tbuckley/cabot-search huggingface dataset:
Benign persistent papular acantholytic and dyskeratotic eruption: a case report and review of the literature
Authors: TH. JOOST, V.D. VUZEVSKI, B. TANK, H.E. MENKE
Journal: British Journal of Dermatology (1991)

We report a case of a 35‐year‐old female with a persistent pruritic acantholytic and dyskeratotic eruption on the chest and vulva. The light and electron microscopic studies showed suprabasal epidermal clefting with acantholysis and dyskeratotic cells. We suggest that the most appropriate term for this case is that of benign persistent papular acantholytic and dyskeratotic eruption.
Effect of the critical care outreach team on patient survival to discharge from hospital and readmission to critical care: non-randomised population based study
Authors: C. Ball
Journal: BMJ (2003)

<h3>Abstract</h3> <b>Objectives</b> To determine the effect of the critical care outreach team on patient survival to discharge from hospital after discharge from critical care and readmission to critical care. <b>Design</b> Non-randomised population based study. <b>Setting</b> Tertiary referral teaching hospital with 1200 beds. <b>Participants</b> Patients discharged from the critical care unit after their first or only admission for two study periods, 26 February 2000 to 25 February 2001 and 26 February 2001 to 25 February 2002. <b>Main outcome measures</b> Survival to discharge from hospital after discharge from critical care and readmission to critical care. <b>Results</b> The introduction of a critical care outreach team improved survival to discharge from hospital after discharge from critical care by 6.8% (risk ratio 1.08). Readmission to critical care decreased by 6.4% (0.48). <b>Conclusions</b> The activity of the critical care outreach team seems to improve patient survival to discharge from hospital and may reduce the number of readmissions to critical care.
The Cancer Genome Atlas Pan-Cancer analysis project
Authors: John N Weinstein, Eric A Collisson, Gordon B Mills, Kenna R Mills Shaw, Brad A Ozenberger, Kyle Ellrott, Ilya Shmulevich, Chris Sander, Joshua M Stuart
Journal: Nature Genetics (2013)

Current clinical practice is organized according to tissue or organ of origin of tumors. Now, The Cancer Genome Atlas (TCGA) Research Network has started to identify genomic and other molecular commonalities among a dozen different types of cancer. Emerging similarities and contrasts will form the basis for targeted therapies of the future and for repurposing existing therapies by molecular rather than histological similarities of the diseases. The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile.
The Hedgehog pathway as targetable vulnerability with 5-azacytidine in myelodysplastic syndrome and acute myeloid leukemia
Authors: Raoul Tibes, Aref Al-Kali, Gavin R Oliver, Devora H Delman, Nanna Hansen, Keerthi Bhagavatula, Jayaram Mohan, Fariborz Rakhshan, Thomas Wood, James M. Foran, Ruben A. Mesa, James M. Bogenberger
Journal: Journal of Hematology & Oncology (2015)

Therapy and outcome for elderly acute myeloid leukemia (AML) patients has not improved for many years. Similarly, there remains a clinical need to improve response rates in advanced myelodysplastic syndrome (MDS) patients treated with hypomethylating agents, and few combination regimens have shown clinical benefit. We conducted a 5-azacytidine (5-Aza) RNA-interference (RNAi) sensitizer screen to identify gene targets within the commonly deleted regions (CDRs) of chromosomes 5 and 7, whose silencing enhances the activity of 5-Aza. An RNAi silencing screen of 270 genes from the CDRs of chromosomes 5 and 7 was performed in combination with 5-Aza treatment in four AML cell lines (TF-1, THP-1, MDS-L, and HEL). Several genes within the hedgehog pathway (HhP), specifically SHH, SMO, and GLI3, were identified as 5-Aza sensitizing hits. The smoothened (SMO) inhibitors LDE225 (erismodegib) and GDC0449 (vismodegib) showed moderate single-agent activity in AML cell lines. Further studies with erismodegib in combination with 5-Aza demonstrated synergistic activity with combination index (CI) values of 0.48 to 0.71 in seven AML lines. Clonogenic growth of primary patient samples was inhibited to a greater extent in the combination than with single-agent erismodegib or 5-Aza in 55 % (6 of 11) primary patient samples examined. There was no association of the 5-Aza/erismodegib sensitization potential to clinical-cytogenetic features or common myeloid mutations. Activation of the HhP, as determined by greater expression of HhP-related genes, showed less responsiveness to single-agent SMO inhibition, while synergy between both agents was similar regardless of HhP gene expression. In vitro experiments suggested that concurrent dosing showed stronger synergy than sequential dosing. Inhibition of the HhP with SMO inhibitors in combination with the hypomethylating agent 5-Aza demonstrates synergy in vitro and inhibits long-term repopulation capacity ex vivo in AML and MDS. A clinical trial combining 5-Aza with LDE225 (erismodegib) in MDS and AML is ongoing based on these results as well as additional publications suggesting a role for HhP signaling in myeloid disease.
Vascular endothelium is critically involved in the hypotensive and hypovolemic actions of atrial natriuretic peptide
Authors: Karim Sabrane, Markus N. Kruse, Larissa Fabritz, Bernd Zetsche, Danuta Mitko, Boris V. Skryabin, Melanie Zwiener, Hideo A. Baba, Masashi Yanagisawa, Michaela Kuhn
Journal: Journal of Clinical Investigation (2005)

Atrial natriuretic peptide (ANP), via its vasodilating and diuretic effects, has an important physiological role in the maintenance of arterial blood pressure and volume. Its guanylyl cyclase-A (GC-A) receptor is highly expressed in vascular endothelium, but the functional relevance of this is controversial. To dissect the endothelium-mediated actions of ANP in vivo, we inactivated the GC-A gene selectively in endothelial cells by homologous loxP/Tie2-Cre–mediated recombination. Notably, despite full preservation of the direct vasodilating effects of ANP, mice with endothelium-restricted deletion of the GC-A gene (EC GC-A KO) exhibited significant arterial hypertension and cardiac hypertrophy. Echocardiographic and Doppler flow evaluations together with the Evan’s blue dilution technique showed that the total plasma volume of EC GC-A KO mice was increased by 11–13%, even under conditions of normal dietary salt intake. Infusion of ANP caused immediate increases in hematocrit in control but not in EC GC-A KO mice, which indicated that ablation of endothelial GC-A completely prevented the acute contraction of intravascular volume produced by ANP. Furthermore, intravenous ANP acutely enhanced the rate of clearance of radio-iodinated albumin from the circulatory system in control but not in EC GC-A KO mice. We conclude that GC-A–mediated increases in endothelial permeability are critically involved in the hypovolemic, hypotensive actions of ANP.
Regulation Dynamics of WGD Genes during Yeast Metabolic Oscillation
Authors: H. Chen, L. Xu, Z. Gu
Journal: Molecular Biology and Evolution (2008)

Saccharomyces cerevisiae and its close relatives are characterized by their propensity to ferment even in the presence of oxygen. It was hypothesized that whole-genome duplication (WGD) led to the development of this efficient fermentative lifestyle (WGD–fermentation hypothesis, Piskur 2001. In this study, we found that a significantly higher proportion of WGD genes than non-WGD genes are dynamically regulated during metabolic oscillation in response to oxygen change. The same data set also shows that the WGD genes, as compared with the smaller scale duplicate genes, are enriched with pairs where both copies have cyclic expression during the metabolic oscillation (either with the same or different phases). These results provide new evidences for the WGD–fermentation hypothesis and new insights into the relationship between the genome duplication and the evolution of new lifestyles in eukaryotic organisms.
Epigenomics and chromatin dynamics
Authors: Veronika Akopian, Michelle M Chan, Kendell Clement, Christina Galonska, Casey A Gifford, Elizabeth Lehtola, Jing Liao, Payman Samavarchi-Tehrani, Camille Sindhu, Zachary D Smith, Alexander M Tsankov, Jamie Webster, Yingying Zhang, Michael J Ziller, Alexander Meissner
Journal: Genome biology (2012)

A report of the 'Joint Keystone Symposium on Epigenomics and Chromatin Dynamics', Keystone, Colorado, 17-22 January 2012.
Evaluation of the symptomatic and structural efficacy of a new hyaluronic acid compound, NRD101, in comparison with diacerein and placebo in a 1 year randomised controlled study in symptomatic knee osteoarthritis
Authors: T Pham
Journal: Annals of the Rheumatic Diseases (2004)

<b>Objective:</b> To evaluate long term efficacy of three iterative courses of three weekly intra-articular (IA) injections of NRD101 in the treatment of symptomatic knee osteoarthritis (OA). <b>Patients and methods:</b> A 1 year prospective, multicentre, randomised, double blind, placebo controlled study of 301 patients aged &gt;50 years with painful and radiological medial knee OA. Patients were randomly assigned into three groups receiving: (1) three courses of three IA injections of hyaluronic acid (HA) + oral placebo; (2) IA injections of saline solution + diacerein 100 mg/day; (3) IA injections of saline solution + oral placebo. Demographic data and symptomatic criteria—pain, Lequesne’s index, patient’s global assessment of disease activity, percentage of painful days—were obtained during the study; primary structural criterion was JSW. Efficacy criteria were changes in pain VAS, joint space narrowing (JSN), and percentage of progressors (JSN &gt;0.5 mm). An intention to treat analysis was used for symptomatic variables, and completer analysis for structural variables. <b>Results:</b> Baseline characteristics were similar between the three groups. Mean (SD) improvement in pain VAS was clinically relevant (−33.9 (27.3), n = 301), but with no difference between the groups (p = 0.96). JSW deteriorated (−0.09 (0.55) mm, n = 277, p = 0.01), but with no difference between the groups (p = 0.82). Percentages of progressors were 17.7, 18.9, and 20.3% (p = 0.90), in groups 1, 2, and 3, respectively. <b>Conclusion:</b> A weak but statistically significant structural deterioration occurred over 1 year, together with clinically relevant symptomatic improvement in patients receiving oral drug and iterative IA injections. Symptomatic and/or structural effects for both this new HA compound and diacerein were not demonstrated.
FXR activation inhibits inflammation and preserves the intestinal barrier in IBD
Authors: M. E. Wildenberg, G. R. van den Brink
Journal: Gut (2011)

Bile salts are produced in the liver and delivered to the duodenum, where they emulsify lipids to facilitate absorption. After passing through the small intestine, the majority of bile salts are reabsorbed for recycling in the terminal ileum. One of the key receptors involved in this reabsorption is the farnesoid X receptor (FXR), a member of the family of nuclear receptors which function as transcription factors. FXR signalling regulates target genes involved in bile acid synthesis (CYP7a), efflux (ABCB11) and absorption of conjugated bile acids (IBABP).

In line with the role of FXR in bile homeostasis, FXR–/– mice were initially described to have aberrancies in bile acid and lipid homeostasis, with elevated cholesterol levels in both liver and serum.1 Interestingly, when these animals were followed up for longer periods, hepatic levels of the proinflammatory cytokines interferon γ, interleukin 6 (IL-6) and tumour necrosis factor α (TNFα) were increased, suggesting an additional role for FXR in immunoregulation.2 This role was further confirmed in ApoE–/– mice, which develop aortic plaques after being fed a high-cholesterol diet. Administration of an FXR agonist reduced plaque formation as well as intraplaque expression of inflammatory mediators, supporting an immunomodulatory …
Tolerant B Lymphocytes Acquire Resistance to Fas-mediated Apoptosis after Treatment with Interleukin 4 but Not after Treatment with Specific Antigen Unless a Surface Immunoglobulin Threshold Is Exceeded
Authors: Linda C. Foote, Ann Marshak-Rothstein, Thomas L. Rothstein
Journal: The Journal of Experimental Medicine (1998)

Susceptibility to Fas-mediated apoptosis in nontolerant B cells is regulated in a receptor-specific fashion. To explore the regulation of Fas killing in tolerant, autoreactive B cells, mice doubly transgenic for hen egg lysozyme (HEL)–specific B cell receptors and soluble HEL were examined. Engagement of CD40 led to enhanced Fas expression and acquisition of sensitivity to Fas-mediated apoptosis in tolerant B cells, similar to that observed in nontolerant, receptor transgenic B cells. Engagement of surface immunoglobulin by specific (HEL) antigen failed to induce Fas resistance in tolerant B cells, in contrast to its effect on nontolerant B cells; however, cross-linking of biotinylated HEL with streptavidin induced similar levels of Fas resistance in tolerant and nontolerant B cells, which approximated the degree of Fas resistance produced by anti-Ig. Unlike surface Ig (sIg) engagement, physiological engagement of IL-4 receptors produced similar levels of Fas resistance in tolerant and nontolerant B cells. Thus, tolerant B cells differ from nontolerant B cells in the diminished capacity of surface immunoglobulin engagement to produce Fas resistance; however, tolerant B cells can be induced to become resistant to Fas-mediated apoptosis by IL-4 or by higher order cross-linking of sIg receptors.
Blood Lead Levels and Death from All Causes, Cardiovascular Disease, and Cancer: Results from the NHANES III Mortality Study
Authors: Susan E. Schober, Lisa B. Mirel, Barry I. Graubard, Debra J. Brody, Katherine M. Flegal
Journal: Environmental Health Perspectives (2006)

BackgroundAnalyses of mortality data for participants examined in 1976–1980 in the second National Health and Nutrition Examination Survey (NHANES II) suggested an increased risk of mortality at blood lead levels > 20 μg/dL. Blood lead levels have decreased markedly since the late 1970s. In NHANES III, conducted during 1988–1994, few adults had levels > 20 μg/dL.ObjectiveOur objective in this study was to determine the risk of mortality in relation to lower blood lead levels observed for adult participants of NHANES III.MethodsWe analyzed mortality information for 9,757 participants who had a blood lead measurement and who were ≥ 40 years of age at the baseline examination. Using blood lead levels categorized as < 5, 5 to < 10, and ≥ 10 μg/dL, we determined the relative risk of mortality from all causes, cancer, and cardiovascular disease through Cox proportional hazard regression analysis.ResultsUsing blood lead levels < 5 μg/dL as the referent, we determined that the relative risk of mortality from all causes was 1.24 [95% confidence interval (CI), 1.05–1.48] for those with blood levels of 5–9 μg/dL and 1.59 (95% CI, 1.28–1.98) for those with blood levels ≥ 10 μg/dL (p for trend < 0.001). The magnitude of risk was similar for deaths due to cardiovascular disease and cancer, and tests for trend were statistically significant (p < 0.01) for both causes of death.ConclusionIn a nationally representative sample of the U.S. population, blood lead levels as low as 5–9 μg/dL were associated with an increased risk of death from all causes, cardiovascular disease, and cancer.
Alpha E: Table I.
Authors: Peter J. Kilshaw, Jonathan M.G. Higgins
Journal: The Journal of Experimental Medicine (2002)

Integrin αEβ7 (CD103) has been an enigmatic and tantalizing molecule (1). The history of experiments on its functional significance is a record of promise and disappointment in equal measure. CD103 has been considered to have a role mainly or exclusively in the mucosal immune system, but this supposition now needs to be reappraised. The molecule is expressed at high levels by mucosal T cells, especially the CD8+ population in the epithelium of the gut, but is found on small subsets of T cells elsewhere. It is also present on mucosal mast cells and mucosal dendritic APCs. This eccentric pattern of expression has recently been extended to include splenic CD4+ CD25+ Treg cells, ∼30% of which are CD103+ (2). A plausible explanation for the expression profile is that the αE subunit is transcriptionally regulated by transforming growth factor (TGF)-β. In fact, no other stimulus has consistently been shown to induce expression. Thus, CD103 is found on T cells residing in tissue microenvironments where bioactive TGF-β is abundant. This is often the case in the vicinity of epithelia and in situations in which chronic inflammation is taking place. The particular association of CD103+ cells with epithelia is also explained by the fact that its principal ligand is E-cadherin, an epithelial homophilic adhesion molecule. The relationships between the integrins discussed here and their ligands are shown in Table I.



Table I.





Studies on CD103 function have, until now, met with mixed fortunes. Like other integrins, when ligated it provides costimulation for T cell proliferation and effector function. Importantly, the interaction between CD103 and E-cadherin will substitute for that between lymphocyte function–associated antigen (LFA)-1 and intercellular adhesion molecule (ICAM)-1 in CD8+-mediated CTL effector function (3). This could be especially significant for epithelial target cells, which often lack ICAM-1. It has been suggested that CD103 could function as a homing receptor encouraging T cells to extravasate to the gut. However, the balance of evidence more clearly favors a role in retention or microlocalization of T cells in the vicinity of epithelia rather than in mucosal-specific homing. In contrast, the sister integrin of CD103, α4β7, is known to play an important role in the homing of leukocytes to mucosal sites. Initial studies on the CD103−/− mouse were somewhat disappointing in that the only noticeable change was a modest reduction in the numbers of mucosal T cells and a T cell–dependent dermatitis of unknown etiology (4–6).
Functional interaction between human histocompatibility leukocyte antigen (HLA) class II and mouse CD4 molecule in antigen recognition by T cells in HLA-DR and DQ transgenic mice.
Authors: K Yamamoto, Y Fukui, Y Esaki, T Inamitsu, T Sudo, K Yamane, N Kamikawaji, A Kimura, T Sasazuki
Journal: The Journal of Experimental Medicine (1994)

Studies in vitro have suggested that a species barrier exists in functional interaction between human histocompatibility leukocyte antigen (HLA) class II and mouse CD4 molecules. However, whether mouse CD4+ T cells restricted by HLA class II molecules are generated in HLA class II transgenic mice and respond to peptide antigens across this barrier has remained unclear. In an analysis of T cell responses to synthetic peptides in mice transgenic for HLA-DR51 and -DQ6, we found that DR51 and DQ6 transgenic mice acquired significant T cell response to influenza hemagglutinin-derived peptide 307-319 (HA 307) and Streptococcus pyogenes M12 protein-derived peptide 347-397 (M6C2), respectively. Inhibition studies with several monoclonal antibodies showed that transgenic HLA class II molecules presented these peptides to mouse CD4+ T cells. Furthermore, T cell lines specific for HA 307 or M6C2 obtained from the transgenic mice could respond to the peptide in the context of relevant HLA class II molecules expressed on mouse L cell transfectants that lack the expression of mouse MHC class II. These findings indicate that interaction between HLA class II and mouse CD4 molecules is sufficient for provoking peptide-specific HLA class II-restricted T cell responses in HLA class II transgenic mice.
METASTASISING ISLET-CELL TUMOUR OF THE PANCREAS ASSOCIATED WITH HYPOGLYCÆMIA AND CARCINOID SYNDROME
Authors: J. van der Sluys Veer, J.C. Choufoer, A. Querido, R.O. Van Der Heul, C.F. Hollander, T.G. Van Rijssel
Journal: The Lancet (1964)
271 MIR-221/MDM2/P53 CONTROL LOOP SENSITIZES HEPATOCELLULAR CARCINOMA CELLS TO ANTI-CANCER TREATMENTS
Authors: F. Fornari, M. Milazzo, C. Giovannini, M. Galassi, M. Negrini, L. Gramantieri, L. Bolondi
Journal: Journal of Hepatology (2012)
Altruism is never self-sacrifice
Authors: Michael Lewis
Journal: Behavioral and Brain Sciences (2002)

Altruism by definition involves the self's evaluation of costs and benefits of an act of the self, which must include cost to the self and benefits to the other. Reinforcement value to the self of such acts is greater than the costs to the self. Without consideration of a self-system of evaluation, there is little meaning to altruistic acts.
Use of Yeast-Secreted <i>In vivo</i> Biotinylated Recombinant Antibodies (Biobodies) in Bead-Based ELISA
Authors: Nathalie Scholler, Kimberly A. Lowe, Lindsay A. Bergan, Archana V. Kampani, Vivian Ng, Robin M. Forrest, Jason D. Thorpe, Jenny A. Gross, Barbara M. Garvik, Ronny Drapkin, Garnet L. Anderson, Nicole Urban
Journal: Clinical Cancer Research (2008)

Abstract Purpose: To measure circulating antigens, sandwich ELISA assays require two complementary affinity reagents. Mouse monoclonal antibodies (mAb) and polyclonal antibodies (pAb) are commonly used, but because their production is lengthy and costly, recombinant antibodies are emerging as an attractive alternative. Experimental Design: We developed a new class of recombinant antibodies called biobodies (Bb) and compared them to mAb for use in serodiagnosis. Bbs were secreted biotinylated in vivo by diploid yeast and used as affinity reagents after Ni purification. Bead-based assays for HE4 and mesothelin were developed using Bbs in combination with pAbs (Bb/pAb assays). To assess precision, reproducibility studies were done using four runs of 16 replicates at six analyte levels for each marker. Pearson correlations and receiver-operator characteristic analyses were done in 214 patient serum samples to directly compare the Bb/pAb assays to mAb assays. Diagnostic performance of the Bb/pAb assay was further assessed in an expanded set of 336 ovarian cancer cases and controls. Results: On average across analyte levels, Bb/pAb assays yielded within-run and between-run coefficients of variations of 11.7 and 23.8, respectively, for HE4 and 14.0 and 14.5, respectively, for mesothelin. In the subset (n = 214), Pearson correlations of 0.95 for HE4 and 0.92 for mesothelin were observed between mAb and Bb/pAb assays. The area under the curves for the mAb and Bb/pAb assays were not significantly different for HE4 (0.88 and 0.84, respectively; P = 0.20) or mesothelin (0.74 and 0.72, respectively; P = 0.38). Conclusion: Yeast-secreted Bbs can be used reliably in cost-effective yet highly sensitive bead–based assays for use in large validation studies.