tbuckley/cabot-search huggingface dataset:
Clinical recovery from surgery correlates with single-cell immune signatures
Authors: Brice Gaudillière, Gabriela K. Fragiadakis, Robert V. Bruggner, Monica Nicolau, Rachel Finck, Martha Tingle, Julian Silva, Edward A. Ganio, Christine G. Yeh, William J. Maloney, James I. Huddleston, Stuart B. Goodman, Mark M. Davis, Sean C. Bendall, Wendy J. Fantl, Martin S. Angst, Garry P. Nolan
Journal: Science Translational Medicine (2014)

Single-cell mass cytometry revealed immune correlates of patient-associated variability in surgical recovery.
The CD44-initiated pathway of T-cell extravasation uses VLA-4 but not LFA-1 for firm adhesion
Authors: Mark H. Siegelman, Diana Stanescu, Pila Estess
Journal: Journal of Clinical Investigation (2000)

Leukocytes extravasate from the blood in response to physiologic or pathologic demands by means of complementary ligand interactions between leukocytes and endothelial cells. The multistep model of leukocyte extravasation involves an initial transient interaction (“rolling” adhesion), followed by secondary (firm) adhesion. We recently showed that binding of CD44 on activated T lymphocytes to endothelial hyaluronan (HA) mediates a primary adhesive interaction under shear stress, permitting extravasation at sites of inflammation. The mechanism for subsequent firm adhesion has not been elucidated. Here we demonstrate that the integrin VLA-4 is used in secondary adhesion after CD44-mediated primary adhesion of human and mouse T cells in vitro, and by mouse T cells in an in vivo model. We show that clonal cell lines and polyclonally activated normal T cells roll under physiologic shear forces on hyaluronate and require VCAM-1, but not ICAM-1, as ligand for subsequent firm adhesion. This firm adhesion is also VLA-4 dependent, as shown by antibody inhibition. Moreover, in vivo short-term homing experiments in a model dependent on CD44 and HA demonstrate that superantigen-activated T cells require VLA-4, but not LFA-1, for entry into an inflamed peritoneal site. Thus, extravasation of activated T cells initiated by CD44 binding to HA depends upon VLA-4–mediated firm adhesion, which may explain the frequent association of these adhesion receptors with diverse chronic inflammatory processes.
XPF Expression Correlates with Clinical Outcome in Squamous Cell Carcinoma of the Head and Neck
Authors: Alec Vaezi, XiaoZhe Wang, Shama Buch, William Gooding, Lin Wang, Raja R. Seethala, David T. Weaver, Alan D. D'Andrea, Athanassios Argiris, Marjorie Romkes, Laura J. Niedernhofer, Jennifer R. Grandis
Journal: Clinical Cancer Research (2011)

Tumor-specific biomarkers that predict resistance to DNA damaging agents may improve therapeutic outcomes by guiding the selection of effective therapies and limiting morbidity related to ineffective approaches. XPF (ERCC4) is an essential component of several DNA repair pathways and XPF-deficient cells are exquisitely sensitive to DNA damaging agents. The purpose of this study was to determine whether XPF expression levels predict clinical response to DNA damaging agents in head and neck squamous cell carcinoma (HNSCC).Quantitative immunohistochemistry was used to measure XPF expression in tumors from a cohort of 80 patients with newly diagnosed HNSCC treated with radiation therapy with or without platinum-based chemotherapy; samples were collected prospectively. Genomic DNA isolated from blood samples was analyzed for nine single nucleotide polymorphisms (SNP) in the XPF gene by using a custom array. The primary endpoint was progression-free survival (PFS).XPF expression was higher in tumors from the oral cavity than from the other sites (P < 0.01). High XPF expression correlated with early time to progression both by univariate (HR = 1.87, P = 0.03) and multivariate analysis (HR = 1.83, P = 0.05). The one year PFS for high expressers was 47% (95% CI = 31-62) compared with 72% (95% CI = 55-83) for low expressers. In addition, we identified four XPF SNPs that showed marginal association with treatment failure.Expression level of XPF in HNSCC tumors correlates with clinical response to DNA damaging agents. XPF has potential to guide next generation personalized cancer therapy.
Mitochondrial depolarization and the role of uncoupling proteins in ischemia tolerance
Authors: M SACK
Journal: Cardiovascular Research (2006)

Modest depolarization of the mitochondrial inner membrane potential is known to attenuate mitochondrial reactive oxygen species generation. Transient pharmacologic uncoupling of mitochondrial oxidative phosphorylation results in modest depolarization of the mitochondrial membrane potential and confers protection against subsequent cardiac ischemia-reperfusion injury. Whether cardiac mitochondria have an innate capacity to temporally self-modulate their membrane potential as a possible adaptive mechanism in the context of cardiac ischemia and early reperfusion is supported by emerging data and is an intriguing concept that warrants further investigation. The objective of this review is to explore the various mechanisms whereby mitochondrial depolarization can be evoked in the context of both cardiac ischemia and reperfusion and in response to the cardioprotective program of ischemic preconditioning. The potential regulatory pathways orchestrating this biological perturbation of mitochondrial function are explored from the level of signal transduction to potential transcription-mediated modulations of nuclear-encoded mitochondrial inner membrane proteins, emphasizing the potential function of the mitochondrial uncoupling proteins.
Economic analysis of physical activity interventions: Table 1
Authors: Christopher Michael Williams, Chung-Wei Christine Lin, Stephen Jan
Journal: British Journal of Sports Medicine (2012)

▶ Wu S, Cohen D, Shi Y, et al. Economic analysis of physical activity interventions. Am J Prev Med 2011;40:149–58.[OpenUrl][1][CrossRef][2][PubMed][3] Physical activity (PA) is beneficial for general health and the prevention and treatment of chronic diseases. Interventions to increase PA range from community-wide interventions such as mass media campaigns to individual interventions such as behaviour change programmes. Previous systematic reviews have investigated the effectiveness of these interventions,1,–,4 but information on the relative cost effectiveness (ie, the costs per unit of benefit gained) of the interventions is limited. To provide a systematic review of interventions to increase PA and to calculate their cost effectiveness. Seven databases were searched for relevant studies published between 2000 and June 2008. Studies included in two systematic reviews1 4 were also considered. The review was restricted to published trials designed to promote PA in healthy individuals. Eligible studies were those that included 50 participants or more and reported an effective PA intervention with an outcome that could be translated into metabolic equivalent (MET) hours gained per person per day. Methodological quality was assessed using a nine-item measure. Interventions were categorised into six broad categories: … [1]: {openurl}?query=rft.jtitle%253DAmerican%2Bjournal%2Bof%2Bpreventive%2Bmedicine%26rft.stitle%253DAm%2BJ%2BPrev%2BMed%26rft.aulast%253DWu%26rft.auinit1%253DS.%26rft.volume%253D40%26rft.issue%253D2%26rft.spage%253D149%26rft.epage%253D158%26rft.atitle%253DEconomic%2Banalysis%2Bof%2Bphysical%2Bactivity%2Binterventions.%26rft_id%253Dinfo%253Adoi%252F10.1016%252Fj.amepre.2010.10.029%26rft_id%253Dinfo%253Apmid%252F21238863%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1016/j.amepre.2010.10.029&link_type=DOI [3]: /lookup/external-ref?access_num=21238863&link_type=MED&atom=%2Fbjsports%2F46%2F6%2F422.atom
Association of white blood cell count with metabolic syndrome in patients undergoing peritoneal dialysis
Authors: Jung Tak Park, Tae Ik Chang, Dong Ki Kim, Hoon Young Choi, Jung Eun Lee, Hyun Wook Kim, Jae Hyun Chang, Sun Young Park, Eunyoung Kim, Tae-Hyun Yoo, Dae-Suk Han, Shin-Wook Kang
Journal: Metabolism (2009)
To resect or not to resect? That is the question
Authors: M. Noureddin, D. E. Kleiner, A. M. Gharib, G. Bratslavsky, T. Heller
Journal: Gut (2010)

<h3>Abstract</h3> Conventional antibodies and their derived fragments are difficult to deploy against intracellular targets in live cells, due to their bulk and structural complexity. Nanobodies provide an alternative modality, with well documented examples of intracellular expression. Despite their promise as intracellular reagents, there has not been a systematic study of nanobody intracellular expression. Here, we examined intracellular expression of 75 nanobodies from the Protein Data Bank. Surprisingly, a majority of nanobodies were unstable in cells, illustrated by aggregation and clearance. Using comparative analysis and framework mutagenesis, we developed a general approach that stabilized a great majority of originally intracellularly unstable nanobodies, without compromising target-binding function. Additionally, we identified distinct sequence features impacting nanobody intracellular stability, and demonstrated mutationally stabilized nanobody expression in vivo, in the murine retina and in <i>E. coli</i>. This work will allow for standardized nanobody engineering for intracellular applications, potentiating a growing field of intracellular interrogation and intervention.
Mesalazine Improves Replication Fidelity in Cultured Colorectal Cells
Authors: Christoph Gasche, Ajay Goel, Loki Natarajan, C. Richard Boland
Journal: Cancer Research (2005)

Abstract Epidemiologic studies indicate that mesalazine has chemopreventive effects in inflammatory bowel disease–associated colorectal cancer. Most of our general understanding of chemoprevention in colorectal cancer is, however, derived from aspirin, which is structurally similar to mesalazine. Herein we determined the influence of aspirin and mesalazine on replication fidelity in cultured colorectal cells. Flow cytometry was used for quantitation of mutation rates at a (CA)13 microsatellite in HCT116 cells (mismatch repair deficient) and HCT116+chr3 cells (mismatch repair proficient) that had been stably transfected with pIREShyg2-EGFP/CA13, an enhanced green fluorescence protein–based plasmid, and cultured in the absence or presence of various concentrations of aspirin or mesalazine. Aspirin at doses above 1.25 mmol/L markedly reduced cell growth. Mesalazine doses up to 5.0 mmol/L had no such effect. The mutation rate in mismatch repair–deficient HCT116 cells was 6.8 × 10−4 ± 9.0 × 10−5. In aspirin-treated cultures the mutation rate was 8.2 × 10−4 ± 1.3 × 10−4 (121% of control). Instead, mesalazine lowered the mutation rate in a dose-dependent fashion (5.5 × 10−4 ± 1.1 × 10−4; 81% of control). The effects of mesalazine were most significant in the M1 fraction (P &amp;lt; 0.0001), which represents a mutant population immediate after the polymerase error and were confirmed in mismatch repair–proficient HCT116+chr3 cells. Our data indicate that mesalazine reduces frameshift mutations at a (CA)13 microsatellite in cultured colorectal cells independent of mismatch repair proficiency. This finding suggests that mesalazine improves replication fidelity, an effect that may be active in reducing mutations independent of its anti-inflammatory properties.
Impact of Cancer on Health-Related Quality of Life of Older Americans
Authors: B. B. Reeve, A. L. Potosky, A. W. Smith, P. K. Han, R. D. Hays, W. W. Davis, N. K. Arora, S. C. Haffer, S. B. Clauser
Journal: JNCI Journal of the National Cancer Institute (2009)

The impact of cancer on health-related quality of life (HRQOL) is poorly understood because of the lack of baseline HRQOL status before cancer diagnosis. To our knowledge, this is the first population-based study to quantify the nature and extent of HRQOL changes from before to after cancer diagnosis for nine types of cancer patients and to compare their health with individuals without cancer. The Surveillance, Epidemiology, and End Results cancer registry data were linked with the Medicare Health Outcomes Survey (MHOS) data; data were collected from Medicare beneficiaries who were aged 65 years and older from 1998 through 2003. Cancer patients (n = 1432; with prostate, breast, colorectal, lung, bladder, endometrial, or kidney cancers; melanoma; or non-Hodgkin lymphoma [NHL]) were selected whose first cancer diagnosis occurred between their baseline and follow-up MHOS assessments. Control subjects without cancer (n = 7160) were matched to cancer patients by use of propensity scores that were estimated from demographics and comorbid medical conditions. Analysis of covariance models were used to estimate changes in HRQOL as assessed with the Medical Outcomes Study Short Form-36 survey (mean score = 50, SD = 10). All statistical tests were two-sided. Patients with all cancer types (except melanoma and endometrial cancer) reported statistically significant declines in physical health (mean scores: prostate cancer = −3.4, 95% confidence interval [CI] = −2.5 to −4.2; breast cancer = −3.5, 95% CI = −2.5 to −4.5; bladder cancer = −4.3, 95% CI = −2.5 to −6.1; colorectal cancer = −4.4, 95% CI = −3.3 to −5.5; kidney cancer = −5.7, 95% CI = −3.2 to −8.2; NHL = −6.7, 95% CI = −4.4 to −9.1; and lung cancer = −7.5, 95% CI = −5.9 to −9.2) compared with the control subjects (mean score = −1.8, 95% CI = −1.6 to −2.0) (all P < .05). However, only lung (mean score = −5.4, 95% CI = −3.5 to −7.2), colorectal (mean score = −3.5, 95% CI = −2.2 to −4.7), and prostate (mean score = −2.8, 95% CI = −1.8 to −3.7) cancer patients showed statistically significant decreases in mental health relative to the mean change of the control subjects (mean score = −1.2, 95% CI = −0.9 to −1.4) (all P < .05). These findings provide validation of the specific deleterious effects of cancer on HRQOL and an evidence base for future research and clinical interventions aimed at understanding and remediating these effects.
A pilot study of the prevalence of lumbar disc degeneration in elite athletes with lower back pain at the Sydney 2000 Olympic Games
Authors: A Ong, J Anderson, J Roche
Journal: British Journal of Sports Medicine (2003)

To observe the prevalence of lumbar intervertebral disc degeneration in elite athletes as compared with published literature of changes seen in non-athletes-that is, normal population.The lumbar spines of 31 Olympic athletes who presented to the Olympic Polyclinic with low back pain and/or sciatica were examined using magnetic resonance imaging. Three criteria were looked at: (a) the loss of disc signal intensity; (b) the loss of disc height; (c) the presence of disc displacement. The results were then recorded and correlated with the lumbar levels.The disc signal intensity was progressively reduced the more caudal the disc space. It was most common at the L5/S1 level, and, of the abnormal group, 36% (n = 11) showed the most degenerative change. Disc height reduction was also found to be most common at the L5/S1 level. However, the most common height reduction was only mild. A similar trend of increased prevalence of disc herniation was noted with more caudal levels. At the L5/S1 level, 58% were found to have an element of disc displacement, most of which were disc bulges. Compared with changes seen in the normal population (non-athletes) as described in the literature, disc degeneration defined by the above criteria was found to be significantly more severe in these Olympic athletes.Although the study was limited, the results suggest that elite athletes have a greater prevalence and greater degree of lumbar disc degeneration than the normal population. A more detailed follow up study should be considered to investigate which particular training activities have the most impact on the lumbar spine, and how to modify training methods so as to avoid the long term sequelae of degenerative disc disease of the lumbar spine.
1356 QUADRUPLE THERAPY WITH BMS-790052, BMS-650032 AND PEG-IFN/RBV FOR 24 WEEKS RESULTS IN 100% SVR12 IN HCV GENOTYPE 1 NULL RESPONDERS
Authors: A. Lok, D. Gardiner, E. Lawitz, C. Martorell, G. Everson, R. Ghalib, R. Reindollar, V. Rustgi, F. McPhee, M. Wind-Rotolo, A. Persson, K. Zhu, D. Dimitrova, T. Eley, T. Guo, D. Grasela, C. Pasquinelli
Journal: Journal of Hepatology (2011)
PANMYELOPHTHISIS WITH HEMORRHAGIC MANIFESTATIONS IN RATS ON A NUTRITIONAL BASIS
Authors: Paul György, Harry Goldblatt, Franklin R. Miller, Robert P. Fulton
Journal: The Journal of Experimental Medicine (1937)

During the 12 months ending May, 1937, 72 rats were observed that manifested typical symptoms of panmyelophthisis. The disease may start as agranulocytosis, thrombocytopenia or pure red cell anemia, leading progressively, often rapidly, to aleukia hemorrhagica with its typical manifestations (epistaxis, melena, hematuria, purpura). Blood examinations revealed correspondingly low white cell, red cell and platelet counts with very pronounced granulocytopenia (0 to 4 per cent). Bone marrow smears and histological findings were consistent with the diagnosis of panmyelophthisis. Suprarenal hemorrhage was a frequent postmortem finding. The pathogenesis of this experimental panmyelophthisis and this hemorrhagic diathesis is confined to special nutritional conditions. These diseases have been observed by us in rats kept on a diet deficient in vitamin B(6), containing cane sugar and supplemented with vitamin B(1) and crystalline natural or synthetic lactoflavin. Lack of vitamin B(6), however, is not a necessary condition, since the disease was encountered in the majority of the animals after the specific deficiency disease which became apparent in rats kept on the B(6) free diet was successfully treated with purified B(6) preparations. Even in the untreated animals kept on the B(6) deficient diet acrodynia was, as a rule, in distinct remission before symptoms of panmyelophthisis and hemorrhagic diathesis became manifest. By means of the addition of Peters' eluate to the basal diet, panmyelophthisis could be prevented and, in animals where it was recognized in an early stage, cured. In view of these facts it is suggested that Peters' eluate contains a specific maturation factor for the primary blood-producing tissue, the reticulo-endothelium, a factor which, being different from lactoflavin, vitamin B(6) and probably also from the so called filtrate factor, constitutes another distinct component of the vitamin B(2) group. Bacteriological studies brought forward no conclusive positive evidence for the infectious etiology of the experimental panmyelophthisis in our rats. The possible relation of this new disease in rats to aleukia hemorrhagica and its partial manifestations in man, as well as to the so called Waterhouse-Friderichsen syndrome, is discussed. Administration of amidopyrine, at least under the conditions chosen, failed to provoke panmyelophthisis in rats kept on the same diet as that given to rats in which the disease spontaneously developed.
Unusual presentation of tropical pulmonary eosinophilia.
Authors: V K Jain, O P Beniwal
Journal: Thorax (1984)

Typical clinical and radiological features of tropical pulmonary eosinophilia were originally described by Weingar- ten.' Cases of tropical pulmonary eosinophilia were ini- tially recorded in India, but the disease is now known to occur throughout the world.Various atypical radiological presentations such as cavitation,2-pleural effusion,3' and patchy pneumonitis5 7 have been reported.Very few cases with a large area of pneumonitis'8 have been recorded.In view of its rarity we present a case of tropical pulmonary eosinophilia in which a large area of pneumonia like con- solidation was present in the right lower zone.
Antitumor Activity of Epidermal Growth Factor Receptor–Related Protein Is Mediated by Inactivation of ErbB Receptors and Nuclear Factor-κB in Pancreatic Cancer
Authors: Yuxiang Zhang, Sanjeev Banerjee, Zhiwei Wang, Hu Xu, Liyue Zhang, Ramzi Mohammad, Amro Aboukameel, Nazmi V. Adsay, Mingxin Che, James L. Abbruzzese, Adhip P.N. Majumdar, Fazlul H. Sarkar
Journal: Cancer Research (2006)

Abstract The erbB family of receptor tyrosine kinases plays critical roles in human cancers, including pancreatic cancer. Discovering a specific agent, which targets multiple members of the erbB family, would be important in pancreatic cancer therapy. Recently, we isolated a novel negative regulator of epidermal growth factor receptor (EGFR), termed EGFR-related protein (ERRP), whose expression attenuates EGFR activation. In the current study, we examined the effects of recombinant ERRP on the growth and ligand-induced activation of multiple members of erbB family in three pancreatic cancer cell lines that express varying levels of EGFR and other member(s) of its family, specifically HER-2. Additionally, we compared the growth inhibitory effect of ERRP with that of Erbitux or Herceptin. Our results showed that ERRP is most effective in inhibiting proliferation of BxPC-3, HPAC, and PANC-1 pancreatic cancer cells. ERRP also inhibited ligand-induced activation of EGFR, HER-2, and HER-3 (ErbB3). In contrast, Erbitux and Herceptin only partially or modestly inhibited activation of EGFR, HER-2, and HER-3. Most importantly, ERRP was found to inhibit pancreatic tumor growth in a severe combined immunodeficient mouse xenograft model. The antitumor activity of ERRP correlates well with tumor differentiation and down-regulation of nuclear factor-κB activity. In summary, our results suggest that ERRP is an effective pan-erbB inhibitor, which could be a potential therapeutic agent for pancreatic cancers expressing different levels and subclasses of erbB family of proteins. (Cancer Res 2006; 66(2): 1025-32)
Pregnancy-Associated Plasma Protein-A Levels Are Related to Glycemic Control but Not to Lipid Profile or Hemostatic Parameters in Type 2 Diabetes
Authors: Silvia Pellitero, Jordi L. Reverter, Eduarda Pizarro, Maria Cruz Pastor, Maria Luisa Granada, Dolors Tàssies, Juan-Carlos Reverter, Isabel Salinas, Anna Sanmartí
Journal: Diabetes Care (2007)

Pregnancy-associated plasma protein-A (PAPP-A) is a zinc-binding matrix metalloproteinase that regulates extracellular matrix remodeling. PAPP-A degrades IGFBP-4, increasing levels of local IGF-1 in response to injury, and could be involved in the pathogenesis of atherosclerosis (1–6). Inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-1β, implicated in insulin resistance (7), are potent stimulators of PAPP-A (8,9). The association between PAPP-A levels and metabolic parameters such as cholesterol and high-sensitivity C-reactive protein (hsCRP) is controversial (2,10,11). We aimed to study the relationship between PAPP-A, glycemic control and other metabolic and hemostatic parameters, inflammatory cytokines, and ankle-brachial pressure index (ABI) in diabetic patients.

Type 2 diabetic patients ( n = 175, 65 of whom were women) with stable glycemic control (variation in A1C <10% in the last 5 years) and without diagnosis of clinical macrovascular disease, inflammatory disease, malignancies, or pregnancy were studied. Fifty-three (20 of whom were women) nondiabetic subjects without previous clinical macrovascular disease and normal ABI (≥0.9) were recruited as control subjects.

Demographic, anthropometric, and clinical data and ABI were recorded in all subjects. Laboratory data were measured by commercially available assays, hsCRP by nephelometry, ultrasensitive PAPP-A using an enzyme-linked immunosorbent assay, and TNF-α and IL-6 concentrations using an enzyme …