tbuckley/cabot-search huggingface dataset:
Abstract 19: Structural insight for the role of Fas binding to FADD and oligomerization degree of Fas/FADD complex in death inducing signaling complex formation
Authors: Qi Yan, Jay M. McDonald, Yuhua Song
Journal: Cancer Research (2011)

Abstract Fas death receptor-activated signaling pathways regulate apoptosis in a variety of cells, including cholangiocarcinoma and other cancer cells. Fas binding to Fas-associated death domain (FADD) activates FADD-caspase-8 binding to form the death-inducing signaling complex (DISC) to trigger apoptosis (Nature reviews 9:231-241, 2008, Cell 81:505-512, 1995). The Fas-Fas association exists primary as a dimer in the Fas-FADD complex and the Fas-FADD tetramer complex has the tendency to form higher oligomers (Nature 457:1019-1022, 2009). The importance of the oligomerized Fas-FADD complex in DISC formation has been confirmed (Nat Struct Mol Biol. 2010 Oct 10). This study sought to provide structural insight for the role of Fas binding to FADD and the oligomerization of Fas/FADD complex in activating FADD-procaspase-8 binding. In this study, we determined the conformational and motion changes of FADD by binding to Fas for the Fas-FADD complex in either dimer or tetramer behavior with molecular dynamics (MD) simulations. The conformational and motion changes in FADD by binding to Fas could directly affect FADD binding to procaspase-8. Results show Fas binding to FADD stabilized FADD conformation, including the increased stability of the critical residues in FADD death effector domain (DED) for FADD-procaspase-8 binding. Fas binding to FADD resulted in the decreased degree of both correlated and anti-correlated motion of the residues in FADD and caused the reversed correlated motion between FADD DED and FADD death domain. The exposure of procaspase-8 binding residues in FADD that allows FADD to interact with procaspase-8 was observed with Fas binding to FADD. We also observed the different degree of the conformational and motion changes of FADD in the Fas-FADD complex with the different degree of oligomerization. The increased conformational stability and the decreased degree of the correlated motion of the residues in FADD in Fas-FADD tetramer complex were observed compared to those in Fas-FADD dimer complex. This study provided structural evidence for the role of Fas binding to FADD and the oligomerization degree of Fas/FADD complex in DISC formation to signal apoptosis. The structural information should facilitate the identification of novel strategies and targets that regulate DISC formation and, thereby, modulate apoptosis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 19. doi:10.1158/1538-7445.AM2011-19
(14) Hereditary multiple fibrofolliculoma: syndrome of Birt, Hogg and Dube
Authors: H.A. Fawcett, K.V. Sanderson
Journal: British Journal of Dermatology (1985)

Journal Article (14) Hereditary multiple fibrofolliculoma: syndrome of Birt, Hogg and Dubé Get access H.A. Fawcett, H.A. Fawcett St George's Hospital, London SW17 Search for other works by this author on: Oxford Academic Google Scholar K.V. Sanderson K.V. Sanderson St George's Hospital, London SW17 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 113, Issue s29, 1 July 1985, Pages 58–59, https://doi.org/10.1111/j.1365-2133.1985.tb13029.x Published: 01 July 1985
Legionnaires' Disease Bacterium (Legionella pneumophila) Multiplies Intracellularly in Human Monocytes
Authors: Marcus A. Horwitz, Samuel C. Silverstein
Journal: Journal of Clinical Investigation (1980)

We have studied the interaction between virulent egg yolk-grown Legionella pneumophila Philadelphia 1 and human blood monocytes in vitro. The leukocytes were cultured in antibiotic-free tissue culture medium supplemented with 15% autologous human serum.
Effects of HIV Protease Inhibitors on Progression of Monocrotaline- and Hypoxia-Induced Pulmonary Hypertension in Rats
Authors: Guillaume Gary-Bobo, Amal Houssaini, Valerie Amsellem, Dominique Rideau, Pierre Pacaud, Aline Perrin, Jérémy Brégeon, Elisabeth Marcos, Jean-Luc Dubois-Randé, Olivier Sitbon, Laurent Savale, Serge Adnot
Journal: Circulation (2010)

Background— Pulmonary hypertension (PH) is among the complications of HIV infection. Combination antiretroviral therapy may influence the progression of HIV-related PH. Because Akt signaling is a potential molecular target of HIV protease inhibitors (HPIs), we hypothesized that these drugs altered monocrotaline- and hypoxia-induced PH in rats by downregulating the Akt pathway, thereby inhibiting pulmonary artery smooth muscle cell proliferation. Methods and Results— Daily treatment with each of 3 first-generation HPIs (ritonavir 30 mg/kg, amprenavir 100 mg/kg, and nelfinavir 500 mg/kg) started 3 weeks after a subcutaneous monocrotaline injection (60 mg/kg) substantially diminished pulmonary artery pressure, right ventricular hypertrophy, number of muscularized pulmonary vessels, pulmonary arterial wall thickness, and proliferating pulmonary vascular Ki67-labeled cells without affecting vessel caspase 3 staining. HPI treatment partially prevented the development of hypoxia- and monocrotaline-induced PH. Monocrotaline-induced PH was associated with marked activation of Akt signaling in the lungs and proximal pulmonary arteries, with increases in phosphorylated Akt, phosphorylated glycogen-synthase-kinase-3β (GSK3), and phosphorylated endothelial nitric oxide synthase, all of which decreased markedly after treatment with each HPI. In contrast, PH-associated increases in phosphorylated extracellular signal-related kinase 1/2 and myosin light-chain phosphatase were unaltered by the HPIs. The 3 HPIs and the phosphatidylinositol 3-kinase inhibitor LY294002 inhibited platelet-derived growth factor–induced phosphorylation of Akt and GSK3 in cultured pulmonary artery smooth muscle cells and blocked cell proliferation; this last effect was abolished by the GSK3 inhibitor SB216763. Conclusion— These results support an effect of HPIs on pulmonary vascular remodeling mediated by inhibition of Akt phosphorylation and consequently of pulmonary artery smooth muscle cell proliferation.
Alpha-Adrenergic Receptor Blockade with Prazosin
Authors: WILSON S. COLUCCI
Journal: Annals of Internal Medicine (1982)

Prazosin, an orally active alpha-1 selective adrenergic antagonist, has been of value in treating patients with hypertension and congestive heart failure. In contrast to non-subtype-selective alpha-adrenergic antagonists and direct-acting vasodilators, prazosin's hypotensive action is accompanied by little or no increase in heart rate, plasma renin, or plasma norepinephrine. Prazosin is a versatile drug that may be used alone or in combination to treat mild, moderate, or severe hypertension. The antihypertensive effect is sustained, and may increase during long-term therapy. The major side effect, postural hypotension after the first drug administration, is related to drug dose and intravascular volume depletion. Other side effects are mild and seldom limit therapy. In patients with congestive heart failure, prazosin results in balanced venous and arterial dilation, similar to that produced by nitroprusside. Attenuation of some or all of prazosin's initial hemodynamic effects has been seen during multiple short-term administrations. However, chronic studies have shown sustained symptomatic and hemodynamic improvement during long-term administration; initial hemodynamic attenuation may be transient or partial, and does not preclude long-term effectiveness, particularly during exercise. Preliminary studies indicate that prazosin may also be effective in treating patients with peripheral vasospasm due to Raynaud's phenomenon or ergotamine overdose.
Controversies in Prostate Cancer Screening
Authors: Mary McNaughton Collins
Journal: JAMA (1996)

The current debate regarding early detection and aggressive treatment of prostate cancer is fueled by the absence of controlled studies defining the risks and benefits of prostate cancer screening, and by the lack of adequately powered trials demonstrating the benefit of curative treatment for early-stage prostate cancer. Pending the results of clinical trials in 10 to 15 years, advocates of early detection of prostate cancer with digital rectal examination and prostate-specific antigen have compared prostate cancer screening with the effective strategy of breast cancer screening, implying that prostate cancer screening should similarly reduce cancer mortality. They have also cited the high burden of disease, the acceptable operating characteristics of digital rectal examination and prostate-specific antigen, a stage shift among cases detected by screening, and the theoretical curability of early-stage disease as sufficient reasons to proceed with screening. These arguments, however, are reminiscent of earlier arguments in favor of lung cancer screening with chest x-ray examination and sputum cytology, a practice ultimately proven ineffective in clinical trials. We reviewed published articles on lung and prostate cancer screening and identified many parallels. While prostate cancer screening may one day prove effective, analogies between the current prostate cancer screening controversy and the older lung cancer screening debate should inject some caution regarding widespread dissemination of prostate cancer screening without experimental evidence that such screening does more good than harm.
Characterization of Gene–Environment Interactions for Colorectal Cancer Susceptibility Loci
Authors: Carolyn M. Hutter, Jenny Chang-Claude, Martha L. Slattery, Bethann M. Pflugeisen, Yi Lin, David Duggan, Hongmei Nan, Mathieu Lemire, Jagadish Rangrej, Jane C. Figueiredo, Shuo Jiao, Tabitha A. Harrison, Yan Liu, Lin S. Chen, Deanna L. Stelling, Greg S. Warnick, Michael Hoffmeister, Sébastien Küry, Charles S. Fuchs, Edward Giovannucci, Aditi Hazra, Peter Kraft, David J. Hunter, Steven Gallinger, Brent W. Zanke, Hermann Brenner, Bernd Frank, Jing Ma, Cornelia M. Ulrich, Emily White, Polly A. Newcomb, Charles Kooperberg, Andrea Z. LaCroix, Ross L. Prentice, Rebecca D. Jackson, Robert E. Schoen, Stephen J. Chanock, Sonja I. Berndt, Richard B. Hayes, Bette J. Caan, John D. Potter, Li Hsu, Stéphane Bézieau, Andrew T. Chan, Thomas J. Hudson, Ulrike Peters
Journal: Cancer Research (2012)

Genome-wide association studies (GWAS) have identified more than a dozen loci associated with colorectal cancer (CRC) risk. Here, we examined potential effect-modification between single-nucleotide polymorphisms (SNP) at 10 of these loci and probable or established environmental risk factors for CRC in 7,016 CRC cases and 9,723 controls from nine cohort and case-control studies. We used meta-analysis of an efficient empirical-Bayes estimator to detect potential multiplicative interactions between each of the SNPs [rs16892766 at 8q23.3 (EIF3H/UTP23), rs6983267 at 8q24 (MYC), rs10795668 at 10p14 (FLJ3802842), rs3802842 at 11q23 (LOC120376), rs4444235 at 14q22.2 (BMP4), rs4779584 at 15q13 (GREM1), rs9929218 at 16q22.1 (CDH1), rs4939827 at 18q21 (SMAD7), rs10411210 at 19q13.1 (RHPN2), and rs961253 at 20p12.3 (BMP2)] and select major CRC risk factors (sex, body mass index, height, smoking status, aspirin/nonsteroidal anti-inflammatory drug use, alcohol use, and dietary intake of calcium, folate, red meat, processed meat, vegetables, fruit, and fiber). The strongest statistical evidence for a gene-environment interaction across studies was for vegetable consumption and rs16892766, located on chromosome 8q23.3, near the EIF3H and UTP23 genes (nominal P(interaction) = 1.3 × 10(-4); adjusted P = 0.02). The magnitude of the main effect of the SNP increased with increasing levels of vegetable consumption. No other interactions were statistically significant after adjusting for multiple comparisons. Overall, the association of most CRC susceptibility loci identified in initial GWAS seems to be invariant to the other risk factors considered; however, our results suggest potential modification of the rs16892766 effect by vegetable consumption.
Intestinal Lipodystrophy (Whipple's Disease)
Authors: Frederick F. Becker
Journal: JAMA (1965)

A CHARACTERISTIC feature of the clinical picture of many cases of intestinal lipodystrophy (Whipple's disease) is the presence of symptoms long before diagnosis.<sup>1-3</sup>Arthralgias, in particular, have been noted for periods of 1 to 15 years before intestinal problems become manifest, and these joint difficulties are often associated with asthenia, weight loss, and pigmentation. The diagnosis, however, is rarely made in the absence of gastrointestinal dysfunction and then finally by histological examination of the intestine or peripheral lymph node.<sup>4</sup> Previously, therefore, it has been impossible to determine if these preexisting symptoms were associated with morphologic alterations and, if they were, to explain the delayed presentation of the intestinal disorder. That the disease may be very slowly progressive is of increasing significance in view of a possible infectious etiology and the reversibility of the bowel disorder after antibiotic treatment.<sup>5-7</sup> In this report the presence of full-blown lesions of
Neuroblastoma, Pheochromocytoma, and Renal Cell Carcinoma
Authors: Richard S. Fairchild
Journal: JAMA (1979)

A 26-year-old woman had a neuroblastoma during infancy; an extra-adrenal pheochromocytoma at age 16 years, with hepatic recurrences during the next ten years; and multifocal renal cell carcinoma. Neuroblastoma and pheochromocytoma, despite their common embryologic origin, to our knowledge have not been previously reported as separate tumors in the same patient. Although many attributes of the patient's tumors suggest a hereditary disorder, thorough investigation disclosed no evidence of heritable conditions associated with any of these tumors in the patient or her family members. Long-term observation of persons surviving after treatment of neuroblastoma will be necessary to determine whether this case represents a previously unidentified tumor predisposition or a sporadic occurrence.
Humana pulls out of UK as another private provider admits reforms are no "gold rush"
Authors: N. Timmins
Journal: BMJ (2011)

Humana, the giant US health insurer, is pulling out of the United Kingdom, unconvinced that Andrew Lansley’s plans to hand over the commissioning of perhaps £70bn (€82bn; $112bn) of NHS care to GPs in England will necessarily open up a lucrative market in commissioning support.

Humana’s decision comes as other potential providers of the wide range of skills needed—from data analysis to negotiating and procurement skills—also seem to be making cautious assessments of the opportunities that the market will yield, at least in the short term. These companies include Bupa, Tribal, and the US owned Aetna and UnitedHealth.

The coalition government’s plans, set out in full in the longest NHS bill in history on 19 January ( BMJ 2011;342:d418, doi:10.1136/bmj.d418), have …
Social enterprise providing services to Wandsworth prison goes bust
Authors: A. Gulland
Journal: BMJ (2009)

A not for profit company providing health care to inmates at Wandsworth Prison has gone bankrupt.

In 2007 Secure Healthcare was the first social enterprise in England to win a contract to provide healthcare services to prisoners, winning a grant from the Department of Health. It promised to give prisoners a voice in the running of the organisation. Prisoners became “members,” and their views were represented up to board level.

The organisation signed a two year contract, which was renewed for a further three years in July this year. However, on 16 September the healthcare provider went into voluntary liquidation, with debts …
Bernard Leo Hoffmann
Authors: Bernard V Lee
Journal: BMJ (2004)

was a renowned nuclear physicist.But what resonates for me, and for the BMJ-at a time when 3000 deaths every day on the world's roads is accepted as the necessary albeit regrettable cost of motorised transportation-is Marcel's contribution as a road safety activist and advocate for justice for those injured and killed.In 1988 Marcel's eldest daughter, Vlasta, died when her car was struck by a speeding driver, who survived, was prosecuted, and was required to pay compensation.Marcel and his family were expected to suffer in silence just like the thousands of other parents who have lost children to road traffic crashes.The state's response to road death is unlike any other form of violent death.There is rarely a proper police investigation, the judicial response is characteristically lackadaisical, and little effort is made to prevent a recurrence.Given the numbers killed and injured each year-over 50 000 deaths and 150 000 permanent disabilities in Europe alone-road death might be thought of as state sanctioned genocide.In many countries, Britain included, road deaths are called "accidents."No one is really responsible and no one is really to blame.Marcel, however, could not accept this.In their fight for justice, those injured on the roads had recruited a formidable ally.Marcel was a scientist, a statesman, and extraordinarily tenacious.He obtained a doctorate in physics at the University of Geneva in 1968.He worked for several years as a
Abstract 304: Feasibility study of next-generation sequencing on residual formalin-fixed paraffin-embedded tissues
Authors: Danielle Mercatante Carrick, Sean Altekruse, Corrine Camalier, Wendy Cozen, Brenda Hernandez, Charles Lynch, Paul McGregor, Michele G. Mehaffey, Lisa McShane, JoyAnn Phillips Rohan, Mickey Williams, Elizabeth M. Gillanders, Leah E. Mechanic, Sheri Schully
Journal: Cancer Research (2014)

Abstract Next Generation Sequencing (NGS) technologies are being used for detection of somatic mutations in tumors and studies of germline variation. However, most NGS studies used DNA isolated either from whole blood or fresh frozen tissue specimens. Meanwhile, the tissue specimens available from most National Cancer Institute (NCI) funded cohorts and the Surveillance, Epidemiology and End Results (SEER) registries (http://seer.cancer.gov/biospecimen/) are primarily formalin fixed paraffin embedded (FFPE). There are limited data, on a small number of FFPE tissue samples, which suggest NGS is feasible. Much less is known about the feasibility of these technologies for large scale studies or using older FFPE specimens (e.g. 5-30 years old). The main objective of this project was to conduct a pilot study to determine whether the DNA obtained from archival FFPE tissue is of sufficient quality and quantity to conduct NGS. Sixty high-grade serous ovarian adenocarcinomas from FFPE tissues which were between 7 and 31 years old were obtained from three SEER registries. DNA was extracted, quantified, quality assessed, and subjected to whole exome sequencing. DNA extraction (yields and quality) and whole exome sequencing (depths of coverage and exome coverage obtained) results from this study will be presented. Ultimately, data derived from this analysis could serve as the basis for determining the utility of archival FFPE biospecimens for characterization and discovery projects utilizing NGS technologies instead of relying on frozen biospecimens. Citation Format: Danielle Mercatante Carrick, Sean Altekruse, Corrine Camalier, Wendy Cozen, Brenda Hernandez, Charles Lynch, Paul McGregor, Michele G. Mehaffey, Lisa McShane, JoyAnn Phillips Rohan, Mickey Williams, Elizabeth M. Gillanders, Leah E. Mechanic, Sheri Schully. Feasibility study of next-generation sequencing on residual formalin-fixed paraffin-embedded tissues. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 304. doi:10.1158/1538-7445.AM2014-304
Gene therapy for cystic fibrosis: challenges and future directions.
Authors: J M Wilson
Journal: Journal of Clinical Investigation (1995)

The initial concept of human gene therapy was permanent cor- rection of a recessive disease by transplantation of ex vivo manipulated stem cells (1).An early and still important model for this strategy is treatment of severe combined immunodeficiency due to adenosine deaminase deficiency by bone marrow- directed gene therapy (2).The autosomal recessive disease cystic fibrosis (CF)' was subsequently considered a candidate for gene therapy when the gene responsible for the disease was isolated in 1989 (3-5).The wide distribution of possible cellular targets for gene transfer in the CF lung and the absence of a known lung epithelial stem cell suggested that an ex vivo approach to gene therapy would not be feasible (6, 7).Research immediately focused on in vivo approaches for gene transfer that could conveniently be delivered into the airway via aerosols.The ensuing research effort has literally dominated the field of human gene therapy of genetic diseases while establishing the basic principles of in vivo gene delivery.This review summarizes critical scientific issues that have emerged in the develop- ment of in vivo gene therapy for CF using adenoviral vectors as a model.The CF conundrum: relationship between defective ion transport and lung disease CF is an autosomal recessive disease affecting many organs.The pulmonary manifestations of CF are the most morbid and life-limiting aspects of the disease and, therefore, have been the target of most pharmacologic and genetic therapeutic interven- tions (8).Autopsy analysis of newborn CF patients who died of meconium ileus suggests that the lung is largely unaffected at birth (9).Some time thereafter, patients develop obstructive lung disease and become colonized with pathogenic microor- ganisms such as Pseudomonas aeruginosa which leads to respi- ratory infection and chronic airway inflammation (8).The end result is severe bronchiectasis and respiratory failure.A recent survey of CF children who underwent bronchoscopy revealed evidence for inflammation (e.g., increased IL-8 in bronchoal-
Rapid Lysis of Coronary Artery Thrombi with Anisoylated Plasminogen: Streptokinase Activator Complex
Authors: VICTOR J. MARDER
Journal: Annals of Internal Medicine (1986)

The ability of anisoylated plasminogen: streptokinase activator complex (APSAC) to induce coronary artery reperfusion after bolus intravenous injection (2 to 4 minutes) was assessed in 29 patients with acute transmural myocardial infarction and complete coronary artery occlusion. A 5-mg dose resulted in reperfusion in 3 of 14 patients (21%); a 5-mg plus 10-mg regimen was successful in 3 of 7 (43%); and a 30-mg dose induced reperfusion in 9 of 15 (60%). Rethrombosis occurred in only 1 of 15 patients (7%) who received 30 mg, as determined by repeat angiography at 24 hours. The mean interval after injection until reperfusion was 35 minutes with the 30-mg dose, and bleeding occurred at the femoral artery catheterization site in only 3 of 15 patients (20%). Intracoronary streptokinase therapy achieved reperfusion in only 2 of the 6 patients in whom the 30-mg dose failed, indicating that this dose of APSAC was sufficient by itself in 9 of 11 (83%) successfully treated patients. Because therapy can be completed within 2 to 4 minutes, APSAC appears to be a most suitable fibrinolytic agent for early treatment of the coronary artery thrombosis associated with acute transmural myocardial infarction.