tbuckley/cabot-search huggingface dataset:
The histone deacetylase inhibitor panobinostat is active in patients with advanced pretreated ovarian sex-cord tumors
Authors: P.A. Cassier, A. Floquet, N. Penel, O. Derbel, B. Bui N'guyen, J.-P. Guastalla, D. Pissaloux, I. Treilleux, C.E. Saba, J.-Y. Blay, I. Ray-Coquard
Journal: Annals of Oncology (2014)
The Role of MicroRNAs in the Control of Innate Immune Response in Cancer
Authors: Simon Jasinski-Bergner, Ofer Mandelboim, Barbara Seliger
Journal: JNCI Journal of the National Cancer Institute (2014)

Ligands for receptors of natural killer (NK) cells and CD8+ cytotoxic T lymphocytes (CTL), such as the inhibitory nonclassical HLA-G, the activating stress-induced major histocompatibility complex class I-related antigens MICA and MICB, and/or the UL16-binding proteins (ULBPs), are often aberrantly expressed upon viral infection and neoplastic transformation, thereby preventing virus-infected or malignant-transformed cells from elimination by immune effector cells. Recently, it has been shown that ligands of both NK and CD8+ T cells are regulated by a number of cellular and/or viral microRNAs (miRs). These miRs are involved in shaping the antiviral and/or antitumoral immune responses as well as neoplastic growth properties. This review summarizes the expression pattern and function of miRs directed against selected NK and T cell receptor ligands, their putative role in shaping immune surveillance and tumorigenicity, and their clinical relevance. In addition, the potential role of RNA-binding proteins in the post-transcriptional gene regulation of these ligands will be discussed.
Suprachoroidal hemorrhage during pars plana vitrectomy
Authors: Homayoun Tabandeh, Paul M Sullivan, Peter Smahliuk, Harry W Flynn, Joyce Schiffman
Journal: Ophthalmology (1999)

Objective Suprachoroidal hemorrhage (SCH) is an uncommon but serious complication of pars plana vitrectomy (PPV) that can be associated with a guarded visual prognosis. The purpose of this study is to document the risk factors and outcomes of this complication. Design Case-control study of consecutive cases of intraoperative SCH occurring during PPV (n = 36) and controls of PPV uncomplicated by SCH (n = 116). Main outcome measures Baseline systemic and ocular characteristics, intraoperative findings, surgical procedures, and final anatomic and visual outcomes were measured. Results Significant risk factors for the development of SCH during PPV included high myopia (22% of cases vs. 5% of controls), history of retinal detachment (RD) surgery (61% vs. 22%), rhegmatogenous RD (97% vs. 60%), use of cryotherapy (75% vs. 33%), scleral buckling at the time of PPV (50% vs. 19%), external drainage of the subretinal fluid (22% vs. 2%), and intraoperative systemic hypertension. In the 34 SCH cases with 3 months' or more follow-up, the final visual acuity was 20/200 or greater in 11 (32%), count fingers in 5 (15%), hand movement in 7 (21%), light perception in 7 (21%), and no light perception in 4 (12%). In the 106 controls with 3 months' or more follow-up, the final visual acuity was 20/200 or greater in 79 (75%), count fingers in 20 (19%), hand movement in 5 (5%), light perception in 1 (1%), and no light perception in 1 (1%). In the eyes with SCH, 17 (50%) had persistent RD, 10 (33%) had secondary glaucoma develop, and 8 (24%) became hypotonic. The visual and anatomic outcomes of the SCH cases were significantly worse than those in the control group (P < 0.001). The visual outcome was more favorable if the SCH did not extend into the posterior pole (P = 0.002). Attempted intraoperative drainage of SCH was not associated with a better outcome. Conclusion Risk factors for the development of intraoperative SCH during PPV are high myopia, previous RD surgery, rhegmatogenous RD, cryotherapy, scleral buckling, external drainage of subretinal fluid, and intraoperative systemic hypertension. Anatomic and visual outcomes are significantly worsened after this complication.
Substance Use Disorders in Patients With Posttraumatic Stress Disorder: A Review of the Literature
Authors: Leslie K. Jacobsen, Steven M. Southwick, Thomas R. Kosten
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: Alcohol use disorders and other substance use disorders are extremely common among patients with posttraumatic stress disorder (PTSD). This article reviews studies pertaining to the epidemiology, clinical phenomenology, and pathophysiology of comorbid PTSD and substance use disorders. METHOD: Studies were identified by means of computerized and manual searches. The review of research on the pathophysiology of PTSD and substance use disorders was focused on studies of the hypothalamic-pituitary-adrenal axis and the noradrenergic system. RESULTS: High rates of comorbidity suggest that PTSD and substance use disorders are functionally related to one another. Most published data support a pathway whereby PTSD precedes substance abuse or dependence. Substances are initially used to modify PTSD symptoms. With the development of dependence, physiologic arousal resulting from substance withdrawal may exacerbate PTSD symptoms, thereby contributing to a relapse of substance use. Preclinical work has led to the proposal that in PTSD, corticotropin-releasing hormone and noradrenergic systems may interact such that the stress response is progressively augmented. Patients may use sedatives, hypnotics, or alcohol in an effort to interrupt this progressive augmentation. CONCLUSIONS: Vigorous control of withdrawal and PTSD-related arousal symptoms should be sought during detoxification of patients with comorbid PTSD and substance use disorders. Inclusion of patients with comorbid PTSD and substance use disorders in neurobiologic research and in clinical trials will be critical for development of effective treatments for this severely symptomatic patient population.
Pharyngeal Pressure and Flow Effects on Genioglossus Activation in Normal Subjects
Authors: ATUL MALHOTRA, GIORA PILLAR, ROBERT B. FOGEL, JILL K. EDWARDS, NAJIB AYAS, TOSHIKI AKAHOSHI, DEAN HESS, DAVID P. WHITE
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Pharyngeal dilator muscles are clearly important in the pathogenesis of obstructive sleep apnea syndrome. Substantial data support the role of local mechanisms in mediating pharyngeal dilator muscle activation in normal humans during wakefulness. Using a recently reported iron lung ventilation model, we sought to determine the stimuli modulating genioglossus activity, dissociating the influences of pharyngeal negative pressure, from inspiratory airflow, resistance, and CO(2). To achieve this aim, we used two gas densities at several levels of end-tidal CO(2) and a number of intrapharyngeal negative pressures. The correlations between genioglossus electromyography (GGEMG) and epiglottic pressure across a breath remained robust under all conditions (R values range from 0.71 +/- 0.07 to 0.83 +/- 0.05). In addition, there was no significant change in the slope of this relationship despite variable gas density or CO(2) levels. Although flow also showed strong correlations with genioglossus activity, there was a significant change in the slope of the GGEMG/flow relationship with altered gas density. For the group averages across conditions (between breath analysis), the correlation with GGEMG was robust for negative pressure (R(2) = 0.98) and less strong for other variables such as flow and resistance. These data suggest that independent of central pattern generator activity, intrapharyngeal negative pressure itself modulates genioglossus activity both within breaths and between breaths.
Pre-B and B cells in rabbits. Ontogeny and allelic exclusion of kappa light chain genes.
Authors: A R Hayward, M A Simons, A R Lawton, R G Mage, M D Cooper
Journal: The Journal of Experimental Medicine (1978)

Pre-B cells in developing rabbits were identified by immunofluorescence as cells containing small amounts of cytoplasmic IgM (cIgM) but lacking surface immunoglobulin (sIg). During ontogeny the first pre-B cells appeared in fetal liver at 23 days gestation, 2 days before the appearance of sIgM+ B lymphocytes. Pre-B cells were relatively frequent in fetal and adult bone marrow, but were not found in other tissues except rarely in fetal spleen. Allelic exclusion is apparently established at this early stage of development, because individual pre-B cells and B lymphocytes from heterozygous rabbits expressed only one of the alternative alleles in amounts sufficient for detection. Development of isotype diversity among rabbit B lymphocytes followed the general pattern seen in mouse and man. sIgM+ cells were detected before birth. Expression of sIgG was detected in neonatal rabbits on cells which were also sIgM+ but in older animals most sIgG+ cells lacked sIgM. Cells bearing sIgA were not found until 5-6 days of age, and had no other isotype on their surface.
A high utility integrated map of the pig genome
Authors: Sean J Humphray, Carol E Scott, Richard Clark, Brandy Marron, Clare Bender, Nick Camm, Jayne Davis, Andrew Jenks, Angela Noon, Manish Patel, Harminder Sehra, Fengtang Yang, Margarita B Rogatcheva, Denis Milan, Patrick Chardon, Gary Rohrer, Dan Nonneman, Pieter de Jong, Stacey N Meyers, Alan Archibald, Jonathan E Beever, Lawrence B Schook, Jane Rogers
Journal: Genome biology (2007)

The domestic pig is being increasingly exploited as a system for modeling human disease. It also has substantial economic importance for meat-based protein production. Physical clone maps have underpinned large-scale genomic sequencing and enabled focused cloning efforts for many genomes. Comparative genetic maps indicate that there is more structural similarity between pig and human than, for example, mouse and human, and we have used this close relationship between human and pig as a way of facilitating map construction.Here we report the construction of the most highly continuous bacterial artificial chromosome (BAC) map of any mammalian genome, for the pig (Sus scrofa domestica) genome. The map provides a template for the generation and assembly of high-quality anchored sequence across the genome. The physical map integrates previous landmark maps with restriction fingerprints and BAC end sequences from over 260,000 BACs derived from 4 BAC libraries and takes advantage of alignments to the human genome to improve the continuity and local ordering of the clone contigs. We estimate that over 98% of the euchromatin of the 18 pig autosomes and the X chromosome along with localized coverage on Y is represented in 172 contigs, with chromosome 13 (218 Mb) represented by a single contig. The map is accessible through pre-Ensembl, where links to marker and sequence data can be found.The map will enable immediate electronic positional cloning of genes, benefiting the pig research community and further facilitating use of the pig as an alternative animal model for human disease. The clone map and BAC end sequence data can also help to support the assembly of maps and genome sequences of other artiodactyls.
Turning off the tap: stopping tuberculosis transmission through active case-finding and prompt effective treatment
Authors: Courtney M Yuen, Farhana Amanullah, Ashwin Dharmadhikari, Edward A Nardell, James A Seddon, Irina Vasilyeva, Yanlin Zhao, Salmaan Keshavjee, Mercedes C Becerra
Journal: The Lancet (2015)

To halt the global tuberculosis epidemic, transmission must be stopped to prevent new infections and new cases. Identification of individuals with tuberculosis and prompt initiation of effective treatment to rapidly render them non-infectious is crucial to this task. However, in settings of high tuberculosis burden, active case-finding is often not implemented, resulting in long delays in diagnosis and treatment. A range of strategies to find cases and ensure prompt and correct treatment have been shown to be effective in high tuberculosis-burden settings. The population-level effect of targeted active case-finding on reducing tuberculosis incidence has been shown by studies and projected by mathematical modelling. The inclusion of targeted active case-finding in a comprehensive epidemic-control strategy for tuberculosis should contribute substantially to a decrease in tuberculosis incidence.
Genome-wide association studies in pharmacogenomics: untapped potential for translation
Authors: Idris Guessous, Marta Gwinn, Muin J Khoury
Journal: Genome Medicine (2009)

Despite large public investments in genome-wide association studies of common human diseases, so far, few gene discoveries have led to applications for clinical medicine or public health. Genome-wide association studies in the context of clinical trials of drug safety and efficacy may be quicker to yield clinical applications. Certain methodological concerns, such as selection bias and confounding, may be mitigated when genome-wide association studies are conducted within clinical trials, in which randomization of exposure, prospective evaluation of outcome and careful definition of phenotype are incorporated by design.
Meta-analysis of air pollution exposure association with allergic sensitization in European birth cohorts
Authors: Olena Gruzieva, Ulrike Gehring, Rob Aalberse, Raymond Agius, Rob Beelen, Heidrun Behrendt, Tom Bellander, Matthias Birk, Johan C. de Jongste, Elaine Fuertes, Joachim Heinrich, Gerard Hoek, Claudia Klümper, Gerard Koppelman, Michal Korek, Ursula Krämer, Sarah Lindley, Anna Mölter, Angela Simpson, Marie Standl, Marianne van Hage, Andrea von Berg, Alet Wijga, Bert Brunekreef, Göran Pershagen
Journal: Journal of Allergy and Clinical Immunology (2013)
Thrombin Activates the Sarcolemmal Na <sup>+</sup> -H <sup>+</sup> Exchanger
Authors: Masahiro Yasutake, Robert S. Haworth, Anna King, Metin Avkiran
Journal: Circulation Research (1996)

Thrombin can activate the plasma membrane Na + -H + exchanger in a variety of noncardiac cells. We have studied (1) the effect of thrombin on the activity of the sarcolemmal Na + -H + exchanger in freshly isolated quiescent ventricular myocytes from the adult rat heart and (2) the signaling mechanism(s) underlying any effect. Reverse-transcription polymerase chain reaction analysis revealed thrombin receptor mRNA expression in a myocyte-enriched cell preparation. As an index of Na + -H + exchanger activity, acid efflux rates ( J H s) were determined in single myocytes (n=4 to 11 per group) loaded with the pH-sensitive fluoroprobe carboxy-seminaphthorhodafluor-1 after two consecutive intracellular acid pulses (induced by transient exposure to 20 mmol/L NH 4 Cl) in bicarbonate-free medium. At a pH i of 6.9, J H did not change significantly during the second pulse relative to the first in control cells. However, when the second pulse occurred in the presence of 0.2, 1, or 5 U/mL thrombin, J H increased by 30%, 62% ( P &lt;.05), and 87% ( P &lt;.05), respectively. A hexameric thrombin receptor–activating peptide (SFLLRN) mimicked the effect of thrombin and increased J H by 73% ( P &lt;.05) at 25 μmol/L. In contrast, an inactive control peptide (FLLRN) was without effect at 25 μmol/L. In cells pretreated with 100 nmol/L GF109203X or 5 μmol/L chelerythrine (protein kinase C inhibitors), neither 5 U/mL thrombin nor 25 μmol/L SFLLRN produced a significant increase in J H . In the presence of 10 μmol/L HOE-694 (a Na + -H + exchanger inhibitor), pH i did not recover after an acid load, even during exposure to 5 U/mL thrombin or 25 μmol/L SFLLRN, confirming that the Na + -H + exchanger was the primary acid efflux mechanism under the conditions used. Neither 5 U/mL thrombin nor 25 μmol/L SFLLRN affected resting pH i and Ca 2+ or background acid loading. We conclude that (1) adult rat ventricular myocytes express a functional thrombin receptor, whose stimulation results in increased activity of the sarcolemmal Na + -H + exchanger, and (2) this effect appears to occur through a protein kinase C–mediated mechanism.
Atherosclerosis, apolipoprotein E, and prevalence of dementia and Alzheimer's disease in the Rotterdam Study
Authors: Albert Hofman, Alewijn Ott, Monique MB Breteler, Michiel L Bots, Arjen JC Slooter, Frans van Harskamp, Cornelia N van Duijn, Christine Van Broeckhoven, Diederick E Grobbee
Journal: The Lancet (1997)
Factors contributing to dyspnoea during bronchoconstriction and exercise in asthmatic subjects
Authors: KJ Killian, E Summers, RM Watson, PM O'Byrne, NL Jones, EJ Campbell
Journal: European Respiratory Journal (1993)

The purpose of the present study was to identify: 1) whether dyspnoea during bronchoconstriction and exercise is related, in asthmatic subjects; and 2) to what extent baseline pulmonary function and respiratory muscle strength contribute to dyspnoea under both conditions. One hundred and seventy five consecutive subjects, referred with suspected asthma, rated the intensity of dyspnoea (Borg scale 0-10): 1) during the administration of doubling concentrations of methacholine to 32 mg.ml-1 methacholine, or until the baseline forced expiratory volume in one second (FEV1) was reduced by 20%; and 2) during incremental cycle ergometry (100 kpm.min-1 each minute) to maximal capacity. 138/175 subjects achieved a 20% reduction in their baseline FEV1; 18 of the 138 were excluded, 2 children and 16 with complicating pulmonary disorders (diffusing capacity of the lung for carbon monoxide (DLCO) and/or total lung capacity (TLC) < 70% predicted). The remaining 120 out of 175 constituted the study population. Dyspnoea following a 20% reduction in the baseline FEV1 (Dys20%) was linearly interpolated, using the rating of dyspnoea and the FEV1 at the two final concentrations of methacholine. In the 120 asthmatic subjects, the mean intensity of dyspnoea was "moderate" (2.9, SD 1.91; Borg 0-10) and the intensity across subjects was not significantly related to baseline FEV1, vital capacity (VC), FEV1/VC, DLCO, TLC and maximal static inspiratory pressure (MIP), alone or in combination.(ABSTRACT TRUNCATED AT 250 WORDS)
Pseudoxanthoma elasticum: biopsy of clinically normal skin in the investigation of patients with angioid streaks
Authors: S.J. Brown, S.J. Talks, S.J. Needham, A.E.M. Taylor
Journal: British Journal of Dermatology (2007)

Pseudoxanthoma elasticum (PXE) is a genetic disorder characterized by fragmentation and calcification of elastic fibres with resultant pathological changes in the dermis, Bruch's membrane and blood vessels. Defects in Bruch's membrane produce angioid streaks on the retina but this appearance is not pathognomonic of PXE. Biopsy of clinically normal skin or scar tissue in patients with angioid streaks may show the histological features of PXE.To test the hypothesis that biopsy of clinically normal skin is a useful investigation in patients with angioid streaks.This prospective study investigated 18 consecutive patients with angioid streaks. Each patient underwent a full dermatological examination and was investigated for diseases known to be associated with angioid streaks. Axillary skin biopsies were taken from 14 consenting patients.Typical PXE was found in 11 patients. No other diseases associated with angioid streaks were identified. Five patients had angioid streaks in the absence of systemic disease. Two patients had nondiagnostic dermatological features which were not clarified by histology. Two of the 11 patients with PXE showed histological evidence of PXE from clinically normal axillary skin. However, in both cases flexural skin elsewhere showed the typical clinical and histological features of PXE.This study demonstrates the association between angioid streaks and PXE. However, it does not support the hypothesis that biopsy of normal-looking skin is helpful in the investigation of adult patients with angioid streaks.
Primary sclerosing cholangitis: a review of its clinical features, cholangiography, and hepatic histology.
Authors: R W Chapman, B A Arborgh, J M Rhodes, J A Summerfield, R Dick, P J Scheuer, S Sherlock
Journal: Gut (1980)

Twenty-nine patients with primary sclerosing cholangitis were reviewed. Males predominated (2:1). Seventy-six per cent presented with cholestasis and cholangitis, 17% with cirrhosis and portal hypertension, and 7% were asymptomatic, presenting with a raised serum alkaline phosphatase. The serum immunoglobulin IgM concentration was raised in 45% of the patients, but no patient had serum mitochondrial antibody present. Seventy-two per cent had ulcerative proctocolitis. There was no relationship between either duration or severity of ulcerative proctocolitis and the development of primary sclerosing cholangitis. Four patients were not benefited by colectomy. None of the patients ahd Crohn9s disease. The prognosis was variable. Corticosteriods and azathioprine were ineffective. Eleven patients (38%) had died with a mean survival time of seven years from diagnosis. Three patients with ulcerative proctocolitis developed bile duct carcinoma. The cholangiograms and liver biopsies were reported without reference to clinical information together with 41 patients with other biliary diseases. Cholangiography was diagnostic in 18/22 (82%). Hepatic histology was diagnostic in 8/22 (36%). Ten showed features of large bile duct disease and three were misdiagnosed as primary biliary cirrhosis. Reduced numbers of bile ducts, ductular proliferation, portal inflammation, and substantial copper deposition, in combination with piecemeal necrosis, are commonly seen in primary sclerosing cholangitis and indicate the need for cholangiography.
Management of melanoma metastasis to the breast: case series and review of the literature
Authors: A. Loffeld, J.R. Marsden
Journal: British Journal of Dermatology (2005)

Background Metastases to the breast from extramammary cancers are rare; melanoma is one of the malignancies that can metastasize to the breast. Objectives To examine the records of a series of patients with a previous diagnosis of melanoma and a metastasis to the breast, and review the published literature of this condition. Methods We report details of eight female patients with breast metastases from melanoma seen over a 36‐month period from 2001. All patients were female aged 28–84 years (median 58). The breast lump was investigated by core‐cut biopsy or fine needle aspiration, with or without a mammogram. Results The time between diagnosis of the primary melanoma and the occurrence of a breast metastasis ranged from 13 to 180 months (median 62). In three patients the breast lump was the first sign of recurrence of melanoma. In three patients melanoma had previously relapsed in regional lymph nodes and in two patients it had already relapsed as locoregional and distant subcutaneous metastases before metastasizing to the breast. In two patients presenting via the breast clinic, the lump was subsequently confirmed on excision to be melanoma in an intramammary lymph node. In seven patients, a lumpectomy was performed after histological confirmation; one of these also had a level 1–3 axillary dissection. The eighth patient deteriorated clinically before further surgery was possible. Six patients developed further metastases within 1–5 months of breast lump detection. In one case a second 9 mm breast lump in the deeper tissue of the same breast was detected on a computed tomography scan and has been removed using stereotactic surgery. Four patients have died. Conclusions Presentation is usually with a palpable mass without skin changes. Investigation must include histology or cytology to confirm the diagnosis. Management of melanoma metastasis to the breast is discussed; in this series it was surgical unless there were many metastases.