tbuckley/cabot-search huggingface dataset:
Overexpression of Phospho-eIF4E Is Associated with Survival through AKT Pathway in Non–Small Cell Lung Cancer
Authors: Akihiko Yoshizawa, Junya Fukuoka, Shigeki Shimizu, Konstantin Shilo, Teri J. Franks, Stephen M. Hewitt, Takeshi Fujii, Carlos Cordon-Cardo, Jin Jen, William D. Travis
Journal: Clinical Cancer Research (2009)

The eukaryotic translation initiation factor complex 4E (eIF4E) is downstream in the mammalian target of rapamycin (mTOR) pathway. This study explored expression of eIF4E and its relationship with the PTEN/AKT and RAS/MEK/ERK pathways in non-small cell lung carcinoma (NSCLC).The status of phosphorylated eIF4E (p-eIF4E), phosphorylated AKT (p-AKT), PTEN, phosphorylated tuberin (p-TSC2), phosphorylated mTOR (p-mTOR), phosphorylated S6 (p-S6), and phosphorylated Erk1/2 (p-Erk1/2) was studied using immunohistochemical analysis applied to a tissue microarray containing 300 NSCLCs. Staining results for each antibody were compared with clinical and pathologic features, and the relationship between staining results was explored.Overexpression of p-eIF4E, p-AKT, p-TSC2, p-mTOR, p-S6, and p-Erk1/2 in NSCLC was found in 39.9%, 78.8%, 5.1%, 46.7%, 27.1%, and 16.6% of tumors, respectively. The phenotype of p-eIF4E correlated positively with that of p-AKT, p-TSC2, and p-S6 (P < 0.001). Overall survival in NSCLC patients was significantly shorter in cases with overexpression of p-eIF4E and p-AKT alone and in combination (log-rank P < 0.001, each). Cases with underexpression of PTEN were limited (6.4%), and this phenotype did not correlate with any clinical variable. In cluster analysis, the p-AKT/p-mTOR/p-eIF4E/p-S6-positive group had significantly shorter survival compared with the survival of all cases (P < 0.001). Multivariate analysis showed that p-eIF4E overexpression is an independent prognostic factor for NSCLC (P = 0.004).This study shows that p-eIF4E expression in addition to p-AKT predicts poor prognosis in NSCLC. Moreover, the correlation between expression of p-eIF4E with p-AKT, as well as p-TSC2 and p-S6, indicates that eIF4E activation through the AKT pathway plays an important role in the progression of NSCLC.
CHEMOKINE RECEPTORS AS HIV-1 CORECEPTORS: Roles in Viral Entry, Tropism, and Disease
Authors: Edward A. Berger, Philip M. Murphy, Joshua M. Farber
Journal: Annual Review of Immunology (1999)

▪ Abstract In addition to CD4, the human immunodeficiency virus (HIV) requires a coreceptor for entry into target cells. The chemokine receptors CXCR4 and CCR5, members of the G protein-coupled receptor superfamily, have been identified as the principal coreceptors for T cell line-tropic and macrophage-tropic HIV-1 isolates, respectively. The updated coreceptor repertoire includes numerous members, mostly chemokine receptors and related orphans. These discoveries provide a new framework for understanding critical features of the basic biology of HIV-1, including the selective tropism of individual viral variants for different CD4 + target cells and the membrane fusion mechanism governing virus entry. The coreceptors also provide molecular perspectives on central puzzles of HIV-1 disease, including the selective transmission of macrophage-tropic variants, the appearance of T cell line-tropic variants in many infected persons during progression to AIDS, and differing susceptibilities of individuals to infection and disease progression. Genetic findings have yielded major insights into the in vivo roles of individual coreceptors and their ligands; of particular importance is the discovery of an inactivating mutation in the CCR5 gene which, in homozygous form, confers strong resistance to HIV-1 infection. Beyond providing new perspectives on fundamental aspects of HIV-1 transmission and pathogenesis, the coreceptors suggest new avenues for developing novel therapeutic and preventative strategies to combat the AIDS epidemic.
Epidemiology of rib fractures in older men: Osteoporotic Fractures in Men (MrOS) prospective cohort study
Authors: E. Barrett-Connor, C. M Nielson, E. Orwoll, D. C Bauer, J. A Cauley
Journal: BMJ (2010)

To study the causes and consequences of radiologically confirmed rib fractures (seldom considered in the context of osteoporosis) in community dwelling older men.Prospective cohort study (Osteoporotic Fractures in Men (MrOS) Study).5995 men aged 65 or over recruited in 2000-2 from six US sites; 99% answered mailed questionnaires about falls and fractures every four months for a mean 6.2 (SD 1.3) year follow-up.New fractures validated by radiology reports; multivariate Cox proportional hazard ratios were used to evaluate factors independently associated with time to incident rib fracture; associations between baseline rib fracture and incident hip and wrist fracture were also evaluated.The incidence of rib fracture was 3.5/1000 person years, and 24% (126/522) of all incident non-spine fractures were rib fractures. Nearly half of new rib fractures (48%; n=61) followed falling from standing height or lower. Independent risk factors for an incident rib fracture were age 80 or above, low bone density, difficulty with instrumental activities of daily living, and a baseline history of rib/chest fracture. Men with a history of rib/chest fracture had at least a twofold increased risk of an incident rib fracture (adjusted hazard ratio 2.71, 95% confidence interval 1.86 to 3.95), hip fracture (2.05, 1.33 to 3.15), and wrist fracture (2.06, 1.14 to 3.70). Only 14/82 of men reported being treated with bone specific drugs after their incident rib fracture.Rib fracture, the most common incident clinical fracture in men, was associated with classic risk markers for osteoporosis, including old age, low hip bone mineral density, and history of fracture. A history of rib fracture predicted a more than twofold increased risk of future fracture of the rib, hip, or wrist, independent of bone density and other covariates. Rib fractures should be considered to be osteoporotic fractures in the evaluation of older men for treatment to prevent future fracture.
Low Health Literacy Associates with Increased Mortality in ESRD
Authors: Kerri L. Cavanaugh, Rebecca L. Wingard, Raymond M. Hakim, Svetlana Eden, Ayumi Shintani, Kenneth A. Wallston, Mary Margaret Huizinga, Tom A. Elasy, Russell L. Rothman, T. Alp Ikizler
Journal: Journal of the American Society of Nephrology (2010)

Limited health literacy is common in the United States and associates with poor clinical outcomes. Little is known about the effect of health literacy in patients with advanced kidney disease. In this prospective cohort study we describe the prevalence of limited health literacy and examine its association with the risk for mortality in hemodialysis patients. We enrolled 480 incident chronic hemodialysis patients from 77 dialysis clinics between 2005 and 2007 and followed them until April 2008. Measured using the Rapid Estimate of Adult Literacy in Medicine, 32% of patients had limited (<9th grade reading level) and 68% had adequate health literacy (≥9th grade reading level). Limited health literacy was more likely in patients who were male and non-white and who had fewer years of education. Compared with adequate literacy, limited health literacy associated with a higher risk for death (HR 1.54; 95% CI 1.01 to 2.36) even after adjustment for age, sex, race, and diabetes. In summary, limited health literacy is common and associates with higher mortality in chronic hemodialysis patients. Addressing health literacy may improve survival for these patients.
Diagnostic Challenges of Clonal Heterogeneity in Prostate Cancer
Authors: Michael C. Haffner, Angelo M. De Marzo, Srinivasan Yegnasubramanian, Jonathan I. Epstein, H. Ballentine Carter
Journal: Journal of Clinical Oncology (2014)

A healthy 64-year-old man underwent a prostate biopsy in 1996 that was triggered by a prostate-specific antigen (PSA) measurement of 7.1 ng/mL, and was found on transrectal ultrasound to have a prostate volume of 63 mL and two small foci of Gleason score 5 adenocarcinoma from the left gland (biopsies from the right were negative).Digital rectal examination (DRE) was normal except for prostatic enlargement (stage T1c).The patient chose to enter an active surveillance program as an alternative to curative intervention, and underwent observation with serial PSA measurements and surveillance prostate biopsies (Fig 1A).His first surveillance biopsy performed 1 year after the diagnostic biopsy revealed a prostate volume of 75 mL and one core of Gleason score 6 adenocarcinoma from the same region as the diagnostic biopsy.In 2007, at age 75 years, after a total of 12 surveillance biopsies failed to demonstrate any high-grade components (Gleason grade 4 or 5), serial biopsies were discontinued and he continued to undergo follow-up with DRE and PSA measurements at 6-month intervals (Fig 1A ; PIN, prostatic intraepithelial neoplasia;
Vertical Distributions of Pulmonary Diffusing Capacity and Capillary Blood Flow in Man
Authors: Edward D. Michaelson, Marvin A. Sackner, Robert L. Johnson
Journal: Journal of Clinical Investigation (1973)

In six normal upright subjects, a 100 mol bolus-composed of equal parts of neon, carbon monoxide, and acetylene (Ne, CO, and C(2)H(2))-was inspired from either residual volume (RV) or functional residual capacity (FRC) during a slow inspiration from RV to total lung capacity (TLC). After breath holding and subsequent collection of the exhalate, diffusing capacity and pulmonary capillary blood flow per liter of lung volume (D(L)/V(A) and Q(C)/V(A)) were calculated from the rates of CO and C(2)H(2) disappearances relative to Ne. The means: D(L)/V(A) = 5.26 ml/min x mm Hg per liter (bolus at RV), 6.54 ml/min x mm Hg per liter (at FRC); Q(C)/V(A) 0.537 liters/minute per liter (bolus at RV), 0.992 liters/minute per liter (at FRC). Similar maneuvers using Xenon-133 confirmed that, during inspiration, more of the bolus goes to the upper zone if introduced at RV and more to the lower, if at FRC. A lung model has been constructed which describes how D(L)/V(A) and Q(C)/V(A) must be distributed to satisfy the experimental data. According to this model, there is a steep gradient of Q(C)/V(A), increasing from apex to base, similar to that previously determined by other techniques-and also a gradient in the same direction, although not as steep, for D(L)/V(A). This more uniform distribution of D(L)/V(A) compared with Q(C)/V(A) indicates a vertical unevenness of diffusing capacity with respect to blood flow (D(L)/Q(C)). However, the relative degree of vertical unevenness of D(L)/V(A) compared with Q(C)/V(A) can account only in part for previous observations attributed to the inhomogeneity of D(L)/V(A) and Q(C)/V(A). Thus, a more generalized unevennes of these ratios must exist throughout the lung, independent of gravitation.
Onset of puberty, menstrual frequency, and body fat in elite rhythmic gymnasts compared with normal controls
Authors: P Klentrou, M Plyley
Journal: British Journal of Sports Medicine (2003)

To assess the prevalence of delayed menarche and abnormal menstrual patterns, as well as the association of menstrual status with physical training in elite rhythmic gymnasts from Greece and Canada.Fifteen Greek (mean (SEM) age 14.5 (0.2) years) and 30 Canadian (mean (SEM) age 14.7 (0.4) years) rhythmic gymnasts were surveyed for age at menarche, menstrual frequency, and training profile, and measured for height, weight, and percentage body fat (%BF). Seventy eight healthy adolescents served as country specific non-active controls: 38 Greek non-athletes (mean (SEM) age 14.5 (0.1) years) and 40 Canadian non-athletes (mean (SEM) 14.2 (0.1) years).Of the Greek gymnasts, 79% had not yet menstruated compared with 34% of the Canadian gymnasts. Menarche was significantly (p<0.01) delayed in the rhythmic gymnasts (composite mean 13.8 (0.3) years, n = 45) compared with the controls (composite mean 12.5 (0.1) years, n = 78). There was no significant difference between Greek and Canadian gymnasts for the age at menarche (14.2 (0.3) v 13.6 (1.2) years respectively). Menstrual irregularities were reported in 78% (61% oligomenorrhoeic and 17% amenorrhoeic) of the menarcheal athletes. Menarcheal gymnasts were found to be significantly (p<0.05) taller and heavier, with a higher %BF and a lower training frequency and training duration (p<0.05) than the premenarcheal gymnasts. Overall, the mean %BF of the gymnasts was significantly lower (p<0.05) than that of the control subjects. The Canadian controls exhibited a significantly (p<0.05) greater %BF than the Greek controls of the same age.Delayed menarche, menstrual irregularities, and low body fat are common in elite rhythmic gymnasts. Premenarcheal gymnasts train more often and for longer, and have a lower body mass index and less body fat, than menarcheal gymnasts. Prospective studies are needed to explore further these and other factors associated with delayed menarche and menstrual irregularities in female athletes.
NEW CONTRACT FOR CONSULTANT
Authors: C.B.T. Adams, P.N. Awdry, J. Badenoch, P.R. Barton, J.H. Barston, L.J. Beilin, R.J. Berry, J.M. Black, F.G. Bolton, E.D. Bower, R. Bryce-Smith, S. Callender, B.H. Colman, R. Doll, M.S. Dunnill, P.M. Emerson, A. Freedman, J.M.D. Gallwey, M.H. Gough, R.A. Griffiths, A.J. Gunning, A.C.L. Houlton, J.T. Hugues, B.E. Juel-Jensen, J.G.G. Ledingham, E.G. Lee, W.S. Lund, R.G. Mitchell, C.H. Paine, R.J. Patterson, J.M. Potter, C. Prys-Roberts, J. Rayne, A.H.T. Robe-Smith, T.J. Ryan, A.A. Sharp, J.C. Smith, J. Stallworthy, A.S. Till, J. Tizard, D.C. Turk, H.R. Vickers, C.U. Webster, C. Westropp, C.W.M. Whitty, G. Wiernik, L. Wollner
Journal: The Lancet (1973)
Human interleukin 17–producing cells originate from a CD161+CD4+ T cell precursor
Authors: Lorenzo Cosmi, Raffaele De Palma, Veronica Santarlasci, Laura Maggi, Manuela Capone, Francesca Frosali, Gabriella Rodolico, Valentina Querci, Gianfranco Abbate, Roberta Angeli, Liberato Berrino, Massimiliano Fambrini, Marzia Caproni, Francesco Tonelli, Elena Lazzeri, Paola Parronchi, Francesco Liotta, Enrico Maggi, Sergio Romagnani, Francesco Annunziato
Journal: The Journal of Experimental Medicine (2008)

We demonstrate that CD161 is a highly up-regulated gene in human interleukin (IL) 17 T helper cell (Th17) clones and that all IL-17-producing cells are contained in the CD161(+) fraction of CD4(+) T cells present in the circulation or in inflamed tissues, although they are not CD1-restricted natural killer T cells. More importantly, we show that all IL-17-producing cells originate from CD161(+) naive CD4(+) T cells of umbilical cord blood, as well as of the postnatal thymus, in response to the combined activity of IL-1 beta and IL-23. These findings implicate CD161 as a novel surface marker for human Th17 cells and demonstrate the exclusive origin of these cells from a CD161(+)CD4(+) T cell progenitor.
THE LANGUAGE OF HEALTH CARE: Walking and cycling transport safety
Authors: P. Clinch
Journal: Journal of the Royal Society of Medicine (2006)

I have recently read Walking and cycling transport safety: an analysis of child road  by Sonkin et al. [J R Soc Med. 2006; 99(8):402-5] and wish to comment as follows: Sonkin et al. describe walking and cycling as 'poor relations in terms of transport safety', though if one comes off the roads and factors in trains and planes then cars would look rather poor, but this does not seem to affect the keenness with which cars are used. The fact is that cars are perceived to be safe 'enough', and if one looks at accidents per unit time rather than per unit distance then a comparable degree of safety to cars can be found for cycling and walking over a lifetime, with 0.55 deaths per 10 million miles accounting for very few deaths in a lifetime of cycling (even keen adults using cycles for everyday transport will typically travel much less than 5000 miles per year). The conclusion that 'more needs to be done' is something that will, inevitably, always be true of transport safety for all modalities, but a first step is realising the true degree of danger. In the UK (and other countries where there is no longer a culture of walking or cycling for transport) the perception that walking and especially cycling is uncommonly dangerous compared to other day-to-day activities is a perception, not a fact. Language: en
Expression of Vascular Endothelial Growth Factor Receptor-2 or Tie-2 on Peripheral Blood Cells Defines Functionally Competent Cell Populations Capable of Reendothelialization
Authors: Grzegorz Nowak, Azza Karrar, Carolina Holmén, Silvia Nava, Mehmet Uzunel, Kjell Hultenby, Suchitra Sumitran-Holgersson
Journal: Circulation (2004)

Background— Receptor tyrosine kinases that include vascular endothelial growth factor (VEGFR)-1, VEGFR-2, and Tie-2 regulate cardiovascular development and physiological and pathological angiogenesis. We were interested in the phenotypic and functional characterization of peripheral blood cells expressing these receptors and their therapeutic potential in vascular injury. Methods and Results— VEGFR-1 + , VEGFR-2 + , and Tie-2 + cells constituted ≈3.0±0.2%, 0.8±0.5%, and 2.0±0.3%, respectively, of the total population of mononuclear cells in blood. Phenotypic analysis demonstrated that all 3 cell populations mainly expressed markers of monocytic/macrophage lineage. Only VEGFR-2 + and Tie-2 + cells phenotypically, morphologically, and functionally differentiated to endothelial cells after culture, whereas VEGFR-1 + cells did not. None of the cell types proliferated in vitro. Only freshly isolated VEGFR-2 + or Tie-2 + cells but not VEGFR-2 − or Tie-2 − cell populations significantly contributed to efficient endothelialization of balloon-injured femoral arteries of nude mice. Furthermore, these cells also differentiated into α-actin–positive smooth muscle cells. Administration of bromodeoxyuridine to animals transplanted with human endothelial progenitor cells showed that VEGFR-2 + and Tie-2 + cells proliferated in vivo. Conclusions— These data demonstrate that expression of VEGFR-2 and/or Tie-2 on peripheral blood cells defines functionally competent cell populations that proliferate in vivo and that contribute to reendothelialization. These findings may have implications for a cell-based approach in vascular diseases.
Pyloric regurgitation and gastric ulcer
Authors: F. J. Flint, P. Grech
Journal: Gut (1970)

Using a radiological test for pyloric regurgitation described by Capper, Airth, and Kilby (1966), it was confirmed that the pylorus is normally competent but incompetent in gastric ulcer and chronic alcoholic gastritis and often incompetent in chronic duodenal ulcer. The significance of pyloric regurgitation in the aetiology of gastric ulcer is discussed.
Is There a Role for TNF-α in Anti-Neutrophil Cytoplasmic Antibody–Associated Vasculitis? Lessons from Other Chronic Inflammatory Diseases
Authors: Marc Feldmann, Charles D. Pusey
Journal: Journal of the American Society of Nephrology (2006)

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is the most common cause of rapidly progressive glomerulonephritis and immune-mediated pulmonary renal syndrome. Now that the acute manifestations of the disease generally can be controlled with immunosuppressive drugs, ANCA-associated vasculitis has become a chronic and relapsing inflammatory disorder. The need to develop safer and more effective treatment has led to great interest in the mediators of chronic inflammation. There are many lessons to be learned from studies of other chronic inflammatory diseases, particularly rheumatoid arthritis (RA). The identification of a TNF-α–dependent cytokine cascade in the in vitro cultures of synovium in joints of patients with RA led to studies of TNF blockade in experimental models of arthritis and subsequently to clinical trials. These have culminated in the widespread introduction of anti-TNF therapy not only in RA but also in Crohn disease, ankylosing spondylitis, and several other chronic inflammatory disorders. Following a similar investigative pathway, studies that show the importance of TNF production by leukocytes and intrinsic renal cells in glomerulonephritis have been followed by the demonstration of the effectiveness of TNF blockade in several experimental models of glomerulonephritis and vasculitis. In experimental autoimmune vasculitis, improvement in disease was paralleled by a reduction in leukocyte transmigration, as demonstrated by intravital microscopy. The benefit of infliximab (a mAb to TNF) in ANCA-associated vasculitis was recently reported in a prospective open-label study. However, the use of etanercept (a soluble TNF receptor fusion protein) was not found to be of significant benefit in a randomized, controlled trial in patients with Wegener granulomatosis. Therefore, there is a need for further evaluation of the use of anti-TNF antibodies in patients with ANCA-associated glomerulonephritis.
Head-to-head comparison between echocardiography and cardiac MRI in the evaluation of the athlete's heart
Authors: Niek H J Prakken, Arco J Teske, Maarten J Cramer, Arend Mosterd, Annieke C Bosker, Willem P Mali, Pieter A Doevendans, Birgitta K Velthuis
Journal: British Journal of Sports Medicine (2011)

Echocardiographic cut-off values are often used for cardiac MRI in athletic persons. This study investigates the difference between echocardiographic and cardiac MRI measurements of ventricular and atrial dimensions and ventricular wall thickness, and its effect on volume and wall mass prediction in athletic subjects compared with non-athletic controls.Healthy non-athletic (59), regular athletic (59) and elite athletic (63) persons, aged 18-39 years and training 2.5±1.9, 13.0±3.0 and 25.0±5.4 h/week, respectively (p<0.001), underwent echocardiography and cardiac MRI consecutively. Left ventricular (LV) and right ventricular (RV) dimensions were measured on both modalities. LV and RV end-diastolic and end-systolic volumes and LV wall mass were determined on cardiac MRI. Echocardiographic M-mode LV volumes (Teichholz formula) and LV wall mass (American Society of Echocardiography formula) were calculated.LV and RV dimensions were smaller on echocardiography (p<0.001), and although the correlation with the cardiac MRI volume was good (p<0.01), the difference in volume was large (LV end-diastolic volume difference 93±32 g, p<0.001). LV wall thickness and calculated wall mass were significantly (p<0.001) larger on echocardiography (wall mass difference -101±34 g, p<0.001). Differences in absolute dimensions did not change significantly between non-athletic and athletic persons; however, the difference in echocardiographic estimations of LV volumes and wall mass did increase significantly with the larger athlete's heart, requiring possible correction of the standard echocardiographic formulas.Echocardiography shows systematically smaller atrial and ventricular dimensions and volumes, and larger wall thickness and mass, compared with cardiac MRI. Correction for the echocardiographic formulas can facilitate better intertechnique comparability. These findings should be taken into account in the interpretation of cardiac MRI findings in athletic subjects in whom cardiomyopathy is suspected on echocardiography.