tbuckley/cabot-search huggingface dataset:
Extracellular HSP60 induces inflammation through activating and up-regulating TLRs in cardiomyocytes
Authors: Jing Tian, Xin Guo, Xue-Mei Liu, Li Liu, Qi-Fang Weng, Shu-Juan Dong, Anne A. Knowlton, Wen-Jun Yuan, Li Lin
Journal: Cardiovascular Research (2013)

The molecular events leading from cardiomyocyte ischaemia to inflammatory cytokine production are not well understood. We previously found that heat shock protein 60 (HSP60) appeared in extracellular space after cardiomyocyte ischaemia. This study examined the activation and regulation of toll-like receptors (TLRs) by HSP60 in cardiomyocytes.Cytokine production and TLRs regulation mediated by TLRs signalling were examined in response to exogenous HSP60 (exHSP60) and endogenous HSP60 (enHSP60) released extracellularly under ischaemia. The results showed that exHSP60 induced inflammatory cytokine production in adult rat cardiomyocytes and H9c2 cells (a standard cardiac cell line derived from embryonic cells), through a pathway dependent on TLR4, myeloid differentiation factor 88 (MyD88), p38, and nuclear factor-κB (NF-κB). Further study revealed up-regulated expression of both TLR2 and TLR4 by exHSP60, which was dependent on the activation of TLR4, MyD88, c-Jun NH2-terminal kinase (JNK), and NF-κB, but not on p38. In myocytes exposed to ischaemia, enHSP60 was released into the media, and triggered cytokine production and TLR2/4 overexpression, through the same pathways as exHSP60. In rats subjected to LAD ligation, the released enHSP60 contributed to cytokine production and TLR2/4 overexpression in the ischaemic myocardium.Extracellular HSP60 induces cytokine production via TLR4-MyD88-p38/NF-κB pathway, and up-regulates TLR2/4 expression via TLR4-MyD88-JNK/NF-κB pathway. Both pathways contribute to myocardial inflammation induced by ischaemia.
The incidence of malignant melanoma in the United States: Issues as we approach the 21st century
Authors: Darrell S. Rigel, Robert J. Friedman, Alfred W. Kopf
Journal: Journal of the American Academy of Dermatology (1996)

The risk of malignant melanoma developing in an American in the United States has now reached 1 in 87 (up more than 1800% since the 1930s). This rising incidence of malignant melanoma is, in fact, real because (1) it is not due to increased surveillance; (2) it is not due to better cancer-counting methods in general; (3) it is not due to changes in histologic diagnostic criteria; (4) it is being noted worldwide; and (5) most importantly, despite rising survival percentages, the mortality rate from malignant melanoma also continues to rise. On the basis of these trends, incidence rates for malignant melanoma will continue to rise for at least the next 10 to 20 years, although the demographics of those affected may change. Effective programs to improve public and professional education must be developed to enhance early clinical detection and behavioral changes. An establishment of a National Melanoma Registry is needed to more effectively assess the magnitude and impact of future incidence and the success of prevention program efforts into the next century.
High-Sensitivity Troponin T and N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) and Risk of Incident Heart Failure in Patients with CKD
Authors: Nisha Bansal, Amanda Hyre Anderson, Wei Yang, Robert H. Christenson, Christopher R. deFilippi, Rajat Deo, Daniel L. Dries, Alan S. Go, Jiang He, John W. Kusek, James P. Lash, Dominic Raj, Sylvia Rosas, Myles Wolf, Xiaoming Zhang, Michael G. Shlipak, Harold I. Feldman
Journal: Journal of the American Society of Nephrology (2014)

High-sensitivity troponin T (hsTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) strongly predict heart failure (HF) in the general population. However, the interpretation of levels of these biomarkers as predictors of HF is uncertain among patients with CKD. Here, we investigated whether hsTnT and NT-proBNP are associated with incident HF among patients with CKD. In a prospective cohort analysis, we studied 3483 people with CKD in the Chronic Renal Insufficiency Cohort (CRIC) Study recruited from June of 2003 to August of 2008 who were free of HF at baseline. We used Cox regression to examine the association of baseline levels of hsTnT and NT-proBNP with incident HF after adjustment for demographic factors, traditional cardiovascular risk factors, markers of kidney disease, pertinent medication use, and mineral metabolism markers. At baseline, hsTnT levels ranged from ≤5.0 to 738.7 pg/ml, and NT-proBNP levels ranged from ≤5 to 35,000 pg/ml. Compared with those who had undetectable hsTnT, participants in the highest quartile (>26.5 pg/ml) had a significantly higher rate of HF (hazard ratio, 4.77; 95% confidence interval, 2.49 to 9.14). Similarly, compared with those in the lowest NT-proBNP quintile (<47.6 pg/ml), participants in the highest quintile (>433.0 pg/ml) experienced a substantially higher rate of HF (hazard ratio, 9.57; 95% confidence interval, 4.40 to 20.83) [corrected]. In conclusion, hsTnT and NT-proBNP were strongly associated with incident HF among a diverse cohort of individuals with mild to severe CKD. Elevations in these biomarkers may indicate subclinical changes in volume and myocardial stress that subsequently contribute to clinical HF.
Psychiatric aspects of dermatitis artefacta
Authors: WALTER FABISCH
Journal: British Journal of Dermatology (1980)

Fifty patients with dermatitis artefacta were investigated psychiatrically over several years and twenty-sic of these were seen independently by a clinical psychologist. The psychological investigations suggest a personality structure characterized by inward-looking self-centered attitudes leading to increasing isolation. The psychiatric investigations suggest a background of emotional disturbances during the formative years and in later life often resulting in feelings of isolation and insecutity. The onset of dermatitis artefacta is very frequently related to definable precipitating events which vary according to age and life situations. The visible skin lesions can be understood as an attempt at non-verbal communication subserving an appeal function. Therapeutic methods and prognosis are discussed in some detail.
T helper 17 cells are involved in the local and systemic inflammatory response in community-acquired pneumonia
Authors: Marthe S Paats, Ingrid M Bergen, Wessel E J J Hanselaar, E Christine Groeninx van Zoelen, Henry A Verbrugh, Henk C Hoogsteden, Bernt van den Blink, Rudi W Hendriks, Menno M van der Eerden
Journal: Thorax (2013)

<h3>Background</h3> Recent findings in mouse models suggest that T helper (Th)17 cells, characterised by production of interleukin (IL)-17A and IL-22, are involved in the immunopathogenesis of pneumonia. <h3>Objective</h3> In this study, we aimed to identify the involvement of Th17 cells in human community-acquired pneumonia (CAP). <h3>Design</h3> Within 24 h of admission, T cells from peripheral blood (n=39) and bronchoalveolar lavage (BAL, n=20) of CAP patients and of 10 healthy individuals were analysed by intracellular flow cytometry for the production of various cytokines, including IL-17A and IL-22. Peripheral blood T cells were also analysed 7 and 30 days after admission. Th17 cytokine profiles were correlated with pneumonia severity index and microbial aetiology. <h3>Results</h3> In the BAL of CAP patients, proportions of IL-17A and IL-22 single positive, as well as IL-17A/IL-22 double positive CD4 T cells were significantly increased compared with healthy individuals. Significantly increased proportions of IL-17A/IL-22 double positive CD4 T cells in BAL were found in non-severe and severe CAP patients, as well as in pneumococcal and non-pneumococcal CAP. In the peripheral blood of CAP patients upon admission, we found significantly increased proportions of IL-17A/IL-22 double positive CD4 T cells. One week after admission, the proportions of these double positive cells were still significantly increased in CAP patients compared with healthy individuals. <h3>Conclusions</h3> These data indicate that Th17 cells are engaged in the local and systemic immune response in human pneumonia. Especially, IL-17A/IL-22 double positive Th17 cells may be involved in the immunopathogenesis of CAP.
Low tension studies of collagen fibres from ligaments of the human spine.
Authors: J S Shah, M I Jayson, W G Hampson
Journal: Annals of the Rheumatic Diseases (1977)

On polarization microscopy collagen fibres from human cadaveric anterior longitudinal, posterior longitudinal, and interspinous ligaments show a series of transmission and extinction bands. By observing changes in this pattern on rotating the polarizing stage and on rotating the fibres a crimped structure of the fibres was deduced and its parameters were calculated. From these data the force/strain behaviour of the fibres under low tension was calculated. This corresponded closely with the results from mechanical measurement. At the same time we documented alterations in the transmission and extinction patterns while under tensile load. The results suggest that it is the crimped structure that is responsible for the high extensibility of the collagen fibres under low tension. The initial extension is by deformity of the crimp segment. This avoids risk of tearing the collagen fibres.
Downstream resistance effects of intracoronary thrombosis in the stenosed canine coronary artery
Authors: M Mansaray
Journal: Cardiovascular Research (1999)

Objective: The presence is well established in unstable angina of intracoronary thrombosis in a stenosed epicardial coronary artery. The effects of the thrombus formation on the distal microcirculation are however still unclear. Methods: We adapted the Folts canine model of left circumflex coronary arterial stenosis and intracoronary thrombosis by the insertion of a pressure catheter distal to the stenosis and by the use of 15 μm radioactive microspheres for measurement of regional myocardial blood flow. This permitted measurement during circumflex artery occlusion of collateral flow, downstream vascular resistance and collateral resistance. Results: Distal circumflex resistance, obtained by dividing the distal circumflex coronary pressure gradient by the collateral flow, significantly increased with thrombosis (94.47±35.72 to 120.06±34.47; p=0.0018) mmHg/ml/min/g. Changes in collateral flow and resistance in the presence of thrombosis, during maximum ischaemic vasodilatation, were inconsistent. Conclusion: Thrombosis causes increased vascular resistance in the microcirculation distal to the site of injury. This may be of clinical relevance in unstable angina, characterised by episodes of thrombus growth and embolization, in which ischaemic episodes may be worsened by generalised downstream vascular changes.
Regulation of large coronary arteries.
Authors: M A Young, S F Vatner
Journal: Circulation Research (1986)

The majority of studies on the control of coronary artery vasoactivity have examined changes in coronary blood flow and coronary vascular resistance, indices that primarily reflect regulation of small arterioles and precapillary vessels. With the emergence of coronary artery vasospasm as a significant cause of angina pectoris, myocardial infarction, and sudden death, the control of large coronary artery caliber has assumed more significance. It is clear that resistance coronary vessels and large coronary arteries differ in response to both pharmacologic and physiologic stimuli. Vasodilation of large coronary arteries may occur by direct action of agents on the arterial smooth muscle or by the indirect action of receptor occupation, changes in blood flow, or liberation of endothelial factors. These indirect factors appear to contribute also to responses to agents that constrict coronary smooth muscle directly or through the autonomic nervous system. Furthermore, the mechanisms responsible for control of large coronary vessels in the normal circulation are likely to be profoundly different from those in the presence of diseased vessels. For example, several factors associated with coronary artery disease--elevated plasma cholesterol levels, endothelial disruption, atherosclerosis, vascular stenosis, and aggregated platelets--all have important actions on the control of large coronary arteries.
Antioxidants in adipose tissue and risk of myocardial infarction: the EURAMIC study
Authors: A.F.M. Kardinaal, P. van't Veer, Fj Kok, J. Ringstad, J. Gómez-Aracena, V.P. Mazaev, L. Kohlmeier, B.C. Martin, A. Aro, J.K. Huttunen, J.D. Kark, M. Delgado-Rodriguez, R.A. Riemersma, J.M. Martin-Moreno, F.J. Kok, J.K. Huttunen, L. Kohlmeier, J.M. Martin-Moreno, P. van 't Veer
Journal: The Lancet (1993)
Medical screening of older drivers is not evidence based
Authors: D. O'Neill
Journal: BMJ (2012)

Older drivers have an enviable crash record,1 but they also increase traffic safety among other generations: the risk of serious injury to children is halved if driven by grandparents rather than parents.2 Yet the belief that older drivers pose a disproportionate risk to other road users refuses to die. Disappointingly, a recent report from a UK parliamentary charity3 overstates the risk of older drivers and recommends training for them—an unnecessary measure of dubious value.4 Likewise, many jurisdictions demand medical screening of all older drivers5 with the tacit or active acquiescence of the medical profession.

Age related testing of drivers breaks almost every tenet of screening proposed by the World Health Organization. Doctors’ lack of resistance typifies a worrying lack of due diligence given that screening persists in the face of mounting evidence of an association with increased traffic fatalities among older road users.6 7 Multiple factors contribute to this professional lassitude. Traffic medicine is at the periphery of much clinical practice, and …
Large scale comparison of global gene expression patterns in human and mouse
Authors: Xiangqun Zheng-Bradley, Johan Rung, Helen Parkinson, Alvis Brazma
Journal: Genome biology (2010)

It is widely accepted that orthologous genes between species are conserved at the sequence level and perform similar functions in different organisms. However, the level of conservation of gene expression patterns of the orthologous genes in different species has been unclear. To address the issue, we compared gene expression of orthologous genes based on 2,557 human and 1,267 mouse samples with high quality gene expression data, selected from experiments stored in the public microarray repository ArrayExpress.In a principal component analysis (PCA) of combined data from human and mouse samples merged on orthologous probesets, samples largely form distinctive clusters based on their tissue sources when projected onto the top principal components. The most prominent groups are the nervous system, muscle/heart tissues, liver and cell lines. Despite the great differences in sample characteristics and experiment conditions, the overall patterns of these prominent clusters are strikingly similar for human and mouse. We further analyzed data for each tissue separately and found that the most variable genes in each tissue are highly enriched with human-mouse tissue-specific orthologs and the least variable genes in each tissue are enriched with human-mouse housekeeping orthologs.The results indicate that the global patterns of tissue-specific expression of orthologous genes are conserved in human and mouse. The expression of groups of orthologous genes co-varies in the two species, both for the most variable genes and the most ubiquitously expressed genes.
PTEN suppresses the oncogenic function of AIB1 through decreasing its protein stability via mechanism involving Fbw7 alpha
Authors: Chunhua Yang, Shujing Li, Miao Wang, Alan K Chang, Ying Liu, Feng Zhao, Liyun Xiao, Lin Han, Dao Wang, Shen Li, Huijian Wu
Journal: Molecular Cancer (2013)

Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a phosphatase having both protein and lipid phosphatase activities, and is known to antagonize the phosphoinositide 3-kinase/AKT (PI3K/AKT) signaling pathway, resulting in tumor suppression. PTEN is also known to play a role in the regulation of numerous transcription factors. Amplified in breast cancer 1 (AIB1) is a transcriptional coactivator that mediates the transcriptional activities of nuclear receptors and other transcription factors. The present study investigated how PTEN may regulate AIB1, which is amplified and/or overexpressed in many human carcinomas, including breast cancers.PTEN interacted with AIB1 via its phophatase domain and regulated the transcriptional activity of AIB1 by enhancing the ubiquitin-mediated degradation of AIB1. This process did not appear to require the phosphatase activity of PTEN, but instead, involved the interaction between PTEN and F-box and WD repeat domain-containing 7 alpha (Fbw7α), the E3 ubiquitin ligase involved in the ubiquitination of AIB1. PTEN interacted with Fbw7α via its C2 domain, thereby acting as a bridge between AIB1 and Fbw7α, and this led to enhanced degradation of AIB1, which eventually accounted for its decreased transcriptional activity. At the cell level, knockdown of PTEN in MCF-7 cells promoted cell proliferation. However when AIB1 was also knocked down, knockdown of PTEN had no effect on cell proliferation.PTEN might act as a negative regulator of AIB1 whereby the association of PTEN with both AIB1 and Fbw7α could lead to the downregulation of AIB1 transcriptional activity, with the consequence of regulating the oncogenic function of AIB1.
Gender Influences the Class III and V β-Tubulin Ability to Predict Poor Outcome in Colorectal Cancer
Authors: Marisa Mariani, Gian Franco Zannoni, Stefano Sioletic, Steven Sieber, Candice Martino, Enrica Martinelli, Claudio Coco, Giovanni Scambia, Shohreh Shahabi, Cristiano Ferlini
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Colorectal cancer is one of the deadliest diseases in Western countries. To predict the outcome of therapy, we assessed the role of class III (TUBB3) and class V β-tubulin (TUBB6) as predictive biomarkers. Experimental Design: Using immunohistochemistry and nanofluidics, the expression of TUBB3 and TUBB6 was assessed in two cohorts of 180 and 134 patients, respectively. The CYP17A1 RS743572 was genotyped to identify GG carriers with enhanced androgen levels. TUBB3 and TUBB6 were investigated in 22 colorectal cancer cell lines in basal conditions and after serum starvation, the latter serving as activator of this prosurvival pathway. To ascertain the role of androgen receptor (AR) in such regulation, we silenced AR and checked TUBB3 and TUBB6 expression and sensitivity to chemotherapy. Results: There was a link between poor survival, the expression of TUBB3/TUBB6, and AR only in females. Conversely, only in males carriers of the GG phenotype exhibited the worst outcome. Importantly, male cell lines were resistant to serum starvation and exhibited higher levels of TUBB6, thereby suggesting that the pathway is activated by androgens. In female cells this phenomenon was absent. In both genders, AR was the main driver of TUBB3/TUBB6 expression, as constitutive silencing of AR was associated with downregulation of TUBB3/TUBB6 expression and increased sensitivity to oxaliplatin and SN-38. Conclusions: The involvement of androgens in the TUBB3 pathway opens the way for clinical trials to assess the efficacy of antiandrogens for increasing the efficacy of chemotherapy in male colorectal cancer patients. Clin Cancer Res; 18(10); 2964–75. ©2012 AACR.
Population Genetic Analysis of the Uncoupling Proteins Supports a Role for UCP3 in Human Cold Resistance
Authors: A. M. Hancock, V. J. Clark, Y. Qian, A. Di Rienzo
Journal: Molecular Biology and Evolution (2010)

Production of heat via nonshivering thermogenesis (NST) is critical for temperature homeostasis in mammals. Uncoupling protein UCP1 plays a central role in NST by uncoupling the proton gradients produced in the inner membranes of mitochondria to produce heat; however, the extent to which UCP1 homologues, UCP2 and UCP3, are involved in NST is the subject of an ongoing debate. We used an evolutionary approach to test the hypotheses that variants that are associated with increased expression of these genes (UCP1 -3826A, UCP2 -866A, and UCP3 -55T) show evidence of adaptation with winter climate. To that end, we calculated correlations between allele frequencies and winter climate variables for these single-nucleotide polymorphisms (SNPs), which we genotyped in a panel of 52 worldwide populations. We found significant correlations with winter climate for UCP1 -3826G/A and UCP3 -55C/T. Further, by analyzing previously published genotype data for these SNPs, we found that the peak of the correlation for the UCP1 region occurred at the disease-associated -3826A/G variant and that the UCP3 region has a striking signal overall, with several individual SNPs showing interesting patterns, including the -55C/T variant. Resequencing of the regions in a set of three diverse population samples helped to clarify the signals that we found with the genotype data. At UCP1, the resequencing data revealed modest evidence that the haplotype carrying the -3826A variant was driven to high frequency by selection. In the UCP3 region, combining results from the climate analysis and resequencing survey suggest a more complex model in which variants on multiple haplotypes may independently be correlated with temperature. This is further supported by an excess of intermediate frequency variants in the UCP3 region in the Han Chinese population. Taken together, our results suggest that adaptation to climate influenced the global distribution of allele frequencies in UCP1 and UCP3 and provide an independent source of evidence for a role in cold resistance for UCP3.
SHORT-TERM AND LONG-TERM EFFECTS OF PITAVASTATIN AND SIMVASTATIN ON FASTING PLASMA GLUCOSE IN PATIENTS WITH PRIMARY HYPERLIPIDEMIA OR MIXED DYSLIPIDEMIA AND &amp;ge;2 RISK FACTORS FOR CORONARY HEART DISEASE
Authors: Vladimir Kryzhanovski, Mats Eriksson, Neil Hounslow, Craig Sponseller
Journal: Journal of the American College of Cardiology (2012)
Prognostic Significance of Partial Tandem Duplications of the <i>MLL</i> Gene in Adult Patients 16 to 60 Years Old With Acute Myeloid Leukemia and Normal Cytogenetics: A Study of the Acute Myeloid Leukemia Study Group Ulm
Authors: Konstanze Döhner, Karen Tobis, Regina Ulrich, Stefan Fröhling, Axel Benner, Richard F. Schlenk, Hartmut Döhner
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To evaluate the incidence and clinical significance of partial tandem duplications (PTDs) of the mixed lineage leukemia (MLL) gene in a large series of newly diagnosed adult patients (16 to 60 years old) with acute myeloid leukemia (AML) intensively treated within the multicenter treatment trials AML-HD93 and AML-HD98A. PATIENTS AND METHODS: Identification of MLL PTD was performed centrally using Southern blot analysis in pretreatment samples from 525 of 683 assessable patients. PTD was confirmed by polymerase chain reaction (PCR) and sequencing of the PCR products. RESULTS: MLL PTD was identified in none of the 129 patients with t(8;21), inv(16), and t(15;17); in 19 (7.7%) of 247 patients with normal karyotype; and in 10 (8.5%) of 119 patients with all other abnormalities, with 30 cases of t(11q23) excluded. In the group of patients with a normal karyotype, there was no difference in the presenting clinical features between the PTD-positive and the PTD-negative cases. Sixteen (89%) of the 18 assessable PTD-positive patients and 158 (78%) of the 203 PTD-negative patients achieved a complete remission. After a median follow-up time of 19 months, 11 of the 16 PTD-positive patients relapsed compared with 54 of the 158 PTD-negative patients; the median remission durations of the PTD-positive and the PTD-negative groups were 7.75 months and 19 months, respectively (P &lt; .001). Multivariate analysis identified the MLL PTD status as the single prognostic factor for remission duration. CONCLUSION: Within the subgroup of young adult AML patients with normal karyotype, MLL PTD is associated with short remission duration.