tbuckley/cabot-search huggingface dataset:
MYCN-Directed Centrosome Amplification Requires MDM2-Mediated Suppression of p53 Activity in Neuroblastoma Cells
Authors: Andrew D. Slack, Zaowen Chen, Andrew D. Ludwig, John Hicks, Jason M. Shohet
Journal: Cancer Research (2007)

Abstract The MYC family oncogenes cause transformation and tumor progression by corrupting multiple cellular pathways, altering cell cycle progression, apoptosis, and genomic instability. Several recent studies show that MYCC (c-Myc) expression alters DNA repair mechanisms, cell cycle checkpoints, and karyotypic stability, and this is likely partially due to alterations in centrosome replication control. In neuroblastoma cell lines, MYCN (N-Myc) expression induces centrosome amplification in response to ionizing radiation. Centrosomes are cytoplasmic domains that critically regulate cytokinesis, and aberrations in their number or structure are linked to mitotic defects and karyotypic instability. Whereas centrosome replication is linked to p53 and Rb/E2F-mediated cell cycle progression, the mechanisms downstream of MYCN that generate centrosome amplification are incompletely characterized. We hypothesized that MDM2, a direct transcriptional target of MYCN with central inhibitory effects on p53, plays a role in MYC-mediated genomic instability by altering p53 responses to DNA damage, facilitating centrosome amplification. Herein we show that MYCN mediates centrosome amplification in a p53-dependent manner. Accordingly, inhibition of the p53-MDM2 interaction with Nutlin 3A (which activates p53) completely ablates the MYCN-dependent contribution to centrosome amplification after ionizing radiation. We further show that modulating MDM2 expression levels by overexpression or RNA interference–mediated posttranscriptional inhibition dramatically affects centrosome amplification in MYCN-induced cells, indicating that MDM2 is a necessary and sufficient mediator of MYCN-mediated centrosome amplification. Finally, we show a significant correlation between centrosome amplification and MYCN amplification in primary neuroblastoma tumors. These data support the hypothesis that elevated MDM2 levels contribute to MYCN-induced genomic instability through altered regulation of centrosome replication in neuroblastoma. [Cancer Res 2007;67(6):2448–55]
An electronic nose distinguishes the exhaled breath of obese patients with obstructive sleep apnoea (OSA) from subjects with a similar body mass index and without OSA
Authors: Silvano Dragonieri, Perluigi Carratu, Antonio Baldassarre, Valentina Ventura, Maria Aliani, Mauro Carone, Onofrio Resta
Journal: European Respiratory Journal (2014)

INTRODUCTION.Airway inflammation plays an important role in Obstructive Sleep Apnoea (OSA) as well as in obesity. Numerous experimental studies have demonstrated an important role of oxidative stress and inflammation in the pathogenesis of OSA. Exhaled breath contains thousands of Volatile Organic Compounds (VOCs) in gaseous form which may be used as markers of airway inflammation and lung disease. The use of electronic nose allows a quick and real-time pattern analysis of VOCs spectrum. Recent studies have shown that an electronic nose may become a diagnostic tool for several lung diseases. It has been shown that exhaled breath of patients with OSA differed from that of controls (Greulich et al, ERJ 2013). However, it is still unclear whether this discrimination may be due to the presence of obesity rather than OSA itself. Therefore we aimed to assess the influence of obesity in the composition of exhaled VOCs.  METHODS. 10 obese patients with established OSA (age 51.2±6.8; BMI 34.3±3.5) and 10 obese controls without OSA (age 56.5±7.6; BMI 33.5±4.1), participated to a cross-sectional study.  Exhaled breath was collected by a previously described method (Dragonieri et al. JACI 2007) and sampled by the electronic nose (Cyranose 320). Breathprints were analyzed by canonical discriminant analysis on principal component reduction. Cross-validation values (CVV) and Mahalanobis distance were calculated (M-dist)  RESULTS. Breathprints from patients with OSA were moderately separated from those without OSA (CVV=75%;M-dist =1,73).  CONCLUSIONS. The presence of OSA seems to alter the exhaled VOCs pattern in obese subjects.
Effects of hypertonic saline, alternate day and daily rhDNase on healthcare use, costs and outcomes in children with cystic fibrosis
Authors: R Suri
Journal: Thorax (2002)

<b>Background:</b> Daily recombinant human deoxyribonuclease (rhDNase) is an established but expensive treatment in cystic fibrosis (CF). An alternative lower cost therapy is hypertonic saline (HS), which has been shown to improve lung function in short term studies. This study compares the costs and consequences of daily rhDNase with alternate day rhDNase and HS in children with CF. <b>Methods:</b> In an open, randomised, crossover trial, 48 children with CF were allocated consecutively to 12 weeks of once daily 2.5 mg rhDNase, alternate day 2.5 mg rhDNase, and twice daily 5 ml 7% HS. Outcomes assessed included forced expiratory volume in 1 second (FEV<sub>1</sub>) and quality of life. All healthcare resource use was prospectively recorded for each patient. Unit costs were collected and combined with resource use data to give the total health service costs per patient for each treatment strategy. <b>Results:</b> Daily rhDNase resulted in a significantly greater increase in mean FEV<sub>1</sub> than HS (8%, 95% CI 2 to 14) but there was no significant difference in FEV<sub>1</sub> between daily and alternate day rhDNase (2%, 95% CI –4 to 9). Over a 12 week period the mean incremental costs of daily rhDNase compared with HS was £1409 (95% CI £440 to £2318), and the incremental cost of using daily rather than alternate day rhDNase was £513 (95% CI –£546 to £1510). <b>Conclusions:</b> Daily rhDNase is more effective than 5 ml 7% HS twice daily delivered by jet nebuliser, but significantly increases healthcare costs. Administering rhDNase on an alternate day rather than a daily basis is as effective, with a potential for cost savings.
Population Variations in the Initial Treatment of Non–Small-Cell Lung Cancer
Authors: Arnold L. Potosky, Scott Saxman, Robert B. Wallace, Charles F. Lynch
Journal: Journal of Clinical Oncology (2004)

Dissemination of recommended therapies for non-small-cell lung cancer (NSCLC) have not been described comprehensively. We report the patterns of initial therapy focusing on the investigation of differences in receipt of recommended therapies according to multiple clinical and nonclinical patient characteristics.A population-based random sample of newly diagnosed NSCLC patients diagnosed in 10 separate geographic areas was collected in 1996 (n = 898). Data were obtained from medical records. Multiple logistic regression was used to assess the use of recommended therapies.Overall, 52% of NSCLC patients received recommended therapy. Approximately 69%, 48%, and 41% of patients with stages I and II, III, or IV NSCLC received recommended therapy, respectively. For all stages combined, the use of recommended therapy was significantly inversely associated with age and stage at diagnosis. Recommended therapy also was more common in white versus black patients, and in married versus single patients. Stage-specific analyses revealed a significant decline in the use of recommended surgery with increasing age at diagnosis for early-stage NSCLC only, and a significantly lower use of recommended therapy (primarily chemoradiotherapy) for stage III black and Hispanic patients compared with white patients.The overall use of recommended therapies for NSCLC is low. Large variations exist in the use of such therapies according to age, race or ethnicity, and marital status. Research combining medical record reviews with other sources of data is needed to better understand the contributions of both patient preferences and physician judgment to these treatment variations.
On the Influence of Altitude and Pressure on the 'Vital Capacity' of Man
Authors: F. C. Hewett
Journal: BMJ (1875)

THz influence of altitude upon the spirometric measurements of the expired air (vital capacity of Hutchinson) is a subject that has not met with much attention.Rattray, in his researches on climate, pub- lished in the Proceedings of the Royal Society (I869-72), incidentally mentions that an ascent of 2,000 feet at Ascension lessened the "vital capacity", as judged of by the spirometer, from 266 to 249 and 243 cubic inches.In seeking to verify these results, I determined, as an opportunity offered, to carry out more extended observations upon the subject.Two officers of H. M. S. Nor-thumberland (Lieutenants Camp- bell and Simpson), whose "vit .1 capacity" had previously been fre- quently noted, volunteered; obs-rvations being taken during a period of three days, the altitude of the place of observation, at Mladeira, as determined by an aneroid barometer, corrected for temperature, being ,950 feet, this agreeing with the altitude given by Dr. Hartung in his
A rapid change in a patient's chest radiograph appearances
Authors: Joseph Hutton, Claire McBrien, Zafeiris Sardelis, Garrett McGann
Journal: Thorax (2014)

A 72-year-old man with a history of rheumatoid arthritis (on multiple immunosuppressants: leflunomide, etanercept and hydroxychloroquine) was admitted with headache and fever. He had no other symptoms or relevant medical history. Clinical examination demonstrated coarse crepitations throughout the right upper zone. Chest radiograph revealed consolidation in the right upper zone, peripherally (figure 1A).



Figure 1 
(A) Admission chest radiograph. (B) Repeat chest radiograph following episode of pleuritic chest pain and haemoptysis.



The patient's immunosuppressive agents were stopped and he was treated with intravenous benzylpenicillin, clarithromycin and a single dose of gentamicin. After several days of treatment, he improved clinically. Unfortunately 7 days into the admission, he awoke feeling dyspnoeic. He coughed and experienced right-sided pleuritic pain, which resolved following an episode of haemoptysis (a few millilitres only). Clinical examination demonstrated decreased air entry in …
Lymphomas with concurrent BCL2 and MYC translocations: the critical factors associated with survival
Authors: Nathalie A. Johnson, Kerry J. Savage, Olga Ludkovski, Susana Ben-Neriah, Ryan Woods, Christian Steidl, Martin J. S. Dyer, Reiner Siebert, John Kuruvilla, Richard Klasa, Joseph M. Connors, Randy D. Gascoyne, Douglas E. Horsman
Journal: Blood (2009)
Maternal anti-D concentrations and outcome in rhesus haemolytic disease of the newborn.
Authors: P Bowell, J S Wainscoat, T E Peto, H H Gunson
Journal: BMJ (1982)

The relation between maternal anti-D concentrations, measured against the British working standard, and outcome of rhesus-sensitised pregnancies was studied. There is a clear relation between increasing anti-D concentrations and the chance of a severely affected baby. Of those pregnancies (78) where serial anti-D concentrations remained below 4 IU/ml, no baby had a cord haemoglobin below 10 g/dl and three had exchange transfusions. In contrast, of those mothers (106) with anti-D concentrations above 4 IU/ml, 23 had babies with a cord haemoglobin below 10 g/dl and 79 babies had exchange transfusions. It is suggested that those pregnancies where anti-D concentrations remain below 4 IU/ml represent a relatively safe group in which amniocentesis may be avoided.
Spirometry interpretation for primary care: A validation study
Authors: Alan Kaplan, Jade Lerner
Journal: European Respiratory Journal (2013)

Objective measurement of lung function with spirometry should be done in primary care to allow immediate feedback on diagnosis and management of respiratory conditions. Lack of training necessitates a teaching program and tool for spirometric interpretation. The Family Physician Airways Group of Canada (www.fpagc.com) has taught this at a five primary care conferences over 3 years. This post program survey reviewed participants’ attitudes to this spirometry algorithm.  121/138 surveys were returned. 40% of the participants had been in practice for less than 10 years and 31% more than 20 years. Most were in a group practice. 63% were currently not doing spirometry, yet they came to learn interpretative skills and were debating the purchase of a machine. Spirometry was annually ordered less than 10 times by 19%, 10-50 times by 46% and more than 100 times by 16%.  21% of physicians were currently using an algorithm tool. 71% of participants said that they would now use the tool provided in the program. 98% of participants found the tool helpful in interpreting spirometry, with 93% of physicians saying that they will use this in their practice in the future. They felt the algorithm would assist them in diagnosing asthma (91%), assessing asthma control (94%) and diagnosing COPD (94%).  Barriers related to the performance of spirometry in primary care; time, cost, technique, monetary reimbursement and interpretation of grey zone cases.  The creation and teaching of a spirometry program and interpretation algorithm tool has successfully created comfort in spirometry interpretation in most participants. This was a particularly strongly motivated group of learners, as had to pay to attend this specially accredited program.
Syringolymphoid hyperplasia with alopecia
Authors: F. VAKILZADEH, E. B. BROCKER
Journal: British Journal of Dermatology (1984)

A 26-year-old man presented with an unusual skin lesion consisting of a hairless area on the left leg studded with reddish-brown papules, together with follicular hyperkeratosis and circumscribed anhidrosis. Skin biopsies showed dense lymphocytic infiltrates in the dermis and around hyperplastic sweat ducts and glands. Similar clinical and histological features have been described in two previous case reports. We propose the term syringolymphoid hyperplasia with alopecia for this unusual skin disease.
Single-Gene Abrogation of Spontaneous Pleomorphic SJL/J Mouse Reticulum Cell Sarcoma Expression&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: J E Bubbers
Journal: JNCI Journal of the National Cancer Institute (1983)

Inbred SJL/J and A.SW/SnJ mice have been bred to produce (SJL female X A.SW male)F1 and A.SW female X SJL male)F1 mice. F1 mice were then crossed to produce (SJL female X A.SW male)F2 and (A.SW female X SJL male)F2 mice. The inbred, F1, and F2 populations were followed for 2 years to determine the incidences of spontaneous reticulum and sarcoma (RCS) expression. SJL mice had a greater than 90% incidence of RCS, although F1 mice showed almost no RCS. The incidence of RCS in the F2 populations was 24.1%. These data were consistent with the hypothesis that in F1 and F2 populations a single dominant A.SW gene is able to suppress the expression of the pleomorphic RCS disease characteristic of the SJL mouse. This gene was not an H-2 gene, since the two strains were congenic with respect to the major histocompatibility complex; this gene was not on the Y-chromosome, and its phenotypic expression was not inherited in an X-linked manner.
SUBUNGUAL EPIDERMOID INCLUSIONS
Authors: KLAUS LEWIN
Journal: British Journal of Dermatology (1969)

SUMMARY.— This paper describes the evolution of subungual epidermoid inclusions and discusses their aetiology. They are shown to develop from the tips of the rete ridges by a process of bulbous proliferation. Ultimately they may lose their connection with the epidermis and come to lie deeply within the dermis of the nail bed. Although the lesions are usually microscopic in size they may be large and should be considered in the differential diagnosis of nail bed swellings. The aetiology of these lesions is still obscure. They may follow trauma and are found in finger clubbing and it is probable that different stimuli can produce them.
Role of the Calcium-Independent Transient Outward Current <i>I</i> <sub>to1</sub> in Shaping Action Potential Morphology and Duration
Authors: Joseph L. Greenstein, Richard Wu, Sunny Po, Gordon F. Tomaselli, Raimond L. Winslow
Journal: Circulation Research (2000)

Abstract —The Kv4.3-encoded current ( I Kv4.3 ) has been identified as the major component of the voltage-dependent Ca 2+ -independent transient outward current ( I to1 ) in human and canine ventricular cells. Experimental evidence supports a correlation between I to1 density and prominence of the phase 1 notch; however, the role of I to1 in modulating action potential duration (APD) remains unclear. To help resolve this role, Markov state models of the human and canine Kv4.3- and Kv1.4-encoded currents at 35°C are developed on the basis of experimental measurements. A model of canine I to1 is formulated as the combination of these Kv4.3 and Kv1.4 currents and is incorporated into an existing canine ventricular myocyte model. Simulations demonstrate strong coupling between L-type Ca 2+ current and I Kv4.3 and predict a bimodal relationship between I Kv4.3 density and APD whereby perturbations in I Kv4.3 density may produce either prolongation or shortening of APD, depending on baseline I to1 current level.
Double-blind trial of the use of transfer factor in the treatment of Crohn's disease.
Authors: F R Vicary, J D Chambers, P Dhillon
Journal: Gut (1979)

We have undertaken a double-blind controlled trial of the use of transfer factor in Crohn9s disease. Thirty-three patients with known Crohn9s disease completed the trial in which half the patients had three injections of transfer factor and the other half were given saline. After six months there was no significant difference in the clinical condition of either of the two groups compared with before receiving treatment. There was also no difference in their in vitro lymphocyte function, although a number of patients exhibited altered responsiveness to skin testing with tuberculin or streptokinase/streptodornase. A signficant fall on Crohn9s disease activity index score occurred over the initial 9acclimatising period9 before the trial was started, probably related to overcoming initial introspection and the placebo effect of being part of a trial.
Randomised crossover study of pressure and volume non-invasive ventilation in chest wall deformity
Authors: J M Tuggey
Journal: Thorax (2005)

<b>Background:</b> Non-invasive ventilation is an established treatment for chronic respiratory failure due to chest wall deformity. There are few data available to inform the choice between volume and pressure ventilators. The aim of this study was to compare pressure and volume targeted ventilation in terms of diurnal arterial blood gas tensions, lung volumes, hypercapnic ventilatory responses, sleep quality, and effect on daytime function and health status when ventilators were carefully set to provide the same minute ventilation. <b>Methods:</b> Thirteen patients with chest wall deformity underwent a 4 week single blind randomised crossover study using the Breas PV403 ventilator in either pressure or volume mode with assessments made at the end of each 4 week period. <b>Results:</b> Minute ventilation at night was less than that set during the day with greater leakage for both modes of ventilation. There was more leakage with pressure than volume ventilation (13.8 (1.9) <i>v</i> 5.9 (1.0) l/min, p = 0.01). There were no significant differences in sleep quality, daytime arterial blood gas tensions, lung mechanics, ventilatory drive, health status or daytime functioning. <b>Conclusions:</b> These data suggest that pressure and volume ventilation are equivalent in terms of the effect on nocturnal and daytime physiology, and resulting daytime function and health status.
Survival of calcium pyrophosphate crystals in stored synovial fluids.
Authors: N W McGill, A Swan, P A Dieppe
Journal: Annals of the Rheumatic Diseases (1991)

Eleven synovial fluids containing calcium pyrophosphate dihydrate (CPPD) were examined repeatedly over an eight week period to assess whether storage conditions and duration influenced the number of crystals present. Aliquots of each fluid were stored at room temperature, 4 degrees C, and -70 degrees C. At -70 degrees C there was no change in crystal count after eight weeks' storage. At room temperature and 4 degrees C crystal counts declined slowly over the eight week period, though CPPD crystals were still readily apparent after eight weeks in 10/11 (4 degrees C) and 8/11 (room temperature) fluids. No change in crystal morphology was detected and, apart from one fluid kept at room temperature in which fungal hyphae were noted at six weeks, no new crystals were seen. Calcium pyrophosphate dihydrate crystals in synovial fluid can be maintained for prolonged periods by freezing.
Estrogen-induced chromatin decondensation and nuclear re-organization linked to regional epigenetic regulation in breast cancer
Authors: Sehrish Rafique, Jeremy S. Thomas, Duncan Sproul, Wendy A. Bickmore
Journal: Genome biology (2015)

Epigenetic changes are being increasingly recognized as a prominent feature of cancer. This occurs not only at individual genes, but also over larger chromosomal domains. To investigate this, we set out to identify large chromosomal domains of epigenetic dysregulation in breast cancers.We identify large regions of coordinate down-regulation of gene expression, and other regions of coordinate activation, in breast cancers and show that these regions are linked to tumor subtype. In particular we show that a group of coordinately regulated regions are expressed in luminal, estrogen-receptor positive breast tumors and cell lines. For one of these regions of coordinate gene activation, we show that regional epigenetic regulation is accompanied by visible unfolding of large-scale chromatin structure and a repositioning of the region within the nucleus. In MCF7 cells, we show that this depends on the presence of estrogen.Our data suggest that the liganded estrogen receptor is linked to long-range changes in higher-order chromatin organization and epigenetic dysregulation in cancer. This may suggest that as well as drugs targeting histone modifications, it will be valuable to investigate the inhibition of protein complexes involved in chromatin folding in cancer cells.
Watchdog finds that NHS is failing stroke patients
Authors: Rebecca Coombes
Journal: BMJ (2005)

The UK National Audit Office has found that the NHS is failing stroke patients at all points of the patient's journey from initial emergency treatment through to rehabilitation.

The study found that stroke costs the economy £7bn ($12.1bn; €10.4bn) a year, making it the most expensive illness in the United Kingdom. But by failing to prioritise stroke cases as medical emergencies the NHS was missing out on savings that would result from shorter hospital stays and higher recovery rates, the watchdog found.

The study found that emergency care was lacking throughout the health service—despite the fact that rapid access to specialised services reduces death and disability in …