tbuckley/cabot-search huggingface dataset:
Nitrocellulose‐Based RAST to Detect IgE Antibodies in Workers Hypersensitive to Diphenylmethane‐4,4′‐Diisocyanate
Authors: E. Grunewalder, M. H. Karol
Journal: Allergy (1986)

RAST was performed using both nitrocellulose (NC) and paper discs to compare these solid supports for ability to detect IgE antibodies in sera from two patients with hypersensitivity to the industrial chemical, diphenylmethane‐4,4′‐diisocynate (MDI). NC discs had distinct advantages in case of coupling the hapten‐conjugate antigen to discs, and in use of lesser amounts of antigen. With regard to sensitivity, NC discs were better able to distinguish the positive sera from 34 control sera including those with elevated levels of total IgE. In both RAST systems, inhibition studies indicated high specificity of antibodies for MDI, with no reactivity detected toward the serum albumin portion of the MDI‐HSA conjugate antigen. However, only in the NC RAST did antibodies from both patients react with p‐tolyl isocyanate inhibitor. Based on the above results, NC discs displayed several advantages in RAST and are recommended for routine serological assay of isocyanate‐specific antibodies.
The national database of the German Collaborative Arthritis Centres: I. Structure, aims, and patients
Authors: A Zink
Journal: Annals of the Rheumatic Diseases (2001)

<h3>OBJECTIVE</h3> To describe the aims, principles, and content of the German rheumatological database and to present data on patient mix and healthcare provision for the year 1998. <h3>METHODS</h3> The German rheumatological database contains clinical and patient derived data of the outpatients with inflammatory rheumatic diseases seen at one of the 24 collaborative arthritis centres. The case mix, institutional context, and demographic features of 25 653 patients from the year 1998 were analysed. <h3>RESULTS</h3> 51% of the patients had rheumatoid arthritis, 23% seronegative spondyloarthropathies, including ankylosing spondylitis, psoriatic arthritis, and reactive arthritis, and 19% had vasculitis, including SLE (5%). The distribution of the age at onset of patients with RA with ⩽2 years9 disease duration was comparable with recent incidence data from population studies. The case mix differed between university departments and rheumatology hospitals as well as individual practices. 65% of the male and 46% of the female patients at ages 18–60 were still in gainful employment, the rates of employment were 14% below the population rates for women, and 11% below those for men. 62% of all patients had seen a rheumatologist within the first year of disease, 73% within the first two years. Ankylosing spondylitis was seen in rheumatological care much later than all other diseases (only 39% within the first year). The mean number of contacts with a rheumatologist was five a year; rheumatologists in individual practices saw their patients seven times a year on the average. Together with visits to the non-specialist doctor mainly treating the patient, the mean number of visits to the doctor for a rheumatic condition was 20 a year. <h3>CONCLUSION</h3> Large databases like this one give information about the patient case mix in different healthcare settings, about treatment practice, and about the consequences of disease. Patients treated in specialised rheumatology units in Germany are referred earlier than in the past, which probably reflects better regional cooperation due to the implementation of arthritis centres. University departments and outpatient clinics of rheumatology hospitals contribute considerably to the specialised care of patients with arthritis and connective tissue diseases.
Chromothripsis is a common mechanism driving genomic rearrangements in primary and metastatic colorectal cancer
Authors: Wigard P Kloosterman, Marlous Hoogstraat, Oscar Paling, Masoumeh Tavakoli-Yaraki, Ivo Renkens, Joost S Vermaat, Markus J van Roosmalen, Stef van Lieshout, Isaac J Nijman, Wijnand Roessingh, Ruben van 't Slot, José van de Belt, Victor Guryev, Marco Koudijs, Emile Voest, Edwin Cuppen
Journal: Genome biology (2011)

Structural rearrangements form a major class of somatic variation in cancer genomes. Local chromosome shattering, termed chromothripsis, is a mechanism proposed to be the cause of clustered chromosomal rearrangements and was recently described to occur in a small percentage of tumors. The significance of these clusters for tumor development or metastatic spread is largely unclear.We used genome-wide long mate-pair sequencing and SNP array profiling to reveal that chromothripsis is a widespread phenomenon in primary colorectal cancer and metastases. We find large and small chromothripsis events in nearly every colorectal tumor sample and show that several breakpoints of chromothripsis clusters and isolated rearrangements affect cancer genes, including NOTCH2, EXO1 and MLL3. We complemented the structural variation studies by sequencing the coding regions of a cancer exome in all colorectal tumor samples and found somatic mutations in 24 genes, including APC, KRAS, SMAD4 and PIK3CA. A pairwise comparison of somatic variations in primary and metastatic samples indicated that many chromothripsis clusters, isolated rearrangements and point mutations are exclusively present in either the primary tumor or the metastasis and may affect cancer genes in a lesion-specific manner.We conclude that chromothripsis is a prevalent mechanism driving structural rearrangements in colorectal cancer and show that a complex interplay between point mutations, simple copy number changes and chromothripsis events drive colorectal tumor development and metastasis.
Multifocal hepatocellular carcinoma presenting as prurigo: two cases
Authors: O. Dereure, J‐J. Guilhou
Journal: British Journal of Dermatology (2000)

Journal Article Multifocal hepatocellular carcinoma presenting as prurigo: two cases Get access O. Dereure, O. Dereure Department of Dermatology‐Phlebology, University Hospital of Montpellier, Hôpital Saint‐Eloi, 80 avenue Augustin Fliche, 34295 Montpellier Cedex 5, France E‐mail: ofdereure@wanadoo.fr Search for other works by this author on: Oxford Academic Google Scholar J‐J. Guilhou J‐J. Guilhou Department of Dermatology‐Phlebology, University Hospital of Montpellier, Hôpital Saint‐Eloi, 80 avenue Augustin Fliche, 34295 Montpellier Cedex 5, France E‐mail: ofdereure@wanadoo.fr Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 143, Issue 6, 1 December 2000, Pages 1331–1332, https://doi.org/10.1046/j.1365-2133.2000.03919.x Published: 01 December 2000
Enteric Neurons and Systemic Signals Couple Nutritional and Reproductive Status with Intestinal Homeostasis
Authors: Paola Cognigni, Andrew P. Bailey, Irene Miguel-Aliaga
Journal: Cell Metabolism (2011)

The gastrointestinal tract is emerging as a key regulator of appetite and metabolism, but daunting neuroanatomical complexity has hampered identification of the relevant signals. Invertebrate models could provide a simple and genetically amenable alternative, but their autonomic nervous system and its visceral functions remain largely unexplored. Here we develop a quantitative method based on defecation behavior to uncover a central role for the Drosophila intestine in the regulation of nutrient intake, fluid, and ion balance. We then identify a key homeostatic role for autonomic neurons and hormones, including a brain-gut circuit of insulin-producing neurons modulating appetite, a vasopressin-like system essential for fluid homeostasis, and enteric neurons mediating sex peptide-induced changes in intestinal physiology. These conserved mechanisms of visceral control, analogous to those found in the enteric nervous system and hypothalamic/pituitary axis, enable the study of autonomic control in a model organism that has proved instrumental in understanding sensory and motor systems.
Does locus-equation linearity really matter in consonant perception?
Authors: Lawrence Brancazio
Journal: Behavioral and Brain Sciences (1998)

This commentary focuses on the claim that perceptual demands have caused the linearity exhibited by locus equations. I discuss results of an experiment demonstrating that, contrary to Sussman et al.'s claims, locus equations do not have relevance for the perception of stop consonants. I therefore argue against the plausibility of the orderly output constraint.
Excess iron induces hepatic oxidative stress and transforming growth factor ?1 in genetic hemochromatosis
Authors: K Houglum, G A Ramm, D H Crawford, J L Witztum, L W Powell, M Chojkier
Journal: Hepatology (1997)

Genetic hemochromatosis (GH) is associated with excess iron deposition in hepatocytes, which results in progressive hepatic injury. The pathogenesis of hepatic injury in GH is poorly understood. In this study, we found enhanced oxidative stress in patients with GH, as evidenced by hepatic malondialdehyde (MDA)-protein adducts and by increased oxidatively modified serum proteins. MDA-lysine epitopes and oxidatively modified serum proteins, as well as immunoglobulin G autoantibodies against MDA-lysine epitopes, were increased in untreated GH patients and to a lesser extent in GH heterozygotes compared with normal individuals. These markers of ongoing oxidative stress decreased with phlebotomy treatment in GH patients. In addition, TGF-β1 colocalized with hepatic iron and MDA protein adducts in hepatocytes and sinusoidal cells of hepatic acinar zone 1 and normalized after iron removal. Our data suggest that iron overload increases both lipid peroxidation and TGF-β1 expression, which together could promote hepatic injury and fibrogenesis.
Single nucleotide polymorphism 25-TGF 1 as a possible marker of response to rituximab in rheumatoid arthritis
Authors: C. I. Daien, S. Fabre, C. Rittore, S. Soler, V. Daien, N. Molinari, I. Touitou, C. Jorgensen
Journal: Annals of the Rheumatic Diseases (2010)

BackgroundThe individual response to biological agents in severe rheumatoid arthritis (RA) is unpredictable in daily clinical practice.Despite improving our knowledge on genetic association using GWS in a large RA cohort, no genetic indicators predictive of clinical response to anti-CD20 treatment (rituximab) have been described.Objectives To analyse the association of several candidate gene polymorphisms with responsiveness to rituximab in patients with severe RA.Methods The clinical response of 47 French Caucasian RA patients was determined according to the European League Against Rheumatism criteria during the fi rst 6 months after rituximab treatment (intravenously 1000 mg one time at day 0, day 15).The clinical response was assessed at months 3 and 6 using the DAS-28 score.Twelve single nucleotide polymorphisms (SNPs) were genotyped: interleukin 10 (IL10) (-1087 IL-10), lymphotoxin A (LTA) (249-LTA and 720-LTA), transforming growth factor β (TGFβ1) (codon 25 TGFβ1), tumour necrosis factor α (TNFα) , TNF receptor II , receptor-associated factor 1 (-C5 TRAF1), signal transducer and activator of transcription 4 (STAT4), TNFα-induced protein 3 (TNFαIP3) and protein tyrosine phosphatase non-receptor type 22 (PTPN22).The Fisher test was used to analyse the impact of specifi c polymorphisms on treatment response.Results Eighteen patients were defi ned as good responders, 13 as moderate responders and 16 as non-responders.The three groups were comparable in terms of gender, rheumatoid on July 11,
Aberrant Polo-Like Kinase 1-Cdc25A Pathway in Metastatic Hepatocellular Carcinoma
Authors: Xiao Qi Wang, Yong Qiang Zhu, Karen S. Lui, Qi Cai, Ping Lu, Ronnie T. Poon
Journal: Clinical Cancer Research (2008)

Most studies on pathogenesis of tumor metastasis focus on cell adhesion and migration. Little is understood of how cell cycle pathways critically affect cell fate of metastatic cells and their sensitivity to anticancer drugs. In this study, we investigated cell cycle checkpoint progression and regulation in the presence of cisplatin in metastatic hepatocellular carcinoma (HCC) cells.Cisplatin-mediated cell cycle progression and Polo-like kinase 1 (Plk1)-Cdc25A pathway were compared between metastatic and nonmetastatic HCC cells by flow cytometry, Western blots, and reverse transcription-PCR. Cdc25A expression in clinical HCC samples was detected using immunohistochemistry and its association with clinical HCC metastasis was analyzed.Cisplatin induced degradation of Cdc25A in nonmetastatic HCC cells but not in metastatic HCC cells. Hence, metastatic HCC cells showed defective S-M cell cycle phase arrest and continued to enter mitosis. Tumor expression of Cdc25A was strongly associated with metastatic diseases in HCC patients, and elevated Cdc25A expression significantly correlated with HCC tumor-node-metastasis staging and venous invasion. Metastatic HCC cells did not show down-regulation of Plk1 that was normally induced by DNA damage. Blockage of Plk1 expression in metastatic HCC cells initiated Cdc25A degradation in response to DNA damage, suggesting that Plk1 could be an upstream regulator of Cdc25A. Deregulated Plk1-Cdc25A pathway in metastatic HCC cells and primary tumors did not result in drug-induced mitotic catastrophe but rather in accumulation of damaged DNA due to checkpoint adaptation.Metastatic HCC cells showed a defective S-M checkpoint following cisplatin treatment and potential aberrant checkpoint adaptation, which might result from deregulation of Plk1-Cdc25A pathway.
Substrate-selective COX-2 inhibition decreases anxiety via endocannabinoid activation
Authors: Daniel J Hermanson, Nolan D Hartley, Joyonna Gamble-George, Naoko Brown, Brian C Shonesy, Phillip J Kingsley, Roger J Colbran, Jeffrey Reese, Lawrence J Marnett, Sachin Patel
Journal: Nature Neuroscience (2013)
Decreased Coagulability Has No Clinically Relevant Effect on Atherogenesis
Authors: A. Šrámek, J.H.C. Reiber, W.B.J. Gerrits, F.R. Rosendaal
Journal: Circulation (2001)

Background Hemostasis affects ischemic cardiovascular disease through its role in formation of occluding arterial thrombi. Several studies suggest that hemostasis also might play a role in atherogenesis. We investigated whether individuals with an inherited bleeding tendency are protected against development of atherosclerosis. Methods and Results A total of 76 individuals with an inherited bleeding tendency (hemophilia and von Willebrand disease) and 142 healthy controls were included in the present study. Early atherosclerotic vessel-wall changes were quantified by measurement of intima-media thickness in the carotid and femoral arteries by B-mode ultrasonography. To validate intima-media thickness measurements, measurements also were performed in 77 individuals with clinically proven atherosclerosis and in 34 healthy, age-matched controls. A large difference in intima-media thickness was found between individuals with proven atherosclerosis and healthy controls, in particular for the femoral artery (difference for carotid artery, 0.16 mm; femoral artery, 0.53 mm). Comparison between patients with a bleeding tendency and healthy controls showed only minimally reduced intima-media in femoral artery in individuals with a bleeding tendency (adjusted difference, −0.078 mm; 95% CI, −0.17 to 0.018 mm). Subgroup analysis revealed that in subjects with moderate to severe hemophilia, vessel walls were thinnest (adjusted difference, −0.10 mm; 95% CI, −0.27 to 0.061 mm). Conclusions Hypocoagulability caused by hemophilia or von Willebrand disease has at most a limited effect on atherogenesis.
Paricalcitol Attenuates Renal Interstitial Fibrosis in Obstructive Nephropathy
Authors: Xiaoyue Tan, Yingjian Li, Youhua Liu
Journal: Journal of the American Society of Nephrology (2006)

Deficiency in vitamin D and its active metabolites is a pathologic feature of chronic kidney diseases. Despite that tubular epithelial cells are the major sites of active vitamin D synthesis, little is known about the role of vitamin D in maintaining the structural and functional integrity of tubular epithelium. This study investigated the effects of paricalcitol (19-nor-1,25-hydroxy-vitamin D<sub>2</sub>), a synthetic vitamin D analogue, on obstructive nephropathy, a model that is characterized by predominant tubulointerstitial lesions. Compared with vehicle controls, paricalcitol significantly attenuated renal interstitial fibrosis in mouse kidney after ureteral obstruction, as demonstrated by a reduced interstitial volume, decreased collagen deposition, and repressed mRNA expression of fibronectin and type I and type III collagens. Paricalcitol largely preserved E-cadherin and reduced α-smooth muscle actin expression <i>in vivo</i>. In addition, paricalcitol suppressed renal TGF-β1 and its type I receptor expression, restored vitamin D receptor abundance, and inhibited cell proliferation and apoptosis after obstructive injury. <i>In vitro</i>, paricalcitol abolished TGF-β1–mediated E-cadherin suppression and α-smooth muscle actin and fibronectin induction in tubular epithelial cells, underscoring its ability to block directly the epithelial to mesenchymal transition (EMT). It is interesting that paricalcitol almost completely suppressed renal induction of Snail, a critical transcription factor that is implicated in EMT programming. Furthermore, paricalcitol inhibited the TGF-β1–mediated Snail induction <i>in vitro</i>, and ectopic expression of Snail repressed E-cadherin promoter activity and downregulated E-cadherin expression in tubular epithelial cells. These studies suggest that paricalcitol is able to ameliorate renal interstitial fibrosis in obstructive nephropathy, possibly by preserving tubular epithelial integrity through suppression of EMT.
Targeting the Notch Ligand Jagged1 in Both Tumor Cells and Stroma in Ovarian Cancer
Authors: Adam D. Steg, Ashwini A. Katre, Blake Goodman, Hee-Dong Han, Alpa M. Nick, Rebecca L. Stone, Robert L. Coleman, Ronald D. Alvarez, Gabriel Lopez-Berestein, Anil K. Sood, Charles N. Landen
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Jagged1, a Notch ligand, is expressed on both tumor epithelial and endothelial cells and therefore may be amenable to dual targeting of the tumor stroma and malignant cell compartments of the tumor microenvironment. Experimental Design: We describe in vitro effects of targeting of Jagged1 on ovarian cancer cells and in vivo effects of independent targeting of stromal and malignant cell Jagged1 using species-specific human or murine siRNA constructs incorporated into chitosan nanoparticles and delivered intravenously in an orthotopic mouse model. Results: Jagged1 expression was prominent in SKOV3ip1 and IGROV-AF1, and significantly overexpressed in SKOV3TRip2, a taxane-resistant SKOV3 subclone. Jagged1 silencing with siRNA decreased cell viability and reversed taxane chemoresistance. In two different orthotopic ovarian cancer models, treatment with anti-human Jagged1 siRNA-CH reduced growth by 54.4% to 58.3% and with anti-murine Jagged1 siRNA-CH reduced growth by 41.7% to 48.8%. The combination of both species-specific constructs reduced tumor weight by 87.5% to 93.1% and sensitized SKOV3TRip2 tumors to docetaxel in vivo. Tumors showed reduced microvessel density with anti-murine Jagged1 constructs and decreased proliferation with anti-human Jagged1 siRNAs-CH. In addition, we show that Jagged1 downregulation does not sensitize cells to taxanes through a reduction in MDR1 expression, but at least in part by cross-talk with the GLI2 mediator of the Hedgehog pathway. Conclusions: Jagged1 plays dual roles in cancer progression through an angiogenic function in tumor endothelial cells and through proliferation and chemoresistance in tumor cells. Dual inhibition represents an attractive therapeutic strategy for ovarian and potentially other malignancies. Clin Cancer Res; 17(17); 5674–85. ©2011 AACR.
Critical Evaluation of Models to Identify Individuals With Insulin Resistance
Authors: Wolfgang Rathmann, Burkhard Haastert, Guido Giani, Rolf Holle, Wolfgang Koenig, Christian Herder, Hannelore Löwel
Journal: Diabetes Care (2005)

Clinical indexes of insulin resistance (IR) have acquired increasing importance with the development of various drugs that improve endogenous insulin action (1). Recently, the largest database on insulin clamp studies has been established. This database includes 2,321 subjects, of whom 2,138 are nondiabetic (92%), from 19 sites worldwide (2). Using classification trees, three models have been derived. Model 1 is based on homeostasis model assessment of insulin resistance (HOMA-IR) >4.65, BMI >28.9 kg/m2, or HOMA-IR >3.60 and BMI >27.5 kg/m2. Model 2 is based on BMI >28.7 kg/m2, …
Genetic identity, biological phenotype, and evolutionary pathways of transmitted/founder viruses in acute and early HIV-1 infection
Authors: Jesus F. Salazar-Gonzalez, Maria G. Salazar, Brandon F. Keele, Gerald H. Learn, Elena E. Giorgi, Hui Li, Julie M. Decker, Shuyi Wang, Joshua Baalwa, Matthias H. Kraus, Nicholas F. Parrish, Katharina S. Shaw, M. Brad Guffey, Katharine J. Bar, Katie L. Davis, Christina Ochsenbauer-Jambor, John C. Kappes, Michael S. Saag, Myron S. Cohen, Joseph Mulenga, Cynthia A. Derdeyn, Susan Allen, Eric Hunter, Martin Markowitz, Peter Hraber, Alan S. Perelson, Tanmoy Bhattacharya, Barton F. Haynes, Bette T. Korber, Beatrice H. Hahn, George M. Shaw
Journal: The Journal of Experimental Medicine (2009)

Identification of full-length transmitted HIV-1 genomes could be instrumental in HIV-1 pathogenesis, microbicide, and vaccine research by enabling the direct analysis of those viruses actually responsible for productive clinical infection. We show in 12 acutely infected subjects (9 clade B and 3 clade C) that complete HIV-1 genomes of transmitted/founder viruses can be inferred by single genome amplification and sequencing of plasma virion RNA. This allowed for the molecular cloning and biological analysis of transmitted/founder viruses and a comprehensive genome-wide assessment of the genetic imprint left on the evolving virus quasispecies by a composite of host selection pressures. Transmitted viruses encoded intact canonical genes (gag-pol-vif-vpr-tat-rev-vpu-env-nef) and replicated efficiently in primary human CD4+ T lymphocytes but much less so in monocyte-derived macrophages. Transmitted viruses were CD4 and CCR5 tropic and demonstrated concealment of coreceptor binding surfaces of the envelope bridging sheet and variable loop 3. 2 mo after infection, transmitted/founder viruses in three subjects were nearly completely replaced by viruses differing at two to five highly selected genomic loci; by 12–20 mo, viruses exhibited concentrated mutations at 17–34 discrete locations. These findings reveal viral properties associated with mucosal HIV-1 transmission and a limited set of rapidly evolving adaptive mutations driven primarily, but not exclusively, by early cytotoxic T cell responses.