tbuckley/cabot-search huggingface dataset:
TCTP promotes glioma cell proliferation in vitro and in vivo via enhanced -catenin/TCF-4 transcription
Authors: X. Gu, L. Yao, G. Ma, L. Cui, Y. Li, W. Liang, B. Zhao, K. Li
Journal: Neuro-Oncology (2013)

The translationally controlled tumor protein (TCTP) is a multifunctional protein that plays important roles in immune responses, cell proliferation, tumorigenicity and cell apoptosis. Here, we examined the clinical value of TCTP in glioma patient survival and investigated the functional roles and mechanism of TCTP in glioma development. TCTP expression was determined through immunohistochemical staining, immunoblotting, and quantitative real-time PCR (qRT-PCR). TCTP or TCF-4 expression was silenced using short hairpin (sh) RNA. In vitro cell proliferation was detected using MTT, BrdU and colony formation assays, and in vivo tumor growth was performed using the xenograft model. TCTP/TCF-4/β-catenin association was detected using a co-immunoprecipitation (co-IP) assay. TCF-4 transcription activity was detected using a TOPflash/FOPflash report gene assay. Wnt/β-catenin-targeted gene expression was detected through Western blotting. TCTP protein levels were significantly elevated in high-grade gliomas compared with low-grade gliomas and normal brain tissues. Importantly, the expression of TCTP was significantly associated with poorer overall survival and disease-free survival, and TCTP also reduced the survival rate after treatment with radiotherapy and temozolomide (RT-TMZ) for glioma patients. The ectopic expression of TCTP enhanced glioma cell proliferation both in vitro and in vivo, whereas the knockdown of TCTP inhibited this effect. Similarly, the overexpression of TCTP increased β-catenin binding to TCF-4, TOPflash report gene transcription activity, and the expression of Wnt/β-catenin signaling target genes including c-Myc and cyclin D1; notably, the knockdown of TCTP reduced these effects. The knockdown of TCF-4 using shRNA rescued the enhanced cell proliferation induced by the overexpression of TCTP. TCTP is associated with reduced survival of glioma patients and induces glioma tumor growth through enhanced Wnt/β-catenin signaling.
Epithelial stress and structural remodelling in childhood asthma
Authors: I A Fedorov
Journal: Thorax (2005)

<b>Background:</b> In adult asthma the bronchial epithelium shows high expression of the epidermal growth factor receptor (EGFR) and the cyclin dependent kinase inhibitor, p21<sup>waf</sup>, linked to ongoing stress and injury. <b>Methods:</b> To determine if these are early markers of disease, sections of bronchial specimens obtained post mortem or by bronchoscopy from non-asthmatic (n = 7), moderate (n = 7), or severe (n = 9) asthmatic children aged 5–15 years were examined immunohistochemically. All severe and one moderately asthmatic children were receiving inhaled corticosteroids. <b>Results:</b> The lamina reticularis of the asthmatic biopsy sections was found to be thicker (p = 0.01) than normal with increased deposition of collagen III (p = 0.007); submucosal eosinophil numbers did not differ between groups. As in adults, there was an asthma-related increase in epithelial EGFR (p&lt;0.002) but there was no evidence of proliferation, with Ki67 being reduced (p = 0.001) and p21<sup>waf</sup> increased (p&lt;0.004). The thickness of the lamina reticularis was significantly correlated with epithelial EGFR (rho = 0.77, p&lt;0.001). <b>Conclusions:</b> These data provide evidence that, in asthmatic children, the epithelium is stressed or injured without significant eosinophilic inflammation. This change in the epithelial phenotype is associated with collagen deposition in the lamina reticularis, suggesting that the epithelial mesenchymal trophic unit is active early in, and may contribute to, the pathogenesis of asthma.
Preventive Care for Colorectal Cancer Survivors: A 5-Year Longitudinal Study
Authors: Claire F. Snyder, Craig C. Earle, Robert J. Herbert, Bridget A. Neville, Amanda L. Blackford, Kevin D. Frick
Journal: Journal of Clinical Oncology (2008)

To explore the mix of physician specialties that long-term survivors visit and how the mix relates to preventive care.Using the Surveillance, Epidemiology, and End Results-Medicare database, we conducted a retrospective, longitudinal study of stage I to III Medicare fee-for-service colorectal cancer patients diagnosed in 1997. We examined physician visits and preventive care each year for 5 years, starting 366 days postdiagnosis, and how preventive service receipt related to the physician mix seen: primary care provider (PCP) only, oncologist only, both, or neither.A total of 1,541 patients met the eligibility criteria (mean age, 76; 43% male; 85% white). During 5 years, PCP visits increased from a mean of 4.2 to 4.7 (P < .0001), and oncology visits decreased from 1.3 to 0.5 (P < .0001). Survivor care by PCPs only increased from 44% to 62%, whereas shared care by PCPs and oncologists dropped from 37% to 21% (P < .0001). Survivors who saw both PCPs and oncologists were most likely to receive influenza vaccination, mammograms, and cervical cancer screening; survivors who saw PCPs only were most likely to receive cholesterol screening and bone densitometry. Higher socioeconomic status was associated with increased influenza vaccination, mammograms, and cervical cancer screening (P < .05). Over time, there was a decrease in mammography and cervical cancer screening and an increase in influenza vaccination (P < .05).As oncologists become less involved in survivor care, cancer-related screening decreases significantly. These results support the need for survivorship care plans that explicitly outline the roles of PCPs and oncologists in sharing care for cancer survivors, and how these roles may change over time.
A Critical Reassessment of the Role of Mitochondria in Tumorigenesis
Authors: Antonio Salas, Yong-Gang Yao, Vincent Macaulay, Ana Vega, Ángel Carracedo, Hans-Jürgen Bandelt
Journal: PLoS Medicine (2005)

Mitochondrial DNA (mtDNA) is being analyzed by an increasing number of laboratories in order to investigate its potential role as an active marker of tumorigenesis in various types of cancer. Here we question the conclusions drawn in most of these investigations, especially those published in high-rank cancer research journals, under the evidence that a significant number of these medical mtDNA studies are based on obviously flawed sequencing results.In our analyses, we take a phylogenetic approach and employ thorough database searches, which together have proven successful for detecting erroneous sequences in the fields of human population genetics and forensics. Apart from conceptual problems concerning the interpretation of mtDNA variation in tumorigenesis, in most cases, blocks of seemingly somatic mutations clearly point to contamination or sample mix-up and, therefore, have nothing to do with tumorigenesis.The role of mitochondria in tumorigenesis remains unclarified. Our findings of laboratory errors in many contributions would represent only the tip of the iceberg since most published studies do not provide the raw sequence data for inspection, thus hindering a posteriori evaluation of the results. There is no precedent for such a concatenation of errors and misconceptions affecting a whole subfield of medical research.
Left ventricular mass and cardiovascular morbidity in essential hypertension: the MAVI study
Authors: Paolo Verdecchia, Giancarlo Carini, Antonio Circo, Emilio Dovellini, Ezio Giovannini, Michele Lombardo, Pasquale Solinas, Marco Gorini, Aldo Pietro Maggioni
Journal: Journal of the American College of Cardiology (2001)
Development and Validation of a Questionnaire to Assess Carbohydrate and Insulin-Dosing Knowledge in Youth With Type 1 Diabetes
Authors: Michaela B. Koontz, Leona Cuttler, Mark R. Palmert, MaryAnn O'Riordan, Elaine A. Borawski, Judy McConnell, Elizabeth O. Kern
Journal: Diabetes Care (2009)

OBJECTIVE The American Diabetes Association advocates insulin regimens for youth with type 1 diabetes that involve adjusting insulin dose based on carbohydrate intake and blood glucose level. Implementing these regimens requires knowledge about carbohydrate content of foods and subsequent calculations of insulin dose, skills that may be difficult to gauge in practice. Therefore, we sought to develop and validate a questionnaire, the PedCarbQuiz (PCQ), to assess carbohydrate and insulin-dosing knowledge in youth with type 1 diabetes. RESEARCH DESIGN AND METHODS After development by an expert panel, the PCQ was administered to 75 youth with type 1 diabetes or their parents. Reliability was assessed by Cronbach α and split-half testing. To assess validity, scores were correlated with A1C, expert assessments, parent educational level, and complexity of insulin regimen. RESULTS PCQ mean score was 87 ± 9.7% (range 42–98%). Cronbach α was 0.88, and correlation of split halves was 0.59 (P &amp;lt; 0.0001). Higher PCQ scores correlated significantly with lower A1C (r = −0.29, P = 0.01) and expert assessments (r = 0.56, P &amp;lt; 0.001). Scores were significantly higher in parents with college degrees than in those without (P = 0.01) and in participants with more complex insulin regimens (P = 0.003). CONCLUSIONS The PCQ is a novel, easily administered instrument to assess knowledge about carbohydrates and insulin dosing calculations. Initial analyses support the reliability and validity of the PCQ.
Is postmenopausal HRT a risk factor for adult-onset asthma?
Authors: A E Tattersfield
Journal: Thorax (2010)

long-term eradication, will minimise drug side effects and antibiotic resistance, but with the least possible upset to schooling, work and family life.Getting there will require every CF centre to participate in multicentre trials and the timely application of evidence to clinical practice.Who will join the ELITE?
Prognostic DNA Methylation Biomarkers in Ovarian Cancer
Authors: Susan H. Wei, Curtis Balch, Henry H. Paik, Yoo-Sung Kim, Rae Lynn Baldwin, Sandya Liyanarachchi, Lang Li, Zailong Wang, Joseph C. Wan, Ramana V. Davuluri, Beth Y. Karlan, Gillian Gifford, Robert Brown, Sun Kim, Tim H-M. Huang, Kenneth P. Nephew
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Aberrant DNA methylation, now recognized as a contributing factor to neoplasia, often shows definitive gene/sequence preferences unique to specific cancer types. Correspondingly, distinct combinations of methylated loci can function as biomarkers for numerous clinical correlates of ovarian and other cancers. Experimental Design: We used a microarray approach to identify methylated loci prognostic for reduced progression-free survival (PFS) in advanced ovarian cancer patients. Two data set classification algorithms, Significance Analysis of Microarray and Prediction Analysis of Microarray, successfully identified 220 candidate PFS-discriminatory methylated loci. Of those, 112 were found capable of predicting PFS with 95% accuracy, by Prediction Analysis of Microarray, using an independent set of 40 advanced ovarian tumors (from 20 short-PFS and 20 long-PFS patients, respectively). Additionally, we showed the use of these predictive loci using two bioinformatics machine-learning algorithms, Support Vector Machine and Multilayer Perceptron. Conclusion: In this report, we show that highly prognostic DNA methylation biomarkers can be successfully identified and characterized, using previously unused, rigorous classifying algorithms. Such ovarian cancer biomarkers represent a promising approach for the assessment and management of this devastating disease.
A prospective polysomnographic study on the evolution of complex sleep apnoea
Authors: W. Cassel, S. Canisius, H.F. Becker, S. Leistner, T. Ploch, A. Jerrentrup, C. Vogelmeier, U. Koehler, J. Heitmann
Journal: European Respiratory Journal (2011)

Complex sleep apnoea (CompSA) may be observed following continuous positive airway pressure (CPAP) treatment. In a prospective study, 675 obstructive sleep apnoea patients (mean age 55.9 yrs; 13.9% female) participated. Full-night polysomnography was performed at diagnosis, during the first night with stable CPAP and after 3 months of CPAP. 12.2% (82 out of 675 patients) had initial CompSA. 28 of those were lost to follow-up. Only 14 out of the remaining 54 patients continued to satisfy criteria for CompSA at follow-up. 16 out of 382 patients not initially diagnosed with CompSA exhibited novel CompSA after 3 months. 30 (6.9%) out of 436 patients had follow-up CompSA. Individuals with CompSA were 5 yrs older and 40% had coronary artery disease. At diagnosis, they had similar sleep quality but more central and mixed apnoeas. On the first CPAP night and at follow-up, sleep quality was impaired (more wakefulness after sleep onset) for patients with CompSA. Sleepiness was improved with CPAP, and was similar for patients with or without CompSA at diagnosis and follow-up. CompSA is not stable over time and is mainly observed in predisposed patients on nights with impaired sleep quality. It remains unclear to what extent sleep impairment is cause or effect of CompSA.
Testosterone Replacement in Hypogonadal Men With Type 2 Diabetes and/or Metabolic Syndrome (the TIMES2 Study)
Authors: T. Hugh Jones, Stefan Arver, Hermann M. Behre, Jacques Buvat, Eric Meuleman, Ignacio Moncada, Antonio Martin Morales, Maurizio Volterrani, Ann Yellowlees, Julian D. Howell, Kevin S. Channer
Journal: Diabetes Care (2011)

OBJECTIVE This study evaluated the effects of testosterone replacement therapy (TRT) on insulin resistance, cardiovascular risk factors, and symptoms in hypogonadal men with type 2 diabetes and/or metabolic syndrome (MetS). RESEARCH DESIGN AND METHODS The efficacy, safety, and tolerability of a novel transdermal 2% testosterone gel was evaluated over 12 months in 220 hypogonadal men with type 2 diabetes and/or MetS in a multicenter, prospective, randomized, double-blind, placebo-controlled study. The primary outcome was mean change from baseline in homeostasis model assessment of insulin resistance (HOMA-IR). Secondary outcomes were measures of body composition, glycemic control, lipids, and sexual function. Efficacy results focused primarily on months 0−6 (phase 1; no changes in medication allowed). Medication changes were allowed in phase 2 (months 6−12). RESULTS TRT reduced HOMA-IR in the overall population by 15.2% at 6 months (P = 0.018) and 16.4% at 12 months (P = 0.006). In type 2 diabetic patients, glycemic control was significantly better in the TRT group than the placebo group at month 9 (HbA1c: treatment difference, −0.446%; P = 0.035). Improvements in total and LDL cholesterol, lipoprotein a (Lpa), body composition, libido, and sexual function occurred in selected patient groups. There were no significant differences between groups in the frequencies of adverse events (AEs) or serious AEs. The majority of AEs (&amp;gt;95%) were mild or moderate. CONCLUSIONS Over a 6-month period, transdermal TRT was associated with beneficial effects on insulin resistance, total and LDL-cholesterol, Lpa, and sexual health in hypogonadal men with type 2 diabetes and/or MetS.
Follow-Up Study of Suicidal Patients Seen in Emergency Room Consultation
Authors: HOWARD M. BOGARD
Journal: American Journal of Psychiatry (1970)

The author describes a study of age, race, and sex distribution, psychiatric diagnoses, and subsequent dispositions of 138 attempted suicides. The large proportion (64.4 percent) of those returned home without arranged-for treatment and the high rate of repeat attempts suggest that present treatment is incomplete; a psychiatric-medical suicide care team is recommended as a possible solution.
RhoA Activation in Mesangial Cells by Mechanical Strain Depends on Caveolae and Caveolin-1 Interaction
Authors: Fangfang Peng, Dongcheng Wu, Alistair J. Ingram, Baifang Zhang, Bo Gao, Joan C. Krepinsky
Journal: Journal of the American Society of Nephrology (2006)

Increased intraglomerular pressure is an important hemodynamic determinant of glomerulosclerosis and can be modeled in vitro by exposing mesangial cells to cyclic mechanical strain. A previous study showed that RhoA mediates strain-induced production of fibronectin; herein is investigated the role of caveolae in RhoA activation. Cyclodextrin and filipin, agents that disrupt caveolae, abrogated strain-induced RhoA activation in mesangial cells. Caveolin-1 (cav-1), the defining protein of caveolae, was Y14 phosphorylated by strain, and this was inhibited by PP1, showing Src dependence. Strain also induced c-SrcY416 phosphorylation and hence activation. Strain increased RhoA association with cav-1, which was blocked by PP1. Cyclodextrin and filipin inhibited the strain-induced RhoA/cav-1 association, indicating dependence on caveolar structural integrity. Restoration of caveolae by coincubation of cyclodextrin with cholesterol rescued both RhoA activation and RhoA/cav-1 association in response to strain. Sucrose gradient detected a significant portion of RhoA in caveolae, with Src located exclusively in these domains. Finally, in cells that were infected with retrovirus that encodes the nonphosphorylatable cav-1 Y14A, RhoA/cav-1 association, RhoA activation, and fibronectin secretion in response to strain were abrogated. It is concluded that strain-induced RhoA activation depends on the integrity of caveolae and on physical association of cav-1 and RhoA. The phosphorylation of cav-1 at Y14 by Src kinases is required for this to occur. These studies define a novel function for cav-1 and caveolae as positive effectors of RhoA activation. Targeting caveolae thus may provide a new therapeutic option for glomerular sclerosis that is associated with elevated intraglomerular pressure.
Serial Magnetic Resonance Imaging of Microvascular Remodeling in the Infarcted Rat Heart
Authors: Christiane Waller, Karl-Heinz Hiller, Elke Kahler, Kai Hu, Matthias Nahrendorf, Sabine Voll, Axel Haase, Georg Ertl, Wolfgang Rudolf Bauer
Journal: Circulation (2001)

Alterations in the coronary circulation are important determinants of myocardial function. Few data are available, however, about microvascular changes in reactive hypertrophy. With MRI, serial determination of myocardial microcirculation after myocardial infarction (MI) is feasible.We quantitatively determined myocardial perfusion and relative intracapillary blood volume using an MRI technique. Infarct size, myocardial mass, and left ventricular volumes were determined with cine MRI. Rats were investigated at 8, 12, and 16 weeks after MI (mean MI size 24.1+/-2.0%) or sham operation. Vasodilation was induced by adenosine. In the infarcted group, maximum perfusion decreased significantly from 8 to 16 weeks (5.6+/-0.3 versus 3.5+/-0.2 mL. g(-1). min(-1), P<0.01) compared with sham animals (5.5+/-0.3 versus 5.0+/-0.2 mL. g(-1). min(-1), P=0.17). Myocardial mass increased significantly (559.1+/-20.8 mg at 8 weeks versus 690.9+/-42.7 mg at 16 weeks, P<0.05) compared with sham-operated animals (516.3+/-41.7 versus 549.2+/-32.3 mg). Basal relative intracapillary blood volume increased significantly to 15.7+/-0.5 vol% at 8 weeks after MI and remained elevated (16.8+/-0.6 vol%) at 16 weeks compared with 12.1+/-0.3 vol% (P<0.01) in sham-operated rats.Our results indicate that significant microvascular changes occur during cardiac remodeling. Hypoperfusion in the hypertrophied myocardium is related to an increase in vascular capacity, suggesting a compensatory vasodilatory response at the capillary level. These microvascular changes may therefore contribute to the development of heart failure.
Acute Coronary Syndrome and Khat Herbal Amphetamine Use
Authors: Waleed M. Ali, K.F. Al Habib, Ahmed Al-Motarreb, Rajvir Singh, Ahmad Hersi, Hussam Al Faleh, Nidal Asaad, Shukri Al Saif, Wael Almahmeed, Kadhim Sulaiman, Haitham Amin, Jawad Al-Lawati, Nizar Al Bustani, Norah Q. Al-Sagheer, Awad Al-Qahtani, Jassim Al Suwaidi
Journal: Circulation (2011)

The khat plant is a stimulant similar to amphetamine and is thought to induce coronary artery spasm. Khat is widely chewed by individuals originating from the Horn of Africa and the Arabian Peninsula. The aim of this study was to evaluate the clinical characteristics and outcome of khat chewers presenting with acute coronary syndrome.From October 1, 2008, through June, 30, 2009, 7399 consecutive patients with acute coronary syndrome were enrolled in the Second Gulf Registry of Acute Coronary Events (Gulf RACE-2). Nineteen percent of patients were khat chewers; 81% were not. Khat chewers were older, more often male, and less likely to have cardiovascular risk factors. Khat chewers were less likely to have a history of coronary artery disease and more likely to present late and to have higher heart rate and advanced Killip class on admission. Khat chewers were more likely to present with ST-segment-elevation myocardial infarction. Overall, khat chewers had higher risk of death, recurrent myocardial ischemia, cardiogenic shock, ventricular arrhythmia, and stroke compared with non-khat chewers. After adjustment for baseline variability, khat chewing was found to be an independent risk factor of death and for recurrent ischemia, heart failure, and stroke.Our data confirm earlier observations of worse in-hospital outcome among acute coronary syndrome patients who chew khat. This worse outcome persists up to 1 year from the index event. This observational report underscores the importance of improving education concerning the cardiovascular risks of khat chewing.
Renal Endothelin-1 and Endothelin Receptor Type B Expression in Glomerular Diseases with Proteinuria
Authors: INGO LEHRKE, RÜDIGER WALDHERR, EBERHARD RITZ, JÜRGEN WAGNER
Journal: Journal of the American Society of Nephrology (2001)

The endothelin (ET) system has been studied extensively in experimental models of progressive chronic renal disease, but there is limited information regarding the ET system in renal patients. First, the expression of human ET-1, as well as ET receptor type A (ET-RA) and ET-RB, was studied in 26 renal biopsies from patients with different renal diseases. Gene expression was assessed by quantitative reverse transcription-PCR. Second, ET-1 and ET-RB protein expression and localization were examined, by immunohistochemical analyses, among a homogeneous cohort of 16 patients with IgA nephropathy and different degrees of proteinuria. ET-RB mRNA expression was threefold higher among patients with higher-grade proteinuria [≥2 g/24 h, n = 10; OD ratio (ODR), i.e., wild-type/mutant mRNA ratio, 1.81 ± 0.3], compared with patients with lower-grade proteinuria (<2 g/24 h, n = 8; ODR, 0.63 ± 0.1; P < 0.01) or control subjects (n = 9; ODR, 0.57 ± 0.1; P < 0.01). ET-1 gene expression was significantly higher among patients with higher-grade proteinuria, compared with patients with lower-grade proteinuria (P < 0.01) or control subjects (P < 0.05). ET-RA mRNA expression was not different among the groups. Patients with higher-grade proteinuria who were receiving angiotensin-converting enzyme inhibitors exhibited significantly (P < 0.05) lower ET-1 and ET-RB mRNA expression, which was comparable to that of control subjects. By using immunohistochemical analyses, an association between proteinuria and expression of ET-1 and ET-RB in proximal tubular epithelial cells and of ET-1 in glomeruli was confirmed in the separate cohort of patients with IgA nephropathy. It is concluded that the increased ET-RB and ET-1 mRNA and protein expression observed in animal models of renal disease is also demonstrable among patients with renal disease and high-grade proteinuria.