tbuckley/cabot-search huggingface dataset:
Atherosclerosis and liver inflammation induced by increased dietary cholesterol intake: a combined transcriptomics and metabolomics analysis
Authors: Robert Kleemann, Lars Verschuren, Marjan J van Erk, Yuri Nikolsky, Nicole HP Cnubben, Elwin R Verheij, Age K Smilde, Henk FJ Hendriks, Susanne Zadelaar, Graham J Smith, Valery Kaznacheev, Tatiana Nikolskaya, Anton Melnikov, Eva Hurt-Camejo, Jan van der Greef, Ben van Ommen, Teake Kooistra
Journal: Genome biology (2007)

Abstract Background Increased dietary cholesterol intake is associated with atherosclerosis. Atherosclerosis development requires a lipid and an inflammatory component. It is unclear where and how the inflammatory component develops. To assess the role of the liver in the evolution of inflammation, we treated ApoE*3Leiden mice with cholesterol-free (Con), low (LC; 0.25%) and high (HC; 1%) cholesterol diets, scored early atherosclerosis and profiled the (patho)physiological state of the liver using novel whole-genome and metabolome technologies. Results Whereas the Con diet did not induce early atherosclerosis, the LC diet did so but only mildly, and the HC diet induced it very strongly. With increasing dietary cholesterol intake, the liver switches from a resilient, adaptive state to an inflammatory, pro-atherosclerotic state. The liver absorbs moderate cholesterol stress (LC) mainly by adjusting metabolic and transport processes. This hepatic resilience is predominantly controlled by SREBP-1/-2, SP-1, RXR and PPARα. A further increase of dietary cholesterol stress (HC) additionally induces pro-inflammatory gene expression, including pro-atherosclerotic candidate genes. These HC-evoked changes occur via specific pro-inflammatory pathways involving specific transcriptional master regulators, some of which are established, others newly identified. Notably, several of these regulators control both lipid metabolism and inflammation, and thereby link the two processes. Conclusion With increasing dietary cholesterol intake the liver switches from a mainly resilient (LC) to a predominantly inflammatory (HC) state, which is associated with early lesion formation. Newly developed, functional systems biology tools allowed the identification of novel regulatory pathways and transcriptional regulators controlling both lipid metabolism and inflammatory responses, thereby providing a rationale for an interrelationship between the two processes.
Does the season at symptom onset influence the long-term severity of radiographic joint destruction in rheumatoid arthritis?
Authors: D P C de Rooy, M L E Andersson, R Knevel, T W J Huizinga, B Svensson, A H M van der Helm-van Mil
Journal: Annals of the Rheumatic Diseases (2012)

Season-associated environmental factors have been related to the onset of rheumatoid arthritis (RA) and the severity of joint complaints.1 ,2 A recent study demonstrated that the onset of arthritis symptoms during winter or spring was associated with more radiographic joint damage after 1 year.3 This led us to evaluate the influence of the season of symptom onset on long-term radiographic progression.

Six hundred and eighty-eight RA-patients, from the Leiden Early Arthritis Clinic (EAC) and 830 RA-patients from the Swedish BARFOT-study were included in the study.4 ,5 These cohorts were similar in the percentage of women patients, age, symptom duration, swollen joint count, C reactive protein and the percentage of anti-cyclic citrullinated protein antibody positive patients (data not shown). During a follow-up period of 5 and 7 years, a total of 6990 hands and feet x-ray sets were obtained and scored for joint damage according to the Sharp-van-der-Heijde method ( all …
Volatile organic compounds in the exhaled breath of young patients with cystic fibrosis
Authors: M. Barker, M. Hengst, J. Schmid, H-J. Buers, B. Mittermaier, D. Klemp, R. Koppmann
Journal: European Respiratory Journal (2006)

Inflammatory mediators in the exhaled breath are receiving growing medical interest as noninvasive disease markers. Volatile organic compounds have been investigated in this context, but clinical information and methodological standards are limited. The levels of ethane, propane, n-pentane, methanol, ethanol, 2-propanol, acetone, isoprene, benzene, toluene, dimethyl sulphide (DMS) and limonene were measured in repeated breath samples from 20 cystic fibrosis patients and 20 healthy controls (aged 8-29 yrs). Three end-exhaled and one ambient air sample were collected per person and analysed on a customised gas chromatography system. Intra-subject coefficients of variation ranged between 9 and 34%, and hydrocarbon breath levels were influenced by their inspired concentrations. The alveolar gradient for pentane was higher in cystic fibrosis patients than in healthy controls (0.36 versus 0.21 ppb) and inversely proportional to forced expiratory volume in one second; highest values were observed in patients with pulmonary exacerbations (0.73 versus 0.24 ppb). Cystic fibrosis patients also exhibited a lower output of DMS (3.9 versus 7.6 ppb). Group differences were not significant for ethane and the remaining substances. It was concluded that chemical breath analysis for volatile organic compounds is feasible and may hold potential for the noninvasive diagnosis and follow-up of inflammatory processes in cystic fibrosis lung disease.
Characterization of Left Atrial Activation in the Intact Human Heart
Authors: Vias Markides, Richard J. Schilling, Siew Yen Ho, Anthony W.C. Chow, D. Wyn Davies, Nicholas S. Peters
Journal: Circulation (2003)

Background— The patterns of activation of the human left atrium (LA), how they relate to atrial myocardial architecture, and their role in arrhythmogenesis remain largely unknown. Methods and Results— Left atrial endocardial activation was mapped in 19 patients with a percutaneous noncontact mapping system. Earliest endocardial breakthrough during sinus rhythm (SR) occurred more frequently in the septal (63%, principally posteroseptal) than anterosuperior (37%) LA and varied little with isoproterenol or high right atrial pacing rate. Regardless of site of breakthrough, LA activation was characterized in all patients by propagation around a variably complete line of functional conduction block, descending on the posterior wall from the roof, passing between the ostia of the superior and then inferior pulmonary veins (PVs) before turning septally, passing below the oval fossa, and merging further anteriorly with the septal mitral annulus. Examination of the myocardial architecture in 10 normal adult postmortem hearts revealed an abrupt change in subendocardial fiber orientation along a line following the same course. During episodes of focal initiation of atrial fibrillation (AF), interaction was observed between wavefronts entering the LA from PVs and this functional line of conduction block that resulted in LA macroreentry or formation of daughter wavefronts. Conclusions— The LA endocardium has complex but characteristic patterns of activation during sinus rhythm, pacing, and AF initiation by PV ectopy that are determined largely by the functional properties of atrial musculature. These findings have important implications for both pacing and ablative strategies for the prevention of initiation of AF.
Receptor activator of nuclear factor-κB ligand is a novel inducer of myocardial inflammation
Authors: Sangmi Ock, Jihyun Ahn, Seok Hong Lee, Hongryeol Park, Jang Won Son, Jae Gyun Oh, Dong Kwon Yang, Wang Soo Lee, Ho-Shik Kim, Jaerang Rho, Goo Taeg Oh, Evan Dale Abel, Woo Jin Park, Jeong-Ki Min, Jaetaek Kim
Journal: Cardiovascular Research (2012)

Although increased levels of myocardial receptor activator of nuclear factor (NF)-κB ligand (RANKL) have been reported in heart failure, the role of this pathway in mediating activation of inflammatory pathways during myocardial remodelling is less well understood. This study sought to determine the role of myocardial RANKL in regulating cytokine expression. A marked increase in RANKL expression occurred as early as 6h following transverse aortic constriction (TAC) in mouse hearts and persisted at 3 and 17 days. An increase in tumour necrosis factor-α (TNF-α), interleukin (IL)-1α, and IL-1β was observed in the hypertrophied hearts only at 3 or 17 days after TAC. Treatment with losartan significantly attenuated TAC-induced cardiac hypertrophy, in parallel with decreased expression of RANKL, TNF-α, IL-1α, and IL-1β. Furthermore, injection of a RANKL-neutralizing monoclonal antibody attenuated RANKL-induced cytokine expression. RANKL stimulated expression of TNF-α, IL-1α, and IL-1β in neonatal rat cardiomyocytes via activation of NF-κB. RANKL-induced NF-κB activation and expression of these cytokines were both attenuated when RANK, receptor for RANKL, or TRAF2 or TRAF6, adaptors for RANK, was silenced by siRNA. Furthermore, inhibitors of phospholipase C (PLC), protein kinase C (PKC), and inhibitor of κB kinase also significantly inhibited RANKL-induced cellular activities, but inhibitors of phosphatidylinositol 3-kinase, extracellular signal-regulated kinase, or p38 mitogen-activated protein kinase were without effect. Our data demonstrate for the first time that the pressure-overloaded myocardium generates RANKL, which induces TNF-α, IL-1α, and IL-1β production via a RANK–TRAF2/TRAF6–PLC–PKC–NF-κB-mediated autocrine mechanism.
Male-pattern alopecia and masculinity
Authors: J.L. BURTON, M.M. HALIM, GAY MEYRICK, W.D. JEANS, D. MURPHY
Journal: British Journal of Dermatology (1979)

Cutaneous processes which are thought to be influenced by androgenic stimulation include the development of male-pattern alopecia, terminal hair distribution, sebum excretion rate, maximal sweat secretion rate and skin thickness. We measured these indices in forty-eight normal men, together with muscle, fat and bone thickness and plasma testosterone. There was a significant correlation between hair density on the forearm, leg and chest, but no other significant correlations were found. We conclude that bald men are no more 'masculine' than those with good scalp hair growth, if masculinity is defined in terms of end-organ response to androgenic stimulation.
Dominant-Negative Fas Mutation Is Reversed by Down-expression of c-FLIP
Authors: Marie Bénéteau, Sophie Daburon, Jean-François Moreau, Jean-Luc Taupin, Patrick Legembre
Journal: Cancer Research (2007)

Fas triggering by agonistic antibodies or by its cognate ligand, FasL, induces apoptotic cell death, whereas mutation in the Fas death domain is associated with lymphoma progression. On prolonged culture in the presence of an agonistic anti-Fas antibody, we raised a Jurkat cell line resistant to agonistic antibodies but still sensitive to soluble FasL, which carried at the heterozygous state, a point mutation into the Fas death domain. Down-modulation of c-FLIP expression reversed the blockade of the Fas pathway. We show that the activation threshold for the Fas receptor is more easily overcome by multimeric FasL than by agonistic antibodies and that the increase of this threshold due to mutation in the Fas death domain can be overcome by acting on a downstream effector of the Fas signal, c-FLIP. These findings put forward a new approach to eradicate Fas-resistant tumor cells.
Association Between Vitiligo Extent and Distribution and Quality-of-Life Impairment
Authors: Jonathan I. Silverberg, Nanette B. Silverberg
Journal: JAMA Dermatology (2012)

To determine whether the extent, distribution, and duration of vitiligo are associated with impairment of specific aspects of quality of life.A prospective questionnaire-based study of 1541 adults with vitiligo.Online questionnaire.Affected body surface area (BSA), distribution and duration of vitiligo, associated symptoms, and quality of life using the Dermatology Life Quality Index (DLQI).Vitiligo had a negative effect on numerous aspects and the total score of the DLQI (mean [SD], 5.9 [5.5]). The DLQI scores in vitiligo were associated with an affected BSA of more than 25% (ordinal logistic regression; adjusted odds ratio, 2.17 [95% CI, 1.71-2.75; P<.001]) and number of body parts affected with vitiligo (P≤.009) but not laterality (P=.06) or duration of disease (P≥.54). Itching and/or burning skin occurred in a sizable percentage of vitiligo patients (35.1%) and were predicted by an affected BSA of more than 25% (adjusted odds ratio, 1.59 [95% CI, 1.26-2.01; P<.001]). Sexual dysfunction occurred in 18% of patients and was predicted by an affected BSA of more than 25% (adjusted odds ratio, 1.94 [95% CI, 1.44-2.61; P<.001]) and vitiligo lesions in the genital area (1.82 [1.30-2.53; P<.001]).Vitiligo extent is associated with increased quality-of-life impairment, including itching and sexual dysfunction. Moreover, different distributions of vitiligo lesions are associated with impairment of different aspects of quality of life.clinicaltrials.gov Identifier: NCT01401374
Genotype, phenotype: upstairs, downstairs in the family of cardiomyopathies
Authors: Kenneth R. Chien
Journal: Journal of Clinical Investigation (2003)

I loved Upstairs, Downstairs . . . you identify with the downstairs people while vicariously enjoying the life of the upstairs people. —Alistair Cooke, Host of Masterpiece Theatre Upstairs, Downstairs was beloved by a generation of Americans who became entranced by this classic story of an upstairs Edwardian family and its downstairs household. The series chronicled the daily repartee and tangled relationships between the upstairs and downstairs contingents, a tale laced with all of the ingredients of human complexity. Despite their diverse perspectives and backgrounds, the lives at 165 Eaton Place became entwined by their core values, conserved traits, and the shared challenges of the day. In terms of human biology, Upstairs, Downstairs was a classic saga of the interplay between genes and environment. In the family of human cardiomyopathies, another complex story is unfolding, this time around the divergent backgrounds and perspectives of clinical cardiology and molecular genetics. In this cardiological version of Upstairs, Downstairs, the theme is Genotype, Phenotype, and the initial storyline revolves around the precept that the primary determinant of the clinical phenotype is the molecular genotype. The clinical viewpoint has been underpinned by noninvasive analyses that can quantitatively assess differences in chamber volume, wall thickness, hypertrophy, systolic versus diastolic dysfunction, and outflow tract obstruction, leading to three clinical subtypes: hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and restrictive cardiomyopathy (RCM). The molecular viewpoint has been driven by: 1) the discovery of diverse cardiomyopathic genotypes, resulting in a detailed examination of the differential phenotypic effects of mutations in a myriad of sarcomeric and cytoskeletal genes, 2) cataloguing the effects of missense mutations by the severity of the charge change within a given disease gene, 3) evaluating differences between haploinsufficiency and missense mutations, and 4) correlating these diverse disease genotypes with differences in the severity, time of onset, and diversity of the cardiomyopathy phenotype. The theme of this early script is that there may be a specific set of molecular pathways
Mimeae: Opportunistic Pathogens
Authors: G. Sheldon Green
Journal: JAMA (1965)

Infections caused by bacteria of the tribe Mimeae were reviewed.<i>Mima polymorpha</i>or<i>Herellea vaginicola</i>was isolated by culture from 56 living patients and 9 autopsy cases, with pure cultures of these organisms from 11 living patients. Mimeae were found to be opportunistic pathogens with a highly variable degree of virulence. In three febrile patients, blood cultures yielded a pure growth of<i>H vaginicola</i>, establishing the apparent pathogenicity of these organisms. Many of the infections were associated with an iatrogenic portal of entry, such as an intravascular catheter, with over half of the 18 wound infections occurring in head- and neck-surgery cases. Sodium colistimethate, kanamycin sulfate, methenamine mandelate, and polymyxin B sulfate were found to be the most effective therapeutic agents.
Heterogeneity among characteristics of hypereosinophilic syndromes
Authors: Grzegorz Helbig, Andrzej Moskwa, Marek Hus, Krzysztof Woźniczka, Agata Wieczorkiewicz, Joanna Dziaczkowska-Suszek, Anna Soja, Aleksandra Bartkowska-Chrobok, Sławomira Kyrcz-Krzemień
Journal: Journal of Allergy and Clinical Immunology (2010)
The incidences of and consultation rate for lower extremity complaints in general practice
Authors: J M van der Waal
Journal: Annals of the Rheumatic Diseases (2005)

<b>Objective:</b> To estimate the incidence and consultation rate of lower extremity complaints in general practice. <b>Methods:</b> Data were obtained from the Second Dutch National Survey of General Practice, in which 195 general practitioners (GPs) in 104 practices recorded all contacts with patients during 12 consecutive months in computerised patient records. GPs classified the symptoms and diagnosis for each patient at each consultation according to the International Classification of Primary Care (ICPC). Incidence densities and consultation rates for different complaints were calculated. <b>Results:</b> During the registration period 63.2 GP consultations per 1000 person-years were attributable to a new complaint of the lower extremities. Highest incidence densities were seen for knee complaints: 21.4 per 1000 person-years for women and 22.8 per 1000 person-years for men. The incidence of most lower extremity complaints was higher for women than for men and higher in older age. <b>Conclusions:</b> Both incidences of and consultation rates for lower extremity complaints are substantial in general practice. This implies a considerable impact on the workload of the GP.
Comparing Screening Mammography for Early Breast Cancer Detection in Vermont and Norway
Authors: S. Hofvind, P. M. Vacek, J. Skelly, D. L. Weaver, B. M. Geller
Journal: JNCI Journal of the National Cancer Institute (2008)

Most screening mammography in the United States differs from that in countries with formal screening programs by having a shorter screening interval and interpretation by a single reader vs independent double reading. We examined how these differences affect early detection of breast cancer by comparing performance measures and histopathologic outcomes in women undergoing opportunistic screening in Vermont and organized screening in Norway. We evaluated recall, screen detection, and interval cancer rates and prognostic tumor characteristics for women aged 50–69 years who underwent screening mammography in Vermont (n = 45 050) and in Norway (n = 194 430) from 1997 through 2003. Rates were directly adjusted for age by weighting the rates within 5-year age intervals to reflect the age distribution in the combined data and were compared using two-sided Z tests. The age-adjusted recall rate was 9.8% in Vermont and 2.7% in Norway ( P < .001). The age-adjusted screen detection rate per 1000 woman-years after 2 years of follow-up was 2.77 in Vermont and 2.57 in Norway ( P = .12), whereas the interval cancer rate per 1000 woman-years was 1.24 and 0.86, respectively ( P < .001). Larger proportions of invasive interval cancers in Vermont than in Norway were 15 mm or smaller (55.9% vs 38.2%, P < .001) and had no lymph node involvement (67.5% vs 57%, P = .01). The prognostic characteristics of all invasive cancers (screen-detected and interval cancer) were similar in Vermont and Norway. Screening mammography detected cancer at about the same rate and at the same prognostic stage in Norway and Vermont, with a statistically significantly lower recall rate in Norway. The interval cancer rate was higher in Vermont than in Norway, but tumors that were diagnosed in the Vermont women tended to be at an earlier stage than those diagnosed in the Norwegian women.
Asynchronous transmural perfusion during coronary reactive hyperaemia
Authors: H F. DOWNEY, G. J CRYSTAL, F. A BASHOUR
Journal: Cardiovascular Research (1983)

Journal Article Asynchronous transmural perfusion during coronary reactive hyperaemia Get access H FRED DOWNEY, H FRED DOWNEY From the Cardiovascular Research Laboratory at the Methodist Hospital and Departments of Physiology and Internal Medicine, University of Texas Health Science Center, Dallas, TX 75235 *Address for reprint requests: Dr H Fred Downey, Cardiovascular Research Laboratory, Methodist Hospital, PO Box 225999, Dallas, TX 75265, USA. Search for other works by this author on: Oxford Academic PubMed Google Scholar GEORGE J CRYSTAL, GEORGE J CRYSTAL From the Cardiovascular Research Laboratory at the Methodist Hospital and Departments of Physiology and Internal Medicine, University of Texas Health Science Center, Dallas, TX 75235 Search for other works by this author on: Oxford Academic PubMed Google Scholar FOUAD A BASHOUR FOUAD A BASHOUR From the Cardiovascular Research Laboratory at the Methodist Hospital and Departments of Physiology and Internal Medicine, University of Texas Health Science Center, Dallas, TX 75235 Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 17, Issue 4, April 1983, Pages 200–206, https://doi.org/10.1093/cvr/17.4.200 Published: 01 April 1983
Malignant pineal germ-cell tumors: An analysis of cases from three tumor registries
Authors: J. Lee Villano, Jennifer M. Propp, Kimberly R. Porter, Andrew K. Stewart, Tibor Valyi-Nagy, Xinyu Li, Herbert H. Engelhard, Bridget J. McCarthy
Journal: Neuro-Oncology (2008)

The exact incidence of pineal germ-cell tumors is largely unknown. The tumors are rare, and the number of patients with these tumors, as reported in clinical series, has been limited. The goal of this study was to describe pineal germ-cell tumors in a large number of patients, using data from available brain tumor databases. Three different databases were used: Surveillance, Epidemiology, and End Results (SEER) database (1973-2001); Central Brain Tumor Registry of the United States (CBTRUS; 1997-2001); and National Cancer Data Base (NCDB; 1985-2003). Tumors were identified using the International Classification of Diseases for Oncology, third edition (ICD-O-3), site code C75.3, and categorized according to histology codes 9060-9085. Data were analyzed using SAS/STAT release 8.2, SEER*Stat version 5.2, and SPSS version 13.0 software. A total of 1,467 cases of malignant pineal germ-cell tumors were identified: 1,159 from NCDB, 196 from SEER, and 112 from CBTRUS. All three databases showed a male predominance for pineal germ-cell tumors (>90%), and >72% of patients were Caucasian. The peak number of cases occurred in the 10- to 14-year age group in the CBTRUS data and in the 15- to 19-year age group in the SEER and NCDB data, and declined significantly thereafter. The majority of tumors (73%-86%) were germinomas, and patients with germinomas had the highest survival rate (>79% at 5 years). Most patients were treated with surgical resection and radiation therapy or with radiation therapy alone. The number of patients included in this study exceeds that of any study published to date. The proportions of malignant pineal germ-cell tumors and intracranial germ-cell tumors are in range with previous studies. Survival rates for malignant pineal germ-cell tumors are lower than results from recent treatment trials for intracranial germ-cell tumors, and patients that received radiation therapy in the treatment plan either with surgery or alone survived the longest.