tbuckley/cabot-search huggingface dataset:
WASH is required for the differentiation commitment of hematopoietic stem cells in a c-Myc–dependent manner
Authors: Pengyan Xia, Shuo Wang, Guanling Huang, Pingping Zhu, Man Li, Buqing Ye, Ying Du, Zusen Fan
Journal: The Journal of Experimental Medicine (2014)

Hematopoiesis is fully dependent on hematopoietic stem cells (HSCs) that possess the capacity to self-renew and differentiate into all blood cell lineages. WASH, Wiskott–Aldrich syndrome protein (WASP) and SCAR homologue (WASH) is involved in endosomal sorting as an actin-nucleating protein. Here, we show that conditional WASH deletion in the hematopoietic system causes defective blood production of the host, leading to severe cytopenia and rapid anemia. WASH deficiency causes the accumulation of long-term (LT)-HSCs in bone marrow and perturbs their differentiation potential to mature blood lineages. Importantly, WASH is located in the nucleus of LT-HSCs and associates with the nucleosome remodeling factor (NURF) complex. WASH assists the NURF complex to the promoter of c-Myc gene through its VCA domain-dependent nuclear actin nucleation. WASH deletion suppresses the transcriptional activation of c-Myc gene and impairs the differentiation of LT-HSCs. WASH acts as an upstream regulator to modulate c-Myc transcription for hematopoietic regulation.
Efficacy of Bladder Training in Older Women With Urinary Incontinence
Authors: J A Fantl, J F Wyman, D K McClish, S W Harkins, R K Elswick, J R Taylor, E C Hadley
Journal: JAMA (1991)

The efficacy of bladder training was evaluated in a randomized clinical trial involving 123 noninstitutionalized women 55 years and older with urinary incontinence. Subjects were urodynamically categorized as those with urethral sphincteric incompetence (N = 88) and those with detrusor instability with or without concomitant sphincteric incompetence (N = 35). Bladder training reduced the number of incontinent episodes by 57%; the effect was similar for both urodynamic diagnostic groups. The quantity of fluid loss was reduced by 54%. This was greater for patients with detrusor instability than for those without it. Diurnal and nocturnal voluntary micturitions were also reduced. The effect on nocturnal micturition, however, was not observed in subjects with unstable detrusor function. It is recommended that bladder training be considered as an initial step in treatment of women with urinary incontinence. Provided prior comprehensive clinical evaluation is done, it can be prescribed without the need for urodynamic characterization. (<i>JAMA</i>. 1991;265:609-613)
Angiotensin-Converting Enzyme Inhibitors Improve Coronary Flow Reserve in Dilated Cardiomyopathy by a Bradykinin-Mediated, Nitric Oxide-Dependent Mechanism
Authors: Lazaros A. Nikolaidis, Aaron Doverspike, Rhonda Huerbin, Teresa Hentosz, Richard P. Shannon
Journal: Circulation (2002)

Background — ACE inhibitors have been used extensively in heart failure, where they induce systemic vasodilatation. ACE inhibitors have also been shown to reduce ischemic events after myocardial infarction, although their mechanisms of action on the coronary circulation are less well understood. The purpose of the present study was to determine the effects and the mechanism of action of the ACE inhibitor enalaprilat and the AT 1 antagonist losartan on regional myocardial perfusion and coronary flow and vasodilator reserve in conscious dogs with pacing-induced dilated cardiomyopathy (DCM). Methods and Results — Twenty-seven conscious, chronically instrumented dogs were studied during advanced stages of dilated cardiomyopathy, which was induced by rapid pacing. Enalaprilat (1.25 mg IV) improved transmural distribution (endocardial/epicardial ratio) at rest (baseline, 0.91±0.11; enalaprilat, 1.02±0.07 mL/min per g; P &lt;0.05) and during atrial pacing (baseline, 0.82±0.11; enalaprilat, 0.98±0.07; P &lt;0.05). Enalaprilat also restored subendocardial coronary flow reserve (CFR) (baseline CFR, 1.89±0.11; enalaprilat CFR, 2.74±0.33; P &lt;0.05) in DCM. These effects were abolished by pretreatment with the NO synthase inhibitor nitro- l -arginine. The effects were recapitulated by the bradykinin 2 receptor agonist cereport but not by the AT 1 antagonist losartan. Conclusions — The ACE inhibitor enalaprilat improves transmural myocardial perfusion at rest and after chronotropic stress and restores impaired subendocardial coronary flow and vasodilator reserve in DCM. The effects of enalaprilat were bradykinin mediated and NO dependent and were not recapitulated by losartan. These data suggest beneficial effects of ACE inhibitors on the coronary circulation in DCM that are not shared by AT 1 receptor antagonists.
Gastrin, gastrin receptors and colorectal carcinoma
Authors: G S BALDWIN, A SHULKES
Journal: Gut (1998)

The possibility that gastrin may play a role in the development of colorectal carcinoma has aroused considerable interest over the past decade. In early reports some colorectal carcinomas and colorectal carcinoma cell lines were shown to produce gastrin,1 to express gastrin receptors,2 and to respond mitogenically to exogenous gastrin.2 The most favoured explanation for these observations was an autocrine or paracrine loop in which gastrin was produced by the tumour, bound to tumour receptors, and stimulated tumour growth. However, gastrin may also have acted as an endocrine agent as hypergastrinaemia has been reported in a number of patients with colorectal carcinoma, although the source of the gastrin has not been defined.3-5 Further studies of the expression of gastrin6-8 and gastrin receptors9 10 in colorectal carcinomas and colorectal carcinoma cell lines, and of hypergastrinaemia in patients with colorectal carcinoma,11-15 indicated that the early positive reports were not universally correct. Recent information on the nature and source of the gastrin produced, and the discovery of novel receptors selective for non-amidated gastrins, makes it timely to reconsider the involvement of progastrin derived peptides in colorectal carcinoma.

There is now abundant evidence that most colorectal carcinomas synthesise progastrin. Gastrin mRNA has been detected by both polymerase chain reaction and northern hybridisation in colorectal carcinoma cell lines, normal human colonic mucosa and colorectal carcinomas.6 16-18 The gastrin mRNA is of low abundance but the major band of 0.7 kilobases is identical in sequence to antral gastrin mRNA.6 16 17 There is, however, considerable disparity in the literature on the proportion of colorectal carcinomas that contain amidated gastrin (table 1). The variable efficiency of translation and extent of postranslational processing of gastrin in peptide producing tumours20 offers an explanation for some of the contradictory reports as …
Nuclear Receptor Nurr1 Is Expressed In and Is Associated With Human Restenosis and Inhibits Vascular Lesion Formation In Mice Involving Inhibition of Smooth Muscle Cell Proliferation and Inflammation
Authors: Peter I. Bonta, Thijs W.H. Pols, Claudia M. van Tiel, Mariska Vos, E. Karin Arkenbout, Jakub Rohlena, Karel T. Koch, Moniek P.M. de Maat, Michael W.T. Tanck, Robbert J. de Winter, Hans Pannekoek, Erik A.L. Biessen, Ilze Bot, Carlie J.M. de Vries
Journal: Circulation (2010)

Restenosis is the major drawback of percutaneous coronary interventions involving excessive activation and proliferation of vascular smooth muscle cells (SMCs). The nuclear receptor Nurr1 is an early response gene known mainly for its critical role in the development of dopamine neurons. In the present study, we investigated Nurr1 in human and experimental vascular restenosis.In a prospective cohort of 601 patients undergoing percutaneous coronary intervention, including stent placement, we found a strong association between Nurr1 haplotypes and in-stent restenosis risk. Furthermore, Nurr1 is specifically expressed in human in-stent restenosis and induced in cultured human SMCs in response to serum or tumor necrosis factor-alpha. Lentivirus-mediated gain- and loss-of-function experiments in SMCs demonstrated that overexpression of Nurr1 inhibited proliferation, consistent with increased expression of the key cell-cycle inhibitor p27(Kip1), whereas Nurr1 silencing enhanced SMC growth. The tumor necrosis factor-alpha-induced proinflammatory response of SMCs is inhibited by Nurr1, as reflected by reduced interleukin-1beta, tumor necrosis factor-alpha, and monocyte chemoattractant protein-1 expression. Consistent with our in vitro data, endogenous Nurr1 reduced wire injury-induced proliferation and vascular lesion formation in carotid arteries of ApoE(-/-) mice.Nurr1 haplotypes are associated with human restenosis risk, and Nurr1 is expressed in human in-stent restenosis. In SMCs, Nurr1 inhibits proliferation and inflammatory responses, which explains the inhibition of SMC-rich lesion formation in mice. The recently identified small-molecule drugs that enhance the activity of Nurr1 reveal this nuclear receptor as an attractive novel target for (local) intervention in restenosis.
The doctor, the patient and the world-wide web: how the internet is changing healthcare
Authors: J A Powell, M Darvell, J A M Gray
Journal: Journal of the Royal Society of Medicine (2003)

To understand individual use of the internet and its impact on individuals, communities and societies is a challenge that is only beginning to be addressed. There are more than 580 million internet users world wide1, and over 16 million active users of the world-wide web in the UK2. This is more than the estimated number of UK smokers yet little has been done to assess the potential health impact of the internet. New developments will lead to further growth in internet usage, and this medium is increasingly being employed for health information and healthcare delivery. Clinicians need to understand the possibilities of this technology, and to be aware of potential threats to health.
Role of Reduced-Intensity Conditioning Allogeneic Hematopoietic Stem-Cell Transplantation in Older Patients With De Novo Myelodysplastic Syndromes: An International Collaborative Decision Analysis
Authors: John Koreth, Joseph Pidala, Waleska S. Perez, H. Joachim Deeg, Guillermo Garcia-Manero, Luca Malcovati, Mario Cazzola, Sophie Park, Raphael Itzykson, Lionel Ades, Pierre Fenaux, Martin Jadersten, Eva Hellstrom-Lindberg, Robert Peter Gale, C.L. Beach, Stephanie J. Lee, Mary M. Horowitz, Peter L. Greenberg, Martin S. Tallman, John F. DiPersio, Donald Bunjes, Daniel J. Weisdorf, Corey Cutler
Journal: Journal of Clinical Oncology (2013)

Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders that are more common in patients aged ≥ 60 years and are incurable with conventional therapies. Reduced-intensity conditioning (RIC) allogeneic hematopoietic stem-cell transplantation is potentially curative but has additional mortality risk. We evaluated RIC transplantation versus nontransplantation therapies in older patients with MDS stratified by International Prognostic Scoring System (IPSS) risk.
Physiological and anthropometric characteristics of amateur rugby league players
Authors: Tim J Gabbett
Journal: British Journal of Sports Medicine (2000)

To investigate the physiological and anthropometric characteristics of amateur rugby league players.Thirty five amateur rugby league players (19 forwards and 16 backs) were measured for height, body mass, percentage body fat (sum of four skinfolds), muscular power (vertical jump), speed (10 m and 40 m sprint), and maximal aerobic power (multistage fitness test). Data were also collected on match frequency, training status, playing experience, and employment related physical activity levels.The 10 m and 40 m sprint, vertical jump, percentage body fat, and multistage fitness test results were 20-42% poorer than previously reported for professional rugby league players. Compared with forwards, backs had significantly (p<0.01) lower body mass (79.7 (74.7-84.7) kg v 90.8 (86.2-95.4) kg) and significantly (p<0.01) greater speed during the 40 m sprint (6.45 (6.35-6.55) v 6.79 (6.69-6.89) seconds). Values for percentage body fat, vertical jump, 10 m sprint, and maximal aerobic power were not significantly different (p>0.05) between forwards and backs. When compared with professional rugby league players, the training status of amateur rugby league players was 30-53% lower, with players devoting less than three hours a week to team training sessions and about 30 minutes a week to individual training sessions. The training time devoted to the development of muscular power (about 13 minutes a week), speed (about eight minutes a week), and aerobic fitness (about 34 minutes a week) did not differ significantly (p>0.05) between forwards and backs. At the time of the field testing, players had participated, on average, in one 60 minute match every eight days.The physiological and anthropometric characteristics of amateur rugby league players are poorly developed. These findings suggest that position specific training does not occur in amateur rugby league. The poor fitness of non-elite players may be due to a low playing intensity, infrequent matches of short duration, and/or an inappropriate training stimulus.
Calcium Exchange in Dog Ventricular Muscle: Relation to Frequency of Contraction and Maintenance of Contractility
Authors: G. A. LANGER, S. D. Serena
Journal: Circulation Research (1965)

Calcium exchange was studied in the arterially-perfused papillary muscle of the dog under the conditions of varying frequency of contraction as well as calcium-free perfusion. The following conclusions are drawn from these studies: (1) The maximum increment in rate of Ca ++ uptake associated with increased rate of contraction occurs in the first 10 to 12 minutes following rate increase. The mean increment over this period of time is 2.5 µmoles/liter tissue water/beat. (2) The increased Ca ++ exchange which occurs in association with the increases in rate of contraction occurs within that portion of the myocardium represented kinetically by phase 2. (3) The Ca ++ associated with phase 2 remains reversibly bound. The maximum capacity of the "phase 2 system" under the present experimental conditions, is approximately 3.2 mmoles Ca ++ /liter tissue water. (4) Exceeding the capacity of the "phase 2 system" for Ca ++ is associated with the onset of contracture in the muscle. This occurs at rates of contraction which produce progressive fall in contractile tension and is associated, presumably, with myocardial hypoxia. That fraction of Ca ++ taken up in excess of the capacity of the "phase 2 system" is released very slowly. (5) The initial increment of Ca ++ uptake, following an increase in rate, is reversed if the rate increment is not associated with progressive fall in systolic tension and contracture. (6) The maintenance of the ability to develop contractile tension depends significantly upon the presence of Ca ++ in the "phase 2 system.". The rate of loss of contractile tension is very nearly the same as the rate of loss of Ca ++ from this system. (7) Ca ++ exchange between vascular and interstitial regions depends upon concentration gradient. In contrast, Ca ++ exchange of phases 2 and 3 ( ? sarcotubular system and intracellular region respectively) is unaffected by change of concentration gradient.
P415 PREVENTION OF CHEMOTHERAPY-INDUCED HBV-RELATED HEPATITIS FLARE IN LYMPHOMA PATIENTS WITH RESOLVED HBV INFECTION: COST ANALYSIS
Authors: H.-H. Tsou, H.-C. Yang, M.-H. Chuang, H.-Y. Wu, Y.-T. Hsu, W.-J. Chang, C.-F. Hsiao, C. Hsu
Journal: Journal of Hepatology (2014)
Improving quality in general practice: qualitative case study of barriers faced by health authorities
Authors: M. N Marshall
Journal: BMJ (1999)

<h3>Abstract</h3> <b>Objectives:</b> To identify and assess the barriers that health authorities face as they manage quality improvements in general practice in the context of the NHS reforms. <b>Design:</b> Qualitative case study. <b>Setting:</b> Three UK health authorities: a rural health authority in the south west, a deprived inner city health authority in the north east, and an affluent suburban health authority in the south east. <b>Participants:</b> Senior and junior managers. <b>Main outcome measures:</b> Structure of strategic and organisational management, and barriers to the leadership and management of quality improvement in general practice. <b>Results:</b> Seven barriers were identified: absence of an explicit strategic plan for general practice, competing priorities for attention of the health authority, sensitivity of health professionals, lack of information due to poor quality of clinical data, lack of authority to implement change, unclear roles and responsibilities of managers within the organisations, and isolation from other authorities or organisations facing similar challenges. <b>Conclusions:</b> The health authorities faced significant barriers that would impede their ability to fulfil their responsibilities in the new NHS and that would reduce their capacity to contribute to quality improvements in general practice. <h3>Key messages</h3> Health authorities fail to take a strategic approach to improving quality in general practice Doctors and health authority managers do not work sufficiently closely together to improve the quality of general practice Health authority managers seem to lack the authority and organisational structure to maximise the role in general practice expected of them in the NHS reforms
Myeloproliferative stem cell disorders by deregulated Rap1 activation in SPA-1-deficient mice
Authors: Daisuke Ishida, Kohei Kometani, Hailin Yang, Kiyokazu Kakugawa, Kyoko Masuda, Kazuhiro Iwai, Misao Suzuki, Shigeyoshi Itohara, Tatsutoshi Nakahata, Hiroshi Hiai, Hiroshi Kawamoto, Masakazu Hattori, Nagahiro Minato
Journal: Cancer Cell (2003)
Whatever happened to meaning?
Authors: Jean M. Mandler
Journal: Behavioral and Brain Sciences (1998)

Even in infancy, concept formation has to do with creating meaning, not with tracking substances. Preverbal infants can identify a substance such as a dog, but their first concept of this substance is not dog but animal. It is difficult to account for such global concepts by the perceptual processes involved in object identification, yet these concepts are the foundation on which later concepts are built.
The effects of ethanol and hyperosmotic perfusates on albumin synthesis and release
Authors: Marcus A. Rothschild, Murray Oratz, Sidney S. Schreiber, Joseph Mongelli
Journal: Hepatology (1986)

Sucrose and ethanol inhibit albumin synthesis; sucrose via an osmotic mechanism and ethanol during its metabolism. The present study was undertaken to compare the effects of both of these agents on albumin synthesis and secretion, and to see if ethanol inhibition could be related to an osmotic effect. Male, fed rabbits served as liver donors in all studies. There were a total of 35 studies: 13 control; 10 ethanol (39 to 52 mM); 4 cycloheximide (0.5 mM), and 8 sucrose (1%). Plasma volume was measured with 125I-albumin (human) and extracellular volume measured with either 99mTc diethylenetriamine pentaacetic acid or [14C]sucrose. During perfusion, rabbit albumin content in the perfusate was measured immunologically every 15 to 30 min for 225 min. Interstitial albumin efflux was measured by the rate of appearance in the perfusate of 125I-albumin given to 10 other rabbits 3 days prior to hepatic removal and perfusion. During the initial 75 min of perfusion, 74% of the in vivo equilibrated exchangeable 125I-albumin appeared in the perfusate, and during this period the rabbit albumin that entered the perfusate was taken to represent efflux from the interstitial volume plus synthesis. Rabbit albumin appearing in the perfusate during the later period of 150 min was taken to represent mainly synthesis and was used to calculate the amount of albumin that would be synthesized in 75 min. The difference between these two values would be hepatic interstitial albumin appearing in the perfusate.(ABSTRACT TRUNCATED AT 250 WORDS)
Disease-free survival after complete mesocolic excision compared with conventional colon cancer surgery: a retrospective, population-based study
Authors: Claus Anders Bertelsen, Anders Ulrich Neuenschwander, Jens Erik Jansen, Michael Wilhelmsen, Anders Kirkegaard-Klitbo, Jutaka Reilin Tenma, Birgitte Bols, Peter Ingeholm, Leif Ahrenst Rasmussen, Lars Vedel Jepsen, Else Refsgaard Iversen, Bent Kristensen, Ismail Gögenur
Journal: The Lancet Oncology (2014)
Sequential Phase I and II Trials of Stereotactic Body Radiotherapy for Locally Advanced Hepatocellular Carcinoma
Authors: Alexis Bujold, Christine A. Massey, John J. Kim, James Brierley, Charles Cho, Rebecca K.S. Wong, Rob E. Dinniwell, Zahra Kassam, Jolie Ringash, Bernard Cummings, Jenna Sykes, Morris Sherman, Jennifer J. Knox, Laura A. Dawson
Journal: Journal of Clinical Oncology (2013)

Purpose To describe outcomes of prospective trials of stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC). Patients and Methods Two trials of SBRT for patients with active HCC unsuitable for standard locoregional therapies were conducted from 2004 to 2010. All patients had Child-Turcotte-Pugh class A disease, with at least 700 mL of non-HCC liver. The SBRT dose range was 24 to 54 Gy in six fractions. Primary end points were toxicity and local control at 1 year (LC1y), defined as no progressive disease (PD) of irradiated HCC by RECIST (Response Evaluation Criteria in Solid Tumors). Results A total of 102 patients were evaluable (Trial 1, 2004 to 2007: n = 50; Trial 2, 2007 to 2010: n = 52). Underlying liver disease was hepatitis B in 38% of patients, hepatitis C in 38%, alcohol related in 25%, other in 14%, and none in 7%. Fifty-two percent received prior therapies (no prior sorafenib). TNM stage was III in 66%, and 61% had multiple lesions. Median gross tumor volume was 117.0 mL (range, 1.3 to 1,913.4 mL). Tumor vascular thrombosis (TVT) was present in 55%, and extrahepatic disease was present in 12%. LC1y was 87% (95% CI, 78% to 93%). SBRT dose (hazard ratio [HR] = 0.96; P = .02) and being in Trial 2 (HR = 0.38; P = .03) were associated with LC1y on univariate analysis. Toxicity ≥ grade 3 was seen in 30% of patients. In seven patients (two with TVT PD), death was possibly related to treatment (1.1 to 7.7 months after SBRT). Median overall survival was 17.0 months (95% CI, 10.4 to 21.3 months), for which only TVT (HR = 2.47; P = .01) and being in Trial 2 (HR = 0.49; P = .01) were significant on multivariate analysis. Conclusion These results provide strong rationale for studying SBRT for HCC in a randomized trial.
Saying Good-bye
Authors: Shannon Keane English
Journal: JAMA (2005)

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