tbuckley/cabot-search huggingface dataset:
The effect of fatigue on frontal plane angular changes in the lumbar spine of elite rowers
Authors: F Wilson, C Simms, G Gormley, C Gissane
Journal: British Journal of Sports Medicine (2011)

Background The incidence of lumbar spine injury is high in rowers. Spinal kinematics and fatigue may influence onset of this injury. Objective To quantify lumbar spine motion in the frontal plane (at L3) and examine the effects of fatigue (measured by changes in blood lactate accumulation) on changes in angular displacement of the lumbar spine during ergometer rowing. Design The lumbar spine kinematics of the study cohort were measured using a Spectrotilt Inclinometer connected to a Biometrics DataLog system. Setting A laboratory based study of elite level rowing. Participants 12 elite rowers, all male, mean age 23.2 (5.2) years, mean weight 79.1 (5) Kg. Assessment of risk factors Lumbar spine angular kinematics were measured in the frontal plane at L3 during an ergometer rowing trial. The trial was an incremental ‘step test’ on a Concept 2 ergometer. Blood lactate was sampled at 3 min intervals throughout the test using a portable lactate analyser. Main outcome measurements Changes in spinal angular displacement between the first and last stage of the test. Fatigue was indicated by accumulation of blood lactate. Results Mean angular displacement was 4.6° (1.4) at the first stage of the test, increasing to 8.7° (2.1) for the last stage. A significant increase in frontal plane angular displacement between the first and last stage of the test was observed (mean increase=4.1° (1.94), 95% CI 2.9 to 5.3°, t=7.36, p=0.000014). Incremental rise in angular displacement was associated with an incremental rise in blood lactate. Conclusion The high values of angular displacement reached by the participants in this study confirm that there is considerable frontal plane motion during rowing and this increases with fatigue and should be considered as a factor for injury.
Expression of SET, an inhibitor of protein phosphatase 2A, in renal development and Wilms' tumor.
Authors: S G Carlson, E Eng, E G Kim, E J Perlman, T D Copeland, B J Ballermann
Journal: Journal of the American Society of Nephrology (1998)

The human gene set was originally identified as a component of the set-can fusion gene produced by a somatic translocation event in a case of acute undifferentiated leukemia. In the developing kidney, set was highly expressed in the zone of nephron morphogenesis. Recently, SET was shown to be a potent and specific inhibitor of protein phosphatase 2A, a family of major serine/threonine phosphatases involved in regulating cell proliferation and differentiation. The current study sought to define further the role of SET in the regulation of renal cell proliferation and tumorigenesis. The mRNA encoding SET was expressed at much higher levels in transformed human and rodent cell lines than in cultured renal epithelial and primary endothelial cells. Consistent with a role for SET in cell proliferation, set mRNA expression was markedly reduced in cells rendered quiescent by serum starvation, contact inhibition, or differentiation. Previous findings during renal development were extended by demonstrating that SET protein expression is also much greater in developing rat and human kidney than in fully differentiated, mature kidney. Finally, high levels of set mRNA and SET protein expression were found in Wilms' tumor, but not in renal cell carcinoma, adult polycystic kidney disease or in transitional cell carcinoma.
Ebola Virus VP24 Targets a Unique NLS Binding Site on Karyopherin Alpha 5 to Selectively Compete with Nuclear Import of Phosphorylated STAT1
Authors: Wei Xu, Megan R. Edwards, Dominika M. Borek, Alicia R. Feagins, Anuradha Mittal, Joshua B. Alinger, Kayla N. Berry, Benjamin Yen, Jennifer Hamilton, Tom J. Brett, Rohit V. Pappu, Daisy W. Leung, Christopher F. Basler, Gaya K. Amarasinghe
Journal: Cell Host & Microbe (2014)
CCT244747 Is a Novel Potent and Selective CHK1 Inhibitor with Oral Efficacy Alone and in Combination with Genotoxic Anticancer Drugs
Authors: Mike I. Walton, Paul D. Eve, Angela Hayes, Melanie R. Valenti, Alexis K. De Haven Brandon, Gary Box, Albert Hallsworth, Elizabeth L. Smith, Kathy J. Boxall, Michael Lainchbury, Thomas P. Matthews, Yann Jamin, Simon P. Robinson, G. Wynne Aherne, John C. Reader, Louis Chesler, Florence I. Raynaud, Suzanne A. Eccles, Ian Collins, Michelle D. Garrett
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Many tumors exhibit defective cell-cycle checkpoint control and increased replicative stress. CHK1 is critically involved in the DNA damage response and maintenance of replication fork stability. We have therefore discovered a novel potent, highly selective, orally active ATP-competitive CHK1 inhibitor, CCT244747, and present its preclinical pharmacology and therapeutic activity. Experimental Design: Cellular CHK1 activity was assessed using an ELISA assay, and cytotoxicity a SRB assay. Biomarker modulation was measured using immunoblotting, and cell-cycle effects by flow cytometry analysis. Single-agent oral CCT244747 antitumor activity was evaluated in a MYCN-driven transgenic mouse model of neuroblastoma by MRI and in genotoxic combinations in human tumor xenografts by growth delay. Results: CCT244747 inhibited cellular CHK1 activity (IC50 29–170 nmol/L), significantly enhanced the cytotoxicity of several anticancer drugs, and abrogated drug-induced S and G2 arrest in multiple tumor cell lines. Biomarkers of CHK1 (pS296 CHK1) activity and cell-cycle inactivity (pY15 CDK1) were induced by genotoxics and inhibited by CCT244747 both in vitro and in vivo, producing enhanced DNA damage and apoptosis. Active tumor concentrations of CCT244747 were obtained following oral administration. The antitumor activity of both gemcitabine and irinotecan were significantly enhanced by CCT244747 in several human tumor xenografts, giving concomitant biomarker modulation indicative of CHK1 inhibition. CCT244747 also showed marked antitumor activity as a single agent in a MYCN-driven neuroblastoma. Conclusion: CCT244747 represents the first structural disclosure of a highly selective, orally active CHK1 inhibitor and warrants further evaluation alone or combined with genotoxic anticancer therapies. Clin Cancer Res; 18(20); 5650–61. ©2012 AACR.
The melanin-concentrating hormone receptor 1, a novel target of autoantibody responses in vitiligo
Authors: E. Helen Kemp, Elizabeth A. Waterman, Brian E. Hawes, Kim O’Neill, Raju V.S.R.K. Gottumukkala, David J. Gawkrodger, Anthony P. Weetman, Philip F. Watson
Journal: Journal of Clinical Investigation (2002)

Vitiligo is a common depigmenting disorder resulting from the loss of melanocytes in the skin. The pathogenesis of the disease remains obscure, although autoimmune mechanisms are thought to be involved. Indeed, autoantibodies and autoreactive T lymphocytes that target melanocytes have been reported in some vitiligo patients. The objective of this study was to identify pigment cell antigens that are recognized by autoantibodies in vitiligo. Using IgG from vitiligo patients to screen a melanocyte cDNA phage-display library, we identified the melanin-concentrating hormone receptor 1 (MCHR1) as a novel autoantigen related to this disorder. Immunoreactivity against the receptor was demonstrated in vitiligo patient sera by using radiobinding assays. Among sera from healthy controls and from patients with autoimmune disease, none exhibited immunoreactivity to MCHR1, indicating a high disease specificity for Ab’s against the receptor. Inhibition of MCH binding to its receptor by IgG from vitiligo patients was also shown.
Prx1 Controls Vascular Smooth Muscle Cell Proliferation and Tenascin-C Expression and Is Upregulated With Prx2 in Pulmonary Vascular Disease
Authors: Frederick S. Jones, Robyn Meech, David B. Edelman, Rebecca J. Oakey, Peter Lloyd Jones
Journal: Circulation Research (2001)

Prx1 and Prx2 are homeobox transcription factors expressed during vasculogenesis. To begin to elucidate how Prx1 and Prx2 are regulated and function in the adult vasculature, in situ hybridization studies were performed. Prx1 and Prx2 mRNAs were not detected in normal adult rat pulmonary arteries; however, both genes were induced with vascular disease, colocalizing to sites of tenascin-C (TN-C) expression. Because catabolism of the extracellular matrix (ECM) is a critical step in the development of vascular disease, we investigated whether changes in vascular smooth muscle cell (SMC)–ECM interactions regulate Prx1 and Prx2. A10 SMCs cultured on native type I collagen showed low levels of Prx1 and Prx2 mRNA expression, whereas cells cultured on denatured collagen showed higher levels of expression of both genes. At a functional level, transfection of SMCs with a Prx1 expression plasmid significantly increased their growth. Because TN-C also promotes SMC growth and its expression is also upregulated by denatured collagen, we tested and thereafter showed that Prx1 expression significantly enhances TN-C gene promoter activity 20-fold. Similar experiments conducted with truncated Prx1 proteins showed that the N-terminal portion and the homeodomain of Prx1 were necessary to induce the bulk of TN-C promoter activity. These findings support the hypothesis that Prx genes are regulated by changes in SMC adhesion and play key morphoregulatory roles during the development and progression of pulmonary vascular disease in adults.
B cell or T cell-dominant recurrence after rituximab therapy in patients with SLE
Authors: Shigeru Iwata, Kazuyoshi Saito, Mikiko Tokunaga, Yoshiya Tanaka
Journal: Annals of the Rheumatic Diseases (2012)

Systemic lupus erythematosus (SLE) is an autoimmune disease induced by autoreactive T cell activation and B cell autoantibody overproduction. The efficacy of rituximab in refractory SLE has been documented, although some patients show partial response only.1,–,9 We report here two patients with SLE who showed T cell-dominant flare-up and two others who showed B cell-dependent flare-up, after long-term remission induced by rituximab administered at 375 mg/m2 twice/week.

Rituximab rapidly depleted peripheral naive and memory B cells in patients with SLE. Patients with prolonged remission had persistent depletion of memory B cells for >2 years, whereas recovery of naive B cells occurred within 3–9 months. The expression levels of CD80 on B cells diminished rapidly and remained downregulated. Furthermore, CD69 and ICOS (inducible T-cell co-stimulator) expression levels on CD4+ T cells also decreased and remained at low levels.10

B cell-dominant recurrence occurred in two patients, who were concurrently positive for anti-ds-DNA antibodies and extractable nuclear antigen, with lupus nephritis (class II) before treatment …
Fetal Cell Microchimerism and Cancer: A Nexus of Reproduction, Immunology, and Tumor Biology
Authors: Lisa R. Kallenbach, Kirby L. Johnson, Diana W. Bianchi
Journal: Cancer Research (2011)

Abstract Fetal cell microchimerism (FCM) is the persistence of fetal cells in the maternal circulation and organs following pregnancy. Proposed hypotheses about the function of fetal cells in the pathogenesis of maternal cancer include promotion of tumorigenesis, protection by providing immunosurveillance, and participation in tissue repair. To date, studies of FCM and cancer have been primarily descriptive and quantitative. More research is needed to understand the cellular phenotype of the microchimeric cells in maternal tumors and whether they have a functional role. This research will require further study using a multidisciplinary approach, incorporating knowledge of the fetomaternal relationship, tumor biology, immunology, and clinical oncology. Cancer Res; 71(1); 8–12. ©2011 AACR.
Determinants of fast- and slow-pathway conduction in patients with dual atrioventricular nodal pathways.
Authors: D Wu, P Denes, R Dhingra, C Wyndham, K M Rosen
Journal: Circulation Research (1975)

Electrophysiological studies were performed in two patients with documented paroxysmal supraventricular tachycardia and dual atrioventricular (AV) nodal pathways as defined by the atrial extra-stimulus technique. Both patients manifested two ranges of A-H intervals (AV nodal conduction times) at critical cycle lengths, reflecting fast- and slow-pathway conduction. The occurrence of fast- and slow-pathway conduction at the same cycle length depended on a long fast-pathway effective refractory period relative to the spontaneous or driven cycle length. At critical cycle lengths with fast-pathway conduction, a shift to slow-pathway conduction could be induced by a premature atrial impulse falling within the effective refractory period of the fast pathway. Repetitive retrograde concealed conduction to the fast pathway then maintained antegrade slow-pathway conduction. Resumption of fast-pathway conduction was induced with premature atrial impulses falling within the effective refractory periods of both the fast and the slow pathways, allowing recovery of the fast pathway for antegrade conduction. Atrial echoes and AV nodal reentrant paroxysmal supraventricular tachycardia occurred when sufficient slow-pathway delay was achieved to allow recovery of the fast pathway for retrograde conduction.
Programmed cell death 4 loss increases tumor cell invasion and is regulated by miR-21 in oral squamous cell carcinoma
Authors: Patricia P Reis, Miranda Tomenson, Nilva K Cervigne, Jerry Machado, Igor Jurisica, Melania Pintilie, Mahadeo A Sukhai, Bayardo Perez-Ordonez, Reidar Grénman, Ralph W Gilbert, Patrick J Gullane, Jonathan C Irish, Suzanne Kamel-Reid
Journal: Molecular Cancer (2010)

Abstract Background The tumor suppressor Programmed Cell Death 4 ( PDCD4 ) has been found to be under-expressed in several cancers and associated with disease progression and metastasis. There are no current studies characterizing PDCD4 expression and its clinical relevance in Oral Squamous Cell Carcinoma (OSCC). Since nodal metastasis is a major prognostic factor in OSCC, we focused on determining whether PDCD4 under-expression was associated with patient nodal status and had functional relevance in OSCC invasion. We also examined PDCD4 regulation by microRNA 21 (miR-21) in OSCC. Results PDCD4 mRNA expression levels were assessed in 50 OSCCs and 25 normal oral tissues. PDCD4 was under-expressed in 43/50 (86%) OSCCs, with significantly reduced mRNA levels in patients with nodal metastasis ( p = 0.0027 ), and marginally associated with T3-T4 tumor stage ( p = 0.054 ). PDCD4 protein expression was assessed, by immunohistochemistry (IHC), in 28/50 OSCCs and adjacent normal tissues; PDCD4 protein was absent/under-expressed in 25/28 (89%) OSCCs, and marginally associated with nodal metastasis ( p = 0.059 ). A matrigel invasion assay showed that PDCD4 expression suppressed invasion, and siRNA-mediated PDCD4 loss was associated with increased invasive potential of oral carcinoma cells. Furthermore, we showed that miR-21 levels were increased in PDCD4-negative tumors, and that PDCD4 expression may be down-regulated in OSCC by direct binding of miR-21 to the 3'UTR PDCD4 mRNA. Conclusions Our data show an association between the loss of PDCD4 expression, tumorigenesis and invasion in OSCC, and also identify a mechanism of PDCD4 down-regulation by microRNA-21 in oral carcinoma. PDCD4 association with nodal metastasis and invasion suggests that PDCD4 may be a clinically relevant biomarker with prognostic value in OSCC.
Probe-based confocal laser endomicroscopy (pCLE) in chronic rejection after lung transplantation: A pilot study
Authors: Jonas Yserbyt, Dooms Christophe, Vos Robin, Dupont Lieven, Decramer Marc, Verleden Geert
Journal: European Respiratory Journal (2014)

Background . Bronchiolitis obliterans syndrome (BOS) remains a significant burden after lung transplantation (LTx). Histopathological diagnosis of BOS on transbronchial biopsies obtained during surveillance bronchoscopy is challenging, making it a clinical diagnosis based upon the absence of other causes of lung functional decline. pCLE is a novel imaging technique enabling real-time & in vivo visualization of the pulmonary acinus.   Methods . In this prospective, observational study, 24 lung transplant recipients were subjected to pCLE on the occasion of surveillance bronchoscopies during the first two years following LTx. Morphometrical data were analyzed for patients with and without BOS development over time.   Results . All patients developing BOS (n= 7) showed a mean decrease in FEV1 of 25% with a significant correlation between FEV1 decline and the change in the area of the alveolar openings at the level of the alveolar duct (AAD) (Pearson r=0.61; p=0.02). Morphometrical analysis showed a mean decrease of 26% in AAD and a mean increase of 9% in the thickness of the elastin framework surrounding the alveolar duct openings (TEF). In all patients without BOS (n=17), we noted a mean increase in FEV1 of 8% over time (p   Conclusion . Morphometrical analysis after pCLE in patients developing BOS, showed a decrease in AAD and a trend for an increase in TEF when compared to other patients. Whether these findings could be specific for BOS and if they represent an ultra-structural substrate for FEV1 decline, should be prospectively confirmed in a larger cohort.
Utility of cyst fluid CEA cut-off of 192ng/ml in the diagnosis of mucinous cysts of the pancreas
Authors: K. Oppong, J. Leeds, K. Elamin, V. Wadehra, R. Charnley, M. Nayar
Journal: Gut (2011)

<h3>Introduction</h3> The differentiation of mucinous from non-mucinous pancreatic cysts is important because of the malignant potential of the latter. EUS-FNA allows for high resolution imaging of pancreatic cysts as well as sampling for markers (CEA), cytology and a visual assessment of cyst content. The Cooperative cyst study found an elevated fluid CEA (&gt;192 ng/ml) to be the single most accurate test in correctly predicting mucinous cysts with a sensitivity of 73%. The CEA value of 192ng/ml has subsequently been widely adopted as a definitive cut-off value. <h3>Methods</h3> The aims of the present study were to assess the utility of a cut-off value of 192 ng/ml in differentiating mucinous from non-mucinous pancreatic cysts and to compare this to general EUS assessment. IPMN and mucinous cyst adenoma/adenocarcinoma (MCA and MCAC) were considered separately. The study population comprised all the patients undergoing EUS-FNA at a tertiary centre for assessment of suspected pancreatic neoplastic cysts between June 2003 and April 2010. <h3>Results</h3> During this period 267 procedures were performed on 235 individuals, of whom 71 had a definitive diagnosis (60 resection histology, 5 histology, 6 malignant cytology), cystic degeneration of pancreatic adenocarcinoma (3) being excluded. 68 patients (51 females), (78 procedures) formed the study group. There were 25 mucinous cyst adenomas (11 MCA, 14 MCAC). There were 22 IPMN (2 malignant) and 21 non-mucinous cysts. For MCA/MCAC using a cut-off of 192 ng/ml the sensitivity, specificity, accuracy and NPV of detecting a mucinous lesion were 62.5%, 94.4%, 79.4%, 73.9%. Combining EUS morphology, cytology and visual assessment of aspirate (mucoid/non-mucoid) gave figures of 100%, 70.8%, 86%, 100%. The combination was significantly more sensitive p=0.007, but no significant difference in specificity. ROC area under the curve was numerically greater 0.861 versus 0.785 (not significant). For the IPMN patients the cut-off 192 ng/ml showed a sensitivity of 20% in the diagnosis of IPMN. EUS diagnosis had a sensitivity of 85%. Sensitivity of aspirate appearance: 87%, cytology: 50%; combining fluid appearance, EUS and cytology: 93%. Comparing the performance of CEA 192 versus combination in differentiating IPMN from non-mucinous cyst, ROC curve area was 0.864 versus 0.623 p =0.02. <h3>Conclusion</h3> A CEA cut-off of 192 ng/ml demonstrated good specificity and moderate sensitivity in the diagnosis of MCA, however it performed poorly in the diagnosis of IPMN. Combining EUS, aspirate appearance and cytology was significantly more sensitive in diagnosing mucinous cysts with a very high NPV.
Detection of anti-colon antibodies in inflammatory bowel disease using human cultured colonic cells
Authors: J C W Lee, A M Cevallos, A Naeem, J E Lennard-Jones, M J G Farthing
Journal: Gut (1999)

Background Investigation of anti-colon antibodies may be simplified if a sensitive method and homogeneous source of antigen were available. Aims To examine the anti-colon antibody response using human colonic carcinoma cell lines as antigen. Subjects Patients with inflammatory bowel disease and other gastrointestinal disorders and healthy controls were studied. Methods Comparative enzyme linked immunosorbent assays (ELISAs) were performed to assess the value of whole Caco-2, HT-29, and LS-180 cells as antigen. The antigenic determinants of the immune response were characterised by western blot analysis. Results Sera demonstrated immunoreactivity against each of the cell lines, but different epitopes were recognised. Applying whole Caco-2 cells as antigen in an ELISA, the prevalence of anti-colon antibodies was significantly greater in patients with ulcerative colitis (36%) than Crohn’s disease (13%), other gastrointestinal disorders (13%) and healthy controls (0) (p&lt;0.05). The immune response was not associated with one predominant antigen. Conclusions Fixed whole cell ELISA is a simple and feasible method for studying the anti-colon antibody response. This response is non-specific, being directed against multiple antigens, and is likely to be an epiphenomenon of inflammatory bowel disease, more so for ulcerative colitis than Crohn’s disease.
423 TREATMENT WITH PIRFENIDONE PRODUCES AN IMPORTANT REDUCTION IN NECROINFLAMMATION SCORE, FIBROSIS INDEX AND INCREASED GENE EXPRESSION OF CB2 IN PATIENTS WITH LIVER CIRRHOSIS
Authors: L. Flores Contreras, A. Sandoval-Rodriguez, S. Lucano-Landeros, I. Arellano-Olivera, J. Armendariz-Borunda
Journal: Journal of Hepatology (2011)
Prevalence and predictors of rhinitis in Danish children and adolescents
Authors: C. S. Ulrik, M.‐L. von Linstow, V. Backer
Journal: Allergy (2000)

Background: The prevalence of self‐reported symptoms of allergic rhinitis is increasing in many countries, but the reasons for this trend are not well understood. Data from a 6‐year follow‐up study of a population sample of children and adolescents ( n =408), aged 7–17 years at enrolment in 1986, were analyzed to investigate the prevalence and predictors of self‐reported rhinitis. Methods: Case history was used to assess the presence or absence of rhinitis (sneezing and running or blocked nose not associated with a cold), asthma, and eczema. Pulmonary function, skin prick test reactivity, and airway responsiveness to histamine were measured in all participants; a screening test for IgE antibodies to common allergens (Magic Lite SQ, Allergy Screen, ALK, Denmark) was performed in 237 (58%) of the participants. Results: The point prevalence of rhinitis increased from the first to the second survey, 14% and 22%, respectively; 54 (13%) of the subjects reported rhinitis only at the second survey (new rhinitis). Confining the analysis to participants without symptoms of rhinitis at the first survey showed that self‐reported eczema (relative risk [RR] 2.3, 95% confidence interval [CI] 1.2–4.7), airway hyperresponsiveness (RR 2.5, CI 1.8–3.0), atopy to grass pollen (RR 2.6, CI 1.7–3.3), atopy to dog dander (RR 2.4, CI 1.6–3.3), and atopy to house‐dust mite (RR 2.7, CI 1.4–5.2) at the first survey predicted an increased risk of the presence of rhinitis at the second survey. A positive Allergy Screen test at enrollment was associated with an increased risk of self‐reported rhinitis at follow‐up (RR 2.4, CI 1.4–3.4). Conclusions: This longitudinal population study of children and adolescents showed an age‐related increase in the point prevalence of self‐reported rhinitis; furthermore, sensitization to common aeroallergens, airway hyperresponsiveness, and the presence of self‐reported eczema were significantly associated with an increased risk of subsequent development of rhinitis.