tbuckley/cabot-search huggingface dataset:
Chronic Oxaliplatin Resistance Induces Epithelial-to-Mesenchymal Transition in Colorectal Cancer Cell Lines
Authors: Anthony D. Yang, Fan Fan, E. Ramsay Camp, George van Buren, Wenbiao Liu, Ray Somcio, Michael J. Gray, Haiyun Cheng, Paulo M. Hoff, Lee M. Ellis
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Epithelial-to-mesenchymal transition (EMT) is a process whereby cells acquire molecular alterations that facilitate cell motility and invasion. In preliminary studies, we observed that oxaliplatin-resistant (OxR) colorectal cancer (CRC) cells underwent morphologic changes suggestive of a migratory phenotype, leading us to hypothesize that OxR CRC cells undergo EMT. Experimental Design: The human CRC cell lines KM12L4 and HT29 were exposed to increasing doses of oxaliplatin to establish stable cell lines resistant to oxaliplatin. Migration and invasion were assessed by modified Boyden chamber assays. Morphologic and molecular changes characteristic of EMT were determined by immunofluorescence staining and Western blot analyses. Results: The OxR cells showed phenotypic changes consistent with EMT: spindle-cell shape, loss of polarity, intercellular separation, and pseudopodia formation. KM12L4 and HT29 OxR cells exhibited an ∼8- to 15-fold increase in migrating and invading cells, respectively (P &amp;lt; 0.005 for both). Immunofluorescence staining of OxR cells revealed translocation of E-cadherin and β-catenin from their usual membrane-bound complex to the cytoplasm and nucleus, respectively. The OxR cells also had decreased expression of the epithelial adhesion molecules E-cadherin and plakoglobin and an increase in the mesenchymal marker vimentin. The KM12L4 OxR cells exhibited increased nuclear expression of Snail, an EMT-regulatory transcription factor, whereas the HT29 OxR cells exhibited an increase in nuclear expression of the EMT-associated transcription factor nuclear factor κB. Conclusion: We hypothesize that induction of EMT may contribute to the decreased efficacy of therapy in chemoresistant CRC, as the tumor cells switch from a proliferative to invasive phenotype. Further understanding of the mechanisms of chemoresistance in CRC will enable improvements in chemotherapy for metastatic disease.
Ultrasound-Guided Peripheral IV Placement
Authors: Scott Joing, Seth Strote, Liberty Caroon, Christopher Wall, Jamie Hess, Chad Roline, Laura Oh, Ben Dolan, Robb Poutre, Kathleen Carney, David Plummer, Robert Reardon
Journal: New England Journal of Medicine (2012)

This video shows the use of ultrasound guidance to place catheters in peripheral veins in the upper extremities. This technique can also be used to cannulate any peripheral vein.
An unusual terminal hair growth on the nose tip associated with gefitinib therapy
Authors: S.Y. Kim, H-J. Choi, H.J. Park, J.Y. Lee, B.K. Cho
Journal: British Journal of Dermatology (2007)

Conflicts of interest: none declared. Sir, The epidermal growth factor receptor (EGFR) pathway, a key driver in regulating normal epithelial cell growth and differentiation, also plays a role in promoting proliferation of malignant epithelial cells1 by increasing proliferation, adhesion and invasive capacity, and also by blocking apoptosis.1–4 For this reason, EGFR expression is associated with metastasis, late‐stage disease, resistance to therapy and poor prognosis. Therapies targeting EGFR are now under development, such as antibodies to EGFR or EGFR‐specific tyrosine kinase inhibitors. Gefitinib, also known as ZD 1839 or Iressa®, is a low‐molecular‐weight compound that inhibits the activation of EGFR tyrosine kinase through competitive binding of the receptor.1–4 A 65‐year‐old woman presented with a 2‐month history of asymptomatic, brown to black hairs on the nose tip that had been gradually thickening and lengthening (Fig. 1). Six months before, she had been diagnosed with metastatic lung adenocarcinoma and had undergone treatment with radiotherapy (whole brain and femur, 3000 cGy × 2 cycles) and chemotherapy (docetaxel 100 mg daily every 3 weeks for 2 months). Two months before, she began treatment with gefitinib 250 mg daily. One week after starting treatment, she noticed tiny brown to black spots on her nose tip. Ever since, hairs have been growing at these sites. When she presented to our department, the hairs were 1–3 mm in length, localized to the nose tip. There were no vellus hairs, which normally there should be. There was no abnormality of hair density or length at other body sites. She denied a personal history of other cutaneous problems, trauma or administration of any drugs such as might induce hair growth. Skin biopsy revealed multiple hair follicles in anagen phase that were located in the superficial dermis (Fig. 2). The hair shaft was 0·054 mm in diameter and was myelinated, indicative of terminal hair. There was also solar elastosis and a mild inflammatory infiltrate in the papillary dermis. On the basis of these findings, the patient was diagnosed with terminal hair growth associated with gefitinib and was recommended to discontinue gefitinib. However, as the patient's lung adenocarcinoma had had a poor response to radiochemotherapy, gefitinib could not be discontinued and the hairs have continued to grow.
Candidate exome capture identifies mutation of SDCCAG8 as the cause of a retinal-renal ciliopathy
Authors: Edgar A Otto, Toby W Hurd, Rannar Airik, Moumita Chaki, Weibin Zhou, Corinne Stoetzel, Suresh B Patil, Shawn Levy, Amiya K Ghosh, Carlos A Murga-Zamalloa, Jeroen van Reeuwijk, Stef J F Letteboer, Liyun Sang, Rachel H Giles, Qin Liu, Karlien L M Coene, Alejandro Estrada-Cuzcano, Rob W J Collin, Heather M McLaughlin, Susanne Held, Jennifer M Kasanuki, Gokul Ramaswami, Jinny Conte, Irma Lopez, Joseph Washburn, James MacDonald, Jinghua Hu, Yukiko Yamashita, Eamonn R Maher, Lisa M Guay-Woodford, Hartmut P H Neumann, Nicholas Obermüller, Robert K Koenekoop, Carsten Bergmann, Xiaoshu Bei, Richard A Lewis, Nicholas Katsanis, Vanda Lopes, David S Williams, Robert H Lyons, Chi V Dang, Daniela A Brito, Mónica Bettencourt Dias, Xinmin Zhang, James D Cavalcoli, Gudrun Nürnberg, Peter Nürnberg, Eric A Pierce, Peter K Jackson, Corinne Antignac, Sophie Saunier, Ronald Roepman, Helene Dollfus, Hemant Khanna, Friedhelm Hildebrandt
Journal: Nature Genetics (2010)
Effects of Fat on Coronary Circulation in Dogs
Authors: PETER T. KUO, ARTHUR F. WHEREAT, ARTHUR A. ALTMAN, JAMES W. WEST
Journal: Circulation Research (1960)

The effects of lipemia upon the coronary circulation and myocardial oxygenation, and arterial oxygen and carbon dioxide contents were studied in 13 control dogs and 20 animals with myocardial scars. Acutely induced lipemia caused a significant decrease in the cardiac output, coronary blood flow and myocardial oxygen consumption in both groups of animals. These changes were similar to those observed in experimental coronary artery embolization. The slow intravenous fat infusion did not cause a significant drop in the mean arterial pressures of these dogs. All animals in this series developed hyperpnea during fat infusion. There was a simultaneous lowering of the arterial oxygen saturation and carbon dioxide content. These changes were in some ways similar to those observed by other investigators in experimental pulmonary embolization. However, the slow fat infusion did not produce a significant elevation of the pulmonary arterial pressures of these dogs. These data suggest that the chylomicra, like most macromolecular substances, may produce mechanical interference to the coronary blood flow and impose a limitation to myocardial oxygenation, while the total oxygen consumption of the animal is unaltered by lipemia.
Circulating levels of the chemokine CCL18 but not CXCL16 are elevated and correlate with disease activity in rheumatoid arthritis
Authors: A. W T van Lieshout, J. Fransen, M. Flendrie, A. M M Eijsbouts, F. H J van den Hoogen, P. L C M van Riel, T. R D J Radstake
Journal: Annals of the Rheumatic Diseases (2007)

Antigen-presenting cells (APC) and T cells are considered to play a significant role in the pathogenesis of rheumatoid arthritis (RA). CCL18 and CXCL16 are two chemokines that facilitate T cell attraction by APC, of which a role in the pathogenesis of RA has been suggested.To compare the circulating levels of CXCL16 and CCL18 in RA with controls and to investigate the relation of CXCL16 and CCL18 with RA disease activity and joint damage.Circulating CCL18 and CXCL16 levels were determined in 61 RA patients with a follow-up of 6 years and a group of 41 healthy controls with ELISA. Chemokine levels were correlated with demographic data, disease activity (DAS28) and joint damage (modified Sharp score). In addition, serum CCL18 and CXCL16 levels from a cohort of 44 RA patients treated with anti-TNF-alpha were correlated with disease activity.CCL18 levels in serum were significantly elevated in RA patients compared with controls, while serum CXCL16 levels were not. In contrast to CXCL16, serum CCL18 was positively correlated with disease activity. Both CCL18 and CXCL16 levels decreased upon treatment with anti-TNF-alpha. Neither CCL18 nor CXCL16 correlated with joint damage and progression.Here, we show, for the first time, that circulating CCL18 and not CXCL16 levels are elevated in RA patients as compared with controls and correlate with disease activity in RA. More knowledge regarding the regulation and function of both CCL18 and CXCL16 is essential to value their role in RA.
Biological and biochemical characterization of a cloned Leu-3- cell surviving infection with the acquired immune deficiency syndrome retrovirus.
Authors: T M Folks, D Powell, M Lightfoote, S Koenig, A S Fauci, S Benn, A Rabson, D Daugherty, H E Gendelman, M D Hoggan
Journal: The Journal of Experimental Medicine (1986)

Leu-3- cells that survive infection with the acquired immune deficiency syndrome (AIDS) retrovirus can be induced with IUdR to express infectious virus. A cellular clone (8E5), isolated by limiting dilution of a mass culture of survivor cells, was found to contain a single, integrated provirus that was constitutively expressed. Although IUdR treatment of 8E5 cells failed to induce infectious virus, cocultivation with Leu-3+ cells generated the characteristic syncytia associated with acute AIDS retrovirus infection. The single integrated copy of proviral DNA directs the synthesis of all major viral structural proteins except p64, as monitored by immunoblotting. The relationship of the 8E5 clone to viral latency and persistence is discussed.
Analysis of Fluorouracil-Based Adjuvant Chemotherapy and Radiation After Pancreaticoduodenectomy for Ductal Adenocarcinoma of the Pancreas: Results of a Large, Prospectively Collected Database at the Johns Hopkins Hospital
Authors: Joseph M. Herman, Michael J. Swartz, Charles C. Hsu, Jordan Winter, Timothy M. Pawlik, Elizabeth Sugar, Ray Robinson, Daniel A. Laheru, Elizabeth Jaffee, Ralph H. Hruban, Kurtis A. Campbell, Christopher L. Wolfgang, Fariba Asrari, Ross Donehower, Manuel Hidalgo, Luis A. Diaz, Charles Yeo, John L. Cameron, Richard D. Schulick, Ross Abrams
Journal: Journal of Clinical Oncology (2008)

To examine the efficacy of adjuvant chemoradiotherapy after pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma (PC) in patients undergoing resection at Johns Hopkins Hospital (JHH; Baltimore, MD).Between August 30, 1993, and February 28, 2005, a total of 908 patients underwent PD for PC at JHH. A prospective database was reviewed to determine which patients received fluorouracil (FU) -based CRT. Excluded patients had metastatic disease, died 60 or fewer days after PD, received preoperative therapy, an experimental vaccine, adjuvant chemotherapy or radiation alone. The final cohort includes 616 patients.The median follow-up was 17.8 months (interquartile range, 9.7 to 33.5 months). Overall median survival was 17.9 months (95% CI, 16.3 to 19.5 months). Groups were similar with respect to tumor size, nodal status, and margin status, but the CRT group was younger (P < .001), and less likely to present with a severe comorbid disease (P = .001). Patients with carcinomas larger than 3 cm (P = .001), grade 3 and 4 (P < .001), margin-positive resection (P = .001), and complications after surgery (P = .017) had poor long-term survival. Patients receiving CRT experienced an improved median (21.2 v 14.4 months; P < .001), 2-year (43.9% v 31.9%), and 5-year (20.1% v 15.4%) survival compared with no CRT. After controlling for high-risk features, CRT was still associated with improved survival (relative risk = 0.74; 95% CI, 0.62 to 0.89).These data suggest that adjuvant concurrent FU-based CRT significantly improves survival after PD for PC when compared with patients not receiving CRT. These data support the use of combined adjuvant CRT for PC.
Phase II randomised trial comparing docetaxel given every 3 weeks with weekly schedule as second-line therapy in patients with advanced non-small-cell lung cancer (NSCLC)
Authors: R. Gervais, A. Ducolone, J.-L. Breton, D. Braun, B. Lebeau, F. Vaylet, D. Debieuvre, J.-L. Pujol, J. Tredaniel, P. Clouet, E. Quoix
Journal: Annals of Oncology (2004)
Hyperplastic Conotruncal Endocardial Cushions and Transposition of Great Arteries in Perlecan-Null Mice
Authors: Mercedes Costell, Rita Carmona, Erika Gustafsson, Mauricio González-Iriarte, Reinhard Fässler, Ramón Muñoz-Chápuli
Journal: Circulation Research (2002)

Perlecan is a heparan-sulfate proteoglycan abundantly expressed in pericellular matrices and basement membranes during development. Inactivation of the perlecan gene in mice is lethal at two developmental stages: around E10 and around birth. We report a high incidence of malformations of the cardiac outflow tract in perlecan-deficient embryos. Complete transposition of great arteries was diagnosed in 11 out of 15 late embryos studied (73%). Three of these 11 embryos also showed malformations of semilunar valves. Mesenchymal cells in the outflow tract were abnormally abundant in mutant embryos by E9.5, when the endocardial-mesenchymal transformation starts in wild-type embryos. At E10.5, mutant embryos lacked well-defined spiral endocardial ridges, and the excess of mesenchymal cells obstructed sometimes the outflow tract lumen. Most of this anomalous mesenchyme expressed the smooth muscle cell-specific alpha-actin isoform, a marker of the neural crest in the outflow tract of the mouse. In wild-type embryos, perlecan is present in the basal surface of myocardium and endocardium, as well as surrounding presumptive neural crest cells. We suggest that the excess of mesenchyme at the earlier stages of conotruncal development precludes the formation of the spiral ridges and the rotation of the septation complex in order to achieve a concordant ventriculoarterial connection. The observed mesenchymal overpopulation might be due to an uncontrolled migration of neural crest cells, which would arrive prematurely to the heart. Thus, perlecan is involved in the control of the outflow tract mesenchymal population size, underscoring the importance of the extracellular matrix in cardiac morphogenesis.
SYMPATHETIC REGULATION OF METABOLISM
Authors: JEAN HIMMS-HAGEN
Journal: Pharmacological Reviews (1967)

This long and extremely detailed study attempts at giving a review of the metabolic regulatory function of the sympathetic nervous system.  The metabolic effects of adrenaline and noradrenaline are considered as it regards lipid metabolism carbohydrate metabolism and protein metabolism.  The study also presents a new hypothesis of the calorigenic effect of catecholamines and a new classification of receptors for the metabolic effects of adrenaline and noradrenaline.  The study concludes with an examination of the role of the sympathetic nervous system in the regulation of metabolism and of the use of drugs that modify sympathetic activity.
Decreased level of antibodies against Helicobacter pylori in patients with rheumatoid arthritis receiving intramuscular gold.
Authors: M Janssen, B A Dijkmans, J P Vandenbroucke, W van Duijn, A S Pena, C B Lamers
Journal: Annals of the Rheumatic Diseases (1992)

BACKGROUND: Sodium aurothiomalate has been reported to have in vitro activity against Helicobacter pylori. Intramuscular gold, as given to patients with rheumatoid arthritis (RA), may therefore influence the colonisation of the gastric mucosa with H pylori. METHODS: Two groups were compared. One group of 42 patients was treated with intramuscular gold; the other group of 58 patients was treated with antimalarial drugs. Antibodies to H pylori (IgA and IgG) were assessed by an enzyme linked immunosorbent assay (ELISA) and total IgA and IgG were measured by nephelometry. RESULTS: IgA and IgG antibody titres against H pylori and total IgA and IgG levels were lower in the patients treated with gold than in the group treated with antimalarial drugs. The ratio of IgA antibodies to H pylori to total IgA antibodies and the ratio of IgG antibodies to H pylori to total IgG antibodies were lower in the group treated with gold. The percentage of seropositivity to H pylori was significantly lower in the group treated with gold than in the group treated with antimalarial drugs for the two IgA antibodies (35 and 55% respectively) and IgG antibodies to H pylori (40 and 65% respectively). CONCLUSIONS: Although this study cannot completely exclude the possibility that a suppressive effect of intramuscular gold on total immunoglobulin production plays a part in the decrease in the titres of IgA antibodies to H pylori and IgG antibodies to H pylori, the lower ratios of antibodies to H pylori to total immunoglobulin antibodies and the lower percentages of seropositivity to H pylori in the group treated with gold suggests that treatment with intramuscular gold decreases H pylori colonisation.
Tumour necrosis factor gene polymorphisms and childhood wheezing
Authors: H. Bilolikar, A. R. Nam, M. Rosenthal, J. C. Davies, D. C. Henderson, I. M. Balfour-Lynn
Journal: European Respiratory Journal (2005)

Tumour necrosis factor (TNF)-alpha is associated with childhood wheezing. A genetic predisposition to increased TNF-alpha production, influenced by single nucleotide gene polymorphisms, may be important. Frequencies of TNF-alpha-308G/A and lymphotoxin (LT)-alpha+252G/A polymorphisms were compared in 115 asthmatic children, 55 wheezy infants and 156 control school children from the UK. Genotype frequencies for the TNF-alpha-308 and LT-alpha+252 polymorphisms were significantly different from controls. Haplotype analysis showed that TNF-alpha-308G, LT-alpha+252A/TNF-alpha-308A, LT-alpha+252A was associated with a markedly increased risk for both asthma and infant wheezing. The TNF-alpha-308G, LT-alpha+252G/TNF-alpha-308G, LT-alpha+252A combination was protective for asthma and infant wheezing. These findings were confirmed by analysis of Caucasian data. Nasal TNF-alpha levels were measured in the infants during acute wheezing episodes and higher, but nonsignificant levels were produced in those with one or two LT-alpha+252A alleles. Unexpectedly, significantly lower nasal TNF-alpha levels were found in the presence of one or two TNF-alpha-308A alleles. TNF-alpha-308/LT-alpha+252 genotype combinations had a significant influence on nasal TNF-alpha levels. In conclusion, these findings may have implications for future early intervention studies by helping to identify infants at increased risk for wheezing and childhood asthma.
24-nor-ursodeoxycholic acid ameliorates inflammatory response and liver fibrosis in a murine model of hepatic schistosomiasis
Authors: Martina Sombetzki, Claudia D. Fuchs, Peter Fickert, Christoph H. Österreicher, Michaela Mueller, Thierry Claudel, Micha Loebermann, Robby Engelmann, Cord Langner, Emine Sahin, Dorothee Schwinge, Nina D. Guenther, Christoph Schramm, Brigitte Mueller-Hilke, Emil C. Reisinger, Michael Trauner
Journal: Journal of Hepatology (2014)

Intrahepatic granuloma formation and fibrosis characterize the pathological features of Schistosoma mansoni infection. Based on previously observed substantial anti-fibrotic effects of 24-nor-ursodeoxycholic acid (norUDCA) in Abcb4/Mdr2(-/-) mice with cholestatic liver injury and biliary fibrosis, we hypothesized that norUDCA improves inflammation-driven liver fibrosis in S. mansoni infection.Adult NMRI mice were infected with 50 S. mansoni cercariae and after 12 weeks received either norUDCA- or ursodeoxycholic acid (UDCA)-enriched diet (0.5% wt/wt) for 4 weeks. Bile acid effects on liver histology, serum biochemistry, key regulatory cytokines, hepatic hydroxyproline content as well as granuloma formation were compared to naive mice and infected controls. In addition, effects of norUDCA on primary T-cell activation/proliferation and maturation of the antigen-presenting-cells (dendritic cells, macrophages) were determined in vitro.UDCA as well as norUDCA attenuated the inflammatory response in livers of S. mansoni infected mice, but exclusively norUDCA changed cellular composition and reduced size of hepatic granulomas as well as TH2-mediated hepatic fibrosis in vivo. Moreover, norUDCA affected surface expression level of major histocompatibility complex (MHC) class II of macrophages and dendritic cells as well as activation/proliferation of T-lymphocytes in vitro, whereas UDCA had no effect.This study demonstrates pronounced anti-inflammatory and anti-fibrotic effects of norUDCA compared to UDCA in S. mansoni induced liver injury, and indicates that norUDCA directly represses antigen presentation of antigen presenting cells and subsequent T-cell activation in vitro. Therefore, norUDCA represents a promising drug for the treatment of this important cause of liver fibrosis.
Ultrastructural study shows morphologic features of apoptosis and para-apoptosis in megakaryocytes from patients with idiopathic thrombocytopenic purpura
Authors: Ewout J. Houwerzijl, Nel R. Blom, Johannes J. L. van der Want, Mariet T. Esselink, Jan J. Koornstra, Jan W. Smit, Henk Louwes, Edo Vellenga, Joost Th. M. de Wolf
Journal: Blood (2003)
Ligated complement receptors do not activate the arachidonic acid cascade in resident peritoneal macrophages.
Authors: A A Aderem, S D Wright, S C Silverstein, Z A Cohn
Journal: The Journal of Experimental Medicine (1985)

Receptors for IgG stimulate the release of approximately 20% of cellular arachidonic acid (20:4) from murine resident peritoneal macrophages. In contrast, C3 receptors do not trigger the secretion of any 20:4 in excess of that released constitutively from the cells. Since the ability of C3 receptors to promote phagocytosis is regulated, we compared resting macrophages, whose C3 receptors do not promote phagocytosis of C3-coated particles, and lymphokine-treated cells, whose receptors do promote ingestion. Despite their ability to promote phagocytosis, the C3 receptor of lymphokine-treated macrophages remain unable to initiate release of 20:4. We speculate that the intracellular signals that initiate phagocytosis are distinct from those that initiate release of 20:4.