Hilfiker-Kleiner, S. Cebotari, I. Tudorache, M. Suprunov, A. Haverich, A. Hilfiker
Journal: Cardiovascular Research (2009)

A problem in generating artificial tissues is supplying nutrients to cells within 3D constructs. The use of a decellularized biological vascularized matrix with preserved pedicles (BioVaM), as a scaffold, appears to aid the generation of perfusable tissue constructs in vitro. To prevent vessel occlusion upon implantation, a functional endothelium must line the graft vessel bed. Here we tested whether the pro-angiogenic factor CCN1 could improve the re-endothelialization of BioVaM in vitro. BioVaM vessel beds were incubated with 100 ng/mL recombinant human CCN1. Human cord blood endothelial cells (hCBEC) were analysed with respect to adhesion behaviour upon CCN1 exposure and seeded onto vessel structures of CCN1 exposed BioVaM (cBioVaM). BioVaMs were fixed in a bioreactor and perfusion cultured for 4 and 14 days (d). BioVaM without CCN1 treatment served as controls. Initial seeding success and endothelialization progression were monitored by fluorescence‐labelled hCBEC. During construct cultivation, pH and lactate production were measured. Degree of endothelialization and characterization of seeded cells, with respect to endothelial markers, were investigated histologically. BioVaM vessel structures showed a 78 ± 17% increase of attached cells when pre-treated with CCN1. Evaluation of re-endothelialization (arbitrary units) was 4.0 ± 0.8 and 2.6 ± 0.8 after 4 d, and 5.0 ± 0.0 and 3.0 ± 0.5 after 14 d in cBioVaM vs. BioVaM, respectively. On day 14, lactate concentration, an indicator of metabolic activity, was increased 12-fold in cBioVaM relative to BioVaM. A preserved endothelial phenotype of seeded cells was verified in all cultures by acetylated low density lipoprotein uptake and positive immunohistochemistry against von Willebrand factor, endothelial nitric oxide synthase, and CD31. Coating of decellularized vessel structures with CCN1 supports adhesion of hCBEC and enhances re-endothelialization of BioVaM. Perfusable, endothelialized constructs may aid in solving the problem of nourishing cells inside 3D tissue‐engineered constructs.
Electrophysiology and ultrastructure of canine subendocardial Purkinje cells isolated from control and 24-hour infarcted hearts.
Authors: P A Boyden, A Albala, K P Dresdner
Journal: Circulation Research (1989)

Ventricular arrhythmias that accompany myocardial infarction in dogs may be secondary to the altered electrophysiological properties of the subendocardial Purkinje fibers that survive 24 hours after the coronary occlusion. To better understand the ionic mechanisms that underlie the altered electrical activity of these fibers, we have dispersed, using an enzymatic technique, Purkinje cells from the subendocardium of the infarcted ventricle (IZPCs) and compared their electrical and structural properties to Purkinje cells dispersed from fiber strands (SPCs) and from the subendocardium of the noninfarcted ventricle (NZPCs). Ultrastructural analysis of these cells shows that IZPCs contain an increased number of lipid droplets when compared with the SPCs and NZPCs. In addition, transmembrane action potentials of IZPCs have reduced resting potentials, action potential amplitudes, and upstroke velocity and are increased in duration when compared with either SPCs or NZPCs. Input resistance of IZPCs is increased over that measured in control cells (SPCs and NZPCs). Furthermore, the time course of the process of electrical restitution of action potential duration is altered in IZPCs with long action potentials. Finally, using K+-sensitive microelectrode techniques, we have determined that intracellular free K+ activity (aKi) in IZPCs (93.7 +/- 15 mM) is not significantly different from control aKi measurements (SPC, 106 +/- 13 mM; NZPC, 103 +/- 12 mM). Thus a reduction in aKi does not provide a basis for the reduced resting potentials observed in IZPCs. By studying the relation between the resting potential and log [K+]o we determined that in IZPCs with reduced resting potentials, there is a significant increase in the PNa/PK ratio when compared with control. In summary, to better understand the cellular basis of ventricular arrhythmias postinfarction, we have developed a single cell model that will allow for more rigorous electrophysiological studies of the specific ionic currents that underlie the abnormal electrophysiology.
Multiple Sclerosis and Epstein-Barr Virus
Authors: Lynn I. Levin, Kassandra L. Munger, Mark V. Rubertone, Charles A. Peck, Evelyne T. Lennette, Donna Spiegelman, Alberto Ascherio
Journal: JAMA (2003)

Infection with Epstein-Barr virus (EBV) has been associated with an increased risk of multiple sclerosis (MS), but the temporal relationship remains unclear.
PWE-192 Does Fibre Reduce the Risk of Clostridium Difficile Diarrhoea in Nasogastric Fed Patients?
Authors: S Antoniou, L Goddard, C Pettitt, T Orchard, J Tyrrell-Price
Journal: Gut (2013)

<h3>Introduction</h3> Tube-feeding has previously been associated with an increased risk of <i>Clostridium difficile</i> (<i>C</i>. <i>difficile</i>) diarrhoea.<sup>1</sup> The absence of dietary fibre has been suggested as a possible cause, but not yet formally assessed in patients fed via a nasogastric (NG) tube. The objective was to determine if there is a difference in acquisition of <i>C. difficile</i> between fibre and fibre-free NG feeds. <h3>Hypothesis</h3> Fibre-free NG feeds are associated with a higher rate of <i>C. difficile</i> infection than fibre containing feeds. <h3>Methods</h3> This was a Retrospective Cohort Study, using data from NG-fed patients in one trust from May to November 2010. <h3>Results</h3> It was found that 8 of 169 patients in the fibre-fed group had <i>C</i>. <i>difficile</i>, compared with 15 of 202 in the non-fibre fed group, equating to 4.7% and 7.4% detection of <i>C</i>. <i>difficile</i> respectively, p value 0.39. Antibiotic usage was similar in both groups. Patients who received fibre free feeds were more likely to develop diarrhoea than those receiving fibre containing feeds (p = 0.0112). <h3>Conclusion</h3> The results show a trend towards fibre reducing the risk of <i>C</i>. <i>difficile</i> diarrhoea. However the effect appears to be subtle, as it failed to reach statistical significance despite the inclusion of over 160 patients in both groups. The previous finding of a link between fibre free NG feeding and <i>C. difficile</i> acquisition may have been due to increased rates of diarrhoea. Fibre reduced the risk of diarrhoea, which may reduce the apparent risk of <i>C</i>. <i>difficile</i> when compared with the fibre free group, as in the latter there is a potential for <i>C. difficile</i> spore shedding from asymptomatic carriers. <h3>Disclosure of Interest</h3> None Declared. <h3>Reference</h3> Bliss D.Z.,<i> et al.</i> (1998). Acquisition of<i> Clostridium difficil</i>e and<i> Clostridium difficil</i>e- Associated Diarrhoea in Hospitalized Patients Receiving Tube Feeding. Ann Intern Med; 129: 1012–1019
Prevalence and outcome in systemic sclerosis associated pulmonary arterial hypertension: application of a registry approach
Authors: D Mukerjee, D St George, B Coleiro, C Knight, C P Denton, J Davar, C M Black, J G Coghlan
Journal: Annals of the Rheumatic Diseases (2003)

<b>Objective:</b> To determine the prevalence of systemic sclerosis associated pulmonary arterial hypertension (SScPAH), evaluate outcome, and identify predictors of mortality in a large patient cohort. <b>Methods:</b> A prospective four year follow up study of 794 patients (722 from our own unit and 72 referrals). All patients screened for PAH using a combination of echocardiography, lung function testing, and clinical assessment. Patients with suspected raised pulmonary artery systolic pressures of &gt;35 mm Hg, carbon monoxide transfer factor (Tlco) &lt;50% predicted, or a precipitous fall in Tlco &gt;20% over a one year period with no pulmonary fibrosis, and patients with SSc with breathlessness with no pulmonary fibrosis found were investigated with right heart catheterisation. All patients with SScPAH were treated in accordance with current best practice. <b>Results:</b> The prevalence of PAH was 12% (89/722) by right heart catheter. The survival was 81%, 63%, and 56% at 1, 2, and 3 years from the diagnosis (in 89 patients from our own cohort and 59/72 referrals). Haemodynamic indices of right ventricular failure—raised mRAP (hazard ratio 21), raised mPAP (hazard ratio 20), and low CI (hazard ratio 11) predicted an adverse outcome There was no significant difference in survival between patients with SScPAH with (n=40) and without (n=108) pulmonary fibrosis (p=0.3). <b>Conclusions:</b> The prevalence of SScPAH in this cohort was similar to that of other catheter based studies and lower than that of previous echo based studies. The 148 patients with SScPAH actively treated had comparable outcomes to those of the cohorts with primary pulmonary hypertension. A high mRAP was the strongest haemodynamic predictor of mortality. To improve prognosis, future treatments need to be implemented at an earlier disease stage to prevent right ventricular decompensation.
HMOX1 and GST variants modify attenuation of FEF25-75% decline due to PM10 reduction
Authors: I. Curjuric, M. Imboden, C. Schindler, S. H. Downs, M. Hersberger, S. L. J. Liu, G. Matyas, E. W. Russi, J. Schwartz, G. A. Thun, D. S. Postma, T. Rochat, N. M. Probst-Hensch
Journal: European Respiratory Journal (2010)

Reduced exposure to particulate matter with a 50% cut-off aerodynamic diameter of 10 μm (PM<sub>10</sub>) attenuated age-related lung function decline in our cohort, particularly in the small airways. We hypothesised that polymorphisms in glutathione <i>S</i>-transferase (<i>GST</i>) and haem oxygenase-1 (<i>HMOX1</i>) genes, important for oxidative stress defence, modify these beneficial effects. A population-based sample of 4,365 adults was followed up after 11 yrs, including questionnaire, spirometry and DNA blood sampling. PM<sub>10</sub> exposure was estimated by dispersion modelling and temporal interpolation. The main effects on annual decline in forced expiratory flow at 25–75% of forced vital capacity (FEF<sub>25–75%</sub>) and interactions with PM<sub>10</sub> reduction were investigated for polymorphisms <i>HMOX1</i> rs2071746 (T/A), rs735266 (T/A) and rs5995098 (G/C), <i>HMOX1</i> (GT)<sub>n</sub> promoter repeat, <i>GSTM1</i> and <i>GSTT1</i> deletions, and <i>GSTP1</i> p.Ile105Val, using mixed linear regression models. <i>HMOX1</i> rs5995098, <i>HMOX1</i> haplotype TTG and <i>GSTP1</i> showed significant genetic main effects. Interactions with PM<sub>10</sub> reduction were detected: a 10 μg·m<sup>−3</sup> reduction significantly attenuated annual FEF<sub>25–75%</sub> decline by 15.3 mL·s<sup>−1</sup> only in the absence of <i>HMOX1</i> haplotype ATC. Similarly, carriers of long (GT)<sub>n</sub> promoter repeat alleles or the <i>GSTP1</i> Val/Val genotype profited significantly more from a 10 μg·m<sup>−3</sup> reduction (26.5 mL·s<sup>−1</sup> and 27.3 mL·s<sup>−1</sup> respectively) than non-carriers. Benefits of a reduction in PM<sub>10</sub> exposure are not equally distributed across the population but are modified by the individual genetic make-up determining oxidative stress defence.
Ethical Issues in Psychiatric Follow-Up Studies
Authors: SCOTT H. NELSON, HENRY GRUNEBAUM
Journal: American Journal of Psychiatry (1972)

Conducting a follow-up study of 23 wrist slashers presented an ethical conflict between consideration of the patients' human and medical rights and the investigators' desire for knowledge to improve treatment. The authors feel that many difficulties now encountered in behavioral research can be avoided by improved confidentiality of hospital records, acquisition of patients' consent regarding possible follow-up contact, and well-planned studies in which ethical problems are more fully anticipated beforehand.
Severe polyposis in Apc<sup>1322T</sup>mice is associated with submaximal Wnt signalling and increased expression of the stem cell marker<i>Lgr5</i>
Authors: Annabelle Lewis, Stefania Segditsas, Maesha Deheragoda, Patrick Pollard, Rosemary Jeffery, Emma Nye, Helen Lockstone, Hayley Davis, Susan Clark, Gordon Stamp, Richard Poulsom, Nicholas Wright, Ian Tomlinson
Journal: Gut (2010)

<h3>Background and aims</h3> Adenomatous polyposis coli (<i>APC</i>) is a tumour suppressor gene mutated in the germline of patients with familial adenomatous polyposis (FAP) and somatically in most colorectal cancers. <i>APC</i> mutations impair β-catenin degradation, resulting in increased Wnt signalling. The most frequent <i>APC</i> mutation is a codon 1309 truncation that is associated with severe FAP. A previous study compared two mouse models of intestinal tumorigenesis, Apc<sup>R850X</sup> (Min) and Apc<sup>1322T</sup> (1322T), the latter a model of human codon 1309 changes. 1322T mice had more severe polyposis but, surprisingly, these tumours had lower levels of nuclear β-catenin than Min tumours. The consequences of these different β-catenin levels were investigated. <h3>Methods</h3> Enterocytes were isolated from 1322T and Min tumours by microdissection and gene expression profiling was performed. Differentially expressed Wnt targets and other stem cell markers were validated using quantitative PCR, in situ hybridisation and immunohistochemistry. <h3>Results</h3> As expected, lower nuclear β-catenin levels in 1322T lesions were associated with generally lower levels of Wnt target expression. However, expression of the Wnt target and stem cell marker Lgr5 was significantly higher in 1322T tumours than in Min tumours. Other stem cell markers (Musashi1, Bmi1 and the Wnt target Cd44) were also at higher levels in 1322T tumours. In addition, expression of the Bmp antagonist Gremlin1 was higher in 1322T tumours, together with lower Bmp2 and Bmp4 expression. <h3>Conclusions</h3> The severe phenotype caused by truncation of Apc at codon 1322 is associated with an increased number of stem cells. Thus, a submaximal level of Wnt signalling favours the stem cell phenotype and this may promote tumorigenesis. A level of Wnt signalling exists that is too high for optimal tumour growth.
Specific interaction of pancreatic elastase and leucocytes to produce oxygen radicals and its implication in pancreatitis.
Authors: N Tsuji, N Watanabe, T Okamoto, Y Niitsu
Journal: Gut (1994)

Many previous reports using experimental animal models of pancreatitis have suggested that oxygen free radicals play an important part in initiation and development of pancreatitis. Infiltration of inflammatory cells--that is, neutrophils, lymphocytes, and monocytes--has been seen in damaged pancreatic glands of animal models and patients with pancreatitis. As neutrophils are known to be the highest producer of oxygen free radicals among these inflammatory cells, it seems plausible that oxygen free radicals produced by neutrophils have some pathoaetiological meaning in pancreatitis. This study measured the superoxide production by neutrophils obtained from patients with acute and chronic pancreatitis and then examined the effects of pancreatic enzymes on superoxide production. Patients showed significantly higher superoxide production by 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA) stimulated neutrophils than healthy controls. Among the three pancreatic enzymes, amylase, trypsin, and elastase, elastase was the only one that increased the superoxide production by PMA stimulated neutrophils, by an increment of 1.5-fold. It also increased the activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase prepared from PMA stimulated neutrophils by a factor of 2.1. High affinity and low affinity binding sites for elastase on neutrophils were identified. These results suggest that elastase plays a part in the development of pancreatitis by enhancing superoxide production of neutrophils.
Heliox Improves Gas Exchange during High-frequency Ventilation in a Pediatric Model of Acute Lung Injury
Authors: ANDREW KATZ, MICHAEL A. GENTILE, DAMIAN M. CRAIG, GEORGE QUICK, JON N. MELIONES, IRA M. CHEIFETZ
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Because heliox has a lower density as compared with air, we postulated that heliox would improve gas exchange during high-frequency oscillatory ventilation (HFOV) in a model of acute lung injury. In a prospective, cross-over trial, we studied 11 piglets with acute lung injury created by saline lavage. With initial conditions of permissive hypercapnia (Pa(CO(2)) 55-80 mm Hg), each piglet underwent HFOV with a fixed mean airway pressure, pressure oscillation, and ventilatory frequency. The following gas mixtures were used: oxygen-enriched air (60% O(2)/40% N(2)) and heliox (60% O(2)/ 40% He and 40% O(2)/60% He). Compared with oxygen-enriched air, the 40% and 60% helium gas mixtures reduced Pa(CO(2)) by an average of 10.5 and 20.3 mm Hg, respectively. A modest improvement in oxygenation was seen with the 40% helium mixture. We conclude that heliox significantly improves carbon dioxide elimination and modestly improves oxygenation during HFOV in a model of acute lung injury. On the basis of test lung data and plethysmography measurements, we also conclude that heliox improves carbon dioxide elimination primarily through increased tidal volume delivery. Although heliox improved gas exchange during HFOV in our model, increased tidal volume delivery may limit clinical applicability.
DLC1 Interaction with S100A10 Mediates Inhibition of <i>In Vitro</i> Cell Invasion and Tumorigenicity of Lung Cancer Cells through a RhoGAP-Independent Mechanism
Authors: Xuyu Yang, Nicholas C. Popescu, Drazen B. Zimonjic
Journal: Cancer Research (2011)

Abstract The DLC1 gene encodes a Rho GTPase-activating protein (RhoGAP) that functions as a tumor suppressor in several common human cancers. The multidomain structure of DLC1 enables interaction with a number of other proteins. Here we report that the proinflammatory protein S100A10 (also known as p11), a key cell surface receptor for plasminogen which regulates pericellular proteolysis and tumor cell invasion, is a new binding partner of DLC1 in human cells. We determined that the 2 proteins colocalize in the cell cytoplasm and that their binding is mediated by central sequences in the central domain of DLC1 and the C-terminus of S100A10. Because the same S100A10 sequence also mediates binding to Annexin 2, we found that DLC1 competed with Annexin 2 for interaction with S100A10. DLC1 binding to S100A10 did not affect DLC1's RhoGAP activity, but it decreased the steady-state level of S100A10 expression in a dose-dependent manner by displacing it from Annexin 2 and making it accessible to ubiquitin-dependent degradation. This process attenuated plasminogen activation and resulted in inhibition of in vitro cell migration, invasion, colony formation, and anchorage-independent growth of aggressive lung cancer cells. These results suggest that a novel GAP-independent mechanism contributes to the tumor suppressive activity of DLC1, and highlight the importance and complexity of protein–protein interactions involving DLC1 in certain cancers. Cancer Res; 71(8); 2916–25. ©2011 AACR.