tbuckley/cabot-search huggingface dataset:
Abstract A67: Canonical WNT/β;-catenin pathway activation suppresses embryonal rhabdomyosarcoma growth and self-renewal
Authors: Eleanor Chen, Michael DeRan, Katherine Brooke Grandinetti, Myron Ignatius, Ryan Clagg, Karin McCarthy, Riadh Lobbardi, Xu Wu, David Langenau
Journal: Cancer Research (2014)

Abstract Embryonal rhabdomyosarcoma (ERMS) is a common pediatric malignancy of muscle with relapse being the major clinical challenge. Self-renewing tumor-propagating cells (TPCs) drive cancer relapse and are confined to a molecularly definable subset of ERMS cells. To identify drugs that suppress TPC function, a large-scale chemical screen comprising of ∼40,000 compounds including 47% FDA-approved drugs was completed, identifying GSK3-inhibitors as potent suppressors of ERMS growth through inducing terminal differentiation of TPCs into myosin-expressing cells. In support of GSK3 inhibitors functioning through activation of the canonical WNT pathway, recombinant WNT3A and a stabilized β-catenin enhanced differentiation and reduced self-renewal in human ERMS cell lines. Moreover, treatment of tumor-bearing zebrafish with a GSK3 inhibitor activated the WNT/β-catenin pathway, resulting in suppressed ERMS growth, depleted TPCs, and diminished self-renewal capacity in vivo. As canonical WNT signaling is essential for transition from muscle stem cell proliferation to myogenic differentiation during regeneration, our findings suggest that the same developmental pathways that regulate muscle stem cell self-renewal also contribute to tumorigenesis in ERMS. GSK3 inhibitors are being assessed for their efficacy in inhibiting growth as well as inducing differentiation of human ERMS in xenograft mouse models. Our work has identified the vital role of canonical WNT pathway in regulating differentiation and self-renewal of ERMS and demonstrated the effective application of small molecule inhibitors to target differentiation of TPCs in ERMS. Citation Format: Eleanor Chen, Michael DeRan, Katherine Brooke Grandinetti, Myron Ignatius, Ryan Clagg, Karin McCarthy, Riadh Lobbardi, Xu Wu, David Langenau. Canonical WNT/β;-catenin pathway activation suppresses embryonal rhabdomyosarcoma growth and self-renewal. [abstract]. In: Proceedings of the AACR Special Conference on Pediatric Cancer at the Crossroads: Translating Discovery into Improved Outcomes; Nov 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;74(20 Suppl):Abstract nr A67.
Assessment of thyroid status in elderly people.
Authors: P Rae, J Farrar, G Beckett, A Toft
Journal: BMJ (1993)

Thyroid function tests are not indicated in ill patients unless there is good clinical evidence that thyroid disease is contributing to their clinical condition * Thyroid function should not be assessed in entirely fit and active elderly people * The test of choice is serum thyroid stimu- lating hormone (TSH) concentration * A normal serum TSH concentration virtually excludes hypothyroidism and hyperthyroidism * Problems with interpreting thyroid function tests in elderly people usually result from nonthyroidal illness or drug treatment
Corrigendum to ‘Impact of the learning curve on outcomes after percutaneous mitral valve repair with MitraClip<sup>®</sup> and lessons learned after the ﬁrst 75 consecutive patients’ [Eur J Heart Fail 2011;13:1331–1339]
Authors: Wolfgang Schillinger, Thomas Athanasiou, Ninja Weicken, Lars Berg, Tobias Tichelbäcker, Miriam Puls, Mark Hünlich, Rolf Wachter, Hans‐Joachim Helms, Ralf Seipelt, Friedrich A. Schöndube, Gerd Hasenfuss
Journal: European Journal of Heart Failure (2012)
Hepatic gene expression and lipid parameters in complement C3−/− mice that do not develop ethanol-induced steatosis
Authors: Igor Bykov, Matti Jauhiainen, Vesa M. Olkkonen, Sirkku T. Saarikoski, Christian Ehnholm, Sami Junnikkala, Antti Väkevä, Kai O. Lindros, Seppo Meri
Journal: Journal of Hepatology (2007)
On Early Syphilitic Epididymitis
Authors: A. Cooper
Journal: BMJ (1885)

during life.From the tapping upon December 7th till February 14th, a period of 68 (days, 2,110 ounces were removed, or rather more thaus 31 ounces per day.The extraordinary fact must be noted that thoughi 117k pints were iemoved, the patient did not lose weiglht.He weighed
LONG-TERM (&gt;2 YEARS) FOLLOW-UP RESULTS OF SIROLIMUS- AND PACLITAXEL-ELUTING STENT IN OPTICAL COHERENCE TOMOGRAPHY: COMPARISON TO 9-MONTHS FOLLOW-UP RESULTS: I2 POSTER CONTRIBUTIONS
Authors: Tae Hoon Kim, Jung-Sun Kim, Young-Guk Ko, Donghoon Choi, Myeong-Ki Hong, Yangsoo Jang, Won Heum Shim, Seung Yun Cho
Journal: Journal of the American College of Cardiology (2010)
Pharmacists should provide oral contraceptive services, says NHS report
Authors: J. Wise
Journal: BMJ (2012)

A report from NHS South East London has recommended that trained community pharmacists provide oral contraceptive consultation services after a successful pilot scheme to widen access to contraception.

The part of the report that has received the most media coverage is a recommendation to “consider providing the service to women under 16 years where appropriate.” The report said that this may help reduce numbers of teenage pregnancies.

The pilot scheme took place in five pharmacies in Southwark and Lambeth, in south London. These boroughs have some of the highest rates of teenage conception in Europe and the highest in London. The proportion of teenagers’ pregnancies ending in abortion in Southwark and Lambeth is higher, at 66% and 60% respectively, than the UK average …
Adrenal insufficiency in patients with cirrhosis and septic shock: Effect of treatment with hydrocortisone on survival
Authors: Javier Fernández, Angels Escorsell, Michel Zabalza, Vanessa Felipe, Miguel Navasa, Antoni Mas, Antonio M. Lacy, Pere Ginès, Vicente Arroyo
Journal: Hepatology (2006)

Relative adrenal insufficiency is frequent in patients with severe sepsis and is associated with hemodynamic instability, renal failure, and increased mortality. This study prospectively evaluated the effects of steroids on shock resolution and hospital survival in a series of 25 consecutive patients with cirrhosis and septic shock (group 1). Adrenal function was evaluated by the short corticotropin test within the first 24 hours of admission. Patients with adrenal insufficiency were treated with stress doses of intravenous hydrocortisone (50 mg/6 h). Data were compared to those obtained from the last 50 consecutive patients with cirrhosis and septic shock admitted to the same intensive care unit in whom adrenal function was not investigated and who did not receive treatment with steroids (group 2). Incidence of adrenal insufficiency in group 1 was 68% (17 patients). Adrenal dysfunction was frequent in patients with advanced cirrhosis (Child C: 76% vs. Child B: 25%, P = .08). Resolution of septic shock (96% vs. 58%, P = .001), survival in the intensive care unit (68% vs. 38%, P = .03), and hospital survival (64% vs. 32%, P = .003) were significantly higher in group 1. The main causes of death in group 1 were hepatorenal syndrome or liver failure (7 of 9 patients). In contrast, refractory shock caused most of the deaths in group 2 (20 of 34 patients). In conclusion , relative adrenal insufficiency is very frequent in patients with advanced cirrhosis and septic shock. Hydrocortisone administration in these patients is associated with a high frequency of shock resolution and high survival rate.
Obstetric Anaesthesia Services in the United Kingdom
Authors: G. Taylor
Journal: BMJ (1971)

In a survey of obstetric anaesthetic services in the United Kingdom questionnaires were sent to 398 hospital maternity units and 347 general-practitioner maternity units, of which 344 and 272 respectively were returned. Many hospitals were unable to provide an anaesthetist for obstetric surgery only, and few consultant anaesthetist sessions were allocated to obstetric surgery, particularly in regional hospitals in England and Wales. Constant supervision of junior anaesthetic staff with under 12 months9 experience was lacking in several hospitals. Endotracheal intubation is widely used throughout the United Kingdom. Though regional analgesic techniques are used by most anaesthetists it is impossible to provide a 24-hour regional analgesic service in all but a few hospitals.
Crunching ice cube syndrome
Authors: Francois L P Fouin
Journal: BMJ (2008)

The sound of crunching ice was obviously beginning to irritate the other members of my regular golfing foursome. Two were fellow doctors, but it was the retired garage proprietor who was getting most unsettled.

It had crept up on me imperceptibly, but now there was no mistaking that something odd was going on. Whatever soft drink I consumed had to be fully topped up with ice, while my regular lunchtime sherry was brimming over with small cubes. It was …
Saw Taik Leong
Authors: R. C Leong
Journal: BMJ (2002)

Former eye surgeon Lethbridge, Alberta, Canada (b Mudon, Burma, 1918; q Punjab 1944; DOMS, DO, FRCS), d 15 October 2001.

Educated in Rangoon, India, London, and Oxford, he served as a captain in the British-Burma army. Dr Leong found his greatest rewards in serving his community and enjoying his life and home in southern Alberta. He leaves a wife, Phyllis; two children; and a grandson.
Trial is started to see whether gene therapy can improve lung function in cystic fibrosis
Authors: Z. Kmietowicz
Journal: BMJ (2012)

A trial of gene therapy that aims to repair the underlying fault in people with cystic fibrosis will begin this month, involving 130 adults and children in the United Kingdom.

The trial, described as the largest of its kind, is coordinated by the UK Cystic Fibrosis Gene Therapy Consortium and funded by a £3.1m (€3.7m; $4.9m) grant from the National Institute for Health Research and the Medical Research Council.

Cystic fibrosis, the commonest inherited disease caused by a single mutation in a gene, affects around 9500 people in the UK …
Scientists use gene therapy to cure immune deficient child
Authors: J. Siegel-Itzkovich
Journal: BMJ (2002)

An international team of scientists has managed to cure a child with severe combined immunodeficiency (SCID) using gene therapy.

Patients with SCID are usually treated by replacing an essential enzyme, adenosine deaminase, which is lacking in such people. But this treatment is effective for only a couple of days at a time and is expensive. Some patients can have a bone marrow transplant, but only if a good match can be found.

The team was headed by Professor Shimon Slavin, of the Hadassah University Hospital in Jerusalem, and his colleagues Dr Shoshana Morecki and Dr Memet Aker. They collaborated with Dr Allesandro Aiuti and other staff from the San Raffaele Institute for …
Maternal affective disorders, illness, and stress: risk for children's psychopathology
Authors: Constance L. Hammen, David Gordon, Dorli Burge, Cheri Adrian, Carol Jaenicke, Donald Hiroto
Journal: American Journal of Psychiatry (1987)

Stressful circumstances that covary with maternal affective disorder may account for some of the risk to children for psychological dysfunction. Children (ages 8-16) of mothers with unipolar or bipolar disorders were compared with children of mothers who had chronic medical illness and children of normal mothers. Comparisons included Kiddie-SADS (Schedule for Affective Disorders and Schizophrenia) diagnoses and evaluations of behavior problems, school functioning, and social competence. Compared to the other groups, children of mothers with affective disorder (especially unipolar) had high rates of diagnosis. With the effects of chronic stress statistically controlled, psychosocial outcome variables showed fewer differences between groups but indicated particular impairment for children of unipolar mothers.
Phenytoin Tolerance Tests
Authors: A. J. Handley
Journal: BMJ (1970)

Oral and intravenous phenytoin tolerance tests showed distinctive biphasic curves with a fall in plasma phenytoin to very low levels after an initial peak and a rise to a secondary peak one to four hours later. It is suggested that this pattern should be borne in mind when intravenous phenytoin is being used, as in the control of status epilepticus or cardiac arrhythmias.
β-Adrenergic receptor stimulation causes cardiac hypertrophy via a Gβγ/Erk-dependent pathway
Authors: Marie Vidal, Thomas Wieland, Martin J. Lohse, Kristina Lorenz
Journal: Cardiovascular Research (2012)

Activation of the β(1)-adrenergic receptor and its G protein, G(s), induces cardiac hypertrophy. However, activation of classic Gα(s) effectors, adenylyl cyclases (AC) and protein kinase A, is not sufficient for induction of hypertrophy, which suggests the involvement of additional pathway(s) activated by G(s). Recently, we discovered that βγ subunits of G(q) induce phosphorylation of the extracellular regulated kinases 1 and 2 (Erk1/2) at threonine188 and thereby induce hypertrophy. Here we investigated whether β-adrenergic receptors might also induce cardiac hypertrophy via Erk(Thr188) phosphorylation.β-Adrenergic receptor activation induced Erk(Thr188) phosphorylation in mouse hearts and in neonatal cardiomyocytes. Inhibition of Erk1/2 or overexpression of Erk(Thr188) phosphorylation-deficient mutants (Erk2(T188A) and Erk2(T188S)) significantly attenuated β-adrenergic cardiomyocyte hypertrophy in vitro. Erk activity was stimulated by both isoproterenol and the direct AC activator forskolin, but only isoproterenol induced Erk(Thr188) phosphorylation. Erk(Thr188) phosphorylation required Gβγ released from G(s) and was prevented by Gβγ inhibition. Similarly, isoproterenol, but not forskolin, induced nuclear accumulation of Erk and cardiomyocyte hypertrophy. Long-term application of isoproterenol in mice caused left ventricular hypertrophy and cardiac remodelling, and this was reduced in Erk2(T188S) transgenic mice, supporting the physiological relevance of Erk(Thr188) phosphorylation.Activation of G(s) by β-adrenergic receptors leads to (i) canonical Erk1/2 activation via AC, and (ii) release of Gβγ, which then associates with activated Erk1/2 and induces Erk(Thr188) phosphorylation, causing nuclear accumulation of Erk and ultimately cardiomyocyte hypertrophy. These findings reveal a new pathway critically involved in β-adrenergically mediated cardiac hypertrophy and may yield new therapeutic strategies against hypertrophic remodelling.
The epigenesis of regional specificity
Authors: Ralph-Axel Müller
Journal: Behavioral and Brain Sciences (1996)

Abstract Chomskyian claims of a genetically hard-wired and cognitively autonomous “universal grammar” are being promoted by generative linguistics as facts about language to the present day. The related doctrine of an evolutionary discontinuity in language emergence, however, is based on misconceptions about the notions of homology and preadaptation. The obvious lack of equivalence between symbolic communicative capacities in existing nonhuman primates and human language does not preclude common roots. Normal and disordered language development is strongly influenced by the genome, but there is no evidence for the existence of specific genes underlying “universal grammar.” In the mature brain, stages of language processing can be distinguished and “first-pass” syntactic analyses appear to precede semantic decoding. However, this partial seriality – as well as behavioral and clinical dissociations between lexical and functional categories – can be best described, not in terms of serially activated and discrete modules, but in terms of classes of cell assemblies that differ in their distributional properties. Whereas cell assemblies involved in semantic interpretation (“content word” assemblies) are widely distributed and are generally less vulnerable to focal lesion, those involved in structural decoding (functor assemblies) are primarily distributed within the left perisylvian cortices and are selectively vulnerable to left perisylvian lesion. These distributional differences are explained in terms of the perceptuomotor components involved in the acquisition of relevant representations. The emerging “motivated” or “toposemantic” brain regional specificity can only be accommodated with “soft” and maturational versions of modularity. The failure to reproduce double dissociations in current connectionist models is due to overly simple neuroscientific assumptions, notably that of overall equipotentiality. Linguistic models should not be expected to be “implemented” in the brain, but need to be constrained by neuroscientific evidence on how biological brains function.
Epigenetic inheritance of fetal genes in allergic asthma
Authors: J. Bousquet, W. Jacot, H. Yssel, A. M. Vignola, M. Humbert
Journal: Allergy (2004)

Asthma has been associated with an exaggerated T‐helper type 2 (Th2) over Th1 responses to allergic and nonallergic stimuli, which leads to chronic airway inflammation and airway remodeling. In the present article, we propose that many of the genes involved in IgE synthesis and airways (re)modeling in asthma are persistent or reminiscent fetal genes which may not be silenced during early infancy (or late pregnancy). Genes of the embryologic differentiation of ectodermic and endodermic tissues may explain some of the patterns of airway remodeling in asthma. In utero programming leads to gene expression, the persistence of which may be associated with epigenetic inheritance phenomena induced by nonspecific environmental factors. Clear delineation of these issues may yield new information on the mechanisms of asthma and new targets for therapeutic intervention and primary prevention.
High risk of false positive results with breast screening
Authors: D. Josefson
Journal: BMJ (1998)

Women who are screened annually for breast cancer over 10 years run a cumulative risk of receiving false positive results up to 50% of the time, according to a US study. This high false positive rate leads to increased healthcare costs and unnecessary emotional distress for the women.

The retrospective cohort study tracked the incidence of false positive results among regularly scheduled mammographic examinations and clinical breast examinations in 2400 healthy women over a 10 year period ( New England Journal of Medicine 1998;338:1089-96). A false positive result was defined as a suspicious or abnormal finding which after one year of follow up (through additional imaging, second opinion, or biopsy) failed to reveal a tumour.

In all, 9762 mammographic …
Abstract 1457: Raf kinase inhibitor protein (RKIP) negatively regulates melanoma differentiation associated gene-9/syntenin-mediated melanoma metastasis
Authors: Swadesh K. Das, Devanand Sarkar, Paul B. Fisher
Journal: Cancer Research (2011)

Abstract Melanoma differentiation associated gene-9 (mda-9/syntenin) functions as a positive regulator of melanoma progression and metastasis by physically interacting with c-Src and promoting the formation of an active FAK/c-Src signaling complex leading to NFκB and matrix metalloproteinase (MMP) activation. In contrast, Raf Kinase Inhibitor Protein (RKIP), an inhibitor of RAF-mediated activation of mitogen-activated protein/extracellular signal-regulated kinase kinase (MEKK), is strongly downregulated in metastatic melanoma cells suggesting a possible inverse relationship between expression of mda-9/syntenin and RKIP. We have now genetically modulated expression of mda-9/syntenin and RKIP in melanocytes and melanoma cells and evaluated biological consequences using invasion, anchorage-independent growth, Western blotting, immunoprecipitation and in vivo confocal imaging assays. These studies confirm an inverse correlation between mda-9/syntenin and RKIP expression. This reciprocal relationship was also documented in vivo using a chick embryo chorioallantoic membrane (CAM) model, which monitors spontaneous intravasation of cells from the upper to the lower layer by polymerase chain reaction (PCR) amplification of human Alu genomic DNA. Using tissue microarrays and a series of cell lines we confirmed a higher expression of MDA-9/syntenin and absence of RKIP in both malignant melanoma tumor sections and cell lines. We also established through gain-of-function and loss-of-function experiments that mda-9/syntenin transcriptionally downregulates RKIP, providing evidence for crosstalk between these two proteins. Moreover, transient overexpression of RKIP in metastatic melanoma cells overrides mda-9/syntenin-mediated signaling resulting in decreased cell invasion, anchorage-independent growth and spontaneous tumor cell dissemination in the CAM assay. RKIP through its RAF1 binding site (amino acids 77-108) physically interacts with MDA-9/syntenin and this interaction inversely correlates with downregulation of FAK and c-Src phosphorylation, crucial steps necessary for forming a stable FAK/c-Src complex and initiating a signaling cascade leading to an MDA-9/syntenin-mediated metastatic phenotype in melanoma cells. These provocative findings highlight a potential therapeutic role of RKIP in melanoma metastasis through its interaction with MDA-9/syntenin. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1457. doi:10.1158/1538-7445.AM2011-1457
Paediatrics on the peace line
Authors: M. Stewart
Journal: BMJ (1999)

See pp 1609, 1636 

Cupar Street Clinic is one of the landmarks in north and west Belfast Situated between the Protestant Shankill and Catholic Falls Roads, it literally formed part of the peace line for many years. A 10 feet high metal fence meant that access from the Shankill was to the front of the clinic and from the Falls was to the back. Pedestrians could pass through a small gate, which was locked at night, but vehicle access was restricted to one or other side of the fence. Attacks across the car park in Cupar Street from both sides of the peace line were regular occurrences, and staff and patients often arrived in the morning to smells of burning and scenes of destruction. Inside the clinic, however, parents including ex-internees—Loyalist and Republican—sat quite happily together, on cramped benches in a small waiting area, in order for their children to be assessed and …