tbuckley/cabot-search huggingface dataset:
Abstract 4201: Activation of p90 ribosomal S6 kinase (RSK) and downstream targets are directly regulated by S100B protein in malignant melanoma
Authors: Adam D. Pierce
Journal: Cancer Research (2014)

Abstract S100B is an effective and extensively used prognostic marker for melanoma, with increasing serum levels of S100B being predictive of disease stage, increased recurrence, and low overall patient survival. We have recently identified a mechanism by which S100B alters ERK-RSK signaling to facilitate the progression of melanoma. Elucidation of this novel mechanism will aid the development of new pharmacological drugs to inhibit tumor progression. We have identified and characterized several ERK-RSK downstream targets regulated by S100B expression. These data are consistent with a mechanism in which elevated S100B binds directly to RSK in a calcium-dependent manner to prevent ERK-mediated phosphorylation of RSK. Our structural studies have further elucidated the S100B-RSK interaction as a novel drug target in melanoma cells and we are currently screening compounds for inhibitors of the S100B-RSK interaction. Citation Format: Adam D. Pierce. Activation of p90 ribosomal S6 kinase (RSK) and downstream targets are directly regulated by S100B protein in malignant melanoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4201. doi:10.1158/1538-7445.AM2014-4201
Abstract 15350: Progressive Aortic Dilatation is Regulated by the mir-17 Cluster
Authors: Jie Wu, Jian Guo, Shu-hong Li, Katherine Tsang, Laura Tumiati, Carolyn M David, Joanne Bos, Maral Ouzounian, Terrence M Yau, Tirone E David, Richard D Weisel, Ren-Ke Li
Journal: Circulation (2014)

Introduction: Ascending aortic aneurysms dilate due to activation of matrix metalloproteinase (MMPs), and matrix disruption. MicroRNAs (miRNAs) may contribute to the pathogenesis of aortic dilatation, but the specific miRNAs responsible have not been determined. We aimed to identify the miRNAs associated with progressive aortic dilation in patients with Marfan syndrome and bicuspid aortic valve (BAV) aortopathy. Methods and Results: Aortic tissue samples (~1х1cm) were collected from the dilated aneurysmal segment and adjacent nondilated segment which appeared normal at aortic surgery. The nondilated segments represent the early stages of aortic matrix degradation (before dilatation) and the dilated segment represents the late stage after aortic remodeling. Fourteen sample pairs were collected from BAV patients and 8 pairs from Marfan patients. miRNA levels were determined by Affymetrix GeneChip miRNA 3.0 Array for miRNA profiling. miRNA expression in the nondilated were compared to the dilated segments. T...
Breast cancer risk associated with genotype polymorphism of the genes involved in cell cycle G1/S regulation.
Authors: Chih-Hao Chang, Wen-Cheng Chou, Hui-Chun Wang, Chung-Pei Cheng, Li-Chung Chuang, Tzu-Ching Yeh, Ya-Lun Hsieh, Hsien-Ling Ting, Alice, Lin-Tsing Yu, Chin-Yang Shen, Pei-Ei Wu
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

5399 

Precise regulation of cell cycle progression has been know to be critical in maintaining proper cell growth and differentiation, abnormality of which leads to tumor formation. Cyclin/Cyclin-dependent kinase and cyclin-dependent kinase inhibitor (CKI) are key components in regulating cell cycle, and, in breast cancer, aberrant expression of Cyclin E and p27, is associated with poor tumor prognosis. Ubiquitin(UB)-mediated proteolysis determines stability of Cyclin E and p27, in which UB-associated E3 ligases, CDC4 and Skp2, play important roles. Thus, it becomes intriguing to examine whether genotypic polymorphisms of these genes are associated with breast cancer development. To examine this hypothesis, we carried out a multigenic case-control study of 561 incident breast cancer patients and 1127 healthy controls. We were also interested in possible interaction between reproductive risk factors reflecting pregnancy history and polymorphisms of these genes, give the fact that differentiation of breast epithelium, triggered by full-term pregnancy, has been known to be protective from tumor formation and is mediated by cell cycle regulators. Support for this hypothesis came from the observations that (i) significant association was found between genotypic polymorphism of CDC4 and increased breast cancer; (ii) a trend toward an increased risk of breast cancer was found in women harboring a greater number of putative high-risk genotypes of these genes; (iii) this association was stronger and more significant in those women who were more susceptible to estrogen [no history of pregnancy or lower numbers of full-term pregnancy]; and (iv) the risks conferred by no history of full-term pregnancy were particularly significant in women with a higher number of putative high-risk genotypes. On the basis of these findings, a comprehensive model is proposed to explain the relationship in cell cycle regulation, UB and pregnancy-associated differentiation in relation to breast cancer development.
Abstract 3733: SilenciX®, novel stable knock-down cellular models to screen new molecular targets through the synthetic lethality approach
Authors: Eric Mennesson, Anne-Marie Renault, Isabelle Fixe, Catherine GRILLON, Claudine Kiéda, Nadia Normand
Journal: Cancer Research (2014)

Abstract PARP inhibitors are promising therapeutic drugs for cancers harboring BRCA1 and BRCA2 mutations. PARP is involved in the Base Excision Repair (BER) DNA repair pathway. Tumors with BRCA mutations are deficient in Homologous Recombination (HR), another DNA repair pathway. To maintain DNA integrity and prevent cell death, at least one one of the BER or HE pathways must be functional, while the other may be inhibited or silenced (eg. mutation, drug). In drug discovery, Synthethic Lethality (SL) used a cancer mutation and a drug in combination to cause the tumor cell's death. SL is thus a promising approach to find new druggable targets by controlling the HR and BER DNA repair pathways in order to selectively kill mutated cancer cells. However, the main technical hurdle in SL approaches is to easily identify cancer-specific molecular interaction in various cancer types, while using robust and validated experimental cellular models. In this presentation we demonstrate how the SilenciX® technology meets SL experimental requirements. BRCA1 and BRCA2 Silencix® cells were treated with PARP1 inhibitors (Olaparib, Veliparib, Rucaparib) and with Gemcitabine. All inhibitors except Gemcitabine were synthetic lethal in BRCA1 SilenciX® cell lines. To mimic the cancer micro-environement, the model was tested under hypoxic conditions. We conclude that SilenciX® cell lines are ingenious gene-specific Knock Down engineered cell lines using a new pEBV derived plasmid, avoiding integration and off-target effects, suitable for a broad range of synthetic lethality studies. Citation Format: Eric Mennesson, Anne-Marie Renault, Isabelle Fixe, Catherine GRILLON, Claudine Kiéda, Nadia Normand. SilenciX®, novel stable knock-down cellular models to screen new molecular targets through the synthetic lethality approach. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3733. doi:10.1158/1538-7445.AM2014-3733
Abstract P016: Preventing Heart Disease, Stroke, and Related Chronic Diseases in the Mississippi Delta Region: Clinical Community Health Worker Initiative
Authors: Vincent Mendy, Tameka Walls, Amanda Cole, Cassandra Dove, Augusta Bilbro
Journal: Circulation (2015)

Background: Community Health Workers (CHW) are increasingly being used to address chronic disease prevention, but knowledge of their use in underserved rural settings is limited. CHW can be instrumental in linking underserved populations to clinical care and navigating the health care system. We report on the influence of our Clinical Community Health Worker Initiative (CCHWI) intervention program on clinical risk factors for heart disease and stroke in the Mississippi Delta region. Methods: Patients diagnosed with hypertension, diabetes or high cholesterol, and ≥18 years and consented to participate in the CCHWI were referred to a CHW for follow-up. CHW conducts an initial home visit, a follow-up phone call 7 to 10 days after the initial visit, a second home visit after 30-45 days and a subsequent recurring 90-day follow-up home visit. CHW activities include appointment scheduling and transportation arrangement, interpretation of health information, demonstrating proper procedures in monitoring blood pressure and blood glucose and encouraging patients to keep monitoring logs, assisting patients in documenting questions or concerns regarding medication and/or treat regimens for next doctors visit, assisting patients in setting nutrition target and goals, explaining the benefits of changing lifestyle habits, performing height, weight, and blood pressure measurements, encouraging patient to enroll in chronic disease self-management classes, and arranging referral for counseling to tobacco cessation treatment programs. Clinical data from 432 participants contacted by CHWs during home visits and phone calls from August 2012 to August 2014 were evaluated. We used paired t tests to assess changes from baseline for the following clinical measures: blood pressure, hemoglobin A1c, total blood cholesterol, high density lipoprotein cholesterol, low density lipoprotein (LDL) cholesterol, triglycerides, and body mass index. Results: Mean age of participants was 57.6 (range 20-89) years; 71.1% were female, and 91.9% were black. The majority of the participants were diagnosed with hypertension (82.4%) and diabetes (72.0%) and more than half (57.2%) with high cholesterol. One in five (21.1%) participants had only one condition, 46.3% had two conditions and a third (32.6%) had all three conditions. We observed statistically significant improvements (baseline vs most recent value) for diastolic blood pressure (p=0.0045), total cholesterol (p=0.0014), LDL cholesterol (p=0.0117), and triglycerides (p=0.0255). Conclusion: The use of CHW may help improve heart disease and stroke clinical risk factors among rural underserved populations.
Abstract 20705: Metallophilic Macrophage Ablation Stabilizes Atherosclerotic Plaques in Mice
Authors: Indira Medina, Cora Beckers, Marijke M Westra, Ilze Bot, Theo J Van Berkel, Masato Tanaka, Erik A Biessen
Journal: Circulation (2010)

Sialoadhesin or CD169 is expressed on a subset of differentiated metallophilic macrophages in the marginal zone of spleen under normal conditions and at inflammation sites in rheumatoid arthritis a...
Treating iron overload in patients with non‐transfusion‐dependent thalassemia
Authors: Ali T. Taher, Vip Viprakasit, Khaled M. Musallam, M. Domenica Cappellini
Journal: American Journal of Hematology (2013)

Despite receiving no or only occasional blood transfusions, patients with non‐transfusion‐dependent thalassemia (NTDT) have increased intestinal iron absorption and can accumulate iron to levels comparable with transfusion‐dependent patients. This iron accumulation occurs more slowly in NTDT patients compared to transfusion‐dependent thalassemia patients, and complications do not arise until later in life. It remains crucial for these patients' health to monitor and appropriately treat their iron burden. Based on recent data, including a randomized clinical trial on iron chelation in NTDT, a simple iron chelation treatment algorithm is presented to assist physicians with monitoring iron burden and initiating chelation therapy in this group of patients. Am. J. Hematol. 88:409–415, 2013. © 2013 Wiley Periodicals, Inc.
Abstract 816: Sympathetic Nerve Protein Analysis, Sympathetic Microneurography and Catecholamine Kinetics in Postural Syncope Phenotypes
Authors: Gautam Vaddadi, Elisabeth Lambert, Ling Guo, Nina Eikelis, Florentia Socratous, Markus Schlaich, Garry Jennings, Gavin Lambert, Murray D Esler
Journal: Circulation (2007)
Activated protein <scp>C</scp> resistance testing for factor V <scp>L</scp>eiden
Authors: Stephan Kadauke, Bernard Khor, Elizabeth M. Van Cott
Journal: American Journal of Hematology (2014)

Activated protein C resistance assays can detect factor V Leiden with high accuracy, depending on the method used. Factor Xa inhibitors such as rivaroxaban and direct thrombin inhibitors including dabigatran, argatroban, and bivalirudin can cause falsely normal results. Lupus anticoagulants can cause incorrect results in most current assays. Assays that include dilution into factor V‐deficient plasma are needed to avoid interference from factor deficiencies or elevations, which can arise from a wide variety of conditions such as warfarin, liver dysfunction, or pregnancy. The pros and cons of the currently available assays are discussed. Am. J. Hematol. 89:1147–1150, 2014. © 2014 Wiley Periodicals, Inc.
Abstract P179: Relation of Diet-Induced Metabolic Acidosis to Blood Pressure
Authors: Gianluca Campanella, Queenie Chan, Martha L Daviglus, Linda Van Horn, Katsuyuki Miura, Hirotsugu Ueshima, Liancheng Zhao, Jeremiah Stamler, Jeremy K Nicholson, Paul Elliott, Marc Chadeau-Hyam
Journal: Circulation (2014)

Background: Influences of nutrition on acid-base balance have long been recognized, and significant pathophysiological effects of diet-induced metabolic acidosis (DIMA) are now acknowledged, making it a potential target for preventive dietary interventions. Despite biological plausibility, recent cross-sectional and prospective studies have failed to provide consistent evidence supporting an association between DIMA and blood pressure (BP), systemic hypertension, or cardiovascular risk. Objective: To assess associations of validated DIMA indices computed from dietary information with BP, using data from the International Study of Macro- and Micro-nutrients and Blood Pressure (INTERMAP). Methods: The INTERMAP Study is a cross-sectional epidemiological investigation with standardized quality-controlled methods. It includes 4,680 participants from four countries (China, Japan, UK, and USA) with detailed lifestyle, anthropometric, and dietary information, as well as two 24-hour urine samples. Participants reporting use of BP-lowering medications were excluded. Two indices were investigated: energy-adjusted Potential Renal Acid Load (PRAL, mEq/MJ/day), which quantifies the dietary acid-forming potential only, and Net Endogenous Acid Production (NEAP, mEq/1.73m 2 /day), which assesses the balance between endogenous acid production and PRAL, and thus provides a more accurate measure of DIMA. Analyses were stratified by ethnic group: non-Hispanic Whites (NHWs, N=1,397), Japanese (N=1,273), Chinese (N=804), and African-Americans (N=253). All models were adjusted for known hypertension risk factors. Additional analyses were conducted to investigate associations of DIMA indices with BMI. Results: NEAP was positively associated with BP in NHWs and Japanese. In NHWs, systolic BP: 0.08 (95% confidence interval: 0.03 to 0.13) mmHg higher per mEq/1.73m 2 /day in men, 0.19 (0.12 to 0.26) mmHg higher in women; diastolic BP: 0.06 (0.03 to 0.1) mmHg higher in men, 0.11 (0.06 to 0.16) mmHg higher in women. In Japanese, systolic BP: 0.11 (0.03 to 0.18) mmHg higher in men, 0.15 (0.07 to 0.25) mmHg higher in women; diastolic BP: 0.08 (0.02 to 0.13) mmHg higher in men, 0.11 (0.05 to 0.18) mmHg higher in women. These associations were not significant after controlling for BMI. PRAL was not significantly associated with BP in any model. NEAP was also significantly associated with BMI across ethnic groups, which is consistent with a possible mediating role of BMI in the association between NEAP and BP. Conclusions: Our data indicate ethnicity-specific positive associations of DIMA (as measured by NEAP) with BP, possibly mediated by obesity.
Comparative Efficacy of a Two-Hour Regimen of Streptokinase Versus Alteplase in Acute Massive Pulmonary Embolism: Immediate Clinical and Hemodynamic Outcome and One-Year Follow-Up 11This study was partly supported by grants from Programme Hospitalier de la Recherche Clinique (Ministère de la Santé Publique), Paris; Boehringer Ingelheim, Reims Cedex, France; and Hoechst France, Puteaux, France.
Authors: Nicolas Meneveau, François Schiele, Damien Metz, Benoît Valette, Pierre Attali, Alain Vuillemenot, Gilles Grollier, Jacques Elaerts, Jean-Marie Mossard, Jean-François Viel, Jean-Pierre Bassand
Journal: Journal of the American College of Cardiology (1998)
Greatest Bacterial Diversity Found in Remote Amazonian People
Authors: M. J. Friedrich
Journal: JAMA (2015)

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What predicts patient (pt) understanding regarding cancer clinical trials (CCT)
Authors: M. Jefford, L. Mileshkin, H. Raunow, C. Okane, T. Cavicchiolo, H. Brasier, M. Robinson, J. Matthews, J. Reynolds
Journal: Journal of Clinical Oncology (2004)

6107 Background: We aimed (a) to assess how well pts newly enrolled on CCT understand the trials and (b) to identify correlates of increased understanding, for example with demographic data, method of giving informed consent (IC), preference re information and decision-making, anxiety, depression and QOL. Methods: Convenience sample of 100 pts from CCT auspiced by CTA. Eligibility -signed IC, enrolment on a therapeutic CCT within the preceding week, ability to complete English versions of the pt-completed measures, age ≥ 18 years. Instruments assessed quality of IC (QuIC), QOL (EORTC QLQ C-30), anxiety and depression (HADS), and preferences for information (Cassileth information styles questionnaire). Results: Data are available for the first 72 pts: 60% male, median age 56 (29–75). Median QuIC objective knowledge score (QuIC-A) was 76.9. Some questions were answered poorly (see table). Median perceived (subjective) understanding (QuIC-B) was 94.6. There was low but significant (sig) correlation between QuIC-A and B (R=0.28, p=0.018). Variation in QuIC-B was associated with English as a first language (EFL), reading the consent form (CF) carefully, an ‘easy to read’ CF and overall satisfaction with consent process (all sig at p=0.05). There was low, but sig correlation between QuIC-B and age (R=0.28, p=0.019). Regarding highest level of education (HLE), both low and possibly high HLE were associated with higher QuIC-B scores. Higher knowledge score (QuIC-A) was associated with EFL (p=0.05) and possibly with overall QOL (p=0.09). No correlation was found between QuIC-A or -B and either depression or anxiety. Conclusions: Overall pt knowledge regarding CCT is reasonable. Deficiencies about particular aspects of trials merit further attention. Improved objective (QuIC-A) and subjective (QuIC-B) knowledge are associated with speaking EFL. QuIC-B is associated with additional factors. No significant financial relationships to disclose.
SIMMONDS' DISEASE (PITUITARY CACHEXIA); REPORT OF A CASE
Authors: Jason E. Farber
Journal: Annals of Internal Medicine (1940)

ExcerptSimmonds' disease or pituitary cachexia is a syndrome ascribed to destruction or physiological exhaustion of the hypophysis (chiefly the anterior portion). The destruction may be caused by embolic infarction, tumor, syphilis, tuberculosis, metastatic abscesses, inflammation, etc. Clinically the Simmonds' syndrome is characterized by cachexia, premature senility, atrophy of the gonads and genitalia, with amenorrhea, atrophy of the breasts, loss of pubic and axillary hair, loss of libido, integumental changes (chiefly dryness of the skin), anorexia and constipation, hypotension and muscular weakness, hypoglycemia, decreased sugar tolerance, lowered basal metabolism and depressed specific dynamic action of proteins, anemia, lymphocytosis and sometimes eosinophilia....
The Entirely Subcutaneous Implantable Cardioverter-Defibrillator
Authors: Louise R.A. Olde Nordkamp, Lara Dabiri Abkenari, Lucas V.A. Boersma, Alexander H. Maass, Joris R. de Groot, Antonie J.H.H.M. van Oostrom, Dominic A.M.J. Theuns, Luc J.L.M. Jordaens, Arthur A.M. Wilde, Reinoud E. Knops
Journal: Journal of the American College of Cardiology (2012)
Abstract 16281: A Diagnosis and Treatment Algorithm for Suspected Myocardial Infarction and New Left Bundle Branch Block
Authors: Vijaya K Pera, David M Larson, Scott W Sharkey, Ross F Garberich, Christopher J Solie, Yale L Wang, Jay H Traverse, Anil K Poulose, Timothy D Henry
Journal: Circulation (2014)

Introduction:  Patients presenting with ischemic symptoms and new LBBB (nLBBB) pose a unique diagnostic and management challenge. ACCF/AHA guidelines recently removed the recommendation for emergency reperfusion therapy in this important subgroup.   Methods:  Using a comprehensive prospective regional STEMI program database, we evaluated the prevalence, clinical and angiographic characteristics, and outcomes in nLBBB patients and validated a simplified hierarchical algorithm incorporating clinical and EKG data.(Figure)   Results:  Of the 3,903 consecutive STEMI patients who presented between 2003 and 2013, 131 (3.3%) patients had nLBBB. These patients had fewer acute culprit arteries (54% vs. 86%; p  Classification of the nLBBB patients using the algorithm led to 45% with STEMI-equivalent undergoing emergent intervention; 31% ACS undergoing urgent intervention and 24% felt not to be acute, therefore no angiography. Based on the identification of a culprit artery, the algorithm yielded a high sensitivity (97%) and negative predictive value (94%).(Figure)   Conclusions:  Patients with acute ischemic symptoms and nLBBB represent a high-risk population with significant risk of cardiac arrest, death and re-infarction. An algorithm using simplified clinical and ECG criteria may improve the diagnostic accuracy regarding reperfusion strategies for nLBBB patients.