tbuckley/cabot-search huggingface dataset:
Association of IRF5 polymorphisms with activation of the interferon α pathway
Authors: Ornella J Rullo, Jennifer M P Woo, Hui Wu, Alice D C Hoftman, Paul Maranian, Brittany A Brahn, Deborah McCurdy, Rita M Cantor, Betty P Tsao
Journal: Annals of the Rheumatic Diseases (2009)

Objective The genetic association of interferon regulatory factor 5 ( IRF5 ) with systemic lupus erythematosus (SLE) susceptibility has been convincingly established. To gain understanding of the effect of IRF5 variation in individuals without SLE, a study was undertaken to examine whether such genetic variation predisposes to activation of the interferon α (IFNα) pathway. Methods Using a computer simulated approach, 14 single nucleotide polymorphisms (SNPs) and haplotypes of IRF5 were tested for association with mRNA expression levels of IRF5, IFNα and IFN-inducible genes and chemokines in lymphoblastoid cell lines (LCLs) from individuals of European (CEU), Han Chinese (CHB), Japanese (JPT) and Yoruba Nigerian (YRI) backgrounds. IFN-inducible gene expression was assessed in LCLs from children with SLE in the presence and absence of IFNα stimulation. Results The major alleles of IRF5 rs13242262 and rs2280714 were associated with increased IRF5 mRNA expression levels in the CEU, CHB+JPT and YRI samples. The minor allele of IRF5 rs10488631 was associated with increased IRF5, IFNα and IFN-inducible chemokine expression in CEU (p c =0.0005, 0.01 and 0.04, respectively). A haplotype containing these risk alleles of rs13242262, rs10488631 and rs2280714 was associated with increased IRF5, IFNα and IFN-inducible chemokine expression in CEU LCLs. In vitro studies showed specific activation of IFN-inducible genes in LCLs by IFNα. Conclusions SNPs of IRF5 in healthy individuals of a number of ethnic groups were associated with increased mRNA expression of IRF5. In European-derived individuals, an IRF5 haplotype was associated with increased IRF5, IFNα and IFN-inducible chemokine expression. Identifying individuals genetically predisposed to increased IFN-inducible gene and chemokine expression may allow early detection of risk for SLE.
Premature escape beats induced by overdrive pacing in canine Purkinje fibers. Evidence for the role of normal automaticity as an underlying cellular mechanism.
Authors: V A Viamonte, M R Rosen
Journal: Circulation (1990)

Premature escape beats induced in conscious dogs with chronic complete atrioventricular block have been defined as escape beats occurring on cessation of overdrive pacing and having a coupling interval to the last paced beat shorter than the coupling interval between the premature escape beat and the second postpacing beat. Triggered activity has been proposed as the primary underlying mechanism. We used standard microelectrode techniques to study the effects of overdrive pacing on normal automatic canine Purkinje fibers to determine if premature escape beats could be induced and if so, to define the underlying cellular mechanism(s). For this purpose, we overdrive-paced Purkinje fibers for 10 and 50 seconds and for 10 and 50 beats at a pacing cycle length (PCL) of 1,000-200 msec. In addition, to help distinguish among major arrhythmogenic mechanisms, we used a matrix of drugs consisting of propranolol, nadolol, lidocaine, ethmozin, and doxorubicin. Fifty-second stimulation trains induced "classic" overdrive suppression of the first three postpacing impulses, whereas 10-second overdrive pacing induced significant overdrive suppression only at a PCL of 200 msec. With 50-beat overdrive pacing and a PCL of 1,000-600 msec, there was overdrive suppression of postpacing impulses, whereas reduced overdrive suppression was observed at a PCL of 400-200 msec. Ten-beat stimulation trains induced a "flat response" of postpacing impulses. Ten- and 50-beat overdrive pacing provoked premature escape beats in 66% of the fibers, with the higher incidence at a PCL of 200 msec for 50-beat stimulation trains. No shortening of the coupling interval of premature escape beats was observed at faster pacing rates. Only lidocaine (which suppresses normal automaticity) abolished premature escape beats. We conclude that normal automaticity is the most likely mechanism underlying premature escape beats in Purkinje fibers with high levels of membrane potential.
Outcomes in African Americans and Hispanics with lupus nephritis
Authors: G. Contreras, O. Lenz, V. Pardo, E. Borja, C. Cely, K. Iqbal, N. Nahar, C. de La Cuesta, A. Hurtado, A. Fornoni, L. Beltran-Garcia, A. Asif, L. Young, J. Diego, M. Zachariah, B. Smith-Norwood
Journal: Kidney International (2006)
Shock during heparin-induced thrombocytopenia: Look for adrenal insufficiency!
Authors: Nicolas Mongardon, Fabrice Bruneel, Matthieu Henry-Lagarrigue, Stéphane Legriel, Laure Revault d’Allonnes, Pierre Guezennec, Gilles Troché, Jean-Pierre Bedos
Journal: Intensive Care Medicine (2006)
Biochemical Alterations Caused by Hypoxia in the Isolated Rabbit Aorta: CORRELATION WITH CHANGES IN ARTERIAL CONTRACTILITY
Authors: DONALD H. NOMM, JOAN L. ZUCKER
Journal: Circulation Research (1973)

A graded reduction in the oxygen tension of the medium bathing aortic strips resulted in a decrease in creatine phosphate and adenosine triphosphate levels in the tissue, but only the fall in creatine phosphate could be correlated with the contractile changes observed during hypoxia. The tissue glycogen concentration was not altered at any oxygen tension, indicating that under the conditions of the experiment glycogenolysis did not contribute substrate in significant amounts. Although lactate concentrations rose as the oxygen tension was progressively lowered, changes in the concentration of this metabolite did not correlate with the contractile response to hypoxia. The reduction in contractile tone induced by lowering oxygen tension of the medium was less when the tissue was exposed to 25 mM glucose than it was with 5 mM glucose. Addition of pyruvate did not mimic this sparing effect of glucose. These results indicate that the loss of contractile tone in arterial muscle exposed to low oxygen tensions is not directly attributable to a deficit in the availability of adenosine triphosphate within the tissue but, rather, is a consequence of more subtle alterations in the energy metabolism of the muscle.
Gene expression changes during hormonal therapy for prostate cancer reveal candidate diagnostic and drug targets
Authors: Spyro Mousses, Lukas Bubendorf, Juha Kononen, Yidong Chen, Micheal Bittner, Pasi Koivisto, Jane Trepel, Jin Woo Kim, Mark Raffeld, Thomas Pretlow, Natalie Goldberger, Robert Cornelison, Urs Wagner, Galen Hostetter, Guido Sauter, Olli Kallioniemi
Journal: Nature Genetics (2001)
Imitation without attitudes
Authors: Eoghan Mac Aogáin
Journal: Behavioral and Brain Sciences (1998)

Byrne &amp; Russon's account of program imitation in primates involves propositional attitudes (expectations and goals), which limits its falsifiability. Yet their account of priming shows exactly how imitation without attitudes would look. The challenge is to upgrade the notion of priming to give an account of low-level program imitation without invoking propositional attitudes.
511. An Enzyme Linked Immunosorbent Assay for the Detection of Herpes Simplex Virus Type 1 Proteins in a Novel rAAV Production and Purification Process
Authors: Guo-jie Ye, Tammy Mandell
Journal: Molecular Therapy (2006)

AGTC has developed a recombinant herpes simplex virus (rHSV-1)-based adeno-associated virus (AAV) production process. This method requires two rHSV-1 viruses; rHSV-1-rep/cap which expresses the AAV2 rep and cap proteins, and a second rHSV-1 that contains the therapeutic gene of interest flanked by AAV2 inverted terminal repeats (ITRs) necessary for rAAV production. Following co-infection of these two helper viruses onto HEK-293 cells, the rAAV DNA is replicated and packaged into rAAV capsids. rAAV is then liberated from the cells and purified. Our proprietary rAAV purification scheme removes all contaminants including HSV-1 proteins; however, it is necessary to develop a sensitive and quantitative method to confirm the absence of HSV-1 proteins within a level of detection, in the final rAAV preparation. Here we report the development of an enzyme-linked Immunosorbent assay (ELISA) for quantitative determination of whole rHSV-1 proteins in purified rAAV preparations derived from rHSV-1 viruses. To facilitate the assay development, we prepared HSV-1 proteins standard from HSV-1 infected cell lysate by immuno-affinity column conjugated with polyclonal antibody to HSV-1 proteins. The fully developed assay enables us to quantitatively determine residual HSV-1 proteins at a level as low as 0.1 ng. Within the detection range of 0.1 ng to 5 ng of HSV proteins, the assay is reproducible with high linearity (R2>0.99). Background levels of rAAV as high as 5E+11 DNase resistant particles (DRP) do not interfere with the assay. Moreover, in contrast to other HSV protein ELISA assays targeted to a single protein such as HSV-1 glycoprotein D, this assay is capable of detecting a full range of HSV-1 proteins.
Influence of cigarette smoking on rate of reopening of the infarct-related coronary artery after myocardial infarction: A multivariate analysis
Authors: Christian de Chillou, Pascal Riff, Nicolas Sadoul, Gérard Éthevenot, Luc Feldmann, Karl Isaaz, Jean-Philippe Simon, Michel Boursier, Khalifé Khalifé, Jean-Yves Thisse, Etienne Aliot
Journal: Journal of the American College of Cardiology (1996)
RECIST: No Longer the Sharpest Tool in the Oncology Clinical Trials Toolbox—Reply to Point
Authors: Antonio T. Fojo, Anne Noonan
Journal: Cancer Research (2012)

See Point by Sharma et al., [p. 5145][1]

We agree with many of the points made by Sharma, Maitland, and Ratain in their well-reasoned opinion. But we also disagree with several.

We agree when they conclude that “RECIST… falls short of the ideal as an assessment of efficacy for cancer
What is rotator cuff disease anyway?
Authors: G. Symonds
Journal: BMJ (2009)

I am not surprised that the study by Ekeberg and colleagues showed no difference between subacromial ultrasound-guided or systemic steroid injection for rotator cuff disease.1

What is rotator cuff disease? I submit no such disease exists. You might as well talk of shoulder pain disease or the long discredited periarthritis.

The diagnostic …
Body-mass index and cancer mortality in the Asia-Pacific Cohort Studies Collaboration: pooled analyses of 424 519 participants
Authors: Christine L Parr, G David Batty, Tai Hing Lam, Federica Barzi, Xianghua Fang, Suzanne C Ho, Sun Ha Jee, Alireza Ansary-Moghaddam, Konrad Jamrozik, Hirotsugu Ueshima, Mark Woodward, Rachel R Huxley
Journal: The Lancet Oncology (2010)
[70] DELETION OF NEMO/IKK-G IN LIVER PARENCHYMAL CELLS CAUSES STEATOHEPATITIS AND HEPATOCELLULAR CARCINOMA
Authors: T. Lvjedde, N. Beraza, G. van Loo, A. Nenci, R. De Vos, T. Roskams, C. Trautwein, M. Pasparakis
Journal: Journal of Hepatology (2007)
Duty Hour Reform: Only a Small Piece of a Larger Problem—Reply
Authors: Srijan Sen, Breck Nichols, Aashish K. Didwania
Journal: JAMA Internal Medicine (2013)

We agree with Dr. Runyan that addressing inter-professional communication and handoff training are critical factors in achieving meaningful improvement in both the quality of care that residents provide and the quality of life that they enjoy. Evidence from multiple studies indicate that the most recent set of ACGME duty hour reforms, which focused almost exclusively on reducing maximum shift length, have not achieved the intended improvements in quality of care or quality of life (1–3). If this experience with interns is instructive, then extending work hour limits to all residents, without address the additional factors raised be Dr. Runyan, will likely be ineffective.

In addition to communication training, an essential piece of the puzzle not addressed by existing duty hour reforms is work compression. House officers now spend fewer hours in the hospital but their clinical workload and educational requirements have not decreased proportionally, resulting in an even more frenetic pace of work — a phenomenon known as “work compression” (4). In 2000 a typical call day lasted 36 hours. This was specifically reduced for interns from 36 hours to 30 hours in 2004 and to 16 hours with the latest duty hour changes. As a result, current interns have fewer hours to complete their work and engage in learning and team building experiences. This leaves the new intern generation in a frustrating situation where they are often criticized or chided for having less work when, in many cases, they are simply given less time to complete it. If we know that timed tests result in more errors than untimed ones, we should not be surprised that giving interns less time to complete the same amount of work would adversely affect their patient care.

Paradoxically, with the addition of new, often untested, educational curriculum in communication skills and systems of care to traditional clinical topics, interns are also being asked to learn more in less time. Collectively, these changes often result in reduced opportunities to double-check orders, follow a disease course, spend time at the patient’s bedside, teach students or share a meal with their team. Incorporating solutions that address the problems associated with work compression are needed to fully achieve the goals of residency duty hour reform.
Frederick Valentine Flynn
Authors: D. Flynn, M. Lapsley, A. Norden
Journal: BMJ (2012)

<b>Introduction:</b> TB remains a significant public health problem through-out the developing world. Pulmonary TB is known to be a risk factor for Obstructive Airways Diseases (OAD). <b>Aims and objectives:</b> To determine the association and prevalence of OAD in patients with past history of Pulmonary Tuberculosis in absence of risk factors of OAD. <b>Methodology:</b> All patients with past H/O diagnosed and treated Pulmonary TB with minimal tobacco smoking or biomass fuel exposure who met the inclusion criteria were recruited. They were divided in 4 groups on the basis of duration after completing TB treatment – 6-12 months,1-2 years, 2-5 years, &gt;5 years. Patients were subjected to detailed history taking, Chest radiograph and Spirometry. <b>Results:</b> 65 patients met the inclusion criteria over a period of 6 months.50% patients were above 50 years and 54% were men.83% patients had microbiologically proven TB. The prevalence of OAD was 44.62%. About 40% were been followed up on a routine basis whereas 50% presented with acute respiratory symptoms. Most of the patients (43%) had been treated for TB more than 5 years ago. Only 24% of patients had a history of smoking (&lt;5 pack-years). The mean FEV1 in patients with OAD was 1.27. Based on Spirometric criteria (GOLD) no patients had mild COPD, 62% moderate disease, 28% had severe and 10% very severe disease. <b>Conclusions:</b> This pilot study reveals a high prevalence of OAD in patients previously treated for Pulmonary TB. Most of the affected subjects have moderate to severe disease who would benefit from bronchodilator±anti-inflammatory treatment. Hence, we hypothesize that Post TB treatment; patients should be followed up long term for the development of OAD.
Maternal vitamin A supplementation improves lung function in offspring
Authors: C. Dardis
Journal: Thorax (2010)

Vitamin A has an important role in fetal lung development. This study tested the hypothesis that maternal vitamin A deficiency could have a long-term adverse effect on the lung function of offspring, quantified by reduced forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC).

The participants were …
Americans are already benefiting from health reform, says Obama
Authors: M. McCarthy
Journal: BMJ (2013)

US President Barack Obama hit back at critics of his 2010 health reform law on 18 July, arguing that the legislation is already guaranteeing Americans better, more secure coverage while saving them billions of dollars a year.

The president made the comments in a White House speech a day after the Republican controlled US House of Representatives voted for the 37th time to repeal all or parts of the law, the 2010 Affordable Care Act.

In recent weeks the White House has stepped up efforts to promote the new law, which comes into full effect next year. …
Prophylactic Eculizumab after Renal Transplantation in Atypical Hemolytic–Uremic Syndrome
Authors: Lothar Bernd Zimmerhackl, Johannes Hofer, Gérard Cortina, Walter Mark, Reinhard Würzner, Therese C. Jungraithmayr, Gus Khursigara, Kay O. Kliche, Wolfgang Radauer
Journal: New England Journal of Medicine (2010)

To the Editor: Atypical hemolytic–uremic syndrome is a rare microangiopathic hemolytic condition characterized by thrombocytopenia and acute renal failure.1 The prognosis for patients with atypical hemolytic–uremic syndrome with a factor H mutation is poor; 60% have end-stage renal disease or die within a year.2 The expected rate of graft failure due to recurrent atypical hemolytic–uremic syndrome among patients with a factor H or factor I mutation is 80% within 1 to 2 years.3 Here, we describe a child with atypical hemolytic–uremic syndrome and a known factor H mutation who had normal renal function 1 year after high-risk kidney transplantation with . . .
Abstract 470: The homing of prostate cancer to bone <i>in vivo</i> is modulated by Zoledronic acid
Authors: Kim J. Reeves, Gabri van der Pluijm, Marco G. Cecchini, Colby L. Eaton, Freddie C. Hamdy, Nicola J. Brown
Journal: Cancer Research (2010)

Abstract Cancer metastasis to the skeleton is a major problem with prostate cancer and requires the development of specialised approaches to treatment. Zoledronic acid, a bone resorptive agent, is currently the only bisphosphonate with proven benefit in prostate cancer. However, there is minimal research investigating whether Zoledronic acid modulates the early mechanisms involved in metastasis. The aim of this study is to determine whether different treatment regimes using Zoledronic acid modulate the early events in tumour/bone interactions. Metatarsals from newborn mice (1-3 day old) are engrafted into a Dorsal Skinfold Chamber (DSC) implanted on a SCID mouse (5-6 weeks old). Prostate (PC3-GFP) cancer cells (1 × 105) are then injected via the heart (i.c) to simulate micrometastatic spread (n=20/group). Animals are treated with either i) weekly s.c injection of Zoledronic acid (25µg/kg/inection=100μg/kg in total) or saline or ii) single s.c injection of Zoledronic acid (100μg/kg) or saline for the 4 week study duration. The groups are further subdivided, so half of the animals receive treatment either before or after injection of tumour cells. Recordings of the chamber tissue and metatarsal are made at 48hr intervals for the duration of the experiment for the presence of PC3-GFP cells within the metatarsal. At the end of the study, tissue is harvested and processed for microCT, multi-photon analysis and histology.TreatmentNumber of PC3-GFP cells homing to metatarsalDay 3Day 9Day 15 Weekly treatment before PC3-GFP cells1.1 ± 0.1*1.3 ± 0.2*2.1 ± 0.3*Weekly treatment after PC3-GFP cells3.2 ± 0.5*3.4 ± 0.8*4.4 ± 0.7*Single treatment before PC3-GFP cells1.7 ± 0.3*8.9 ± 0.9*13.6 ± 0.8Control3.2 ± 0.714.7 ± 1.015.9 ± 1.4 Table 1. Number of PC3-GFP cells present in metatarsal after i.c. injection (*p&amp;lt;0.05 compared to control). Treatment with Zoledronic acid reduces tumour cell homing to bone. Weekly treatment of Zoledronic acid prior to prostate cancer cell administration reduces homing to bone to a greater extent than the other treatment regimes test. Funded by Sixth European Framework Programme (PROMET). Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 470.
Reducing Suicidal Ideation and Depression in Older Primary Care Patients: 24-Month Outcomes of the PROSPECT Study
Authors: George S. Alexopoulos, Charles F. Reynolds, Martha L. Bruce, Ira R. Katz, Patrick J. Raue, Benoit H. Mulsant, David W. Oslin, Thomas Ten Have
Journal: American Journal of Psychiatry (2009)

Objective: The Prevention of Suicide in Primary Care Elderly: Collaborative Trial (PROSPECT) evaluated the impact of a care management intervention on suicidal ideation and depression in older primary care patients. This is the first report of outcomes over a 2-year period. Method: Study participants were patients 60 years of age or older (N=599) with major or minor depression selected after screening 9,072 randomly identified patients of 20 primary care practices randomly assigned to provide either the PROSPECT intervention or usual care. The intervention consisted of services of 15 trained care managers, who offered algorithm-based recommendations to physicians and helped patients with treatment adherence over 24 months. Results: Compared with patients receiving usual care, those receiving the intervention had a higher likelihood of receiving antidepressants and/or psychotherapy (84.9%–89% versus 49%–62%) and had a 2.2 times greater decline in suicidal ideation over 24 months. Treatment response occurred earlier on average in the intervention group and increased from months 18 to 24, while no appreciable increase in treatment response occurred in the usual care group during the same period. Among patients with major depression, a greater number achieved remission in the intervention group than in the usual-care group at 4 months (26.6% versus 15.2%), 8 months (36% versus 22.5%), and 24 months (45.4% versus 31.5%). Patients with minor depression had favorable outcomes regardless of treatment assignment. Conclusions: Sustained collaborative care maintains high utilization of depression treatment, reduces suicidal ideation, and improves the outcomes of major depression over 2 years.
Zidovudine-induced alterations in the heart and vascular smooth muscle of the rat
Authors: Ezia Ruga, Sergio Bova, Gastone Nussdorfer, Giuseppina Mazzocchi, Piera Rebuffat, Ornella Milanesi, Gabriella Cargnelli
Journal: Cardiovascular Research (2003)

Objective: We investigated the effects of zidovudine (AZT) on cardiac and vascular smooth muscle function and morphology in rats. Methods: Four adult male Wistar–Kyoto rats received AZT in drinking water for 240 days; four rats served as controls. Echocardiographic examination and systolic blood pressure (SBP) measurement were performed. At the end of treatment the rats were sacrificed, their hearts were weighed and vascular smooth muscle contractile and relaxing properties were evaluated in vitro on endothelium-intact aortic rings. Morphological studies were performed on cardiac and aortic myocytes by light and electron microscopy. Results: AZT-treated rats (AZT-Rs) showed higher SBP, greater heart weight and, as revealed by echocardiography, greater interventricular septum thickness. Electron microscopy revealed mitochondrial swelling in myocardiocytes in AZT-Rs. Reduced response to contractile stimuli and enhanced relaxation in response to charbacol were observed in the aortic rings of AZT-Rs. The aortic myocytes of AZT-Rs contained apparently unaffected ultrastructural features, but light microscopy suggested their marked enlargement. Conclusions: AZT treatment for 240 days in rats induces a modest increase in SBP, hypertrophy of the interventricular septum and modified vascular smooth muscle responsiveness. The role of mitochondria in these AZT-induced cardiovascular alterations remains to be established.
Preoperative Prophylactic use of Levosimendan in Patients with Severely Depressed Left Ventricle
Authors: Ahmet Ümit Güllü, Sahin Senay, Fevzi Toraman, Hasan Karabulut, Muharrem Kocyigit, Eyüp Murat Ökten, Cem Aritürk, Aleks Degirmencioglu, Seden Erten Çelik, Sinan Dagdelen, Cem Alhan
Journal: Journal of the American College of Cardiology (2013)