tbuckley/cabot-search huggingface dataset:
Review on uremic toxins: Classification, concentration, and interindividual variability
Authors: Raymond Vanholder, Rita De Smet, Griet Glorieux, Angel Argilés, Ulrich Baurmeister, Philippe Brunet, William Clark, Gerald Cohen, Peter Paul De Deyn, Reinhold Deppisch, Beatrice Descamps-Latscha, Thomas Henle, Achim Jörres, Horst Dieter Lemke, Ziad A. Massy, Jutta Passlick-Deetjen, Mariano Rodriguez, Bernd Stegmayr, Peter Stenvinkel, Ciro Tetta, Christoph Wanner, Walter Zidek
Journal: Kidney International (2003)
Recognition of pollen-derived phosphatidyl-ethanolamine by human CD1d-restricted γδ T cells
Authors: Anna M. Russano, Elisabetta Agea, Lanfranco Corazzi, Antyony D. Postle, Gennaro De Libero, Steven Porcelli, Fernando M. de Benedictis, Fabrizio Spinozzi
Journal: Journal of Allergy and Clinical Immunology (2006)
Constitutively Active TRPC Channels of Adipocytes Confer a Mechanism for Sensing Dietary Fatty Acids and Regulating Adiponectin
Authors: Piruthivi Sukumar, Alicia Sedo, Jing Li, Lesley A. Wilson, David O'Regan, Jonathan D. Lippiat, Karen E. Porter, Mark T. Kearney, Justin F.X. Ainscough, David J. Beech
Journal: Circulation Research (2012)

Calcium entry is pivotal in the heart and blood vessels, but its significance and mechanisms in adipose tissue are largely unknown. An important factor produced by adipocytes is adiponectin, which confers myocardial protection, insulin-sensitization, and antiatherosclerotic effects.To investigate the relevance of calcium channels to adipocytes and the production of adiponectin.Microarray analysis led to identification of transient receptor potential canonical (TRPC)1 and TRPC5 as channel subunits that are induced when adipocytes mature. Both subunits were found in perivascular fat of patients with atherosclerosis. Intracellular calcium and patch-clamp measurements showed that adipocytes exhibit constitutively active calcium-permeable nonselective cationic channels that depend on TRPC1 and TRPC5. The activity could be enhanced by lanthanum or rosiglitazone, known stimulators of TRPC5 and TRPC5-containing channels. Screening identified lipid modulators of the channels that are relevant to adipose biology. Dietary ω-3 fatty acids (eg, α-linolenic acid) were inhibitory at concentrations that are achieved by ingestion. The adipocyte TRPC1/TRPC5-containing channel was functionally negative for the generation of adiponectin because channel blockade by antibodies, knock-down of TRPC1-TRPC5 in vitro, or conditional disruption of calcium permeability in TRPC5-incorporating channels in vivo increased the generation of adiponectin. The previously recognized capability of α-linolenic acid to stimulate the generation of adiponectin was lost when calcium permeability in the channels was disrupted.The data suggest that TRPC1 and TRPC5 contribute a constitutively active heteromultimeric channel of adipocytes that negatively regulates adiponectin and through which ω-3 fatty acids enhance the anti-inflammatory adipokine, adiponectin.
International Union of Basic and Clinical Pharmacology. XCVII. G Protein–Coupled Estrogen Receptor and Its Pharmacologic Modulators
Authors: Eric R. Prossnitz, Jeffrey B. Arterburn
Journal: Pharmacological Reviews (2015)

Estrogens are critical mediators of multiple and diverse physiologic effects throughout the body in both sexes, including the reproductive, cardiovascular, endocrine, nervous, and immune systems. As such, alterations in estrogen function play important roles in many diseases and pathophysiological conditions (including cancer), exemplified by the lower prevalence of many diseases in premenopausal women. Estrogens mediate their effects through multiple cellular receptors, including the nuclear receptor family (ER<i>α</i> and ER<i>β</i>) and the G protein–coupled receptor (GPCR) family (GPR30/G protein–coupled estrogen receptor [GPER]). Although both receptor families can initiate rapid cell signaling and transcriptional regulation, the nuclear receptors are traditionally associated with regulating gene expression, whereas GPCRs are recognized as mediating rapid cellular signaling. Estrogen-activated pathways are not only the target of multiple therapeutic agents (e.g., tamoxifen, fulvestrant, raloxifene, and aromatase inhibitors) but are also affected by a plethora of phyto- and xeno-estrogens (e.g., genistein, coumestrol, bisphenol A, dichlorodiphenyltrichloroethane). Because of the existence of multiple estrogen receptors with overlapping ligand specificities, expression patterns, and signaling pathways, the roles of the individual receptors with respect to the diverse array of endogenous and exogenous ligands have been challenging to ascertain. The identification of GPER-selective ligands however has led to a much greater understanding of the roles of this receptor in normal physiology and disease as well as its interactions with the classic estrogen receptors ER<i>α</i> and ER<i>β</i> and their signaling pathways. In this review, we describe the history and characterization of GPER over the past 15 years focusing on the pharmacology of steroidal and nonsteroidal compounds that have been employed to unravel the biology of this most recently recognized estrogen receptor.
Risk of treatment-related esophageal cancer among breast cancer survivors
Authors: L.M. Morton, E.S. Gilbert, P. Hall, M. Andersson, H. Joensuu, L. Vaalavirta, G.M. Dores, M. Stovall, E.J. Holowaty, C.F. Lynch, R.E. Curtis, S.A. Smith, R.A. Kleinerman, M. Kaijser, H.H. Storm, E. Pukkala, R.E. Weathers, M.S. Linet, P. Rajaraman, J.F. Fraumeni, L.M. Brown, F.E. van Leeuwen, S.D. Fossa, T.B. Johannesen, F. Langmark, S. Lamart, L.B. Travis, B.M.P. Aleman
Journal: Annals of Oncology (2012)
Catamenial and Noncatamenial, Endometriosis-related or Nonendometriosis-related Pneumothorax Referred for Surgery
Authors: Marco Alifano, Christine Jablonski, Habiba Kadiri, Pierre Falcoz, Anne Gompel, Sophie Camilleri-Broet, Jean-François Regnard
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Catamenial and endometriosis-related pneumothorax are considered relatively rare entities. Their clinical characteristics and outcome are incompletely known.To evaluate the frequencies, clinical characteristics, and outcomes of catamenial and endometriosis-related pneumothoraces occurring in women with no underlying lung disease referred for surgical treatment.Clinical files of all the women of reproductive age referred to our center during a 6-year period for surgical treatment of spontaneous pneumothorax were retrospectively reviewed. Catamenial pneumothorax (CP) was defined as recurrent pneumothorax occurring between the day before and within 72 hours after the onset of menses. All histologic slides were reviewed to confirm initial diagnoses.A total of 114 women underwent video-assisted thoracic surgery; 28 women (24.6%) had CP (right-sided in all but one), and diaphragmatic abnormalities (perforations and/or nodules) were observed in 22 of them. Diaphragmatic abnormalities were seen in 21 of 86 patients with non-CP. Histologic examination found endometriosis, mainly diaphragmatic, in 18 of 28 CPs and 11 of 86 non-CPs. A 6-month antigonadotropic treatment was prescribed postoperatively to women with either CP or endometriosis-related pneumothorax. Mean follow-up was 32.7 (+/-18.5) months. Recurrence rates in CP, non-CP but endometriosis-related, and non-CP non-endometriosis-related pneumothoraces were 32, 27, and 5.3%, respectively.Our experience shows that (1) CP and/or endometriosis-related pneumothoraces account for an important percentage of spontaneous pneumothoraces referred for surgery, (2) diaphragmatic abnormalities seem to play a fundamental role in their pathogenesis, and (3) management is difficult because of the high recurrence rate.
Sodium-dependent taurocholic cotransporting polypeptide: a candidate receptor for human hepatitis B virus
Authors: Christoph Seeger, William S Mason
Journal: Gut (2013)

There has been a long-running search for the cellular receptor of hepatitis B virus (HBV). This search has been hampered by the lack of cell lines permissive for HBV infection and the difficulty of producing HBV vectors with selectable reporter genes, akin to vectors used to determine the HIV and hepatitis C virus host cell receptors. The discovery many years ago that primary duck hepatocytes are susceptible to duck HBV (DHBV) infection and, subsequently, that primary human hepatocytes are susceptible to infection by HBV, and the satellite hepatitis delta virus (HDV), opened the door for investigations on viral and cellular determinants of virus entry. The DHBV model seemed particularly suitable, because duck primary hepatocytes (dPHCs) are easy to prepare and a large fraction can be productively infected in culture with DHBV. Moreover, virus-binding experiments demonstrated high-affinity binding sites or receptors on duck hepatocytes and, importantly, showed that these binding sites exhibit species- and tissue-specificity, consistent with the restricted host range and tissue tropism characteristic of the Hepadnaviridae.1 ,2 In the meantime, Tupaias (treeshrews), belonging to the family Tupaiidae, and not considered primates, were shown to be susceptible to HBV infection.3 Tupaia primary hepatocyte cultures (tPHCs) are also permissive for HBV and HDV infection, and provided a new tool in the search for the HBV receptor.4 Finally, lentiviruses pseudotyped with HBV envelope proteins were shown to infect human primary hepatocytes (hPHCs).5

Using these and other model systems, different laboratories over the past 25 years reported the identification of host proteins that could bind to HBV, DHBV or recombinant envelope components of these viruses.6 One of the best-studied receptor candidates was carboxypeptidase D (CPD), a transmembrane protein that binds to DHBV and to its envelope protein, L, in a host species-specific manner.7––9 However, CPD …
Global prevalence of, and risk factors for, uninvestigated dyspepsia: a meta-analysis
Authors: Alexander C Ford, Avantika Marwaha, Ruchit Sood, Paul Moayyedi
Journal: Gut (2014)

<h3>Objectives</h3> Many cross-sectional surveys have reported the prevalence of uninvestigated dyspepsia, but there has been no recent systematic review of data from all studies to determine its global prevalence and risk factors. <h3>Design</h3> MEDLINE, EMBASE and EMBASE Classic were searched (until January 2014) to identify population-based studies that reported the prevalence of uninvestigated dyspepsia in adults (≥15 years old); dyspepsia was defined using symptom-based criteria or questionnaires. The prevalence of dyspepsia was extracted for all studies and according to the criteria used to define it. Pooled prevalence, according to study location and certain other characteristics, ORs and 95% CIs were calculated. <h3>Results</h3> Of the 306 citations evaluated, 103 reported the prevalence of uninvestigated dyspepsia in 100 separate study populations, containing 312 415 subjects. Overall pooled prevalence in all studies was 20.8% (95% CI 17.8% to 23.9%). The prevalence varied according to country (from 1.8% to 57.0%) and criteria used to define dyspepsia. The greatest prevalence values were found when a broad definition of dyspepsia (29.5%; 95% CI 25.3% to 33.8%) or upper abdominal or epigastric pain or discomfort (20.4%; 95% CI 16.3% to 24.8%) were used. The prevalence was higher in women (OR 1.24; 95% CI 1.13 to 1.36), smokers (OR 1.25; 95% CI 1.12 to 1.40), non-steroidal anti-inflammatory drug (NSAID) users (OR 1.59; 95% CI 1.27 to 1.99) and <i>Helicobacter pylori</i>-positive individuals (OR 1.18; 95% CI 1.04 to 1.33). <h3>Conclusions</h3> The overall pooled prevalence of uninvestigated dyspepsia was 21%, but varied among countries and according to the criteria used to define its presence. Prevalence is significantly higher in women, smokers, NSAID users and <i>H. pylori</i>-positive individuals, although these associations were modest.
Long-term, intermittent treatment of chronic hand eczema with mometasone furoate
Authors: N K Veien, P Ølholm Larsen, K Thestrup-Pedersen, G Schou
Journal: British Journal of Dermatology (1999)

Chronic hand eczema can be incapacitating, and there is little knowledge of the efficacy and safety of long-term treatment with topical corticosteroids. We compared the efficacy and safety of two different schedules for the treatment of chronic hand eczema with a potent topical corticosteroid, mometasone furoate. In a prospective, open, randomized trial, 120 patients with chronic hand eczema were treated daily with mometasone furoate fatty cream until the dermatitis cleared or for a maximum of 9 weeks. Those who cleared were randomized to treatment for up to 36 weeks with mometasone furoate on Sunday, Tuesday and Thursday (group A), mometasone furoate on Saturday and Sunday (group B) or no further corticosteroid treatment (group C). In the event of relapse, patients were permitted daily treatment with mometasone furoate for 3 weeks on two separate occasions. For 50 of 106 randomized patients, daily treatment for 3 weeks controlled their dermatitis; 29 needed 6 weeks and 27 needed 9 weeks of treatment. During the maintenance phase, 29 of 35 (83%) in group A, 25 of 37 (68%) in group B and nine of 34 (26%) in group C had no recurrences (P = 0.001, χ2-test). Side-effects were minimal. It is concluded that long-term, intermittent treatment of chronic hand eczema with mometasone furoate fatty cream is effective and safe.
A rapid diagnostic test for ventilator associated pneumonia?
Authors: S Zachariah
Journal: Thorax (2004)

▴ Gibot S, Cravoisy A, Levy B, et al . Soluble triggering receptor expressed on myeloid cells and the diagnosis of pneumonia. N Engl J Med2004;350:451–8 [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] The diagnosis of ventilator associated pneumonia (VAP) is both contentious and frustrating for the intensivist. This study evaluates the effectiveness of using soluble triggering receptor expressed on myeloid cells (sTREM)-1, a member of the immunoglobulin superfamily expressed in response to bacterial or … [1]: {openurl}?query=rft.jtitle%253DNew%2BEngland%2BJournal%2Bof%2BMedicine%26rft.stitle%253DNEJM%26rft.issn%253D0028-4793%26rft.aulast%253DGibot%26rft.auinit1%253DS.%26rft.volume%253D350%26rft.issue%253D5%26rft.spage%253D451%26rft.epage%253D458%26rft.atitle%253DSoluble%2BTriggering%2BReceptor%2BExpressed%2Bon%2BMyeloid%2BCells%2Band%2Bthe%2BDiagnosis%2Bof%2BPneumonia%26rft_id%253Dinfo%253Adoi%252F10.1056%252FNEJMoa031544%26rft_id%253Dinfo%253Apmid%252F14749453%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1056/NEJMoa031544&link_type=DOI [3]: /lookup/external-ref?access_num=14749453&link_type=MED&atom=%2Fthoraxjnl%2F59%2F5%2F413.atom [4]: /lookup/external-ref?access_num=000188463900007&link_type=ISI
A Grainyhead-Like 2/Ovo-Like 2 Pathway Regulates Renal Epithelial Barrier Function and Lumen Expansion
Authors: Annekatrin Aue, Christian Hinze, Katharina Walentin, Janett Ruffert, Yesim Yurtdas, Max Werth, Wei Chen, Anja Rabien, Ergin Kilic, Jörg-Dieter Schulzke, Michael Schumann, Kai M. Schmidt-Ott
Journal: Journal of the American Society of Nephrology (2015)

Grainyhead transcription factors control epithelial barriers, tissue morphogenesis, and differentiation, but their role in the kidney is poorly understood. Here, we report that nephric duct, ureteric bud, and collecting duct epithelia express high levels of grainyhead-like homolog 2 (Grhl2) and that nephric duct lumen expansion is defective in Grhl2-deficient mice. In collecting duct epithelial cells, Grhl2 inactivation impaired epithelial barrier formation and inhibited lumen expansion. Molecular analyses showed that GRHL2 acts as a transcriptional activator and strongly associates with histone H3 lysine 4 trimethylation. Integrating genome-wide GRHL2 binding as well as H3 lysine 4 trimethylation chromatin immunoprecipitation sequencing and gene expression data allowed us to derive a high-confidence GRHL2 target set. GRHL2 transactivated a group of genes including Ovol2, encoding the ovo-like 2 zinc finger transcription factor, as well as E-cadherin, claudin 4 (Cldn4), and the small GTPase Rab25. Ovol2 induction alone was sufficient to bypass the requirement of Grhl2 for E-cadherin, Cldn4, and Rab25 expression. Re-expression of either Ovol2 or a combination of Cldn4 and Rab25 was sufficient to rescue lumen expansion and barrier formation in Grhl2-deficient collecting duct cells. Hence, we identified a Grhl2/Ovol2 network controlling Cldn4 and Rab25 expression that facilitates lumen expansion and barrier formation in subtypes of renal epithelia.
Amino acid residues that flank core peptide epitopes and the extracellular domains of CD4 modulate differential signaling through the T cell receptor.
Authors: D A Vignali, J L Strominger
Journal: The Journal of Experimental Medicine (1994)

Hen egg lysozyme 52-61-specific CD4+ T cells responded by interleukin 2 (IL-2) secretion to any peptide containing this epitope regardless of length of NH2- and COOH-terminal composition. However, CD4- variants could only respond to peptides containing the two COOH-terminal tryptophans at positions 62 and 63. Substitutions at these positions defined patterns of reactivity that were specific for individual T cells inferring a T cell receptor (TCR)-based phenomenon. Thus, the fine specificity of major histocompatibility complex (MHC)-peptide recognition by the TCR was dramatically affected by CD4 and the COOH-terminal peptide composition. Peptides that failed to induce IL-2 secretion in the CD4- variants nevertheless induced strong tyrosine phosphorylation of CD3 zeta. Thus, whereas the TCR still recognized and bound to the MHC class II-peptide complex resulting in protein phosphorylation, this interaction failed to induce effective signal transduction manifested by IL-2 secretion. This provides a clear example of differential signaling mediated by peptides known to be naturally processed. In addition, the external domains of CD4, rather than its cytoplasmic tail, were critical in aiding TCR recognition of all peptides derived from a single epitope. These data suggest that the nested flanking residues, which are present on MHC class II but not class I bound peptides, are functionally relevant.
Reference Pricing With Evidence Development: A Way Forward for Proton Therapy
Authors: Justin E. Bekelman, Stephen M. Hahn
Journal: Journal of Clinical Oncology (2014)

Next month, the Washington State Health Technology Assessment Program (HTAP) will decide whether and under what circumstances the state’s public payers will pay for proton therapy, a promising but expensive cancer treatment. HTAP has a unique legislative mandate in the United States to evaluate health technologies and translate evidence of comparative cost-effectiveness into payment policy. HTAP’s decisions are closely scrutinized, and they influence the payment policy of other payers in the US health care system. HTAP’s examination of proton therapy comes at a decisive moment: major insurers have recently announced policies that restrict coverage for proton therapy to narrow indications. 1 HTAP should not follow suit. Proton therapy comparative effectiveness research is a particular priority. Compared with photon therapies such as intensitymodulated radiotherapy (IMRT), proton therapy reduces low and intermediate radiation dose to nearby normal tissue, holding promise as more effective or better tolerated radiation treatment. However, proton therapy has greater physical and biologic uncertainties. For example, because we cannot determine where proton therapy terminates in tissue with enough precision, we routinely overshoot tumor targets to ensure adequate radiation coverage. Proton therapy uncertainties could affect clinical outcomes; thus, we must establish whether its novel advantages actually translate into clinical benefits. Yet, as the HTAP appraisal shows, high-quality comparative effectiveness evidence is woefully lacking. 2 Moreover, the costs are consequential; median Medicare reimbursement for proton therapy is $13,000 higher than that for IMRT for prostate cancer and substantially greater in the commercial insurance market. Washington State and other payers face an unenviable choice: pay for an expensive therapy that has not been shown to be better than less expensive alternatives for prevalent malignancies or restrict coverage to rare tumors in which clinical benefit appears compelling. We propose a better way forward: reference pricing with evidence development. Reference pricing establishes a common level of payment for different therapies with similar outcomes. Under reference pricing,
Assessment of Severe Malnutrition Among Hospitalized Children in Rural Kenya
Authors: James Berkley, Isaiah Mwangi, Karen Griffiths, Ismail Ahmed, Sadik Mithwani, Mike English, Charles Newton, Kathryn Maitland
Journal: JAMA (2005)

Severe malnutrition has a high mortality rate among hospitalized children in sub-Saharan Africa. However, reports suggest that malnutrition is often poorly assessed. The World Health Organization recommends using weight for height, but this method is problematic and often not undertaken in practice. Mid upper arm circumference (MUAC) and the clinical sign "visible severe wasting" are simple and inexpensive methods but have not been evaluated in this setting.To evaluate MUAC and visible severe wasting as predictors of inpatient mortality at a district hospital in sub-Saharan Africa and to compare these with weight-for-height z score (WHZ).Cohort study with data collected at admission and at discharge or death. Predictive values for inpatient death were determined using the area under receiver operating characteristic curves. Participants were children aged 12 to 59 months admitted to a district hospital in rural Kenya between April 1, 1999, and July 31, 2002.MUAC, WHZ, and visible severe wasting as predictors of inpatient death.Overall, 4.4% (359) of children included in the study died while in the hospital. Sixteen percent (1282/8190) of admitted children had severe wasting (WHZ < or =-3) (n = 756), kwashiorkor (n = 778), or both. The areas under the receiver operating characteristic curves for predicting inpatient death did not significantly differ (MUAC: 0.75 [95% confidence interval, 0.72-0.78]; WHZ: 0.74 [95% confidence interval, 0.71-0.77]) (P = .39). Although sensitivity and specificity for subsequent inpatient death were 46% and 91%, respectively, for MUAC less than or equal to 11.5 cm, 42% and 92% for WHZ less than or equal to -3, and 47% and 93% for visible severe wasting, the 3 indices identified different sets of children and were independently associated with mortality. Clinical features of malnutrition were significantly more common among children with MUAC less than or equal to 11.5 cm than among those with WHZ less than or equal to -3.MUAC is a practical screening tool that performs at least as well as WHZ in predicting subsequent inpatient mortality among severely malnourished children hospitalized in rural Kenya. Visible severe wasting is also a potentially useful sign at this level, providing appropriate training has been given.
2-Arachidonoylglycerol
Authors: Kasem Nithipatikom, Michael P. Endsley, Marilyn A. Isbell, John R. Falck, Yoshiki Iwamoto, Cecilia J. Hillard, William B. Campbell
Journal: Cancer Research (2004)

Abstract Endocannabinoids have been implicated in cancer. Increasing endogenous 2-arachidonoylglycerol (2-AG) by blocking its metabolism inhibits invasion of androgen-independent prostate cancer (PC-3 and DU-145) cells. Noladin ether (a stable 2-AG analog) and exogenous CB1 receptor agonists possess similar effects. Conversely, reducing endogenous 2-AG by inhibiting its synthesis or blocking its binding to CB1 receptors with antagonists increases the cell invasion. 2-AG and noladin ether decrease protein kinase A activity in these cells, indicating coupling of the CB1 receptor to downstream effectors. The results suggest that cellular 2-AG, acting through the CB1 receptor, is an endogenous inhibitor of invasive prostate cancer cells.