tbuckley/cabot-search huggingface dataset:
FoxM1B Is Overexpressed in Human Glioblastomas and Critically Regulates the Tumorigenicity of Glioma Cells
Authors: Mingguang Liu, Bingbing Dai, Shin-Hyuk Kang, Kechen Ban, Feng-Ju Huang, Frederick F. Lang, Kenneth D. Aldape, Tong-xin Xie, Christopher E. Pelloski, Keping Xie, Raymond Sawaya, Suyun Huang
Journal: Cancer Research (2006)

Abstract The transcription factor Forkhead box M1 (FoxM1) is overexpressed in malignant glioma. However, the functional importance of this factor in human glioma is not known. In the present study, we found that FoxM1B was the predominant FoxM1 isoform expressed in human glioma but not in normal brain tissue. The level of FoxM1 protein expression in human glioma tissues was directly correlated with the glioma grade. The level of FoxM1 protein expression in human glioblastoma tissues was inversely correlated with patient survival. Enforced FoxM1B expression caused SW1783 and Hs683 glioma cells, which do not form tumor xenografts, to regain tumorigenicity in nude mouse model systems. Moreover, gliomas that arose from FoxM1B-transfected anaplastic astrocytoma SW1783 cells displayed glioblastoma multiforme phenotypes. Inhibition of FoxM1 expression in glioblastoma U-87MG cells suppressed their anchorage-independent growth in vitro and tumorigenicity in vivo. Furthermore, we found that FoxM1 regulates the expression of Skp2 protein, which is known to promote degradation of the cell cycle regulator p27Kip1. These results showed that FoxM1 is overexpressed in human glioblastomas and contributes to glioma tumorigenicity. Therefore, FoxM1 might be a new potential target of therapy for human malignant gliomas. (Cancer Res 2006; 66(7): 3593-602)
Autoimmune and Chronic Inflammatory Disorders and Risk of Non-Hodgkin Lymphoma by Subtype
Authors: Karin Ekström Smedby, Henrik Hjalgrim, Johan Askling, Ellen T. Chang, Henrik Gregersen, Anna Porwit-MacDonald, Christer Sundström, Måns Åkerman, Mads Melbye, Bengt Glimelius, Hans-Olov Adami
Journal: JNCI Journal of the National Cancer Institute (2006)

Background: Some autoimmune and chronic inflammatory disorders are associated with increased risks of non-Hodgkin lymphoma (NHL). Because different NHL subtypes develop at different stages of lymphocyte differentiation, associations of autoimmune and inflammatory disorders with specific NHL subtypes could lead to a better understanding of lymphomagenic mechanisms. Methods: In a population-based case–control study in Denmark and Sweden, 3055 NHL patients and 3187 matched control subjects were asked about their history of autoimmune and chronic inflammatory disorders, markers of severity, and treatment. Logistic regression with adjustment for study matching factors was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for NHL overall and for NHL subtypes. Results: Risks of all NHL were increased in association with rheumatoid arthritis (OR = 1.5, 95% CI = 1.1 to 1.9), primary Sjögren syndrome (OR = 6.1, 95% CI = 1.4 to 27), systemic lupus erythematosus (OR = 4.6, 95% CI = 1.0 to 22), and celiac disease (OR = 2.1, 95% CI = 1.0 to 4.8). All of these conditions were also associated with diffuse large B-cell lymphoma, and some were associated with marginal zone, lymphoplasmacytic, or T-cell lymphoma. Ever use of nonsteroidal anti-inflammatory drugs, systemic corticosteroids, and selected immunosuppressants was associated with risk of NHL in rheumatoid arthritis patients but not in subjects without rheumatoid arthritis. Also, multivariable adjustment for treatment had little impact on risk estimates. Psoriasis, sarcoidosis, and inflammatory bowel disorders were not associated with increased risk of NHL overall or of any NHL subtype. Conclusions: Our results confirm the associations between certain autoimmune disorders and risk of NHL and suggest that the associations may not be general but rather mediated through specific NHL subtypes. These NHL subtypes develop during postantigen exposure stages of lymphocyte differentiation, consistent with a role of antigenic drive in autoimmunity-related lymphomagenesis.
Hypoxia and Mucosal Inflammation
Authors: Sean P. Colgan, Eric L. Campbell, Douglas J. Kominsky
Journal: Annual Review of Pathology Mechanisms of Disease (2016)

Sites of inflammation are defined by significant changes in metabolic activity. Recent studies have suggested that O2 metabolism and hypoxia play a prominent role in inflammation so-called "inflammatory hypoxia," which results from a combination of recruited inflammatory cells (e.g., neutrophils and monocytes), the local proliferation of multiple cell types, and the activation of multiple O2-consuming enzymes during inflammation. These shifts in energy supply and demand result in localized regions of hypoxia and have revealed the important function off the transcription factor HIF (hypoxia-inducible factor) in the regulation of key target genes that promote inflammatory resolution. Analysis of these pathways has provided multiple opportunities for understanding basic mechanisms of inflammation and has defined new targets for intervention. Here, we review recent work addressing tissue hypoxia and metabolic control of inflammation and immunity.
Determining the intensity and energy expenditure during commuter cycling
Authors: B de Geus, S De Smet, J Nijs, R Meeusen
Journal: British Journal of Sports Medicine (2006)

Objectives: To determine the intensity and energy expenditure during commuter cycling, and to investigate whether cycling to work at a self-chosen intensity corresponds to recommendations of the Centers for Disease Control and Prevention (CDC) and American College of Sports Medicine (ACSM) for health improvement and ACSM recommendations for fitness improvement. Methods: 18 healthy, untrained middle-aged people, who did not cycle to work, underwent two maximal exercise tests (MT and MT2) in order to measure their maximal heart rate and oxygen consumption (VO 2 ). MT2 was performed 24 weeks after MT. Participants were asked to cycle at least three times a week to their workplace over a one-way minimum distance of 2 km. Data on cycling were recorded in a diary. 12 weeks after MT, a field test was conducted, where participants had to cycle to or from their workplace. The same measurements were taken as during MT as markers of exercise intensity. Metabolic equivalents (METs) and energy expenditure were calculated. Results: The intensity during the field test was &gt;75% of their maximal aerobic capacity. The mean (SD) MET value was 6.8 (1.9). The energy expenditure during the field test was 220 (115) kcal or 540 (139) kcal/h and 1539 (892) kcal/week. Men consumed significantly (p&lt;0.01) more energy per hour than women. Conclusion: Commuter cycling at a self-selected intensity meets the CDC and ACSM recommendations for health improvement and the ACSM recommendations for improvement of cardiorespiratory fitness. However, as the participants cycled faster during the field test than during daily cycling, the results should be interpreted with caution.
Expression of chemokines CXCL4 and CXCL7 by synovial macrophages defines an early stage of rheumatoid arthritis
Authors: L Yeo, N Adlard, M Biehl, M Juarez, T Smallie, M Snow, C D Buckley, K Raza, A Filer, D Scheel-Toellner
Journal: Annals of the Rheumatic Diseases (2015)

Background and objectives For our understanding of the pathogenesis of rheumatoid arthritis (RA), it is important to elucidate the mechanisms underlying early stages of synovitis. Here, synovial cytokine production was investigated in patients with very early arthritis. Methods Synovial biopsies were obtained from patients with at least one clinically swollen joint within 12 weeks of symptom onset. At an 18-month follow-up visit, patients who went on to develop RA, or whose arthritis spontaneously resolved, were identified. Biopsies were also obtained from patients with RA with longer symptom duration (&gt;12 weeks) and individuals with no clinically apparent inflammation. Synovial mRNA expression of 117 cytokines was quantified using PCR techniques and analysed using standard and novel methods of data analysis. Synovial tissue sections were stained for CXCL4, CXCL7, CD41, CD68 and von Willebrand factor. Results A machine learning approach identified expression of mRNA for CXCL4 and CXCL7 as potentially important in the classification of early RA versus resolving arthritis. mRNA levels for these chemokines were significantly elevated in patients with early RA compared with uninflamed controls. Significantly increased CXCL4 and CXCL7 protein expression was observed in patients with early RA compared with those with resolving arthritis or longer established disease. CXCL4 and CXCL7 co-localised with blood vessels, platelets and CD68 + macrophages. Extravascular CXCL7 expression was significantly higher in patients with very early RA compared with longer duration RA or resolving arthritis Conclusions Taken together, these observations suggest a transient increase in synovial CXCL4 and CXCL7 levels in early RA.
Drug reaction with eosinophilia and systemic symptoms: is cutaneous phenotype a prognostic marker for outcome? A review of clinicopathological features of 27 cases
Authors: S. Walsh, S. Diaz-Cano, E. Higgins, R. Morris-Jones, S. Bashir, W. Bernal, D. Creamer
Journal: British Journal of Dermatology (2012)

Drug reaction with eosinophilia and systemic symptoms (DRESS) describes a heterogeneous group of severe adverse reactions to medications. The cutaneous phenotype has a number of guises, accompanied by a variety of systemic features including fever, haematological abnormalities and visceral involvement, most commonly the liver. Clinical markers of prognosis have not been identified.To assess the cutaneous signs and dermatopathological features of DRESS in order to identify potential prognostic markers.We reviewed the clinical features, dermatopathology and outcomes of 27 consecutive cases of DRESS presenting to a single unit.Four distinct patterns of cutaneous involvement were identified: an urticated papular exanthem (13/27 patients), a morbilliform erythema (three of 27), an exfoliative erythroderma (three of 27) and an erythema multiforme-like (EM-like) reaction consisting of atypical targets (eight of 27). All patients mounted a fever, most developed lymphadenopathy (24/27) and peripheral eosinophilia (25/27) and the most common organ involved was the liver (27/27). Review of the dermatopathic features of patients with DRESS demonstrated a superficial spongiotic dermatitis in the majority of cases (16/27). A smaller number of cases showed basal cell vacuolar degeneration and necrotic keratinocytes (nine of 27). The patients with these biopsy findings more commonly had an EM-like cutaneous phenotype, and more severe hepatic involvement. Three patients died, two following failed liver transplants.Our series is the first in which a detailed dermatological assessment has been made of consecutive patients presenting with DRESS, and the largest U.K. series to date. Our results suggest a possible prognostic role of the cutaneous and dermatopathic findings in DRESS in predicting the severity of visceral involvement in this syndrome. What's already known about this topic? • Drug reaction with eosinophilia and systemic symptoms (DRESS) has a heterogeneous clinical presentation, with a skin eruption of variable morphology. • DRESS carries considerable morbidity and mortality, usually hepatic in origin, although renal, pulmonary and pericardial involvement can be seen. What does this study add? • The cutaneous phenotype in DRESS can be categorized as an urticated papular exanthem, a morbilliform erythema, exfoliative erythroderma or erythema multiforme-like (EM-like). • An EM-like eruption DRESS may be prognostic of more severe hepatic involvement.
Sympathetic Neural Activation in Visceral Obesity
Authors: Guy E. Alvarez, Stacy D. Beske, Tasha P. Ballard, Kevin P. Davy
Journal: Circulation (2002)

Background— Muscle sympathetic nerve activity (MSNA) is elevated in obese humans. However, the potential role of abdominal visceral fat as an important adipose tissue depot linking obesity to elevated MSNA has not been explored. Accordingly, we tested the hypothesis that MSNA would be increased in men (age=18 to 40 years, body mass index ≤35 kg/m 2 ) with higher abdominal visceral fat (HAVF; n=13, abdominal visceral fat=118.1±15.8 cm 2 ) compared with their age- (28.7±2.4 versus 25.5±2.0 years, P &gt;0.05), total fat mass-matched (20.6±2.1 versus 20.8±2.4 kg, P &gt;0.05) and abdominal subcutaneous fat-matched (230.6±24.9 versus 261.4±34.8 cm 2 , P &gt;0.05) peers with lower abdominal visceral fat levels (LAVF; n=13, visceral fat= 73.0±6.0 cm 2 ). Methods and Results— MSNA (microneurography), body composition (dual energy x-ray absorptiometry), and abdominal visceral and subcutaneous fat (computed tomography) were measured in 37 sedentary men across a wide range of adiposity. MSNA was ≈55% higher in men with HAVF compared with men with LAVF (33±4 versus 21±2 bursts/min, P &lt;0.05). Furthermore, MSNA was more closely associated with the level of abdominal visceral fat ( r =0.65, P &lt;0.05) than total fat mass ( r =0.323, P &lt;0.05) or abdominal subcutaneous fat ( r =0.27, P =0.05). The relation between MSNA and abdominal visceral fat was independent of total body fat ( r =0.61, P &lt;0.05). Conclusions— The results of our study indicate that MSNA is elevated in men with visceral obesity. Our observations are consistent with the idea that abdominal visceral fat is an important adipose tissue depot linking obesity with sympathetic neural activation in humans. Furthermore, these findings may have important implications for understanding the increased risk of developing cardiovascular diseases in individuals with visceral obesity.
Risk of neoplastic progression in Barrett’s esophagus diagnosed as indefinite for dysplasia: a nationwide cohort study
Authors: Christine Kestens, Max Leenders, G. Offerhaus, Jantine van Baal, Peter Siersema
Journal: Endoscopy (2014)

<b>Background and study aims:</b> A histological diagnosis of "indefinite for dysplasia" (IND) in Barrett's esophagus is used when a diagnosis of genuine dysplasia is equivocal. The aim of the present study was to assess the risk of progression to high grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) after a diagnosis of IND in a nationwide cohort of patients with Barrett's esophagus. <b>Patients and methods</b>: Patients with a first diagnosis of IND in Barrett's esophagus between 2002 and 2011 were selected from a nationwide registry of histopathology diagnoses in The Netherlands. Patients were followed up until treatment for HGD, detection of EAC, or date of last endoscopy contact with biopsy sampling. <b>Results</b>: In total, 1258 patients met the inclusion criteria, of whom 842 (66.9 %) underwent endoscopic follow-up. Patients were followed for a total of 2585 person-years (mean ± SD 3.01 ± 2.6). Median duration until first follow-up endoscopy was 1.2 years (interquartile range 0.3 – 1.8 years). The progression rate from IND to the combined end point of HGD or EAC was 2.0 (95 % confidence interval [CI] 1.5 – 2.6) per 100 person-years and progression to EAC was 1.2 (95 %CI 0.8 – 1.6). After excluding cases with HGD or EAC within 1 year after IND diagnosis (n = 16), the progression rates were 1.4 (95 %CI 1.0 – 1.9) and 0.8 (95 %CI 0.5 – 1.2) per 100 person-years for HGD or EAC and EAC, respectively. <b>Conclusion</b>: In this large, population-based, cohort of patients with Barrett's esophagus, the incidence rate of HGD or EAC following a diagnosis of IND was 1.4 per 100 person-years. The results demonstrate the need for additional studies to select the subgroup of IND patients with an increased risk of neoplastic progression.
GENETIC CONTROL OF IMMUNE RESPONSES IN VITRO
Authors: Baruj Benacerraf, Judith A. Kapp, Carl W. Pierce, David H. Katz
Journal: The Journal of Experimental Medicine (1974)

The conditions for cooperative interactions between nonresponder B10.S B cells and GAT-primed irradiated (C57BL/6 x SJL)F(1) T cells in the response by cultures of mouse spleen cells to GAT were investigated. GAT-specific antibody responses could be elicited by soluble GAT in cultures of GAT-primed irradiated (C57BL/6 x SJL)F(1) T cells with C57BL/6 B cells but not with B10.S B cells. In contrast, when GAT was presented to the cultures on F(1) macrophages or as aggregates of GAT with MBSA, GAT-specific PFC responses were observed with both B10.S or C57BL/6 B cells. Irradiated GAT-primed T cells were nevertheless essential for the development of these responses. The GAT-specific response of B10.S B cells in these cultures was inhibited by the addition of soluble GAT at culture initiation. These results indicate that genetic disparity at Ir loci is not an absolute barrier to T-B-cell cooperative interactions in the response to antigens under Ir gene control. The significance of these data for the function of Ir gene products in immunocompetent cells is discussed.
A New Zealand Linkage Study Examining the Associations Between A1C Concentration and Mortality
Authors: Naomi Brewer, Craig S. Wright, Noémie Travier, Chris W. Cunningham, John Hornell, Neil Pearce, Mona Jeffreys
Journal: Diabetes Care (2008)

To examine associations between A1C concentration and mortality in a New Zealand population.During a Hepatitis Foundation screening campaign for hepatitis B (1999-2001), participants were offered A1C testing. The participants were anonymously linked to the national mortality collection to 31 December 2004. Hazard ratios (HRs) and 95% CIs adjusted for age, ethnicity, smoking, and sex were estimated using Cox regression.There were 47,904 participants (71% Mâori, 12% Pacific, 5% Asian, and 12% other). A1C measurements were categorized as <4.0% (n = 142), 4.0 to <5.0% (reference category; n = 12,867), 5.0 to <6.0% (n = 30,222), 6.0 to <7.0% (n = 2,669), and >or=7.0% (n = 1,596); there were also 408 participants with a previous diabetes diagnosis. During the follow-up period, 815 individuals died. In those without a prior diabetes diagnosis, there were steadily increasing HRs from the A1C reference category to the highest category (>or=7.0%; HR 2.36 [95% CI 1.72-3.25]). As well as all-cause mortality, A1C was associated with mortality from diseases of the circulatory system; endocrine, nutritional, metabolic, and immunity disorders; and other and unknown causes. Mortality was also elevated in those with a prior diabetes diagnosis (5.19 [3.67-7.35]), but this was only partially explained by their elevated A1C levels.This is the largest study to date of A1C levels and subsequent mortality risk. It confirms previous findings that A1C levels are strongly associated with subsequent mortality in both men and women without a prior diabetes diagnosis.
Immunopathogenic Mechanisms of HIV Infection
Authors: Anthony S. Fauci
Journal: Annals of Internal Medicine (1996)

A complex array of multiphasic and multifactorial immunopathogenic mechanisms are involved in the establishment and progression of human immunodeficiency virus (HIV) disease.After primary infection, acute viremia occurs with wide dissemination of HIV. During this early viremic phase, the virus is trapped within the processes of follicular dendritic cells in the germinal centers of lymphoid tissue. Also, during this phase of primary infection, some patients show major expansions of certain subsets of CD8+ T cells that are identified by the expression of a particular variable region of the β chain of the T-cell receptor. These expansions are manifestations of responses to HIV that may be important in controlling the progression of HIV infection. In addition, inappropriate immune activation and elevated secretion of certain proinflammatory cytokines occur during HIV infection; these cytokines play a role in the regulation of HIV expression in the tissues. Infection of progenitor cells in bone marrow and the thymus contribute to the lack of regeneration of immunocompetent cells. Dendritic cells are involved in the initiation and propagation of HIV infection in CD4+ T cells. In studies of long-term nonprogressors—persons who have stable CD4+ T-cell counts and no HIV disease progression despite years of HIV infection—preserved lymph node architecture, low viral burden, and viral expression were found.
The analysis of population survey data on DNA sequence variation.
Authors: M Lynch, T J Crease
Journal: Molecular Biology and Evolution (1990)

A technique is presented for the partitioning of nucleotide diversity into within- and between-population components for the case in which multiple populations have been surveyed for restriction-site variation. This allows the estimation of an analogue of FST at the DNA level. Approximate expressions are given for the variance of these estimates resulting from nucleotide, individual, and population sampling. Application of the technique to existing studies on mitochondrial DNA in several animal species and on several nuclear genes in Drosophila indicates that the standard errors of genetic diversity estimates are usually quite large. Thus, comparative studies of nucleotide diversity need to be substantially larger than the current standards. Normally, only a very small fraction of the sampling variance is caused by sampling of individuals. Even when 20 or so restriction enzymes are employed, nucleotide sampling is a major source of error, and population sampling is often quite important. Generally, the degree of population subdivision at the nucleotide level is comparable with that at the haplotype level, but significant differences do arise as a result of inequalities in the genetic distances between haplotypes.
Efficacy of Combining GMX1777 with Radiation Therapy for Human Head and Neck Carcinoma
Authors: Hisayuki Kato, Emma Ito, Wei Shi, Nehad M. Alajez, Shijun Yue, Carolina Lee, Norman Chan, Nirmal Bhogal, Carla L. Coackley, Doug Vines, David Green, John Waldron, Patrick Gullane, Rob Bristow, Fei-Fei Liu
Journal: Clinical Cancer Research (2010)

Rapidly metabolizing tumor cells have elevated levels of nicotinamide phosphoribosyltransferase, an enzyme involved in NAD(+) biosynthesis, which serves as an important substrate for proteins involved in DNA repair. GMX1777, which inhibits nicotinamide phosphoribosyltransferase, was evaluated in two human head and neck cancer models in combination with radiotherapy.Effects of GMX1777-mediated radiosensitization were examined via metabolic and cytotoxicity assays in vitro; mechanism of action, in vivo antitumor efficacy, and radiosensitization were also investigated.IC(50) values of GMX1777 for FaDu and C666-1 cells were 10 and 5 nmol/L, respectively, which interacted synergistically with radiotherapy. GMX1777 induced a rapid decline in intracellular NAD(+) followed by ATP reduction associated with significant cytotoxicity. These metabolic changes were slightly increased with the addition of radiotherapy, although poly(ADP-ribose) polymerase activity was significantly reduced when GMX1777 was combined with radiotherapy, thereby accounting for the synergistic cytotoxicity of these two modalities. Systemic GMX1777 administration with local tumor radiotherapy caused complete disappearance of FaDu and C666-1 tumors for 50 and 20 days, respectively. There was also significant reduction in tumor vascularity, particularly for the more sensitive FaDu model. [(18)F]FDG-positron emission tomography/computed tomography images showed reduction in [(18)F]FDG uptake after GMX1777 administration, showing decreased glucose metabolism in vivo.Our data represent the first report showing that GMX1777 plus radiotherapy is an effective therapeutic strategy for head and neck cancer, mediated via pleiotropic effects of inhibition of DNA repair and tumor angiogenesis, while sparing normal tissues. Therefore, GMX1777 combined with radiotherapy definitely warrants clinical evaluation in human head and neck cancer patients.