tbuckley/cabot-search huggingface dataset:
Distinct patterns of 1p and 19q alterations identify subtypes of human gliomas that have different prognoses†
Authors: Artemis P. Vogazianou, Raymond Chan, L. Magnus Bäcklund, Danita M. Pearson, Lu Liu, Cordelia F. Langford, Simon G. Gregory, V. Peter Collins, Koichi Ichimura
Journal: Neuro-Oncology (2010)

We studied the status of chromosomes 1 and 19 in 363 astrocytic and oligodendroglial tumors. Whereas the predominant pattern of copy number abnormality was a concurrent loss of the entire 1p and 19q regions (total 1p/19q loss) among oligodendroglial tumors and partial deletions of 1p and/or 19q in astrocytic tumors, a subset of apparently astrocytic tumors also had total 1p/19q loss. The presence of total 1p/19q loss was associated with longer survival of patients with all types of adult gliomas independent of age and diagnosis (P = .041). The most commonly deleted region on 19q in astrocytic tumors spans 885 kb in 19q13.33–q13.41, which is telomeric to the previously proposed region. Novel regions of homozygous deletion, including a part of DPYD (1p21.3) or the KLK cluster (19q13.33), were observed in anaplastic oligodendrogliomas. Amplifications encompassing AKT2 (19q13.2) or CCNE1 (19q12) were identified in some glioblastomas. Deletion mapping of the centromeric regions of 1p and 19q in the tumors that had total 1p/19q loss, indicating that the breakpoints lie centromeric to NOTCH2 within the pericentromeric regions of 1p and 19q. Thus, we show that the copy number abnormalities of 1p and 19q in human gliomas are complex and have distinct patterns that are prognostically predictive independent of age and pathological diagnosis. An accurate identification of total 1p/19q loss and discriminating this from other 1p/19q changes is, however, critical when the 1p/19q copy number status is used to stratify patients in clinical trials.
DNA Structure-induced Genomic Instability In Vivo
Authors: Guliang Wang, Steve Carbajal, Jan Vijg, John DiGiovanni, Karen M. Vasquez
Journal: JNCI Journal of the National Cancer Institute (2008)

Copy numbers were estimated by combining the results of quantitative polymerase chain reaction (PCR) and real-time PCR by comparing the signal intensity or ⌬ ⌬ Ct of integrated fragments to the Gapdh gene.† Mouse tail DNA showing a positive signal in any one of the PCRs using AmpF/R, NonBF/R, or NeoF/R primers was considered as "positive".
Effect of aspirin and NSAIDs on risk and survival from colorectal cancer
Authors: Farhat V N Din, Evropi Theodoratou, Susan M Farrington, Albert Tenesa, Rebecca A Barnetson, Roseanne Cetnarskyj, Lesley Stark, Mary E Porteous, Harry Campbell, Malcolm G Dunlop
Journal: Gut (2010)

<h3>Background</h3> Previous studies have shown that aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) lower colorectal cancer (CRC) risk. However, the lowest effective NSAID dose, treatment duration, and effects on survival are not defined. In a large population-based case–control study, we have explored the relationship between NSAID dose and duration, CRC risk and overall CRC-specific survival. <h3>Methods</h3> The relationship between NSAID use and CRC risk was examined in 2279 cases and 2907 controls. Subjects completed food-frequency and lifestyle questionnaires. NSAID categories were low-dose aspirin (75 mg), non-aspirin NSAIDs (NA-NSAIDs) and any NSAID. Users were defined as taking &gt;4 tablets/week for &gt;1 month. ORs were calculated by logistic regression models and adjusted for potential confounding factors. Effect of NSAID use on all-cause and CRC-specific mortality was estimated using Logrank tests and Cox9s hazard models. <h3>Results</h3> In all, 354 cases (15.5%) were taking low-dose aspirin compared to 526 controls (18.1%). Low-dose aspirin use was associated with decreased CRC risk (OR 0.78 95% CI 0.65 to 0.92, p=0.004), evident after 1 year and increasing with duration of use (p<sub>trend</sub>=0.004). NA-NSAID and any NSAID use were also inversely associated with CRC. There was no demonstrable effect of NSAIDS on all-cause (HR 1.11, p=0.22, 0.94–1.33) or CRC-specific survival (HR 1.01, p=0.93, 0.83–1.23). <h3>Conclusion</h3> This is the first study to demonstrate a protective effect against CRC associated with the lowest dose of aspirin (75 mg per day) after only 5 years use in the general population. NSAID use prior to CRC diagnosis does not influence survival from the disease.
Dicrotic pulse after open heart surgery.
Authors: R C Orchard, E Craige
Journal: Circulation (1980)

Pre- and postoperative echophonocardiograms (EPCGs) and preoperative hemodynamic data of 108 patients who underwent valve replacement were reviewed to establish the frequency and significance of a dicrotic pulse (DP) postoperatively. DP occurred almost exclusively in patients who underwent valve replacement for regurgitant lesions (20 of 28 with aortic regurgitation, nine of 25 with mitral regurgitation, and four of six with both aortic and mitral regurgitation). These patients were divided into dicrotic and nondicrotic groups. Preoperatively, the dicrotic group had significantly larger end-diastolic volumes (p < 0.01) and end-systolic volumes (p < 0.01) and significantly lower ejection fractions (p < 0.01). Echocardiographically, the dicrotic group had larger left ventricular dimensions, both systolic (p < 0.01) and diastolic (p < 0.05), reduced percentage fractional shortening of the left ventricular cavity (p < 0.01) and poor thickening properties of the left ventricular posterior wall (% delta Th-LVPW) (p < 0.01). Postoperatively the dicrotic group had a slightly larger end-diastolic dimension (p = NS) and markedly depressed % delta Th-LVPW (p < 0.001) compared with the nondicrotic group. On follow-up EPCG the persistence of a DP correlated with continued left ventricular dysfunction by echocardiographic and hemodynamic studies and an extremely poor clinical course. DP after valve replacement is therefore an important prognostic sign.
Improved Quality of Life After 1 Year With an Invasive Versus a Noninvasive Treatment Strategy in Claudicants
Authors: Joakim Nordanstig, Charles Taft, Marlene Hensäter, Angelica Perlander, Klas Österberg, Lennart Jivegård
Journal: Circulation (2014)

Background— The quality of evidence for invasive revascularization in intermittent claudication is low or very low. This prospective, randomized, controlled study tested the hypothesis that an invasive treatment strategy versus continued noninvasive treatment improves health-related quality of life after 1 year in unselected patients with intermittent claudication. Methods and Results— After clinical and duplex ultrasound assessment, unselected patients with intermittent claudication requesting treatment for claudication were randomly assigned to invasive (n=79) or noninvasive (n=79) treatment groups. Primary end point was health-related quality of life after 1 year, assessed with Medical Outcomes Study Short Form 36 version 1 and Vascular Quality of Life Questionnaire, and secondary end points included walking distances on a graded treadmill. The Medical Outcomes Study Short Form 36 version 1 physical component summary ( P &lt;0.001) and 2 Medical Outcomes Study Short Form 36 version 1 physical subscales improved significantly more in the invasive versus the noninvasive treatment group. Overall, Vascular Quality of Life Questionnaire score ( P &lt;0.01) and 3 of 5 domain scores improved significantly more in the invasive versus the noninvasive treatment group. Intermittent claudication distance improved significantly in the invasive (+124 m) versus the noninvasive (+50 m) group ( P =0.003), whereas the change in maximum walking distance was not significantly different between groups. Conclusions— An invasive treatment strategy improves health-related quality of life and intermittent claudication distance after 1 year in patients with stable lifestyle-limiting claudication receiving current medical management. Long-term follow-up data and health-economic assessments are warranted to further establish the role for revascularization in intermittent claudication. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01219842.
Role of EGFR family receptors in proliferation of squamous carcinoma cells induced by wound healing fluids of head and neck cancer patients
Authors: L. Licitra, F. Perrone, E. Tamborini, L. Bertola, C. Ghirelli, T. Negri, M. Orsenigo, P. Filipazzi, E. Pastore, M. Pompilio, P. Bossi, L.D. Locati, G. Cantu’, G. Scaramellini, S. Pilotti, E. Tagliabue
Journal: Annals of Oncology (2011)
Delivery of Preventive Services to Older Adults by Primary Care Physicians
Authors: Hoangmai H. Pham, Deborah Schrag, J. Lee Hargraves, Peter B. Bach
Journal: JAMA (2005)

THAT MANY US patients receive suboptimal care and that subgroups disadvantaged on the basis of demographic or socioeconomic characteristics are at special risk. 1,2 Even among advantaged patients, the quality of US health care has been shown to lag well below national goals. 3,4In the landmark Community Quality Index study, McGlynn et al 3 and Kerr et al 5 documented not only that quality of care is suboptimal, but that quality problems are not limited to a specific set of conditions or communities.An emerging body of literature now suggests that quality of care may vary in association with the characteristics of individual physicians and their practices. 4,6,7[10][11][12] We studied the relationship between attributes of physicians and their practices, such as experience, training, sex, and practice setting, and the extent to which their Medicare patients received preventive services.We hypothesized that patients treated by less well-trained physicians, or in less
Company providing NHS IT system is set to receive 1bn more despite failing to deliver
Authors: A. O'Dowd
Journal: BMJ (2013)

The government is set to pay a further £1.1bn (€1.3bn; $1.7bn) to the company that was meant to have delivered a care records system for NHS trusts in parts of England, though the system has not materialised in most areas, MPs have been told.

In addition, £110m is to be paid in compensation to the company in question, CSC (Computer Sciences Corporation), which secured a contract in 2002 to provide the Lorenzo care records system to trusts in the north, Midlands, and east of England.

To date CSC had received around £1.1bn from the government as part of a renegotiated contract, but MPs on the Committee of Public Accounts found out about additional costs during an evidence session held on 12 June as part of their inquiry into the NHS’s national programme for IT.

David Nicholson, chief executive of the …
Regression of atherosclerosis with anti-CD3 antibody via augmenting a regulatory T-cell response in mice
Authors: Tomoyuki Kita, Tomoya Yamashita, Naoto Sasaki, Kazuyuki Kasahara, Yoshihiro Sasaki, Keiko Yodoi, Masafumi Takeda, Kenji Nakajima, Ken-ichi Hirata
Journal: Cardiovascular Research (2014)

Although recent animal studies have investigated the cellular and molecular mechanisms underlying the process of atherosclerosis regression, it remains unknown whether adaptive immune responses including T cells are involved in this process. We investigated the role of T cells in atherosclerosis regression. LDL receptor-deficient mice were fed a high-cholesterol diet for 8 weeks to form atherosclerotic lesions and were then changed to a standard diet, and atherosclerosis was assessed 4 weeks later. Just before changing the diet, the mice received an iv injection of anti-CD3 antibody (CD3-Ab) or control immunoglobulin G for 5 consecutive days. CD3-Ab treatment regressed atherosclerosis and decreased the accumulation of macrophages and CD4+ T cells in the plaques. CD3-Ab treatment also dramatically reduced CD4+ T cells and increased the proportion of regulatory T cells (Tregs). Depletion of Tregs by anti-CD25 antibody injection abolished the regression of atherosclerosis seen in CD3-Ab-treated mice, indicating the essential role for Tregs in this process. CD3-Ab treatment induced rapid regression of established atherosclerosis via reducing CD4+ T cells and increasing the proportion of Tregs. These findings suggest that therapeutic intervention for T-cell-mediated immune responses may represent a novel strategy to induce atherosclerosis regression in combination with lipid-lowering therapy.
Treatment of chronic hepatitis D with famciclovir: A pilot study
Authors: C. Yurdaydin, H. Bozkaya, S. Gürel, Ö. Erkan, E. Erden, F. Memik, H. Deǧertekin, M. Bozdayi, Ö. Uzunalimoǧlu
Journal: Journal of Hepatology (2000)
The valosin-containing protein promotes cardiac survival through the inducible isoform of nitric oxide synthase
Authors: Paulo Lizano, Eman Rashed, Hobin Kang, Huacheng Dai, Xiangzhen Sui, Lin Yan, Hongyu Qiu, Christophe Depre
Journal: Cardiovascular Research (2013)

Expression of the heat shock protein 22 (Hsp22) in the heart stimulates cardiac cell survival through activation of the Akt pathway and expression of the inducible nitric oxide (NO) synthase (iNOS), the mediator of ischaemic preconditioning and the most powerful prophylaxis against cardiac cell death. The goal of the present study was to elucidate the downstream effector by which Hsp22 and Akt increase iNOS expression. We tested both in vivo and in vitro the hypothesis that such an effector is the valosin-containing protein (VCP), an Akt substrate, which activates the transcription factor NF-κB, using a transgenic mouse with cardiac-specific over-expression of Hsp22, as well as isolated rat cardiac myocytes.Using two-dimensional gel electrophoresis and mass spectrometry combined with immunoprecipitation, we found that Hsp22 and Akt co-localize and interact together with VCP. Adeno-mediated over-expression of VCP in isolated cardiac myocytes activated NF-κB and dose-dependently increased the expression of iNOS, which was abolished upon NF-κB inhibition. Over-expression of a dominant-negative (DN) mutant of VCP did not increase iNOS expression. VCP, but not its DN mutant, protected against chelerythrine-induced apoptosis, which was suppressed by inhibition of either NF-κB or iNOS. VCP-mediated activation of the NF-κB/iNOS pathway was also prevented upon inhibition of Akt.We conclude that the Akt substrate, VCP, mediates the increased expression of iNOS downstream from Hsp22 through an NF-κB-dependent mechanism.
Sipuleucel-T Immunotherapy for Castration-Resistant Prostate Cancer
Authors: Philip W. Kantoff, Celestia S. Higano, Neal D. Shore, E. Roy Berger, Eric J. Small, David F. Penson, Charles H. Redfern, Anna C. Ferrari, Robert Dreicer, Robert B. Sims, Yi Xu, Mark W. Frohlich, Paul F. Schellhammer
Journal: New England Journal of Medicine (2010)

Sipuleucel-T, an autologous active cellular immunotherapy, has shown evidence of efficacy in reducing the risk of death among men with metastatic castration-resistant prostate cancer.
Efficacy of Endoscopic Closure of Acute Perforations of the Gastrointestinal Tract
Authors: Rogier P. Voermans, Olivier Le Moine, Daniel von Renteln, Thierry Ponchon, Marc Giovannini, Marco Bruno, Bas Weusten, Stefan Seewald, Guido Costamagna, Pierre Deprez, Paul Fockens
Journal: Clinical Gastroenterology and Hepatology (2012)
Eosinophilic fibrohistiocytic lesion of bone marrow associated with monoclonal gammopathy and osteolytic lesions
Authors: A. Nagler, Y. Ben‐Arieh, B. Brenner, I. Tatarsky, S. Pollack
Journal: American Journal of Hematology (1986)

Abstract We describe a 63‐year‐old male patient with severe osteoporosis, multiple lytic bone lesions, and monoclonal gammopathy (IgGλ). Whereas the tentative diagnosis in this case was multiple myeloma, bone marrow trephine biopsies of the iliac crest and from an osteolytic lesion of the tibia both showed a peculiar infiltrate consisting of numcrous clongated mast cells, eosinophils, and some plasma cells and lymphocytes. The bone marrow lesions fit the diagnosis of eosinophilic fibrohistiocytic lesion of bone marrow (EFHBM). The patient had no abnormality that could be related to a known allcrgic disease, and no relationship to drug hypersensitivity could be established. The features of the bone marrow infiltrate and its association with monoclonal gammopathy may suggest a linkage between EFHBM and the monoclonal gammopathy.
β-Sitosterolemia and Xanthomatosis
Authors: Ashim K. Bhattacharyya, William E. Connor
Journal: Journal of Clinical Investigation (1974)

Although the usual diet may contain 150-250 mg of plant sterols, chiefly beta-sitosterol, only trace amounts of these sterols have heretofore been found in human or animal blood and tissues. We now report elevated plant sterol levels in the blood and tissues of two sisters with extensive tendon xanthomas but normal plasma cholesterol levels. Besides beta-sitosterolemia and xanthomatosis, no other physical, mental, or biochemical abnormalities were detected.Repeatedly, the plasmas of the two sisters have contained 27.1 and 17.7 mg/100 ml of beta-sitosterol, 9.7 and 8.2 mg/100 ml of campesterol, and 0.5 and 0.5 mg/100 ml of stigmasterol, respectively. These plant sterols constituted 15.6 and 11.3% of the total plasma sterols. Some 60% of the plasma beta-sitosterol and campesterol was esterified; the measurable stigmasterol was entirely unesterified. The transport of the plasma beta-sitosterol and campesterol was largely in low density lipoproteins (76 and 83%, respectively). High density lipoproteins carried the remainder. Plant sterols were barely detectable in the very low density lipoprotein fraction. Only trace amounts of stigmasterol could be detected in the low density and high density lipoprotein fractions. The plant sterol content of the red blood cells averaged 12-13 mg/100 ml packed cells or about 13% of the total sterols. Two tendon xanthoma biopsies with the usual high concentration of cholesterol had 36.7 and 4.0 mg of plant sterols/g dry wt, of which 25.7 and 2.9 mg were beta-sitosterol, entirely in the free form. Plant sterols were also found in adipose tissue (0.2 mg/g wet wt) and in skin surface lipids (3.2 mg/g of lipid). The intestinal absorption of beta-sitosterol in both the patients, measured by two techniques, indicated greatly increased absorption of this sterol (about 24 and 28% in the patients L. H. and R. H., respectively, normal absorption being <5%). We suggest that increased absorption of beta-sitosterol must be considered as one cause of this disease. The reason for the extensive xanthomatosis in these two patients remains unknown. Perhaps in some way plant sterols initiated the development of xanthomas with otherwise normal plasma cholesterol levels. Clinical atherosclerosis has not yet occurred. The occurrence of beta-sitosterolemia in these two sisters with un-affected parents suggests an inherited recessive trait.
Breast cancer vaccines: a clinical reality or fairy tale?
Authors: G. Curigliano, G. Spitaleri, E. Pietri, M. Rescigno, F. de Braud, A. Cardillo, E. Munzone, A. Rocca, G. Bonizzi, V. Brichard, L. Orlando, A. Goldhirsch
Journal: Annals of Oncology (2005)
Rosiglitazone Improves Postprandial Triglyceride and Free Fatty Acid Metabolism in Type 2 Diabetes
Authors: Jeroen P.H. van Wijk, Eelco J.P. de Koning, Manuel Castro Cabezas, Ton J. Rabelink
Journal: Diabetes Care (2005)

OBJECTIVE—Increased postprandial lipemia is part of diabetic dyslipidemia and is associated with accelerated atherosclerosis. We investigated the effects of the peroxisome proliferator–activated receptor-γ agonist rosiglitazone on postprandial lipemia in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS—A randomized, 8-week, crossover, placebo-controlled, double-blind trial was performed in which rosiglitazone at 4 mg was administrated twice daily in 19 patients with type 2 diabetes. Standardized 6-h oral fat-loading tests were performed after each treatment period. Postprandial curves were calculated as the total area under the curve (AUC) and the incremental area under the curve (dAUC). RESULTS—Rosiglitazone did not change fasting plasma triglycerides compared with placebo (1.97 ± 0.22 vs. 1.88 ± 0.20 mmol/l, respectively) but decreased postprandial triglyceride levels, leading to significantly lower triglyceride dAUC (−37%, P &amp;lt; 0.05), without changing total triglyceride AUC. Significant postprandial triglyceride reductions in the chylomicron fraction (Svedberg flotation rate [Sf] &amp;gt;400) were achieved with rosiglitazone, which resulted in a significant lower triglyceride AUC (−22%) in this fraction. The postprandial triglyceride increase in VLDL1 (Sf 60–400) was also lower after rosiglitazone (−27%), but this did not result in a significant lower triglyceride AUC. In VLDL2 (Sf 20–60), there were no significant differences in triglyceride AUC and triglyceride dAUC between rosiglitazone and placebo. Rosiglitazone decreased free fatty acid (FFA) AUC (−12%) and FFA dAUC (−18%) compared with placebo. CONCLUSIONS—Rosiglitazone improves the metabolism of large triglyceride-rich lipoproteins and decreases postprandial FFA concentrations in type 2 diabetes. This may have clinical implications, as these effects may contribute to cardiovascular risk reduction.
Prediction of Active Drug Plasma Concentrations Achieved in Cancer Patients by Pharmacodynamic Biomarkers Identified from the Geo Human Colon Carcinoma Xenograft Model
Authors: Feng R. Luo, Zheng Yang, Huijin Dong, Amy Camuso, Kelly McGlinchey, Krista Fager, Christine Flefleh, David Kan, Ivan Inigo, Stephen Castaneda, Tai W. Wong, Robert A. Kramer, Robert Wild, Francis Y. Lee
Journal: Clinical Cancer Research (2005)

Epidermal growth factor receptor (EGFR), a protein tyrosine kinase expressed in many types of human cancers, has been strongly associated with tumor progression. Cetuximab is an IgG(1) anti-EGFR chimeric mouse/human monoclonal antibody that has been approved for the treatment of advanced colon cancer. Using human tumor xenografts grown in nude mice, we have determined the in vivo pharmacodynamic response of cetuximab at efficacious doses. Three pharmacodynamic end points were evaluated: tumoral phospho-EGFR, tumoral mitogen-activated protein kinase (MAPK) phosphorylation, and Ki67 expression.The pharmacodynamic study was conducted in nude mice bearing Geo tumors following a single i.p. administration of 0.25 and 0.04 mg. The tumors were analyzed by immunohistochemistry. The levels of phospho-EGFR were quantitated by an ELISA assay.At 0.25 mg, phospho-EGFR was maximally inhibited by 91% at 24 hours, whereas the level of inhibition decreased to 72% by 72 hours. At 0.04 mg, the maximum inhibition of phospho-EGFR was 53% at 24 hours, whereas the level of inhibition decreased to 37% by 72 hours. The time course of phospho-EGFR inhibition and recovery seemed to correlate with the pharmacokinetics of cetuximab. Immunohistochemical analysis showed that phospho-MAPK and Ki67 expression were inhibited between 24 and 72 hours at 0.25 and 0.04 mg. A pharmacokinetic/pharmacodynamic model was established and predicted that the plasma concentration of cetuximab required to inhibit 90% of phospho-EGFR was 67.5 mug/mL.Phospho-EGFR/phospho-MAPK could be useful clinical biomarkers to assess EGFR inhibition by cetuximab.