tbuckley/cabot-search huggingface dataset:
The anti-inflammatory agent bindarit inhibits neointima formation in both rats and hyperlipidaemic mice
Authors: G. Grassia, M. Maddaluno, A. Guglielmotti, G. Mangano, G. Biondi, P. Maffia, A. Ialenti
Journal: Cardiovascular Research (2009)

Bindarit is an original compound with peculiar anti-inflammatory activity due to a selective inhibition of a subfamily of inflammatory chemokines, including the monocyte chemotactic proteins MCP-1/CCL2, MCP-3/CCL7, and MCP-2/CCL8. In this study, we investigated the effect of bindarit on neointima formation using two animal models of arterial injury: rat carotid artery balloon angioplasty and wire-induced carotid injury in apolipoprotein E-deficient (apoE−/−) mice. Treatment of rats with bindarit (200 mg/kg/day) significantly reduced balloon injury-induced neointima formation by 39% at day 14 without affecting re-endothelialization and reduced the number of medial and neointimal proliferating cells at day 7 by 54 and 30%, respectively. These effects were associated with a significant reduction of MCP-1 levels both in sera and in injured carotid arteries of rats treated with bindarit. In addition, in vitro data showed that bindarit (10–300 µM) reduced rat vascular smooth muscle cell (VSMC) proliferation, migration, and invasion, processes contributing to the injury-induced neointima formation in vivo. Similar results were observed in hypercholesterolaemic apoE−/− mice in which bindarit administration resulted in a 42% reduction of the number of proliferating cells at day 7 after carotid injury and in a 47% inhibition of neointima formation at day 28. Analysis of the cellular composition in neointimal lesions of apoE−/− mice treated with bindarit showed that the relative content of macrophages and the number of VSMCs were reduced by 66 and 30%, respectively, compared with the control group. This study demonstrates that bindarit is effective in reducing neointima formation in both non-hyperlipidaemic and hyperlipidaemic animal models of vascular injury by a direct effect on VSMC proliferation and migration and by reducing neointimal macrophage content. All of these data were associated with the inhibition of MCP-1 production.
14-3-3σ Modulates Pancreatic Cancer Cell Survival and Invasiveness
Authors: Divas Neupane, Murray Korc
Journal: Clinical Cancer Research (2008)

Abstract Purpose: The purpose of the present study was to investigate the potential role of 14-3-3σ in pancreatic ductal adenocarcinoma (PDAC). Experimental Design: 14-3-3 isoform expression was determined by real-time quantitative PCR in laser capture normal pancreatic ductal cells and pancreatic cancer cells and in 5 pancreatic cancer cell lines. PANC-1 cells, with low levels of 14-3-3σ, were stably transfected with a human 14-3-3σ cDNA. Conversely, high endogenous 14-3-3σ levels in T3M4 cells were suppressed by specific short hairpin RNA. Apoptosis, motility, and invasiveness were studied. Results: The cancer cells in 7 PDAC samples expressed high levels of 14-3-3σ mRNA by quantitative PCR when compared with normal pancreatic duct cells. 14-3-3σ protein levels were high in BxPC3, COLO-357, and T3M4 cells, intermediate in ASPC-1 cells, and low in PANC-1 cells. Most cell lines released detectable amount of 14-3-3σ into conditioned medium. Overexpression of 14-3-3σ in PANC-1 cells led to resistance to cisplatinum-induced apoptosis, increased basal migration, and increased invasion in response to epidermal growth factor and insulin-like growth factor-I. By contrast, short hairpin RNA-mediated knockdown of endogenous 14-3-3σ in T3M4 cells did not alter migration but led to enhanced cisplatinum sensitivity, increased invasiveness in response to epidermal growth factor, and decreased invasiveness in response to insulin-like growth factor-I. Conclusions: 14-3-3σ contributes to the chemoresistance of pancreatic cancer cells and exerts cell type-dependent effects on cell migration and invasion. Therefore, strategies aimed at suppressing 14-3-3σ expression and function may have a therapeutic benefit in subgroups of patients with PDAC.
Neurological complications of enteric disease.
Authors: A Dunk
Journal: Gut (1997)

Neurological complications of enteric disease EDITOR,-I read the leading article on neuro- logical complications of enteric disease by Drs Wills and Hovell (Gut 1996; 39: 501-4) immediately after seeing a young woman with achalasia of the cardia and ataxia as a result of cerebellar degeneration in my outpatient clinic.Such an association is not described in the article.As gastroenterologists, we consider achalasia an "enteric disease" in the broadest sense of the phrase, but it is, of course, primarily a disease of the enteric nervous system.This perhaps explains why achalasia and other gastrointestinal disorders which are caused by enteric nervous dysfunction are not described in the article, even though several such disorders have neurological associations.To complete the picture, I draw your readers' attention to a recent comprehensive review on the enteric nervous system,' in which I was delighted to find the reference to a paper2 which seemed to describe the young woman in my clinic.
Release of Neutrophil Extracellular Traps by Neutrophils Stimulated With Antiphospholipid Antibodies: A Newly Identified Mechanism of Thrombosis in the Antiphospholipid Syndrome
Authors: Srilakshmi Yalavarthi, Travis J. Gould, Ashish N. Rao, Levi F. Mazza, Alexandra E. Morris, Carlos Núñez‐Álvarez, Diego Hernández‐Ramírez, Paula L. Bockenstedt, Patricia C. Liaw, Antonio R. Cabral, Jason S. Knight
Journal: Arthritis & Rheumatology (2015)

Antiphospholipid antibodies (aPL), especially those targeting β2 -glycoprotein I (β2 GPI), are well known to activate endothelial cells, monocytes, and platelets, with prothrombotic implications. In contrast, the interaction of aPL with neutrophils has not been extensively studied. Neutrophil extracellular traps (NETs) have recently been recognized as an important activator of the coagulation cascade, as well as an integral component of arterial and venous thrombi. This study was undertaken to determine whether aPL activate neutrophils to release NETs, thereby predisposing to the arterial and venous thrombosis inherent in the antiphospholipid syndrome (APS).Neutrophils, sera, and plasma were prepared from patients with primary APS (n = 52) or from healthy volunteers and characterized. No patient had concomitant systemic lupus erythematosus.Sera and plasma from patients with primary APS had elevated levels of both cell-free DNA and NETs, as compared to healthy volunteers. Freshly isolated neutrophils from patients with APS were predisposed to high levels of spontaneous NET release. Further, APS patient sera, as well as IgG purified from APS patients, stimulated NET release from control neutrophils. Human aPL monoclonal antibodies, especially those targeting β2 GPI, also enhanced NET release. The induction of APS NETs was abrogated with inhibitors of reactive oxygen species formation and Toll-like receptor 4 signaling. Highlighting the potential clinical relevance of these findings, APS NETs promoted thrombin generation.Our findings indicate that NET release warrants further investigation as a novel therapeutic target in APS.
Optimal Methods for Staging Rectal Cancer
Authors: V. Raman Muthusamy, Kenneth J. Chang
Journal: Clinical Cancer Research (2007)

Abstract At present, several modalities exist for the preoperative staging of rectal lesions, including computed tomography (CT), body coil or endorectal coil magnetic resonance imaging (MRI), endoscopic ultrasonography (EUS) done by rigid or flexible probes, and positron emission tomography (PET). Staging accuracy for CT ranges from 53% to 94% for T-stage accuracy and from 54% to 70% for N-stage accuracy. Improved CT accuracy is observed at higher disease stages. Body coil MRI has shown T- and N-stage accuracy ranging from 59% to 95% and 39% to 95%, respectively. Endorectal coil MRI has shown improved T- and N-stage accuracy, with rates of 66% to 91% and 72% to 79%, respectively. The development of phased-array MRI, combining high spatial resolution with a larger field of view, offers promise to improve on these rates. EUS, considered the current gold standard, has shown T-stage accuracy ranging from 75% to 95%, with N-stage accuracy ranging from 65% to 80%. Flexible EUS probes have the advantage of being able to access and sample iliac nodes. Recent studies also suggest that three-dimensional EUS may provide greater accuracy than conventional two-dimensional EUS. Limited studies exist on the use of PET in primary tumor staging. PET may upstage disease in 8% to 24% of patients and has also been used in posttreatment restaging and surveillance. Postradiation edema, necrosis, and fibrosis seem to decrease restaging accuracy in all modalities. This article reviews the current literature about the staging accuracy of the various modalities and suggests a staging algorithm for rectal cancer.
Genetic variants and risk of lung cancer in never smokers: a genome-wide association study
Authors: Yafei Li, Chau-Chyun Sheu, Yuanqing Ye, Mariza de Andrade, Liang Wang, Shen-Chih Chang, Marie C Aubry, Jeremiah A Aakre, Mark S Allen, Feng Chen, Julie M Cunningham, Claude Deschamps, Ruoxiang Jiang, Jie Lin, Randolph S Marks, V Shane Pankratz, Li Su, Yan Li, Zhifu Sun, Hui Tang, George Vasmatzis, Curtis C Harris, Margaret R Spitz, Jin Jen, Renyi Wang, Zuo-Feng Zhang, David C Christiani, Xifeng Wu, Ping Yang
Journal: The Lancet Oncology (2010)
Fertility and Risk Factors for Elevated Infertility Concern in 10-Year Hematopoietic Cell Transplant Survivors and Case-Matched Controls
Authors: Camille Hammond, Janet R. Abrams, Karen L. Syrjala
Journal: Journal of Clinical Oncology (2007)

Purpose To describe fertility status and the prevalence of and risk factors for elevated infertility concern in 10-year adult cancer survivors who underwent myeloablative stem cell transplant (SCT). Patients and Methods Perceived fertility status, conception efforts, and infertility concern were reported before transplant and after 10 years by 120 cancer survivors who received myeloablative SCT and their case-matched controls. Results Respondents (including cases and controls) were predominantly white and married. Sex, age, race, ethnicity and education level were case matched. Four survivors (all males) conceived after completing cancer treatment, one with unassisted conception. Twenty-two percent of survivors compared with 9% of controls reported that they had looked into family-building options because of infertility (P = .009). Fourteen survivors (12%) compared with eight controls (7%) indicated that they had tried unsuccessfully to have children in the previous 10 years (P = not significant). One quarter of survivors had moderate to high levels of concern about infertility, compared with 7% of controls. A majority of survivors younger than age 40 years (n = 20; 54%) expressed elevated infertility concern. Survivors without children before transplant had greater risk of elevated concern after 10 years (odds ratio, 3.41; 95% CI, 1.93 to 11.30; P = .05). Although female controls were more likely to express elevated infertility concern (P = .007), sex did not discriminate concern among survivors. Conclusion The prevalence of infertility and related concerns is higher among long-term SCT survivors than among age-, sex-, and education-matched controls. Younger SCT recipients and those without children have persistent fertility-related needs even 10 years after treatment.
Breast Cancer Survival and Tumor Characteristics in Premenopausal Women Carrying the <i>CHEK2*1100delC</i> Germline Mutation
Authors: Marjanka K. Schmidt, Rob A.E.M. Tollenaar, Sanne R. de Kemp, Annegien Broeks, Cees J. Cornelisse, Vincent T.H.B.M. Smit, Johannes L. Peterse, Flora E. van Leeuwen, Laura J. Van 't Veer
Journal: Journal of Clinical Oncology (2006)

Purpose Women carrying a CHEK2*1100delC germline mutation have an increased risk of developing breast cancer. This study aims to determine the proportion of CHEK2*1100delC carriers in a premenopausal breast cancer population, unselected for family history of breast cancer, and to investigate tumor characteristics and disease outcome with sufficient follow-up. Patients and Methods We identified a retrospective cohort of 1,479 patients, who received surgery for invasive breast cancer between 1970 and 1994. All patients were diagnosed before age 50. Paraffin-embedded tissue blocks were collected for DNA isolation (normal tissue), subsequent CHEK2*1100delC analysis, and tumor revision. Median follow-up was 10.1 years. Results We detected a CHEK2*1100delC germline mutation in 54 patients (3.7%). Tumor characteristics of CHEK2*1100delC carriers did not differ significantly from those of noncarriers. CHEK2*1100delC carriers had a two-fold increased risk (hazard ratio [HR], 2.1; 95% CI, 1.0 to 4.3; P = .049) of developing a second breast cancer and they had worse recurrence-free survival (HR, 1.7; 95% CI, 1.2 to 2.4; P = .006) and worse breast cancer–specific survival (HR, 1.4; 95% CI, 1.0 to 2.1; P = .072) compared with noncarriers. The poorer disease outcome of CHEK2*1100delC carriers could not be explained by the increased risk of second breast cancer. Conclusion Our study, which is representative for the premenopausal breast cancer population, reveals approximately 4% CHEK2*1100delC carriers have an increased risk of second breast cancer and a worse long-term recurrence-free survival rate. Their identification at time of diagnosis and prolonged intensive follow-up should be considered to optimize clinical management.
Get Set: prevent sports injuries with exercise!
Authors: Evert Verhagen
Journal: British Journal of Sports Medicine (2015)

The Get Set app provides the amateur and elite athlete with injury preventive exercises for a range of sports. The app has been created by the International Olympic Committee with input from athletes and an international panel of experts. The clean and crisp interface presents the user with various exercises that aim to reduce the risk of injury. After a short introduction, the user can choose either sports-specific exercises or exercises targeting a specific body region. The app contains …
The effects of hyaluronidase on coronary blood flow following coronary artery occlusion in the dog.
Authors: J Askenazi, L D Hillis, P E Diaz, M A Davis, E Braunwald, P R Maroko
Journal: Circulation Research (1977)

In an attempt to determine the mechanism by which hyaluronidase reduces myocardial injury following coronary artery occlusion, myocardial blood flow was studied in 20 open-chest dogs with occlusion of the left anterior descending coronary artery. Ten dogs served as controls, and 10 received hyaluronidase (500 NF units/kg) intravenously 20 minutes after occlusion. At 15 minutes and at 6 hours after occlusion, regional myocardial blood flow in the epicardial and endocardial halves of both ischemic and nonischemic zones were determined with radiolabeled microspheres. Mean arterial pressure, heart rate, and cardiac output were similar in the untreated and treated dogs through the 6 hours of the experiment. Moreover, regional blood flow to nonischemic myocardium (areas without epicardial S-T segment elevation 15 minutes after occlusion) was similar in the two groups 15 minutes and 6 hours after occlusion. Fifteen minutes after occlusion, the flow to the ischemic myocardium subjacent to sites with S-T segment elevation exceeding 2 mV) in the untreated group was: transmural, 28.1 +/- 2.2 (mean +/- SE) ml/min per 100 g; endocardial, 20.7 +/- 1.8; and epicardial, 38.5 +/- 3.1. The endocardial-epicardial flow ratio was 0.56 +/- 0.04. Six hours after occlusion, the untreated group demonstrated a further decrease in blood flow to the ischemic myocardium: transmural, 15.2 +/- 1.4 ml/min per 100 g; endocardial, 6.8 +/- 1.1; and epicardial, 24.3 +/- 1.9. The endocardial-epicardial flow ratio fell to 0.28 +/- 0.04. In contrast, the hyaluronidase-treated dogs showed no further reduction in blood flow to ischemic myocardium 6 hours after occlusion: transmural, 30.3 +/- 3.1 ml/min per 100 g; endocardial, 21.3 +/- 2.5; and epicardial, 38.8 +/- 3.8. These regional myocardial flows were significantly higher than those of the untreated dogs 6 hours after occlusion. Thus, salvage of damaged myocardium by hyaluronidase might be explained by its beneficial effect on collateral blood flow to the ischemic tissue, though this effect on collateral flow could be the consequence rather than the cause of this salvage.
The paternal inheritance of the centrosome, the cell's microtubule-organizing center, in humans, and the implications for infertility
Authors: Calvin Simerly, Gwo-Jang Wu, Sara Zoran, Teri Ord, Richard Rawlins, Jeffrey Jones, Christopher Navara, Marybeth Gerrity, John Rinehart, Zvi Binor, Ricardo Asch, Gerald Schatten
Journal: Nature Medicine (1995)
Key Role of CRF in the Skin Stress Response System
Authors: Andrzej T. Slominski, Michal A. Zmijewski, Blazej Zbytek, Desmond J. Tobin, Theoharis C. Theoharides, Jean Rivier
Journal: Endocrine Reviews (2013)

The discovery of corticotropin-releasing factor (CRF) or CRH defining the upper regulatory arm of the hypothalamic-pituitary-adrenal (HPA) axis, along with the identification of the corresponding receptors (CRFRs 1 and 2), represents a milestone in our understanding of central mechanisms regulating body and local homeostasis. We focused on the CRF-led signaling systems in the skin and offer a model for regulation of peripheral homeostasis based on the interaction of CRF and the structurally related urocortins with corresponding receptors and the resulting direct or indirect phenotypic effects that include regulation of epidermal barrier function, skin immune, pigmentary, adnexal, and dermal functions necessary to maintain local and systemic homeostasis. The regulatory modes of action include the classical CRF-led cutaneous equivalent of the central HPA axis, the expression and function of CRF and related peptides, and the stimulation of pro-opiomelanocortin peptides or cytokines. The key regulatory role is assigned to the CRFR-1α receptor, with other isoforms having modulatory effects. CRF can be released from sensory nerves and immune cells in response to emotional and environmental stressors. The expression sequence of peptides includes urocortin/CRF→pro-opiomelanocortin→ACTH, MSH, and β-endorphin. Expression of these peptides and of CRFR-1α is environmentally regulated, and their dysfunction can lead to skin and systemic diseases. Environmentally stressed skin can activate both the central and local HPA axis through either sensory nerves or humoral factors to turn on homeostatic responses counteracting cutaneous and systemic environmental damage. CRF and CRFR-1 may constitute novel targets through the use of specific agonists or antagonists, especially for therapy of skin diseases that worsen with stress, such as atopic dermatitis and psoriasis.
A 61-year-old female with chronic cough and purulent sputum
Authors: Luca Bilucaglia, Stefano Aliberti, Egidio Franco Viganò, Annalisa Pantosti, Monica Monaco, Alessandra Ciervo, Fabiola Mancini, Paola Faverio, Alberto Pesci
Journal: European Respiratory Journal (2013)

To the Editor: 

A 61-yr-old Caucasian female was referred to our outpatient clinic for persistent cough, right scapular pain and purulent sputum for the past 9 months.

Her past medical history was consistent with a diagnosis of pneumonia almost 20 yrs previously. She reported no allergies and was not taking any medications at home. She lived in an urban setting working as a hairdresser, and had no pets at home. She had received all the standard vaccinations based on the Italian law, including diphtheria, smallpox, tetanus, hepatitis A and typhus. She was married and had two daughters in good health. She went on vacation to Cuba 2 yrs previously, India (Rajasthan) 1 yr previously and Portugal 6 months ago.

Her history of present illness was consistent with cough and mucopurulent sputum without fever for 9 months prior to visiting our clinic. She reported a scapolar right pain that had occurred 15 days prior to admission to the hospital which was not related to positioning or breathing. A negative chest radiograph had been performed 3 months prior to the visit, and at that point she was treated with oral prednisone (25 mg every 24 h for 15 days) with no evidence of clinical improvement. Finally, she underwent a chest computed tomography (CT) scan with the evidence of lung opacities with enhancement in the medium lobe and in the lingual (fig. 1a …
Diagnostic Accuracy of MALDI Mass Spectrometric Analysis of Unfractionated Serum in Lung Cancer
Authors: Pinar B. Yildiz, Yu Shyr, Jamshedur S.M. Rahman, Noel R. Wardwell, Lisa J. Zimmerman, Bashar Shakhtour, William H. Gray, Shuo Chen, Ming Li, Heinrich Roder, Daniel C. Liebler, William L. Bigbee, Jill M. Siegfried, Joel L. Weissfeld, Adriana L. Gonzalez, Mathew Ninan, David H. Johnson, David P. Carbone, Richard M. Caprioli, Pierre P. Massion
Journal: Journal of Thoracic Oncology (2007)
Progression-Free Survival Benefit or Health-Related Quality-of-Life Advantage: Which One to Choose?
Authors: Cengiz Gemici
Journal: Journal of Clinical Oncology (2013)

Soffietti et al,1 in their recent randomized phase III trial, assessed whether the addition of adjuvant whole-brain radiotherapy (WBRT) improves results in patients with solid tumors and one to three brain metastases who are treated with surgical resection or stereotactic radiosurgery (SRS) alone.The authors suggested that WBRT, either after complete surgical resection or SRS, does not affect overall and functionally independent survival or even negatively affect some aspects of health-related quality of life (HRQOL). 1,2They consider these arguments against WBRT administration after surgical resection or SRS for patients with a limited number of brain metastases from solid tumors.However, the reality is not so simple, and adjuvant WBRT in these patients in fact provides many advantages.These can be summarized as higher progression-free survival (PFS) rates, lower neurologic death rates (intracranial failure as a component of cause of death),