tbuckley/cabot-search huggingface dataset:
Inhibition of the Sodium-Potassium-Chloride Cotransporter Isoform-1 Reduces Glioma Invasion
Authors: Brian R. Haas, Harald Sontheimer
Journal: Cancer Research (2010)

Abstract Malignant gliomas metastasize throughout the brain by infiltrative cell migration into peritumoral areas. Invading cells undergo profound changes in cell shape and volume as they navigate extracellular spaces along blood vessels and white matter tracts. Volume changes are aided by the concerted release of osmotically active ions, most notably K+ and Cl−. Their efflux through ion channels along with obligated water causes rapid cell shrinkage. Suitable ionic gradients must be established and maintained through the activity of ion transport systems. Here, we show that the Sodium-Potassium-Chloride Cotransporter Isoform-1 (NKCC1) provides the major pathway for Cl− accumulation in glioma cells. NKCC1 localizes to the leading edge of invading processes, and pharmacologic inhibition using the loop diuretic bumetanide inhibits in vitro Transwell migration by 25% to 50%. Short hairpin RNA knockdowns of NKCC1 yielded a similar inhibition and a loss of bumetanide-sensitive cell volume regulation. A loss of NKCC1 function did not affect cell motility in two-dimensional assays lacking spatial constraints but manifested only when cells had to undergo volume changes during migration. Intracranial implantation of human gliomas into severe combined immunodeficient mice showed a marked reduction in cell invasion when NKCC1 function was disrupted genetically or by twice daily injection of the Food and Drug Administration–approved NKCC1 inhibitor Bumex. These data support the consideration of Bumex as adjuvant therapy for patients with high-grade gliomas. Cancer Res; 70(13); 5597–606. ©2010 AACR.
Human bone marrow mesenchymal stem cells and chondrocytes promote and/or suppress the in vitro proliferation of lymphocytes stimulated by interleukins 2, 7 and 15
Authors: C Bocelli-Tyndall, L Bracci, S Schaeren, C Feder-Mengus, A Barbero, A Tyndall, G C Spagnoli
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objectives:</h3> To investigate whether human bone marrow-derived mesenchymal stem cells (BM-MSCs) and articular chondrocytes (ACs) affect the in vitro proliferation of T lymphocytes and peripheral blood mononuclear cells (PBMCs) driven by the homeostatic interleukin (IL)2, IL7 and IL15 cytokines binding to the common cytokine receptor γ-chain (γ<sub>c</sub>) in the absence of T cell receptor (TCR) triggering. <h3>Methods:</h3> PBMCs, total T cells and T cell subsets (CD4+ and CD8+) were stimulated with IL2, IL7 or IL15 and exposed to cultured BM-MSCs and ACs at varying cell:cell ratio either in contact or in transwell conditions. Lymphocyte proliferation was measured by <sup>3</sup>H-thymidine uptake or by flow cytometry of carboxyfluorescein succinimidyl ester (CFSE)-labelled lymphocytes. <h3>Results:</h3> MSCs and ACs enhanced and inhibited lymphocyte proliferation depending on the extent of lymphocyte baseline proliferation and on the MSC/AC to lymphocyte ratio. Enhancement was significant on poorly proliferating lymphocytes and mostly at lower MSC/AC to lymphocyte ratio. Suppression occurred only on actively proliferating lymphocytes and at high MSC/AC to lymphocyte ratio. Neither enhancement nor inhibition required cell–cell contact. <h3>Conclusions:</h3> There is a dichotomous effect of MSCs/ACs on lymphocytes proliferating in response to the homeostatic IL2, IL7 and IL15 cytokines likely to be encountered in homeostatic and autoimmune inflammatory conditions. The effect is determined by baseline lymphocyte proliferation, cell:cell ratio and is dependent on soluble factor(s). This should be taken into account when planning cellular therapy for autoimmune disease (AD) using stromal-derived cells such as MSCs.
Enhanced PIP3 signaling in POMC neurons causes KATP channel activation and leads to diet-sensitive obesity
Authors: L. Plum
Journal: Journal of Clinical Investigation (2006)

Leptin and insulin have been identified as fuel sensors acting in part through their hypothalamic receptors to inhibit food intake and stimulate energy expenditure. As their intracellular signaling converges at the PI3K pathway, we directly addressed the role of phosphatidylinositol3,4,5-trisphosphate–mediated (PIP3-mediated) signals in hypothalamic proopiomelanocortin (POMC) neurons by inactivating the gene for the PIP3 phosphatase Pten specifically in this cell type. Here we show that POMC-specific disruption of Pten resulted in hyperphagia and sexually dimorphic diet-sensitive obesity. Although leptin potently stimulated Stat3 phosphorylation in POMC neurons of POMC cell–restricted Pten knockout (PPKO) mice, it failed to significantly inhibit food intake in vivo. POMC neurons of PPKO mice showed a marked hyperpolarization and a reduction in basal firing rate due to increased ATP-sensitive potassium (KATP) channel activity. Leptin was not able to elicit electrical activity in PPKO POMC neurons, but application of the PI3K inhibitor LY294002 and the KATP blocker tolbutamide restored electrical activity and leptin-evoked firing of POMC neurons in these mice. Moreover, icv administration of tolbutamide abolished hyperphagia in PPKO mice. These data indicate that PIP3-mediated signals are critical regulators of the melanocortin system via modulation of KATP channels.
Hospital-based cluster randomised controlled trial to assess effects of a multi-faceted programme on influenza vaccine coverage among hospital healthcare workers and nosocomial influenza in the Netherlands, 2009 to 2011
Authors: J Riphagen-Dalhuisen, J G Burgerhof, G Frijstein, A D van der Geest-Blankert, M B Danhof-Pont, H J de Jager, A A Bos, E E Smeets, M J de Vries, P M Gallee, E Hak
Journal: Eurosurveillance (2013)

Nosocomial influenza is a large burden in hospitals. Despite recommendations from the World Health Organization to vaccinate healthcare workers against influenza, vaccine uptake remains low in most European countries. We performed a pragmatic cluster randomised controlled trial in order to assess the effects of implementing a multi-faceted influenza immunisation programme on vaccine coverage in hospital healthcare workers (HCWs) and on in-patient morbidity. We included hospital HCWs of three intervention and three control University Medical Centers (UMCs), and 3,367 patients. An implementation programme was offered to the intervention UMCs to assess the effects on both vaccine uptake among hospital staff and patient morbidity. In 2009/10, the coverage of seasonal, the first and second dose of pandemic influenza vaccine as well as seasonal vaccine in 2010/11 was higher in intervention UMCs than control UMCs (all p&lt;0.05). At the internal medicine departments of the intervention group with higher vaccine coverage compared to the control group, nosocomial influenza and/or pneumonia was recorded in 3.9% and 9.7% of patients of intervention and control UMCs, respectively (p=0.015). Though potential bias could not be completely ruled out, an increase in vaccine coverage was associated with decreased patient in-hospital morbidity from influenza and/or pneumonia.
Amino acid replacements and wavelength absorption of visual pigments in vertebrates.
Authors: S Yokoyama
Journal: Molecular Biology and Evolution (1995)

An important unanswered question in phototransduction is how visual pigments (VPs) regulate their wavelength of maximal absorption (lambda max). By constructing the evolutionary tree for 28 opsins with known lambda max values, we can identify the times and directions of lambda max shift of different VPs. A total of 55 amino acid changes are shown to correlate with the directions of lambda max shift and might have been important in determining lambda max of a VP. Among these, three amino acid changes are already proven to be responsible in modifying the green-sensitive VP to the red-sensitive VP. The present evolutionary analysis opens a new direction in understanding the mechanism for the regulation of wavelength absorption by a VP and, more generally, in studying molecular mechanism involved in adaptive evolution.
Bronchiectasis and homozygous (P1ZZ) alpha 1-antitrypsin deficiency in a young man.
Authors: W Rodriguez-Cintron, K Guntupalli, A E Fraire
Journal: Thorax (1995)

Pulmonary complications of alpha 1-antitrypsin deficiency are most commonly manifested by panlobular emphysema. This report describes histologically proven bronchiectasis in a 21 year old man with massive haemoptysis and homozygous deficiency of alpha 1-antitrypsin. Neither panlobular emphysema nor cirrhosis of the liver were present. Bronchiectasis must be considered part of the spectrum of the pulmonary pathology that may be encountered in individuals with alpha 1-antitrypsin deficiency.
Progestogens do not affect aortic accumulation of cholesterol in ovariectomized cholesterol-fed rabbits.
Authors: J Haarbo, O L Svendsen, C Christiansen
Journal: Circulation Research (1992)

Cardiovascular disease is a major killer in postmenopausal women in the industrialized societies. To investigate the effect of progestogen and 17 beta-estradiol replacement therapy on atherogenesis, we studied 60 cholesterol-fed ovariectomized rabbits for 13 weeks. They were randomly assigned to four groups of 15 rabbits each and received oral treatment with norethisterone acetate, levonorgestrel, 17 beta-estradiol, or placebo. The active treatment groups achieved serum hormone concentrations, which produced physiological effects on the uterus. No significant differences in serum total cholesterol or ultracentrifuged lipoproteins (very low density, intermediate density, low density, or high density lipoproteins) were found between the four groups during the experimental period. There were no significant differences between the progestogen and placebo groups in the aortic accumulation of cholesterol. The estradiol group had only accumulated about half the aortic cholesterol as compared with the placebo group and the progestogen groups (p less than 0.05). The antiatherogenic effect of 17 beta-estradiol was estimated to be equal to a 40-50% reduction in serum total cholesterol. These findings suggest that two commonly prescribed 19-nortestosterone-derived progestogens, which are considered to be "atherogenic," do not affect atherogenesis in cholesterol-fed ovariectomized rabbits, whereas 17 beta-estradiol produces a significant antiatherogenic effect that is independent of lipid metabolism in plasma, possibly the result of a direct action on the arterial wall.
The American Heart Association as a National Voluntary Public Health Agency
Authors: W. P. SHEPARD
Journal: Circulation (1950)

The role of the voluntary health agencies in this country is well understood. Tuberculosis, blindness, venereal disease, cancer, and other major public health problems have been attacked by them with notable success, some for as long as 50 years. There is a well established pattern of cooperation with official health agencies and with organized medicine. In its newly added role as a voluntary public health agency, it is important for the American Heart Association to understand these principles and patterns that are discussed here briefly with special emphasis on partnership with nonmedical community leaders, the relationship with the official agencies, including the National Institutes of Health, and on socialized medicine. Good public health work by voluntary organizations is a manifest of the concern of the medical profession with the health of the public and our first bulwark against compulsory government controlled medicine.
Defibrotide for prophylaxis of hepatic veno-occlusive disease in paediatric haemopoietic stem-cell transplantation: an open-label, phase 3, randomised controlled trial
Authors: Selim Corbacioglu, Simone Cesaro, Maura Faraci, Dominique Valteau-Couanet, Bernd Gruhn, Attilio Rovelli, Jaap J Boelens, Annette Hewitt, Johanna Schrum, Ansgar S Schulz, Ingo Müller, Jerry Stein, Robert Wynn, Johann Greil, Karl-Walter Sykora, Susanne Matthes-Martin, Monika Führer, Anne O'Meara, Jacek Toporski, Petr Sedlacek, Paul G Schlegel, Karoline Ehlert, Anders Fasth, Jacek Winiarski, Johan Arvidson, Christine Mauz-Körholz, Hulya Ozsahin, Andre Schrauder, Peter Bader, Joseph Massaro, Ralph D'Agostino, Margaret Hoyle, Massimo Iacobelli, Klaus-Michael Debatin, Christina Peters, Giorgio Dini
Journal: The Lancet (2012)
Rising from the crypt: decreasing DNA methylation during differentiation of the small intestine
Authors: Sean M Cullen, Margaret A Goodell
Journal: Genome biology (2013)

The differentiation of intestinal stem cells involves few DNA methylation changes, assayed by bisulfite sequencing, in contrast to other adult somatic stem cell hierarchies. Please see related Research article: http://genomebiology.com/2013/14/5/R50
Strong correlation of maximal squat strength with sprint performance and vertical jump height in elite soccer players: Figure 1
Authors: U Wisløff, C Castagna, J Helgerud, R Jones, J Hoff
Journal: British Journal of Sports Medicine (2004)

A high level of strength is inherent in elite soccer play, but the relation between maximal strength and sprint and jumping performance has not been studied thoroughly.To determine whether maximal strength correlates with sprint and vertical jump height in elite male soccer players.Seventeen international male soccer players (mean (SD) age 25.8 (2.9) years, height 177.3 (4.1) cm, weight 76.5 (7.6) kg, and maximal oxygen uptake 65.7 (4.3) ml/kg/min) were tested for maximal strength in half squats and sprinting ability (0-30 m and 10 m shuttle run sprint) and vertical jumping height.There was a strong correlation between maximal strength in half squats and sprint performance and jumping height.Maximal strength in half squats determines sprint performance and jumping height in high level soccer players. High squat strength did not imply reduced maximal oxygen consumption. Elite soccer players should focus on maximal strength training, with emphasis on maximal mobilisation of concentric movements, which may improve their sprinting and jumping performance.
The Genetic Structure of Domestic Rabbits
Authors: M. Carneiro, S. Afonso, A. Geraldes, H. Garreau, G. Bolet, S. Boucher, A. Tircazes, G. Queney, M. W. Nachman, N. Ferrand
Journal: Molecular Biology and Evolution (2011)

Understanding the genetic structure of domestic species provides a window into the process of domestication and motivates the design of studies aimed at making links between genotype and phenotype. Rabbits exhibit exceptional phenotypic diversity, are of great commercial value, and serve as important animal models in biomedical research. Here, we provide the first comprehensive survey of nucleotide polymorphism and linkage disequilibrium (LD) within and among rabbit breeds. We resequenced 16 genomic regions in population samples of both wild and domestic rabbits and additional 35 fragments in 150 rabbits representing six commonly used breeds. Patterns of genetic variation suggest a single origin of domestication in wild populations from France, supporting historical records that place rabbit domestication in French monasteries. Levels of nucleotide diversity both within and among breeds were ~0.2%, but only 60% of the diversity present in wild populations from France was captured by domestic rabbits. Despite the recent origin of most breeds, levels of population differentiation were high (F(ST) = 17.9%), but the majority of polymorphisms were shared and thus transferable among breeds. Coalescent simulations suggest that domestication began with a small founding population of less than 1,200 individuals. Taking into account the complex demographic history of domestication with two successive bottlenecks, two loci showed deviations that were consistent with artificial selection, including GPC4, which is known to be associated with growth rates in humans. Levels of diversity were not significantly different between autosomal and X-linked loci, providing no evidence for differential contributions of males and females to the domesticated gene pool. The structure of LD differed substantially within and among breeds. Within breeds, LD extends over large genomic distances. Markers separated by 400 kb typically showed r(2) higher than 0.2, and some LD extended up to 3,200 kb. Much less LD was found among breeds. This advantageous LD structure holds great promise for reducing the interval of association in future mapping studies.
Treatment of Seasonal Allergic Rhinitis with Budesonide and Disodium Cromoglycate
Authors: P. BJERRUM, P. ILLUM
Journal: Allergy (1985)

The aim of this study was to compare the efficacy and side effects of budesonide and disodium Cromoglycate (DSCG) in seasonal allergic rhinitis. In a double‐blind, double‐dummy comparative study, 43 patients with seasonal allergic rhinitis were either treated with budesonide (200 fig b.d.) or DSCG (5.2 mg 5 times daily). After a 1 week run‐in period treatment was given for 3 weeks. The patient scorings for nasal secretion, nasal itching, sneezing bouts and total nasal symptoms were significantly different between the treatment groups during the whole treatment period. The scorings for nasal blockage were significantly different during the last 2 weeks of treatment. All differences were in favour of budesonide treatment. The patients' assessment of the treatment favoured budesonide (P &lt; 0.02). Side effects were few and mild, but one patient from the budesonide group stopped treatment because of headache.
Increase of the delayed rectifier K+ and Na(+)-K+ pump currents by hypotonic solutions in guinea pig cardiac myocytes.
Authors: N Sasaki, T Mitsuiye, Z Wang, A Noma
Journal: Circulation Research (1994)

To investigate the membrane current changes induced by membrane stretching, single guinea pig ventricular myocytes were superfused with solutions of various osmolarities, and the whole-cell current was recorded by the patch-clamp technique. The application of 70% and 130% osmolar bath solutions increased and decreased the amplitude of delayed rectifier K+ current (IK), respectively, whereas no obvious change was observed in the L-type Ca2+ current or the inward rectifier K+ current. When the Na(+)-K+ pump current (Ipump) was recorded by the use of high-Na+ (&gt; 35 mmol/L) pipette solutions, Ipump was also increased and decreased by the superfusion of hypotonic and hypertonic solutions, respectively, in approximately half of the cells. An increase of the Ipump was also observed in the absence of external Na+, excluding a possibility that the enhancement of Ipump was secondary to an elevation of cytosolic Na+. In most cells that did not show the increase of Ipump, the hypotonic superfusion induced a gradual activation of Cl- current. The hypertonic superfusion did not cause any consistent change in the membrane Cl- conductance. Since the response of IK was observed in all experiments, its mechanism was studied. We failed to observe marked changes in the kinetic and conductance properties of IK in the hypotonic solution. The involvements of either the protein kinases or Ca2+ were also ruled out as major mechanisms underlying the IK response.
MENSURATION IN THE PSYCHOSES
Authors: D. Ewen Cameron
Journal: American Journal of Psychiatry (1933)

In considering the findings it is to be kept in mind that the point of interest is not the effects of the drugs on the series of cases, butthe study of the varying correlations in the four fields of enquiry as shown by the individual cases. A correlation was considered to exist whenever one of the other readings seemed to move concurrently and significantly with the behavior chart irrespective of the direction of the trend. On this basis it was found that the tests at the level of mentation gave the best correlations with the behavior chart, the mental tests being rather the more sensitive but requiring the behavior chart for their proper evaluation. The indirect tests gave less close correlation with the behavior chart. Their results were hard to evaluate as they were influenced both by the drug and by the improvement or deterioration in the patient's condition. The patient's own statement was the least reliable. Moreover, improvement was reported later than by the behavior chart, and in a qualitative manner, i. e., improvement in sleep was usually first reported, improvement in mood came very late and was rarely reported. This is an important point when one considers the extent to which our records rest upon the patient's statement both in checking up the course in hospital and in the anamnesis. The correlations between the reaction time and the test for perseveration were not sufficiently great to allow one to consider them as testing the same thing. On the basis of these findings I would suggest that with the aid of such a synthesis of methods and hierarchy of tests we are in a position to make more exact investigations into disorders than is at present possible by the various methods used alone.
Treatment of solar keratoses with a 5-fluorouracil and salicylic acid varnish
Authors: J.C.ALMEIDA GONCALVES
Journal: British Journal of Dermatology (2006)

In an attempt to avoid the side-effects of treating solar keratoses with 5% 5-fluorouracil (5-FU) ointment, a new pharmacological varnish containing 5% 5-FU and 5-10% salicylic acid to collodium was tried. Twenty patients with such lesions were treated. A drop of the varnish was applied on each lesion every 3 weeks. Only one to five applications on facial lesions were necessary to obtain apparent cure in all patients. Lesions reappeared in four patients, but were cured after a second and similar treatment. The keratoses of the hands were more resistant and needed seven applications in one patient and nine in the other.
Health data chiefs promise safer, more transparent system to protect patient information
Authors: A. O'Dowd
Journal: BMJ (2014)

Patient privacy will be protected by a more transparent and scrutinised system for handling health and social care data, MPs have been told.

Repeated assurances were given to MPs during a hostile evidence session of the parliamentary health committee on 1 July for its inquiry into handling of NHS patient data.

The committee quizzed heads of the Health and Social Care Information Centre, the body in charge of health and social care data in England.

Much of the discussion focused on a review published last month, carried out by PricewaterhouseCoopers into the centre’s predecessor body, the NHS Information Centre, and its handling of data releases.1

The NHS Information Centre was criticised earlier this year …