tbuckley/cabot-search huggingface dataset:
Adjuvant therapy of ovarian germ cell tumors with cisplatin, etoposide, and bleomycin: a trial of the Gynecologic Oncology Group.
Authors: S Williams, J A Blessing, S Y Liao, H Ball, P Hanjani
Journal: Journal of Clinical Oncology (1994)

PURPOSE This study was performed to determine the effectiveness of postoperative adjuvant chemotherapy in patients with surgically resected ovarian germ cell tumors. PATIENTS AND METHODS After tumor removal and thorough surgical staging, patients were enrolled on this study and treated with three courses of cisplatin, etoposide, and bleomycin (BEP). Reassessment laparotomy was required of consenting, appropriate patients initially, but became an optional procedure in 1989. RESULTS Of 93 patients assessable on this trial, 89 are continuously free of germ cell cancer. At second-look laparotomy, two other patients were found to have small foci of immature teratoma; both remain clinically free of recurrence. One received subsequent alternate chemotherapy and one did not. Thus, 91 of 93 patients are currently free of germ cell cancer. Follow-up duration ranges from 4.0 to 90.3 months, with 67 patients monitored for longer than 2 years. Acute toxicity was moderate. One patient developed acute myelomonocytic leukemia 22 months after diagnosis. Another patient was noted to have a malignant lymphoma 69 months after protocol treatment. CONCLUSION Three courses of BEP will nearly always prevent recurrence in well-staged patients with completely resected ovarian germ cell tumors and should be given to all such patients. The development of acute leukemia as a complication of treatment is disturbing and mandates careful long-term follow-up, but is unusual and does not alter the risk-to-benefit ratio of treatment.
Effect of physiological concentrations of vitamin C on gastric cancer cells and Helicobacter pylori
Authors: Z-W Zhang
Journal: Gut (2002)

Background: Gastric juice vitamin C may be protective against gastric carcinogenesis but concentrations are significantly reduced by <i>Helicobacter pylori</i> infection. We investigated the in vitro effects of vitamin C at concentrations comparable with those found in gastric juice on gastric cancer cells and <i>H pylori</i>. Methods: Gastric cancer cell lines and various <i>H pylori</i> strains were treated with l-ascorbic acid for up to 72 hours. Cell viability, and protein and DNA synthesis were determined. Flow cytometry was used for assessment of <i>H pylori</i> adherence, cell cycle distribution, and apoptosis. <i>H pylori</i> growth and its haemagglutination activity were determined using viability count and microtitration assay. Results: Vitamin C induced a significant dose dependent growth inhibition of gastric AGS and MKN45 cells but this effect was significantly reduced at levels similar to those in gastric juice of <i>H pylori</i> infected patients (&lt;50 μM). Although vitamin C had no obvious effect on <i>H pylori</i> growth, haemagglutination activity, or adherence ability to gastric AGS cells compared with untreated controls, it significantly enhanced <i>H pylori</i> associated apoptosis and induced cell cycle arrest in these cells. Conclusion: Vitamin C may inhibit gastric cancer cell growth and alter <i>H pylori</i> induced cell cycle events at concentrations comparable with those in gastric juice, but has no effect on <i>H pylori</i> growth or pathogenicity. However, the inhibitory effect on gastric cancer cells was lost at vitamin C concentrations found in patients with <i>H pylori</i> infection.
Xuezhikang, an Extract of Cholestin, Protects Endothelial Function Through Antiinflammatory and Lipid-Lowering Mechanisms in Patients With Coronary Heart Disease
Authors: Shui Ping Zhao, Ling Liu, Yan Chun Cheng, Mehdi H. Shishehbor, Ming Hui Liu, Dao Quan Peng, Yu Ling Li
Journal: Circulation (2004)

Endothelial dysfunction is associated with inflammation and postprandial hypertriglyceridemia. Xuezhikang, an extract of Cholestin, a dietary supplement, has lipid-modulating and antiinflammatory effects. We explored the effects of xuezhikang on endothelial function and high-sensitivity C-reactive protein (hs-CRP) in patients with coronary heart disease (CHD).We prospectively randomized 50 CHD patients to xuezhikang 1200 mg/d or placebo for 6 weeks. Fasting hs-CRP concentrations, flow-mediated vasodilation (FMD) at 0 and 4 hours, and lipid parameters at 0, 2, 4, and 6 hours were monitored after a high-fat meal (800 calories; 50 g fat) in all patients. All patients underwent a high-fat meal test at the beginning of the study and after 6 weeks of treatment. Postprandial FMD was significantly worse at 4 hours after a high-fat meal (P<0.05), and this was associated with the area under the triglyceride curve (TG-AUC) (r=0.345, P<0.01). After 6 weeks of xuezhikang, fasting hs-CRP levels and TG-AUC (P<0.001 for each) decreased. Furthermore, preprandial and postprandial FMD significantly improved (P<0.001). There were no significant changes in serum lipids and FMD in the placebo arm. In multivariable regression analysis, changes in TG-AUC and fasting hs-CRP levels were predictive of improvement in preprandial FMD (P<0.05).Xuezhikang effectively improved preprandial and postprandial endothelial function through its potent antiinflammatory and lipid-lowering effects.
Livedo reticularis—a clinical sign not a disease
Authors: P.W.M. Copeman
Journal: British Journal of Dermatology (1974)

Journal Article Livedo reticularis—a clinical sign not a disease Get access P.W.M. Copeman P.W.M. Copeman Westminster Hospital, London Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 91, Issue s10, 1 July 1974, Pages 20–21, https://doi.org/10.1111/j.1365-2133.1974.tb12483.x Published: 01 July 1974
Differential Wnt Pathway Gene Expression and E-Cadherin Truncation in Sporadic Colorectal Cancers with and without Microsatellite Instability
Authors: Paloma Ortega, Alberto Morán, Carmen de Juan, Cristina Frías, Susana Hernández, Jose-Antonio López-Asenjo, Andrés Sánchez-Pernaute, Antonio Torres, Pilar Iniesta, Manuel Benito
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Alterations in the Wnt pathway play a major role in colorectal cancer with high (MSI-H) or low microsatellite instability (MSS/MSI-L). However, the differential impact of the Wnt pathway components on these tumors is poorly understood. MMP-3 (stromelysin-1) promoter is a target of the mutator phenotype in sporadic colorectal cancer. Among MMP-3 targets, we investigated E-cadherin integrity status in both groups of tumors. Because beta-catenin is the main effector of the Wnt pathway, we have also investigated the differential cellular status of beta-catenin. Experimental Design: Expression profiles of 114 genes related to the Wnt pathway were analyzed by oligo microarrays in 48 tumors classified by their MSI status. In addition, we analyzed 48 sporadic colorectal cancers for E-cadherin integrity status. We performed investigation of beta-catenin and cyclin D1 by immunohistochemistry using tissue arrays containing 96 tumors. Results: Our data show that a group of genes that negatively regulate Wnt signaling are downregulated in MSS/MSI-L as compared with MSI-H colorectal tumors. E-cadherin truncation was significantly higher in MSS/MSI-L as compared with MSI-H tumors. Moreover, MSI-H tumors showed low or null beta-catenin nuclear presence, whereas the group of tumors classified as MSS or MSI-L displayed a high content of the nuclear beta-catenin location. Conclusions: Our results suggest that the differential expression of genes that negatively regulate the Wnt pathway, as well as the status of E-cadherin and beta-catenin in MSI-H or MSS/MSI-L colorectal tumors, shed some light on the different clinical behavior showed by the two groups.
PMO-101 Enteral nutrition in acute pancreatitis: nasogastric or nasojejunal?
Authors: D J Malde, A Suppiah, T Arab, K Menon, A M Smith
Journal: Gut (2012)

<h3>Introduction</h3> Enteral feeding is beneficial in patients with severe acute pancreatitis. A published series suggests 100% can be fed via the nasogastic (NG) route. <h3>Methods</h3> 146 consecutive patients (January–December 2010) admitted with acute pancreatitis (AP) were reviewed to assess the safety and tolerance of NG feed. In all severe AP patients nutrition was initially delivered via an NG tube, if they were not absorbing a nasojejunal (NJ) tube was inserted. <h3>Results</h3> 29 patients were identified as having poor outcome. 127 (87%) patients were able to commence oral intake within 72 h of admission. 19 (13%) patients required additional enteral or parenteral nutritional support. 16 patients were commenced on NG feed but two patients needed conversion to NJ feed. Three patients were directly commenced on NJ feed but one needed conversion to parenteral feed. Only one patient had been commenced on parenteral feed prior to transfer. Need for nutritional support was a significant indicator of poor outcome; morbidity 13/19 vs 12/127 (p&lt;0.0001) and mortality 6/19 vs 1/127 (p&lt;0.0001). <h3>Conclusion</h3> Nasogastric feeding is well tolerated in the majority (73.7%) of patients with severe AP. NG feeding should be first line, but if failing a rapid change to the NJ route instituted. <h3>Competing interests</h3> None declared.
"Blind" protected specimen brushing <I>versus</I> bronchoscopic techniques in the aetiolological diagnosis of ventilator-associated pneumonia
Authors: S. Bello, A. Tejada, E. Chacón, M.C. Villuendas, A. Senar, M. Gascón, F.J. Suarez
Journal: European Respiratory Journal (1996)

The aetiological diagnosis of nosocomial pneumonia in intensive care unit (ICU) patients requires a valid, cheap and safe method. This method should be suitable for all mechanically-ventilated patients and all ICUs. The aim of this study was to assess the diagnostic yields of three methods: "blind" bronchial brushing (Accu-Cath)(protective specimen brush-nonbronchofibroscopic (PSB-non BF)); bronchofibroscopic protected specimen brushing (PSB-BF) and bronchoalveolar lavage (BAL). We prospectively studied the diagnostic values of the three methods as well as the agreement between microbiological results in 74 patients with 88 episodes of clinically suspected ventilator-associated pneumonia (VAP) and 22 control subjects. VAP episodes were also divided into those with (n = 24) and without antibiotic pretreatment (n = 64), and into those with (n = 78) and without (n = 10) right lower lobe infiltrates on chest radiography. No differences were found as regards the bacteriological yield of the three techniques. Furthermore, the rate of concordant results was high; 92% for PSB-BF and BAL; 84% for PSB-nonBF and BAL; 85% for PSB-nonBF and PSB-BF; and 85% for PSB-nonBF combined with both bronchoscopic techniques. The diagnostic yields in suspected VAP were 66, 59 and 56% for PSB-nonBF, PSB-BF and BAL, respectively. We conclude that "blind" bronchial brushing has similar accuracy to bronchoscopic techniques commonly used in the diagnosis of ventilator-associated pneumonia, constituting an interesting alternative in hospitals where fibreoptic bronchoscopy is not available.
The Receptor SIGIRR Suppresses Th17 Cell Proliferation via Inhibition of the Interleukin-1 Receptor Pathway and mTOR Kinase Activation
Authors: Muhammet F. Gulen, Zizhen Kang, Katarzyna Bulek, Wan Youzhong, Tae Whan Kim, Yi Chen, Cengiz Z. Altuntas, Kristian Sass Bak-Jensen, Mandy J. McGeachy, Jeong-Su Do, Hui Xiao, Greg M. Delgoffe, Booki Min, Jonathan D. Powell, Vincent K. Tuohy, Daniel J. Cua, Xiaoxia Li
Journal: Immunity (2010)
Molecular Evolution of the Arthropod Hemocyanin Superfamily
Authors: Thorsten Burmester
Journal: Molecular Biology and Evolution (2001)

Arthropod hemocyanins are members of a protein superfamily that also comprises the arthropod phenoloxidases (tyrosinases), crustacean pseudohemocyanins (cryptocyanins), and insect storage hexamerins. The evolution of these proteins was inferred by neighbor-joining, maximum-parsimony, and maximum-likelihood methods. Monte Carlo shuffling approaches provided evidence against a discernible relationship of the arthropod hemocyanin superfamily and molluscan hemocyanins or nonarthropodan tyrosinases. Within the arthropod hemocyanin superfamily, the phenoloxidase probably emerged early in the (eu-)arthropod stemline and thus form the most likely outgroup. The respiratory hemocyanins evolved from these enzymes before the radiation of the extant euarthropodan subphyla. Due to different functional constraints, replacement rates greatly vary between the clades. Divergence times were thus estimated assuming local molecular clocks using several substitution models. The results were consistent and indicated the separation of the cheliceratan and crustacean hemocyanins close to 600 MYA. The different subunit types of the multihexameric cheliceratan hemocyanin have a rather conservative structure and diversified in the arachnidan stemline between 550 and 450 MYA. By contrast, the separation of the crustacean (malacostracan) hemocyanin subunits probably occurred only about 200 MYA. The nonrespiratory pseudohemocyanins evolved within the Decapoda about 215 MYA. The insect hemocyanins and storage hexamerins emerged independently from the crustacean hemocyanins. The time of divergence of the insect proteins from the malacostracan hemocyanins was estimated to be about 430-440 MYA, providing support for the notion that the Hexapoda evolved from the same crustacean lineage as the Malacostraca.
<i>miR-1</i> Overexpression Enhances Ca <sup>2+</sup> Release and Promotes Cardiac Arrhythmogenesis by Targeting PP2A Regulatory Subunit B56α and Causing CaMKII-Dependent Hyperphosphorylation of RyR2
Authors: Dmitry Terentyev, Andriy E. Belevych, Radmila Terentyeva, Mickey M. Martin, Geraldine E. Malana, Donald E. Kuhn, Maha Abdellatif, David S. Feldman, Terry S. Elton, Sandor Györke
Journal: Circulation Research (2009)

MicroRNAs are small endogenous noncoding RNAs that regulate protein expression by hybridization to imprecise complementary sequences of target mRNAs. Changes in abundance of muscle-specific microRNA, miR-1 , have been implicated in cardiac disease, including arrhythmia and heart failure. However, the specific molecular targets and cellular mechanisms involved in the action of miR-1 in the heart are only beginning to emerge. In this study we investigated the effects of increased expression of miR-1 on excitation–contraction coupling and Ca 2+ cycling in rat ventricular myocytes using methods of electrophysiology, Ca 2+ imaging and quantitative immunoblotting. Adenoviral-mediated overexpression of miR-1 in myocytes resulted in a marked increase in the amplitude of the inward Ca 2+ current, flattening of Ca 2+ transients voltage dependence, and enhanced frequency of spontaneous Ca 2+ sparks while reducing the sarcoplasmic reticulum Ca 2+ content as compared with control. In the presence of isoproterenol, rhythmically paced, miR-1 –overexpressing myocytes exhibited spontaneous arrhythmogenic oscillations of intracellular Ca 2+ , events that occurred rarely in control myocytes under the same conditions. The effects of miR-1 were completely reversed by the CaMKII inhibitor KN93. Although phosphorylation of phospholamban was not altered, miR-1 overexpression increased phosphorylation of the ryanodine receptor (RyR2) at S2814 (Ca 2+ /calmodulin-dependent protein kinase) but not at S2808 (protein kinase A). Overexpression of miR-1 was accompanied by a selective decrease in expression of the protein phosphatase PP2A regulatory subunit B56α involved in PP2A targeting to specialized subcellular domains. We conclude that miR-1 enhances cardiac excitation–contraction coupling by selectively increasing phosphorylation of the L-type and RyR2 channels via disrupting localization of PP2A activity to these channels.
Microglia activation in hepatic encephalopathy in rats and humans
Authors: Irina Zemtsova, Boris Görg, Verena Keitel, Hans-Jürgen Bidmon, Karsten Schrör, Dieter Häussinger
Journal: Hepatology (2011)

Abstract: Astrocytes play an important role in the pathogenesis of hepatic encephalopathy (HE) and ammonia toxicity, whereas little is known about microglia and neuroinflammation under these conditions. We therefore studied the effects of ammonia on rat microglia in vitro and in vivo and analyzed markers of neuroinflammation in post mortem brain tissue from patients with cirrhosis with and without HE and non-cirrhotic controls. In cultured rat microglia, ammonia stimulated cell migration and induced oxidative stress and an up-regulation of the microglial activation marker ionized calcium-binding adaptor molecule-1 (Iba-1). Up-regulation of Iba-1 was also found in the cerebral cortex from acutely ammonia-intoxicated rats and in the cerebral cortex from patients with cirrhosis who have HE, but not from patients with cirrhosis who do not have HE. However, ammonia had no effect on microglial glutamate release, prostaglandin synthesis, and messenger RNA (mRNA) levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and the proinflammatory cytokines interleukin (IL)-1α/β, tumor necrosis factor α, or IL-6, whereas in cultured astrocytes ammonia induced the release of glutamate, prostaglandins, and increased IL-1β mRNA. mRNA and protein expression of iNOS and COX-2 or mRNA expression of proinflammatory cytokines and chemokine monocyte chemoattractive protein-1 in cerebral cortex from patients with liver cirrhosis and HE were not different from those found in patients with cirrhosis who did not have HE or control patients without cirrhosis. Conclusion: These data suggest that microglia become activated in experimental hyperammonemia and HE in humans and may contribute to the generation of oxidative stress. However, HE in patients with liver cirrhosis is not associated with an up-regulation of inflammatory cytokines in cerebral cortex, despite microglia activation. (HEPATOLOGY 2011;)
Telomere Erosion in Memory T Cells Induced by Telomerase Inhibition at the Site of Antigenic Challenge In Vivo
Authors: John R. Reed, Milica Vukmanovic-Stejic, Jean M. Fletcher, Maria Vieira D. Soares, Joanne E. Cook, Catherine H. Orteu, Sarah E. Jackson, Katie E. Birch, Graham R. Foster, Mike Salmon, Peter C.L. Beverley, Malcolm H.A. Rustin, Arne N. Akbar
Journal: The Journal of Experimental Medicine (2004)

The extent of human memory T cell proliferation, differentiation, and telomere erosion that occurs after a single episode of immune challenge in vivo is unclear. To investigate this, we injected tuberculin purified protein derivative (PPD) into the skin of immune individuals and isolated responsive T cells from the site of antigenic challenge at different times. PPD-specific CD4+ T cells proliferated and differentiated extensively in the skin during this secondary response. Furthermore, significant telomere erosion occurred in specific T cells that respond in the skin, but not in those that are found in the blood from the same individuals. Tissue fluid obtained from the site of PPD challenge in the skin inhibited the induction of the enzyme telomerase in T cells in vitro. Antibody inhibition studies indicated that type I interferon (IFN), which was identified at high levels in the tissue fluid and by immunohistology, was responsible in part for the telomerase inhibition. Furthermore, the addition of IFN-α to PPD-stimulated CD4+ T cells directly inhibited telomerase activity in vitro. Therefore, these results suggest that the rate of telomere erosion in proliferating, antigen-specific CD4+ T cells may be accelerated by type I IFN during a secondary response in vivo.
Effect of Parapharyngeal Fat on Dynamic Obstruction of the Upper Airway in Patients with Obstructive Sleep Apnea
Authors: Min-Seok Jang, Hyo Yeol Kim, Hun-Jong Dhong, Seung-Kyu Chung, Sang Duk Hong, Hyun-Jin Cho, Tae-Young Jung
Journal: American Journal of Respiratory and Critical Care Medicine (2014)
Clinicopathological characteristics of colorectal carcinoma complicating ulcerative colitis.
Authors: W R Connell, I C Talbot, N Harpaz, N Britto, K H Wilkinson, M A Kamm, J E Lennard-Jones
Journal: Gut (1994)

This study examined three features associated with colorectal carcinoma complicating ulcerative colitis: (a) the distribution of 157 cancers in 120 patients with ulcerative colitis treated at St Mark's Hospital between 1947 and 1992; (b) the frequency at which dysplasia was found at a distance from the tumour in 50 total proctocolectomy specimens in which an average of 27 histology blocks were reviewed, and (c) the five year survival rate according to Dukes's stage and participation in a surveillance programme. Of 157 carcinomas, 88 (56%) occurred in the rectosigmoid, 19 (12%) in the descending colon or splenic flexure, and 50 (32%) in the proximal colon. Among the 120 patients, the rectum or sigmoid colon contained cancer in 81 (67.5%). Dysplasia was detected in 41 of 50 reviewed proctocolectomy specimens (82%). Dysplasia distant to a malignancy occurred in 37 (74%); two were classified indefinite, probably positive, 19 were low grade, and 16 were high grade; in 18 specimens there was an elevated dysplastic lesion. Survival was related to the Dukes's stage: about 90% of patients with Dukes's A or B cancer were alive at five years. The five year survival of 16 patients in whom cancer developed during surveillance was 87% compared with 55% of 104 patients who did not participate in surveillance (p = 0.024).
Rituximab inhibits structural joint damage in patients with rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitor therapies
Authors: E Keystone, P Emery, C G Peterfy, P P Tak, S Cohen, M C Genovese, M Dougados, G R Burmester, M Greenwald, T K Kvien, S Williams, D Hagerty, M W Cravets, T Shaw
Journal: Annals of the Rheumatic Diseases (2008)

To determine if treatment with a B cell-targeted therapy can inhibit the progression of structural joint damage in patients with rheumatoid arthritis (RA), exhibiting an inadequate response to tumour necrosis factor (TNF) inhibitors.In this phase III study, patients with an inadequate response to a TNF inhibitor and receiving methotrexate were randomised to rituximab or placebo. Radiographs were obtained at baseline, week 24 and week 56 after randomisation. Patients with an inadequate response to their randomised therapy could receive rescue medication from week 16. From week 24, eligible patients from both treatment arms could receive open-label rituximab. Patients were analysed according to their original treatment group. Radiographs were scored using the Genant-modified Sharp method. The primary radiographic endpoint was change in total Genant-modified Sharp score at week 56.Rituximab treatment caused significant reduction in joint damage progression compared with placebo. The mean change from baseline in the total Genant-modified Sharp score at week 56 was significantly lower for patients treated with rituximab than for patients treated with placebo (1.00 vs 2.31; p = 0.005), and was supported by changes in erosion score (0.59 and 1.32 for rituximab plus methotrexate vs placebo plus methotrexate, respectively; p = 0.011) and joint space narrowing score (0.41 and 0.99, respectively; p<0.001).This study provides the first evidence that a B cell-targeted therapy-rituximab-can significantly inhibit the progression of structural joint damage in patients with RA with long-standing, active and treatment-resistant disease.
399 PNPLA3 I148M AFFECTS LIVER STEATOSIS IN PATIENTS WITH CHRONIC HEPATITIS B
Authors: M. Vigano', L. Valenti, P. Lampertico, B.M. Motta, R. D'Ambrosio, F. Facchetti, P. Dongiovanni, S. Fargion, M. Colombo
Journal: Journal of Hepatology (2013)