tbuckley/cabot-search huggingface dataset:
Abstract 5156: Upstream activation of PTEN.
Authors: Adam Naguib, Gyula Bencze, Christopher R. Faehnle, Thomas Schalch, Zsolt Lazar, Cristian I. Ruse, Leemor Joshua-Tor, Darryl J. Pappin, Lloyd C. Trotman
Journal: Cancer Research (2013)

Abstract The PTEN tumor suppressor is among the most frequently altered genes of cancer. PTEN suppression at the protein level is critically associated with disease since PTEN is haploinsufficient in many cancer types, including prostate. We have recently shown strong cooperation between protein phosphatases and PTEN to suppress PI 3-Kinase and AKT signaling in prostate cancer. Intriguingly, our findings showed that PTEN status orchestrates a PHLPP2 response by controlling the protein levels of this phosphatase. Yet, little is known about genes that control the levels and activity of PTEN to a degree that they critically maintain its function in disease. Therefore, it is assumed that PTEN is constitutively active in normal cells. Here we identify the upstream activation mechanism of PTEN and discuss the consequences for cancer diagnosis and therapy with PI 3-Kinase pathway inhibitors. Citation Format: Adam Naguib, Gyula Bencze, Christopher R. Faehnle, Thomas Schalch, Zsolt Lazar, Cristian I. Ruse, Leemor Joshua-Tor, Darryl J. Pappin, Lloyd C. Trotman. Upstream activation of PTEN. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5156. doi:10.1158/1538-7445.AM2013-5156
The medical service increment for teaching (SIFT): a 400m anachronism for the English NHS?
Authors: G. Bevan
Journal: BMJ (1999)

In 1997-8, over £400m ($640m) of NHS money was designated as the medical service increment for teaching (SIFT).1 The manifest purpose of SIFT is to ensure that the NHS supports quality and innovation in undergraduate medical education. This includes supporting the increasing role of teaching in hospitals other than the main university hospital affiliated with each medical school, general practices, and other community settings.2 3 SIFT is designed to be paid in addition to income gained by medical schools for teaching medical students. The latent purpose of SIFT, which paradoxically dominates its distribution, is to ensure a “level playing field” in the healthcare market by covering “historic infrastructure costs, whether or not they are currently required for education.”2 As designed, SIFT is thus in conflict with one of the aims of the government's white paper, The New NHS , which sought to end the way in which instability in the healthcare market resulted in “shoring up the status quo rather than creating the space to plan and implement major improvement.”4

Allocations of SIFT are based on the product of the annual SIFT rate (about £36 000 for institutions outside London and £39 000 in London) and the number of whole time equivalent students who are in the last three years of the five year curriculum, which are traditionally the years of clinical teaching.2 Thus a medical school that has an annual intake of 150 students will have about £16m in SIFT funding available for distribution to healthcare trusts and general practices that teach students. In 1996-7, nearly 90% of SIFT funds were allocated to the main acute teaching trusts (or teaching hospitals); most of the £170m allocated to the Thames regions is spent in London.1 Details are not published, but income from SIFT for …
Prominent Microvascular Proliferation in Clinically Aggressive Neuroblastoma
Authors: Radhika Peddinti, Rana Zeine, Dragos Luca, Roopa Seshadri, Alexandre Chlenski, Kristina Cole, Bruce Pawel, Helen R. Salwen, John M. Maris, Susan L. Cohn
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Tumor vasculature is disorganized and glomeruloid microvascular proliferation (MVP) has been identified as a poor prognosticator in some adult cancers. To determine the clinical significance of MVP, including glomeruloid MVP in neuroblastoma, we initially examined vessel architecture in tumor sections from 51 children diagnosed at Children's Memorial Hospital (CMH) and subsequently evaluated 154 neuroblastoma tumors on a tissue microarray constructed at Children's Hospital of Philadelphia (CHOP). Experimental Design: H&amp;E sections were examined for the presence of structurally abnormal vessels and further characterized by immunostaining for CD31 and von Willebrand factor to highlight endothelial cells and α-smooth muscle actin for pericytes. Tumors with thickened walls containing a complete layer of hypertrophic endothelial cells plus additional layers of vascular mural cells were classified as MVP positive. Associations between MVP and established clinicopathologic features and outcome were assessed. Results: In both series, MVP was significantly associated with Schwannian stroma-poor histology (CMH, P = 0.008; CHOP, P &amp;lt; 0.001) and decreased survival probability (CMH, P = 0.017; CHOP, P = 0.014). In the CHOP series, MVP was associated with high-risk group classification (P &amp;lt; 0.001), although this association was not seen in the smaller CMH cohort. Conclusions: The association between MVP and poor outcome provides further support for the concept that angiogenesis plays an important role in determining the biological behavior of neuroblastoma tumors. Our results also indicate that angiogenesis is regulated differently in Schwannian stroma-rich versus stroma-poor neuroblastoma tumors. Further studies investigating the activity of angiogenic inhibitors in children with clinically aggressive stroma-poor neuroblastoma are warranted.
HIGH-DOSE CLOPIDOGREL LOADING IS SAFE AND EFFECTIVE IN PATIENTS WITH ST-ELEVATION MYOCARDIAL INFARCTION UNDERGOING PRIMARY PERCUTANEOUS CORONARY INTERVENTION
Authors: Doo Sun Sim, Myung Ho Jeong, Youngkeun Ahn, Young Jo Kim, Sung Chull Chae, Taek Jong Hong, In Whan Seong, Jei Keon Chae, Chong Jin Kim, Myeong Chan Cho, Ki Bae Seung, Seung Jung Park
Journal: Journal of the American College of Cardiology (2010)
Risk Factors and Characterization of Vitiligo and Alopecia Areata in Patients With Chronic Graft-vs-Host Disease
Authors: Rena C. Zuo, Haley B. Naik, Seth M. Steinberg, Kristin Baird, Sandra A. Mitchell, Zoya Kuzmina, Steven Z. Pavletic, Edward W. Cowen
Journal: JAMA Dermatology (2014)

Cutaneous manifestations of chronic graft-vs-host disease (GvHD) are highly variable and may recapitulate well-characterized autoimmune diseases, including systemic sclerosis and Sjögren syndrome. However, vitiligo and alopecia areata (AA) have not been well characterized in the chronic GvHD setting.To determine laboratory markers, transplant-related factors, and other systemic manifestations associated with vitiligo and/or AA in patients with chronic GvHD.A cross-sectional, retrospective study conducted by the National Institutes of Health (NIH) of 282 adult and pediatric patients with chronic GvHD seen under the NIH natural history protocol between 2004 and 2013.Demographic, clinical, and laboratory data, including measures of 11 antibodies, were included in the analysis. Patients with vitiligo and/or AA were identified from dermatologist documentation and photographic evidence. Univariate and multivariable logistic regression analyses were used to determine risk factors for vitiligo and AA development.Fifteen (5.3%) of 282 patients demonstrated vitiligo (14 of 282; 4.9%) and/or AA (2 of 282; 0.7%) (1 patient had both vitiligo and AA). Univariate analysis identified female donor to male recipient sex mismatch (P = .003), positive test results for anticardiolipin (ACA) IgG (P = .03) or antiparietal antibody (P = .049), elevated CD19 level (P = .045), and normal or elevated IgG level (P = .02) as risk factors for vitiligo or AA. Female donor to male recipient sex mismatch (P = .003) and positive findings for ACA-IgG (P = .01) retained significance in the multivariable analysis.Female donor and female donor to male recipient sex mismatch, in particular, are significantly associated with the development of vitiligo and/or AA. Further studies are needed to explore transplant-related risk factors that may lead to better understanding of the pathomechanisms of chronic GvHD.
Carboxyhemoglobin concentrations in smokers of sheesha and cigarettes in Saudi Arabia.
Authors: F M Zahran, M S Ardawi, S F Al-Fayez
Journal: BMJ (1985)

dominant fingers, or the sharp edge of the opened base injures the palmar aspect of the non-dominant fingers if the base is held too close to the unprotected edge.Thus the dorsal aspects of the dominant fingers and the palmar aspects of the non-dominant fingers will be selectively at risk when opening a corned beef can, while injuries from other types ofcan are random.Corned beefis almost uniformly sold in tapered, key opened cans, the design of which is over 100 years old.These cans were originally chosen for their robustness and easy opening.Although the inevitable expense of redesigning corned beef cans may result in higher prices and initial consumer resistance, the design of the can should be reviewed.The cost of the resulting morbidity from these injuries is difficult to quantify, but added to costs of treatment must be those of enforced absences from employment.This study shows that corned beef cans cause a disproportionate number of injuries to the hands of their users and that such injuries are common.
DeLisa’s Physical Medicine &amp; Rehabilitation: Principles and Practice
Authors: Brian M. Kelly
Journal: JAMA (2011)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Prognostic Factors in Pancreatic Endocrine Neoplasms: An Analysis of 136 Cases With a Proposal for Low-Grade and Intermediate-Grade Groups
Authors: Steven N. Hochwald, Sui Zee, Kevin C. Conlon, Roberto Colleoni, Otway Louie, Murray F. Brennan, David S. Klimstra
Journal: Journal of Clinical Oncology (2002)

In some organs (eg, the lung), endocrine tumors are classified on the basis of mitotic rate and necrosis. The purpose of this study was to evaluate prognostic factors in pancreatic endocrine neoplasms recently treated at a single institution.In 136 patients undergoing surgery from 1979 to 1998, the influence on disease-free survival (DFS) and disease-specific survival (DSS) of tumor size, mitotic rate, vascular invasion, necrosis, metastases, and nuclear grade was determined. Cases were further grouped according to an existing proposed classification system and then regrouped on the basis of mitotic rate (< 2 mitoses per 50 high-power fields v higher) and necrosis (present or absent) into low- and intermediate-grade groups.Correlations with DFS and DSS in univariate analysis included < or = 2 mitoses per 50 high-power fields (P =.001, P =.002), vascular invasion (P =.02, P =.04), size < or = 2 cm (P =.01, P =.05), metastases (P =.0002, P =.07), necrosis (P =.002, P =.16), and nuclear grade (P =.04, P =.33), respectively. By multivariate analysis, for DFS, tumor necrosis and presence of metastases retained significance (P =.01, P =.04, respectively). For DSS, only mitotic rate was a prognostic factor (P =.02). Among the 18 macroadenomas, eight borderline tumors, and 48 low-grade carcinomas, there was no significant difference in DSS between any groups (P =.3). However, in evaluating our newly proposed groups, the differences in DFS and DSS between low- and intermediate-grade groups were highly significant (P =.0007, P =.006, respectively).Pancreatic endocrine neoplasms exhibit a spectrum of biologic behavior, and the proposed benign (macroadenoma) and borderline groups contain potentially aggressive tumors. An alternative system based on mitotic rate and necrosis correlates strongly with survival without specifically designating any group as benign.
Is the Glasgow Blatchford Score useful in the risk assessment of patients presenting with variceal haemorrhage?
Authors: B. Reed, H. R. Dalton, O. Blatchford, D. Ashley, C. Mowat, D. R. Gaya, A. Cahill, U. Warshow, N. Hare, H. Begum, A. Cheung, E. Thompson, M. Groome, E. H. Forrest, A. J. Morris, A. J. Stanley
Journal: Gut (2011)

<h3>Introduction</h3> The Glasgow Blatchford Score (GBS) is a pre-endoscopic risk assessment tool for patients presenting with upper gastrointestinal haemorrhage (UGIH). It can predict need for intervention or death and identifies low risk patients suitable for out-patient management.1 There are no published data assessing its use in variceal haemorrhage. Our aim was to compare the GBS with both admission and full Rockall scores in assessment of patients with variceal bleeding. <h3>Methods</h3> Data on consecutive patients presenting to four UK hospitals (Glasgow Royal Infirmary, Royal Cornwall Hospital Truro, University Hospital of North Tees and Ninewells Hospital Dundee) were collected. Admission history, clinical and laboratory data, endoscopic findings, intervention and follow-up were recorded. We compared the ability of GBS and both Rockall scores to predict intervention and death in those patients with a final diagnosis of variceal bleeding. <h3>Results</h3> 1556 patients presented with UGIH to the four hospitals during the study period. 78 had a final diagnosis of variceal bleeding. The mortality of these patients was higher than the non-variceal patients (18% vs 4%; p &lt; 0.0005). On presentation, no variceal bleeding patient had a GBS &lt;3; however, six had an admission Rockall score of zero. The median(range) GBS, admission Rockall and full Rockall scores for the variceal bleeding group were 10(2–18), 3(0–7) and 5(1–10), respectively. The comparable figures for all other patients were 3(0–19), 1(0–7) and 3(0–9), respectively (all p &lt; 0.00005 vs varices). When comparing variceal bleeding patients with those who required intervention or died from another bleeding source, there was no difference using any of the three scores. In predicting need for intervention in the variceal bleeding group, AUC (95% CI) for GBS, admission Rockall and full Rockall scores were: 0.72 (0.56–0.89), 0.46 (0.30–0.62) and 0.66 (0.51–0.83), respectively. For predicting death, the figures were: 0.58 (0.41–0.75), 0.68 (0.54–0.82) and 0.72 (0.58–0.86), respectively. <h3>Conclusion</h3> At presentation, the GBS correctly identifies patients with variceal bleeding as being at high risk for requiring intervention and appears superior to the admission Rockall score for this. However, it is a poor predictor of mortality in this patient group.
Myosin isozyme synthesis and mRNA levels in pressure-overloaded rabbit hearts.
Authors: R Nagai, N Pritzl, R B Low, W S Stirewalt, R Zak, N R Alpert, R Z Litten
Journal: Circulation Research (1987)

The in vivo synthesis rates of myosin isozyme heavy chains beta and alpha were measured in right ventricular (RV) muscle at 2 and 4 days following pulmonary artery constriction in rabbits, together with measurements of their relative mRNA levels. The synthesis rate of beta-myosin heavy chains was elevated in 2-day (0.27 +/- 0.06 day-1 or 2.5 +/- 0.7 mg/g RV/day, mean +/- SD) and in 4-day (0.25 +/- 0.08 day-1 or 2.8 +/- 1.0 mg/g RV/day) pressure overload, when compared to untreated rabbits (0.15 +/- 0.04 day-1 or 1.5 +/- 0.4 mg/g RV/day). However, the synthesis rates of alpha-myosin heavy chains in the same hearts were not altered significantly. There was a differential increase in the fractional synthesis rate of beta vs. alpha heavy chains in 2-day and 4-day pressure overload and in 2-day shams, suggesting switching toward beta heavy chain synthesis had occurred at these time points. beta heavy chain synthesis, as a proportion of total (alpha + beta) heavy chain synthesis, was significantly higher in 4-day pressure overload (78 +/- 9%) than in 4-day sham rabbits (63 +/- 6%). This increase in relative beta-synthesis was associated with a significant increase in the relative proportion of beta heavy chain mRNA level (76 +/- 13% vs. 56 +/- 7%). Furthermore, relative beta-synthesis and the beta-mRNA levels correlated linearly with each other in all experimental groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Source of endogenous arachidonate and 5-lipoxygenase products in human neutrophils stimulated by bradykinin and A23187.
Authors: O H Nielsen, K Bukhave, I Ahnfelt-Ronne, J Rask-Madsen
Journal: Gut (1988)

The lipoxygenase products of arachidonic acid (AA) metabolism, 5-hydroxyeicosatetraenoic acid (5-HETE) and leucotriene B4 (LTB4), are considered to have an important pathophysiological role in inflammatory bowel disease by stimulating the inflammatory response and by contributing to the diarrhoea. The present studies were designed to investigate the effect of the physiological stimulants bradykinin (BK) and 5-hydroxytryptamine (5-HT), in addition to the influence of the calcium ionophore A23187, on the source of AA release and 5-lipoxygenation in human neutrophils (PMNs) in vitro. This was done to elucidate the specificity of the mechanism by which PMNs respond to physiological, extracellular Ca2+ dependent agonists. The results of the study indicate that stimulation of 1-14C-AA-prelabelled PMNs with BK liberates AA mainly from phosphatidylinositol, while A23187 causes release of AA from phosphatidylcholine, phosphatidylethanolamine, and possibly phosphatidylserine. Furthermore BK (10(-9)-10(-6)M) dose-dependently stimulated the formation of 5-HETE and LTB4, reaching a maximum at 10(-7)M, while 5-HT (10(-8)-10(-4)M) released only negligible amounts of eicosanoids, similar to those observed in control experiments. Stimulation with A23187 (10(-5)M) caused a high release of both 5-HETE and LTB4. These results offer evidence that BK, but not 5-HT, initiates formation of lipoxygenase products by binding to specific receptors on the external surface of PMNs, whereas A23187 accelerates 5-lipoxygenation through mechanisms which do not involve a cell surface receptor.
The role of the FPR2/ALX receptor in atherosclerosis development and plaque stability
Authors: Marcelo H. Petri, Andrés Laguna-Fernández, Maria Gonzalez-Diez, Gabrielle Paulsson-Berne, Göran K. Hansson, Magnus Bäck
Journal: Cardiovascular Research (2014)

The formyl peptide receptor (FPR) subtype FPR2/ALX transduces pro-inflammatory responses and participates in the resolution of inflammation depending on activation. The aim of the present study was to unravel the role of FPR2/ALX signalling in atherosclerosis. Expression of FPR2/ALX was analysed in 127 human carotid atherosclerotic lesions and revealed that this receptor was expressed on macrophages, smooth muscle cells (SMCs), and endothelial cells. Furthermore, FPR2/ALX mRNA levels were significantly up-regulated in atherosclerotic lesions compared with healthy vessels. In multiple regression, age, creatinine, and clinical signs of increased cerebral ischaemia were independent predictors of FPR2/ALX expression. To provide mechanistic insights into these observations, we generated Ldlr−/−xFpr2−/− mice, which exhibited delayed atherosclerosis development and less macrophage infiltration compared with Ldlr−/−xFpr2+/+ mice. These findings were reproduced by transplantation of Fpr2−/− bone marrow into Ldlr−/− mice and further extended by in vitro experiments, demonstrating a lower inflammatory state in Fpr2−/− macrophages. FPR2/ALX expression correlated with chemo- and cytokines in human atherosclerotic lesions and leucocytes. Finally, atherosclerotic lesions in Ldlr−/−xFpr2−/− mice exhibited decreased collagen content, and Fpr2−/− SMCs exhibited a profile of increased collagenase and decreased collagen production pathways. FPR2/ALX is proatherogenic due to effects on bone marrow-derived cells, but promoted a more stable plaque phenotype through effects on SMCs. Taken together, these results suggest a dual role of FPR2/ALX signalling in atherosclerosis by way of promoting disease progression and but increasing plaque stability.
DETERMINANTS OF MORTALITY IN ADULTS WITH PULMONARY ARTERIAL HYPERTENSION DUE TO CONGENITAL HEART DISEASE AFTER INITIATION OF ADVANCED THERAPY
Authors: Annelieke CMJ van Riel, Mark Schuuring, Jeroen Vis, Marielle Duffels, Berto Bouma, Barbara Mulder
Journal: Journal of the American College of Cardiology (2012)
Percutaneous Closure of Postinfarction Ventricular Septal Defect
Authors: Patrick A. Calvert, James Cockburn, Dylan Wynne, Peter Ludman, Bushra S. Rana, David Northridge, Michael J. Mullen, Iqbal Malik, Mark Turner, Saib Khogali, Gruschen R. Veldtman, Martin Been, Rob Butler, John Thomson, Jonathan Byrne, Philip MacCarthy, Lindsay Morrison, Len M. Shapiro, Ben Bridgewater, Jo de Giovanni, David Hildick-Smith
Journal: Circulation (2014)

Postinfarction ventricular septal defect carries a grim prognosis. Surgical repair offers reasonable outcomes in patients who survive a healing phase. Percutaneous device implantation represents a potentially attractive early alternative.Postinfarction ventricular septal defect closure was attempted in 53 patients from 11 centers (1997-2012; aged 72±11 years; 42% female). Nineteen percent had previous surgical closure. Myocardial infarction was anterior (66%) or inferior (34%). Time from myocardial infarction to closure procedure was 13 (first and third quartiles, 5-54) days. Devices were successfully implanted in 89% of patients. Major immediate complications included procedural death (3.8%) and emergency cardiac surgery (7.5%). Immediate shunt reduction was graded as complete (23%), partial (62%), or none (15%). Median length of stay after the procedure was 5.0 (2.0-9.0) days. Fifty-eight percent survived to discharge and were followed up for 395 (63-1522) days, during which time 4 additional patients died (7.5%). Factors associated with death after postinfarction ventricular septal defect closure included the following: age (hazard ratio [HR]=1.04; P=0.039), female sex (HR=2.33; P=0.043), New York Heart Association class IV (HR=4.42; P=0.002), cardiogenic shock (HR=3.75; P=0.003), creatinine (HR=1.007; P=0.003), defect size (HR=1.09; P=0.026), inotropes (HR=4.18; P=0.005), and absence of revascularization therapy for presenting myocardial infarction (HR=3.28; P=0.009). Prior surgical closure (HR=0.12; P=0.040) and immediate shunt reduction (HR=0.49; P=0.037) were associated with survival.Percutaneous closure of postinfarction ventricular septal defect is a reasonably effective treatment for these extremely high-risk patients. Mortality remains high, but patients who survive to discharge do well in the longer term.
US pro-choice groups prepare for fight over Supreme Court nominee
Authors: Janice Hopkins Tanne
Journal: BMJ (2004)

US organisations supporting women's right to have an abortion are gearing up for a battle over the nomination of a conservative, anti-abortion candidate for a vacancy on the nine member Supreme Court. A change of only one justice on the court could end legal abortions in the United States.

President Bush will almost certainly be able to appoint one, two, three, or even four new justices to the court. He has often said that he opposes all forms …