tbuckley/cabot-search huggingface dataset:
Abstract 1133: Inactivation of BRG1 in non-small cell lung cancer (NSCLC) cell lines
Authors: Wei Zhang, Ilse Valencia, Jingsheng Yan, Raj Chari, Luc Girard, Junichi Soh, Kit Tam, Yang Xie, Wan Lam, John Minna, Adi Gazdar
Journal: Cancer Research (2010)

Abstract Purpose: To study the frequency and gene expression profile of BRG1 inactivation in NSCLC cell lines. Background: BRG1 is the catalytic subunit of SWI/SNF chromatin remodeling complex and provides ATPase activity necessary for transcriptional regulation of many genes. BRG1 is frequently inactivated in lung cancers and loss of BRG1 correlated with poor prognosis. Methods: Forty NSCLC cell lines containing various gene mutations were analyzed. BRG1 cDNA was sequenced and SNP analysis was used to confirm the large deletion mutants. Gene expression profile was determined by Illumina human WG-6 V3 beadchip (detecting ∼ 48,000 transcripts, ∼25,000 genes). BRG1 mRNA levels were determined by both RNA microarray and qPCR methods. BRG1 protein expression was analyzed by immuno-blotting. Results: Thirteen of forty (33%) NSCLC cell lines had no BRG1 protein expression (n =11) or expressed abnormal size of BRG1 (n =2). BRG1 cDNA was sequenced in these cell lines as well as control cell lines. While 10 control cell lines with normal BRG1 protein expression were not found to contain mutations, eleven cell lines without BRG1 protein expression and one containing abnormal size BRG1 protein were found to have mutations, including deletions, point mutations and insertion. The deletions and point mutations of BRG1 are homozygous. Mutant BRG1 expressed either no or lower than normal levels of BRG1 mRNA. BRG1 inactivation was found more frequent in smokers (50%) than non-smokers (15%), and coexisted with KRAS mutation, but was mutually exclusive to EGFR mutation. Furthermore, inactivation of BRG1 and LKB1, a tumor suppressor gene also located on chromosome 19p and adjacent to BRG1, showed 73% concordance (P=0.03). Finally, RNA microarray analysis showed nearly 800 transcripts (False Discovery Rate &amp;lt;5%) down or up regulated in NSCLC cell lines with BRG1 inactivation compared to cell lines with wild type BRG1. Conclusions: 1) BRG1 is frequently mutated in NSCLC cell lines by deletions or point mutations. 2) There is excellent concordance (98 %) between mutation status and loss of protein expression. 3) Inactivation of BRG1 shows concordance with smoking history and LKB1 mutation, and is negatively correlated with EGFR mutation. 4) Inactivation of BRG1 has a major impact on gene expression profile of NSCLC cell lines. These data indicate that BRG1 may play an important role in lung tumorigenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1133.
Therapeutic, Prophylactic, Untoward, and Contraceptive Effects of Combined Oral Contraceptives: Catholic Teaching, Natural Law, and the Principle of Double Effect When Deciding to Prescribe and Use
Authors: Murray Joseph Casey, Todd A. Salzman
Journal: The American Journal of Bioethics (2014)

Combined oral contraceptives (COC) have been demonstrated to have significant benefits for the treatment and prevention of disease. These medications also are associated with untoward health effects, and they may be directly contraceptive. Prescribers and users must compare and weigh the intended beneficial health effects against foreseeable but unintended possible adverse effects in their decisions to prescribe and use. Additionally, those who intend to abide by Catholic teachings must consider prohibitions against contraception. Ethical judgments concerning both health benefits and contraception are approached in this essay through an overview of the therapeutic, prophylactic, untoward, and contraceptive effects of COC and discussion of magisterial and traditional Catholic teachings from natural law. Discerning through the principle of double effect, proportionate reason, and evidence gathered from the sciences, medical and moral conclusions are drawn that we believe to be fully compliant with good medicine and Catholic teaching.
The in vivo performance of magnetic particle-loaded injectable, in situ gelling, carriers for the delivery of local hyperthermia
Authors: Pol-Edern Le Renard, Olivier Jordan, Antonin Faes, Alke Petri-Fink, Heinrich Hofmann, Daniel Rüfenacht, Frederik Bosman, Franz Buchegger, Eric Doelker
Journal: Biomaterials (2009)
Mechanical properties of the colon: comparison of the features of the African and European colon in vitro.
Authors: D A Watters, A N Smith, M A Eastwood, K C Anderson, R A Elton, J W Mugerwa
Journal: Gut (1985)

The tensile properties of the colon have been examined using methods which gave repeatable results. They showed little change after storage in salt for up to five weeks. The burst strength remained unchanged along the length of the colon. The tensile strength fell distally, as the thickness of the colonic wall increased. The width at burst decreased distally as did the internal diameter. The visco-elastic property of stress relaxation was constant in all regions. The tensile property of the colon was well developed at birth, but fell with age as did the width at burst and the internal diameter. Stress relaxation was unaffected. Because there may be a mechanical abnormality of the colonic wall in diverticular disease and as Europeans are prone to this condition while Africans are not commonly affected, European and African colons were compared. The tensile strength in a Kampala group was greater than in an Edinburgh one, but fell significantly in both groups with age. The width at burst was greater in the Kampala group, but also declined with age. Stress-relaxation was similar in both groups. In view of the similar properties in childhood of colons from Edinburgh and Kampala, the strength of the adult African compared with European colons may derive later from environmental factors such as diet. There were, however, no differences between the colons with and without diverticular disease in European subjects over the age of 50 years.
The Yersinia tyrosine phosphatase: specificity of a bacterial virulence determinant for phosphoproteins in the J774A.1 macrophage.
Authors: J B Bliska, J C Clemens, J E Dixon, S Falkow
Journal: The Journal of Experimental Medicine (1992)

YopH is a plasmid-encoded protein tyrosine phosphatase (PTPase) secreted by pathogenic Yersinia. Although the enzyme likely acts to dephosphorylate eukaryotic proteins during Yersinia infection of the mammalian host, the targets of YopH have not been identified. We infected the murine macrophage-like cell line J774A.1 with Yersinia pseudotuberculosis and investigated the specificity of YopH and YopHC403A, a catalytically inactive mutant derivative, for eukaryotic phosphoproteins. Upon infection, YopH specifically and rapidly dephosphorylated a macrophage protein of 120 kD. The 120-kD protein and a previously detected 55-kD substrate of YopH coprecipitated with YopHC403A. Coprecipitation of these proteins required tyrosine phosphorylation and could be competitively inhibited with excess phosphotyrosine. The 120- and 55-kD proteins that coprecipitate with YopHC403A exhibited the in vitro activity of protein tyrosine kinases (PTKases), suggesting that YopH dephosphorylates activated tyrosine kinases in vivo.
Role of<i>VHL</i>Gene Mutation in Human Cancer
Authors: William Y. Kim, William G. Kaelin
Journal: Journal of Clinical Oncology (2004)

Germline inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene causes the von Hippel-Lindau hereditary cancer syndrome, and somatic mutations of this gene have been linked to the development of sporadic hemangioblastomas and clear-cell renal carcinomas. The VHL tumor suppressor protein (pVHL), through its oxygen-dependent polyubiquitylation of hypoxia-inducible factor (HIF), plays a central role in the mammalian oxygen-sensing pathway. This interaction between pVHL and HIF is governed by post-translational prolyl hydroxylation of HIF in the presence of oxygen by a conserved family of Egl-nine (EGLN) enzymes. In the absence of pVHL, HIF becomes stabilized and is free to induce the expression of its target genes, many of which are important in regulating angiogenesis, cell growth, or cell survival. Moreover, preliminary data indicate that HIF plays a critical role in pVHL-defective tumor formation, raising the possibility that drugs directed against HIF or its downstream targets (such as vascular endothelial growth factor) might one day play a role in the treatment of hemangioblastoma and renal cell carcinoma. On the other hand, clear genotype-phenotype correlations are emerging in VHL disease and can be rationalized if pVHL has functions separate from its control of HIF.
Half as many animals used in medical research as 20 years ago
Authors: Z. Kmietowicz
Journal: BMJ (2002)

The number of animals used annually in medical research has halved over the last 20 years, a UK group representing medical researchers has said.

Just over 2.7m scientific procedures using animals were performed last year. Slightly fewer animals were used than the number of procedures performed, because some animals were used more than once, a new booklet produced by the Research Defence Society has stated.

The booklet, The Hope, the Challenge, the People , is aimed at increasing public understanding of how animals are used in medical research.

Animal technician Pauline Tamplin is one of the six …
Transcriptional and Translational Dual-regulated Oncolytic Herpes Simplex Virus Type 1 for Targeting Prostate Tumors
Authors: Cleo YF Lee, Luke XX Bu, Arrigo DeBenedetti, B Jill Williams, Paul S Rennie, William WG Jia
Journal: Molecular Therapy (2010)

The aim of this project was to demonstrate that an oncolytic herpes simplex virus type 1 (HSV-1) can replicate in a tissue- and tumor-specific fashion through both transcriptional (prostate-specific promoter, ARR2PB) and translational (5′-untranslated regions (5′UTRs) of rFGF-2) regulation of an essential viral gene, ICP27. We generated two recombinant viruses, ARR2PB-ICP27 (A27) and ARR2PB-5′UTR-ICP27 (AU27) and tested their efficacy and toxicity both in vitro and in vivo. The ARR2PB promoter caused overexpression of ICP27 gene in the presence of activated androgen receptors (ARs) and increased viral replication in prostate cells. However, this transcriptional upregulation was effectively constrained by the 5′UTR-mediated translational regulation. Mice bearing human prostate LNCaP tumors, treated with a single intravenous injection of 5 × 107 plaque-forming units (pfu) of AU27 virus exhibited a >85% reduction in tumor size at day 28 after viral injection. Although active viral replication was readily evident in the tumors, no viral DNA was detectable in normal organs as measured by real-time PCR analyses. In conclusion, a transcriptional and translational dual-regulated (TTDR) viral essential gene expression can increase both viral lytic activity and tumor specificity, and this provides a basis for the development of a novel tumor-specific oncolytic virus for systemic treatment of locally advanced and metastatic prostate cancers. The aim of this project was to demonstrate that an oncolytic herpes simplex virus type 1 (HSV-1) can replicate in a tissue- and tumor-specific fashion through both transcriptional (prostate-specific promoter, ARR2PB) and translational (5′-untranslated regions (5′UTRs) of rFGF-2) regulation of an essential viral gene, ICP27. We generated two recombinant viruses, ARR2PB-ICP27 (A27) and ARR2PB-5′UTR-ICP27 (AU27) and tested their efficacy and toxicity both in vitro and in vivo. The ARR2PB promoter caused overexpression of ICP27 gene in the presence of activated androgen receptors (ARs) and increased viral replication in prostate cells. However, this transcriptional upregulation was effectively constrained by the 5′UTR-mediated translational regulation. Mice bearing human prostate LNCaP tumors, treated with a single intravenous injection of 5 × 107 plaque-forming units (pfu) of AU27 virus exhibited a >85% reduction in tumor size at day 28 after viral injection. Although active viral replication was readily evident in the tumors, no viral DNA was detectable in normal organs as measured by real-time PCR analyses. In conclusion, a transcriptional and translational dual-regulated (TTDR) viral essential gene expression can increase both viral lytic activity and tumor specificity, and this provides a basis for the development of a novel tumor-specific oncolytic virus for systemic treatment of locally advanced and metastatic prostate cancers.
Alcohol Consumption, Specific Alcoholic Beverages, and Abdominal Aortic Aneurysm
Authors: Otto Stackelberg, Martin Björck, Susanna C. Larsson, Nicola Orsini, Alicja Wolk
Journal: Circulation (2014)

Studies investigating the role of alcohol consumption in the development of abdominal aortic aneurysm (AAA) are scarce. We aimed to examine associations between total alcohol consumption and specific alcoholic beverages and the hazard of AAA.The study population was made up of 44 715 men from the Cohort of Swedish Men and 35 569 women from the Swedish Mammography Cohort who were 46 to 84 years of age at baseline in 1998. Cox proportional hazards models were used to estimate hazard ratios with 95% confidence intervals for the associations between alcohol consumption, assessed through a food frequency questionnaire, and AAA, identified by means of linkage to the Swedish Inpatient Register and the Swedish Vascular Registry (Swedvasc). Over the 14-year follow-up until December 2011 (1 019 954 person-years), AAAs occurred in 1020 men and 194 women. Compared with the consumption of 1 glass of alcohol per week (12 g of ethanol), the hazard ratio of AAA among men who consumed 10 glasses per week was 0.80 (95% confidence interval, 0.68-0.94). The corresponding hazard ratio among women who consumed 5 glasses per week was 0.57 (95% confidence interval, 0.40-0.82). Among participants free from cardiovascular disease, total alcohol consumption did not seem to be associated with hazard of the disease. The most commonly consumed alcoholic beverages, beer among men and wine among women, were inversely associated, whereas no association was observed for liquor.Moderate alcohol consumption, specifically wine and beer, was associated with a lower hazard of abdominal aortic aneurysm. The associations between higher doses of alcohol and risk of the disease remain unknown.
Effects of Renal Transplantation on Uremic Neuropathy
Authors: Charles F. Bolton, Marcel A. Baltzan, Richard B. Baltzan
Journal: New England Journal of Medicine (1971)

In three of 10 patients with uremic neuropathy improvement began two months after successful renal transplantation, and functional recovery was complete in a year, although residual clinical signs and electrophysiologic abnormalities remained. Of two patients with moderately severe polyneuropathy, one recovered in eight months, but an older patient had only partial recovery after a year. The remaining five cases were subclinical; in three of these, nerve-conduction velocities returned to normal in four to six months. Compressive mononeuropathy, an additional complication in two patients, also improved. Electrophysiologic studies suggest that segmental remyelination and nerve axon regeneration are both a part of the reparative process.
Nondiabetic Kidney Disease
Authors: Andrew S. Levey
Journal: New England Journal of Medicine (2002)

A 66-year-old man without diabetes has worsening hypertension. He has a serum creatinine level of 1.8 mg per deciliter (159 μmol per liter), proteinuria (2+), and a fasting serum low-density lipoprotein cholesterol level of 140 mg per deciliter (3.6 mmol per liter). He smokes half a pack of cigarettes per day. Ultrasonography reveals small, symmetric kidneys without hydronephrosis or cysts. How should this patient be evaluated and treated to slow the progression of kidney disease?
Interferon alfa for chronic hepatitis B infection: Increased efficacy of prolonged treatment
Authors: Harry L. Janssen, Guido Gerken, Vicente Carreño, Patrick Marcellin, Nikolai V. Naoumov, Antonio Craxi, Helmer Ring-Larsen, George Kitis, Jan van Hattum, Richard A. de Vries, Peter P. Michielsen, Fiebo J. ten Kate, Wim C. Hop, Rudolf A. Heijtink, Pieter Honkoop, Solko W. Schalm
Journal: Hepatology (1999)

Interferon alfa (IFN-α) is the primary treatment for chronic hepatitis B. The standard duration of IFN-α therapy is considered 16 weeks; however, the optimal treatment length is still poorly defined. We evaluated the efficacy and acceptability of prolonged IFN-α treatment in patients with chronic hepatitis B. To investigate whether treatment prolongation could enhance the rate of hepatitis B e antigen (HBeAg) seroconversion, we conducted a prospective, controlled, multicenter trial in which all patients were treated with a standard regimen of 10 million units IFN-α 3 times per week over 16 weeks. Patients who were still HBeAg-positive after 16 weeks of therapy were randomized to prolongation of the identical regimen up to 32 weeks (prolonged therapy) or discontinuation of treatment (standard therapy). Among the 162 patients who entered the study, 27 (17%) were HBeAg-negative after the first 16 weeks of treatment, and 118 were randomized to standard or prolonged therapy. After randomization, a response (HBeAg seroconversion and sustained hepatitis B virus [HBV]-DNA negativity) was observed in 7 of the 57 (12%) patients assigned to standard therapy versus 17 of the 61 (28%) patients assigned to prolonged therapy ( P = .04). A low level of viral replication after 16 weeks of treatment, as indicated by serum HBV-DNA values under 10 pg/mL, was found to be the only independent predictor of response (52% vs. 0%; P &lt; .001) during prolonged therapy. The prolonged IFN-α schedule was well tolerated in the large majority of patients. In chronic hepatitis B, prolongation of IFN-α therapy up to 32 weeks is superior to a standard course of 16 weeks. Those patients who exhibit a low level of viral replication at the end of the standard regimen benefit most from prolonged treatment.
ATRIAL FIBRILLATION IN HEART FAILURE IS ASSOCIATED WITH AN INCREASED RISK OF DEATH ONLY IN PATIENTS WITH ISCHEMIC HEART DISEASE
Authors: Jakob Raunso, Ole D. Pedersen, Helena Dominguez, Morten L. Hansen, Jacob E. Moller, Jesper Kjaergaard, Christian Hassager, Christian Torp-Pedersen, Lars Køber
Journal: Journal of the American College of Cardiology (2010)
Planning and control: Are they separable in the brain? Entia non sunt multiplicanda praeter necessitatem
Authors: Myrka Zago, Francesco Lacquaniti, Alexandra Battaglia-Mayer, Roberto Caminiti
Journal: Behavioral and Brain Sciences (2004)

We argue that planning and control may not be separable entities, either at the behavioural level or at the neurophysiological level. We review studies that show the involvement of superior and inferior parietal cortex in both planning and control. We propose an alternative view to the localization theory put forth by Glover.
Serum neutralizing antibody response to the vacuolating cytotoxin of Helicobacter pylori.
Authors: T L Cover, P Cao, U K Murthy, M S Sipple, M J Blaser
Journal: Journal of Clinical Investigation (1992)

Approximately 50% of Helicobacter pylori isolates produce a cytotoxin in vitro that induces vacuolation of eukaryotic cells. To determine the in vivo relevance of this phenomenon, we sought to detect cytotoxin-neutralizing antibodies in sera from H. pylori-infected persons. As a group, sera from 29 H. pylori-infected patients neutralized the activity of the purified cytotoxin to a significantly greater extent than sera from 24 uninfected persons (P = 0.007). The cytotoxin neutralizing activity in sera from H. pylori-infected persons was mediated predominantly by the purified IgG fraction. Sera from H. pylori-infected persons neutralized the cytotoxins produced by multiple H. pylori strains, but failed to neutralize trimethylamine-induced cell vacuolation. Neutralization of cytotoxin activity by human or immune rabbit sera was associated with immunoblot IgG recognition of an 87-kD H. pylori protein. Similarly, neutralization of the toxin by sera was associated with IgG recognition of the purified cytotoxin in an enzyme-linked immunosorbent assay (P less than 0.0001). The presence of cytotoxin-neutralizing antibodies in sera from H. pylori-infected persons indicates that the cytotoxin is synthesized in vivo.
F-18 FDG PET in Insular Thyroid Cancer
Authors: Michaela Diehl, Sinikka Graichen, Christian Menzel, Elmar Lindhorst, Frank Gr??nwald
Journal: Clinical Nuclear Medicine (2003)

Insular thyroid cancer (ITC) is known to be a rare subtype of follicular thyroid carcinoma showing poor differentiation and an unfavorable prognosis. The authors evaluated the use of F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) for restaging and follow-up in ITC.Five patients (2 male, 3 female) with elevated thyroglobulin levels (mean, 86 ng/mL; range 1.3-180 ng/mL) during follow-up underwent FDG PET (Siemens ECAT Exact 47). PET results were correlated to histopathologic and radiologic findings as well as to the results of whole-body radioiodine scintigraphy. In 1 patient a series of 4 PET scans was done.FDG PET showed a total of 10 tumor sites, at least 1 in each patient. Four of those lesions were detected by computed tomography (CT) as well, which in addition revealed 3 lesions that had normal glucose consumption. Five PET lesions were missed by the CT scan because they were found outside the examined volume of CT. Only 1 PET-positive lesion was also radioiodine positive. Three radioiodine-positive lesions with normal glucose metabolism were detected.As known for well and poorly differentiated thyroid cancer of the follicular epithelium, ITC may also show discordance between radioiodine studies and FDG-positive lesions. Given their initially poor differentiation, the ITC clearly showed the expected dominance of less well-differentiated, FDG-positive lesions. Therefore, FDG PET seems to be a very useful tool for the staging and restaging of such tumors.
Stromal cell–derived factor-1α/CXCL12–induced chemotaxis of T cells involves activation of the RasGAP-associated docking protein p62Dok-1
Authors: Seiichi Okabe, Seiji Fukuda, Young-June Kim, Masaru Niki, Louis M. Pelus, Kazuma Ohyashiki, Pier Paolo Pandolfi, Hal E. Broxmeyer
Journal: Blood (2004)
Vitamin E doesn't slow progression to Alzheimer's disease
Authors: David Spurgeon
Journal: BMJ (2005)

Vitamin E, a widely used early intervention for Alzheimer's disease, had no effect on 769 patients with mild cognitive impairment enrolled in a three year randomised placebo controlled doubleblind study published online on 13 April by the New England Journal of Medicine (www.nejm.org, doi:10.1056/NEJMoa050151). The study also showed that although donepezil (Aricept)showed no slowing of the rate of progression of the disease after three years compared with placebo, the drug was associated with a lower rate of progression during the first 12 months of treatment. Patients with an apolipoprotein E allele, which is a risk factor for Alzheimer's disease, showed a significant effect at one, two, and …