tbuckley/cabot-search huggingface dataset:
Monovalent and unpoised status of most genes in undifferentiated cell-enriched Drosophila testis
Authors: Qiang Gan, Dustin E Schones, Suk Ho Eun, Gang Wei, Kairong Cui, Keji Zhao, Xin Chen
Journal: Genome biology (2010)

Abstract Background Increasing evidence demonstrates that stem cells maintain their identities by a unique transcription network and chromatin structure. Opposing epigenetic modifications H3K27me3 and H3K4me3 have been proposed to label differentiation-associated genes in stem cells, progenitor and precursor cells. In addition, many differentiation-associated genes are maintained at a poised status by recruitment of the initiative RNA Polymerase II (Pol II) at their promoter regions, in preparation for lineage-specific expression upon differentiation. Previous studies have been performed using cultured mammalian embryonic stem cells. To a lesser extent, chromatin structure has been delineated in other model organisms, such as Drosophila , to open new avenues for genetic analyses. Results Here we use testes isolated from a Drosophila bag of marbles mutant strain, from which germ cells are in their undifferentiated status. We use these testes to study the endogenous chromatin structure of undifferentiated cells using ChIP-seq. We integrate the ChIP-seq with RNA-seq data, which measures the digital transcriptome. Our genome-wide analyses indicate that most differentiation-associated genes in undifferentiated cells lack an active chromatin mark and initiative Pol II; instead, they are associated with either the repressive H3K27me3 mark or no detectable mark. Conclusions Our results reveal that most of the differentiation-associated genes in undifferentiated-cell-enriched Drosophila testes are associated with monovalent but not bivalent modifications, a chromatin signature that is distinct from the data reported in mammalian stem or precursor cells, which may reflect cell type specificity, species specificity, or both.
Encouraging Patients to Ask Questions
Authors: Timothy J. Judson, Allan S. Detsky, Matthew J. Press
Journal: JAMA (2013)

THE FOCUS OF AN ONGOING EFFORT IN HEALTH CARE quality improvement is to encourage patients to ask questions during their care. In September 2011, the Agency for Healthcare Research and Quality (AHRQ) launched the Questions Are the Answer campaign (TABLE) and has used $20 million of donated marketing outreach toward building patient engagement through asking questions (Farah Englert, AHRQ, November 15, 2012, written communication). In 2002, the Joint Commission created Speak Up, an initiative that promotes patient involvement in care and emphasizes the importance of asking questions (Table). Encouraging patients to ask questions makes sense; it has the potential to enable shared decision making between patients and physicians. As a result, patient adherence may improve, patient satisfaction may increase, and patients may be more likely to receive care that is in accordance with their values and preferences. While patient engagement is unproven and potentially inappropriate as a safety net for catching medical errors, it may be a valuable tool for facilitating communication that empowers patients. But the barriers that prevent patients and physicians from meaningfulquestion-and-answerexchangesaresubstantial.Simplyencouragingpatientstoaskquestionsandprovidingexamples are not enough. This Viewpoint describes these barriers and presents suggestions for how they may be overcome.
Male Sexual Dysfunction
Authors: John B. Nanninga
Journal: JAMA (1985)

This multiauthor book seeks to pull together several specialties that deal with male sexual dysfunction. As the editors point out, the urologist has, in many instances, become the primary coordinator for the patient with impotence, ejaculatory disturbance, or whatever may be altering normal sexual function. Also, because of the development of penile prostheses, it is important to know the cause of the sexual dysfunction so as to pick the proper operative candidates. The book consists of 25 chapters, the first four presenting the physiology of normal male sexual function. Current areas of investigation are covered in these chapters, including studies on the sympathetic innervation and receptors. The remaining chapters cover the various neurological, endocrine, pharmacologic, vascular, and behavioral factors that affect sexual function. Unfortunately, the book probably went to print before the publication of Brindley, which describes the technique of producing an erection by the injection of sympathetic α-blocking agent
Ocular Complications of Measles—The Country Doctor.
Authors: J. Bernstein
Journal: JAMA (1906)

Kalamazoo, Mich., June 11, 1906. <h3>To the Editor:</h3> —InThe Journal, May 26, there appears an item in Therapeutics on "The Ocular Complications In Measles." While in many respects there is a great deal of good advice in the article there are one or two things which it seems to me few oculists would advise. First, I am pretty sure that no one would think of using solution of cocain when intense photophobia is present. This symptom is most usually due to erosion of the cornea, and one of the great objections to cocain solution is just this propensity to bring about such conditions. It is better to use 5 per cent. dionin or 0.5 per cent, solution of atropin sulphate p. r. n. Second, when intense itching of the eyelids occurs, it has not been my fortune to see any good result from the Pagenstecher ointment. I should think
900. Specific AAV Serotypes Stably Transduce Hippocampal and Cortical Cultures with High Efficiency and Low Toxicity
Authors: Nicolas C. Royo, Luk H. Vandenberghe, Julie Johnston, Margaret Maronski, Marc A. Dichter, James M. Wilson, Deborah J. Watson
Journal: Molecular Therapy (2006)

Cultures of dissociated neurons and astrocytes are frequently used by neurobiologists to study neuronal physiology and pathophysiology. However, current methods for gene delivery into neurons in vitro are limited by very low efficiency, short-term gene expression, toxicity and/or the requirement to transfect on the day of plating. We hypothesized that adeno-associated viral (AAV) vectors might represent an efficient and less toxic method for neuronal transduction. We tested AAV transduction of primary cultures of 150,000 E18 rat cortical or hippocampal neurons and astrocytes using six serotypes (AAV1, 2, 6, 7, 8, and 9), each containing the same AAV-2-based genome encoding CMV-GFP. Mature cultures of hippocampal neurons were transduced at 4 weeks post-plating by AAV1, 2, 7, 8 and 9, resulting in GFP expression for at least 1 week. AAV2 (2.5 E+11 genome equivalents, GE) was particularly effective in transducing the mature hippocampal cultures. Expression of GFP was detectable by 1 week post-transduction in 40–60% of the cells, localized predominantly in cells expressing the neuronal marker MAP2, and stable for up to 4 weeks (the life of the culture) without inducing cell death. Immature hippocampal cultures were exposed at 1 day post-plating to AAV1, 2, 6, 7 and 9, and transduced by AAV1, 2, 7 and 9. The AAV9 serotype (5E+11GE) transduced 50–70% of cells in the d1 hippocampal cultures and GFP expression was stable for 4 weeks. The AAV6 serotype caused cell death in both the mature and immature hippocampal cultures and the AAV7 serotype transduced both neurons and astrocytes. To determine whether cortical neurons were transduced by the same vectors, AAV1, 6, 7 and 9 were applied to cortical cultures at 4 weeks post-plating. All 4 serotypes transduced cortical cells and the GFP expression was stable for 1–2 weeks. In both hippocampal and cortical cultures, cell death occurred at later time points (2–4 weeks) after transduction although toxicity was not related to the volume of vector applied or GFP expression. Work is ongoing to quantify the percentages of neurons and astrocytes transduced by each serotype and to explore the in vitro transduction patterns of AAV vectors with engineered capsid proteins. These results should make possible a wide range of neurobiological experiments in cultured neurons, including delivery of shRNAs. Supported by NS040978 (DW) and P30-DK-047757.
Isolation of a heterogeneous population of temperature-sensitive mutants of measles virus from persistently infected human lymphoblastoid cell lines.
Authors: G Ju, S Udem, B Rager-Zisman, B R Bloom
Journal: The Journal of Experimental Medicine (1978)

Two human lymphoblastoid B-cell lines, WI-L2 and 8866, were infected with the Edmonston strain of measles virus at a multiplicity of infection of 10(-6), and stable persistent infections were established. By immunofluorescence and electron microscopy, the vast majority of cells from both cell lines were expressing viral antigens and releasing virion-like particles. However, very little infectious virus could be detected at 37 degrees C, either by an infectious centers assay or by titration of supernates from persistently infected cultures. When cultures were shifted to 31 degrees C, the cells released a population of virus that was temperature-sensitive. Clonal analysis of supernatant virus at 31 degrees C revealed a highly heterogeneous population of temperature-sensitive mutants, differing in plating efficiency ratios, thermolability, and antigen production at the nonpermissive temperature. Factors such as interferon, defective interfering particles, and extracellular virus do not appear to be important in maintaining the persistent carrier state. These studies have important implications for persistent infections of lymphoid cells in vivo, and the slow neurological diseases associated with measles, subacute sclerosing panencephalitis, and multiple sclerosis.
Sweet's syndrome in chronic lymphocytic leukemia associated with neutropenic fever and granulocyte colony stimulation factor
Authors: Michael A. Thompson, Senait W. Dyson, Stefan Faderl
Journal: American Journal of Hematology (2006)

Abstract Granulocyte colony stimulation factor (G‐CSF) is commonly used in the treatment of chemotherapy‐induced myelosuppression. We report the case of a 62‐year‐old man with chronic lymphocytic leukemia who presented with neutropenic fever and sepsis. After treatment with G‐CSF he developed Sweet's syndrome. Sweet's syndrome is a rare disorder but has been associated with cancer recurrence as well as administration of G‐CSF. We present clinical and pathologic images that highlight the salient features of this entity. Am. J. Hematol., 2006. © 2006 Wiley‐Liss, Inc.
Orthopaedic surgeons and thromboprophylaxis
Authors: C B D Lavy, T W R Briggs
Journal: BMJ (1991)

many of whom would not risk epidural cannulation in a patient receiving standard unfractionated heparin.There is evidence that the period of greatest risk of thrombosis in hip replacement surgery is during surgery itself, when the femoral vein is subject to stress from the heat of polymerisation of bone cement and from the hip being maintained in a forced position in which the vein may be folded or kinked.'As the addition of the drug to the formulary was based on studies in which the first dose was given 12 hours preoperatively this cleared the way for enoxaparin to be added to the formulary.
siRNA Nanoparticle Functionalization of Nanostructured Scaffolds Enables Controlled Multilineage Differentiation of Stem Cells
Authors: Morten Ø Andersen, Jens V Nygaard, Jorge S Burns, Merete K Raarup, Jens R Nyengaard, Cody Bünger, Flemming Besenbacher, Kenneth A Howard, Moustapha Kassem, Jørgen Kjems
Journal: Molecular Therapy (2010)

The creation of complex tissues and organs is the ultimate goal in tissue engineering. Engineered morphogenesis necessitates spatially controlled development of multiple cell types within a scaffold implant. We present a novel method to achieve this by adhering nanoparticles containing different small-interfering RNAs (siRNAs) into nanostructured scaffolds. This allows spatial retention of the RNAs within nanopores until their cellular delivery. The released siRNAs were capable of gene silencing BCL2L2 and TRIB2, in mesenchymal stem cells (MSCs), enhancing osteogenic and adipogenic differentiation, respectively. This approach for enhancing a single type of differentiation is immediately applicable to all areas of tissue engineering. Different nanoparticles localized to spatially distinct locations within a single implant allowed two different tissue types to develop in controllable areas of an implant. As a consequence of this, we predict that complex tissues and organs can be engineered by the in situ development of multiple cell types guided by spatially restricted nanoparticles.
Bronchial biopsy evidence for leukocyte infiltration and upregulation of leukocyte-endothelial cell adhesion molecules 6 hours after local allergen challenge of sensitized asthmatic airways.
Authors: S Montefort, C Gratziou, D Goulding, R Polosa, D O Haskard, P H Howarth, S T Holgate, M P Carroll
Journal: Journal of Clinical Investigation (1994)

We have examined the mucosal changes occurring in bronchial biopsies from six atopic asthmatics 5-6 h after local endobronchial allergen challenge and compared them with biopsies from saline-challenged segments from the same subjects at the same time point. All the subjects developed localized bronchoconstriction in the allergen-challenged segment and had a decrease in forced expiratory volume in 1 s (FEV1) (P < 0.01) and a decrease in their methacholine provocative concentration of agonist required to reduce FEV1 from baseline by 20% (P < 0.05) 24 h postchallenge. At 6 h we observed an increase in neutrophils (P = 0.03), eosinophils (P = 0.025), mast cells (P = 0.03), and CD3+ lymphocytes (P = 0.025), but not in CD4+ or CD8+ lymphocyte counts. We also detected an increase in endothelial intercellular adhesion molecule type 1 (P < 0.05) and E-selectin (P < 0.005), but not vascular cell adhesion molecule type 1 expression with a correlative increase in submucosal and epithelial LFA+ leucocytes (P < 0.01). Thus, in sensitized asthmatics, local endobronchial allergen instillation leads to an increased inflammatory cell infiltrate of the airway mucosa that involves upregulation of specific adhesion molecules expressed on the microvasculature.
Zinc finger transcription factor 191, directly binding to β-catenin promoter, promotes cell proliferation of hepatocellular carcinoma
Authors: Guoyuan Liu, Songmin Jiang, Chenji Wang, Wei Jiang, Zulong Liu, Chao Liu, Hexige Saiyin, Xianmei Yang, Suqin Shen, Deke Jiang, Ping Zhou, Dingding Han, Xiaohui Hu, Qing Yi, Long Yu
Journal: Hepatology (2011)

Activation of β-catenin, the central effector of the canonical wingless-type (Wnt) pathway, has been implicated in hepatocellular carcinoma (HCC). However, the transcription regulation mechanism of the β-catenin gene in HCC remains unknown. Here we report that human zinc finger protein 191 (ZNF191) is a potential regulator of β-catenin transcription. ZNF191, a Krüppel-like protein, specifically interacts with the TCAT motif, which constitutes the HUMTH01 microsatellite in the tyrosine hydroxylase ( TH ) gene ex vivo . We demonstrate that ZNF191 is significantly overexpressed in human HCC specimens and is associated with growth of human HCC cells. Global profiling of gene expression in ZNF191 knockdown human hepatic L02 cells revealed that the important Wnt signal pathway genes β-catenin and cyclin D1 messenger RNAs (mRNAs) are significantly down-regulated. In agreement with transcription level, β-catenin and cyclin D1 proteins are also down-regulated in transient and stable ZNF191 knockdown L02 and hepatoma Hep3B cell lines. Moreover, significant correlation between ZNF191 and β-catenin mRNA expression was detected in human HCCs. Promoter luciferase assay indicated that ZNF191 can increase transcription activity of the full-length β-catenin (CTNNB1) promoter, and nucleotide (nt)-1407/-907 of the CTNNB1 promoter exhibited the maximum transcriptional activity. Electrophoretic mobility shift assay showed that purified ZNF191 protein can directly bind to the CTNNB1 promoter, and the binding region is located at nt-1254/-1224. Finally, we demonstrate that the key binding sequence of ZNF191 in vivo is ATTAATT. Conclusion: ZNF191 can directly bind to the CTNNB1 promoter and activate the expression of β-catenin and its downstream target genes such as cyclin D1 in hepatoma cell lines. This study uncovers a new molecular mechanism of transcription regulation of the β-catenin gene in HCC.
The Benevolent Fund
Authors: J. Lee
Journal: BMJ (1844)

former labors-the size of her childreni-her con- tracte(d pelvis and dimiiiislied strength, had she becii perm<iitted to go the full term of utero-gestation, her delivery would have been a solemn and serious task.But as the method adopted in this case has fulfilled the most sanguine expectations of my friend and self, we are truly gratified-and the husband and wife, friends and relatives, are all thankful that Divine Providence lias smiled upon the means used to alle-
Metabolic and Cardiovascular Effects of Carvedilol and Atenolol in Non-Insulin-Dependent Diabetes Mellitus and Hypertension
Authors: Dario Giugliano
Journal: Annals of Internal Medicine (1997)

Background: Diabetic patients are considered less suitable than nondiabetic patients for β-blocker therapy because of the risk for worsened glucose and lipid metabolism and more severe hypoglycemic attacks. Objective: To compare the metabolic and cardiovascular effects of carvedilol with those of atenolol in diabetic patients with hypertension. Design: Randomized, double-blind, 24-week trial. Setting: University hospital clinic. Patients: 45 patients with non–insulin-dependent diabetes mellitus and hypertension. Intervention: After a 4- to 6-week run-in period during which placebo was given in a single-blind manner, patients were randomly assigned to carvedilol or atenolol. Measurements: An oral glucose tolerance test; assessment of insulin sensitivity and hormonal responses to insulin hypoglycemia; and assessment of lipid levels, blood pressure, left ventricular mass, and lipid peroxidation. Results: Changes in systolic and diastolic blood pressure and left ventricular mass index were similar with carvedilol and atenolol (P > 0.2). Fasting plasma glucose and insulin levels decreased with carvedilol and increased with atenolol. Responses to carvedilol were greater than those to atenolol, as follows: increase in total glucose disposal, 9.54 µmol/kg of body weight per minute (95% CI, 7 to 11.9 µmol/kg per minute); decrease in plasma glucose response to oral glucose, 61 mmol/L × 180 minutes (CI, −101 to −21 mmol/L × 180 minutes); decrease in insulin response to oral glucose, 6.2 nmol/L × 180 minutes (CI, −9.8 to −2.6 nmol/L × 180 minutes); decrease in triglyceride level, 0.56 mmol/L (CI, −0.75 to −0.37 mmol/L; P < 0.001); increase in high-density lipoprotein cholesterol level, 0.13 mmol/L (CI, 0.09 to 0.17 mmol/L; P < 0.001); and decrease in lipid peroxidation, 0.25 µmol/L (CI, −0.34 to −0.16µmol/L). Conclusions: By improving glucose and lipid metabolism and reducing lipid peroxidation, carvedilol may offer advantages in patients with diabetes and hypertension.
Mindfulness-Based Cognitive Therapy Improves Polysomnographic and Subjective Sleep Profiles in Antidepressant Users with Sleep Complaints
Authors: Willoughby B. Britton, Patricia L. Haynes, Keith W. Fridel, Richard R. Bootzin
Journal: Psychotherapy and Psychosomatics (2012)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Many antidepressant medications (ADM) are associated with disruptions in sleep continuity that can compromise medication adherence and impede successful treatment. The present study investigated whether mindfulness meditation (MM) training could improve self-reported and objectively measured polysomnographic (PSG) sleep profiles in depressed individuals who had achieved at least partial remission with ADM, but still had residual sleep complaints. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Twenty-three ADM users with sleep complaints were randomized into an 8-week Mindfulness-Based Cognitive Therapy (MBCT) course or a waitlist control condition. Pre-post measurements included PSG sleep studies and subjectively reported sleep, residual depression symptoms. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Compared to controls, the MBCT participants improved on both PSG and subjective measures of sleep. They showed a pattern of decreased wake time and increased sleep efficiency. Sleep depth, as measured by stage 1 and slow-wave sleep, did not change as a result of mindfulness training. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; MM is associated with increases in both objectively and subjectively measured sleep continuity in ADM users. MM training may serve as more desirable and cost-effective alternative to discontinuation or supplementation with hypnotics, and may contribute to a more sustainable recovery from depression.
The Chernobyl Accident 20 Years On: An Assessment of the Health Consequencesand the International Response
Authors: Keith Baverstock, Dillwyn Williams
Journal: Environmental Health Perspectives (2006)

BackgroundThe Chernobyl accident in 1986 caused widespread radioactive contamination and enormous concern. Twenty years later, the World Health Organization and the International Atomic Energy Authority issued a generally reassuring statement about the consequences. Accurate assessment of the consequences is important to the current debate on nuclear power.ObjectivesOur objectives in this study were to evaluate the health impact of the Chernobyl accident, assess the international response to the accident, and consider how to improve responses to future accidents.DiscussionSo far, radiation to the thyroid from radioisotopes of iodine has caused several thousand cases of thyroid cancer but very few deaths; exposed children were most susceptible. The focus on thyroid cancer has diverted attention from possible nonthyroid effects, such as mini-satellite instability, which is potentially important. The international response to the accident was inadequate and uncoordinated, and has been unjustifiably reassuring. Accurate assessment of Chernobyl's future health effects is not currently possible in the light of dose uncertainties, current debates over radiation actions, and the lessons from the late consequences of atomic bomb exposure.ConclusionsBecause of the uncertainties over the dose from and the consequences of the Chernobyl accident, it is essential that investigations of its effects should be broadened and supported for the long term. Because of the problems with the international response to Chernobyl, the United Nations should initiate an independent review of the actions and assignments of the agencies concerned, with recommendations for dealing with future international-scale accidents. These should involve independent scientists and ensure cooperation rather than rivalry.
High-Throughput Luminescent Reporter of Insulin Secretion for Discovering Regulators of Pancreatic Beta-Cell Function
Authors: Sean M. Burns, Amedeo Vetere, Deepika Walpita, Vlado Dančík, Carol Khodier, Jose Perez, Paul A. Clemons, Bridget K. Wagner, David Altshuler
Journal: Cell Metabolism (2015)
Basophils, eosinophils, and mast cells in atopic and nonatopic asthma and in late-phase allergic reactions in the lung and skin
Authors: Alison J. Macfarlane, Onn M. Kon, Susan J. Smith, Kyriaki Zeibecoglou, L.Nasreen Khan, Luis T. Barata, Alan R. McEuen, Mark G. Buckley, Andrew F. Walls, Qiu Meng, Marc Humbert, Neil C. Barnes, Douglas S. Robinson, Sun Ying, A.Barry Kay
Journal: Journal of Allergy and Clinical Immunology (2000)