tbuckley/cabot-search huggingface dataset:
A hormone-dependent feedback-loop controls androgen receptor levels by limiting MID1, a novel translation enhancer and promoter of oncogenic signaling
Authors: Andrea Köhler, Ümmühan Demir, Eva Kickstein, Sybille Krauss, Johanna Aigner, Beatriz Aranda-Orgillés, Antonios I Karagiannidis, Clemens Achmüller, Huajie Bu, Andrea Wunderlich, Michal-Ruth Schweiger, Georg Schaefer, Susann Schweiger, Helmut Klocker, Rainer Schneider
Journal: Molecular Cancer (2014)

High androgen receptor (AR) level in primary tumour predicts increased prostate cancer (PCa)-specific mortality. Furthermore, activations of the AR, PI3K, mTOR, NFκB and Hedgehog (Hh) signaling pathways are involved in the fatal development of castration-resistant prostate cancer during androgen ablation therapy. MID1, a negative regulator of the tumor-suppressor PP2A, is known to promote PI3K, mTOR, NFκB and Hh signaling. Here we investigate the interaction of MID1 and AR.AR and MID1 mRNA and protein levels were measured by qPCR, Western blot and immunohistochemistry. Co-immunoprecipitation followed by PCR and RNA-pull-down followed by Western blot was used to investigate protein-mRNA interaction, chromatin-immunoprecipitation followed by next-generation sequencing for identification of AR chromatin binding sites. AR transcriptional activity and activity of promoter binding sites for AR were analyzed by reporter gene assays. For knockdown or overexpression of proteins of interest prostate cancer cells were transfected with siRNA or expression plasmids, respectively.The microtubule-associated MID1 protein complex associates with AR mRNA via purine-rich trinucleotide repeats, expansions of which are known to correlate with ataxia and cancer. The level of MID1 directly correlates with the AR protein level in PCa cells. Overexpression of MID1 results in a several fold increase in AR protein and activity without major changes in mRNA-levels, whereas siRNA-triggered knockdown of MID1 mRNA reduces AR-protein levels significantly. Upregulation of AR protein by MID1 occurs via increased translation as no major changes in AR protein stability could be observed. AR on the other hand, regulates MID1 via several functional AR binding sites in the MID1 gene, and, in the presence of androgens, exerts a negative feedback loop on MID1 transcription. Thus, androgen withdrawal increases MID1 and concomitantly AR-protein levels. In line with this, MID1 is significantly over-expressed in PCa in a stage-dependent manner.Promotion of AR, in addition to enhancement of the Akt-, NFκB-, and Hh-pathways by sustained MID1-upregulation during androgen deprivation therapy provides a powerful proliferative scenario for PCa progression into castration resistance. Thus MID1 represents a novel, multi-faceted player in PCa and a promising target to treat castration resistant prostate cancer.
Nonvenous Origin of Dermal Lymphatic Vasculature
Authors: Ines Martinez-Corral, Maria H. Ulvmar, Lukas Stanczuk, Florence Tatin, Krishnakumar Kizhatil, Simon W.M. John, Kari Alitalo, Sagrario Ortega, Taija Makinen
Journal: Circulation Research (2015)

The formation of the blood vasculature is achieved via 2 fundamentally different mechanisms, de novo formation of vessels from endothelial progenitors (vasculogenesis) and sprouting of vessels from pre-existing ones (angiogenesis). In contrast, mammalian lymphatic vasculature is thought to form exclusively by sprouting from embryonic veins (lymphangiogenesis). Alternative nonvenous sources of lymphatic endothelial cells have been suggested in chicken and Xenopus, but it is unclear whether they exist in mammals.We aimed to clarify the origin of the murine dermal lymphatic vasculature.We performed lineage tracing experiments and analyzed mutants lacking the Prox1 transcription factor, a master regulator of lymphatic endothelial cell identity, in Tie2 lineage venous-derived lymphatic endothelial cells. We show that, contrary to current dogma, a significant part of the dermal lymphatic vasculature forms independently of sprouting from veins. Although lymphatic vessels of cervical and thoracic skin develop via sprouting from venous-derived lymph sacs, vessels of lumbar and dorsal midline skin form via assembly of non-Tie2-lineage cells into clusters and vessels through a process defined as lymphvasculogenesis.Our results demonstrate a significant contribution of nonvenous-derived cells to the dermal lymphatic vasculature. Demonstration of a previously unknown lymphatic endothelial cell progenitor population will now allow further characterization of their origin, identity, and functions during normal lymphatic development and in pathology, as well as their potential therapeutic use for lymphatic regeneration.
Reporting of Noninferiority and Equivalence Randomized Trials
Authors: Gilda Piaggio, Diana R. Elbourne, Stuart J. Pocock, Stephen J. W. Evans, Douglas G. Altman, for the CONSORT Group
Journal: JAMA (2012)

The CONSORT (Consolidated Standards of Reporting Trials) Statement, which includes a checklist and a flow diagram, is a guideline developed to help authors improve the reporting of the findings from randomized controlled trials. It was updated most recently in 2010. Its primary focus is on individually randomized trials with 2 parallel groups that assess the possible superiority of one treatment compared with another. The CONSORT Statement has been extended to other trial designs such as cluster randomization, and recommendations for noninferiority and equivalence trials were made in 2006. In this article, we present an updated extension of the CONSORT checklist for reporting noninferiority and equivalence trials, based on the 2010 version of the CONSORT Statement and the 2008 CONSORT Statement for the reporting of abstracts, and provide illustrative examples and explanations for those items that differ from the main 2010 CONSORT checklist. The intent is to improve reporting of noninferiority and equivalence trials, enabling readers to assess the reliability of their results and conclusions.
Could the long-term persistence of low serum calcium levels and high serum parathyroid hormone levels during bisphosphonate treatment predispose metastatic breast cancer patients to undergo osteonecrosis of the jaw?
Authors: M. Ardine, D. Generali, M. Donadio, S. Bonardi, M. Scoletta, A.M. Vandone, M. Mozzati, O. Bertetto, A. Bottini, L. Dogliotti, A. Berruti
Journal: Annals of Oncology (2006)
Exploring Neural Cell Dynamics with Digital Holographic Microscopy
Authors: P. Marquet, C. Depeursinge, P.J. Magistretti
Journal: Annual Review of Biomedical Engineering (2013)

In this review, we summarize how the new concept of digital optics applied to the field of holographic microscopy has allowed the development of a reliable and flexible digital holographic quantitative phase microscopy (DH-QPM) technique at the nanoscale particularly suitable for cell imaging. Particular emphasis is placed on the original biological information provided by the quantitative phase signal. We present the most relevant DH-QPM applications in the field of cell biology, including automated cell counts, recognition, classification, three-dimensional tracking, discrimination between physiological and pathophysiological states, and the study of cell membrane fluctuations at the nanoscale. In the last part, original results show how DH-QPM can address two important issues in the field of neurobiology, namely, multiple-site optical recording of neuronal activity and noninvasive visualization of dendritic spine dynamics resulting from a full digital holographic microscopy tomographic approach.
The Thermal Baths of the Island of Nevis, B.W.I
Authors: J. N. Rat
Journal: BMJ (1909)

DmC. 25, XM09 unemployed, or with any able-bodied men in health (including vagrants).We hold . . .that unemployment can be dealt with effectually only by a national authority.... What is needed, however, in our judgement, is the establishment of a Government department charged not merely with eorganizins a complete system of labour exchanges, but also with making use of the information thereby obtsined.The plan recommended is practically the same aq that laid down in the Minority Report for England and Wales.The Care of Children.The Minority recommend that the whole provision of school age should be entrusted to the Local Education AMthority-The Establish7nent of a Common Registerfor all Forms of Public Assistance and of a Public Registrar. The Minority stateThat this scheme of deliberately breaking up the Poor Law, and of transferriDg each of its services tb a specialized and preventive authority, has the incidental ad- vantage that it brings into promineDne the pressing need for a Common Register of all forms of Public Assistance, and makes indispensable the appointment of some such officer as a Registrar of Public Assistance.They go into detail with regard to the working of this proposed' scheme.The whole of the recommendations of the Minority for breaking up the Poor Law will be found at p.
Complex carbohydrate malabsorption in exocrine pancreatic insufficiency.
Authors: S D Ladas, K Giorgiotis, S A Raptis
Journal: Gut (1993)

The magnitude of complex carbohydrate malabsorption in exocrine pancreatic insufficiency has not been well quantified in the past. The quantity of carbohydrate malabsorbed after a rice starch (100 g) meal in 20 patients with chronic pancreatitis (n = 10) or pancreatic cancer (n = 10) was therefore estimated. Patients had a three day stool fat collection (80 g/24 hour fat intake), a lactulose (20 g), and a rice flour (100 g) breath hydrogen test. Normal controls (n = 29) had a postprandial H2 increase &lt; or = 14 ppm and malabsorbed (mean (SEM)) 1.12 (0.44) (range 0-11.10) g of the 100 g of carbohydrate ingested. Patients malabsorbed significantly more carbohydrate (11.36 (2.23) (range 8.90-32.60) g, F1.47 = 29.92, p &lt; 0.001). The number of patients with fat (&gt; 7 g, n = 8) or carbohydrate (increase in H2 &gt; or = 20 ppm, n = 10) malabsorption was not different (chi 2 = 0.10, p = 0.75). There was a significant correlation between faecal fat and amount of malabsorbed carbohydrate (r = 0.60, F1.17 = 9.70, p = 0.006) and faecal fat and stool wet weight (r = 0.57, F1.18 = 8.67, p &lt; 0.009), but not between stool wet weight and amount of malabsorbed carbohydrate (r = 0.28, F1.17 = 1.45, p = 0.25). Although patients with exocrine pancreatic insufficiency malabsorb 10%-30% of the ingested complex carbohydrate, the main determinant of stool wet weight could be faecal fat.
Attenuation of reflex forearm vasoconstriction by alpha-human atrial natriuretic peptide in men.
Authors: A Takeshita, T Imaizumi, N Nakamura, H Higashi, T Sasaki, M Nakamura, K Kangawa, H Matsuo
Journal: Circulation Research (1987)

This study examined whether atrial natriuretic peptide (ANP) modulates reflex forearm vasoconstriction in humans. Synthetic alpha-human ANP (alpha-hANP) was infused at a rate of 0.03 microgram/kg/min in 8 healthy men (mean age 23 +/- 0.7 years, mean +/- SEM). The alpha-hANP decreased systolic blood pressure and central venous pressure (CVP) but did not significantly alter resting heart rate and forearm vascular resistance (FVR). The magnitudes of reflex increases in FVR during lower body negative pressure (LBNP) at -110, -20, and -40 mm Hg were less during infusion of alpha-ANP than those magnitudes during infusion of saline solution. The slope of the regression line relating changes in CVP and those in FVR was less during infusion of alpha-hANP than the slope during infusion of saline solution. Forearm vascular responses to intra-arterial infusion of norepinephrine at doses of 100, 200, and 500 ng/min did not significantly differ during infusion of alpha-hANP and saline solution. These results suggest that alpha-hANP attenuates cardiopulmonary baroreflex control of FVR in normal men.
Parasympathetic cerebrovasodilator center of the facial nerve.
Authors: M Nakai, K Tamaki, J Ogata, Y Matsui, M Maeda
Journal: Circulation Research (1993)

Functional studies have yet to be undertaken to establish which brain region subserves the parasympathetic regulation of the cerebral circulation. Using 31 anesthetized rats with precluded cervical sympathetic trunks, we therefore attempted to perform chemical stimulation of the greater petrosal nerve (GPN) cell group, which is a subgroup of the superior salivatory nucleus and sends off axons largely to the parasympathetic pterygopalatine ganglion via the GPN component of the facial nerve. The cerebrocortical blood flow was monitored with a laser-Doppler flowmeter. Unilateral stimulation of the GPN cell group by microinjection of L-glutamate reduced the ipsilateral cerebrocortical vascular resistance, maximally by 16.4 +/- 4.1% (mean +/- SD, n = 61). The response was not mediated by the classic muscarinic receptors of the cerebral vessel wall. However, pharmacological blockade of the peripheral parasympathetic ganglia and acute and chronic bilateral removal of the parasympathetic postganglionic fibers originating in the pterygopalatine ganglion abolished the response. The present data thus provide functional evidence that the GPN cell group may constitute a parasympathetic cerebrovasodilator center.
THE INTERRELATION OF THE SURVIVING HEART AND PANCREAS OF THE DOG IN SUGAR METABOLISM
Authors: Admont H. Clark
Journal: The Journal of Experimental Medicine (1917)

When the pancreas of a dog is perfused aseptically with a Locke's solution containing dextrose in physiological concentrations, the optical rotation of the perfusate is diminished, but its reducing power is unaltered. This change also occurs if dextrose is added to a sugarfree pancreatic perfusate and the mixture incubated. These perfusates yield osazones with lower melting points than glucosazone, but when the perfusates are hydrolyzed with weak acid their optical, rotations and the melting points of their osazones are increased. These changes do not occur with levulose, or with an extract of the pancreas and dextrose. When the heart, spleen, or kidneys are perfused with dextrose solutions hydrolysis of the perfusates does not increase their optical rotation or power of reduction. When a pancreatic perfusate containing dextrose is circulated through a living heart not only do the above changes take place but, in addition, the reducing properties of the perfusate are altered. Hydrolysis of such a perfusate increases its reducing power, its optical rotation, and the melting point of its osazone. A heart does not cause this effect either alone or when perfused together with the spleen or kidneys. Levulose perfused through the heart and pancreas is unchanged. These phenomena are believed to be due to an enzyme or enzymes obtained from the perfused pancreas. The changes in optical rotation, in reduction, and in the osazones are accounted for by different degrees of dextrose condensation. While the living heart can destroy both dextrose and levulose to some extent, the experimental results suggest that the enzyme or enzymes derived from the perfused pancreas have a specific action on dextrose and are responsible for certain essential steps by which dextrose is prepared for normal utilization.
Consensus statement on epidemiological studies of medical conditions in tennis, April 2009
Authors: B M Pluim, C W Fuller, M E Batt, L Chase, B Hainline, S Miller, B Montalvan, P Renström, K A Stroia, K Weber, T O Wood
Journal: British Journal of Sports Medicine (2009)

Background: The reported incidence, severity and nature of injuries sustained in tennis vary considerably between studies. While some of these variations can be explained by differences in sample populations and conditions, the main reasons are related to differences in definitions and methodologies employed in the studies. Objective: This statement aims to review existing consensus statements for injury surveillance in other sports in order to establish definitions, methods and reporting procedures that are applicable to the specific requirements of tennis. Design: The International Tennis Federation facilitated a meeting of 11 experts from seven countries representing a range of tennis stakeholders. Using a mixed methods consensus approach, key issues related to definitions, methodology and implementation were discussed and voted on by the group during a structured 1-day meeting. Following this meeting, two members of the group collaborated to produce a draft statement, based on the group discussions and voting outcomes. Three revisions were prepared and circulated for comment before the final consensus statement was produced. Results: A definition of medical conditions (injuries and illnesses) that should be recorded in tennis epidemiological studies and criteria for recording the severity and nature of these conditions are proposed. Suggestions are made for recording players’ baseline information together with recommendations on how medical conditions sustained during match play and training should be reported. Conclusions: The definitions and methodology proposed for recording injuries and illnesses sustained during tennis activities will lead to more consistent and comparable data being collected. The surveillance procedures presented here may also be applicable to other racket sports.
Therapeutic performance of videoassisted thoracoscopic surgery (VATS) in compare of pleuroscopy and intercosatal drain (ICD) + intra pleural fibrinolytic therapy (IPFT) in investigation and management of pleural diseases
Authors: Varun Patel, Mukesh Patel, Amrish Patel, Harjit Dumra, Gopal Raval, Tushar Patel
Journal: European Respiratory Journal (2013)

Introduction: Thoracoscopy aid greatly in the diagnostic evaluation and potentially in therapy for a number of patients with pleural disease. Thoracoscopic pleural biopsy, fluid drainage, and pleurodesis are now recognized components of the interventional pulmonologists practice. Aim and Objective: To evaluate the efficacy, safety, effectiveness and loss of man hours of the VATS against pleruoscopy and ICD + IPFT. Material & Methods: A prospective, 3 parallel arm observational study done over a span of 2 and half years at tertiary care centre. 69 patients with pleural disease who required intervention for Pneumothorax or empyema were enrolled in the study. All patients were explained about VATS, Pleuroscopy and ICD + IPFT; they chose modality of treatment. Anthropometry, co-morbidity, duration of ICD, hospitalization and loss of man hours were calculated. Results: 60% were male and mean age of cohort was 54 years. Mean ICD duration-1.5 days and days of hospitalization-2 days, antibiotic requirement-14 days and man hour losses-48 hours in VATS group are significantly low then Pleuroscopy, ICD+IPFT. 4 patients in VATS arm converted to thorecotomy, 2 for bleeding & 1 for large sarcoma, 1 with Tb. 1 patient got subcutaneous emphysema, 3 patients had per operative bleeding, 3 had peroperative desaturation and 3 had rise ETCO2. Conclusion: VATS done by Interventional pulmonologist in pleural disease were safe with good therapeutic outcome, lesser ICD duration, minimal complications, less hospitalization and relatively cost effective by reduction in loss of human hour.
Familial Thoracic Aortic Aneurysms and Dissections
Authors: Dongchuan Guo, Sumera Hasham, Shao-Qing Kuang, Carl J. Vaughan, Eric Boerwinkle, Hua Chen, Dianne Abuelo, Harry C. Dietz, Craig T. Basson, Sanjay S. Shete, Dianna M. Milewicz
Journal: Circulation (2001)

Background —Aneurysms and dissections affecting the ascending aorta are associated primarily with degeneration of the aortic media, called medial necrosis. Families identified with dominant inheritance of thoracic aortic aneurysms and dissections (TAA/dissections) indicate that single gene mutations can cause medial necrosis in the absence of an associated syndrome. Methods and Results —Fifteen families were identified with multiple members with TAAs/dissections. DNA from affected members from 2 of the families was used for a genome-wide search for the location of the defective gene by use of random polymorphic markers. The data were analyzed by the affected-pedigree-member method of linkage analysis. This analysis revealed 3 chromosomal loci with multiple markers demonstrating evidence of linkage to the phenotype. Linkage analysis using further markers in these regions and DNA from 15 families confirmed linkage of some of the families to 5q13-14. Genetic heterogeneity for the condition was confirmed by a heterogeneity test. Data from 9 families with the highest conditional probability of being linked to 5q were used to calculate the pairwise and multipoint logarithm of the odds (LOD) scores, with a maximum LOD of 4.74, with no recombination being obtained for the marker D5S2029 . In 6 families, the phenotype was not linked to the 5q locus. Conclusions —A major locus for familial TAAs and dissections maps to 5q13-14, with the majority (9 of 15) of the families identified demonstrating evidence of linkage to this locus. The condition is genetically heterogeneous, with 6 families not demonstrating evidence of linkage to any loci previously associated with aneurysm formation.
Changes in plasma levels of fat-derived hormones adiponectin, leptin, resistin and visfatin in patients with rheumatoid arthritis
Authors: M Otero, R Lago, R Gomez, F Lago, C Dieguez, J J Gomez-Reino, O Gualillo
Journal: Annals of the Rheumatic Diseases (2006)

<b>Background:</b> Rheumatoid arthritis is a chronic autoimmune inflammatory condition characterised by polyarthritis and severe change in body mass and neuroendocrine environment. <b>Objectives:</b> To investigate plasma levels of adipocytokines (leptin, adiponectin, visfatin and resistin) in patients with rheumatoid arthritis and to compare them with levels in healthy controls. <b>Methods:</b> Adiponectin, resistin, visfatin and leptin concentrations were measured in 31 patients with rheumatoid arthritis and 18 healthy controls by using specific enzyme-linked immunosorbent assays. <b>Results:</b> Patients with rheumatoid arthritis showed considerably higher plasma levels of leptin, adiponectin and visfatin than healthy controls. No marked difference was observed in resistin levels between patients and controls. <b>Conclusion:</b> A marked increase in plasma levels of leptin, adiponectin and visfatin was noted in patients with rheumatoid arthritis, whereas resistin levels were similar to those observed in healthy controls. Coordinated roles for adiponectin, leptin and visfatin are suggested in the modulation of the inflammatory environment in patients with rheumatoid arthritis, whereas the lack of modulation in resistin levels is predictive of an irrelevant role for this peptide, suggesting that resistin level is probably not one of the main signals associated with the pathogenesis of this disease.