tbuckley/cabot-search huggingface dataset:
40 EBP50, A PDZ-CONTAINING PROTEIN, REGULATES EGFR-INDUCED CELL SCATTERING AND MIGRATION IN HUMAN CANCER BILIARY EPITHELIAL CELLS
Authors: A. Clapéron, M. Mergey, N. Guedj, B. de Singly, Y. Chrétien, V. Paradis, C. Housset, L. Fouassier
Journal: Journal of Hepatology (2010)
Renal Epithelium Is a Previously Unrecognized Site of HIV-1 Infection
Authors: LESLIE A. BRUGGEMAN, MICHAEL D. ROSS, NOZOMU TANJI, ANDREA CARA, STEVEN DIKMAN, RONALD E. GORDON, GODFREY C. BURNS, VIVETTE D. D'AGATI, JONATHAN A. WINSTON, MARY E. KLOTMAN, PAUL E. KLOTMAN
Journal: Journal of the American Society of Nephrology (2000)

Abstract. The striking emergence of an epidemic of HIV-related renal disease in patients with end-stage renal disease provided the rationale for the exploration of whether HIV-1 directly infects renal parenchymal cells. Renal glomerular and tubular epithelial cells contain HIV-1 mRNA and DNA, indicating infection by HIV-1. In addition, circularized viral DNA, a marker of recent nuclear import of full-length, reverse-transcribed RNA, was detected in the biopsies, suggesting active replication in renal tissue. Infiltrating infected leukocytes harbored more viral mRNA than renal epithelium. Identification of this novel reservoir suggests that effectively targeting the kidney with antiretrovirals may be critical for patients who are seropositive with renal disease. Thus, renal epithelium constitutes a unique and previously unrecognized cell target for HIV-1 infection.
Aberrant Chemokine Receptor Expression and Chemokine Production by Langerhans Cells Underlies the Pathogenesis of Langerhans Cell Histiocytosis
Authors: Nicola E. Annels, Cristiana E.T. da Costa, Frans A. Prins, Annemieke Willemze, Pancras C.W. Hogendoorn, R. Maarten Egeler
Journal: The Journal of Experimental Medicine (2003)

Langerhans cell histiocytosis (LCH) is characterized by a clonal proliferation and retention of cells with a Langerhans cell (LC)-like phenotype at various sites within the body. The present study set out to elucidate whether aberrant expression of chemokine receptors or dysregulation of chemokine production in LCH lesions could explain abnormal retention of these cells. Immunohistochemical analysis on 13 LCH biopsies of bone, skin, and lymph node all expressed the immature dendritic cell (DC) marker CCR6 on the lesional LCs and absence of the mature DC marker CCR7. Furthermore, regardless of the tissue site, LCH lesions markedly overexpressed CCL20/MIP-3α, the ligand for CCR6. The lesional LCs appeared to be the source of this CCL20/MIP-3α production as well as other inflammatory chemokines such as CCL5/RANTES and CXCL11/I-TAC. These may explain the recruitment of eosinophils and CD4+CD45RO+ T cells commonly found in LCH lesions. The findings of this study emphasize that, despite abundant TNF-α, lesional LCs remain in an immature state and are induced to produce chemokines, which via autocrine and paracrine mechanisms cause not only the retention of the lesional LCs but also the recruitment and retention of other lesional cells. We postulate that the lesional LCs themselves control the persistence and progression of LCH.
Somatic and Germ-Line Mutations of the<i>HRPT2</i>Gene in Sporadic Parathyroid Carcinoma
Authors: Trisha M. Shattuck, Stiina Välimäki, Takao Obara, Randall D. Gaz, Orlo H. Clark, Dolores Shoback, Margaret E. Wierman, Katsuyoshi Tojo, Christiane M. Robbins, John D. Carpten, Lars-Ove Farnebo, Catharina Larsson, Andrew Arnold
Journal: New England Journal of Medicine (2003)

We looked for mutations of the HRPT2 gene, which encodes the parafibromin protein, in sporadic parathyroid carcinoma because germ-line inactivating HRPT2 mutations have been found in a type of familial hyperparathyroidism--hyperparathyroidism-jaw tumor (HPT-JT) syndrome--that carries an increased risk of parathyroid cancer.We directly sequenced the full coding and flanking splice-junctional regions of the HRPT2 gene in 21 parathyroid carcinomas from 15 patients who had no known family history of primary hyperparathyroidism or the HPT-JT syndrome at presentation. We also sought to confirm the somatic nature of the identified mutations and tested the carcinomas for tumor-specific loss of heterozygosity at HRPT2.Parathyroid carcinomas from 10 of the 15 patients had HRPT2 mutations, all of which were predicted to inactivate the encoded parafibromin protein. Two distinct HRPT2 mutations were found in tumors from five patients, and biallelic inactivation as a result of a mutation and loss of heterozygosity was found in one tumor. At least one HRPT2 mutation was demonstrably somatic in carcinomas from six patients. Unexpectedly, HRPT2 mutations in the parathyroid carcinomas of three patients were identified as germ-line mutations.Sporadic parathyroid carcinomas frequently have HRPT2 mutations that are likely to be of pathogenetic importance. Certain patients with apparently sporadic parathyroid carcinoma carry germ-line mutations in HRPT2 and may have the HPT-JT syndrome or a phenotypic variant.
Elicitation of delayed-type hypersensitivity to phosphorylcholine by monoclonal anti-idiotypic antibodies in an allogeneic environment.
Authors: B Arnold, R Wallich, G J Hämmerling
Journal: The Journal of Experimental Medicine (1982)

Delayed-type hypersensitivity (DTH) to phosphorylcholine (PC) could be elicited by mixtures of monoclonal anti-idiotypic antibodies. Using this system in DTH transfers, the question was asked of whether anti-idiotypic antibodies could elicit antigen induced DTH in H-2-incompatible mice. Transfer of PC-activated BALB/c lymph node cells into BALB.K mice and subsequent elicitation with anti-idiotypic antibodies resulted in a positive DTH response. In contrast, elicitation with the antigen PC showed the expected H-2 restriction.
Transcript Level Modulates the Inherent Oncogenicity of RET/PTC Oncoproteins
Authors: Douglas S. Richardson, Taranjit S. Gujral, Susan Peng, Sylvia L. Asa, Lois M. Mulligan
Journal: Cancer Research (2009)

Abstract Mutations to the RET proto-oncogene occur in as many as one in three cases of thyroid cancer and have been detected in both the medullary (MTC) and the papillary (PTC) forms of the disease. Of the nearly 400 chromosomal rearrangements resulting in oncogenic fusion proteins that have been identified to date, the rearrangements that give rise to RET fusion oncogenes in PTC remain the paradigm for chimeric oncoprotein involvement in solid tumors. RET-associated PTC tumors are phenotypically indolent and relatively less aggressive than RET-related MTCs. The mechanism(s) contributing to the differences in oncogenicity of RET-related MTC and PTC remains unexplained. Here, through cellular and molecular characterization of the two most common RET/PTC rearrangements (PTC1 and PTC3), we show that RET/PTC oncoproteins are highly oncogenic when overexpressed, with the ability to increase cell proliferation and transformation. Further, RET/PTCs activate similar downstream signaling cascades to wild-type RET, although at different levels, and are relatively more stable as they avoid lysosomal degradation. Absolute quantitation of transcript levels of RET, CCDC6, and NCOA4 (the 5′ fusion genes involved in PTC1 and PTC3, respectively) suggest that these rearrangements result in lower RET expression in PTCs relative to MTCs. Together, our findings suggest PTC1 and PTC3 are highly oncogenic proteins when overexpressed, but result in indolent disease compared with RET-related MTCs due to their relatively low expression from the NCOA4 and CCDC6 promoters in vivo. [Cancer Res 2009;69(11):4861–9]
Conversion of <i>Helicobacter pylori</i> CagA from senescence inducer to oncogenic driver through polarity-dependent regulation of p21
Authors: Yasuhiro Saito, Naoko Murata-Kamiya, Toshiya Hirayama, Yusuke Ohba, Masanori Hatakeyama
Journal: The Journal of Experimental Medicine (2010)

The Helicobacter pylori CagA bacterial oncoprotein plays a critical role in gastric carcinogenesis. Upon delivery into epithelial cells, CagA causes loss of polarity and activates aberrant Erk signaling. We show that CagA-induced Erk activation results in senescence and mitogenesis in nonpolarized and polarized epithelial cells, respectively. In nonpolarized epithelial cells, Erk activation results in oncogenic stress, up-regulation of the p21(Waf1/Cip1) cyclin-dependent kinase inhibitor, and induction of senescence. In polarized epithelial cells, CagA-driven Erk signals prevent p21(Waf1/Cip1) expression by activating a guanine nucleotide exchange factor-H1-RhoA-RhoA-associated kinase-c-Myc pathway. The microRNAs miR-17 and miR-20a, induced by c-Myc, are needed to suppress p21(Waf1/Cip1) expression. CagA also drives an epithelial-mesenchymal transition in polarized epithelial cells. These findings suggest that CagA exploits a polarity-signaling pathway to induce oncogenesis.
Autoantibodies against IL-17A, IL-17F, and IL-22 in patients with chronic mucocutaneous candidiasis and autoimmune polyendocrine syndrome type I
Authors: Anne Puel, Rainer Döffinger, Angels Natividad, Maya Chrabieh, Gabriela Barcenas-Morales, Capucine Picard, Aurélie Cobat, Marie Ouachée-Chardin, Antoine Toulon, Jacinta Bustamante, Saleh Al-Muhsen, Mohammed Al-Owain, Peter D. Arkwright, Colm Costigan, Vivienne McConnell, Andrew J. Cant, Mario Abinun, Michel Polak, Pierre-François Bougnères, Dinakantha Kumararatne, László Marodi, Amit Nahum, Chaim Roifman, Stéphane Blanche, Alain Fischer, Christine Bodemer, Laurent Abel, Desa Lilic, Jean-Laurent Casanova
Journal: The Journal of Experimental Medicine (2010)

Most patients with autoimmune polyendocrine syndrome type I (APS-I) display chronic mucocutaneous candidiasis (CMC). We hypothesized that this CMC might result from autoimmunity to interleukin (IL)-17 cytokines. We found high titers of autoantibodies (auto-Abs) against IL-17A, IL-17F, and/or IL-22 in the sera of all 33 patients tested, as detected by multiplex particle-based flow cytometry. The auto-Abs against IL-17A, IL-17F, and IL-22 were specific in the five patients tested, as shown by Western blotting. The auto-Abs against IL-17A were neutralizing in the only patient tested, as shown by bioassays of IL-17A activity. None of the 37 healthy controls and none of the 103 patients with other autoimmune disorders tested had such auto-Abs. None of the patients with APS-I had auto-Abs against cytokines previously shown to cause other well-defined clinical syndromes in other patients (IL-6, interferon [IFN]-gamma, or granulocyte/macrophage colony-stimulating factor) or against other cytokines (IL-1beta, IL-10, IL-12, IL-18, IL-21, IL-23, IL-26, IFN-beta, tumor necrosis factor [alpha], or transforming growth factor beta). These findings suggest that auto-Abs against IL-17A, IL-17F, and IL-22 may cause CMC in patients with APS-I.
The responsiveness and validity of the CAMPHOR Utility Index
Authors: D. M. Meads, S. P. McKenna, N. Doughty, C. Das, W. Gin-Sing, J. Langley, J. Pepke-Zaba
Journal: European Respiratory Journal (2008)

The aim of the present study was to validate and determine the mininal important difference (MID) and responsiveness of the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) Utility Index, a new tool enabling cost utility analyses. CAMPHOR, 6-min walking test (6MWT) and New York Heart Association (NYHA) data for 869 pulmonary hypertension patients (545 (63%) female; mean± sd age 56.6±15.4 yrs) from three centres were analysed. Utility was correlated with 6MWT data and calculated by NYHA class to assess validity. Effect sizes were calculated for those with two CAMPHOR assessments. Distribution and anchor-based MIDs were calculated. Analyses were carried out in patients receiving bosentan in order to determine whether or not those remaining in NYHA class III following treatment improved. The Utility Index distinguished between adjacent NYHA classes and correlated with 6MWT results. CAMPHOR subscales and utility were as responsive as the 6MWT (effect sizes ranged 0.31–0.69 for the CAMPHOR and 0.16–0.34 for the 6MWT). The within-group MID for the Utility Index was estimated to be ∼0.09. Patients remaining in NYHA class III experienced, on average, a significant improvement (CAMPHOR Utility Index and functioning), which exceeded the MID. The CAMPHOR Utility Index is valid and responsive to change. Patients can experience significant and important improvements even if they do not improve on the basis of traditional outcomes, such as NYHA functional class.
Multidetector Computed Tomography for Acute Pulmonary Embolism
Authors: Paul D. Stein, Sarah E. Fowler, Lawrence R. Goodman, Alexander Gottschalk, Charles A. Hales, Russell D. Hull, Kenneth V. Leeper, John Popovich, Deborah A. Quinn, Thomas A. Sos, H. Dirk Sostman, Victor F. Tapson, Thomas W. Wakefield, John G. Weg, Pamela K. Woodard
Journal: New England Journal of Medicine (2006)

The accuracy of multidetector computed tomographic angiography (CTA) for the diagnosis of acute pulmonary embolism has not been determined conclusively.The Prospective Investigation of Pulmonary Embolism Diagnosis II trial was a prospective, multicenter investigation of the accuracy of multidetector CTA alone and combined with venous-phase imaging (CTA-CTV) for the diagnosis of acute pulmonary embolism. We used a composite reference test to confirm or rule out the diagnosis of pulmonary embolism.Among 824 patients with a reference diagnosis and a completed CT study, CTA was inconclusive in 51 because of poor image quality. Excluding such inconclusive studies, the sensitivity of CTA was 83 percent and the specificity was 96 percent. Positive predictive values were 96 percent with a concordantly high or low probability on clinical assessment, 92 percent with an intermediate probability on clinical assessment, and nondiagnostic if clinical probability was discordant. CTA-CTV was inconclusive in 87 of 824 patients because the image quality of either CTA or CTV was poor. The sensitivity of CTA-CTV for pulmonary embolism was 90 percent, and specificity was 95 percent. CTA-CTV was also nondiagnostic with a discordant clinical probability.In patients with suspected pulmonary embolism, multidetector CTA-CTV has a higher diagnostic sensitivity than does CTA alone, with similar specificity. The predictive value of either CTA or CTA-CTV is high with a concordant clinical assessment, but additional testing is necessary when the clinical probability is inconsistent with the imaging results.
Increases in walking distance in patients with peripheral vascular disease treated with L-carnitine: a double-blind, cross-over study.
Authors: G Brevetti, M Chiariello, G Ferulano, A Policicchio, E Nevola, A Rossini, T Attisano, G Ambrosio, N Siliprandi, C Angelini
Journal: Circulation (1988)

A double-blind, cross-over study was designed to evaluate the effects of L-carnitine in patients with peripheral vascular disease. After drug washout, 20 patients were randomly assigned to receive placebo or L-carnitine (2 g bid, orally) for a period of 3 weeks and were then crossed over to the other treatment for an additional 3 weeks. The effect on walking distance at the end of each treatment period was measured by treadmill test. Absolute walking distance rose from 174 +/- 63 m with placebo to 306 +/- 122 m (p less than .01) with carnitine. Biopsy of the ischemic muscle, carried out before and after 15 days of L-carnitine administration in four additional patients, showed that treatment significantly increased total carnitine levels. An additional goal of this study was to ascertain the effects of L-carnitine on the metabolic changes induced by exercise in the affected limb. In six patients under control conditions, arterial and popliteal venous lactate and pyruvate concentrations were determined at rest, when the maximal walking distance was reached, and 5 min after the walking test. Twenty-four hours later, L-carnitine was administered intravenously (3 g as a bolus followed by an infusion of 2 mg/kg/min for 30 min) and metabolic assessments were repeated. Five minutes after the walking test, popliteal venous lactate concentration increased by 107 +/- 16% before treatment and by only 54 +/- 32% (p less than .01) after carnitine. Furthermore, carnitine induced a more rapid recovery to the resting value of the lactate/pyruvate ratio.(ABSTRACT TRUNCATED AT 250 WORDS)
Renal Bone Morphogenetic Protein-7 Protects against Diabetic Nephropathy
Authors: Shinong Wang, Mark de Caestecker, Jeffrey Kopp, Grace Mitu, Janine LaPage, Raimund Hirschberg
Journal: Journal of the American Society of Nephrology (2006)

Longstanding diabetes causes renal injury with early dropout of podocytes, albuminuria, glomerular and tubulointerstitial fibrosis, and progressive renal failure. The renal pathology seems to be driven, in part, by TGF-beta and is associated with a loss of renal bone morphogenic protein-7 (BMP-7) expression. Here, the hypothesis that maintenance of renal (especially podocyte) BMP-7 by transgenic expression reduces diabetic renal injury was tested. Diabetic mice that expressed the phosphoenolpyruvate carboxykinase promoter-driven BMP-7 transgene and nondiabetic, transgenic mice as well as diabetic and nondiabetic wild-type controls were studied for up to 1 yr. Transgenic expression of BMP-7 in glomerular podocytes and proximal tubules prevents podocyte dropout and reductions in nephrin levels in diabetic mice. Maintenance of BMP-7 also reduces glomerular fibrosis and interstitial collagen accumulation as well as collagen I and fibronectin expression. Diabetic wild-type mice develop progressive albuminuria, which is substantially reduced in transgenic mice. These effects of the BMP-7 transgene occur without changing renal TGF-beta levels. It is concluded that maintenance of renal BMP-7 during the evolution of diabetic nephropathy reduces diabetic renal injury, especially podocyte dropout. The findings also establish a role for endogenous glomerular BMP-7 as an autocrine regulator of podocyte integrity in vivo.
Excessive Alcohol Use in Manic-Depressive Illness
Authors: LOUIS H. REICH, JONATHAN M. HIMMELHOCH, ROBERT K. DAVIES
Journal: American Journal of Psychiatry (1974)

Of various factors the authors examined, only the excessive use of alcohol distinguished those manic patients with a history of hospitalization from those without one. Half of the hospitalized subjects had a history of an inordinate use of alcohol; this excessive use predominated during the manic phase, a fact that does not support the popular view that alcohol is used to counteract depression. Patients themselves frequently reported a deliberale use of alcohol to decrease manic symptoms and a tendency to shun alcohol during the depressive phase. Alcohol did not seem to alter the presenting symptoms of hospitalized manic patients, since irritability and the loss of impulse control were similar among the drinkers and nondrinkers.
Seroepidemiology of Middle East respiratory syndrome (MERS) coronavirus in Saudi Arabia (1993) and Australia (2014) and characterisation of assay specificity
Authors: M G Hemida, R A Perera, R A Al Jassim, G Kayali, L Y Siu, P Wang, K W Chu, S Perlman, M A Ali, A Alnaeem, Y Guan, L L Poon, L Saif, M Peiris
Journal: Eurosurveillance (2014)

The pseudoparticle virus neutralisation test (ppNT) and a conventional microneutralisation (MN) assay are specific for detecting antibodies to Middle East respiratory syndrome coronavirus (MERS-CoV) when used in seroepidemiological studies in animals. Genetically diverse MERS-CoV appear antigenically similar in MN tests. We confirm that MERS-CoV was circulating in dromedaries in Saudi Arabia in 1993. Preliminary data suggest that feral Australian dromedaries may be free of MERS-CoV but larger confirmatory studies are needed.
Evaluability Assessment to Improve Public Health Policies, Programs, and Practices
Authors: Laura C. Leviton, Laura Kettel Khan, Debra Rog, Nicola Dawkins, David Cotton
Journal: Annual Review of Public Health (2010)

Evaluability assessment, also commonly known as exploratory evaluation, has assisted the field of public health to improve programs and to develop a pragmatic, practice-based research agenda. Evaluability assessment was originally developed as a low-cost pre-evaluation activity to prepare better for conventional evaluations of programs, practices, and some policies. For public health programs, however, it serves several other important purposes: (a) giving program staff rapid, constructive feedback about program operations; (b) assisting the core public health planning and assurance functions by helping to develop realistic objectives and providing low-cost, rapid feedback on implementation; (c) navigating federal performance measurement requirements; (d) translating research into practice by examining the feasibility, acceptability, and adaptation of evidence-based practices in new settings and populations; and (e) translating practice into research by identifying promising new approaches to achieve public health goals.
In Vitro Desensitization of Beta Adrenergic Receptors in Human Neutrophils. ATTENUATION BY CORTICOSTEROIDS
Authors: Albert O. Davies, Robert J. Lefkowitz
Journal: Journal of Clinical Investigation (1983)

The receptor alterations involved in catecholamine-induced desensitization of adenylate cyclase in human neutrophils have been investigated as has the ability of hydrocortisone to modify such alterations. Incubation of human neutrophils with isoproterenol for 3 h in vitro resulted in an 86% reduction in the ability of isoproterenol to stimulate cyclic AMP accumulation in the cells. Two types of receptor alterations were documented. There was a 40% reduction in the number of beta adrenergic receptors (42 vs. 25 fmol/mg protein, P < 0.005) present after desensitization as assessed by [3H]dihydroalprenolol ([3H]DHA) binding. In addition the receptors appeared to be relatively uncoupled from adenylate cyclase. This uncoupling was assessed by examining the ability of the agonist isoproterenol to stabilize a high-affinity form of the receptor, detected by computer modelling of competition curves for [3H]DHA binding. Desensitized receptors were characterized by rightward-shifted agonist competition curves. When hydrocortisone was added to the desensitizing incubations (combined treatment) there was a statistically significant attenuation in the desensitization process as assessed by the ability of isoproterenol to increase cyclic AMP levels in the cells. Although combined treatment did not prevent the decline in receptor number, it did attenuate the uncoupling of the receptors. Combined treatment resulted in competition curves intermediate between the control and the rightward-shifted desensitization curves. Prednisolone was similar to hydrocortisone in attenuating isoproterenol-induced uncoupling. Thus, steroids appeared to attenuate agonist-induced desensitization of the beta adrenergic receptor-adenylate cyclase system by dampening the ability of agonists to uncouple receptors without modifying their ability to promote down-regulation of beta adrenergic receptors.
THE MECHANISM OF BLOCKADE OF THE RETICULOENDOTHELIAL SYSTEM
Authors: I. MacKay Murray
Journal: The Journal of Experimental Medicine (1963)

Rats were injected intravenously with various particulate materials with and without the addition of various stabilizing agents. One hour after the injection of the blockading colloid, a tracer dose of similar or different colloidal material was injected. A half-time clearance rate of the tracer dose greater than 4 minutes was taken as evidence of blockade of the RES. Blockade of the tracer dose occurred when the surface properties of the particles in both blockading and tracer doses were identical. Different particles stabilized by the same agent behaved as identical particles and identical particles stabilized by different agents behaved as different particles. The opsonization of a tracer dose of gelatin-stabilized colloid in vitro by a specific globulin fraction obtained from heterologous and homologous plasma prevented its blockade, while opsonization of both blockading and tracer doses with the same proteins resulted in blockade. However, when both blockading and tracer doses were opsonized with isologous globulins, blockade did not occur.