tbuckley/cabot-search huggingface dataset:
OPTIMAL CONTACT FORCE TO PREVENT ACUTE PULMONARY VEIN RECONNECTION DURING RADIOFREQUENCY CATHETER ABLATION FOR ATRIAL FIBRILLATION
Authors: Yohei Sotomi, Takayuki Kikkawa, Koichi Inoue, Koji Tanaka, Yuko Toyoshima, Takafumi Oka, Nobuaki Tanaka, Yoichi Nozato, Katsuomi Iwakura, Kenshi Fujii
Journal: Journal of the American College of Cardiology (2014)
Early application of high frequency oscillatory ventilation in ‘H1N1 influenza’ related ARDS is associated with better outcome: a retrospective study
Authors: Sameer Jog, Divyesh Patel, Tejal Dravid, Prasad Rajhans, Prasad Akole, Balasaheb Pawar, Monika Kothari, Bhagyashri Bhurke, Aniruddh Deshpande
Journal: Intensive Care Medicine (2013)
Antibody blockade of semaphorin 4D breaks down barriers to enhance tumoricidal immune infiltration and supports rational immunotherapy combinations
Authors: Elizabeth E Evans, Siwen Hu-Lieskovan, Holm Bussler, Sebold Torno, Crystal Mallow, Christine Reilly, Maria Scrivens, Ekaterina Klimatcheva, Laurie A Winter, Renee Kirk, Alan Howell, Leslie Balch, Janaki Veeraraghavan, Alan S Jonason, John E Leonard, Mark Paris, Terrence L Fisher, Antoni Ribas, Ernest S Smith, Maurice Zauderer
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Semaphorin 4D (SEMA4D, CD100) and its receptor plexin-B1 are broadly expressed in cancer and expression correlates with invasive disease in several human tumors. SEMA4D normally functions to regulate the motility and differentiation of multiple cell types, including those of the
Effects of Nurse-Managed Protocols in the Outpatient Management of Adults with Chronic Conditions
Authors: Ryan J Shaw, Jennifer R McDuffie, Cristina C Hendrix, Alison Edie, Linda Lindsey-Davis, John W Williams
Journal: Annals of Internal Medicine (2013)

The Patient Protection and Affordable Care Act has resulted in more access to medical care for patients with chronic disease. Nurse-managed protocols for outpatient management of patients with chro...
Tolerance of thymocytes to allogeneic i region determinants encountered prethymically. Evidence for expression of anti-Ia receptors by T cell precursors before their entry into the thymus
Authors: SM Bradley, PJ Morrissey, SO Sharrow, A Singer
Journal: The Journal of Experimental Medicine (1982)

The present study has assessed whether precursor T cells express receptors specific for the recognition of allogeneic I region-encoded determinants before their entry into the thymus. Because the ability of thymocytes to proliferate in response to allogeneic stimulator cells was shown to primarily result from the recognition of allogeneic I region determinants, thymocytes must already express anti-Ia receptors. In contrast, the expression of anti- Ia receptors by functionally immature thymocyte precursors could not be directly assessed by mixed lymphocyte reaction reactivity. However, expression of anti-Ia receptors by thymocyte precursors could be assessed by their ability to be specifically tolerized by the allogeneic Ia determinants that they encountered during their differentiation. To determine whether T cell precursors could specifically recognize and be tolerized to allogeneic Ia determinants expressed prethymically, thymus- engrafted radiation bone marrow chimeras were constructed [A {arrow} A x B (Tx + A Thy)] such that strain A T cells would be differentiating within a syngeneic strain A thymus but would have been previously exposed to the allogeneic strain B Ia determinants of the irradiated A x B host. The strain A thymocytes from these experimental animals were indeed tolerant to the extrathymic allogeneic strain B Ia determinants expressed by the irradiated host. Such tolerance was not mediated by detectable suppression and was not explained by the presence intrathymically of extrathymic allogeneic Ia determinants. Thus, these results suggest that T cell precursors can be specifically tolerized entry into the thymus. In addition, the failure to detect the generation of thymocytes with specificity for the allogeneic Ia determinants of the irradiated host, which were not deleted prethymically, argues that novel anti-allo Ia receptor specificities are not generated intrathymically.
Leptin produced by joint white adipose tissue induces cartilage degradation via upregulation and activation of matrix metalloproteinases
Authors: Wang Hui, Gary J Litherland, Martina S Elias, Gareth I Kitson, Tim E Cawston, Andrew D Rowan, David A Young
Journal: Annals of the Rheumatic Diseases (2011)

Objectives To investigate the effect of leptin on cartilage destruction. Methods Collagen release was assessed in bovine cartilage explant cultures, while collagenolytic and gelatinolytic activities in culture supernatants were determined by bioassay and gelatin zymography. The expression of matrix metalloproteinases (MMP) was analysed by real-time RT–PCR. Signalling pathway activation was studied by immunoblotting. Leptin levels in cultured osteoarthritic joint infrapatellar fat pad or peri-enthesal deposit supernatants were measured by immunoassay. Results Leptin, either alone or in synergy with IL-1, significantly induced collagen release from bovine cartilage by upregulating collagenolytic and gelatinolytic activity. In chondrocytes, leptin induced MMP1 and MMP13 expression with a concomitant activation of STAT1, STAT3, STAT5, MAPK (JNK, Erk, p38), Akt and NF-κB signalling pathways. Selective inhibitor blockade of PI3K, p38, Erk and Akt pathways significantly reduced MMP1 and MMP13 expression in chondrocytes, and reduced cartilage collagen release induced by leptin or leptin plus IL-1. JNK inhibition had no effect on leptin-induced MMP13 expression or leptin plus IL-1-induced cartilage collagen release. Conditioned media from cultured white adipose tissue (WAT) from osteoarthritis knee joint fat pads contained leptin, induced cartilage collagen release and increased MMP1 and MMP13 expression in chondrocytes; the latter being partly blocked with an anti-leptin antibody. Conclusions Leptin acts as a pro-inflammatory adipokine with a catabolic role on cartilage metabolism via the upregulation of proteolytic enzymes and acts synergistically with other pro-inflammatory stimuli. This suggests that the infrapatellar fat pad and other WAT in arthritic joints are local producers of leptin, which may contribute to the inflammatory and degenerative processes in cartilage catabolism, providing a mechanistic link between obesity and osteoarthritis.
Use of localised gene transfer to develop new treatment strategies for the salivary component of Sjogren's syndrome
Authors: M R Kok
Journal: Annals of the Rheumatic Diseases (2003)

Effective treatment for Sjögren's syndrome (SS) might be developed locally by introducing genes encoding cytokines, which are potentially anti-inflammatory, or by introducing a cDNA encoding a soluble form of a key cytokine receptor, which can act as an antagonist and decrease the availability of certain cytokines, such as soluble tumour necrosis factor alpha receptors. Currently, the preferred choice of viral vector for immunomodulatory gene transfer is recombinant adeno-associated virus. The use of gene transfer to help determine the pathophysiology and to alter the course of the SS-like disease in the NOD mouse model can ultimately lead to the development of new treatments for managing the salivary component in patients with SS.
Prevalence of temporomandibular dysfunction in a group of scuba divers
Authors: R D Aldridge, M R Fenlon
Journal: British Journal of Sports Medicine (2004)

Temporomandibular dysfunction (TMD) has been reported to be a common problem in divers, with a prevalence of up to 68%. No evidence for this is available.To investigate the prevalence of TMD in divers.Sixty three subjects were asked to retrospectively complete a questionnaire on symptoms of TMD after diving in warm and cold water areas and in daily life.The prevalence of TMD was greater in female divers. The prevalence of TMD while diving was about 26%, comparable to that experienced in daily life.Improvements in mouthpiece design and lighter demand valves mean that TMD is now probably exacerbated by diving rather than caused by it.
Metabolite Traits and Genetic Risk Provide Complementary Information for the Prediction of Future Type 2 Diabetes
Authors: Geoffrey A. Walford, Bianca C. Porneala, Marco Dauriz, Jason L. Vassy, Susan Cheng, Eugene P. Rhee, Thomas J. Wang, James B. Meigs, Robert E. Gerszten, Jose C. Florez
Journal: Diabetes Care (2014)

A genetic risk score (GRS) comprised of single nucleotide polymorphisms (SNPs) and metabolite biomarkers have each been shown, separately, to predict incident type 2 diabetes. We tested whether genetic and metabolite markers provide complementary information for type 2 diabetes prediction and, together, improve the accuracy of prediction models containing clinical traits.Diabetes risk was modeled with a 62-SNP GRS, nine metabolites, and clinical traits. We fit age- and sex-adjusted logistic regression models to test the association of these sources of information, separately and jointly, with incident type 2 diabetes among 1,622 initially nondiabetic participants from the Framingham Offspring Study. The predictive capacity of each model was assessed by area under the curve (AUC).Two hundred and six new diabetes cases were observed during 13.5 years of follow-up. The AUC was greater for the model containing the GRS and metabolite measurements together versus GRS or metabolites alone (0.820 vs. 0.641, P < 0.0001, or 0.820 vs. 0.803, P = 0.01, respectively). Odds ratios for association of GRS or metabolites with type 2 diabetes were not attenuated in the combined model. The AUC was greater for the model containing the GRS, metabolites, and clinical traits versus clinical traits only (0.880 vs. 0.856, P = 0.002).Metabolite and genetic traits provide complementary information to each other for the prediction of future type 2 diabetes. These novel markers of diabetes risk modestly improve the predictive accuracy of incident type 2 diabetes based only on traditional clinical risk factors.
Integrin α5β1 Plays a Critical Role in Resistance to Temozolomide by Interfering with the p53 Pathway in High-Grade Glioma
Authors: Hana Janouskova, Anne Maglott, David Y. Leger, Catherine Bossert, Fanny Noulet, Eric Guerin, Dominique Guenot, Sophie Pinel, Pascal Chastagner, François Plenat, Natacha Entz-Werle, Jacqueline Lehmann-Che, Julien Godet, Sophie Martin, Jan Teisinger, Monique Dontenwill
Journal: Cancer Research (2012)

Integrins play a role in the resistance of advanced cancers to radiotherapy and chemotherapy. In this study, we show that high expression of the α5 integrin subunit compromises temozolomide-induced tumor suppressor p53 activity in human glioblastoma cells. We found that depletion of the α5 integrin subunit increased p53 activity and temozolomide sensitivity. However, when cells were treated with the p53 activator nutlin-3a, the protective effect of α5 integrin on p53 activation and cell survival was lost. In a functional p53 background, nutlin-3a downregulated the α5 integrin subunit, thereby increasing the cytotoxic effect of temozolomide. Clinically, α5β1 integrin expression was associated with a more aggressive phenotype in brain tumors, and high α5 integrin gene expression was associated with decreased survival of patients with high-grade glioma. Taken together, our findings indicate that negative cross-talk between α5β1 integrin and p53 supports glioma resistance to temozolomide, providing preclinical proof-of-concept that α5β1 integrin represents a therapeutic target for high-grade brain tumors. Direct activation of p53 may remain a therapeutic option in the subset of patients with high-grade gliomas that express both functional p53 and a high level of α5β1 integrin.
Development of Autosomal Recessive Polycystic Kidney Disease in BALB/c-cpk/cpk Mice
Authors: JUSTIN L. RICKER, VINCENT H. GATTONE, JAMES P. CALVET, CAROLYN A. RANKIN
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Autosomal recessive polycystic kidney disease (ARPKD) is a rare but devastating inherited disease in humans. Various strains of mice that are homozygous for the cpk gene display renal pathology similar to that seen in human ARPKD. The PKD progresses to renal insufficiency, azotemia, and ultimately a uremic death by approximately 3 wk of age. This study characterizes PKD in mice that are homozygous for the cpk gene on a BALB/c inbred mouse background. The BALB/c- cpk/cpk murine model displays renal as well as extrarenal pathology similar to that found in human ARPKD. The renal pathology includes the well-characterized early proximal tubule and, later, massive collecting duct cysts. The extrarenal defects in this murine model include common bile duct dilation, intrahepatic biliary duct cysts with periductal hyperplasia, and pancreatic dysplasia with cysts. Renal mRNA expression of c-myc , a proto-oncogene, and clusterin ( SGP-2 ), a marker associated with immature collecting ducts, decreases during normal development but is upregulated in murine ARPKD. Expression of epidermal growth factor (EGF) mRNA is significantly diminished, whereas EGF receptor mRNA is upregulated in the BALB/c- cpk/cpk kidney compared with phenotypically normal littermates. To determine whether the altered EGF expression contributes to the development of PKD, neonatal mice were treated with exogenous EGF (1 μg/g body wt injected subcutaneously on postnatal days 3 through 9). EGF treatment reduced the relative kidney weight and common bile duct dilation and downregulated renal expression of clusterin and EGF receptor. However, exogenous EGF did not affect the degree of renal failure, the pancreatic pathology, or the misregulated renal expression of c-myc . In summary, the present study characterizes the renal and extrarenal pathology in the BALB/c- cpk/cpk murine model of ARPKD. Renal mRNA expression of EGF is diminished in this mouse model. EGF treatment did not prevent renal failure but ameliorated pathologic changes in the kidney and the biliary ducts of the BALB/c- cpk/cpk mouse.
Increased secretion of atrial natriuretic polypeptide from the left ventricle in patients with dilated cardiomyopathy.
Authors: H Yasue, K Obata, K Okumura, M Kurose, H Ogawa, K Matsuyama, M Jougasaki, Y Saito, K Nakao, H Imura
Journal: Journal of Clinical Investigation (1989)

To examine whether atrial natriuretic polypeptide (ANP) is released from the left ventricle in patients with dilated cardiomyopathy (DCM) we measured plasma ANP level in the aortic root (Ao), the anterior interventricular vein (AIV), the great cardiac vein (GCV), and the coronary sinus (CS) in 11 patients with DCM and 18 control subjects. Plasma ANP levels in Ao, AIV, GCV, and CS were 454 +/- 360, 915 +/- 584, 1,308 +/- 926, and 1,884 +/- 1,194 pg/ml, respectively, in the patients with DCM and 108 +/- 42, 127 +/- 55, 461 +/- 224, and 682 +/- 341 pg/ml, respectively, in the control subjects. There was no significant difference in the plasma ANP levels between Ao and AIV in the control subjects. On the contrary, there was a significant (P less than 0.001) step-up in plasma ANP levels between Ao and AIV in patients with DCM. Thus, the difference in ANP levels between Ao and AIV was significantly increased in patients with DCM as compared with the control subjects (461 +/- 248 vs. 19 +/- 59 pg/ml, P less than 0.001). The difference in ANP levels between Ao and CS was also significantly increased in patients with DCM as compared with the control subjects (1,429 +/- 890 vs. 577 +/- 318 pg/ml, P less than 0.001). We conclude that ANP is released in increased amounts into the circulation from the left ventricle as well as from the heart as a whole in patients with DCM.
Integrated Genomic Analysis Identifies Clinically Relevant Subtypes of Glioblastoma Characterized by Abnormalities in PDGFRA, IDH1, EGFR, and NF1
Authors: Roel G.W. Verhaak, Katherine A. Hoadley, Elizabeth Purdom, Victoria Wang, Yuan Qi, Matthew D. Wilkerson, C. Ryan Miller, Li Ding, Todd Golub, Jill P. Mesirov, Gabriele Alexe, Michael Lawrence, Michael O'Kelly, Pablo Tamayo, Barbara A. Weir, Stacey Gabriel, Wendy Winckler, Supriya Gupta, Lakshmi Jakkula, Heidi S. Feiler, J. Graeme Hodgson, C. David James, Jann N. Sarkaria, Cameron Brennan, Ari Kahn, Paul T. Spellman, Richard K. Wilson, Terence P. Speed, Joe W. Gray, Matthew Meyerson, Gad Getz, Charles M. Perou, D. Neil Hayes
Journal: Cancer Cell (2010)
Postexercise heart rates and pulse palpation as a means of determining exercising intensity in an aerobic dance class.
Authors: J M Bell, E J Bassey
Journal: British Journal of Sports Medicine (1996)

To establish the accuracy of the traditional method of measuring the intensity of exercise in aerobic dance classes, that is, intermittent pulse palpation performed during a brief cessation of activity.A short wave telemetry system was used to record heart rates during a class in a group of 12 healthy women aged 26 (SD 6) years. Subjects palpated their pulses for 10 s following high and low intensity exercise [78(8)% and 69(9)% of mean predicted maximum heart rate respectively]. Recorded exercising heart rates, averaged over 60 s preceding pulse palpation [ExHR(rec)], were compared with the recorded postexercise heart rates averaged over the 10 s palpation period [PostExHR(rec)] and with the palpated counts (PalpHR). Differences were assessed using Student's t test and Wilcoxon signed rank test.Differences between ExHR(rec) and PostExHR(rec) following high and low intensity exercise [3(6) beats.min-1 and 5(7) beats.min-1 respectively] were not significant. However, the wide variation between subjects means that a postexercise heart rate is unreliable as a measure of individual exercise intensity. PalpHR was significantly lower than ExHR(rec) (P < 0.01). Every individually palpated count underestimated the exercising heart rate (range 9 to 95 beats.min-1).While postexercise heart rate adequately represents the exercise heart rate for a group, the individual variation is too wide for this to be a useful measurement.
P01.14 * PRESENCE OF A STEM CELL-LIKE CELL SUBPOPULATION IS ASSOCIATED WITH ENHANCED SURVIVAL OF GLIOBLASTOMA PATIENTS
Authors: D. Loetsch, S. Spiegl-Kreinecker, B. Kiesel, G. Widhalm, M. Laaber, E. Knosp, J. Hainfellner, C. Marosi, W. Berger
Journal: Neuro-Oncology (2014)

Glioblastoma multiforme (GBM) is the most aggressive type of primary brain tumours characterised by a dismal prognosis and limited treatment response. The current standard of care for GBM patients includes after tumour resection, radiotherapy (RT) followed by concomitant and adjuvant chemotherapy with the alkylating agent temozolomide (TMZ). Even at this maximal therapy the prognosis of GBM patients remains poor with a median survival of 15 months. It is believed that a subpopulation of glioma stem cells (GSC) is responsible for maintaining a tumour after therapy thus causing recurrence after gross total resection. Accordingly aim of this study was to correlate the presence of GSCs with the predictive and prognostic glioblastoma biomarkers MGMT promoter methylation and TERT promoter mutation, respectively. In addition we investigated the prognostic quality of a GSC subpopulation on patient overall survival. For that purpose 33 primary and recurrent GBM patients operated at the Medical University of Vienna since September 2009 were included in this project. Every resected tumour sample was cultured in parallel as adherent monolayer under standard and as spheroids under GSC culture conditions. Fourteen out of 33 GBM tissue specimens (42%) developed into adherent and neurosphere cultures (termed GCSpos), while the remaining 19 (58%) could solely grow as adherent monolayer (termed GSCneg). The mean age of GSCpos patients was significantly lower as compared to the GSCneg subgroup (53 versus 63 years). The GSCpos cohort was characterized by significantly enhanced occurrence of MGMT promoter methylation and TERT promoter mutation. Surprisingly, GCSpos compared to GCSneg patients showed a significant prolonged overall survival (p = 0.0045). Summarizing our data suggest that GBM tumours harbouring GSC characteristics might be more likely to respond to standard therapy with TMZ due to the favourable MGMT promoter methylation status explaining, beside lower patient age, enhanced survival.
Effect of the Addition of Montelukast to Inhaled Fluticasone Propionate on Airway Inflammation
Authors: Siobhán O'Sullivan, Martijn Akveld, Conor M. Burke, Leonard W. Poulter
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

The aim of the study was to investigate the effect of addition of montelukast to inhaled fluticasone propionate (FP) therapy, compared with FP therapy alone (100 microg twice a day) on airway immunopathology in individuals with mild asthma. Twenty-eight subjects received FP (100 microg twice a day) or FP (100 microg twice a day) plus montelukast (10 mg at night) for 8 weeks and were then crossed over to the alternate treatment for a further 8 weeks. Physiological measurements and bronchial biopsies were obtained at +/- 2 days before treatment and +/- 2 days at the end of each treatment period. A two-period crossover analysis was performed and the mean and SE were calculated. There was no significant difference in percent predicted FEV1 (p = 0.51) or PC20 mg/ml (p = 0.81) between the two treatment regimes after 8 weeks of therapy. There was no difference in the efficacy of either treatment in decreasing T cell (p = 0.97), CD45RO+ (p = 0.37), mast cell (p = 0.37), or activated eosinophils (p = 0.55) numbers in bronchial biopsies. There was no significant difference in the percentage area stained for IFN-gamma (p = 0.76) or interleukin-4 (p = 0.61) between treatments. Reduction of inflammatory cell numbers in the bronchial mucosa achieved with FP plus montelukast was not significantly different from the reduction observed with FP alone in individuals with mild asthma.
Transcriptional Upregulation of Mitochondrial Uncoupling Protein 2 Protects Against Oxidative Stress-Associated Neurogenic Hypertension
Authors: Samuel H.H. Chan, Chiung-Ai Wu, Kay L.H. Wu, Ying-Hao Ho, Alice Y.W. Chang, Julie Y.H. Chan
Journal: Circulation Research (2009)

Rationale : Mitochondrial uncoupling proteins (UCPs) belong to a superfamily of mitochondrial anion transporters that uncouple ATP synthesis from oxidative phosphorylation and mitigates mitochondrial reactive oxygen species production. Objective : We assessed the hypothesis that UCP2 participates in central cardiovascular regulation by maintaining reactive oxygen species homeostasis in the rostral ventrolateral medulla (RVLM), where sympathetic premotor neurons that maintain vasomotor tone located. We also elucidated the molecular mechanisms that underlie transcriptional upregulation of UCP2 in response to oxidative stress in RVLM. Methods and Results : In Sprague–Dawley rats, transcriptional upregulation of UCP2 in RVLM by rosiglitazone, an activator of its transcription factor peroxisome proliferator-activated receptor (PPAR)γ, reduced mitochondrial hydrogen peroxide level in RVLM and systemic arterial pressure. Oxidative stress induced by microinjection of angiotensin II into RVLM augmented UCP2 mRNA or protein expression in RVLM, which was antagonized by comicroinjection of NADPH oxidase inhibitor (diphenyleneiodonium chloride), superoxide dismutase mimetic (tempol), or p38 mitogen-activated protein kinase inhibitor (SB203580) but not by extracellular signal-regulated kinase 1/2 inhibitor (U0126). Angiotensin II also induced phosphorylation of the PPARγ coactivator, PPARγ coactivator (PGC)-1α, and an increase in formation of PGC-1α/PPARγ complexes in a p38 mitogen-activated protein kinase–dependent manner. Intracerebroventricular infusion of angiotensin II promoted an increase in mitochondrial hydrogen peroxide production in RVLM and chronic pressor response, which was potentiated by gene knockdown of UCP2 but blunted by rosiglitazone. Conclusions : These results suggest that transcriptional upregulation of mitochondrial UCP2 in response to an elevation in superoxide plays an active role in feedback regulation of reactive oxygen species production in RVLM and neurogenic hypertension associated with chronic oxidative stress.