tbuckley/cabot-search huggingface dataset:
Evidence that bone mineral density plays a role in degenerative disc disease: the UK Twin Spine Study
Authors: Gregory Livshits, Sergey Ermakov, Maria Popham, Alex J MacGregor, Philip N Sambrook, Timothy D Spector, Frances M K Williams
Journal: Annals of the Rheumatic Diseases (2010)

Objective Osteoarthritis (OA) and osteoporosis are often considered to lie at opposite ends of a spectrum of bone phenotypes. Lumbar degenerative disc disease (LDD) may be associated with low back pain (LBP) and is similar in many ways to OA. LDD is reported in small studies to be associated with increased spine bone mineral density (BMD). The present work aimed to confirm this association in a large population sample using MRI and explore the relationship further, in particular to determine whether it is mediated genetically. Methods A population based sample (N=908, age range 32–74 years) of UK female twins having MRI of the lumbar spine was used in this study. LDD traits and summary measures and their relationship with BMD at the lumbar spine and hip were examined using multivariate multiple regression and maximum likelihood based variance decomposition. Results There was a significant positive correlation between LDD and BMD at the lumbar spine and hip, which remained significant after adjustment for confounders. Both traits were highly heritable and the associations between them were mediated genetically. Conclusions A clear, significant and independent association of BMD at hip and lumbar spine with LDD was found which is, in part, genetically mediated. The association with the non-axial site, the hip, is of particular interest and suggests a systemic bone effect. This should encourage the search for pleiotropic genes to help in the understanding of the bone–cartilage relationship. Moreover, genetic variants identified could provide novel therapeutic targets in the management of LBP.
Community-acquired methicillin-resistant Staphylococcus aureus in Switzerland : first surveillance report
Authors: C Aramburu, S Harbarth, N Liassine, M Girard, A Gervaix, J Scherenzel, G Renzi, P Sudre
Journal: Eurosurveillance (2006)

Methicillin-resistant Staphylococcus aureus (MRSA) is an emerging community pathogen. Community-acquired MRSA (CA-MRSA) has been associated with virulent strains producing Panton-Valentine leukocidin (PVL) and a variety of other exotoxins. In Geneva, PVL-producing CA-MRSA was first reported in 2002 and a surveillance system based on voluntary reporting was set up. Each MRSA-positive culture result with an antibiotic resistance profile different from the endemic strain prevailing in the Geneva healthcare setting diagnosed in a patient without a history of hospital admission in the previous 12 months was notified to the local health department. A questionnaire was completed by the attending physician with demographic, clinical and exposure information. From January 2002 until December 2004, data on 58 cases were reported, including 26 cases grouped in 13 distinct transmission clusters. Most were family related and for two of them, colonisation persisted over a 12 month period despite treatment. Thirty three patients (57%) were male. Median age was 32 years, 22% being younger than 10 years. Forty one cases (71%) were infected and 17 (29%) colonised. Symptomatic skin lesions such as furunculosis, impetigo or abscess were present in 40 (97%) of the 41 infected cases. Most cases had no underlying disease. Thirty eight cases (65%) had travelled abroad. Forty (69%) of 58 isolates carried the PVL toxin. CA-MRSA infections in Geneva appear to be an emerging problem in the canton. Surveillance should continue and should possibly be extended to other parts of the country to better describe transmission patterns and the spread of this pathogen. Prevention and control of CA-MRSA infections represent a challenge for the future, requiring contact tracing, education and treatment of infected and colonised contacts.
Tumor-Selective Induction of Apoptosis and the Small-Molecule Immune Response Modifier Imiquimod
Authors: M. Schon, A. B. Bong, C. Drewniok, J. Herz, C. C. Geilen, J. Reifenberger, B. Benninghoff, H. B. Slade, H. Gollnick, M. P. Schon
Journal: JNCI Journal of the National Cancer Institute (2003)

Background: The incidence of nonmelanoma skin cancer, basal cell carcinomas (BCCs), and squamous cell carcinomas (SCCs) is increasing, representing a major medical and economic problem. Imiquimod, a topical small-molecule immune response modifier, has shown efficacy toward BCC and actinic keratoses in clinical trials. Imiquimod acts both indirectly, via cytokine-mediated stimulation of cellular immune responses, and directly, through unknown mechanisms against tumor cells. We examined the mechanism by which imiquimod induces apoptosis in cancer cells. Methods: Apoptosis was assessed by enzyme-linked immunosorbent assay, western blot analysis, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assays in five SCC cell lines, HaCaT cells (a spontaneously immortalized human keratinocyte cell line), and normal keratinocytes treated with imiquimod, with its analog resiquimod, or with neither. Expression of death receptors, caspases, and cytochrome c in the apoptotic signaling cascade was analyzed using western blot and flow cytometric analyses. The functional relevance of imiquimod-induced cytochrome c release was assessed by transfection of HaCaT cells with Bcl-2. Apoptosis in BCCs in vivo was assessed by TUNEL assays of imiquimod-treated and untreated tumors from three patients. Differences between treated and untreated cells and tumors were determined using a two-tailed Student’s t test. Results: Imiquimod, but not resiquimod, induced apoptosis in all SCC cell lines and HaCaT cells. This induction involved activation of several caspases and Bcl-2–dependent cytosolic translocation of cytochrome c but was independent of the membrane-bound death receptors Fas, tumor necrosis factor–related apoptosis-inducing ligand (TRAIL)-R1–R4 receptors, and tumor necrosis factor-R1 and -R2 receptors. Topical application of imiquimod to BCC tumors in vivo induced apoptosis. Conclusion: Imiquimod has the potential to induce apoptosis in skin cancer cells, possibly by circumventing mechanisms developed by malignant tumors to resist apoptotic signals.
P97 Do intravenous antibiotics influence arterial stiffness in adults with cystic fibrosis?
Authors: J. H. Hull, R. Garrod, T. B. Ho, R. K. Knight, J. R. Cockcroft, D. J. Shale, C. E. Bolton
Journal: Thorax (2010)

<h3>Introduction and objectives</h3> Adults with cystic fibrosis (CF) have evidence of increased arterial stiffness which is associated with a chronic systemic inflammatory status (1). We hypothesised that an intervention which decreased inflammation in patients with CF would improve arterial stiffness and we therefore evaluated a 2-week course of intravenous antibiotics on large artery haemodynamics in adults with CF. <h3>Methods</h3> We recruited 18 adult patients with CF immediately preceding (visit 1) and following 14 days of intravenous antibiotics (visit 2); prompted by clinical indication. Arterial stiffness was determined by supine applanation tonometry to obtain augmentation index (AIx) which was heart rate adjusted, and aortic pulse wave velocity (aPWV) (SphygmoCor). In addition, heart rate (HR), blood pressure (BP), spirometry and CRP were measured. <h3>Results</h3> Complete data was available for 15 patients (n=3 not suitable); mean (SD) age 28 (6) years and BMI 21.2 (2.4) kg/m<sup>2</sup>. All but one patient reported symptomatic improvement following treatment. Percent predicted forced expiratory volume in one second (FEV<sub>1</sub>) improved and CRP was reduced at visit 2 (Abstract P97 Table 1). There was a trend towards reduction in HR (p=0.06) whilst peripheral and central BP and aPWV were similar between visits. However, of particular note, HR adjusted AIx was reduced (Abstract P97 Table 1). The change in AIx was related to FEV<sub>1</sub> % predicted (r=0.77) and BMI (r=0.71) at visit 1 (both p&lt;0.01), but not CRP (p=0.13). <h3>Conclusions</h3> Intervention with intravenous antibiotics in adults with CF is associated with a reduction in AIx, a composite measure of systemic arterial stiffness and wave reflection. Modulation of systemic inflammation results in beneficial haemodynamic changes that may be key in maintaining cardiovascular health in adults with CF.
Transforming growth factor–β: The elusive hepatic chalone?
Authors: Alastair J. Strain
Journal: Hepatology (1992)

Incubation of fetal rat hepatocytes (FRH) with transforming growth factor β1 (TGF-β1) resulted in growth arrest and a biphasic effect on epidermal growth factor (EGF) receptor. After 2 h of exposure, EGF receptor (EGFR) was reduced by 43%. From 6 to 24 h, TGF-β1 exposure resulted in progressive increase in EGFR up to 74% over control. The increased binding was due to increase in high affinity EGF binding sites. FRH grown in medium containing EGF exhibited down-regulated EGFR with loss of high affinity EGF binding sites. With TGF-β1 exposure, high affinity EGFR was not down-regulated by EGF. Since downregulation of EGFR involves internalization, the kinetics of EGF receptor-mediated endocytosis were examined. In TGF-β1 exposed FRH, EGF endocytosis was inhibited, with a reduction in the first order rate constant for the process from 0.078 to 0.043 min−1. Despite inhibition of growth, receptor downregulation, and EGF endocytosis after TGF-β1 exposure, EGF-induced receptor autophosphorylation was preserved as demonstrated by [32P]phosphatelabeling of immunoprecipitated EGFR. These observations provide direct evidence that TGF-β1 regulates growth of fetal cells. Further, they suggest that TGF-β1 regulates endocytosis of EGF and possibly of other ligands.
Increased sputum amino acid concentrations and auxotrophy of Pseudomonas aeruginosa in severe cystic fibrosis lung disease
Authors: S. R Thomas
Journal: Thorax (2000)

<h3>BACKGROUND</h3> <i>Pseudomonas aeruginosa</i> may undergo a phenotypic change from the wild (prototrophic) type to an auxotrophic phenotype in the course of respiratory infection in patients with cystic fibrosis. The clinical significance of this is unclear. A study was undertaken to investigate whether the presence of auxotrophs of <i>P aeruginosa</i> in the sputum of patients with cystic fibrosis correlated with severity of respiratory disease, and whether increased sputum concentrations of amino acids were associated with the emergence of these forms. <h3>METHODS</h3> Sixty adult patients with cystic fibrosis, colonised by <i>P aeruginosa</i>, were recruited and baseline clinical data including lung function were recorded. Serial sputum samples were obtained before, during, and after infective exacerbations where possible. These samples were used for routine microbiological culture, assessment of auxotrophy of <i>P aeruginosa</i>, measurement of amino acid content, and neutrophil elastase assay. <h3>RESULTS</h3> Auxotrophy was common in patients with cystic fibrosis and 20 (33%) had a mean percentage auxotroph count of more than 50% total cfu/ml. The mean percentage auxotroph count was inversely correlated with forced expiratory volume in one second (FEV<sub>1</sub>; τ = –0.194, p = 0.031). The median sputum amino acid concentration of the group was 12.5 mmol/l (range 0.13–40.6). The mean amino acid concentration in 33 subjects during infective exacerbations was 18.2 mmol/l (95% CI 15.1 to 21.3) compared with 12.3 mmol/l (95% CI 9.8 to 14.8) when well (p = 0.001). The amino acid content of sputum was inversely correlated with FEV<sub>1</sub> (τ = –0.253, p = 0.005). <h3>CONCLUSIONS</h3> <i>P aeruginosa</i> frequently exhibits auxotrophy in patients with cystic fibrosis, particularly in those with severe underlying pulmonary disease. The sputum amino acid content of patients with cystic fibrosis is high during infective exacerbations and correlates with pulmonary disease severity.
Anandamide Decreases Glomerular Filtration Rate through Predominant Vasodilation of Efferent Arterioles in Rat Kidneys
Authors: Yukako Koura, Atsuhiro Ichihara, Yuko Tada, Yuki Kaneshiro, Hirokazu Okada, Constance J. Temm, Matsuhiko Hayashi, Takao Saruta
Journal: Journal of the American Society of Nephrology (2004)

For determining the effects of anandamide (ANA) on renal hemodynamics and microcirculation, a clearance study was performed in Sprague-Dawley rats that received injections of ANA in doses of 15, 150, and 1500 pmol/kg. At doses up to 150 pmol/g, ANA significantly decreased GFR and increased renal blood flow (RBF) without affecting mean arterial pressure (MAP). In the presence of the cannabinoid type 1 (CB1) receptor antagonist AM251, only the 15-pmol/kg dose significantly increased GFR and RBF without altering MAP, with higher doses having no effect on GFR, RBF, or MAP. By contrast, AM281, which antagonizes cannabinoid receptors nonselectively, inhibited the GFR, RBF, and MAP responses to ANA. The arteriolar responses to ANA were also assessed in vitro by the blood-perfused juxtamedullary nephron technique. Higher doses of ANA significantly increased the diameter of both afferent and efferent arterioles, whereas lower doses elicited predominant efferent arteriolar dilation. AM251 attenuated the afferent arteriolar response to ANA and inhibited the efferent arteriolar response to ANA, whereas AM281 inhibited the responses in both arterioles. The CB1 receptor mRNA was expressed in afferent arterioles, and immunohistochemical staining demonstrated the presence of CB1 receptors in both afferent and efferent arterioles. These results suggest that ANA causes afferent arteriolar dilation via both CB1 and non-CB1 receptors and greater efferent arteriolar dilation via CB1 receptors, resulting in a decreased GFR and an increased RBF without affecting MAP.
Thiazolidenediones Mediate Apoptosis in Prostate Cancer Cells in Part through Inhibition of Bcl-xL/Bcl-2 Functions Independently of PPARγ
Authors: Chung-Wai Shiau, Chih-Cheng Yang, Samuel K. Kulp, Kuen-Feng Chen, Chang-Shi Chen, Jui-Wen Huang, Ching-Shih Chen
Journal: Cancer Research (2005)

Certain members of the thiazolidenedione family of the peroxisome proliferator-activated receptor gamma (PPARgamma) agonists, such as troglitazone and ciglitazone, exhibit antitumor effects; however, the underlying mechanism remains inconclusive. This study shows that the effect of these thiazolidenedione members on apoptosis in prostate cancer cells is independent of PPARgamma activation. First, close structural analogues of thiazolidenediones, whereas devoid of PPARgamma activity, retain the ability to induce apoptosis with equal potency. Second, both PC-3 (PPARgamma-expressing) and LNCaP (PPARgamma-deficient) cells are sensitive to apoptosis induction by troglitazone and its PPARgamma-inactive analogue irrespective of their PPARgamma expression status. Third, rosiglitazone and pioglitazone, potent PPARgamma agonists, show marginal effects on apoptosis even at high concentrations. Evidence indicates that the apoptotic effect of troglitazone, ciglitazone, and their PPARgamma-inactive analogues 5-[4-(6-hydroxy-2,5,7,8-tetramethyl-chroman-2-ylmethoxy)-benzylidene]-2,4-thiazolidine-dione (Delta2-TG) and 5-[4-(1-methyl-cyclohexylmethoxy)-benzylidene]-thiazolidine-2,4-dione, respectively, is in part attributable to their ability to inhibit the anti-apoptotic functions of Bcl-xL and Bcl-2. Treatment of PC-3 cells with troglitazone or Delta2-TG led to reduced association of Bcl-2 and Bcl-xL with Bak, leading to caspase-dependent apoptosis. Bcl-xL overexpression protects LNCaP cells from apoptosis induction by troglitazone and Delta2-TG in an expression level-dependent manner. Considering the pivotal role of Bcl-xL/Bcl-2 in regulating mitochondrial integrity, this new mode of mechanism provides a framework to account for the PPARgamma-independent action of thiazolidenediones in inducing apoptosis in cancer cells. Moreover, dissociation of these two pharmacologic activities provides a molecular basis to develop novel Bcl-xL/Bcl-2 inhibitors, of which the proof of principle is illustrated by a Delta2-TG analogue with potent in vivo antitumor activities.
Respiratory Chlamydophyla pneumoniae resides primarily in the lower airway
Authors: F. Wang, P.G. Gibson
Journal: European Respiratory Journal (2011)

From the authors:

We thank W.C. Webley and D.L. Hahn for their correspondence regarding our article [1]. In our study, we hypothesised that Chlamydophyla pneumoniae infection may be an aetiological agent for noneosinophilic forms of asthma and sought to test this hypothesis using a sensitive and validated PCR for C. pneumoniae . We did not detect C. pneumoniae and concluded that C. pneumoniae infection was unlikely to be the cause of noneosinophilic asthma. We stand by these results because we studied a large number of subjects, who were carefully classified into inflammatory asthma phenotypes and who were assessed using valid methods. Induced sputum samples material from the lower airways, as evidenced by the recovery of pulmonary macrophages …
Tetralogy of Fallot: postoperative electrophysiologic studies.
Authors: W H Neches, S C Park, R A Mathews, C C Lenox, J Marin-Garcia, J R Zuberbuhler
Journal: Circulation (1977)

Electrophysiologic studies performed during postoperative cardiac catheterization in 51 patients following repair of tetralogy of Fallot (TF) were compared with studies performed in a control group of 30 patients. These studies include His bundle electrograms, measurement of atrioventricular (A-V) conduction at progressively increasing atrial pacing rates, and evaluation of sinus node recovery time. More postoperative TF patients (20%) had prolonged H-V intervals compared to the controls (7%). With atrial pacing, no patient in the control group developed second degree A-V block below 160 beats/min, while 23% of the postoperative TF patients developed block below this level. Half of these patients had normal His bundle studies. Stress of the A-V conduction system by atrial pacing may unmask conduction abnormalities not present on the surface electrocardiogram or on His bundle electrogram. Two-thirds of the patients had some form of conduction abnormality on the basis of evaluation of one or more parameters but about half of the patients with a given abnormality had normal findings in other areas. The high incidence of electrophysiologic abnormalities following TF repair may have future prognostic significance. Systematic evaluation of atrioventricular conduction during preoperative and postoperative cardiac catheterization may be of value.
The History and Empirical Status of Key Psychoanalytic Concepts
Authors: Lester Luborsky, Marna S. Barrett
Journal: Annual Review of Clinical Psychology (2005)

Over the past century, the ideas set out in psychoanalytic theory have permeated the field of psychology as well as literature, art, and culture. Despite this popularity, analytic theory has only recently received empirical support. In this chapter, we seek to highlight several fundamental concepts of analytic theory (the unconscious, drives, defenses, object relations, Oedipus complex) and psychodynamic treatments (transference, countertransference, interpretations, resistance). The first section of the chapter offers a comprehensive definition and historical background for each concept. This foundation is followed by a review of the empirical evidence supporting the reliability and validity of these concepts, their impact on treatment, and their broader influence on the future of psychology.
Coronary artery spasm during exercise in patients with variant angina.
Authors: D D Waters, B R Chaitman, G Dupras, P Théroux, H F Mizgala
Journal: Circulation (1979)

Seven patients with typical variant angina without coronary stenoses greater than 50% developed angina and ST-segment elevation during treadmill exercise testing. In all cases the ST-segment elevation occurred in the same leads during exercise testing as during spontaneous attacks at rest. Five of the patients had developed spontaneous coronary spasm during coronary arteriography, in each case in the artery corresponding to the site of ST-segment elevation. In five patients, thallium was injected during the exercise test during which angina and ST-segment elevation occurred. In each case, a large perfusion defect not present at rest was found in the zone corresponding to the site of ST-segment elevation. These findings suggest that coronary artery spasm may occur during exercise in patients with variant angina.
Randomized Phase II Trial Evaluating Two Paclitaxel and Cisplatin–Containing Chemoradiation Regimens As Adjuvant Therapy in Resected Gastric Cancer (RTOG-0114)
Authors: Gary K. Schwartz, Kathryn Winter, Bruce D. Minsky, Christopher Crane, P. John Thomson, Pramila Anne, Howard Gross, Christopher Willett, David Kelsen
Journal: Journal of Clinical Oncology (2009)

The investigational arm of INT0116, a fluorouracil (FU) and leucovorin-containing chemoradiotherapy regimen, is a standard treatment for patients with resected gastric cancer with a 2-year disease-free survival rate (DFS) of 52%. Toxicity is also significant. More beneficial and safer regimens are needed.We performed a randomized phase II study among 39 cancer centers to evaluate two paclitaxel and cisplatin-containing regimens, one with FU (PCF) and the other without (PC) in patients with resected gastric cancer. Patients received two cycles of postoperative chemotherapy followed by 45 Gy of radiation with either concurrent FU and paclitaxel or paclitaxel and cisplatin. The primary objective was to show an improvement in 2-year DFS to 67% as compared with INT 0116.From May 2001 to February 2004 (study closure), 78 patients entered this study, and 73 were evaluable. At the planned interim analysis of 22 patients on PCF, grade 3 or higher GI toxicity was 59%. This was significantly worse than INT0116, and this arm was closed. Accrual continued on PC. The median DFS was 14.6 months for PCF and has not been reached for PC. For PC the 2-year DFS is 52% (95% CI, 36% to 68%).Though PC appears to be safe and the median DFS favorable, the DFS failed to exceed the lower bound of 52.9% for the targeted 67% DFS at 2 years and can not be recommended as the adjuvant arm for future randomized trials.