tbuckley/cabot-search huggingface dataset:
Abstract P038: Cadmium Exposure is Prospectively Associated to Cardiovascular Risk in the Strong Heart Study
Authors: Maria Tellez-Plaza, Eliseo Guallar, Barbara Howard, Jason Umans, Kevin Francesconi, Walter Goessler, Ellen K. Silbergeld, Richard B. Devereux, Ana Navas-Acien
Journal: Circulation (2012)

Introduction: Cadmium is a widespread toxic metal with potential cardiovascular effects, but establishing cadmium as a cardiovascular risk factor has been limited by the lack of data on its association with incident cardiovascular events. Hypothesis: We tested the hypothesis that urine cadmium concentrations would be associated with cardiovascular disease mortality and incidence. Methods: Prospective cohort study of 3,347 American Indian adults 45-74 years old without prevalent cardiovascular disease from Arizona, Oklahoma and North and South Dakota who participated in the Strong Heart Study (SHS) in 1989-91 and had urine cadmium measures available. Urine cadmium was measured using inductively coupled plasma mass spectrometry. Follow-up extended through December 30 th 2007. Results: We identified 1,028 cardiovascular events, including 372 deaths. After adjustment for known cardiovascular risk factors, the hazard ratios (95% CI) for cardiovascular and coronary heart disease mortality, comparing the 80 th to the 20 th percentiles of urine cadmium concentrations, were 1.43 (1.21, 1.69) and 1.33 (1.09, 1.62), respectively. The corresponding hazard ratios for incident cardiovascular disease, coronary heart disease, stroke, and heart failure were 1.16 (1.04, 1.29), 1.11 (0.98, 1.27), 1.50 (1.01, 2.22) and 1.22 (1.01, 1.47), respectively. The associations were similar in different study subgroups, including never-smokers. The figure shows increasing dose-response relations between urine cadmium concentrations and all cardiovascular disease mortality and incidence endpoints except for incident stroke. Conclusions: Urine cadmium, a biomarker of long-term exposure, was positively and consistently associated with cardiovascular disease mortality and incidence, overall and across subgroups. These findings support that cadmium exposure is a cardiovascular risk factor irrespective of the source of exposure. Efforts to reduce cadmium exposure in the population are needed.
TCT-479 Patients consider PCI and CABG equal: Derivation of a novel patient-centered, quantitative analysis of Major Adverse Cardiac Events (MACE) and its application to trials comparing PCI to CABG
Authors: Yousif Ahmad, Sukhjinder S. Nijjer, Christopher Cook, Ricardo Petraco, Iqbal S. Malik, Christopher S. Baker, Ghada Mikhail, Raffi R. Kaprielian, Michael Bellamy, Justin E. Davies, Jamil Mayet, Darrel P. Francis, Sayan Sen
Journal: Journal of the American College of Cardiology (2015)
Glycosaminoglycans Synthesized by Tumorigenic and Nontumorigenic Mouse Melanoma Cells in Culture&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: J Heaney-Kieras, F J Kieras
Journal: JNCI Journal of the National Cancer Institute (1980)

Glycosaminoglycans (GG) synthesized by two tumorigenic cell lines and a nontumorigenic, immunoprotective cell line derived from the B16 mouse melanoma were metabolically labeled with Na235SO4 and [3H]glucosamine. The radioactive GG synthesized at low and high cell densities were prepared from cells and culture media and analyzed by enzymatic and chromatographic methods. The cell-associated and medium GG from both low- and high-density cultures of the nontumorigenic, immunoprotective line contained a significantly higher proportion of heparin and heparan sulfate (85-95% of total) relative to comparable fractions from the tumorigenic lines. In addition to synthesizing less heparin and heparan sulfate and more chondroitin 4-sulfate plus chondroitin 6-sulfate, the tumorigenic lines differed in that the amelanotic line produced significant amounts of dermatan sulfate which remained cell associated. None of the lines produced measurable amounts of hyaluronic acid. In addition, the nontumorigenic immunoprotective line incorporated two to six times more precursor into total GG and released a higher proportion into the growth medium than did the tumorigenic lines.
Response to rituximab in B-CLL patients is adversely impacted by frequency of IL-10 competent B cells and FcγRIIIa polymorphism. A study of FCGCLL/WM and GOELAMS groups
Authors: A-L Gagez, E Tuaillon, R Cezar, C Dartigeas, B Mahé, R Letestu, H Maisonneuve, V Gouilleux-Gruart, K Bollore, E Ferrant, T Aurran, P Feugier, S Leprêtre, G Cartron
Journal: Blood Cancer Journal (2016)

émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
Abstract 18830: Mitochondrial Suppression Due to Loss of Sirt3 Deacetylase Activity Causes Pulmonary Arterial Hypertension
Authors: Roxane PAULIN, Peter Dromparis, Gopinath Sutendra, Steeve Provencher, Sebastien Bonnet, Evangelos D Michelakis
Journal: Circulation (2013)

Pulmonary arterial hypertension (PAH) is characterized by suppressed apoptosis in the pulmonary artery (PA) wall, leading to an obstructive vascular remodeling and premature death. The suppressed apoptosis is partly due to suppressed mitochondrial function. Recently PAH patients have been shown to have clinical evidence of insulin resistance. Sirtuin 3 (Sirt3), is a mitochondria-localized deacetylase that regulates mitochondrial function. Loss of Sirt3 activity promotes acetylation and inhibition of many mitochondrial enzymes, resulting in mitochondrial suppression. Loss-of-function polymorphisms in the SIRT3 gene have been associated with metabolic syndrome. We hypothesized that loss of SIRT3 promotes PAH. In vitro, we used resistance PA smooth muscle cells (PASMC) isolated from WT and KO SIRT3 mice. Normoxic-KO-PASMCs had a global decrease in Kreb’s cycle intermediates (mass spectrometry) and respiration, increased mitochondrial membrane potential and decreased mitochondrial reactive oxygen species compared to WT-PASMCs, mimicking the profile of WT-PASMC exposed to hypoxia. They also had activation of Hif-1a (luciferase activity assays), confirming a “pseudohypoxic” state, increased proliferation (%Ki67) and suppressed apoptosis (%TUNEL). In vivo, compared to WT, Sirt3 KO normoxic mice developed spontaneous PAH (mPAP, 30.9±3.13mmHg vs 14±1.41mmHg) which did not worsen by chronic-hypoxia CH (10% for 3 weeks), associated with right ventricle hypertrophy and significant vascular remodeling. Systemic blood pressures did not differ between groups. In the monocrotaline MCT rat model, intra-tracheal nebulization of Sirt3 adenovirus at day 21-post MCT injection, improved mPAP and vascular remodeling compared to the GFP-only adenovirus treated rats. We showed for the first time a critical role of SIRT3 in PAH. In a parallel abstract submission (Gurtu et al) we describe increased frequency of a characterized loss-of-function SIRT3 single nucleotide polymorphism in PAH patients. The loss of SIRT3 function causes a mitochondrial suppression perhaps explaining both the anti-apoptotic diathesis in PAH vessels and the extra-pulmonary metabolic abnormalities recently described in these patients.
The munich sleep endoscopy protocoll (MSEP)
Authors: Clemens Heiser, Ulrich Straßen, Constanze Gahleitner, Philippe Fthenakis, Klaus Wagner, Günther Edenharter, Yumiko Matsuba
Journal: European Respiratory Journal (2014)

Introduction: Before performing surgery in patients with obstructive sleep apnea a drug induced sleep endoscopy (DISE) should be done. DISE is useful to identify the location and pattern of upper airway obstructions. The aim of the study was to investigate, if the depth of anesthesia has an influence on the degree of obstruction and the occurrence of different patterns of the upper airway.  Methods: 20 patients with obstructive sleep apnea (CPAP incompliant), which decided to have surgery, underwent a DISE. For DISE propofol was infused via target controlled infusion pump (TCI). The depth of anesthesia was measured by spectral entropy. The degree of obstruction and the occurrence of different patterns of the upper airway were measured with VOTE-classification for velum, oropharynx lateral walls, tongue base and epiglottis during light, medium and deep sedation.  Results: No significant changes in the degree of obstruction and obstruction pattern were observed with an increasing sedation.  Conclusion: With increasing depth of sedation, associated with an increase in propofol, there have been no significant changes in the pattern of obstruction. A change in obstruction places (from cranial to caudal) was detected between light and medium depth of sedation in 2 patients. Furthermore in these 2 patients the collapse changed from anterior-posterior to a concentric collapse.
Herpesvirus saimiri-Induced Malignant Lymphoma in Rabbits2
Authors: S. R. S. Rangan, Louis N. Martin, Frederick M. Enright, William P. Allen
Journal: JNCI Journal of the National Cancer Institute (1976)

Of 9 New Zealand White rabbits inoculated at multiple sc and im sites with a single dose of Herpesvirus saimiri (HVS), 2 developed malignant lymphomas 40–50 days post inoculation. At least 1 animal developed a terminal leukemic phase of the disease. HVS was isolated from the oral and conjunctival swabs and blood and tissue lymphocytes, but not from monolayer cell cultures derived from kidney or lung tissues of the diseased animals. The inoculated rabbits developed low titers of neutralizing antibodies against the virus. Antibodies against HVS specific early and late antigens were not detected in the sera of 7 animals that failed to develop clinical disease, but were detected in the serum of the 1 rabbit with lymphoma. The immunologic response of rabbits to HVS infection was compared to similar responses in infected nonhuman primates.
High-dose paclitaxel, cyclophosphamide, and cisplatin with autologous hematopoietic progenitor-cell support: a phase I trial.
Authors: S M Stemmer, P J Cagnoni, E J Shpall, S I Bearman, S Matthes, C Dufton, T Day, S Taffs, L Hami, C Martinez, M H Purdy, J Arron, R B Jones
Journal: Journal of Clinical Oncology (1996)

PURPOSE To determine the maximal-tolerated dose (MTD) of paclitaxel in combination with high-dose cyclophosphamide (CPA) and cisplatin (cDDP) followed by autologous hematopoietic progenitor-cell support (AHPCS). PATIENTS AND METHODS Forty-nine patients with poor-prognosis breast cancer, non-Hodgkin's lymphoma (NHL), or ovarian cancer were treated with escalating doses of paclitaxel infused over 24 hours, followed by CPA (5,625 mg/m2 intravenously over 1 hour in three divided doses) and cDDP (165 mg/m2 intravenously as a continuous infusion over 72 hours) and AHPCS. Pharmacokinetic measurements for each drug were performed. RESULTS Dose-limiting toxicities were encountered in two patients at 825 mg/m2 of paclitaxel; one patient died of multiorgan failure that involved the lung, CNS, and kidneys, and the other developed grade 3 respiratory, CNS, and renal toxicity, which resolved. The MTD of this combination was determined to be paclitaxel 775 mg/m2, CPA 5,625 mg/m2, and cDDP 165 mg/m2 followed by AHPCS. Sensory polyneuropathy and mucositis were prominent toxicities, but both were reversible and tolerable. The pharmacokinetics of paclitaxel correlated significantly with the severity of mucositis (P &lt; .001) and peripheral neuropathy (P &lt; .00004). Eighteen of 33 patients (54%) with measurable, heavily pretreated metastatic breast cancer achieved a partial response (PR). Responses were also observed in patients with NHL (four of five patients) and ovarian cancer (two of two). CONCLUSION It is possible to escalate the dose of paclitaxel to 775 mg/m2 in combination with 5,625 mg/m2 of CPA, 165 mg/m2 of cDDP, and AHPCS. An encouraging response rate in poor-prognosis patients with breast cancer, NHL, and ovarian cancer warrants further study.
Basophil Recruitment into Tumor-Draining Lymph Nodes Correlates with Th2 Inflammation and Reduced Survival in Pancreatic Cancer Patients
Authors: Lucia De Monte, Sonja Wörmann, Emanuela Brunetto, Silvia Heltai, Gilda Magliacane, Michele Reni, Anna Maria Paganoni, Helios Recalde, Anna Mondino, Massimo Falconi, Francesca Aleotti, Gianpaolo Balzano, Hana Algül, Claudio Doglioni, Maria Pia Protti
Journal: Cancer Research (2016)

Abstract In pancreatic ductal adenocarcinomas (PDAC), lymphoid infiltrates, comprised mainly of Th2 cells, predict a poor survival outcome in patients. IL4 signaling has been suggested to stabilize the Th2 phenotype in this setting, but the cellular source of IL4 in PDAC is unclear. Here, we show that basophils expressing IL4 are enriched in tumor-draining lymph nodes (TDLN) of PDAC patients. Basophils present in TDLNs correlated significantly with the Th2/Th1 cell ratio in tumors, where they served as an independent prognostic biomarker of patient survival after surgery. Investigations in mouse models of pancreatic cancer confirmed a functional role for basophils during tumor progression. The recruitment of basophils into TDLN relied partly upon the release of chemokine CCL7/MCP3 by "alternatively activated" monocytes, whereas basophil activation was induced by T-cell–derived IL3. Our results show how basophils recruited and activated in TDLNs under the influence of the tumor microenvironment regulate tumor-promoting Th2 inflammation in PDAC, helping in illuminating a key element of the immune milieu of pancreatic cancer. Cancer Res; 76(7); 1792–803. ©2016 AACR.
The high-dose aldesleukin (HD IL-2) “SELECT” trial in patients with metastatic renal cell carcinoma (mRCC).
Authors: D. F. McDermott, M. S. Ghebremichael, S. Signoretti, K. A. Margolin, J. Clark, J. A. Sosman, J. P. Dutcher, T. Logan, R. A. Figlin, M. B. Atkins
Journal: Journal of Clinical Oncology (2010)

4514 Background: HD IL-2 received FDA approval for mRCC in 1992, producing a 14% major response (CR + PR) rate and durable remissions in phase II trials. The Cytokine Working Group conducted the present trial to identify patients (pts) likely to respond to treatment in order to improve the therapeutic index of HD IL-2. Methods: In this multicenter, prospective study pts with histologically confirmed RCC that was metastatic or unresectable, measurable disease, age ≥ 18 years, ECOG PS 0-1 and adequate organ function received HD IL-2 (600,000 U/kg/dose intravenously every 8 hours on days 1 through 5 and 15 to 19 (maximum 28 doses) every 12 weeks. The primary endpoint of the study was to determine the major response rate (RR) of pts with "favorable" predictive features. All pts were consented to provide archived tumor tissue that would be used for pathology risk classification, carbonic anhydrase IX (CAIX) staining and in creation of a tissue microarray. Results: One hundred twenty eligible pts enrolled between November 2007 and July 2009. Seventy-two percent had ECOG PS 0, 71% were MSKCC intermediate risk, 96% had clear cell RCC and 99% had prior nephrectomy. No unanticipated toxicities were observed. There were two treatment-related deaths. At the time of this analysis, the investigator assessed RR was 29% (35/120) (7 CR, 28 PR) and was significantly greater than the historical RR (95% CI = 21%-38%, p=0.0009). The median PFS was 4.4 months (mo) and 20 responses are ongoing (range 4-35+ mo). The RR for pts with clear cell RCC was 30% (35/115) (95% CI = 22%-40%, p=0.0004). Response to IL-2 was not associated with any pre-treatment clinical factor or seen in pts with non-clear cell histology (5 pts) and high UCLA SANI (survival after nephrectomy and immunotherapy) score (8 pts). Tumor (98%) and blood (94%) samples were collected on most eligible pts. Conclusions: The RR to HD IL-2 in this trial was significantly better than the historical experience. Clear cell histology may select pts who respond to IL-2. Analysis of tumor (central pathology review and staining for CAIX) and blood based predictive markers is ongoing to further improve the selection criteria for HD IL-2 in pts with mRCC and will be updated at the meeting. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis Novartis
The impact of obesity on outcomes in a population-based cohort of women with early-onset breast cancer
Authors: S. Loi, R. L. Milne, M. L. Friedlander, M. R. E. McCredie, G. G. Giles, J. L. Hopper, K.-A. Phillips
Journal: Journal of Clinical Oncology (2004)

9540 Background: Obesity (defined by body mass index, BMI≥30kg/m2) has been associated with adverse outcomes in postmenopausal women with breast cancer (BC). In premenopausal women the relationship is less clear. The impact of obesity on disease recurrence and death was studied in the population-based Australian Breast Cancer Family Study (ABCFS). Methods: 1108 early-stage BC patients, 47% diagnosed age< 40, were followed prospectively. Details on weight and height were collected by face-to-face interview at recruitment to the ABCFS. BC treatment and outcome data were abstracted from medical records. Ideal dose of chemotherapy was calculated and compared to actual dose received at cycle 1. The hazard ratio (HR) for disease recurrence and death associated with obesity was estimated using Cox proportional hazard survival models adjusting for number of axillary nodes, age, tumor size, grade and ER/PR at diagnosis. Results: Median follow-up was 5(0.4–10.8) years. 133 were obese. 75%(817/1108) were premenopausal. Obesity was associated with increased tumor size (p=0.001), more involved axillary nodes (p=0.005) but not hormone receptor status. Multivariate analysis found that compared with those non-obese, obese women were more likely to develop both BC recurrence, HR 1.57(95% CI:1.11–2.22) or die HR 1.55(95%CI:1.01–2.39). In obese premenopausal women the HRs for disease recurrence and death were 1.50(95%CI:1.00–2.26) and 1.71(95%CI:1.05–2.77) respectively. No differences in prescribing patterns or underdosing of adjuvant chemotherapy were observed. Conclusions: A BMI ≥30kg/m2 is associated with poorer BC outcomes in both pre- and post-menopausal women. Other biological and hormonal factors apart from estrogen are probably responsible for this increased risk. Targeting obesity is a potential approach to reduce the risk of BC recurrence in young women. No significant financial relationships to disclose.
Abstract 12584: Combined Treatment With Irbesartan and Amlodipine Potently Prevents Acute Myocardial Infarction in Subtotally Nephrectomized Triple Nitric Oxide Synthases-Deficient Mice
Authors: Masato Tsutsui, Taro Uchida, Yumi Furuno, Akihide Tanimoto, Mika Kina-Tanada, Haruaki Kubota, Mayuko Sakanashi, Toshihiro Matsuzaki, Katsuhiko Noguchi, Katsuhiko Noguchi, Junko Nakasone, Yusuke Ohya, Nobuyuki Yanagihara, Hiroaki Shimokawa, Masahito Tamura, Yutaka Otsuji
Journal: Circulation (2015)

Background: Since there are few experimentally useful models that develop acute myocardial infarction (AMI), research and development of therapeutic strategies for preventing AMI have made little progress. We have recently demonstrated that 2/3 nephrectomized (NX) triple nitric oxide synthases (NOSs)-deficient mice cause sudden death due to AMI as early as 4 months after the surgery, succeeding in the establishment of an experimentally useful AMI model ( JMCC 2014). In this study, we examined the effects of an angiotensin II type 1 receptor blocker, irbesartan (irbe), and a calcium channel antagonist, amlodipine (amlo), in this model. Method and Results: The 2/3NX triple NOSs -/- mice were treated with irbe (50 mg/ml/day in chow); amlo (250 mg/ml in drinking water); a combination of both; or an anti-hypertensive agent, hydralazine (0.25 mg/ml in drinking water) for 6 months (n=20-49). We used the clinical therapeutic dosage. In this model, the mono-treatment with irbe or amlo significantly reduced the incidence of AMI and mortality, while the co-treatment with irbe and amlo more potently suppressed them. The 2/3NX triple NOSs -/- mice exhibited cardiovascular risk factors (hypertension, hypercholesterolemia, and hyperglycemia), higher urinary 8-isoprostane levels (a marker of oxidative stress), and increased circulating bone marrow (BM)-derived vascular smooth muscle cell (VSMC) progenitor cells (a pro-arteriosclerotic factor). The sole treatment with irbe or amlo significantly improved these pro-arteriosclerotic parameters, while the simultaneous treatment with irbe and amlo more powerfully ameliorated them. Although the hydralazine treatment significantly lowered blood pressure to the same extent as the irbe/amlo treatment, it did not significantly affect any other pro-arteriosclerotic parameters, suggesting a minor role of an anti-hypertensive effect. Conclusions: Combined treatment with the clinical dosage of irbesartan and amlodipine potently prevented AMI and improved prognosis in the 2/3NX triple NOSs -/- mice via ameliorating cardiovascular risk factors, oxidative stress, and increased BM-derived VSMC progenitor cells. These results suggest the therapeutic importance of those agents to prevent AMI in humans.
CTO穿通用ガイドワイヤー(Conquest Pro 8‐20)の使用経験について
Authors: 田中裕之, 光藤和明, 井上勝美, 後藤剛, 門田一繁, 藤井理樹, 加藤晴美, 山本浩之, 福康志, 竹中創, 廣野明寿, 田場正直, 池田篤史, 前川潤平, 前川祐子, 羽原誠二, 中村幸伸, 宮地剛, 山田千夏, 岡本陽地, 大鶴優
Journal: Circulation (2006)
Abstract 11253: EF<50% Strongly Predicts Abnormal PET/CT Imaging Results in Patients Being Evaluated for Cardiac Sarcoidosis
Authors: Vladyslava Bazylevska, Herman H Feringa, Samala Venkata, Lavanya Bellumkonda, Raymond R Russell, Daniel Jacoby
Journal: Circulation (2014)

Background:  18F-FDG positron emission tomography (PET) along with 82Rubidium radiotracer imaging is a non-invasive semi-quantitative technique that aids in the diagnosis of cardiac sarcoidosis, as defined by the Japanese Ministry of Health and Welfare Criteria (JMHC). The study’s objective was to identify characteristics in cardiac presentation associated with positive PET results.   Methods:  We retrospectively analyzed 83 patients with proven or suspected cardiac sarcoidosis, referred for PET imaging between 2009-2013. PET scans were classified as normal or abnormal with positive FDG uptake and/or Rubidium perfusion defect. Multivariate logistic regression analysis adjusted for age, race, gender, HTN, DM, and CAD was performed to assess PET results as associated with significant baseline cardiac characteristics.   Results:  Mean age was 54 + 12 years, 60% were male, 6% had CAD, 4.8% were survivors of SCD, 12% had AICD discharges for VT, 21.7% had sustained VT and 48.2% had CHF. 55.4% of patients had abnormal FDG uptake in the heart. Significant predictors for a positive PET scan are shown in the Table.   Conclusion:  Patients with suspected or known cardiac sarcoidosis and EF
A synthetic consensus anti–spike protein DNA vaccine induces protective immunity against Middle East respiratory syndrome coronavirus in nonhuman primates
Authors: Karuppiah Muthumani, Darryl Falzarano, Emma L. Reuschel, Colleen Tingey, Seleeke Flingai, Daniel O. Villarreal, Megan Wise, Ami Patel, Abdullah Izmirly, Abdulelah Aljuaid, Alecia M. Seliga, Geoff Soule, Matthew Morrow, Kimberly A. Kraynyak, Amir S. Khan, Dana P. Scott, Friederike Feldmann, Rachel LaCasse, Kimberly Meade-White, Atsushi Okumura, Kenneth E. Ugen, Niranjan Y. Sardesai, J. Joseph Kim, Gary Kobinger, Heinz Feldmann, David B. Weiner
Journal: Science Translational Medicine (2015)

A consensus MERS spike protein synthetic DNA vaccine can induce protective responses against viral challenge.