tbuckley/cabot-search huggingface dataset:
Knockout of the neural and heart expressed gene results in apical deficits of ventricular structure and activation
Authors: K HEWETT, L NORMAN, D SEDMERA, R BARKER, C JUSTUS, J ZHANG, S KUBALAK, R GOURDIE
Journal: Cardiovascular Research (2005)

Journal Article Knockout of the neural and heart expressed gene HF-1b results in apical deficits of ventricular structure and activation Get access Kenneth W. Hewett, Kenneth W. Hewett Department of Cell Biology and Anatomy, Cardiovascular Developmental Biology Center, Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC 29425 United States Search for other works by this author on: Oxford Academic PubMed Google Scholar Lisa W. Norman, Lisa W. Norman Department of Cell Biology and Anatomy, Cardiovascular Developmental Biology Center, Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC 29425 United States Search for other works by this author on: Oxford Academic PubMed Google Scholar David Sedmera, David Sedmera Department of Cell Biology and Anatomy, Cardiovascular Developmental Biology Center, Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC 29425 United States Search for other works by this author on: Oxford Academic PubMed Google Scholar Ralph J. Barker, Ralph J. Barker Department of Cell Biology and Anatomy, Cardiovascular Developmental Biology Center, Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC 29425 United States Search for other works by this author on: Oxford Academic PubMed Google Scholar Charles Justus, Charles Justus Department of Cell Biology and Anatomy, Cardiovascular Developmental Biology Center, Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC 29425 United States Search for other works by this author on: Oxford Academic PubMed Google Scholar Jing Zhang, Jing Zhang Department of Cell Biology and Anatomy, Cardiovascular Developmental Biology Center, Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC 29425 United States Search for other works by this author on: Oxford Academic PubMed Google Scholar Steven W. Kubalak, Steven W. Kubalak Department of Cell Biology and Anatomy, Cardiovascular Developmental Biology Center, Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC 29425 United States Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert G. Gourdie Robert G. Gourdie * Department of Cell Biology and Anatomy, Cardiovascular Developmental Biology Center, Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC 29425 United States *Corresponding author. Tel.: +1 843 792 8181; fax: +1 843 792 0664. Email address: [email protected] Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 67, Issue 3, August 2005, Pages 548–560, https://doi.org/10.1016/j.cardiores.2005.04.002 Published: 15 August 2005 Article history Received: 31 December 2004 Revision received: 31 March 2005 Accepted: 04 April 2005 Published: 15 August 2005
FURTHER STUDIES ON ADOPTIVE TRANSFER OF SENSITIVITY TO SKIN HOMOGRAFTS
Authors: R. E. Billingham, Willys K. Silvers, Darcy B. Wilson
Journal: The Journal of Experimental Medicine (1963)

Mice or rats that have been rendered tolerant of skin homografts from an alien donor strain furnish the basis of a very sensitive and objective test system for investigating the competence of cellular inocula from specifically immunized isologous donors to transfer sensitivity adoptively. By means of this test system it has been shown that immunologically "activated" cells, capable of transferring homograft sensitivity, are present in the blood, peritoneal exudates, and regional nodes of animals that have rejected skin homografts. Leucocytes were as effective as regional node cells. Activated cells were first demonstrable in the regional nodes and blood of skin homograft recipients at the same time,—on the 6th postoperative day,—suggesting that these cells must enter the circulation very soon after their formation in the nodes. Moreover, when sensitization was effected by skin homografts, but not by means of splenic cell suspensions inoculated intraperitoneally, activated cells are highly persistent, still being demonstrable in both the blood and the nodes more than a year after sensitization. The finding that thoracic duct cells, which are almost exclusively lymphocytes, were just as effective as leucocytes or regional nodes in transferring sensitivity in rats formally identifies the cell type responsible for transferring sensitivity in the various tissues tested. Attempts to transfer sensitivity to homografts in normal mice or tolerant mice by means of larger dosages of activated lymphoid cells sequestered in Millipore chambers inserted intraperitoneally were unsuccessful. All this, and other evidence presented, lends strength to the thesis that skin homograft immunity is a cell-mediated reaction.
Randomized Phase II Trial of Concurrent Cisplatin-Radiotherapy With or Without Neoadjuvant Docetaxel and Cisplatin in Advanced Nasopharyngeal Carcinoma
Authors: Edwin P. Hui, Brigette B. Ma, Sing F. Leung, Ann D. King, Frankie Mo, Michael K. Kam, Brian K. Yu, Samuel K. Chiu, Wing H. Kwan, Rosalie Ho, Iris Chan, Anil T. Ahuja, Benny C. Zee, Anthony T. Chan
Journal: Journal of Clinical Oncology (2008)

To compare the toxicities, tumor control, survival, and quality of life of nasopharyngeal cancer (NPC) patients treated with sequential neoadjuvant chemotherapy followed by concurrent cisplatin-radiotherapy (CRT) or CRT alone.Previously untreated stage III to IVB NPC were randomly assigned to (1) neoadjuvant docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2) every 3 weeks for two cycles, followed by cisplatin 40 mg/m(2)/wk concurrent with radiotherapy, or (2) CRT alone. Planned accrual was 30 patients per arm to detect 20% difference of toxicities based on 95% CIs.From November 2002 to November 2004, 65 eligible patients were randomly assigned to neoadjuvant chemotherapy followed by CRT (n = 34) or CRT alone (n = 31). There was a high rate of grade 3/4 neutropenia (97%) but not neutropenic fever (12%) during neoadjuvant chemotherapy. No significant differences in rates of acute toxicities were observed between the two arms during CRT. Dose intensities of concurrent cisplatin, late RT toxicities and quality of life scores were comparable in both arms. The 3-year progression-free survival for neoadjuvant versus control arm was 88.2% and 59.5% (hazard ratio = 0.49; 95% CI, 0.20 to 1.19; P = .12). The 3-year overall survival for neoadjuvant versus control arm was 94.1% and 67.7% (hazard ratio = 0.24; 95% CI, 0.078 to 0.73; P = .012).Neoadjuvant docetaxel-cisplatin followed by CRT was well tolerated with a manageable toxicity profile that allowed subsequent delivery of full-dose CRT. Preliminary results suggested a positive impact on survival. A phase III study to definitively test this neoadjuvant-concurrent strategy is warranted.
Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study
Authors: Caicun Zhou, Yi-Long Wu, Gongyan Chen, Jifeng Feng, Xiao-Qing Liu, Changli Wang, Shucai Zhang, Jie Wang, Songwen Zhou, Shengxiang Ren, Shun Lu, Li Zhang, Chengping Hu, Chunhong Hu, Yi Luo, Lei Chen, Ming Ye, Jianan Huang, Xiuyi Zhi, Yiping Zhang, Qingyu Xiu, Jun Ma, Li Zhang, Changxuan You
Journal: The Lancet Oncology (2011)
Plasma Angiotensin-Converting Enzyme Activity and Left Ventricular Dilation After Myocardial Infarction
Authors: Margreeth Oosterga, Adriaan A. Voors, Pieter-Jan de Kam, Heribert Schunkert, Yigal M. Pinto, J. Herre Kingma, Wiek H. van Gilst
Journal: Circulation (1997)

Background Left ventricular dilation after acute myocardial infarction (MI) is mainly determined by infarct size. In addition, this detrimental structural adaptation seems to be augmented in patients with the ACE DD genotype. The ACE DD genotype is associated with increased ACE activity. The aim of the present study was to evaluate whether ACE activity per se may carry prognostic significance for subsequent left ventricular dilation as assessed by echocardiography during 1-year follow-up after acute MI. Methods and Results Left ventricular end-systolic and end-diastolic volume indexes were assessed by two-dimensional echocardiography. In 102 consecutive patients, plasma ACE activity was determined 3.7±0.1 hours after the onset of MI. In 64 of these patients, left ventricular volume indexes obtained at baseline and 1 year after MI were used for the present analysis. Patients were divided into a group having low ACE activity (≤12 IU/L, n=15) and a group having high ACE activity (&gt;12 IU/L, n=49). Infarct size was a significant predictor of the increase in left ventricular volume indexes ( P =.0001) in these patients. Multivariate regression analysis, after correction for infarct size, demonstrated that elevated plasma ACE activity is a significant predictor of the increase in left ventricular end-diastolic and end-systolic volume indexes ( P =.0006 and P =.02, respectively) 1 year after MI. Conclusions Elevated plasma ACE activity determined soon after the onset of MI may be a significant predictor of the development of left ventricular dilation and may identify patients at risk.
TRP channels: new targets for visceral pain
Authors: L A Blackshaw, S M Brierley, P A Hughes
Journal: Gut (2009)

How often do gastroenterologists advise patients to “avoid spicy food” without really knowing why? The answer may lie in the family of transient receptor potential (TRP) channels, which includes receptors for compounds found in common herbs and spices. This aim of this review is not really to answer this question, but it will shed light on why spices may cause symptoms. Instead, its aim is to explore the TRP family for potential targets that may in fact reduce gut symptoms. Chronic pain and discomfort of unknown origin in functional gastrointestinal disorders represent a large unmet need for treatment and consequent economic impact. There are also features of other gut disease which generate symptoms with obscure origins. In order to understand how symptoms are generated in the gut and transmitted to the central nervous system, we need to know at least three principles of extrinsic sensory nerve function—first, what types are there and what do they signal?; secondly, what is the molecular basis of sensory transduction?; and thirdly, how does all of this change in disease? These questions are a key focus of this article, with a particular emphasis on the role of TRP channels in each case. Although there are no drugs yet available for clinical use that target TRP channels, some of the early pointers are identified that hold promise for their use in pharmacotherapy of gastrointestinal sensory dysfunction.

### Subtypes of sensory fibres

Peripheral endings of sensory afferent fibres can be classified into five subtypes in the mouse gastrointestinal tract according to the location of their mechanoreceptive fields.1 2 These are: mucosal, muscular (or tension receptor), muscular–mucosal (or tension–mucosal), serosal and mesenteric afferents (fig 1).1 2 3 4 Mucosal afferents respond exclusively to fine tactile stimulation of the luminal surface. Anatomically, they appear as bare endings in the lamina propria …
PD-005 Combined analysis of two randomised Phase II trials comparing the efficacy and safety of nintedanib versus sorafenib in Caucasian and Asian patients with advanced hepatocellular carcinoma
Authors: D. Palmer, T. Meyer, Y. Chao, A. Deptala, L. Fartoux, Y.-H. Feng, J. Graham, D.-Y. Lin, Y.T. Ma, M. Peck-Radosavljevic, P. Ross, B.-Y. Ryoo, C.-J. Yen, J. Hocke, S. Vlassak, A. Wenz, A.-B. Loembe, A.-L. Cheng
Journal: Annals of Oncology (2015)
High Fitness Costs and Instability of Gene Duplications Reduce Rates of Evolution of New Genes by Duplication-Divergence Mechanisms
Authors: M. Adler, M. Anjum, O. G. Berg, D. I. Andersson, L. Sandegren
Journal: Molecular Biology and Evolution (2014)

An important mechanism for generation of new genes is by duplication-divergence of existing genes. Duplication-divergence includes several different submodels, such as subfunctionalization where after accumulation of neutral mutations the original function is distributed between two partially functional and complementary genes, and neofunctionalization where a new function evolves in one of the duplicated copies while the old function is maintained in another copy. The likelihood of these mechanisms depends on the longevity of the duplicated state, which in turn depends on the fitness cost and genetic stability of the duplications. Here, we determined the fitness cost and stability of defined gene duplications/amplifications on a low copy number plasmid. Our experimental results show that the costs of carrying extra gene copies are substantial and that each additional kilo base pairs of DNA reduces fitness by approximately 0.15%. Furthermore, gene amplifications are highly unstable and rapidly segregate to lower copy numbers in absence of selection. Mathematical modeling shows that the fitness costs and instability strongly reduces the likelihood of both sub- and neofunctionalization, but that these effects can be offset by positive selection for novel beneficial functions.
886 IMPACT OF THE VIRAL KINETICS OF CHRONIC HEPATITIS C PATIENTS TREATED WITH TELAPREVIR IN COMBINATION WITH PEGYLATED INTERFERON a2b AND RIBAVIRIN
Authors: E. Ogawa, N. Furusyo, M. Nakamuta, E. Kajiwara, H. Nomura, K. Dohmen, K. Takahashi, T. Satoh, K. Azuma, A. Kawano, Y. Tanabe, K. Kotoh, S. Shimoda, J. Hayashi
Journal: Journal of Hepatology (2013)
Cognitive Behavioral Therapy vs Zopiclone for Treatment of Chronic Primary Insomnia in Older Adults
Authors: Børge Sivertsen, Siri Omvik, Ståle Pallesen, Bjørn Bjorvatn, Odd E Havik, Gerd Kvale, Geir Høstmark Nielsen, Inger Hilde Nordhus
Journal: JAMA (2006)

ContextInsomnia is a common condition in older adults and is associated with a number of adverse medical, social, and psychological consequences. Previous research has suggested beneficial outcomes of both psychological and pharmacological treatments, but blinded placebo-controlled trials comparing the effects of these treatments are lacking.ObjectiveTo examine short- and long-term clinical efficacy of cognitive behavioral therapy (CBT) and pharmacological treatment in older adults experiencing chronic primary insomnia.Design, Setting, and ParticipantsA randomized, double-blinded, placebo-controlled trial of 46 adults (mean age, 60.8 y; 22 women) with chronic primary insomnia conducted between January 2004 and December 2005 in a single Norwegian university-based outpatient clinic for adults and elderly patients.InterventionCBT (sleep hygiene, sleep restriction, stimulus control, cognitive therapy, and relaxation; n = 18), sleep medication (7.5-mg zopiclone each night; n = 16), or placebo medication (n = 12). All treatment duration was 6 weeks, and the 2 active treatments were followed up at 6 months.Main Outcome MeasuresAmbulant clinical polysomnographic data and sleep diaries were used to determine total wake time, total sleep time, sleep efficiency, and slow-wave sleep (only assessed using polysomnography) on all 3 assessment points.ResultsCBT resulted in improved short- and long-term outcomes compared with zopiclone on 3 out of 4 outcome measures. For most outcomes, zopiclone did not differ from placebo. Participants receiving CBT improved their sleep efficiency from 81.4% at pretreatment to 90.1% at 6-month follow-up compared with a decrease from 82.3% to 81.9% in the zopiclone group. Participants in the CBT group spent much more time in slow-wave sleep (stages 3 and 4) compared with those in other groups, and spent less time awake during the night. Total sleep time was similar in all 3 groups; at 6 months, patients receiving CBT had better sleep efficiency using polysomnography than those taking zopiclone.ConclusionThese results suggest that interventions based on CBT are superior to zopiclone treatment both in short- and long-term management of insomnia in older adults.Trial Registrationclinicaltrials.gov Identifier: NCT00295386
Activation of the transcription factor NF-kappa B in the rat air pouch model of inflammation
Authors: L Ellis
Journal: Annals of the Rheumatic Diseases (2000)

<h3>OBJECTIVE</h3> To investigate the activation of NF-κB in the carrageenan rat air pouch model of inflammation in a time course experiment, and the effect of dexamethasone on NF-κB activation. <h3>METHODS</h3> Air pouch tissue treated with carrageenan (inflamed tissue) was obtained from rats killed at days 1, 2, 3, 6, 14, 21, 28 and 35 after carrageenan challenge. Tissue was also taken from non-carrageenan treated pouches (non-inflamed tissue) at day 3, and from inflamed tissues treated with dexamethasone. Tissue sections were wax embedded and stained with an “activity specific” monoclonal antibody raised against the nuclear localisation signal (NLS) of the p65 sub-unit of NF-κB. <h3>RESULTS</h3> Cells containing activated NF-κB were detected in the intimal and sub-intimal regions of the air pouches as early as day 1. There was a significant increase in cells staining for activated NF-κB as the inflammation progressed. Initially cells staining were more prominent in the intimal versus sub-intimal region (p&lt;0.001 for day 1) and at later time points the pattern was reversed (p&lt;0.001 for day 6). There was a significant reduction in the number of cells staining for activated NF-κB in tissue taken from dexamethasone treated rats, compared with inflamed pouches alone (p&lt;0.001). At no time point was positive staining for activated NF-κB observed in blood vessels. <h3>CONCLUSIONS</h3> Activated NF-κB is present in the inflamed air pouch and the activation is associated with the inflammatory response to carrageenan. Treatment with dexamethasone resulted in reduced numbers of cells staining for activated NF-κB.
The Neuropsychopharmacology of Fronto-Executive Function: Monoaminergic Modulation
Authors: T.W. Robbins, A.F.T. Arnsten
Journal: Annual Review of Neuroscience (2009)

We review the modulatory effects of the catecholamine neurotransmitters noradrenaline and dopamine on prefrontal cortical function. The effects of pharmacologic manipulations of these systems, sometimes in comparison with the indoleamine serotonin (5-HT), on performance on a variety of tasks that tap working memory, attentional-set formation and shifting, reversal learning, and response inhibition are compared in rodents, nonhuman primates, and humans using, in a behavioral context, several techniques ranging from microiontophoresis and single-cell electrophysiological recording to pharmacologic functional magnetic resonance imaging. Dissociable effects of drugs and neurotoxins affecting these monoamine systems suggest new ways of conceptualizing state-dependent fronto-executive functions, with implications for understanding the molecular genetic basis of mental illness and its treatment.
Twenty-five years of progress in bilirubin metabolism (1952-77).
Authors: B H Billing
Journal: Gut (1978)

This review deals with the development of our understanding of the chemistry of bilirubin and its glucuronide derivatives during the years 1952-1977. It examines the relation between haem metabolism and bilirubin formation and our present knowledge of hepatic transport of bilirubin. The heterogeneity of familial hyperbilirubinaemia is discussed.
Interrogating the interactions between myeloid derived suppressor cells and cancer stem cells in glioblastoma
Authors: Balint Otvos, James Finke, Michael Vogelbaum, Justin D Lathia
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts Cellular and molecular regulation of the immune system is exquisitely controlled in the brain and is disrupted in neoplasia. Despite accumulation of immune cells in the tumor microenvironment, glioblastoma (GBM) growth persists while the mechanisms suppressing immune function
Doctor, What Are My Chances of Having a Positive Sentinel Node? A Validated Nomogram for Risk Estimation
Authors: José Luiz B. Bevilacqua, Michael W. Kattan, Jane V. Fey, Hiram S. Cody, Patrick I. Borgen, Kimberly J. Van Zee
Journal: Journal of Clinical Oncology (2007)

Purpose Lymph node metastasis is a multifactorial event. Several variables have been described as predictors of lymph node metastasis in breast cancer. However, it is difficult to apply these data—usually expressed as odds ratios—to calculate the probability of sentinel lymph node (SLN) metastasis for a specific patient. We developed a user-friendly prediction model (nomogram) based on a large data set to assist in predicting the presence of SLN metastasis. Patients and Methods Clinical and pathologic features of 3,786 sequential SLN biopsy procedures were assessed with multivariable logistic regression to predict the presence of SLN metastasis in breast cancer. The model was subsequently applied to 1,545 sequential SLN biopsies. A nomogram was created from the logistic regression model. A computerized version of the nomogram was developed and is available on the Memorial Sloan-Kettering Cancer Center (New York, NY) Web site. Results Age, tumor size, tumor type, lymphovascular invasion, tumor location, multifocality, and estrogen and progesterone receptors were associated with SLN metastasis in multivariate analysis. The nomogram was accurate and discriminating, with an area under the receiver operating characteristic curve of 0.754 when applied to the validation group. Conclusion Newly diagnosed breast cancer patients are increasingly interested in information about their disease. This nomogram is a useful tool that helps physicians and patients to accurately predict the likelihood of SLN metastasis.
In Vivo–Directed Evolution of a New Adeno-Associated Virus for Therapeutic Outer Retinal Gene Delivery from the Vitreous
Authors: Deniz Dalkara, Leah C. Byrne, Ryan R. Klimczak, Meike Visel, Lu Yin, William H. Merigan, John G. Flannery, David V. Schaffer
Journal: Science Translational Medicine (2013)

Injection of a new gene therapy vector into the easily accessible vitreous transduced the entire retina and rescued disease phenotypes.
Long-Term Prognosis of Diabetic Patients With Critical Limb Ischemia
Authors: Ezio Faglia, Giacomo Clerici, Jacques Clerissi, Livio Gabrielli, Sergio Losa, Manuela Mantero, Maurizio Caminiti, Vincenzo Curci, Antonella Quarantiello, Tommaso Luppattelli, Alberto Morabito
Journal: Diabetes Care (2009)

OBJECTIVE To evaluate the long-term prognosis of critical limb ischemia (CLI) in diabetic patients. RESEARCH DESIGN AND METHODS A total of 564 consecutive diabetic patients were hospitalized for CLI from January 1999 to December 2003; 554 were followed until December 2007. RESULTS The mean follow-up was 5.93 ± 1.28 years. Peripheral angioplasty (PTA) was performed in 420 (74.5%) and bypass graft (BPG) in 117 (20.6%) patients. Neither PTA nor BPG were possible in 27 (4.9%) patients. Major amputations were performed in 74 (13.4%) patients: 34 (8.2%) in PTA, 24 (21.1%) in BPG, and 16 (59.2%) in a group that received no revascularization. Restenosis occurred in 94 patients, bypass failures in 36 patients, and recurrent ulcers in 71 patients. CLI was observed in the contralateral limb of 225 (39.9%) patients; of these, 15 (6.7%) required major amputations (rate in contralateral compared with initial limb, P = 0.007). At total of 276 (49.82%) patients died. The Cox model showed significant hazard ratios (HRs) for mortality with age (1.05 for 1 year [95% CI 1.03–1.07]), unfeasible revascularization (3.06 [1.40–6.70]), dialysis (3.00 [1.63–5.53]), cardiac disease history (1.37 [1.05–1.79]), and impaired ejection fraction (1.08 for 1% point [1.05–1.09]). CONCLUSIONS Diabetic patients with CLI have high risks of amputation and death. In a dedicated diabetic foot center, the major amputation, ulcer recurrence, and major contralateral limb amputation rates were low. Coronary artery disease (CAD) is the leading cause of death, and in patients with CAD history the impaired ejection fraction is the major independent prognostic factor.