tbuckley/cabot-search huggingface dataset:
Blood Pressure Lowering in Type 2 Diabetes
Authors: Connor A. Emdin, Kazem Rahimi, Bruce Neal, Thomas Callender, Vlado Perkovic, Anushka Patel
Journal: JAMA (2015)

<h3>Importance</h3> Lowering blood pressure (BP) is widely used to reduce vascular risk in individuals with diabetes. <h3>Objective</h3> To determine the associations between BP–lowering treatment and vascular disease in type 2 diabetes. <h3>Data Sources and Study Selection</h3> We searched MEDLINE for large-scale randomized controlled trials of BP–lowering treatment including patients with diabetes, published between January 1966 and October 2014. <h3>Data Extraction and Synthesis</h3> Two reviewers independently extracted study characteristics and vascular outcome data. Estimates were stratified by baseline BP and achieved BP, and pooled using fixed-effects meta-analysis. <h3>Main Outcomes and Measures</h3> All-cause mortality, cardiovascular events, coronary heart disease events, stroke, heart failure, retinopathy, new or worsening albuminuria, and renal failure. <h3>Results</h3> Forty trials judged to be of low risk of bias (100 354 participants) were included. Each 10–mm Hg lower systolic BP was associated with a significantly lower risk of mortality (relative risk [RR], 0.87; 95% CI, 0.78-0.96); absolute risk reduction (ARR) in events per 1000 patient-years (3.16; 95% CI, 0.90-5.22), cardiovascular events (RR, 0.89 [95% CI, 0.83-0.95]; ARR, 3.90 [95% CI, 1.57-6.06]), coronary heart disease (RR, 0.88 [95% CI, 0.80-0.98]; ARR, 1.81 [95% CI, 0.35-3.11]), stroke (RR, 0.73 [95% CI, 0.64-0.83]; ARR, 4.06 [95% CI, 2.53-5.40]), albuminuria (RR, 0.83 [95% CI, 0.79-0.87]; ARR, 9.33 [95% CI, 7.13-11.37]), and retinopathy (RR, 0.87 [95% CI, 0.76-0.99]; ARR, 2.23 [95% CI, 0.15-4.04]). When trials were stratified by mean baseline systolic BP at greater than or less than 140 mm Hg, RRs for outcomes other than stroke, retinopathy, and renal failure were lower in studies with greater baseline systolic BP (<i>P</i>interaction &lt;0.1). The associations between BP-lowering treatments and outcomes were not significantly different, irrespective of drug class, except for stroke and heart failure. Estimates were similar when all trials, regardless of risk of bias, were included. <h3>Conclusions and Relevance</h3> Among patients with type 2 diabetes, BP lowering was associated with improved mortality and other clinical outcomes with lower RRs observed among those with baseline BP of 140 mm Hg and greater. These findings support the use of medications for BP lowering in these patients.
Technique and Results of Linear Ablation at the Mitral Isthmus
Authors: Pierre Jaïs, Mélèze Hocini, Li-Fern Hsu, Prashanthan Sanders, Christophe Scavee, Rukshen Weerasooriya, Laurent Macle, Florence Raybaud, Stéphane Garrigue, Dipen C. Shah, Philippe Le Metayer, Jacques Clémenty, Michel Haïssaguerre
Journal: Circulation (2004)

This prospective clinical study evaluates the feasibility and efficacy of combined linear mitral isthmus ablation and pulmonary vein (PV) isolation in patients with paroxysmal atrial fibrillation (AF).One hundred consecutive patients (13 women; age 55+/-10 years) with drug-refractory, symptomatic paroxysmal AF underwent PV isolation and linear ablation of the cavotricuspid isthmus and the mitral isthmus (lateral mitral annulus to the left inferior PV). They were compared with 100 consecutive patients (14 women; age, 52+/-10 years) undergoing PV isolation and cavotricuspid ablation without mitral isthmus ablation. Bidirectional mitral isthmus block was confirmed by demonstrating (1) a parallel corridor of double potentials during coronary sinus (CS) pacing, (2) an activation detour by pacing either side of the line, and (3) differential pacing techniques. Isolation of all PVs and cavotricuspid isthmus ablation were performed successfully in all. Mitral isthmus block was achieved in 92 patients after 20+/-10 minutes of endocardial radiofrequency application and an additional 5+/-4 minutes of epicardial radiofrequency application from within the CS in 68, resulting in a conduction delay of 151+/-26 ms during CS pacing. Thirty-two patients with mitral isthmus ablation compared with 49 without had recurrent atrial arrhythmia (P=0.02) requiring further ablation. At 1 year after the last procedure, 87 patients with mitral isthmus ablation and 69 without (P=0.002) were arrhythmia free without antiarrhythmic drugs, mitral isthmus ablation being the only factor associated with long-term success (RR for AF recurrence, 0.2; CI, 0.1 to 0.4; P<0.001).Catheter ablation of the mitral isthmus results consistently in demonstrable conduction block and is associated with a high cure rate for paroxysmal AF.
Fostering Sustainable, Integrated Medical and Behavioral Health Services in Medical Settings
Authors: Ron Manderscheid, Roger Kathol
Journal: Annals of Internal Medicine (2014)

The integration of behavioral health (BH) and primary care services has been the subject of considerable attention for almost a decade. Such work has been motivated by the prevalence of chronic health problems in persons with BH conditions and correspondingly high rates of early death. Service integration efforts typically included cross-referral or bidirectional efforts to add some features of primary care to specialty BH settings or the reverse. This article proposes a third approach based on full service and financial integration and shows how it differs substantially from the other 2 models. This new model has the potential to bring much-needed BH services to persons served in primary care settings who have these conditions, while fostering integrated services in specialty settings for those with the most severe mental or substance use conditions. The Patient Protection and Affordable Care Act could provide a valuable opportunity to implement this third model.
The Stoke CNEP Saga – did it need to take so long?
Authors: Frank Wells
Journal: Journal of the Royal Society of Medicine (2010)

In 1999, the Royal College of Physicians of Edinburgh, the Royal College of Physicians and Surgeons of Glasgow, the Royal College of Physicians of London, and the Faculty of Pharmaceutical Medicine convened a consensus conference on Misconduct in Biomedical Research. The conference concluded that a national panel should be established – with public representation – to provide advice and assistance (on issues of research misconduct) on request.1 It was suggested that the panel might develop and promote models of good practice for local implementation; provide assistance with the investigation of alleged research misconduct; and collect, collate and publish information on incidents of research misconduct. It was hoped that the report of the Conference would be given the fullest possible dissemination by the sponsoring bodies, and that they would convene at the earliest opportunity a meeting with the General Medical Council and appropriate partners to establish and consider the remit of the national panel.2
Antineoplastic effects of an Aurora B kinase inhibitor in breast cancer
Authors: Christopher P Gully, Fanmao Zhang, Jian Chen, James A Yeung, Guermarie Velazquez-Torres, Edward Wang, Sai-Ching Jim Yeung, Mong-Hong Lee
Journal: Molecular Cancer (2010)

Abstract Background Aurora B kinase is an important mitotic kinase involved in chromosome segregation and cytokinesis. It is overexpressed in many cancers and thus may be an important molecular target for chemotherapy. AZD1152 is the prodrug for AZD1152-HQPA, which is a selective inhibitor of Aurora B kinase activity. Preclinical antineoplastic activity of AZD1152 against acute myelogenous leukemia, multiple myeloma and colorectal cancer has been reported. However, this compound has not been evaluated in breast cancer, the second leading cause of cancer deaths among women. Results The antineoplastic activity of AZD1152-HQPA in six human breast cancer cell lines, three of which overexpress HER2, is demonstrated. AZD1152-HQPA specifically inhibited Aurora B kinase activity in breast cancer cells, thereby causing mitotic catastrophe, polyploidy and apoptosis, which in turn led to apoptotic death. AZD1152 administration efficiently suppressed the tumor growth in a breast cancer cell xenograft model. In addition, AZD1152 also inhibited pulmonary metastatic nodule formation in a metastatic breast cancer model. Notably, it was also found that the protein level of Aurora B kinase declined after inhibition of Aurora B kinase activity by AZD1152-HQPA in a time- and dose-dependent manner. Investigation of the underlying mechanism suggested that AZD1152-HQPA accelerated protein turnover of Aurora B via enhancing its ubiquitination. Conclusions It was shown that AZD1152 is an effective antineoplastic agent for breast cancer, and our results define a novel mechanism for posttranscriptional regulation of Aurora B after AZD1152 treatment and provide insight into dosing regimen design for this kinase inhibitor in metastatic breast cancer treatment.
Transmission of Virus From Field Cases of Avian Lymphomatosis. I. Isolation of Virus in Line 151 Chickens&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: B. R. Burmester, T. N. Fredrickson
Journal: JNCI Journal of the National Cancer Institute (1964)

Journal Article Transmission of Virus From Field Cases of Avian Lymphomatosis. I. Isolation of Virus in Line 151 Chickens Get access B. R. Burmester, B. R. Burmester U.S. Department of Agriculture, Poultry Research Branch, Animal Husbandry Research Division, ARS, Regional Poultry Research Laboratory, East Lansing, Michigan Search for other works by this author on: Oxford Academic PubMed Google Scholar T. N. Fredrickson T. N. Fredrickson U.S. Department of Agriculture, Poultry Research Branch, Animal Husbandry Research Division, ARS, Regional Poultry Research Laboratory, East Lansing, Michigan Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 32, Issue 1, January 1964, Pages 37–63, https://doi.org/10.1093/jnci/32.1.37 Published: 01 January 1964 Article history Received: 07 May 1963 Published: 01 January 1964
Nonsense-mediated mRNA decay affects nonsense transcript levels and governs response of cystic fibrosis patients to gentamicin
Authors: Liat Linde, Stephanie Boelz, Malka Nissim-Rafinia, Yifat S. Oren, Michael Wilschanski, Yasmin Yaacov, Dov Virgilis, Gabriele Neu-Yilik, Andreas E. Kulozik, Eitan Kerem, Batsheva Kerem
Journal: Journal of Clinical Investigation (2007)

Aminoglycosides can readthrough premature termination codons (PTCs), permitting translation of full-length proteins. Previously we have found variable efficiency of readthrough in response to the aminoglycoside gentamicin among cystic fibrosis (CF) patients, all carrying the W1282X nonsense mutation. Here we demonstrate that there are patients in whom the level of CF transmembrane conductance regulator (CFTR) nonsense transcripts is markedly reduced, while in others it is significantly higher. Response to gentamicin was found only in patients with the higher level. We further investigated the possibility that the nonsense-mediated mRNA decay (NMD) might vary among cells and hence governs the level of nonsense transcripts available for readthrough. Our results demonstrate differences in NMD efficiency of CFTR transcripts carrying the W1282X mutation among different epithelial cell lines derived from the same tissue. Variability was also found for 5 physiologic NMD substrates, RPL3, SC35 1.6 kb, SC35 1.7 kb, ASNS, and CARS. Importantly, our results demonstrate the existence of cells in which NMD of all transcripts was efficient and others in which the NMD was less efficient. Downregulation of NMD in cells carrying the W1282X mutation increased the level of CFTR nonsense transcripts and enhanced the CFTR chloride channel activity in response to gentamicin. Together our results suggest that the efficiency of NMD might vary and hence have an important role in governing the response to treatments aiming to promote readthrough of PTCs in many genetic diseases.
Primary culture of bovine gall bladder epithelial cells.
Authors: J N Plevris, S W Walker, D J Harrison, A Dhariwal, P C Hayes, I A Bouchier
Journal: Gut (1993)

Gall bladder epithelial cells serve numerous biological functions and abnormalities in their function are important in the pathogenesis of several gall bladder diseases. Direct studies on cell function are rare due to lack of reliable methods to culture this epithelium. This study reports a reliable and reproducible method of harvesting and culturing gall bladder epithelial cells. Normal bovine gall bladder epithelium, obtained within 20 minutes of slaughter, was rinsed with modified Hanks9s balanced salt solution, the mucosa separated and incubated in trypsin--EDTA solution at 37 degrees C. The cells were isolated and resuspended in Dulbeco9s modification of Eagles9 medium containing 10% fetal calf serum and, after filtration and centrifugation, were plated under aseptic conditions. The growth rate was established by flow cytometry and the morphological characteristics of the growing cells by electron microscopy. Gall bladder epithelial cells grew successfully and visible clusters of cells were present by day two, confluency being reached at 8 to 10 days in collagen coated plates and 12 to 14 days in uncoated plates. Electron microscopy showed typical gall bladder epithelia with microvilli, tight junctions, and mucus droplets. This method proved reliable and reproducible for the culture of gall bladder epithelial cells and should allow direct studies of the biological properties of these cells in human tissue.
Perspectives on the Discovery of Central Monoaminergic Neurotransmission
Authors: A Carlsson
Journal: Annual Review of Neuroscience (1987)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Structure of the BRAF-MEK Complex Reveals a Kinase Activity Independent Role for BRAF in MAPK Signaling
Authors: Jacob R. Haling, Jawahar Sudhamsu, Ivana Yen, Steve Sideris, Wendy Sandoval, Wilson Phung, Brandon J. Bravo, Anthony M. Giannetti, Ariana Peck, Alexandre Masselot, Tony Morales, Darin Smith, Barbara J. Brandhuber, Sarah G. Hymowitz, Shiva Malek
Journal: Cancer Cell (2014)
DEOXYRTBONUCLEIC ACID (DNA) LOSS, CELL LOSS AND CELL TURNOVER IN EXFOLTATIVE PSORIASIS
Authors: D. N. CROFT, C. C. LIM, J. F. N. TAYLOR
Journal: British Journal of Dermatology (1968)

SUMMARY. DNA was measured in the naturally exfoliated skin scales from 2 patients with generalized exfoliative psoriasis. The mean DNA values indicated that the rate of loss of cells from the skin in these 2 patients was approximately 4 million/min. No DNA was found in skin scales from 3 patients with ichthyosis vulgaris. The difference in DNA content of scales in these disorders appeared to reflect the fact that psoriatic scales were nucleated, whereas the ichthyotic ones were not. It is suggested that the DNA content of psoriatic scales is a reflection of the high turnover of epithelial cells in this condition.
Use of peak flow-based self-management plans by adult asthmatic patients
Authors: D Fishwick, R Beasley
Journal: European Respiratory Journal (1996)

It is intriguing to reflect on the major changes that have occurred over the last few decades in the recommended role of peak flow monitoring in the clinical management of asthma. From the situation in the late 1970s, when the use of peak flow recordings as part of an asthma self-management strategy was raised hypothetically [1], the recent International Consensus Report on the Diagnosis and Management of Asthma now recommends that peak flow monitoring is essential for the objective assessment of asthma severity, and that a peak flowbased management plan should be used by most asthmatic patients [2]. Despite these recommendations, some remain unconvinced as to the importance of the widespread use of peak flow monitoring and its incorporation into asthma self-management plans. In this editorial, we briefly review the studies on which the current recommendations are based, and comment on three articles published in this edition of the European Respiratory Journal, which provide valuable additional knowledge in this area [3‐5]. Finally, we attempt to bring together the published literature to propose practical and simple guidelines for the use of peak flow-based selfmanagement plans by adult asthmatic patients.
The role of the sports and exercise medicine physician in the national health service
Authors: P O'Halloran, V Tzortziou Brown, K Morgan, N Maffulli, M Perry, D Morrissey
Journal: British Journal of Sports Medicine (2011)

Objectives To investigate the opinions of general practitioners, orthopaedic surgeons, rheumatologists, sport and exercise medicine (SEM) registrars and public health consultants on training, caseload, the most appropriate setting and the position of SEM within the National Health Service (NHS) in the UK. Method A cross-sectional questionnaire-based survey investigated the opinions of the above professionals from three primary care trusts and associated hospitals in London and Birmingham. Results With a 50% response rate (n = 226), 93% (208/224) of participants felt that there was a role for SEM in the NHS. 56% (124/223) agreed that this role should be in both primary and secondary care. 64% (136/212) of participants felt that their practice would benefit from the input of a SEM physician and 95% (191/202) would consider referring patients to SEM services. 74% (165/222) agreed that SEM should have a public health role, and 63% (140/222) believed that these responsibilities should be evenly balanced with the treatment of sports injuries. Despite the emphasis on public health work from SEM policy makers, none of the SEM registrars selected public health as an important training area. 31% (44/140) of participants felt that a lack of education in the medical profession regarding SEM represented the greatest hindrance to its development in the NHS. Conclusion Several areas of agreement were demonstrated across the specialties, many of which matched the views of policy makers. This study involved participants from a range of cognate disciplines and was the first to investigate this issue since SEM was recognised as a specialty in 2005.
A phase II trial of gemcitabine in combination with 5-fluorouracil (24-hour) and folinic acid in patients with chemonaive advanced pancreatic cancer
Authors: H. Oettle, M. Arning, U. Pelzer, D. Arnold, C. Stroszczynski, J. Langrehr, P. Reitzig, M. Kindler, J. Herrenberger, R. Musch, F.W. Korsten, D. Huhn, H. Riess
Journal: Annals of Oncology (2000)
SPARC Represses E-Cadherin and Induces Mesenchymal Transition during Melanoma Development
Authors: Guillaume Robert, Cédric Gaggioli, Olivier Bailet, Carine Chavey, Patricia Abbe, Edith Aberdam, Emilie Sabatié, Amparo Cano, Antonio Garcia de Herreros, Robert Ballotti, Sophie Tartare-Deckert
Journal: Cancer Research (2006)

Abstract During progression of melanoma, loss of the cell-cell adhesion molecule E-cadherin contributes to uncontrolled growth and invasive behavior of transformed melanocytes. Secreted protein acidic and rich in cysteine (SPARC) is a nonstructural matricellular protein that regulates cell-matrix interactions leading to alterations in cell adhesion and proliferation. Overexpression of SPARC has been associated with progression of various cancers, including melanoma; however, its role in primary tumor development is not well defined. We show that normal human melanocytes overexpressing SPARC adopt a fibroblast-like morphology, concomitant with loss of E-cadherin and P-cadherin expression, and increased expression of mesenchymal markers. Concurrent with these changes, SPARC expression stimulates melanocyte motility and melanoma cell invasion. Expression of SPARC results in transcriptional down-regulation of E-cadherin that correlates with induction of Snail, a repressor of E-cadherin. Conversely, SPARC depletion leads to up-regulation of E-cadherin and reduces Snail levels, and SPARC-null cells exhibit a marked change in their mesenchymal phenotype. Finally, analysis of SPARC, Snail, and E-cadherin levels in melanocytes and malignant melanoma cell lines further supports the functional relationship among these proteins during melanoma progression. Our findings provide evidence for the role of SPARC in early transformation of melanocytes and identify a novel mechanism, whereby tumor-derived SPARC promotes tumorigenesis by mediating Snail induction and E-cadherin suppression. (Cancer Res 2006; 66(15): 7516-23)
Antigen-pulsed CD8α+ Dendritic Cells Generate an Immune Response after Subcutaneous Injection without Homing to the Draining Lymph Node
Authors: Adrian L. Smith, Barbara Fazekas de St. Groth
Journal: The Journal of Experimental Medicine (1999)

Two subsets of murine splenic dendritic cells, derived from distinct precursors, can be distinguished by surface expression of CD8α homodimers. The functions of the two subsets remain controversial, although it has been suggested that the lymphoid-derived (CD8α+) subset induces tolerance, whereas the myeloid-derived (CD8α−) subset has been shown to prime naive T cells and to generate memory responses. To study their capacity to prime or tolerize naive CD4+ T cells in vivo, purified CD8α+ or CD8α− dendritic cells were injected subcutaneously into normal mice. In contrast to CD8α− dendritic cells, the CD8α+ fraction failed to traffic to the draining lymph node and did not generate responses to intravenous peptide. However, after in vitro pulsing with peptide, strong in vivo T cell responses to purified CD8α+ dendritic cells could be detected. Such responses may have been initiated via transfer of peptide–major histocompatibility complex complexes to migratory host CD8α− dendritic cells after injection. These data suggest that correlation of T helper cell type 1 (Th1) and Th2 priming with injection of CD8α+ and CD8α− dendritic cells, respectively, may not result from direct T cell activation by lymphoid versus myeloid dendritic cells, but rather from indirect modification of the response to immunogenic CD8α− dendritic cells by CD8α+ dendritic cells.
Phase I (Safety) Study of Autologous Tolerogenic Dendritic Cells in Type 1 Diabetic Patients
Authors: Nick Giannoukakis, Brett Phillips, David Finegold, Jo Harnaha, Massimo Trucco
Journal: Diabetes Care (2011)

The safety of dendritic cells to selectively suppress autoimmunity, especially in type 1 diabetes, has never been ascertained. We investigated the safety of autologous dendritic cells, stabilized into an immunosuppressive state, in established adult type 1 diabetic patients.A randomized, double-blind, phase I study was conducted. A total of 10, otherwise generally healthy, insulin-requiring type 1 diabetic patients between 18 and 60 years of age, without any other known or suspected health conditions, received autologous dendritic cells, unmanipulated or engineered ex vivo toward an immunosuppressive state. Ten million cells were administered intradermally in the abdomen once every 2 weeks for a total of four administrations. The primary end point determined the proportion of patients with adverse events on the basis of the physician's global assessment, hematology, biochemistry, and immune monitoring for a period of 12 months.The dendritic cells were safely tolerated. There were no discernible adverse events in any patient throughout the study. Other than a significant increase in the frequency of peripheral B220+ CD11c- B cells, mainly seen in the recipients of engineered dendritic cells during the dendritic cell administration period, there were no statistically relevant differences in other immune populations or biochemical, hematological, and immune biomarkers compared with baseline.Treatment with autologous dendritic cells, in a native state or directed ex vivo toward a tolerogenic immunosuppressive state, is safe and well tolerated. Dendritic cells upregulated the frequency of a potentially beneficial B220+ CD11c- B-cell population, at least in type 1 diabetes autoimmunity.