tbuckley/cabot-search huggingface dataset:
Noncardiac surgery ≤ 2 y after coronary stent placement was linked to perioperative MI and all-cause mortality
Authors: Shashank S. Sinha, Kim A. Eagle
Journal: Annals of Internal Medicine (2015)

ACP Journal Club16 June 2015Noncardiac surgery ≤ 2 y after coronary stent placement was linked to perioperative MI and all-cause mortalityShashank S. Sinha, MD, Kim A. Eagle, MDShashank S. Sinha, MDUniversity of Michigan, Ann Arbor, Michigan, USA (S.S.S., K.A.E.)Search for more papers by this author, Kim A. Eagle, MDUniversity of Michigan, Ann Arbor, Michigan, USA (S.S.S., K.A.E.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJC-2015-162-12-011 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationHolcomb CN, Graham LA, Richman JS, et al. The incremental risk of noncardiac surgery on adverse cardiac events following coronary stenting. J Am Coll Cardiol. 2014;64:2730-9. https://pubmed.ncbi.nlm.nih.gov/25541124Clinical Impact RatingsCardiology: References1. Gandhi NK, Abdel-Karim AR, Banerjee S, Brilakis ES. Frequency and risk of noncardiac surgery after drug-eluting stent implantation. Catheter Cardiovasc Interv. 2011;77:972-6. [PMID: 20824750] Google Scholar2. Alshawabkeh LI, Banerjee S, Brilakis ES. Systematic review of the frequency and outcomes of non-cardiac surgery after drug-eluting stent implantation. Hellenic J Cardiol. 2011;52:141-8. [PMID: 21478124] Google Scholar3. Kristensen SD, Knuuti J, Saraste A, et al. 2014 ESC/ESA guidelines on non-cardiac surgery: cardiovascular assessment and management: The Joint Task Force on non-cardiac surgery: cardiovascular assessment and management of the European Society of Cardiology (ESC) and the European Society of Anaesthesiology (ESA). Eur Heart J. 2014;35:2383-431. [PMID: 25086026] Google Scholar Author, Article, and Disclosure InformationAffiliations: University of Michigan, Ann Arbor, Michigan, USA (S.S.S., K.A.E.)This article was published at Annals.org on 2 June 2015. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byApproach to Evaluating the Multimorbid Patient with Cardiovascular Disease Undergoing Noncardiac Surgery 16 June 2015Volume 162, Issue 12Page: JC11KeywordsCardiac surgeryCohort studiesCoronary revascularizationCoronary stentingHeart diseasesMyocardial infarctionStent implantationSurgeryVascular surgery ePublished: 16 June 2015 Issue Published: 16 June 2015 Copyright & PermissionsCopyright © 2015 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Abstract 488: Sinoatrial Nodal Pacemaker Cells (SANC) Exhibit High Basal CA Activated Adenylyl Cyclase (AC) Activity and Express Multiple Distinctly Localized AC Types
Authors: David R Graham, Antoine Younes, Alexey Lyashkov, Anna Sheydina, Maria Volkova, Megan Mitsak, Tatiana Vinogradova, Abdul Ruknudin, Kenneth Boheler, Jennifer Van Eyk, Edward Lakatta
Journal: Circulation (2007)

In SANC constituitive AC generates high basal cAMP, inducing PKA-dependent phosphorylation that regulates Ca2+ cycling, that is essential for normal pacemaker function. Our goals were to identify, in rabbit SANC, the types of AC expressed, and their Ca2+ sensitivity and location. Radioimmunoassay (with total phosphodiasterase inhibition) showed a high Ca2+ activated basal AC activity. AC activity increased 5-fold from Ca2+ free (EGTA) to 1 uM free Ca2+. RT PCR (using specifically designed rabbit primers) showed that AC types II and V, and Ca2+ activated types, I and VIII, are expressed in SANC. The organization of these distinct AC types within calveolar or non-calveolar membrane microdomains was determined in pooled SANC isolated from 5 hearts, using triton x100, and sucrose gradient ultracentrifugation. Lipid domains segregated into caveolin containing and non-caveolin containing membrane microdomains, where AC activity was concentrated (fig , AC activity). Immunoblots demonstrated localization of different AC types between these two membrane domains, with AC I, II, V/VI localizing to caveolin containing lipid rafts, and AC VIII present in both caveolin and GM1 lipid domains, and also in the soluble fraction (fig ). In summary, multiple ACs, both Ca2+ activated and non-CA2+ activated types, are expressed in SANC, and these reside in distinct calveolar and non-calveolar lipid domains. We conclude that constituitive basal AC activity is, generated, in part, at least, by a Ca2+ activated AC. type.
Abstract 2823: Low merlin level as a biomarker for sensitivity of ovarian cancer cell lines to FAK inhibition
Authors: Nina R. Shah, Isabelle Tancioni, Kristy K. Ward, Christine Lawson, Xiao Lei Chen, Nichol L.G. Miller, Florian J. Sulzmaier, Sean Uryu, David D. Schlaepfer
Journal: Cancer Research (2014)

Abstract Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase that undergoes gene amplification in &amp;gt;20% of serous ovarian cancers. In addition to increased tumor growth and spread, ovarian cancer patients with FAK amplification have a poorer prognosis with decreased overall survival. Merlin, a product of the NF2 tumor suppressor gene, is being evaluated as a biomarker for sensitivity to FAK inhibition in human clinical trials for malignant mesothelioma. As it remains undetermined whether linkages exist between merlin and FAK in other tumor types, we evaluated nine human and two murine ovarian cancer cell lines with sub-micromolar levels of FAK inhibitor (PF-271) for effects on anchorage-independent cell growth. Cells were identified as sensitive (OVCAR3, OVCAR8, HEY, ID8-IP), intermediate (A2780, IGROV1), or resistant (OVCAR10, IGROV1-IP, SKOV3, SKOV3-IP, 5009) to FAK inhibition. Notably, merlin protein levels were high in all resistant cell lines, moderate in intermediate cell lines, and low or undetectable in sensitive cell lines. Oral FAK inhibitor administration reduced orthotopic tumor growth of sensitive (ID8-IP, low merlin) but not resistant (5009, high merlin) murine ovarian carcinoma cells. However, stable knockdown of merlin expression in resistant SKOV3-IP and OVCAR10 human ovarian carcinoma cells did not induce sensitivity to FAK inhibition in vitro. These results support the notion that high merlin expression is correlated with a FAK-inhibitor resistant phenotype, likely through an indirect mechanistic linkage. Nevertheless, merlin protein levels may serve as a biomarker to predict ovarian cancer sensitivity or resistance to FAK inhibitor treatment. Supported by NIH CA102310 Citation Format: Nina R. Shah, Isabelle Tancioni, Kristy K. Ward, Christine Lawson, Xiao Lei Chen, Nichol L.G. Miller, Florian J. Sulzmaier, Sean Uryu, David D. Schlaepfer. Low merlin level as a biomarker for sensitivity of ovarian cancer cell lines to FAK inhibition. [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 2823. doi:10.1158/1538-7445.AM2014-2823
Abstract 29: Loss of Ideal Total Cholesterol Early in Life: The National Health and Nutrition Examination Survey (NHANES)
Authors: Joseph C Engeda, Katelyn M Holliday, Shakia T Hardy, Sujatro Chakladar, Gerardo Heiss, Danyu Lin, Donglin Zeng, Christina M Shay, Christy L Avery
Journal: Circulation (2015)

Introduction: Ideal total blood cholesterol (TC) levels are associated with lower cardiovascular disease (CVD) morbidity and mortality. In the U.S. TC increases up to middle age, but declines at older ages. Few studies have characterized the transition from ideal to intermediate and poor TC levels in different life epochs and in minorities. Methods: Cross-sectional 2007-2012 NHANES data (N = 11,140) were used to estimate the age-, race-, and sex- specific prevalence of ideal (≥20 years: &lt;200 mg/dL untreated, 16-19 years: &lt;170 mg/dL), intermediate (≥20 years: 200-239 mg/dL or treated to goal, 16-19 years: 170-199 mg/dL), and poor (≥20 years: ≥240 mg/dL, 16-19 years: ≥200 mg/dL) TC, defined per American Heart Association criteria. We then used these data and novel Markov-type models to estimate net transition probabilities between ideal, intermediate and poor TC. Results: Between the ages of 16 and 18, the prevalence of ideal TC among European American (EA) and African American (AA) men was approximately 68%, notably higher than the prevalence in EA women (63%) and AA women (61%). Variation in the loss of ideal TC was also observed by race and sex. Between 16-50 years of age, the proportion of AA men, EA men and EA women with ideal levels of TC declined approximately 2.0% (95% CI: 1.8%, 2.2%) per year. In AA women by contrast, the age-specific decline in ideal TC was not uniform between 16-50 years of age. The proportion of AA women with ideal levels of TC declined 0.7% (95% CI: 0.2%, 1.2%) per year from 16-20 years of age but increased to 2.8% (95% CI: 2.4%, 3.3%) per year by age 50. Among populations with intermediate TC levels, estimated 1-year net transitions to poor TC peaked at age 16, the earliest age under investigation, for EA men, EA women, and AA men but remained stable for AA women through 70 years of age, where a net 0.6% (95% CI: 0.1%, 1.3%) of the population with intermediate TC levels transitioned to poor TC levels one year later. In all demographic groups and life epochs, greater proportions of the population transitioned from intermediate to poor TC than from poor to intermediate TC. Conclusions: Loss of ideal TC begins early in life and shows divergent patters by gender and race. Difficulties re-attaining ideal TC once classified as intermediate or poor support interventions that promote ideal TC levels in younger ages, especially among AA women.
Abstract 125: Protein kinase C loss-of-function mutations in cancer reveal role as tumor suppressor
Authors: Corina E. Antal, Andrew M. Hudson, Emily Kang, Ciro Zanca, Christopher Wirth, Natalie L. Stephenson, Eleanor W. Trotter, Lisa L. Gallegos, Crispin Miller, Frank Furnari, Tony Hunter, John Brognard, Alexandra C. Newton
Journal: Cancer Research (2015)

Abstract Protein kinase C (PKC) remains an elusive chemotherapeutic target despite decades of research. To determine whether PKC isozymes function as oncogenes or tumor suppressors, we analyzed 8% of PKC mutations identified in human cancers. Surprisingly, the majority were loss-of-function and none were activating. Loss-of-function mutations were found in all PKC subgroups and acted by impeding 2nd messenger binding or preventing processing phosphorylations. Bioinformatic analysis revealed that PKC mutations might cooperate with co-occurring mutations in cancer drivers. Correction of a patient-identified, loss-of-function PKCβ mutation by CRISPR-mediated genome editing, in a colon cancer cell line, suppressed anchorage-independent growth and reduced tumor growth in xenograft models. Hemizygous deletion provided an anchorage-independent growth advantage, revealing PKC is haploinsufficient for tumor suppression. Several mutations were dominant-negative, suppressing global PKC signaling output. These data establish that PKC isozymes generally function as tumor suppressors, indicating that therapeutic strategies should focus on restoring PKC activity, not inhibiting it. Citation Format: Corina E. Antal, Andrew M. Hudson, Emily Kang, Ciro Zanca, Christopher Wirth, Natalie L. Stephenson, Eleanor W. Trotter, Lisa L. Gallegos, Crispin Miller, Frank Furnari, Tony Hunter, John Brognard, Alexandra C. Newton. Protein kinase C loss-of-function mutations in cancer reveal role as tumor suppressor. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 125. doi:10.1158/1538-7445.AM2015-125
Kinetics of CXCR4 and CCR5 up-regulation and human immunodeficiency virus expansion after antigenic stimulation of primary CD4+ T lymphocytes
Authors: Reinhard Maier, Marı́a Matilde Bartolomé-Rodrı́guez, Corinne Moulon, Hans Ulrich Weltzien, Andreas Meyerhans
Journal: Blood (2000)
130. Targeting of Adenovirus Vectors to Mesothelin Via a Bispecific Antibody Reveals Enhanced Gene Transfer to Human Pancreatic Cancer Cells
Authors: MA van Geer, [No Value] Pastan, VW van Beusechem, HJ Haisma, PJ Bosma, DJ Gouma, JG Wesseling
Journal: Molecular Therapy (2004)

Pancreatic cancer is the 5th leading cause of cancer death in the Western world with no effective treatment yet. Adenoviral (Ad) 5 vectors have been studied for gene delivery into human pancreatic cancer, showing that wild type Ad5 has a limited transduction efficiency. Since the extracellular mesothelin protein is upregulated on primary human pancreatic cancer cells (Argani et al. (2001) Clin Canc Res 7, 3862), while no or limited expression is detected on normal pancreatic cells, we chose to target Ad5 to this surface antigen by using the bispecific antibody approach. We cloned the cDNA encoding for the single-chain and bispecific antibody that binds to mesothelin into an expression vector, and produced the bispecific antibody that binds both to adenovirus fiber knob and to mesothelin. Ad5 could indeed be targeted to mesothelin expressing OVCAR-3 control cells as shown by improved transduction with Ad5CMVGFP complexed with bispecific antibody compared to wt Ad5CMVGFP without bispecific antibody. Subsequently, two near primary and four established pancreatic cancer cells were infected with the AdCMVGFP-bispecific antibody complex, in the presence or in the absence of Ad5 fiber protein and single-chain antibody. It was shown that adenovirus complexed with bispecific antibody revealed a significant enhanced gene transfer to one established and two near primary CAR negative and mesothelin positive pancreatic carcinoma cells, compared to wt Ad5. This effect could be prevented by competitive pre-incubation of the cells with the single-chain antibody. We conclude that adenovirus vectors complexed with bispecific antibody directed to mesothelin can enter mesothelin expressing pancreatic tumor cells with a high efficiency and efficacy compared to wt Ad5, suggesting that mesothelin might be a promising antigen for targeted adenoviral gene therapy of pancreatic cancer.
Abstract 3859: MicoRNAs in regulation of colon cancer stem cells
Authors: Yingjie Yu, Nangia-Makker Pratima, Sindhu Rajendra, Edi Levi, Adhip P. N. Majumdar
Journal: Cancer Research (2014)

Abstract Accumulating evidence supports the contention that epithelial cancers, including sporadic colorectal cancer (CRC), the incidence of which increases sharply after the age of 50 years, are diseases driven by self-renewing cancer stem/stem-like cells (CSCs). We have reported that CSC population in the colonic mucosa increases with advancing age. This was accompanied by a concomitant rise in microRNA-21 (miR-21) and reduction in miR-145 in the colonic mucosa. Interestingly, increased levels of miR-21 and reduction in miR-145 were noted in the colonic mucosa of patients with adenomatous polyps or CRC. These observations prompted us to speculate a role for miR-21 and miR-145 in regulating CSCs in the colonic mucosa. Indeed, we found that overexpression of miR-21 in colon cancer cells greatly increases CSCs and also induces tumor growth. An opposite phenomenon was noted in colon cancer cells where miR-145 was upregulated through stable transfection. In addition, studies utilizing SCID mice xenograft model of colon cancer showed that administration of either antagomir-21 (anti-sense miR-21) or excess miR-145 greatly inhibited the growth of tumors of colon cancer cells, when compared with the controls. This reduction in growth was associated with decreased expression of CD44, B-catenin and Sox-2 and induction of CK-20. In vitro cell culture studies have further demonstrated miR-21 to regulate miR-145 and vice versa. Although the precise mechanism(s) by which miR-21 or miR-145 regulates CSCs in the colonic mucosa during the progression of CRC is unknown, our in vitro studies suggest that they induce differentiation of colon CSCs. The latter was evidenced by the increased expression of CK-20 in colon cancer cells following downregulation of miR-21 and upregulation of 145. In contrast, Sox-2 expression is decreased following overexpression of miR-145. In conclusion, our current observations suggest that miR-21 and miR-145, that are upregulated and downregulated, respectively, in the colonic mucosa during aging and CRC, play critical roles in regulating CSCs in the colon. Citation Format: Yingjie Yu, Nangia-Makker Pratima, Sindhu Rajendra, Edi Levi, Adhip P. N. Majumdar. MicoRNAs in regulation of colon cancer stem cells. [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 3859. doi:10.1158/1538-7445.AM2014-3859
Abstract 15362: Pre-participation Screening of Young Competitive Athletes for the Prevention of Sudden Cardiac Death Using a New Electrocardiographic Device
Authors: Jae Hyung Cho, Mats A Selen, Abraham G Kocheril
Journal: Circulation (2014)

Introduction: Routine 12-lead electrocardiogram screening for the prevention of sudden cardiac death in young athletes is not recommended due to the enormous cost per life saved. The application of less expensive electrocardiographic devices has not been investigated. Hypothesis: The purpose of this pilot study was to investigate the utility of a new 3-lead wireless electrocardiographic device for the pre-participation screening of young competitive athletes. Methods: Twenty-seven college football players were enrolled in this study. During the pre-participation screening sessions, each player underwent evaluation using a conventional 12-lead electrocardiogram and a new 3-lead electrocardiogram coupled to our wireless electrocardiographic device. The new 3-lead electrocardiography is a compact device that yields high quality electrocardiographic signals. We compared several electrocardiographic parameters (QRS duration, QRS amplitude, left ventricular hypertrophy, ST deviation and corrected QT interval) using Pearson’s correlation coefficient. Results: The QRS duration, QRS amplitude and corrected QT interval values exhibited significant correlation between the two types of electrocardiograms (correlation coefficient 0.723, 0.537 and 0.734, respectively with P value of 0.01, 0.004 and 0.01, respectively). ST deviation in V1 was weakly correlated with ST deviation in lead Z without statistical significance (correlation coefficient 0.227 with P value of 0.256). Assessment of left ventricular hypertrophy using the Cornell voltage or Sokolow-Lyon criteria and average QRS amplitude also revealed weak correlation without statistical significance (correlation coefficient 0.221 and 0.246, respectively with P value of 0.268 and 0.216, respectively). Conclusions: Our newly developed 3-lead electrocardiogram results correlated well with those of a conventional 12-lead electrocardiogram in terms of QRS duration, QRS amplitude and corrected QT interval. Thus, the 3-lead electrocardiogram might represent a useful screening tool for the prevention of sudden cardiac death in young competitive athletes.
Localized scleroderma: response to occlusive treatment with tacrolimus ointment
Authors: G. Mancuso, R.M. Berdondini
Journal: British Journal of Dermatology (2005)

Journal Article Localized scleroderma: response to occlusive treatment with tacrolimus ointment Get access G. Mancuso, G. Mancuso Department of Dermatology, Municipal Hospital of Lugo, Ravenna, Italy E‐mail: mavelabs@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar R.M. Berdondini R.M. Berdondini Department of Dermatology, Municipal Hospital of Lugo, Ravenna, Italy E‐mail: mavelabs@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 152, Issue 1, 1 January 2005, Pages 180–182, https://doi.org/10.1111/j.1365-2133.2004.06318.x Published: 01 January 2005
Abstract OT3-1-07: MotHER: A US registry for women with breast cancer who have received trastuzumab, pertuzumab in combination with trastuzumab, or trastuzumab emtansine (T-DM1) during pregnancy or within 7 months prior to conception
Authors: Vikki Brown, Richard K Miller, Laura Chu, Cheryl Chow, Caroline Trudeau, Elizabeth B Andrews
Journal: Cancer Research (2015)

Abstract Background: Trastuzumab (Herceptin) and pertuzumab (Perjeta) are HER2-targeted monoclonal antibodies, and T-DM1 (Kadcyla) is a HER2-targeted antibody–drug conjugate. These molecules are classified as FDA Pregnancy Category D, indicating evidence of fetal harm; there have been postmarketing reports of oligohydramnios in women who received trastuzumab during pregnancy; in non-clinical studies of pertuzumab, oligohydramnios, delayed renal development, and embryo-fetal death occurred in pregnant cynomolgus monkeys. Furthermore, maytansine, the parent molecule of DM1, has demonstrated embryotoxicity in mice. The MotHER pregnancy registry was established in 2008 as an FDA postmarketing commitment to evaluate the effects of trastuzumab on pregnancy outcome. Pertuzumab and T-DM1 were included in the registry following their respective FDA approvals in 2012 and 2013. Study design: MotHER is a US pregnancy registry and uses a prospective, observational cohort design. Enrollment is voluntary and can be initiated by the patient or her healthcare provider. Women are followed up until pregnancy outcome; infants are followed up through the first year of life. Eligibility criteria: Pregnant women ≥18 years of age and resident in the US are eligible if they have received at least one dose of trastuzumab, pertuzumab in combination with trastuzumab, or T-DM1 for breast cancer during pregnancy or within 7 months prior to conception. Enrollment must be initiated before pregnancy outcome is known. Specific aims: The primary outcome measures are pregnancy outcomes and the incidence of pregnancy complications, such as oligohydramnios, congenital anomalies, and fetal/infant functional deficits. Information on potential birth defects, noted either at birth or during pediatric follow-up, is evaluated and classified by a birth defect evaluator/clinical geneticist. Statistical methods: The study is descriptive and not designed for formal hypothesis testing; event rates with 95% confidence intervals will be calculated. Accrual: There is no pre-specified sample size. Data collection is ongoing, from 2009 to 2019 for trastuzumab, from 2012 to 2022 for pertuzumab plus trastuzumab, and from 2013 to 2023 for T-DM1. Fourteen women have enrolled as of January 31, 2014. Citation Format: Vikki Brown, Richard K Miller, Laura Chu, Cheryl Chow, Caroline Trudeau, Elizabeth B Andrews. MotHER: A US registry for women with breast cancer who have received trastuzumab, pertuzumab in combination with trastuzumab, or trastuzumab emtansine (T-DM1) during pregnancy or within 7 months prior to conception [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr OT3-1-07.