tbuckley/cabot-search huggingface dataset:
Aortic Arch Curvature and Atherosclerosis Have Overlapping Quantitative Trait Loci in a Cross Between 129S6/SvEvTac and C57BL/6J Apolipoprotein E–Null Mice
Authors: Hirofumi Tomita, Svetlana Zhilicheva, Shinja Kim, Nobuyo Maeda
Journal: Circulation Research (2010)

Apolipoprotein E-null mice with a 129S6/SvEvTac strain background (129-apoE) develop atherosclerotic plaques faster in the aortic arch but slower in the aortic root than those with a C57BL/6J background (B6-apoE). The shape of the aortic arch also differs in the 2 strains.Because circulating plasma factors are the same at both locations, we tested the hypothesis that genetic factors affecting vascular geometry also affect the location and extent of atherosclerotic plaque development.Tests on the F2 progeny from a cross between 129-apoE-null and B6-apoE-null mice showed that the extent of atherosclerosis in the aortic arch is significantly correlated in males, but not in females, with the shape of arch curvature (r=0.34, P<0.0001) and weakly with the arch diameter (r=0.20, P=0.02). Quantitative trait locus (QTL) analysis identified 2 significant peaks for aortic arch lesion size on chromosome 1 (105 Mb, LOD=5.0, and 163 Mb, LOD=6.8), and a suggestive QTL on chromosome 15 (96 Mb, LOD=4.7). A significant QTL for aortic root lesion size was on chromosome 9 (61 Mb, LOD=6.9), but it was distinct from the QTLs for arch lesion size. Remarkably, the QTLs for susceptibility to atherosclerosis in the arch overlapped with a significant QTL that affects curvature of the arch on chromosome 1 (121 Mb, LOD=5.6) and a suggestive QTL on chromosome 15 (76 Mb, LOD=3.5).The overlapping QTLs for curvature of the aortic arch and atherosclerosis support that the ontogeny of the aortic arch formation is a potential risk factor for atherosclerosis.
Testing for boosting at the Paralympic games: policies, results and future directions
Authors: Cheri A Blauwet, Harry Benjamin-Laing, Jaap Stomphorst, Peter Van de Vliet, Pia Pit-Grosheide, Stuart E Willick
Journal: British Journal of Sports Medicine (2013)

'Boosting' is defined as the intentional induction of autonomic dysreflexia (AD) by athletes with a spinal cord injury (SCI) at or above the level of T6 for the purpose of improving sports performance. Boosting has been shown to confer up to a 9.7% improvement in race time. Additionally, to compete in a hazardous dysreflexic state, whether intentional or unintentional, would present an extreme health risk to the athlete. For these reasons, the International Paralympic Committee strictly bans the practice of boosting, and has developed a protocol to test for its presence.Testing was performed at three major international Paralympic events. Education regarding the dangers of AD was provided to athletes and team staff. Testing was conducted on athletes from the relevant sport classes: Athletics (wheelchair racing classes T51/T52/T53) and Handcycling (H1). Key parameters included the athlete's demographics (gender, country of origin), classification and blood pressure measurements. An extremely elevated blood pressure was considered to be a proxy maker for AD, and a systolic blood pressure of ≥180 mm Hg was considered a positive test.A total of 78 tests for the presence of AD were performed during the three games combined. No athlete tested positive. The number of athletes tested, by classification, was: 6 in Athletics T51, 47 in Athletics T52, 9 in Athletics T53 and 16 in Handcycling H1. Of those tested, the average systolic and diastolic blood pressures were 135 mm Hg (range 98-178) and 82 mm Hg (range 44-112), respectively. All athletes were compliant with testing. No athletes were withdrawn from competition due to the presence of AD.Testing for the presence of AD in paralympic athletes with SCI prior to competition has been carried out for the first time at three major international paralympic competitions. There have been no positive tests thus far. Knowledge gained during these early testing experiences will be used to guide ongoing refinement of the testing protocol and the development of further educational initiatives.
A randomised trial of self-management planning for adult patients admitted to hospital with acute asthma
Authors: L M Osman
Journal: Thorax (2002)

There is still debate over the benefit of self-management programmes for adults with asthma. A brief self-management programme given during a hospital admission for acute asthma was tested to determine whether it would reduce readmission.A randomised controlled trial was performed in 280 adult patients with acute asthma admitted over 29 months. Patients on the self-management programme (SMP) received 40-60 minutes of education supporting a written self-management plan. Control patients received standard care (SC).One month after discharge SMP patients were more likely than SC patients to report no daytime wheeze (OR 2.6, 95% CI 1.5 to 5.3), no night disturbance (OR 2.0, 95% CI 1.2 to 3.5), and no activity limitation (OR 1.5, 95% CI 0.9 to 2.7). Over 12 months 17% of SMP patients were re-admitted compared with 27% of SC patients (OR 0.5, 95% CI 0.3 to 1.0). Among first admission patients, OR readmission (SMP v SC) was 0.2 (95% CI 0.1 to 0.7), p<0.01. For patients with a previous admission, OR readmission was 0.8 (95% CI 0.4 to 1.6), p=0.6. SMP patients were more likely than SC patients to be prescribed inhaled steroids at discharge (99% v 92%, p=0.03), oral steroids (98% v 90%, p=0.06), and to have hospital follow up (98% v 84%, p<0.01) but adjustment for these differences did not diminish the effect of the self-management programme.A brief self-management programme during hospital admission reduced post discharge morbidity and readmission for adult asthma patients. The benefit of the programme may have been greater for patients admitted for the first time. The programme also had a small but significant effect on medical management at discharge.
Sustained Increase in Aortic Endothelial Nitric Oxide Synthase Expression In Vivo in a Model of Chronic High Blood Flow
Authors: Sophie Nadaud, Monique Philippe, Jean-Francois Arnal, Jean-Baptiste Michel, Florent Soubrier
Journal: Circulation Research (1996)

Physiological adaptation of normal blood vessels to acute or chronic changes in blood flow is endothelium dependent. In vitro studies have shown that, among other genes, NO synthase (NOS) 3 mRNA and protein expression is enhanced by acute elevation of shear stress in endothelial cells. We have investigated the effect of chronic high blood flow on NOS3 mRNA and protein expression in rat aorta. NOS3 mRNA levels were measured by quantitative polymerase chain reaction (PCR) in the aortas of 12 rats with arteriovenous fistulas and 9 sham-operated control rats. The PCR assay indicated that NOS3 mRNA levels were significantly enhanced (twofold) during high blood flow. Western blots showed that immunoreactive NOS3 levels were also increased to a similar extent. Furthermore, the Ca 2+ -dependent NOS activity, measured by the l -arginine to l -citrulline conversion assay, and the cGMP content were also significantly increased in the proximal aortic wall submitted to the arteriovenous shunt. These results indicate that NOS3 mRNA and protein expression is enhanced in vivo during chronic high blood flow.
Hepatic venous outflow obstruction in autosomal dominant polycystic kidney disease.
Authors: V E Torres, S Rastogi, B F King, A W Stanson, J B Gross, D M Nogorney
Journal: Journal of the American Society of Nephrology (1994)

To discuss the clinical presentation, diagnosis, and treatment of hepatic venous outflow obstruction as a complication of polycystic liver disease, four cases diagnosed and treated at our institution have been reviewed and the information from six previously published case reports has been summarized. Eight of the 10 patients were women. All presented with severe ascites. Nine had polycystic kidneys. Three had moderate-to-advanced renal insufficiency, four were on hemodialysis, and one had a renal allograft. Possible predisposing factors were identified in seven patients; the most common was recent abdominal surgery, which, in three cases, was a bilateral nephrectomy. All patients had extrinsic compression of the hepatic veins and the inferior vena cava by hepatic cysts, and four had proven superimposed thrombosis of the inferior vena cava and/or hepatic veins. In the patients seen in this institution, magnetic resonance imaging was helpful in determining the level of obstruction in the inferior vena cava and the patency of the hepatic and portal veins. The outcome was worse in the patients with thrombosis; one recovered after a portocaval shunt, and the remaining three patients died. On the other hand, five of the six patients without thrombosis recovered after alcohol sclerosis of a large dominant cyst (one patient) or after hepatic resection and cyst fenestration (four patients). Hepatic venous outflow obstruction probably has been underrecognized as a cause of portal hypertension, ascites, and liver dysfunction in polycystic liver disease. The diagnosis can be reliably established with current imaging techniques, especially magnetic resonance imaging.(ABSTRACT TRUNCATED AT 250 WORDS)
Nuclear Localization of PTEN Is Regulated by Ca2+ through a Tyrosil Phosphorylation–Independent Conformational Modification in Major Vault Protein
Authors: Takeo Minaguchi, Kristin A. Waite, Charis Eng
Journal: Cancer Research (2006)

Abstract We have recently shown in MCF-7 cells that nuclear phosphatase and tensin homologue deleted on chromosome 10 (PTEN) down-regulates phosphorylation of p44/42 and cyclin D1 and induces G1 cell cycle arrest, whereas cytoplasmic PTEN down-regulates phosphorylation of Akt, up-regulates p27, and induces apoptosis. In this manner, nucleocytoplasmic partitioning of PTEN seems to differentially regulate the cell cycle and apoptosis. We have also reported that PTEN has nuclear localization signal–like sequences required for major vault protein (MVP)–mediated nuclear translocation. To date, several other proteins are reported to interact with MVP, including extracellular signal-regulated kinases and steroid receptors, suggesting that MVP is likely to be involved in signal transduction through nucleocytoplasmic transport. However, the exact mechanism of MVP-mediated nucleocytoplasmic shuttling remains elusive. PTEN reportedly interacts in vitro with the EF hand–like motif of MVP in a Ca2+-dependent manner. The current study shows that small interfering RNA–mediated MVP silencing decreases the nuclear localization of PTEN and increases phosphorylation of nuclear p44/42. We show in situ that PTEN-MVP interaction is Ca2+ dependent and is abolished by Mg2+. Nuclear localization of PTEN is decreased by increasing Ca2+ levels in culture medium in a dose-dependent manner. Ca2+ ionophore A23187 increases nuclear localization of PTEN and decreases phosphorylation of nuclear p44/42. Finally, we show that Ca2+-dependent PTEN-MVP interaction is not related to MVP's tyrosil phosphorylation but rather due to its conformational modification. Our observations suggest that Ca2+ regulates PTEN's nuclear entry through a tyrosil phosphorylation–independent conformational change in MVP. Collectively, our data present evidence of a novel crosstalk between the Ca2+ signaling–mediated regulation of the cell cycle and MVP-mediated nuclear PTEN localization and function. (Cancer Res 2006; 66(24): 11677-82)
Evaluation of KRAS, NRAS, and BRAF Mutations in Prime: Panitumumab with FOLFOX4 as First-Line Treatment in Metastatic Colorectal Cancer (MCRC)
Authors: Kelly Oliner, Jean-Yves Douillard, Salvatore Siena, Josep Tabernero, Ronald Burkes, Mario Barugel, Yves Humblet, György Bodoky, David Cunningham, Jacek Jassem, Fernando Rivera, Ilona kocakova, Paul Ruff, Maria Blasinska Morawiec, Martin Smakal, Richard Williams, Alan Rong, Jeffrey Wiezorek, Roger Sidhu, Scott Patterson
Journal: Annals of Oncology (2013)
Glycolytic Enzymes Can Modulate Cellular Life Span
Authors: Hiroshi Kondoh, Matilde E. Lleonart, Jesus Gil, Jing Wang, Paolo Degan, Gordon Peters, Dolores Martinez, Amancio Carnero, David Beach
Journal: Cancer Research (2005)

An unbiased screen for genes that can immortalize mouse embryonic fibroblasts identified the glycolytic enzyme phosphoglycerate mutase (PGM). A 2-fold increase in PGM activity enhances glycolytic flux, allows indefinite proliferation, and renders cells resistant to ras-induced arrest. Glucosephosphate isomerase, another glycolytic enzyme, displays similar activity and, conversely, depletion of PGM or glucosephosphate isomerase with short interfering RNA triggers premature senescence. Immortalized mouse embryonic fibroblasts and mouse embryonic stem cells display higher glycolytic flux and more resistance to oxidative damage than senescent cells. Because wild-type p53 down-regulates PGM, mutation of p53 can facilitate immortalization via effects on PGM levels and glycolysis.
Solubilization of G (Gross) Antigens on the Surface of G Leukemia Cells2
Authors: Ronald B. Herberman, Tadao Aoki, Myrthel E. Nunn
Journal: JNCI Journal of the National Cancer Institute (1973)

Cell and virus surface antigens specific for leukemia induced by Gross virus were obtained in soluble form. Some antigen was in soluble form in the serum of mice bearing a Gross leukemia and in the tumor cells themselves. Additional soluble antigen was obtained from the cells by repeated washing with saline and by autolytic and papain digestion of a crude cell-membrane extract. Fractionation of the soluble antigens by ammonium sulfate precipitation and by Sephadex G-150 chromatography indicated heterogeneity in the molecular forms of the antigen.
CF and antistaphylococcal prophylaxis
Authors: A SMYTH
Journal: Thorax (2001)

seem to be specific to PCH, demonstrating the usefulness of HRCT scanning for diagnosis of this disease.Other previously reported CT findings of the disease include increased soft tissue density of the mediastinum 1 2 and mediastinal and hilar lymph adenopathies, 7 but such findings were absent in our case.Possible explanations for the stable condition of our case over a long period are either that it was a chance discovery of an early phase of the disease by HRCT scanning or that PCH has separate subtypes with diVering speeds of progression.Wider use of HRCT scanning and more extensive understanding of PCH would resolve this issue in the future.
Glycosylation and sulphation of colonic mucus glycoproteins in patients with ulcerative colitis and in healthy subjects.
Authors: H Morita, M G Kettlewell, D P Jewell, P W Kent
Journal: Gut (1993)

Studies have been made of mucus glycoprotein biosynthesis in different regions of the lower gastrointestinal tract in normal patients and those with ulcerative colitis (UC), active or inactive, by means of 3H-glucosamine (3H-GlcNH2)--35S-sulphate double labelling of epithelial biopsy specimens under culture conditions. The time based rate of 3H-GlcNH2 labelling of mucus in rectal tissue was similar to that in active or inactive UC whereas the rate of 35SO4(2) labelling was significantly increased in active disease. The 3H specific activities measuring the amount of isotopic incorporation into surface and tissue mucus glycoproteins were increased in patients with active UC compared with normal or inactive subjects. The 35S specific activities did not differ significantly between patients with active UC and those in remission. In the rectum, glycosylation of mucus glycoproteins decreases with the increasing age of the patient. Regional differences in 3H-labelling of mucus components are reported for ascending colon, transverse colon, sigmoid colon, and rectum. Sulphation (35S-labelling) was higher in all parts of the colon in left sided UC. Results point to accelerated glycosylation of core proteins in the active phase of UC.
Antigen-specific t lymphocyte clones. II. Purifcation and biological characterization of an antigen-specific suppressive protein synthesized by cloned T cells
Authors: M Fresno, L McVay-Boudreau, G Nabel, H Cantor
Journal: The Journal of Experimental Medicine (1981)

We have generated an antigen-specific T suppressor clone that synthesizes 70,000-mol wt peptides that have antigen-specific-binding activity. Although these data also indicated that antigen-binding peptides completely inhibited the in vitro primary response to a complex antigen, suppression might reflect the combined biologic activities of many different 70-mol wt polypeptides or polypeptides associated with the 70,000-mol wt material by noncovalent interactions. The protein responsible for antigen-specific suppression was therefore purified to virtual homogeneity after sequential separation of internally labeled supernate peptides on Sephacryl S-200 and DEAE-cellulose columns followed by isoeleetrofocusing. The resulting protein is greater than 95 percent homogeneous according to sodium dodeeyl sulfate-polyacrylamide electrophoresis and represents two peptides having two very close but distinguishable isoelectric point values of approximately 5.0. The purified molecules are retained by columns coated with lentil lectin or antigen but not by columns coated with antisera specific for immunoglobulins, the I region of the major histocompatibility complex or Ly-1 or Ly-2 antigens. Less than 50 pg of the purified glycoprotein specifically and completely suppresses production of anti-sheep erythrocyte plaque-forming cell by mixtures of 10(6) Ly-1 cells and B cells and this is a result of inactivation of Ly-l-mediated helper function. Specific inactivation of T (Th) cells by the 70,000-mol wt molecule is rapid, specific, and requires the presence of antigen. The mechanism of specific suppression of Th function may depend upon two functionally distinct regions of the 70,000-mol wt molecule: one that binds antigen and a second that mediates suppression.
Successful Cardiopulmonary Resuscitation After Cardiac Arrest as a “Sepsis-Like” Syndrome
Authors: Christophe Adrie, Minou Adib-Conquy, Ivan Laurent, Mehran Monchi, Christophe Vinsonneau, Catherine Fitting, François Fraisse, A. Tuan Dinh-Xuan, Pierre Carli, Christian Spaulding, Jean-François Dhainaut, Jean-Marc Cavaillon
Journal: Circulation (2002)

Background — We investigated the immunoinflammatory profile of patients successfully resuscitated after cardiac arrest, representing a model of whole-body ischemia/reperfusion syndrome. Methods and Results — Plasma cytokine, endotoxin, and ex vivo cytokine production in whole-blood assays was assessed in 61, 35, and 11 patients, respectively. On admission, high levels of plasma interleukin (IL)-6, IL-8, IL-10, and soluble tumor necrosis factor (TNF) receptor type II could discriminate between survivors and nonsurvivors. Among nonsurvivors, the initial need for a vasopressor agent was associated with higher levels of IL-1 receptor antagonist, IL-10, and IL-6 on day 1. Plasma endotoxin was detected in 46% of the analyzed patients within the 2 first days. Endotoxin-induced TNF and IL-6 productions were dramatically impaired in these patients compared with healthy control subjects, whereas an unaltered production was observed with heat-killed Staphylococcus aureus . In contrast, IL-1 receptor antagonist productions were enhanced in these patients compared with healthy control subjects. The productions of T-cell–derived IL-10 and interferon-γ were also impaired in these patients. Finally, using in vitro plasma exchange between healthy control subjects and patients, we demonstrated that the endotoxin-dependent hyporeactivity was an intrinsic property of patients’ leukocytes and that an immunosuppressive activity was also present in their plasma. Conclusions — Altogether, the high levels of circulating cytokines, the presence of endotoxin in plasma, and the dysregulated production of cytokines found in these patients recall the immunological profile found in patients with sepsis.
miR-335 and miR-34a Promote Renal Senescence by Suppressing Mitochondrial Antioxidative Enzymes
Authors: Xue-Yuan Bai, Yuxiang Ma, Rui Ding, Bo Fu, Suozhu Shi, Xiang-Mei Chen
Journal: Journal of the American Society of Nephrology (2011)

The molecular basis for aging of the kidney is not well understood. MicroRNAs (miRNAs) contribute to processes such as development, differentiation, and apoptosis, but their contribution to the aging process is unknown. Here, we analyzed the miRNA expression profile of young (3-month) and old (24-month) rat kidneys and identified the biologic pathways and genes regulated by differentially expressed miRNAs. We observed upregulation of 18 miRNAs with aging, mainly regulating the genes associated with energy metabolism, cell proliferation, antioxidative defense, and extracellular matrix degradation; in contrast, we observed downregulation of 7 miRNAs with aging, principally targeting the genes associated with the immune inflammatory response and cell-cycle arrest. Bioinformatics analysis suggested that superoxide dismutase 2 (SOD2) and thioredoxin reductase 2 (Txnrd2), located in the mitochondria, are potential targets of miR-335 and miR-34a, respectively. Aging mesangial cells exhibited significant upregulation of miR-335 and miR-34a and marked downregulation of SOD2 and Txnrd2. miR-335 and miR-34a inhibited expression of SOD2 and Txnrd2 by binding to the 3′-untranslated regions of each gene, respectively. Overexpression of miR-335 and miR-34a induced premature senescence of young mesangial cells via suppression of SOD2 and Txnrd2 with a concomitant increase in reactive oxygen species (ROS). Conversely, antisense miR-335 and miR-34a inhibited senescence of old mesangial cells via upregulation of SOD2 and Txnrd2 with a concomitant decrease in ROS. In conclusion, these results suggest that miRNAs may contribute to renal aging by inhibiting intracellular pathways such as those involving the mitochondrial antioxidative enzymes SOD2 and Txnrd2.
Automatic Control of the Inspired Oxygen Fraction in Preterm Infants
Authors: Michael S. Urschitz, Werner Horn, Andreas Seyfang, Antonella Hallenberger, Tina Herberts, Silvia Miksch, Christian Popow, Ingo Müller-Hansen, Christian F. Poets
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

In preterm infants receiving supplemental oxygen, manual control of the inspired oxygen fraction is often time-consuming and inappropriate. We developed a system for automatic oxygen control and hypothesized that this system is more effective than routine manual oxygen control in maintaining target arterial oxygen saturation levels. We performed a randomized controlled crossover clinical trial in 12 preterm infants receiving nasal continuous positive airway pressure and supplemental oxygen. Periods with automatic and routine manual oxygen control were compared with periods of optimal control by a fully dedicated person. The median (range) percentage of time with arterial oxygen saturation levels within target range (87-96%) was 81.7% (39.0-99.8) for routine manual oxygen control, 91.0% (41.4-99.3) for optimal control, and 90.5% (59.0-99.4) for automatic control (ANOVA: p = 0.01). Pairwise post hoc comparisons revealed a statistically significant difference between automatic and routine manual oxygen control (Dunnett's test: p = 0.02). The frequency of manual oxygen adjustments was lowest in automatic control (Friedman's test: p < 0.001). Automatic oxygen control may optimize oxygen administration to preterm infants receiving nasal continuous positive airway pressure and reduce nursing time spent with oxygen control.