tbuckley/cabot-search huggingface dataset:
The RASSF gene family members RASSF5, RASSF6 and RASSF7 show frequent DNA methylation in neuroblastoma
Authors: Anna Djos, Tommy Martinsson, Per Kogner, Helena Carén
Journal: Molecular Cancer (2012)

Abstract Background Hypermethylation of promotor CpG islands is a common mechanism that inactivates tumor suppressor genes in cancer. Genes belonging to the RASSF gene family have frequently been reported as epigenetically silenced by promotor methylation in human cancers. Two members of this gene family, RASSF1A and RASSF5A have been reported as methylated in neuroblastoma. Data from our previously performed genome-wide DNA methylation array analysis indicated that other members of the RASSF gene family are targeted by DNA methylation in neuroblastoma. Results In the current study, we found that several of the RASSF family genes ( RASSF2 , RASSF4 , RASSF5 , RASSF6 , RASSF7 , and RASSF10 ) to various degrees were methylated in neuroblastoma cell lines and primary tumors. In addition, several of the RASSF family genes showed low or absent mRNA expression in neuroblastoma cell lines. RASSF5 and RASSF6 were to various degrees methylated in a large portion of neuroblastoma tumors and RASSF7 was heavily methylated in most tumors. Further, CpG methylation sites in the CpG islands of some RASSF family members could be used to significantly discriminate between biological subgroups of neuroblastoma tumors. For example, RASSF5 methylation highly correlated to MYCN amplification and INRG stage M. Furthermore, high methylation of RASSF6 was correlated to unfavorable outcome, 1p deletion and MYCN amplification in our tumor material. In conclusion This study shows that several genes belonging to the RASSF gene family are methylated in neuroblastoma. The genes RASSF5 , RASSF6 and RASSF7 stand out as the most promising candidate genes for further investigations in neuroblastoma.
Benefit of Glycoprotein IIb/IIIa Inhibition in Patients With Acute Coronary Syndromes and Troponin T–Positive Status
Authors: L. Kristin Newby, E. Magnus Ohman, Robert H. Christenson, David J. Moliterno, Robert A. Harrington, Harvey D. White, Paul W. Armstrong, Frans Van de Werf, Matthias Pfisterer, Vic Hasselblad, Robert M. Califf, Eric J. Topol
Journal: Circulation (2001)

Background —Troponin T (TnT) is valuable for short- and long-term risk stratification of patients with acute coronary syndromes (ACS). It also may predict which ACS patients will benefit from glycoprotein (GP) IIb/IIIa blockade. Methods and Results —We prospectively studied 1160 patients with non–ST-segment elevation ACS randomized in PARAGON-B to receive lamifiban, an intravenous GP IIb/IIIa antagonist, or placebo. TnT levels were obtained before study treatment began and 24 to 72 hours later; assays were performed by a blinded core laboratory. At baseline, 40.2% of patients were TnT-positive (≥0.1 ng/mL); these patients were older and more often male or smokers. Patients positive at baseline had a significantly higher rate of the primary end point (composite of death, myocardial [re]infarction, or severe recurrent ischemia at 30 days; odds ratio, 1.5; 95% CI, 1.1 to 2.1) than those who were TnT-negative. Lamifiban was associated with significant reduction in the primary end point (from 19.4% to 11.0%, P =0.01) among TnT-positive patients but not among TnT-negative patients (11.2% for placebo versus 10.8% for lamifiban, P =0.86; P =0.08 for test of interaction between TnT status and treatment assignment). This pattern held for the end points of death alone and death or myocardial (re)infarction at 30 days. Peak TnT level at 48 hours did not differ with lamifiban treatment. Conclusions —TnT predicts poor short-term outcomes in non–ST-segment elevation ACS. Treatment benefit with lamifiban is limited almost exclusively to TnT-positive patients, reducing 30-day adverse outcomes to a rate nearly identical to that of negative patients.
INFUSION OF VINCRISTINE AND DOXORUBICIN WITH ORAL DEXAMETHASONE AS FIRST-LINE THERAPY FOR MULTIPLE MYELOMA
Authors: Diana Samson, Adrian Newland, Joseph Kearney, Miles Joyner, Terry Mitchell, A.John Barrett, Elizabeth Gaminara, John Van De Pette, Donald McCarthy, Lyn Aston, Mike Hamon, Maggie Evans
Journal: The Lancet (1989)
Clinical Management of Tuberculosis in the Context of HIV Infection
Authors: Bouke C. de Jong, Dennis M. Israelski, Elizabeth L. Corbett, Peter M. Small
Journal: Annual Review of Medicine (2004)

Globally, the HIV and tuberculosis epidemics are stoking each other, creating a public health crisis of enormous proportions. At the level of individuals, contemporaneous infection with M. tuberculosis and HIV poses great challenges to clinical management. This chapter provides an overview of active and latent tuberculosis treatment in HIV-infected and -uninfected individuals. The discussion focuses on medication issues, including interactions between antitubercular drugs, antiretroviral drugs, and medicines used for opportunistic infections and treatment in the face of comorbidities. Clinical questions specific to coinfection are discussed, including duration and timing initiation of therapy and immune reconstitution. Most of the data presented were generated in industrialized settings and are presented to assist patient management in such settings. However, given the disproportionate amount of TB/HIV in less-developed nations and the increasing availability of antiretroviral therapy in resource-limited settings, the issues presented will become increasingly relevant globally.
Cimetidine and duodenal ulcer.
Authors: J H Baron, J Alexander-Williams, J R Bennett
Journal: BMJ (1979)

Effective rational treatment of duodenal ulcer disease, a life-long diathesis with bouts and remissions, is based on ill-understood pathophysiology: excessive acid enters the duodenum with peptic digestion and ulceration.Most ulcers heal over a period of weeks, but the natural healing rate can be improved by increasing mucosal resistance with drugs such as carbenoxolone or by decreasing gastric secretion with drugs such as the H2 receptor antagonist cimetidine.Patients with clinically intractable or chronic recurrent duodenal ulcers used to be advised operation.In the early 1900s gastroenterostomy diverted gastric juice away from the bulb and allowed almost every duodenal ulcer to heal.This .operationwas abandoned because ulceration occurred in the jejunum receiving the diverted stream of acid pepsin.Vagotomy and/or antrectomy or partial gastrectomy reduce peak acid output by 60% to 80% and prevent ulcer recurrence in about 90%.In my model (fig 1) there is a threshold peak acid output
Risk factors for recent transmission of<i>Mycobacterium tuberculosis</i>
Authors: E. Heldal, U.R. Dahle, P. Sandven, D.A. Caugant, N. Brattaas, H.T. Waaler, D.A. Enarson, A. Tverdal, J. Kongerud
Journal: European Respiratory Journal (2003)

In recent decades, the decline of tuberculosis has stopped in Western Europe, mainly due to increased immigration from high-prevalence countries. The objective of the current study was to identify risk factors for developing tuberculosis following recent infection, in order to better target interventions. Strains from 861 culture-positive cases, diagnosed in Norway in 1994–1999, were analysed by use of restriction fragment length polymorphism (RFLP). A cluster was defined as two or more isolates with identical RFLP patterns. Risk factors for being part of a cluster were identified by univariate and multivariate analysis. A total of 134 patients were part of a cluster. These constituted 5% Asian-born, 18% Norwegian-born, 24% European-born and 29% African-born patients. Four independent risk factors for being part of a cluster were identified: being born in Norway, being of young age, being infected with an isoniazid-resistant strain and being infected with a multidrug-resistant strain. Transmission of tuberculosis may be further reduced by improving case management, contact tracing, preventive treatment, screening of immigrants and access to health services for the foreign-born population.
Extracellular nucleotides are potent stimulators of human hematopoietic stem cells in vitro and in vivo
Authors: Roberto M. Lemoli, Davide Ferrari, Miriam Fogli, Lara Rossi, Cinzia Pizzirani, Sylvia Forchap, Paola Chiozzi, Diletta Vaselli, Francesco Bertolini, Thomas Foutz, Michela Aluigi, Michele Baccarani, Francesco Di Virgilio
Journal: Blood (2004)
Percutaneous and Minimally Invasive Valve Procedures
Authors: Todd K. Rosengart, Ted Feldman, Michael A. Borger, Thomas A. Vassiliades, A. Marc Gillinov, Katherine J. Hoercher, Alec Vahanian, Robert O. Bonow, William O’Neill
Journal: Circulation (2008)

The incidence of valvular heart disease is expected to increase over the next several decades as a large proportion of the US demographic advances into the later decades of life. At the same time, the next several years can be anticipated to bring a broad transition of surgical therapy to minimally invasive (minithoracotomy and small port) access and the more gradual introduction of percutaneous approaches for the correction of valvular heart disease. Broad acceptance of these technologies will require careful and sometimes perplexing comparisons of the outcomes of these new technologies with existing standards of care. The validation of percutaneous techniques, in particular, will require the collaboration of cardiologists and cardiac surgeons in centers with excellent surgical and catheter experience and a commitment to trial participation. For the near term, percutaneous techniques will likely remain investigational and will be limited in use to patients considered to be high risk or to inoperable surgical candidates. Although current-generation devices and techniques require significant modification before widespread clinical use can be adopted, it must be expected that less invasive and even percutaneous valve therapies will likely have a major impact on the management of patients with valvular heart disease over the next several years.
Does Barrett's surveillance really detect more dysplasia?
Authors: S. Zeki, S. Oke, J. Deacon, D. Morris
Journal: Gut (2011)

<h3>Introduction</h3> Barrett9s oesophagus is a premalignant condition affecting 2% of the UK population with a lifetime risk of developing oesophageal adenocarcinoma of 1%. UK Guidelines released in 2005 recommend endoscopic surveillance 2 yearly or sooner depending on histology.1 The impact of surveillance is contentious. In our Trust formal Barrett9s surveillance did not commence until after the guidelines were introduced – prior to this, the surveillance interval varied between the consultants. The introduction of the guidelines locally provided a unique opportunity for comparison with non surveillance. <h3>Methods</h3> The hospitals involved serve a catchment area of 500,000 patients. Patient records were searched for all patients who underwent a gastroscopy for any indication and who had an endoscopic diagnosis of CLO between January 2004 and December 2009 at a district general hospital in the UK. Oesophageal dysplasia and cancer records were obtained separately and cross referenced with the CLO database. <h3>Results</h3> The results of 1270 gastroscopies detecting CLO in 791 patients are shown in table 1. <h3>Conclusion</h3> Although the study was observational and not powered to show significant differences, the results suggest that in our population, CLO associated dysplasia is just as likely to be diagnosed in those undergoing surveillance as in symptomatic patients. This argues in favour of a surveillance programme as without it the number of detected dysplasias would be significantly less. Although not significant, more cancers were diagnosed on interim endoscopies in those already on a surveillance programme. This may argue for increased vigilance at the time of surveillance or a decreased interval between surveillance endoscopies. Randomised prospective studies such as the BOSS study will answer the question fully in time.
Molecular analysis of immunoglobulin genes reveals frequent clonal relatedness in double monoclonal gammopathies
Authors: R C Tschumper, A Dispenzieri, R S Abraham, K J Henderson, D F Jelinek
Journal: Blood Cancer Journal (2013)

Monoclonal gammopathies (MGs) are hematological diseases characterized by high levels of a monoclonal immunoglobulin (Ig) or M-protein. Within this group are patients with more than one M-protein, referred to as double MGs (DMGs). The M-proteins in DMG patients may have different heavy chain (HC) isotypes that are associated with different light chains (LCs), or different HCs that are LC matched. In this study, we examined the clonal relatedness of the M-proteins in the latter type in a cohort of 14 DMG patients. By using PCR, we identified 7/14 DMG patients that expressed two Ig HC isotypes with identical Ig HC variable (IGHV), diversity (IGHD), joining (IGHJ), and complementarity determining region (HCDR3) sequences. Two additional DMG patients had two Ig transcripts using the same IGHV, IGHD and IGHJ genes but with slight differences in variable region or HCDR3 mutations. LC analysis confirmed that a single LC was expressed in 3/7 DMG patients with identical HC transcripts and in the two DMGs with highly similar transcripts. The PCR findings were confirmed by immunofluorescence for HC and LC expression. Clonally related HC-dissimilar/LC-matched DMGs may occur often and defines a new subtype of MG that may serve as a tool for studies of disease pathogenesis.
Loss of receptor-mediated lipid uptake via scavenger receptor A or CD36 pathways does not ameliorate atherosclerosis in hyperlipidemic mice
Authors: Kathryn J. Moore, Vidya V. Kunjathoor, Stephanie L. Koehn, Jennifer J. Manning, Anita A. Tseng, Jessica M. Silver, Mary McKee, Mason W. Freeman
Journal: Journal of Clinical Investigation (2005)

Macrophage internalization of modified lipoproteins is thought to play a critical role in the initiation of atherogenesis. Two scavenger receptors, scavenger receptor A (SR-A) and CD36, have been centrally implicated in this lipid uptake process. Previous studies showed that these receptors mediated the majority of cholesterol ester accumulation in macrophages exposed to oxidized LDL and that mice with deletions of either receptor exhibited marked reductions in atherosclerosis. This work has contributed to an atherosclerosis paradigm: scavenger receptor–mediated oxidized lipoprotein uptake is required for foam cell formation and atherogenesis. In this study, Apoe–/– mice lacking SR-A or CD36, backcrossed into the C57BL/6 strain for 7 generations, were fed an atherogenic diet for 8 weeks. Hyperlipidemic Cd36–/–Apoe–/– and Msr1–/–Apoe–/– mice showed significant reductions in peritoneal macrophage lipid accumulation in vivo; however, in contrast with previous reports, this was associated with increased aortic sinus lesion areas. Characterization of aortic sinus lesions by electron microscopy and immunohistochemistry showed abundant macrophage foam cells, indicating that lipid uptake by intimal macrophages occurs in the absence of CD36 or SR-A. These data show that alternative lipid uptake mechanisms may contribute to macrophage cholesterol ester accumulation in vivo and suggest that the roles of SR-A and CD36 as proatherosclerotic mediators of modified LDL uptake in vivo need to be reassessed.
Efficacy and safety of the selective co-stimulation modulator abatacept following 2 years of treatment in patients with rheumatoid arthritis and an inadequate response to anti-tumour necrosis factor therapy
Authors: M C Genovese, M Schiff, M Luggen, J-C Becker, R Aranda, J Teng, T Li, N Schmidely, M Le Bars, M Dougados
Journal: Annals of the Rheumatic Diseases (2007)

Objective: To evaluate the safety and efficacy of abatacept during 2 years of the ATTAIN ( A batacept T rial in T reatment of A nti-TNF IN adequate responders) trial in patients with rheumatoid arthritis. Methods: Patients completing the 6-month, double-blind period were eligible to enter the long-term extension; patients received abatacept ∼10 mg/kg, plus disease-modifying antirheumatic drugs. Safety and efficacy (American College of Rheumatology (ACR) criteria responses, DAS28 (C-reactive protein), HAQ-DI, SF-36, Medical Outcomes Study Sleep Problems Index, fatigue VAS) were assessed through 2 years. Results: 317 patients (218 from the abatacept and 99 from the placebo group) entered and 222 (70%) completed 18 months of long-term extension treatment. The incidence and type of adverse events were consistent between the double-blind and cumulative (double-blind plus long-term extension) periods. Rates of serious adverse events were 25.6 and 23.4 per 100 patient-years in the double-blind versus cumulative period. At 6 months and 2 years, using non-responder analyses, ACR responses in abatacept-treated patients were: ACR 20, 59.4% and 56.2%; ACR 50, 23.5% and 33.2%; ACR 70, 11.5% and 16.1%; HAQ-DI responses were 54.4% and 47.9%. At 6 months and 2 years, using post-hoc as-observed analyses, the percentage of patients (95% confidence interval) achieving DAS28 (C-reactive protein) low disease activity score (⩽3.2) and DAS28 (C-reactive protein)-defined remission (&lt;2.6) increased from 18.3% (13.0, 23.5) to 32.0% (24.6, 39.4) and 11.1% (6.8, 15.3) to 20.3% (13.9, 26.6). Clinically meaningful improvements in SF-36, pain, fatigue and sleep problems were also maintained throughout the 2 years of abatacept treatment. Conclusion: No unique safety observations were reported during open-label exposure. Improvements in the signs and symptoms of rheumatoid arthritis, physical function and health-related quality of life observed after 6 months, were maintained throughout the 2 years in this population with difficult-to-treat disease. Trial registration number: NCT00124982.
Heat Shock Protein 27 Associates with Basolateral Cell Boundaries in Heat-Shocked and ATP-Depleted Epithelial Cells
Authors: Eric A. Shelden, Michael J. Borrelli, Fiona M. Pollock, Rita Bonham
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Heat stress alters epithelial barrier function, and heat stress preconditioning protects epithelial function from injury. Hsp27 is a small stress protein that has previously been shown to modulate actin assembly. Thus, by regulating actin filaments associated with cell junctions, hsp27 could alter epithelial function. To begin to address this hypothesis, the regulation and distribution of a human hsp27-green fluorescence fusion protein (EGFPhHsp27) that is expressed in cultured renal epithelial cells was assessed. EGFPhHsp27, like the endogenous hsp27, associated with the cytoskeleton in heat-stressed and chemically ATP-depleted cells, and both proteins were regulated similarly. Confocal microscopy of intact and detergent-lysed cells revealed novel distribution patterns in which EGFPhHsp27 associated with basolateral, but not apical, cell borders in injured cells. Double labeling studies revealed EGFPhHsp27 and actin filament colocalization in ATP-depleted cells. However, during heat shock, granules of EGFPhHsp27 were found at sites of cell-cell contact and in the cell body, but colocalization with actin was not apparent. Thus, heat stress and ATP depletion induce distinct patterns of hsp27 redistribution in epithelial cells, and sites of cell-cell and cell-substrate attachment are unique in their ability to recruit hsp27 during injury. The association of EGFPhHsp27 with basolateral cell boundaries supports a potential role for hsp27 in protection or regulation of epithelial cell-cell and cell-substrate attachments.
Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis
Authors: Paolo Prandoni, Anthonie W. A. Lensing, Andrea Piccioli, Enrico Bernardi, Paolo Simioni, Bruno Girolami, Antonio Marchiori, Paola Sabbion, Martin H. Prins, Franco Noventa, Antonio Girolami
Journal: Blood (2002)
Incidence of Colectomy During Long-term Follow-up After Cyclosporine-Induced Remission of Severe Ulcerative Colitis
Authors: David N. Moskovitz, Gert Van Assche, Benedikte Maenhout, Joris Arts, Marc Ferrante, Severine Vermeire, Paul Rutgeerts
Journal: Clinical Gastroenterology and Hepatology (2006)
Spontaneous pneumothorax and tuberculosis: long-term follow-up
Authors: J. L. Freixinet, J. A. Caminero, J. Marchena, P. M. Rodriguez, J. A. Casimiro, M. Hussein
Journal: European Respiratory Journal (2010)

Though spontaneous pneumothorax (SP) is a well-known complication of pulmonary tuberculosis (TB), there are very few reports addressing this topic. For this reason, we retrospectively analysed the experience of SP in patients diagnosed with TB in our hospital between 1989 and 2010. Out of 872 patients treated for SP during this period, 47 (5.4%) had TB antecedents, 21 with active TB (0.95% of the 2,089 TB cases diagnosed during this period) and 26 with residual inactive TB. 46 cases were treated with pleural drainage (PD): 40 (85%) with only one PD, two with two, and four with three. The mean ± SD length of PD treatment was 12.9 ± 11.3 days. In 11 (23%) cases, a relapse of SP occurred, with no statistical relationship between the different studied variables. In 13 (28%) cases, it became necessary to carry out a resection (atypical segmentectomy in all cases) for persistent air leaks with PD. Survival statistics were unfavourable only in elderly patients and those infected with HIV. We conclude that the treatment of SP secondary to TB with PD is usually a sound response, with a good general prognosis and a low percentage of cases that require another PD and surgical treatment.
Evaluation of Pulmonary Arterial End-Diastolic Pressure as an Indirect Estimate of Left Atrial Mean Pressure
Authors: B. S. JENKINS, R. D. BRADLEY, M. A. BRANTHWAITE
Journal: Circulation (1970)

Simultaneously recorded values for mean left atrial pressure (LAMP) and end-diastolic pulmonary arterial pressure (PAEDP) were compared in 28 patients with acute or chronic cardiac disease. Atrial pressure was varied by alterations in blood volume or the administration of inotropic agents. One hundred twenty paired values were divided into three groups according to the pulmonary vascular resistance which was calculated on each occasion. Although LAMP and PAEDP were shown to correlate significantly at all levels of pulmonary vascular resistance, worthwhile estimates of LAMP could only be obtained from PAEDP when the pulmonary vascular resistance was normal.
Combination of PI3K/mTOR Inhibitors: Antitumor Activity and Molecular Correlates
Authors: Marco Mazzoletti, Francesca Bortolin, Laura Brunelli, Roberta Pastorelli, Silvana Di Giandomenico, Eugenio Erba, Paolo Ubezio, Massimo Broggini
Journal: Cancer Research (2011)

The phosphatidylinositol-3-kinase (PI3K)/Akt/mTOR pathway is a major target for cancer therapy. As a strategy to induce the maximal inhibition of this pathway in cancer cells, we combined allosteric mTOR inhibitors (rapamycin and RAD001) with a dual PI3K/mTOR kinase inhibitor (PI-103). Both in vitro and in vivo, the combination exhibited more activity than single agents in human ovarian and prostate cancer cells that harbor alterations in the pathway. At the molecular level, combined inhibition of mTOR prevented the rebound activation of Akt that is seen after treatment with rapamycin and its analogues and caused more sustained inhibition of Akt phosphorylation. Furthermore, the combination strongly inhibited the expression of PI3K/Akt/mTOR downstream proteins. In particular, it showed greater activity than the single agents in inhibiting the phosphorylation of 4EBP1, both in vitro and in vivo, resulting in selective inhibition of CAP-dependent translation. A proteomic approach was used to confirm the identification of c-Myc as the key regulator for the reduction in downstream proteins affected by the combined inhibition of mTOR. In conclusion, the combination of a catalytic and an allosteric inhibitor of mTOR shows greater activity, without a concomitant increase in toxicity, than either drug alone, and this may have therapeutic implications for inhibiting this pathway in the clinical setting.