tbuckley/cabot-search huggingface dataset:
Expression of the Receptor Tyrosine Kinase Axl Promotes Ocular Melanoma Cell Survival
Authors: Paul R. van Ginkel, Ricardo L. Gee, Rebecca L. Shearer, Lalita Subramanian, Teresa M. Walker, Daniel M. Albert, Lorraine F. Meisner, Brian C. Varnum, Arthur S. Polans
Journal: Cancer Research (2004)

Abstract Metastatic tumor cells originating from cancers of a variety of tissues such as breast, skin, and prostate may remain dormant for long periods of time. In the case of uveal melanoma, the principal malignancy of the eye, complete removal of the primary tumor by enucleation can nonetheless be followed by metastatic tumor growth in distant organs months, years, or even decades later. This suggests that tumor cells have already spread to secondary sites at the time of treatment and remain dormant as micrometastases. Identifying factors that govern long-lived survival of metastatic tumor cells is therefore key to decreasing mortality associated with this and other diseases. While investigating factors differentially expressed in melanoma cells and normal melanocytes, we identified the receptor tyrosine kinase Axl and found up-regulation of Axl in uveal melanomas and melanoma cell lines by RNase protection, Western analysis, and immunohistochemistry. Axl has been shown to mediate cell growth and survival through its ligand Gas6 in non-transformed cells. To test whether stimulation of Axl can enhance survival of uveal melanoma cells, we assessed the degree of mitogenesis and cell survival by bromodeoxyuridine incorporation and trypan blue exclusion, respectively, upon stimulation of Mel 290 uveal melanoma cells with Gas6 in vitro. We show that Gas6 mediates mitogenesis and cell survival in Mel 290 cells. We further demonstrate that these effects occur specifically through the Axl receptor by modulating the expression of Axl with an antisense construct. cDNA microarray analysis of 12,687 genes then revealed that Gas6 stimulation of Axl in Mel 290 cells results primarily in the down-regulation of Cyr61, a member of the CCN protein family involved in tumor progression. These data show that the Axl pathway mediates increased survival of uveal melanoma cells, potentially advantageous during cancer dormancy, and that Axl may function in part through regulation of Cyr61.
Release in vitro of adipsin, vascular cell adhesion molecule 1, angiotensin 1–converting enzyme, and soluble tumor necrosis factor receptor 2 by human omental adipose tissue as well as by the nonfat cells and adipocytes
Authors: John N. Fain, Amanda S. Nesbit, Fara F. Sudlow, Paramjeet Cheema, Jeanette M. Peeples, Atul K. Madan, David S. Tichansky
Journal: Metabolism (2007)
The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection
Authors: M Rudwaleit, D van der Heijde, R Landewe, J Listing, N Akkoc, J Brandt, J Braun, C T Chou, E Collantes-Estevez, M Dougados, F Huang, J Gu, M A Khan, Y Kirazli, W P Maksymowych, H Mielants, I J Sorensen, S Ozgocmen, E Roussou, R Valle-Onate, U Weber, J Wei, J Sieper
Journal: Annals of the Rheumatic Diseases (2009)

<h3>Objective:</h3> To validate and refine two sets of candidate criteria for the classification/diagnosis of axial spondyloarthritis (SpA). <h3>Methods:</h3> All Assessment of SpondyloArthritis international Society (ASAS) members were invited to include consecutively new patients with chronic (⩾3 months) back pain of unknown origin that began before 45 years of age. The candidate criteria were first tested in the entire cohort of 649 patients from 25 centres, and then refined in a random selection of 40% of cases and thereafter validated in the remaining 60%. <h3>Results:</h3> Upon diagnostic work-up, axial SpA was diagnosed in 60.2% of the cohort. Of these, 70% did not fulfil modified New York criteria and, therefore, were classified as having "non-radiographic" axial SpA. Refinement of the candidate criteria resulted in new ASAS classification criteria that are defined as: the presence of sacroiliitis by radiography or by magnetic resonance imaging (MRI) plus at least one SpA feature ("imaging arm") or the presence of HLA-B27 plus at least two SpA features ("clinical arm"). The sensitivity and specificity of the entire set of the new criteria were 82.9% and 84.4%, and for the imaging arm alone 66.2% and 97.3%, respectively. The specificity of the new criteria was much better than that of the European Spondylarthropathy Study Group criteria modified for MRI (sensitivity 85.1%, specificity 65.1%) and slightly better than that of the modified Amor criteria (sensitivity 82.9, specificity 77.5%). <h3>Conclusion:</h3> The new ASAS classification criteria for axial SpA can reliably classify patients for clinical studies and may help rheumatologists in clinical practice in diagnosing axial SpA in those with chronic back pain. <h3>Trial registration number:</h3> NCT00328068.
The Concept of Child Advocacy
Authors: JOHN F. MCDERMOTT, WILLIAM M. BOLMAN, ALFRED M. ARENSDORF, RICHARD A. MARKOFF
Journal: American Journal of Psychiatry (1973)

The authors examine the concept of child advocacy in historical perspective, describing its antecedents as reflected in law, education, welfare, and child labor. Although it is not yet realized in practice, child advocacy seems to represent the recognition by society that the developmental needs of its children are so important that they must be ensured as rights to be promoted and protected.
Transplantation of Human Pericyte Progenitor Cells Improves the Repair of Infarcted Heart Through Activation of an Angiogenic Program Involving Micro-RNA-132
Authors: Rajesh Katare, Federica Riu, Kathryn Mitchell, Miriam Gubernator, Paola Campagnolo, Yuxin Cui, Orazio Fortunato, Elisa Avolio, Daniela Cesselli, Antonio Paolo Beltrami, Gianni Angelini, Costanza Emanueli, Paolo Madeddu
Journal: Circulation Research (2011)

Pericytes are key regulators of vascular maturation, but their value for cardiac repair remains unknown.We investigated the therapeutic activity and mechanistic targets of saphenous vein-derived pericyte progenitor cells (SVPs) in a mouse myocardial infarction (MI) model.SVPs have a low immunogenic profile and are resistant to hypoxia/starvation (H/S). Transplantation of SVPs into the peri-infarct zone of immunodeficient CD1/Foxn-1(nu/nu) or immunocompetent CD1 mice attenuated left ventricular dilatation and improved ejection fraction compared to vehicle. Moreover, SVPs reduced myocardial scar, cardiomyocyte apoptosis and interstitial fibrosis, improved myocardial blood flow and neovascularization, and attenuated vascular permeability. SVPs secrete vascular endothelial growth factor A, angiopoietin-1, and chemokines and induce an endogenous angiocrine response by the host, through recruitment of vascular endothelial growth factor B expressing monocytes. The association of donor- and recipient-derived stimuli activates the proangiogenic and prosurvival Akt/eNOS/Bcl-2 signaling pathway. Moreover, microRNA-132 (miR-132) was constitutively expressed and secreted by SVPs and remarkably upregulated, together with its transcriptional activator cyclic AMP response element-binding protein, on stimulation by H/S or vascular endothelial growth factor B. We next investigated if SVP-secreted miR-132 acts as a paracrine activator of cardiac healing. In vitro studies showed that SVP conditioned medium stimulates endothelial tube formation and reduces myofibroblast differentiation, through inhibition of Ras-GTPase activating protein and methyl-CpG-binding protein 2, which are validated miR-132 targets. Furthermore, miR-132 inhibition by antimiR-132 decreased SVP capacity to improve contractility, reparative angiogenesis, and interstitial fibrosis in infarcted hearts.SVP transplantation produces long-term improvement of cardiac function through a novel paracrine mechanism involving the secretion of miR-132 and inhibition of its target genes.
Opening of Mitochondrial K <sub>ATP</sub> Channels Attenuates the Ouabain-Induced Calcium Overload in Mitochondria
Authors: Hideyuki Ishida, Yuki Hirota, Chokoh Genka, Hiroe Nakazawa, Haruaki Nakaya, Toshiaki Sato
Journal: Circulation Research (2001)

We tested whether opening of mitochondrial ATP-sensitive K + (mitoK ATP ) channels depolarizes mitochondrial membrane potential (ΔΨ m ) and thereby prevents the mitochondrial Ca 2+ overload. With the use of a Nipkow disk confocal system, the mitochondrial Ca 2+ concentration ([Ca 2+ ] m ) and ΔΨ m in rat ventricular myocytes were measured by loading cells with Rhod-2 and JC-1, respectively. Exposure to ouabain (1 mmol/L) for 30 minutes produced mitochondrial Ca 2+ overload, and the intensity of Rhod-2 fluorescence significantly increased to 173±16% of baseline ( P &lt;0.001). Treatment of myocytes with the mitoK ATP channel opener diazoxide (100 μmol/L) blunted the ouabain-induced mitochondrial Ca 2+ overload (131±10% of baseline; P &lt;0.001 versus ouabain). Moreover, diazoxide significantly depolarized the ΔΨ m and reduced the intensity of JC-1 fluorescence during application of ouabain to 89±2% of baseline ( P &lt;0.05). These effects of diazoxide were blocked by the mitoK ATP channel blocker 5-hydroxydecanoate (500 μmol/L). These results indicate that opening of mitoK ATP channels prevents a mitochondrial Ca 2+ overload in association with ΔΨ m depolarization and thereby protects myocardium against ischemic damage.
Neurodegenerative Diseases: Expanding the Prion Concept
Authors: Lary C. Walker, Mathias Jucker
Journal: Annual Review of Neuroscience (2015)

The prion paradigm has emerged as a unifying molecular principle for the pathogenesis of many age-related neurodegenerative diseases. This paradigm holds that a fundamental cause of specific disorders is the misfolding and seeded aggregation of certain proteins. The concept arose from the discovery that devastating brain diseases called spongiform encephalopathies are transmissible to new hosts by agents consisting solely of a misfolded protein, now known as the prion protein. Accordingly, "prion" was defined as a "proteinaceous infectious particle." As the concept has expanded to include other diseases, many of which are not infectious by any conventional definition, the designation of prions as infectious agents has become problematic. We propose to define prions as "proteinaceous nucleating particles" to highlight the molecular action of the agents, lessen unwarranted apprehension about the transmissibility of noninfectious proteopathies, and promote the wider acceptance of this revolutionary paradigm by the biomedical community.
Classification and pharmacological treatment of preschool wheezing: changes since 2008
Authors: Paul L.P. Brand, Daan Caudri, Ernst Eber, Erol A. Gaillard, Luis Garcia-Marcos, Gunilla Hedlin, John Henderson, Claudia E. Kuehni, Peter J.F.M. Merkus, Soren Pedersen, Arunas Valiulis, Göran Wennergren, Andrew Bush
Journal: European Respiratory Journal (2014)

Since the publication of the European Respiratory Society Task Force report in 2008, significant new evidence has become available on the classification and management of preschool wheezing disorders. In this report, an international consensus group reviews this new evidence and proposes some modifications to the recommendations made in 2008. Specifically, the consensus group acknowledges that wheeze patterns in young children vary over time and with treatment, rendering the distinction between episodic viral wheeze and multiple-trigger wheeze unclear in many patients. Inhaled corticosteroids remain first-line treatment for multiple-trigger wheeze, but may also be considered in patients with episodic viral wheeze with frequent or severe episodes, or when the clinician suspects that interval symptoms are being under reported. Any controller therapy should be viewed as a treatment trial, with scheduled close follow-up to monitor treatment effect. The group recommends discontinuing treatment if there is no benefit and taking favourable natural history into account when making decisions about long-term therapy. Oral corticosteroids are not indicated in mild-to-moderate acute wheeze episodes and should be reserved for severe exacerbations in hospitalised patients. Future research should focus on better clinical and genetic markers, as well as biomarkers, of disease severity.
Screening for Hyperlipidemia in Childhood
Authors: H. Peter Chase
Journal: JAMA (1974)

Victims of early heart attacks were found to have elevated levels of serum cholesterol or triglycerides or both in 38 of 58 cases (66%). Blood lipid levels were determined in 179 offspring of 71 probands and were elevated in 52 (29%). It is recommended that all children of early heart attack victims be screened for hyperlipidemia. (<i>JAMA</i>230:1535-1537, 1974)
A toolkit to support the implementation of electronic prescribing systems into UK hospitals: preliminary recommendations
Authors: Kathrin Cresswell, Jamie Coleman, Ann Slee, Zoe Morrison, Aziz Sheikh
Journal: Journal of the Royal Society of Medicine (2013)

Hospital electronic prescribing (or ePrescribing) systems have the potential to reduce drug-related morbidity and mortality. However, their implementation and adoption has been slow to date, despite the considerable service interest in implementing systems and the long-standing policy drive towards computerization. The underlying reasons may include the demise of the National Programme for Information Technology; a lack of change management expertise and capacity in the National Health Service (NHS); the relatively immature and fragmented market; limited standards guiding procurement, functional specifications and expected benefits; and lack of resources.
High MMP-9 activity characterises pleural tuberculosis correlating with granuloma formation
Authors: P. Sheen, C. M. O’Kane, K. Chaudhary, M. Tovar, C. Santillan, J. Sosa, L. Caviedes, R. H. Gilman, G. Stamp, J. S. Friedland
Journal: European Respiratory Journal (2008)

Tuberculosis (TB) pleural disease is complicated by extensive tissue destruction. Matrix metalloproteinase (MMP)-1 and -9 are implicated in immunopathology of pulmonary and central nervous system TB. There are few data on MMP activity in TB pleurisy. The present study investigated MMP-1, -2 and -9 and their specific inhibitors (tissue inhibitor of metalloproteinase (TIMP)-1 and -2) in tuberculous effusions, and correlated these with clinical and histopathological features. Clinical data, routine blood tests, and pleural fluid/biopsy material were obtained from 89 patients presenting with pleural effusions in a TB-endemic area. MMP-1, -2 and -9 were measured by zymography or western blot, and TIMP-1 and -2 by ELISA. Pleural biopsies were examined microscopically, cultured for acid–alcohol fast bacilli and immunostained for MMP-9. Tuberculous pleural effusions contained the highest concentrations of MMP-9 compared with malignant effusions or heart failure transudates. MMP-9 concentrations were highest in effusions from patients with granulomatous biopsies: median (interquartile range) 108 (61–218) pg·mL −1 versus 43 (12–83) pg·mL −1 in those with nongranulomatous pleural biopsies. MMP-1 and -2 were not upregulated in tuberculous pleural fluid. The ratio of MMP-9:TIMP-1 was significantly higher in TB effusions. Tuberculous pleurisy is characterised by a specific pattern of matrix metalloproteinase-9 upregulation, correlating with the presence of granulomas and suggesting a specific role for matrix metalloproteinase-9 in inflammatory responses in tuberculous pleural disease.
Komen/ASCO Program Aims To Swell Ranks of Minority Oncologists
Authors: Charlie Schmidt
Journal: JNCI Journal of the National Cancer Institute (2009)

for the Cure, a breast cancer advocacy group in Dallas, Texas, and the American Society of Clinical Oncology (ASCO) teamed on a $4 million initiative to combat disparities in cancer care.The initiative builds on a growing response to the problem of cancer disparities in the United States: Racial and ethnic minorities -including African Americans, Hispanics, Asian/Pacific Islanders, and Native Americans -suffer a disproportionate share of some cancers.
Health Care Insurance, Financial Concerns in Accessing Care, and Delays to Hospital Presentation in Acute Myocardial Infarction
Authors: Kim G. Smolderen
Journal: JAMA (2010)

Little is known about how health insurance status affects decisions to seek care during emergency medical conditions such as acute myocardial infarction (AMI).To examine the association between lack of health insurance and financial concerns about accessing care among those with health insurance, and the time from symptom onset to hospital presentation (prehospital delays) during AMI.Multicenter, prospective study using a registry of 3721 AMI patients enrolled between April 11, 2005, and December 31, 2008, at 24 US hospitals. Health insurance status was categorized as insured without financial concerns, insured but have financial concerns about accessing care, and uninsured. Insurance information was determined from medical records while financial concerns among those with health insurance were determined from structured interviews.Prehospital delay times (< or = 2 hours, > 2-6 hours, or > 6 hours), adjusted for demographic, clinical, and social and psychological factors using hierarchical ordinal regression models.Of 3721 patients, 2294 were insured without financial concerns (61.7%), 689 were insured but had financial concerns about accessing care (18.5%), and 738 were uninsured (19.8%). Uninsured and insured patients with financial concerns were more likely to delay seeking care during AMI and had prehospital delays of greater than 6 hours among 48.6% of uninsured patients and 44.6% of insured patients with financial concerns compared with only 39.3% of insured patients without financial concerns. Prehospital delays of less than 2 hours during AMI occurred among 36.6% of those insured without financial concerns compared with 33.5% of insured patients with financial concerns and 27.5% of uninsured patients (P < .001). After adjusting for potential confounders, prehospital delays were associated with insured patients with financial concerns (adjusted odds ratio, 1.21 [95% confidence interval, 1.05-1.41]; P = .01) and with uninsured patients (adjusted odds ratio, 1.38 [95% confidence interval, 1.17-1.63]; P < .001).Lack of health insurance and financial concerns about accessing care among those with health insurance were each associated with delays in seeking emergency care for AMI.
Clinical outcomes in adults with chronic hepatitis B in association with patient and viral characteristics: A systematic review of evidence
Authors: Brent C. Taylor, Jian-Min Yuan, Tatyana A. Shamliyan, Aasma Shaukat, Robert L. Kane, Timothy J. Wilt
Journal: Hepatology (2009)

We systematically reviewed the literature on the extent to which population characteristics or clinical features predict groups of individuals likely to develop advanced liver disease or die from chronic infection with hepatitis B virus (HBV). We searched Medline to include studies with reported cirrhosis, liver failure, liver cancer, or death outcomes after at least 1 year of follow-up from the measurement of predictive factors (age, age at infection, geographic location, race/ethnicity, sex, positive family history, presence of coinfections, HBV viral level, change in hepatitis B e antigen [HBeAg] status, genotype, HBV mutations, nonalcoholic fatty liver disease, alcohol consumption, liver enzymes, and liver biopsy finding). Evidence from 41 included articles suggested that cirrhosis, higher HBV viral level, and male sex were consistently associated with significantly increased risk of death and liver cancer. Evidence about the role of HBV genotype, HBeAg status, age and duration of infection, coinfections with hepatitis C virus, human immunodeficiency virus, hepatitis delta virus, and alanine aminotransferase levels were limited and inconsistent, but were deemed promising to identify patients at higher risk of clinical outcomes. Adults with chronic hepatitis B had increased risk for poorer health outcomes compared to the general population; however, the magnitude of risk varied greatly depending on baseline patient and disease characteristics, and typically clinical outcomes required many years to become manifest. Many adults with chronic hepatitis B had low absolute risks of clinical outcomes and likely would not benefit from immediate treatment. Baseline patient and disease characteristics provide important information about the risk of clinical outcomes and should be incorporated into monitoring or treatment decisions.
Cocarcinogenic and Tumor-Promoting Agents in Tobacco Carcinogenesis2
Authors: B. L. Van Duuren, B. M. Goldschmidt
Journal: JNCI Journal of the National Cancer Institute (1976)

A series of 21 tobacco smoke components and related compounds werere applied to mouse skin (50 female ICR/Ha Swiss mice/group) three times weekly with a low dose (5 mug/application) of benzo[a]pyrene (B[a]P). The test compounds were of five classes: aliphatic hydrocarbons, aromatic hydrocarbons, phenols, and long-chain acids and alcohols. The following compounds enhanced remarkably the carcinogenicity of B[a]P: catechol, pyrogallol, decane, undecane, pyrene, benzo[e]pyrene, and fluoranthene. The following compounds inhibited B[a]P carcinogenicity completely: esculin, quercetin, squalene, and oleic acid. Phenol, eugenol, resorcinol, hydroquinone, hexadecane, and limonene partially inhibited B[a]P carcinogenicity. Six of the 21 compounds were also tested as tumor promoters im two-stage carcinogenesis. No direct correlation existed between tumor-promoting activity and cocarcinogenic activity. The cocarcinogens pyrogallol and catechol did not show tumor-promoting activity. Decane, tetradecane, anthralin, and phorbol myristate acetate showed both types of activity. Structure-activity relationships and possible modes of action were described.
Amplified Transmural Dispersion of Repolarization as the Basis for Arrhythmogenesis in a Canine Ventricular-Wedge Model of Short-QT Syndrome
Authors: Fabrice Extramiana, Charles Antzelevitch
Journal: Circulation (2004)

The short-QT syndrome is a new clinical entity characterized by corrected QT intervals <300 ms and a high incidence of ventricular tachycardia (VT) and fibrillation (VF). Gain-of-function mutations in the gene for outward potassium currents have been shown to underlie the congenital syndrome. The present study examined the cellular basis of VT/VF in an experimental model associated with short QT intervals created with a potassium channel activator.Transmembrane action potentials from epicardial and M regions, 4 transmural unipolar electrograms, and a pseudo-ECG were simultaneously recorded in canine arterially perfused left ventricular wedge preparations. At a basic cycle length of 2000 ms, pinacidil (2 to 3 mumol/L) abbreviated the QT interval from 303.7+/-5.4 to 247.3+/-6.9 ms (mean+/-SEM, P<0.0001). The maximal transmural dispersion of repolarization (TDR(max)) increased from 27.0+/-3.8 to 64.9+/-9.2 ms (P<0.01), and an S2 applied to the endocardium induced a polymorphic VT (pVT) in 9 of 12 wedge preparations (P<0.01). Addition of isoproterenol (100 nmol/L, n=5) led to greater abbreviation of the QT interval, a further increase in TDR(max) (from 55.4+/-13.7 to 69.7+/-8.3 ms), and more enduring pVT. TDR(max) was correlated significantly with the T(peak)-T(end) interval under all conditions. The effects of pinacidil were completely reversed by glybenclamide (10 micromol/L, n=4) and partially reversed by E4031 (5 micromol/L, n=5), which prevented induction of pVT in 3 of 5 preparations.Our data suggest that heterogeneous abbreviation of the action potential duration among different cell types spanning the ventricular wall creates the substrate for the genesis of VT under conditions associated with short QT intervals.