tbuckley/cabot-search huggingface dataset:
High Mobility Group A1 Is a Molecular Target for MYCN in Human Neuroblastoma
Authors: Giuseppe Giannini, Fabio Cerignoli, Massimiliano Mellone, Isabella Massimi, Cinzia Ambrosi, Christian Rinaldi, Carlo Dominici, Luigi Frati, Isabella Screpanti, Alberto Gulino
Journal: Cancer Research (2005)

Abstract High mobility group A1 (HMGA1) is an architectural transcription factor and a putative protoncogene. Deregulation of its expression has been shown in most human cancers. We have previously shown that the expression of the HMGA family members is deregulated in neuroblastoma cell lines and primary tumors. On retinoic acid (RA) treatment of MYCN-amplified neuroblastoma cell lines, HMGA1 decreases with a kinetics that strictly follows MYCN repression. In addition, MYCN constitutive expression abolishes HMGA1 repression by RA. Here we explored the possibility that HMGA1 expression might be sustained by MYCN in amplified cells. Indeed, MYCN transfection induced HMGA1 expression in several neuroblastoma cell lines. HMGA1 expression increased in a transgene dose–dependent fashion in neuroblastoma-like tumors of MYCN transgenic mice. In addition, it was significantly more expressed in MYCN-amplified compared with MYCN single-copy primary human neuroblastomas. MYCN cotransfection activated a promoter/luciferase reporter containing a 1,600 bp region surrounding the first three transcription start sites of the human HMGA1 and eight imperfect E-boxes. By heterodimerizing with its partner MAX, MYCN could bind to multiple DNA fragments within the 1,600 bp. Either 5′ or 3′ deletion variants of the 1,600 bp promoter/luciferase reporter strongly decreased luciferase activity, suggesting that, more than a single site, the cooperative function of multiple cis-acting elements mediates direct HMGA1 transactivation by MYCN. Finally, HMGA1 repression by RNA interference reduced neuroblastoma cell proliferation, indicating that HMGA1 is a novel MYCN target gene relevant for neuroblastoma tumorigenesis.
Consequences of Diabetes
Authors: Zachary T. Bloomgarden
Journal: Diabetes Care (2004)

This is the third of three articles dealing with the International Diabetes Federation meeting, which was held in Paris, 24–29 August 2003.

Paul Valensi (Bobigny, France) discussed approaches to silent myocardial ischemia in persons with diabetes. Addressing the question of whether it is in fact advisable to detect cardiovascular disease (CVD) in persons without history of myocardial infarction or angina, he noted the poor prognosis of persons with diabetes, whose risk of myocardial infarction in the absence of CVD is similar to that of persons without diabetes and with a prior myocardial infarction. Those having evidence of CVD are at particularly increased risk, with half dying within 8 years (1). One-year mortality after thrombolysis is increased by half in persons with diabetes, and survival of persons without diabetes who have had a second myocardial infarction is similar to that of those with diabetes after an initial event (2). The prevalence at autopsy of high grade and multilevel coronary atherosclerosis in diabetic individuals without clinical coronary artery disease (CAD) is similar to that of persons without diabetes with clinical CAD, both for males and for females (3). In a French multicenter study of 417 asymptomatic diabetic persons with at least two additional risk factors undergoing thallium scintigraphy with exercise or dipyridamole, 162 had positive nuclear study, and of 70 having angiography, 39 were found to have evidence of CAD, a positive predictive value of only 56%. Other studies suggest that approximately one-third of asymptomatic persons with diabetes have a positive screening test, but that only approximately one-third of these have positive results on angiography, suggesting poor correlation between functional and morphological abnormality. Alternatively, Valensi suggested, scintigraphy may actually be more sensitive than angiography to the presence of CAD, noting that there certainly is evidence that an abnormal study is associated with …
VCAM-1 expression on dystrophic muscle vessels has a critical role in the recruitment of human blood-derived CD133+ stem cells after intra-arterial transplantation
Authors: M. Gavina, M. Belicchi, B. Rossi, L. Ottoboni, F. Colombo, M. Meregalli, M. Battistelli, L. Forzenigo, P. Biondetti, F. Pisati, D. Parolini, A. Farini, A. C Issekutz, N. Bresolin, F. Rustichelli, G. Constantin, Y. Torrente
Journal: Blood (2006)
Bedside tracer gas technique accurately predicts outcome in aspiration of spontaneous pneumothorax
Authors: D G Kiely
Journal: Thorax (2001)

There is no technique in general use that reliably predicts the outcome of manual aspiration of spontaneous pneumothorax. We have hypothesised that the absence of a pleural leak at the time of aspiration will identify a group of patients in whom immediate discharge is unlikely to be complicated by early lung re-collapse and have tested this hypothesis by using a simple bedside tracer gas technique.Eighty four episodes of primary spontaneous pneumothorax and 35 episodes of secondary spontaneous pneumothorax were studied prospectively. Patients breathed air containing a tracer (propellant gas from a pressurised metered dose inhaler) while the pneumothorax was aspirated percutaneously. Tracer gas in the aspirate was detected at the bedside using a portable flame ioniser and episodes were categorised as tracer gas positive (>1 part per million of tracer gas) or negative. The presence of tracer gas was taken to imply a persistent pleural leak. Failure of manual aspiration and the need for a further intervention was based on chest radiographic appearances showing either failure of the lung to re-expand or re-collapse following initial re-expansion.A negative tracer gas test alone implied that manual aspiration would be successful in the treatment of 93% of episodes of primary spontaneous pneumothorax (p<0.001) and in 86% of episodes of secondary spontaneous pneumothorax (p=0.01). A positive test implied that manual aspiration would either fail to re-expand the lung or that early re-collapse would occur despite initial re-expansion in 66% of episodes of primary spontaneous pneumothorax and 71% of episodes of secondary spontaneous pneumothorax. Lung re-inflation on the chest radiograph taken immediately after aspiration was a poor predictor of successful aspiration, with lung re-collapse occurring in 34% of episodes by the following day such that a further intervention was required.National guidelines currently recommend immediate discharge of patients with primary spontaneous pneumothorax based primarily on the outcome of the post-aspiration chest radiograph which we have shown to be a poor predictor of early lung re-collapse. Using a simple bedside test in combination with the post-aspiration chest radiograph, we can predict with high accuracy the success of aspiration in achieving sustained lung re-inflation, thereby identifying patients with primary spontaneous pneumothorax who can be safely and immediately discharged home and those who should be observed overnight because of a significant risk of re-collapse, with an estimated re-admission rate of 1%.
Electrophysiological Characteristics and Catheter Ablation in Patients With Paroxysmal Right Atrial Fibrillation
Authors: Yenn-Jiang Lin, Ching-Tai Tai, Tsair Kao, Han-Wen Tso, Jin-Long Huang, Satoshi Higa, Yoga Yuniadi, Bien-Hsien Huang, Tu-Ying Liu, Pi-Chang Lee, Ming-Hsiung Hsieh, Shih-Ann Chen
Journal: Circulation (2005)

Catheter ablation of the right atrial (RA) substrate has had variable efficacy in curing paroxysmal atrial fibrillation (PAF), suggesting that RA substrate ablation can play an important role in the treatment of atrial fibrillation (AF) in some patients. The aim of this study was to investigate the electrophysiological characteristics and ablation strategy and its results in a specific group of patients with paroxysmal RA-AF.The study population consisted of 13 patients (8 men; age, 64+/-15 years) with drug-refractory (2+/-1 drugs), frequent episodes of PAF. Provocation maneuvers did not reveal any ectopic beat-initiating AF. However, rapid atrial pacing easily induced AF. Activation mapping during sinus rhythm, atrial pacing, and AF was visualized by using a noncontact mapping system. Noncontact mapping revealed RA reentry (6 patients with single-loop circuits and 7 with double-loop circuits) with conduction through channels between lines of block, crista terminalis gaps, and the cavotricuspid isthmus, which could be identified during sinus rhythm and atrial pacing, resulting in fibrillatory conduction in other parts of the RA. The consistency of wavefront activation was confirmed by frequency analysis from equally distributed mapping sites in the RA. Short lines of ablation lesions were aimed at the conduction channels between the lines of block, crista terminalis gaps, and the cavotricuspid isthmus, resulting in bidirectional block. AF was eliminated in 11 (85%) of 13 patients, and those 11 patients with acute success were free of AF without any antiarrhythmic drugs during the long-term follow-up period (16+/-6 months).RA ablation still can cure selected patients with PAF. Linear ablation of the RA substrate guided by the electrophysiological characteristics of RA-AF is an effective approach for treating this specific group of patients with AF.
O4 PROLONGED THERAPY OF HEPATITIS DELTA FOR 96 WEEKS WITH PEGYLATED-INTERFERON-α-2a PLUS TENOFOVIR OR PLACEBO DOES NOT PREVENT HDVRNA RELAPSE AFTER TREATMENT: THE HIDIT-2 STUDY
Authors: H. Wedemeyer, C. Yurdaydin, S. Ernst, F.A. Caruntu, M.G. Curescu, K. Yalcin, U.S. Akarca, S. Gürel, S. Zeuzem, A. Erhardt, S. Lüth, G.V. Papatheodoridis, O. Keskin, K. Port, M. Radu, M.K. Celen, R. Ildeman, J. Stift, B. Heidrich, I. Mederacke, S. Hardtke, A. Koch, H.P. Dienes, M.P. Manns
Journal: Journal of Hepatology (2014)
Stimulant Medication Use in Children: A 12-Year Perspective
Authors: Samuel H. Zuvekas, Benedetto Vitiello
Journal: American Journal of Psychiatry (2011)

Objective: The authors examined the utilization of stimulant medications for the treatment of ADHD in U.S. children during the period 1996–2008 to determine trends by age, sex, race/ethnicity, family income, and geographic region. Method: The 1996–2008 database of the Medical Expenditure Panel Survey, a nationally representative annual survey of U.S. households, was analyzed for therapeutic stimulant use in children age 18 and younger. The data for 1987 were also recalculated for reference. Results: An estimated 3.5% (95% confidence interval=3.0–4.1) of U.S. children received stimulant medication in 2008, up from 2.4% in 1996. Over the period 1996–2008, stimulant use increased consistently at an overall annual growth rate of 3.4%. Use increased in adolescents (annual growth, 6.5%), but it did not significantly change in 6- to 12-year-olds, and it decreased in preschoolers. Use remained higher in boys than in girls, and it remained consistently lower in the West than in other U.S. regions. While differences by family income have disappeared over time, use of stimulants in ADHD treatment is significantly lower in racial/ethnic minorities. Conclusions: Overall, pediatric stimulant use has been slowly but steadily increasing since 1996, primarily as a result of greater use in adolescents. Use in preschoolers remains low and has declined over time. Important variations related to racial/ethnic background and geographic region persist, thus indicating a substantial heterogeneity in the approach to the treatment of ADHD in U.S. communities.
Suppressive mechanisms in alloantigen-induced T cell responses.
Authors: M Beckwith, S Rich
Journal: The Journal of Experimental Medicine (1983)

In this report we examined the possibility that suppression of the mixed lymphocyte response by MLR-TsF results from interference with IL-2 regulation of T cell proliferation. Two distinct processes of inhibition involving both a direct effect on IL-2-driven proliferation of responder T cells, and induction of a second-order suppressor cell (Ts2) were described. Exogenous IL-2 did not abrogate MLR-TsF-induced suppression, and activated responder cells from suppressed cultures expressed functional IL-2 receptors by IL-2 adsorption analysis. Thus, suppression is not due to lack of available IL-2 or to abnormal acquisition of receptors for IL-2 during T cell activation. In contrast, a profound MLR-TsF effect on IL-2-induced proliferation of HT2 cells as well as MLR-activated cells was observed even after presaturation of receptors with excess IL-2. These results differentiated the direct responder cell effect of MLR-TsF from its Ts2 inductive capacity, and localized the defect in responder cell proliferation to events occurring subsequent to IL-2 binding. When analyzed in terms of proposed models for hormone-receptor interactions, characteristic dose-response curves similarly predict a postreceptor defect. Examination of the Ts2 pathway of suppression revealed a late-acting inhibitory effect peaking 72 h after MLR initiation. A minor part of Ts2 activity was susceptible to exogenous IL-2, and may reflect a requirement for IL-2 during Ts2 expansion. However, the most significant component of Ts2-mediated suppression was resistant to excess IL-2, and IL-2 production was normal in Ts2-regulated cultures, thus ruling out limitation of IL-2 for responder cell use as the major mechanism of Ts2 suppression. The complete pathway of Ts2 suppression and its functional relationship to other MLR-TsF inhibitory activities is not yet fully understood. However, these results suggest that the ultimate mechanisms of alloantigen-induced suppression involve late events of the IL-2-dependent lymphokine cascade.
And we thought the British were obsessed with the weather
Authors: J. E Graham
Journal: BMJ (2006)

to attain.However, this quality framework emphasises the need to strive for designs that have favourable effects on decision quality.The criteria are not meant to be prescriptive, and an unresolved debate remains about what constitutes a minimum set of domains and criteria that should be met by a patient decision aid. ImplicationsQuality criteria for patient decision aids are relevant to patients, healthcare professionals, healthcare service purchasers, and policy makers.The IPDAS Collaboration checklist is designed for existing users and for developers of new decision aids.To take the field forward, two things are now needed: firstly, to use the IPDAS framework as a basis for developing a validated instrument for assessing the internal quality of the decision tool; secondly, to develop an agreed way to measure the impact of such tools on a range of outcomes.
Differential human leucocyte allele association between psoriasis and psoriatic arthritis: a family-based association study
Authors: Lihi Eder, Vinod Chandran, Fawnda Pellett, Sutha Shanmugarajah, Cheryl F Rosen, Shelley B Bull, Dafna D Gladman
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objective</h3> A recent population-based study identified several HLA alleles as conferring a risk for psoriatic arthritis (PsA) among patients with psoriasis. The authors aimed to confirm these results using a family-based association study. <h3>Methods</h3> PsA probands, psoriasis probands and their first-degree family members were included. All participants were evaluated for the presence of psoriasis and inflammatory arthritis. HLA-B and -C genotyping was performed. The family-based association test was used to test for differences between PsA and psoriasis patients in transmission of candidate alleles from parents to offspring. <h3>Results</h3> A total of 178 PsA and 30 psoriasis probands and 561 first degree family members were analysed. The following HLA alleles were over-transmitted to PsA compared with psoriasis: HLA-C*12 (p=0.005), HLA-B*38 (p=0.04), HLA-B*39 (p=0.03), HLA-B*27 (p=0.002). <h3>Conclusions</h3> HLA-B*27, HLA-B*38, HLA-B*39 and HLA-C*12 alleles are potential PsA-specific genetic markers among patients with psoriasis.
Summer Birth and Deficit Schizophrenia in Dumfries and Galloway, Southwestern Scotland
Authors: Brian Kirkpatrick, Cenk Tek, Judith Allardyce, Gary Morrison, Robin G. McCreadie
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: An association between deficit schizophrenia and summer birth has previously been reported. Confirmation of a separate risk factor for this group of patients is potentially important, but the number of subjects with deficit schizophrenia in previous reports has been small. This analysis used data from an epidemiological study of incident cases of psychosis to test the hypothesis that deficit schizophrenia is associated with summer birth. METHOD: Data were drawn from records for the first year of clinical contact for all new patients coming into treatment for psychosis in the region of Dumfries and Galloway, Scotland, from 1979 to 1998. Patients with schizophrenia were classified as having deficit (N=65) or nondeficit (N=277) schizophrenia. Time of birth in the deficit and nondeficit groups was compared, and time of birth in the deficit group was compared with that for all births in Dumfries and Galloway during the study period. RESULTS: The deficit schizophrenia group had an excess of summer births, compared to both the nondeficit schizophrenia group and all births in Dumfries and Galloway. The difference between the deficit and nondeficit schizophrenia groups remained significant after accounting for demographic characteristics and symptoms of disorganization and hallucinations plus delusions. A measure of negative symptoms (as opposed to deficit schizophrenia) was a weaker predictor of summer birth. CONCLUSIONS: This study confirmed an association between deficit schizophrenia and summer birth in the nontropical regions of the Northern Hemisphere. The existence of a risk factor for deficit but not nondeficit schizophrenia is also consistent with other evidence that the pathophysiology of deficit schizophrenia differs from that for other types of the disorder.
The Pathophysiology of the Peritoneal Membrane
Authors: Olivier Devuyst, Peter J. Margetts, Nicholas Topley
Journal: Journal of the American Society of Nephrology (2010)

The development of peritoneal dialysis (PD) as a successful therapy has and still depends on experimental models to test and understand critical pieces of pathophysiology. To date, the majority of studies performed in rat and rabbit models derive mechanistic insights primarily on the basis of interventional pharmacologic agents, blocking antibodies, or transient expression systems. Because body size no longer limits the performance of in vivo studies of PD, genetic mouse models are increasingly available to investigate the molecular and pathophysiologic mechanisms of the peritoneal membrane. We illustrate in this review how these investigations are catching up with other areas of biomedical research and provide direct evidence for understanding transport and ultrafiltration, responses to infection, and structural changes including fibrosis and angiogenesis. These studies are relevant to mechanisms responsible not only for the major complications of PD but also for endothelial biology, host defense, inflammation, and tissue repair processes.
Clinical Phenotype Classifications Based on Static Varus Alignment and Varus Thrust in Japanese Patients With Medial Knee Osteoarthritis
Authors: Hirotaka Iijima, Naoto Fukutani, Tomoki Aoyama, Takahiko Fukumoto, Daisuke Uritani, Eishi Kaneda, Kazuo Ota, Hiroshi Kuroki, Shuichi Matsuda
Journal: Arthritis & Rheumatology (2015)

Objective To investigate the association between knee pain during gait and 4 clinical phenotypes based on static varus alignment and varus thrust in patients with medial knee osteoarthritis (OA). Methods Patients in an orthopedic clinic (n = 266) diagnosed as having knee OA (Kellgren/Lawrence [K/L] grade ≥1) were divided into 4 phenotype groups according to the presence or absence of static varus alignment and varus thrust (dynamic varus): no varus (n = 173), dynamic varus (n = 17), static varus (n = 50), and static varus + dynamic varus (n = 26). The knee range of motion, spatiotemporal gait parameters, visual analog scale scores for knee pain, and scores on the Japanese Knee Osteoarthritis Measure were used to assess clinical outcomes. Multiple logistic regression analyses identified the relationship between knee pain during gait and the 4 phenotypes, adjusted for possible risk factors, including age, sex, body mass index, K/L grade, and gait velocity. Results Multiple logistic regression analysis showed that varus thrust without varus alignment was associated with knee pain during gait (odds ratio [OR] 3.30, 95% confidence interval [95% CI] 1.08–12.4), and that varus thrust combined with varus alignment was strongly associated with knee pain during gait (OR 17.1, 95% CI 3.19–320.0). Sensitivity analyses applying alternative cutoff values for defining static varus alignment showed comparable results. Conclusion Varus thrust with or without static varus alignment was associated with the occurrence of knee pain during gait. Tailored interventions based on individual malalignment phenotypes may improve clinical outcomes in patients with knee OA.
Decationized polyplexes as stable and safe carrier systems for improved biodistribution in systemic gene therapy
Authors: Luís Novo, Larissa Y. Rizzo, Susanne K. Golombek, George R. Dakwar, Bo Lou, Katrien Remaut, Enrico Mastrobattista, Cornelus F. van Nostrum, Wilhelm Jahnen-Dechent, Fabian Kiessling, Kevin Braeckmans, Twan Lammers, Wim E. Hennink
Journal: Journal of Controlled Release (2014)
Soluble cytokine receptors are present in normal human urine.
Authors: D Novick, H Engelmann, D Wallach, M Rubinstein
Journal: The Journal of Experimental Medicine (1989)

Affinity chromatography of crude human urinary proteins on either human rIL-6, human rIFN-gamma, or anti-IFN-gamma-R mAb yielded the two respective soluble receptors in significant quantities. A single sequence of 30 amino acid residues was obtained by NH2-terminal microsequencing of the protein peak purified in tandem by affinity chromatography on an IL-6 column and reversed-phase HPLC. This sequence was identical to the predicted NH2-terminal sequence of IL-6-R as previously reported. Analysis of the eluted proteins from both IFN-gamma and anti-IFN-gamma-R columns by inhibition of solid phase RIA, ELISA, SDS-PAGE, and Western blotting proved the existence of soluble IFN-gamma-R in normal urine. Our finding, together with the already known presence of urinary TNF binding proteins and a soluble IL-2-R both in plasma and in urine, indicates that release of soluble cytokine receptors into body fluids is a general phenomenon that occurs under normal physiological conditions.
Oleic acid, the main monounsaturated fatty acid of olive oil, suppresses Her-2/neu (erbB-2) expression and synergistically enhances the growth inhibitory effects of trastuzumab (Herceptin™) in breast cancer cells with Her-2/neu oncogene amplification
Authors: J.A. Menendez, L. Vellon, R. Colomer, R. Lupu
Journal: Annals of Oncology (2005)