tbuckley/cabot-search huggingface dataset:
Heart-specific isoform of tropomyosin4 is essential for heartbeat in zebrafish embryos
Authors: Long Zhao, Xinyi Zhao, Tian Tian, Quanlong Lu, Nirma Skrbo-Larssen, Di Wu, Zheng Kuang, Xiaofeng Zheng, Yanchao Han, Shuyan Yang, Chuanmao Zhang, Anming Meng
Journal: Cardiovascular Research (2008)

Tropomyosin (Tpm) proteins, encoded by four Tpm genes (Tpm1–4), are associated with the stabilization of the F-actin filaments and play important roles in modulating muscle contraction. So far, little is known about Tpm4 function in embryonic heart development and its involvement in the cardiovascular diseases. In this study, we investigated functions of different isoforms of tpm4 in embryonic heartbeat in zebrafish. The transgenic zebrafish line, T2EGEZ8, was generated by insertion of a Tol2 transposon gene trap vector, and homozygous mutants (T2EGEZ8m/m) of this line showed failure of embryonic heartbeat without other detectable phenotypes. Observation by transmission electron microscopy revealed that the ventricular myocytes of mutant fish contained fewer, disorganized myofibrillar filaments. The transposon genome in T2EGEZ8 fish was found by thermal asymmetric interlaced-polymerase chain reaction (TAIL-PCR) and reverse transcription-polymerase chain reaction to have inserted into the ninth intron of the tpm4 locus, which resulted in production of Tpm4-GFP fusion proteins and loss of normal transcripts tpm4-tv1 and tpm4-tv2. Whole-mount in situ hybridization indicated that tpm4-tv1, encoding a peptide of 284 residues, is specifically expressed in the heart of zebrafish embryos, while tpm4-tv2, encoding a peptide of 248 residues, is mainly present in the vasculature but absent in the heart. Knockdown of tpm4-tv1 and tpm4-tv2 within wild-type embryos led to the failure of heartbeat, which could be rescued by coinjection with tpm4-tv1 mRNA but not with tpm4-tv2 mRNA. Tpm4-tv1 is a heart-specific isoform of Tpm4 and is essential for heartbeat in zebrafish embryos.
O11 RETREATMENT OF RELAPSERS TO SOFOSBUVIR/RIBAVIRIN WITH SOFOSBUVIR/LEDIPASVIR: COMPLETE AND RAPID VIROLOGIC SUPPRESSION BY WEEK 4
Authors: A. Osinusi, M. Marti, K. Townsend, A. Nelson, A. Kohli, R. Silk, P. Pang, W.T. Symonds, J. McHutchison, H. Masur, S. Kottilil
Journal: Journal of Hepatology (2014)
GLOMERULAR FILTRATION RESPONSE TO ACUTE PROTEIN LOAD
Authors: Y. Vanrenterghem, R. Verberckmoes, L. Roels, P. Michielsen, Hatem Mansy, J.S. Tapson, J. Fernandez, S. Tapster, R. Wilkinson, Michel Dhaene, Jean-Pierre Sabot, Yvan Philippart, Jean-Marc Doutrelepont, Jean-Louis Vanherweghem, Charles Toussaint
Journal: The Lancet (1985)
Position of patient and respiratory function in immediate postoperative period.
Authors: W J Russell
Journal: BMJ (1981)

Respiratory function was studied in 19 patients placed in both the supine and sitting positions in the early postoperative period. Although the sitting position was expected to improve respiratory function, no such advantage was found; instead, a small but statistically significant deterioration in arterial oxygenation was found in most patients when sitting up. It is concluded that no respiratory benefit should be expected from sitting patients up in the early postoperative period.
Transcriptional and Epigenetic Regulation of Opioid Receptor Genes: Present and Future
Authors: Li-Na Wei, Horace H. Loh
Journal: The Annual Review of Pharmacology and Toxicology (2011)

Three opioid receptors (ORs) are known: μ opioid receptors (MORs), δ opioid receptors (DORs), and κ opioid receptors (KORs). Each is encoded by a distinct gene, and the three OR genes share a highly conserved genomic structure and promoter features, including an absence of TATA boxes and sensitivity to extracellular stimuli and epigenetic regulation. However, each of the genes is differentially expressed. Transcriptional regulation engages both basal and regulated transcriptional machineries and employs activating and silencing mechanisms. In retinoic acid-induced neuronal differentiation, the opioid receptor genes undergo drastically different chromatin remodeling processes and display varied patterns of epigenetic marks. Regulation of KOR expression is distinctly complex, and KOR exerts a unique function in neurite extension, indicating that KOR is not simply a pharmacological cousin of MOR and DOR. As the expression of OR proteins is ultimately controlled by extensive posttranscriptional processing, the pharmacological implication of OR gene regulation at the transcriptional level remains to be determined.
The p53 Family Protein p73 Provides New Insights into Cancer Chemosensitivity and Targeting
Authors: Paolo Lunghi, Antonio Costanzo, Laura Mazzera, Vittorio Rizzoli, Massimo Levrero, Antonio Bonati
Journal: Clinical Cancer Research (2009)

Abstract The p53 tumor suppressor is part of a small family of related proteins that includes two other members, p73 and p63. Interest in the p53 family members, their functions and their complex interactions and regulation, has steadily grown over recent years and does not show signs of waning. p73 is a major determinant of chemosensitivity in humans, and mutant p53 proteins carrying specific polymorphisms can induce drug resistance by inhibiting TAp73. Cooperation between TA (transactivating, proapoptotic, antiproliferative) and ΔN (truncated, antiapoptotic, pro-proliferative) p73 isoforms and among the three family members guarantees equilibrium between proliferation, differentiation, and cell death, thus creating a harmony that is lost in several human cancers. In this article, we review our current knowledge of the role of p73 in cancer chemosensitivity and the real prospect of therapy targeting this molecule. We also draw attention to the crucial role of specific phosphorylation and acetylation events for p73-induced apoptosis and drug chemosensitivity. (Clin Cancer Res 2009;15(21):6495–502)
Targeted Imaging of Ewing Sarcoma in Preclinical Models Using a 64Cu-Labeled Anti-CD99 Antibody
Authors: Allison F. O'Neill, Jason L.J. Dearling, Yuchuan Wang, Tanya Tupper, Yanping Sun, Jon C. Aster, Monica L. Calicchio, Antonio R. Perez-Atayde, Alan B. Packard, Andrew L. Kung
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Ewing sarcoma is a tumor of the bone and soft tissue characterized by diffuse cell membrane expression of CD99 (MIC2). Single-site, surgically resectable disease is associated with an excellent 5-year event-free survival; conversely, patients with distant metastases have a poor prognosis. Noninvasive imaging is the standard approach to identifying sites of metastatic disease. We sought to develop a CD99-targeted imaging agent for staging Ewing sarcoma and other CD99-expressing tumors. Experimental Design: We identified a CD99 antibody with highly specific binding in vitro and labeled this antibody with 64Cu. Mice with either subcutaneous Ewing sarcoma xenograft tumors or micrometastases were imaged with the 64Cu-labeled anti-CD99 antibody and these results were compared with conventional MRI and 2[18F]fluoro-2-deoxy-d-glucose–positron emission tomography (FDG–PET) imaging. Results: 64Cu-labeled anti-CD99 antibody demonstrated high avidity for the CD99-positive subcutaneous tumors, with a high tumor-to-background ratio, greater than that demonstrated with FDG–PET. Micrometastases, measuring 1 to 2 mm on MRI, were not detected with FDG–PET but were readily visualized with the 64Cu-labeled anti-CD99 antibody. Probe biodistribution studies demonstrated high specificity of the probe for CD99-positive tumors. Conclusions: 64Cu-labeled anti-CD99 antibody can detect subcutaneous Ewing sarcoma tumors and metastatic sites with high sensitivity, outperforming FDG–PET in preclinical studies. This targeted radiotracer may have important implications for the diagnosis, surveillance, and treatment of Ewing sarcoma. Similarly, it may impact the management of other CD99 positive tumors. Clin Cancer Res; 20(3); 678–87. ©2013 AACR.
Animal Solutions to Problems of Movement Control: The Role of Proprioceptors
Authors: Z Hasan, D G Stuart
Journal: Annual Review of Neuroscience (1988)

In this review we address some of the problems encountered by the central nervous system (CNS) for the control of limb movement, and the strategies employed for their resolution by the utilization of proprioceptive infor­ mation.l The problems to be discussed arise partly from the mechanics of the musculoskeletal system and partly from the interactions of this system with the physical environment; they are subsequently considered under these two headings. That the CNS is able to make the available mechanical structures do its bidding is self evident. The feasibility of such proficient control in the field of robotics, however, remains only a future possibility. In fact, the motor performance of biological organisms is regarded as an existence proof of this feasibility (Raibert 1986). Although in this review we do not discuss the strategies adopted by roboticists (e.g. Shin & Malin 1984), we recognize that the elucidation of these strategies and the study of biological motor
Management of Thyroid Carcinoma: Hahnemann Experience.
Authors: Simin Dadparvar, John E. Lahaniatis, Fariba Asrari, Athar A. Shaikh, Nasrin V. Ghesani, Mark Tülchinsky, Mingzhi Pan, Walter J. Slizofski, Luther W. Brady
Journal: Clinical Nuclear Medicine (1999)

Scientific Abstracts And Posters From The 44Th Annual Meeting Of The Southwestern Chapter Of The Society Of Nuclear Medicine, And From The 12Th Northeastern Regional Scientific Meeting Of The New England And New York Chapters Of The Society Of Nuclear Medicine
Prognostic Significance of T-Cell or Cytotoxic Molecules Phenotype in Classical Hodgkin’s Lymphoma: A Clinicopathologic Study
Authors: Naoko Asano, Aya Oshiro, Keitaro Matsuo, Yoshitoyo Kagami, Fumihiro Ishida, Ritsuro Suzuki, Tomohiro Kinoshita, Yoshie Shimoyama, Jun-Ichi Tamaru, Tadashi Yoshino, Kunio Kitamura, Hisashi Fukutani, Yasuo Morishima, Shigeo Nakamura
Journal: Journal of Clinical Oncology (2006)

Classical Hodgkin's lymphoma (CHL) is characterized by Hodgkin's and Reed-Sternberg (H-RS) cells, most of which are derived from germinal-center B cells. Nevertheless, one or more markers for T cells and follicular dendritic cells (FDC) may be expressed in a minority of H-RS cells in some CHL patients, although the clinical significance of this remains controversial. The aim of this study was to clarify the association between phenotypic expression and clinical outcome in CHL.Participants were 324 consecutive CHL patients, comprising 132 patients with nodular sclerosis (NS), 35 patients with NS grade 2 (NS2), and 157 patients with mixed cellularity (MC). We evaluated the presenting features and prognosis of patients on categorization into four phenotypically defined groups: B-cell (CD20+ and/or CD79a+; n = 63), T-cell and/or cytotoxic molecules (CD3+, CD4+, CD8+, CD45RO+, TIA-1+, and/or granzyme B+; n = 27), FDC (CD21+ without B-cell marker; n = 22), and null-cell types (n = 212). Other potential prognostic factors were examined.The T-cell and/or cytotoxic molecules group showed a significantly poorer prognosis than the other three groups (P < .0001). This finding was seen consistently in multivariate analyses. Morphologic subtyping (NS/NS2/MC) and Epstein-Barr virus positivity were not identified as independent prognostic factors.The presence of T-cell and/or cytotoxic antigens in H-RS cells may represent a poor prognostic factor in CHL, even if their expression is not regarded as lineage specific. Examination of T-cell and/or cytotoxic molecules phenotype in CHL patients is recommended as a routine pathologic practice.
Direct Cardiac Effects of Dopamine
Authors: John C. Holmes, Nobel O. Fowler
Journal: Circulation Research (1962)

The cardiac effects of dopaminie, an epinephrine precursor, were studied in 20 dog heart-lung preparations. In 8 uncontrolled rate preparations. dopamine, 0.5 to 1 mg., increased the heart rate an average of 18 pet cent. In controlled rate preparations. dopamine, 100 to 500 µg ., consistently increased ventricular contractile force, cardiac output and blood pressure; there was a consistent decrease of right and left atrial pressure. Comparable hemodynamic effects were produced by 1 to 5 µg . of levarterenol, except that the effects of dopamine tended to be of longer duration and were less likely to be followed by cardiac depression. It is concluded that doparnine has significant positive inotropic and chronotropic effects in the dog heart-lung preparation.
Fluorescence Proteins, Live-Cell Imaging, and Mechanobiology: Seeing Is Believing
Authors: Yingxiao Wang, John Y.-J. Shyy, Shu Chien
Journal: Annual Review of Biomedical Engineering (2008)

Fluorescence proteins (FPs) have been widely used for live-cell imaging in the past decade. This review summarizes the recent advances in FP development and imaging technologies using FPs to monitor molecular localization and activities and gene expressions in live cells. We also discuss the utilization of FPs to develop molecular biosensors and the principles and application of advanced technologies such as fluorescence resonance energy transfer (FRET), fluorescence recovery after photobleaching (FRAP), fluorescence lifetime imaging microscopy (FLIM), and chromophore-assisted light inactivation (CALI). We present examples of the application of FPs and biosensors to visualize mechanotransduction events with high spatiotemporal resolutions in live cells. These live-cell imaging technologies, which represent a frontier area in biomedical engineering, can shed new light on the mechanisms regulating mechanobiology at cellular and molecular levels in normal and pathophysiological conditions.
Critical science gaps impede use of no-take fishery reserves
Authors: Peter F. Sale, Robert K. Cowen, Bret S. Danilowicz, Geoffrey P. Jones, Jacob P. Kritzer, Kenyon C. Lindeman, Serge Planes, Nicholas V.C. Polunin, Garry R. Russ, Yvonne J. Sadovy, Robert S. Steneck
Journal: Trends in Ecology & Evolution (2004)
Use of multiperspective qualitative interviews to understand patients' and carers' beliefs, experiences, and needs
Authors: M. Kendall, S. A Murray, E. Carduff, A. Worth, F. Harris, A. Lloyd, D. Cavers, L. Grant, K. Boyd, A. Sheikh
Journal: BMJ (2009)

A better understanding of the needs of patients and their carers can help improve services.Marilyn Kendall and colleagues describe how to conduct multiperspective studies Linked interviews conducted with patients and their informal and professional carers can generate a richer understanding of needs and experiences than the single perspective most commonly used in qualitative studies.Interview dyads or triads, where two or three participants are interviewed as a set or case study, can explore complex complementary as well as contradictory perspectives, and there is considerable scope for using this method in a range of long term conditions.
Louse-borne relapsing fever (Borrelia recurrentis) diagnosed in 15 refugees from northeast Africa: epidemiology and preventive control measures, Bavaria, Germany, July to October 2015
Authors: Martin Hoch, Andreas Wieser, Thomas Löscher, Gabriele Margos, Friedrich Pürner, Jürgen Zühl, Michael Seilmaier, Lukas Balzer, Wolfgang Guggemos, Anita Rack-Hoch, Ulrich von Both, Katja Hauptvogel, Katharina Schönberger, Wolfgang Hautmann, Andreas Sing, Volker Fingerle
Journal: Eurosurveillance (2015)

We report 15 imported louse-borne relapsing fever (LBRF) cases in refugees in Bavaria, Germany. One patient died. Epidemiological findings confirmed that all were young males from the Horn of Africa (12 from Somalia), who had similar migration routes converging in Sudan continuing through Libya and Italy. The majority likely acquired their infection during migration. Healthcare workers should be aware of LBRF in refugees passing through north Africa to ensure correct treatment and preventive measures.
Antitumor Effects in Hepatocarcinoma of Isoform-Selective Inhibition of HDAC2
Authors: Yun-Han Lee, Daekwan Seo, Kyung-Ju Choi, Jesper B. Andersen, Min-Ah Won, Mitsuteru Kitade, Luis E. Gómez-Quiroz, Adam D. Judge, Jens U. Marquardt, Chiara Raggi, Elizabeth A. Conner, Ian MacLachlan, Valentina M. Factor, Snorri S. Thorgeirsson
Journal: Cancer Research (2014)

Abstract Histone deacetylase 2 (HDAC2) is a chromatin modifier involved in epigenetic regulation of cell cycle, apoptosis, and differentiation that is upregulated commonly in human hepatocellular carcinoma (HCC). In this study, we show that specific targeting of this HDAC isoform is sufficient to inhibit HCC progression. siRNA-mediated silencing of HDAC inhibited HCC cell growth by blocking cell-cycle progression and inducing apoptosis. These effects were associated with deregulation of HDAC-regulated genes that control cell cycle, apoptosis, and lipid metabolism, specifically, by upregulation of p27 and acetylated p53 and by downregulation of CDK6 and BCL2. We found that HDAC2 silencing in HCC cells also strongly inhibited PPARγ signaling and other regulators of glycolysis (ChREBPα and GLUT4) and lipogenesis (SREBP1C and FAS), eliciting a marked decrease in fat accumulation. Notably, systemic delivery of HDAC2 siRNA encapsulated in lipid nanoparticles was sufficient to blunt the growth of human HCC in a murine xenograft model. Our findings offer preclinical proof-of-concept for HDAC2 blockade as a systemic therapy for liver cancer. Cancer Res; 74(17); 4752–61. ©2014 AACR.
CD4-guided scheduled treatment interruptions compared with continuous therapy for patients infected with HIV-1: results of the Staccato randomised trial
Authors: Jintanat Ananworanich, Angèle Gayet-Ageron, Michelle Le Braz, Wisit Prasithsirikul, Ploenchan Chetchotisakd, Sasisopin Kiertiburanakul, Warangkana Munsakul, Phitsanu Raksakulkarn, Somboon Tansuphasawasdikul, Sunee Sirivichayakul, Matthias Cavassini, Urs Karrer, Daniel Genné, Reto Nüesch, Pietro Vernazza, Enos Bernasconi, Dominic Leduc, Claudette Satchell, Sabine Yerly, Luc Perrin, Andrew Hill, Thomas Perneger, Praphan Phanuphak, Hansjakob Furrer, David Cooper, Kiat Ruxrungtham, Bernard Hirschel
Journal: The Lancet (2006)
Use of System-Wide Outcomes Monitoring Data to Compare the Effectiveness of Atypical Neuroleptic Medications
Authors: Michael J. Sernyak, Douglas Leslie, Robert Rosenheck
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: Outcomes monitoring data in a large health care system were used to evaluate the effectiveness of atypical neuroleptic medications in actual clinical practice. METHOD: National administrative data from the Department of Veterans Affairs were used to identify patients with schizophrenia who had no change in antipsychotic medication over a 3-month index period in 1999 and for whom Global Assessment of Functioning Scale ratings were available from both the index period and the following year (N=9,066). Analysis of covariance, including potentially confounding factors, was used to compare change in functioning scores between patients who continued to take the same medication and those whose medication was switched during the follow-up year. Among patients whose medication was switched, change in functioning scores was compared by whether patients received a conventional neuroleptic or each of the four then available atypical neuroleptics after the medication switch. RESULTS: Patients who continued to take the same medication (N=7,157, 78.9%) had improved functioning scores from the index period to the follow-up year, while patients whose medication was switched (N=1,909, 21.1%) had declining functioning scores (mean change in scores of 0.6% and –3.7%, respectively). Among the patients whose medication was switched, no significant differences in functioning were found between patients grouped by the new type of medication received. CONCLUSIONS: In this large administrative database, patients with schizophrenia whose neuroleptic medication was switched showed significantly less improvement in Global Assessment of Functioning Scale scores than patients who continued to take their original medication. No significant differences in functioning scores were found for patients whose medication was switched to any of the atypical neuroleptics.
Randomized Dose-Escalation Study Evaluating Peginterferon Alfa-2a in Patients With Metastatic Malignant Melanoma
Authors: Reinhard Dummer, Claus Garbe, John A. Thompson, Alexander M. Eggermont, Kisook Yoo, Tanja Maier, Bengt Bergstrom
Journal: Journal of Clinical Oncology (2006)

A pegylated interferon, peginterferon alfa-2a (PEG-IFNalpha-2a; 40 kd), has the potential for improved tumor response and survival with lower toxicity than IFNalpha. This open-label, randomized study evaluated the safety, tolerability, and efficacy of subcutaneous PEG-IFNalpha-2a in patients with metastatic malignant melanoma (stage IV American Joint Committee on Cancer staging system).PEG-IFNalpha-2a was administered subcutaneously at 180 (n = 48), 360 (n = 53), or 450 mug (n = 49) once weekly for 24 weeks, with maintenance therapy for responders. Efficacy was assessed by the proportion of patients with complete response (CR) or partial response (PR).The major response rate (CR or PR) was 6% in the 180-mug group (CR, 2%; PR, 4%), 8% in the 360-mug group (CR, 2%; PR, 6%), and 12% in the 450-mug group (CR, 6%; PR, 6%). The times to achieve a major response, duration of major response, rate of disease progression, and 12-month survival were similar between groups, although overall median survival was significantly different among the three groups (P = .0136). More patients required dose adjustment for safety reasons in the higher dose groups, but PEG-IFNalpha-2a was generally well tolerated, with few withdrawals because of adverse events (6%, 19%, and 16% in the 180-, 360-, and 450-mug groups, respectively). The most common adverse events were fatigue, pyrexia, and nausea.PEG-IFNalpha-2a at doses up to 450 mug once weekly has shown good tolerability and similar efficacy to conventional IFNalpha and monochemotherapy in stage IV metastatic melanoma.
Effect of urbanisation on the relationship between total serum IgE and asthma
Authors: William Checkley, Colin L. Robinson, Lauren M. Baumann, Karina Romero, Juan M. Combe, Robert H. Gilman, Robert A. Wise, Robert G. Hamilton, Guillermo Gonzalvez, Vitaliano Cama, Nadia N. Hansel
Journal: European Respiratory Journal (2012)

It is unclear if the relationship of total serum IgE with asthma varies with degree of urbanisation. We hypothesised that the relationship of total serum IgE to asthma is more pronounced in an urban <i>versus</i> a rural environment. We enrolled 1441 children aged 13–15 years in a peri-urban shanty town in Lima, Peru (n=725) and 23 villages in rural Tumbes, Peru (n=716). We asked participants about asthma and allergy symptoms, environmental exposures and sociodemographics; and performed spirometry, and exhaled nitric oxide and allergy skin testing. We obtained blood for total serum IgE in 1143 (79%) participants. Geometric means for total serum IgE were higher in Lima <i>versus</i> Tumbes (262 <i>versus</i> 192 kU·L<sup>−1</sup>; p&lt;0.001). The odds of asthma increased by factors of 1.6 (95% CI 1.3–2.0) <i>versus</i> 1.4 (95% CI 0.9–2.1) per log unit increase in total serum IgE in Lima <i>versus</i> Tumbes, respectively. Atopy was an effect modifier of the relationship of total serum IgE on asthma. Among atopics and non-atopics, the odds of asthma increased by a factor of 2.0 (95% CI 1.5–2.7) and 1.0 (95% CI 0.7–1.4) per log unit increase in total serum IgE, respectively. Total serum IgE was associated with atopic asthma but not with non-atopic asthma. Urbanisation did not appear to be an effect modifier of this relationship.