tbuckley/cabot-search huggingface dataset:
Curcumin sensitizes TRAIL-resistant xenografts: molecular mechanisms of apoptosis, metastasis and angiogenesis
Authors: Sharmila Shankar, Suthakar Ganapathy, Qinghe Chen, Rakesh K Srivastava
Journal: Molecular Cancer (2008)

Abstract Background We have recently shown that curcumin (a diferuloylmethane, the yellow pigment in turmeric) enhances apoptosis-inducing potential of TRAIL in prostate cancer PC-3 cells, and sensitizes TRAIL-resistant LNCaP cells in vitro through multiple mechanisms. The objectives of this study were to investigate the molecular mechanisms by which curcumin sensitized TRAIL-resistant LNCaP xenografts in vivo . Methods Prostate cancer TRAIL-resistant LNCaP cells were implanted in Balb c nude mice to examine the effects of curcumin and/or TRAIL on tumor growth and genes related to apoptosis, metastasis and angiogenesis. Results Curcumin inhibited growth of LNCaP xenografts in nude mice by inducing apoptosis (TUNEL staining) and inhibiting proliferation (PCNA and Ki67 staining), and sensitized these tumors to undergo apoptosis by TRAIL. In xenogrfated tumors, curcumin upregulated the expression of TRAIL-R1/DR4, TRAIL-R2/DR5, Bax, Bak, p21 /WAF1 , and p27 /KIP1 , and inhibited the activation of NFκB and its gene products such as cyclin D1, VEGF, uPA, MMP-2, MMP-9, Bcl-2 and Bcl-X L . The regulation of death receptors and members of Bcl-2 family, and inactivation of NFκB may sensitize TRAIL-resistant LNCaP xenografts. Curcumin also inhibited number of blood vessels in tumors, and circulating endothelial growth factor receptor 2-positive endothelial cells in mice. Conclusion The ability of curcumin to inhibit tumor growth, metastasis and angiogenesis, and enhance the therapeutic potential of TRAIL suggests that curcumin alone or in combination with TRAIL can be used for prostate cancer prevention and/or therapy.
Viral Immune Evasion Due to Persistence of Activated T Cells Without Effector Function
Authors: Allan J. Zajac, Joseph N. Blattman, Kaja Murali-Krishna, David J.D. Sourdive, M. Suresh, John D. Altman, Rafi Ahmed
Journal: The Journal of Experimental Medicine (1998)

We examined the regulation of virus-specific CD8 T cell responses during chronic lymphocytic choriomeningitis virus (LCMV) infection of mice. Our study shows that within the same persistently infected host, different mechanisms can operate to silence antiviral T cell responses; CD8 T cells specific to one dominant viral epitope were deleted, whereas CD8 T cells responding to another dominant epitope persisted indefinitely. These virus-specific CD8 T cells expressed activation markers (CD69(hi), CD44(hi), CD62Llo) and proliferated in vivo but were unable to elaborate any antiviral effector functions. This unresponsive phenotype was more pronounced under conditions of CD4 T cell deficiency, highlighting the importance of CD8- CD4 T cell collaboration in controlling persistent infections. Importantly, in the presence of CD4 T cell help, adequate CD8 effector activity was maintained and the chronic viral infection eventually resolved. The persistence of activated virus-specific CD8 T cells without effector function reveals a novel mechanism for silencing antiviral immune responses and also offers new possibilities for enhancing CD8 T cell immunity in chronically infected hosts.
Relation Between Lesion Characteristics and Risk With Percutaneous Intervention in the Stent and Glycoprotein IIb/IIIa Era
Authors: Stephen G. Ellis, Victor Guetta, Dave Miller, Patrick L. Whitlow, Eric J. Topol
Journal: Circulation (1999)

The currently used American College of Cardiology/American Heart Association lesion classification scheme dates from an era when balloon angioplasty was the only percutaneous treatment available and major complications occurred in approximately 7% of patients. Major advances in treatment options would suggest that this scheme may be outmoded, but the schemes that have been suggested to update lesion classification have not been widely accepted.Four thousand one hundred eighty-one consecutive patients (6,676 lesions) formed a training set and 2,146 patients (4,231 lesions) formed a validation set treated from 1995 to 1997 at a single center used by 3 hospital groups. Twenty-seven pretreatment candidate variables were analyzed with the use of stepwise proportional logistic regression, and 9 (nonchronic total occlusion with TIMI flow 0, degenerated vein graft, vein graft age >10 years, lesion length >/= 10 mm, severe calcium, lesion irregularity, large filling defect, angulated >/= 45 degrees plus calcium, and eccentricity) were independently correlated (P<0.05) with ranked adverse outcome (death, Q-wave or creatine kinase >/= 3x normal myocardial infarction, or emergency coronary artery bypass grafting>>creatine kinase 2 to 3x myocardial infarction>>possibly related to non-Q-wave myocardial infarction>>no complication). A scheme based on these findings and the old American College of Cardiology/American Heart Association scheme were found to have c-statistics in the validation set of 0.672 and 0.620 (P = 0.010 vs old scheme), respectively.Appreciation of these contemporary risk factors for complications of coronary intervention may assist in patient selection and in risk adjustment for comparison of outcomes between providers.
CHANGING HAND POSITIONS ALTERS LOWER EXTREMITY BIOMECHANICS DURING LANDING
Authors: J Ambegaonkar, E Oladipo, SV Caswell, Y Shimokochi, N Cortes
Journal: British Journal of Sports Medicine (2014)

Background During gameplay, athletes frequently change their trunk and hand placement positions (e.g. ball handling). Changing trunk positions alters lower extremity (LE) biomechanics and subsequent injury risk during sport. However, whether changing hand positions also alters LE biomechanics during landing (a high LE injury-risk activity) is unclear. Objective To examine if changing hand positions during landing affects LE biomechanics. Design Repeated measures. Setting Laboratory. Participants 30 healthy participants (23.4±4.3 years, 170.7±7.7 cm, 70.2±18.9 kg). Interventions Participants performed 5 landings from a 45cm box in 4 different hand placement (HP) conditions: 1) Holding a basketball at chest level (CH), 2) Holding a basketball at chest with arms straight in front (FR), 3) Holding a basketball straight up over head (UP), and 4) Placing hands on hips (HIP). Main outcome measurements Sagittal hip, knee, ankle angles (°) from initial touchdown to lowest point of the vertical Center of Mass (COM min) displacement were assessed using 3-D motion analyses. Repeated measures ANOVAs and Bonferroni pairwise comparisons examined differences across HP conditions. Results At touchdown, participants had differing hip (P&lt;.001), but not knee (P=.09), or ankle (P=.22) flexion angles across conditions. At COMmin, participants had differing hip (P=.01), knee (P=&lt;.001), and ankle (P&lt;.001)angles across conditions, resulting in differing hip (P=.01)and knee (P&lt;.001) but similar ankle (P=.06) flexion excursions across conditions. Specifically, participants had lower hip excursions in UP than in FR (P=.03) and HIP (P=.009), and lower knee excursions in CH than in FR (P=.02), UP (P=.003), and UP (P&lt;.001). Conclusions Overall, when landing with hands up or across the chest, participants landed in an extended posture and with decreased range of motion. Conversely, when landing with hands in front, participants had increased joint flexion angles associated with an increased range of motion. Changing hand placements during landing may alter LE biomechanics, and influence subsequent injury risk during landing. Clinicians should incorporate exercises that include hand position changes when designing injury prevention programs to decrease LE injury risk.
Sitting time and cardiometabolic risk in US adults: associations by sex, race, socioeconomic status and activity level
Authors: A E Staiano, D M Harrington, T V Barreira, P T Katzmarzyk
Journal: British Journal of Sports Medicine (2013)

Background Sitting time is associated with adverse health outcomes including chronic disease and premature mortality. However, it is not known if the association of sitting time with cardiometabolic risk factors varies across sociodemographic or health factors. Methods The sample included 4560 adults (≥20 years) who participated in the cross-sectional 2007–2010 US National Health and Nutrition Examination Survey. Participants self-reported typical daily sitting time. Weight, height, blood pressure, and fasting triglycerides, high-density lipoprotein-cholesterol (HDL-C), glucose and insulin were measured. Homeostatic model assessment-insulin resistance (HOMA-IR) and β cell function (HOMA-%B) were calculated. A subsample of 3727 participants underwent an oral glucose tolerance test to obtain 2 h postload glucose levels. Population-weighted linear regression analysis was used to examine the association between sitting time and each cardiometabolic risk factor, stratified by sex, race, socioeconomic status and activity level. Analyses were controlled for demographics, socioeconomic status, survey cycle, personal and family medical history, diet and physical activity. Results Sitting time was significantly associated with adverse levels of waist circumference, body mass index, triglycerides, HDL-C, insulin, HOMA-IR, HOMA-%B and 2 h postload glucose, but not with blood pressure or glucose level. In stratified analyses, sitting time was most consistently related to cardiometabolic risk factors among low and middle socioeconomic groups and for those who reported no weekly physical activity, but there were few differences between sex or race groups. Conclusions Self-reported sitting time was associated with adverse cardiometabolic risk factors consistently across sex and race groups in a representative US sample, independent of other risk factors. Excessive sitting warrants a public health concern.
Exercise Tolerance Testing To Screen for Coronary Heart Disease: A Systematic Review for the Technical Support for the U.S. Preventive Services Task Force
Authors: Angela Fowler-Brown, Michael Pignone, Mark Pletcher, Jeffrey A. Tice, Sonya F. Sutton, Kathleen N. Lohr
Journal: Annals of Internal Medicine (2004)

Background: Coronary heart disease is the leading cause of morbidity and mortality in the United States. Exercise tolerance testing has been proposed as a means of better identifying asymptomatic patients at high risk for coronary heart disease events. Purpose: To review the evidence on the use of exercise tolerance testing to screen adults with no history of cardiovascular disease for coronary heart disease. Data Sources: The MEDLINE database from 1966 through February 2003, hand-searching of bibliographies, and expert input. Study Selection: Eligible studies evaluated the benefits or harms of exercise tolerance testing when added to traditional risk assessment for adults with no known history of cardiovascular events. Data Extraction: One reviewer extracted information from eligible articles into evidence tables, and another reviewer checked the tables. Disagreements were resolved by consensus. Data Synthesis: No study has directly examined the effect of screening asymptomatic patients with exercise tolerance testing on coronary heart disease outcomes or risk-reducing behaviors or therapies. Multiple cohort studies demonstrate that screening exercise tolerance testing identifies a small proportion of asymptomatic persons (up to 2.7% of those screened) with severe coronary artery obstruction who may benefit from revascularization. Several large prospective cohort studies, conducted principally in middle-aged men, suggest that exercise tolerance testing can provide independent prognostic information about the risk for future coronary heart disease events (relative risk with abnormal exercise tolerance testing, 2.0 to 5.0). However, when the risk for coronary heart disease events is low, most positive findings will be false and may result in unnecessary further testing or worry. The risk level at which the benefits of additional prognostic information outweigh the harms of false-positive results is unclear and requires further study. Conclusions: Although screening exercise tolerance testing detects severe coronary artery obstruction in a small proportion of persons screened and can provide independent prognostic information about the risk for coronary heart disease events, the effect of this information on clinical management and disease outcomes in asymptomatic patients is unclear.
Calcium ATPase and respiratory muscle function
Authors: M Aubier, N Viires
Journal: European Respiratory Journal (1998)

The sarcoplasmic reticulum (SR) of striated muscle is a highly specialized intracellular membrane system that plays a key role in the contraction-relaxation cycle of muscle. Its primary function is the regulation of cytoplasmic Ca2+ concentration. A key element in this regulation is the Sarco(endo)plasmic reticulum Ca2+-adenosine triphosphatase (SERCA), which by sequestering Ca2+ into the SR, induces and maintains relaxation. It has been extensively studied with respect to structure and mechanism of action, and more recently to gene expression. Three separate genes encode five SERCA isoforms, two of which, SERCA 1 and SERCA 2, are expressed in skeletal muscle. In the first part of this review we focus on the general properties of the Ca2+ pump (structure and function and regulation of activity). In the second part we describe variations in SERCA expression in various physiological and pathological situations. These have essentially been studied in the heart and skeletal muscles, with data in respiratory muscles being very limited.
Of flies, mice and men: a systematic approach to understanding the early life origins of chronic lung disease
Authors: Susanne Krauss-Etschmann, Andrew Bush, Saverio Bellusci, Guy G Brusselle, Sven Erik K Dahlén, Stefan Dehmel, Oliver Eickelberg, Greg Gibson, Machteld N Hylkema, Petra Knaus, Melanie Königshoff, Clare M Lloyd, Paolo Macciarini, Arnaud Mailleux, Benjamin J Marsland, Dirkje S Postma, Graham Roberts, Christos Samakovlis, Janet Stocks, Joke Vandesompele, Matthias Wjst, John Holloway
Journal: Thorax (2012)

Despite intensive research efforts, the aetiology of the majority of chronic lung diseases (CLD) in both, children and adults, remains elusive. Current therapeutic options are limited, providing only symptomatic relief, rather than treating the underlying condition, or preventing its development in the first place. Thus, there is a strong and unmet clinical need for the development of both, novel effective therapies and preventative strategies for CLD. Many studies suggest that modifications of prenatal and/or early postnatal lung development will have important implications for future lung function and risk of CLD throughout life. This view represents a fundamental change of current pathophysiological concepts and treatment paradigms, and holds the potential to develop novel preventative and/or therapeutic strategies. However, for the successful development of such approaches, key questions, such as a clear understanding of underlying mechanisms of impaired lung development, the identification and validation of relevant preclinical models to facilitate translational research, and the development of concepts for correction of aberrant development, all need to be solved. Accordingly, a European Science Foundation Exploratory Workshop was held where clinical, translational and basic research scientists from different disciplines met to discuss potential mechanisms of developmental origins of CLD, and to identify major knowledge gaps in order to delineate a roadmap for future integrative research.
Silent Information Regulator 2α, a Longevity Factor and Class III Histone Deacetylase, Is an Essential Endogenous Apoptosis Inhibitor in Cardiac Myocytes
Authors: Ralph R. Alcendor, Lorrie A. Kirshenbaum, Shin-ichiro Imai, Stephen F. Vatner, Junichi Sadoshima
Journal: Circulation Research (2004)

Yeast silent information regulator 2 (Sir2), a nicotinamide adenine dinucleotide-dependent histone deacetylase (HDAC) and founding member of the HDAC class III family, functions in a wide array of cellular processes, including gene silencing, longevity, and DNA damage repair. We examined whether or not the mammalian ortholog Sir2 affects growth and death of cardiac myocytes. Cardiac myocytes express Sir2alpha predominantly in the nucleus. Neonatal rat cardiac myocytes were treated with 20 mmol/L nicotinamide (NAM), a Sir2 inhibitor, or 50 nmol/L Trichostatin A (TSA), a class I and II HDAC inhibitor. NAM induced a significant increase in nuclear fragmentation (2.2-fold) and cleaved caspase-3, as did sirtinol, a specific Sir2 inhibitor, and expression of dominant-negative Sir2alpha. TSA also modestly increased cell death (1.5-fold) but without accompanying caspase-3 activation. Although TSA induced a 1.5-fold increase in cardiac myocyte size and protein content, NAM reduced both. In addition, NAM caused acetylation and increases in the transcriptional activity of p53, whereas TSA did not. NAM-induced cardiac myocyte apoptosis was inhibited in the presence of dominant-negative p53, suggesting that Sir2alpha inhibition causes apoptosis through p53. Overexpression of Sir2alpha protected cardiac myocytes from apoptosis in response to serum starvation and significantly increased the size of cardiac myocytes. Furthermore, Sir2 expression was increased significantly in hearts from dogs with heart failure induced by rapid pacing superimposed on stable, severe hypertrophy. These results suggest that endogenous Sir2alpha plays an essential role in mediating cell survival, whereas Sir2alpha overexpression protects myocytes from apoptosis and causes modest hypertrophy. In contrast, inhibition of endogenous class I and II HDACs primarily causes cardiac myocyte hypertrophy and also induces modest cell death. An increase in Sir2 expression during heart failure suggests that Sir2 may play a cardioprotective role in pathologic hearts in vivo.
Mammography Rates 3 Years After the 2009 US Preventive Services Task Force Guidelines Changes
Authors: J. Frank Wharam, Bruce Landon, Fang Zhang, Xin Xu, Stephen Soumerai, Dennis Ross-Degnan
Journal: Journal of Clinical Oncology (2015)

Purpose In November 2009, the US Preventive Services Task Force (USPSTF) changed its mammography recommendations from every 1 to 2 years among women age ≥ 40 years to personalized screening decisions for women age 40 to 49 years and screening every 2 years for women age 50 to 74 years. Methods We studied mammography trends among 5.5 million women age 40 to 64 years enrolled in a large national health insurer. We used 2005 to 2009 mammography trends to predict 2012 rates. Our primary measure was the estimated difference between observed and predicted 2012 annual and biennial mammography rates. We stratified results by age group and race/ethnicity. Results Among women age 40 to 49 years, 2012 mammography rates declined by 9.9% (95% CI, −10.4% to −9.3%) relative to the predicted 2012 rate. Decreases were lowest among black women (−2.3%; 95% CI, −6.3% to 1.8%) and highest among Asian women (−17.4; 95% CI, −20.0 to −14.8). Annual mammography rates among women age 50 to 64 years declined by 6.1% (95% CI, −6.5% to −5.7%) by 2012. Regarding biennial mammography rates, women age 40 to 49 years experienced a 9.0% relative reduction (95% CI, −9.6% to −8.4%). White, Hispanic, and Asian women age 40 to 49 years demonstrated similar relative reductions of approximately 9% to 11%, whereas black women had no detectable changes (0.1%; 95% CI, −4.0% to 4.3%). Women age 50 to 64 years had a 6.2% relative reduction (95% CI, −6.6% to −5.7%) in biennial mammography that was similar among white, Hispanic, and Asian women. Black women age 50 to 64 years did not have changes in biennial mammography (0.4%; 95% CI, −2.6% to 3.5%). Conclusion Three years after publication of the 2009 USPSTF guidelines, mammography rates declined by 6% to 17% among white, Hispanic, and Asian women but not among black women. Small reductions in biennial mammography might be an unintended consequence of the updated guidelines.
Reproducibility along a 10 cm vertical visual analogue scale.
Authors: J S Dixon, H A Bird
Journal: Annals of the Rheumatic Diseases (1981)

Reproducibility along a vertical 10 cm visual analogue scale (VAS) was investigated. Eight normal volunteers attempted to duplicate a set of marked VAS. There was a tendency to estimate too high on the scale, and reproducibility was found to be variable along its length. This indicates that the error involved in the use of VASs is even more complex than previously thought.
TH2 cytokines increase kallikrein 7 expression and function in patients with atopic dermatitis
Authors: Shin Morizane, Kenshi Yamasaki, Ai Kajita, Kazuko Ikeda, Maosheng Zhan, Yumi Aoyama, Richard L. Gallo, Keiji Iwatsuki
Journal: Journal of Allergy and Clinical Immunology (2012)
Atypical pathogens and respiratory tract infections
Authors: F. Blasi
Journal: European Respiratory Journal (2004)

The atypical respiratory pathogens Chlamydia pneumoniae , Mycoplasma pneumoniae and Legionella pneumophila are now recognised as a significant cause of acute respiratory-tract infections, implicated in community-acquired pneumonia, acute exacerbations of chronic bronchitis, asthma, and less frequently, upper respiratory-tract infections. Chronic infection with C. pneumoniae is common among patients with chronic obstructive pulmonary disease and may also play a role in the natural history of asthma, including exacerbations. The lack of a gold standard for diagnosis of these pathogens still handicaps the current understanding of their true prevalence and role in the pathogenesis of acute and chronic respiratory infections. While molecular diagnostic techniques, such as polymerase chain reaction, offer improvements in sensitivity, specificity and rapidity over culture and serology, the need remains for a consistent and reproducible diagnostic technique, available to all microbiology laboratories. Current treatment guidelines for community-acquired pneumonia recognise the importance of atypical respiratory pathogens in its aetiology, for which macrolides are considered suitable first-line agents. The value of atypical coverage in antibiotic therapy for acute exacerbations of chronic bronchitis and exacerbations of asthma is less clear, while there is no evidence to suggest that atypical pathogens should be covered in antibiotic treatment of upper respiratory-tract infections.