tbuckley/cabot-search huggingface dataset:
Abstract 258: Coronary Perfusion Pressure Response to Administration of Intraosseous Epinephrine After Prolonged Cardiac Arrest
Authors: Joshua L Harris, Ryan A Coute, Scot A Millay, Adam R Kellogg, Timothy J Mader
Journal: Circulation (2012)

Background: While provision of vasopressors during attempted resuscitation of OHCA victims has never been shown to improve neurologically intact survival, its short-term benefits are clear. Despite evidence that the IO dose should be substantially higher than that given IV to achieve pharmacokinetic and hemodynamic equivalency, current guidelines still recommend a dose of 0.01 mg/kg regardless of delivery route (IO or IV). Objective: To compare the effect of epinephrine 0.1 mg/kg (HDE) IO with 0.01 mg/kg (SDE) IV on coronary perfusion pressure (CPP) during resuscitation in a swine model of prolonged VF. Methods: This was a secondary analysis of prospectively collected data from two IACUC approved protocols. Seventy-nine Yorkshire swine (25-30 kg) were surgically instrumented under anesthesia and VF was electrically induced. After 10 minutes of untreated VF in the IO study (n=26) and 12 minutes of untreated VF in the IV study (n=53), resuscitation commenced with precordial chest compressions. After 30 seconds of initial chest compressions, a single dose of epinephrine (HDE IO or SDE IV, respectively) was given followed by a large volume saline flush. An additional 2.5 minutes of compressions were provided after injection to circulate the medication before the first rescue shock (RS) was delivered. CPR and RS attempts were standardized for all animals. The CPP was defined as aortic diastolic pressure minus right atrial diastolic pressure and the values were extracted immediately following the last compression before defibrillation for the first RS in each animal. Descriptive statistics were used to analyze the data. Results: After 10 minutes of untreated VF, HDE IO epinephrine resulted in a mean CPP of 33.2 mmHg (95%CI: 26.6, 39.9) just prior to RS1. After 12 minutes of untreated VF, SDE IV epinephrine resulted in a mean CPP of 25.0 mmHg (95%CI: 20.5, 29.4) just prior to RS1. Conclusion: This observation study reaffirms the assertion that HDE may be required to generate CPP values similar to SDE delivered IV during resuscitation of prolonged VF. A randomized comparison of HDE and SDE IO in the metabolic phase of VF is needed to test this hypothesis and to determine the impact on ROSC and short-term survival.
Age, not therapy intensity, determines outcomes of adults with acute myeloid leukemia
Authors: T Büchner, U O Krug, R Peter Gale, A Heinecke, M C Sauerland, C Haferlach, S Schnittger, T Haferlach, C Müller-Tidow, M Stelljes, R M Mesters, H L Serve, J Braess, K Spiekermann, P Staib, A Grüneisen, A Reichle, L Balleisen, H Eimermacher, A Giagounidis, H Rasche, E Lengfelder, D Görlich, A Faldum, W Köpcke, R Hehlmann, B J Wörmann, W E Berdel, W Hiddemann
Journal: Leukemia (2016)
Abstract 268: Differential Activation and Subcellular Targeting of Erk1/2 and Akt in Response to β-Adrenergic Receptor-Mediated Transactivation of Epidermal Growth Factor Receptor in Cardiomyocytes
Authors: Laurel A Grisanti, Jennifer A Talarico, Rhonda C Carter, Scott W Radcliffe, Douglas G Tilley
Journal: Circulation Research (2012)

β-adrenergic receptors (βAR) are critical regulators of cardiac function whose dysregulation during heart failure are associated with diminished cardiac function, however βAR-mediated EGFR transactivation has been shown to relay cardioprotection via unknown mechanisms. We hypothesized that EGFR transactivation may result in differential activation and subcellular targeting of prosurvival kinases known to be downstream of EGFR, namely ERK1/2 and Akt. Thus, ERK1/2 and Akt phosphorylation and subcellular distribution was assessed in rat neonatal cardiomyocytes (RNCM). Treatment of RNCM with the βAR agonist isoproterenol (Iso) resulted in significant phosphorylation of both ERK1/2 (P-ERK) and Akt (P-Akt), in the cytosolic, plasma membrane and nuclear fractions. EGFR inhibition with AG1478 resulted in complete ablation of Iso-induced P-ERK in all fractions, as did MEK1/2 inhibition with PD184352. Total ERK levels did not change in any fraction under any condition, which along with the PD184352 data suggests Iso-mediated EGFR-dependent effects on ERK1/2 activity at different cellular locations is reliant upon MEK1/2 trafficking. While Akt phosphorylation in response to Iso-mediated EGFR transactivation was not sensitive to EGFR inhibition in the cytosol, the P-Akt response was completely abrogated by AG1478 in the plasma membrane and nuclear fractions. The PI3K inhibitor LY-294002 blocked Iso-induced Akt phosphorylation in all fractions, confirming reliance upon PI3K activity for Iso-mediated Akt activation. Additionally, total Akt levels remained constant over all treatments except at the plasma membrane, where AG 1478 reduced T-Akt, suggesting that Akt recruitment and PI3K activity each contribute to an increase in plasma membrane-associated P-Akt, whereas increased nuclear P-Akt in response to Iso-induced EGFR signaling depends solely on PI3K activity. In all, these results demonstrate differential impact of βAR-mediated EGFR transactivation on the subcellular activation and targeting of cardiomyocyte ERK1/2 and Akt. Further understanding of the downstream consequences of these effects in response to βAR-mediated EGFR transactivation could lead to improved therapies for the treatment of heart failure.
Study of Amino Acid Requirements for Increase in Cell Population of NCTC Clone 929 (Strain L)
Authors: Katherine K. Sanford, William T. McQuilkin, Mary C. Fioramonti, Virginia J. Evans, Wilton R. Earle
Journal: JNCI Journal of the National Cancer Institute (1958)

Study of Amino Acid Requirements for Increase in Cell Population of NCTC Clone 929 (Strain L) Get access Katherine K. Sanford, Katherine K. Sanford Tissue Culture Section, Laboratory of Biology, National Cancer Institute,2Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar William T. McQuilkin, William T. McQuilkin Tissue Culture Section, Laboratory of Biology, National Cancer Institute,2Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar Mary C. Fioramonti, Mary C. Fioramonti Tissue Culture Section, Laboratory of Biology, National Cancer Institute,2Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar Virginia J. Evans, Virginia J. Evans Tissue Culture Section, Laboratory of Biology, National Cancer Institute,2Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar Wilton R. Earle Wilton R. Earle Tissue Culture Section, Laboratory of Biology, National Cancer Institute,2Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 20, Issue 4, April 1958, Pages 775–785, https://doi.org/10.1093/jnci/20.4.775 Published: 01 April 1958 Article history Received: 23 October 1957 Published: 01 April 1958
SAR245409 Monotherapy In Relapsed/Refractory Follicular Lymphoma: Preliminary Results From The Phase II ARD12130 Study
Authors: Jennifer R Brown, Mehdi Hamadani, Jon Arnason, Lionel Karlin, John Hayslip, Nina Wagner-Johnston, Guillaume Cartron, Vincent Ribrag, Sophie de Guibert, Stephen Opat, Hervé Tilly, Paul Cannell, Ann Janssens, Fritz Offner, Siddhartha Ganguly, Sikander Ailawadhi, Michael Millenson, Dominique Bron, Yi Xu, Rodrigo Ruiz-Soto, Marie José Kersten
Journal: Blood (2013)
Adjusting the 17β–Estradiol-to-Androgen Ratio Ameliorates Diabetic Nephropathy
Authors: Akari Inada, Oogi Inada, Nobuharu L. Fujii, Seiho Nagafuchi, Hitoshi Katsuta, Yohichi Yasunami, Takeshi Matsubara, Hidenori Arai, Atsushi Fukatsu, Yo-ichi Nabeshima
Journal: Journal of the American Society of Nephrology (2016)

Diabetes is manifested predominantly in males in experimental models, and compelling evidence suggests that 17 β -estradiol (E2) supplementation improves hyperglycemia in humans. We previously generated a severely diabetic transgenic (Tg) mouse model by β -cell–specific overexpression of inducible cAMP early repressor (ICER) and found that male but not female ICER-Tg mice exhibit sustained hyperglycemia and develop major clinical and pathologic features of human diabetic nephropathy (DN). Thus, we hypothesized that differences in circulating hormone levels have a key role in determining susceptibility to diabetes. Here, we examined whether DN in male ICER-Tg mice is rescued by adjusting the androgen-to-E2 ratio to approximate that in normoglycemic female ICER-Tg mice. We treated hyperglycemic male ICER-Tg mice with orchiectomy (ORX), E2 pellet implantation, or both. E2 pellet implantation at an early stage of DN with or without ORX caused a rapid drop in blood glucose and a dramatic increase in β -cell number, and it markedly inhibited DN progression [namely, E2 reduced glomerulosclerosis, collagen IV deposition and albuminuria, and prevented hyperfiltration]. Furthermore, E2 pellet implantation was more effective than ORX alone and induced a remarkable improvement, even when initiated at advanced-stage DN. In contrast, induction of normoglycemia by islet transplant in ICER-Tg mice eliminated albuminuria but was less effective than E2+ORX in reducing glomerulosclerosis or collagen IV deposition and hyperfiltration. These findings indicate that E2 treatment is effective, even after establishment of DN, whereas glucose normalization alone does not improve sclerotic lesions. We propose that E2 intervention is a potential therapeutic option for DN.
Developmental Origins for Kidney Disease Due to Shroom3 Deficiency
Authors: Hadiseh Khalili, Alexandra Sull, Sanjay Sarin, Felix J. Boivin, Rami Halabi, Bruno Svajger, Aihua Li, Valerie Wenche Cui, Thomas Drysdale, Darren Bridgewater
Journal: Journal of the American Society of Nephrology (2016)

CKD is a significant health concern with an underlying genetic component. Multiple genome-wide association studies (GWASs) strongly associated CKD with the shroom family member 3 (SHROOM3) gene, which encodes an actin-associated protein important in epithelial morphogenesis. However, the role of SHROOM3 in kidney development and function is virtually unknown. Studies in zebrafish and rat showed that alterations in Shroom3 can result in glomerular dysfunction. Furthermore, human SHROOM3 variants can induce impaired kidney function in animal models. Here, we examined the temporal and spatial expression of Shroom3 in the mammalian kidney. We detected Shroom3 expression in the condensing mesenchyme, Bowman's capsule, and developing and mature podocytes in mice. Shroom3 null (Shroom3Gt/Gt) mice showed marked glomerular abnormalities, including cystic and collapsing/degenerating glomeruli, and marked disruptions in podocyte arrangement and morphology. These podocyte-specific abnormalities are associated with altered Rho-kinase/myosin II signaling and loss of apically distributed actin. Additionally, Shroom3 heterozygous (Shroom3Gt/+) mice showed developmental irregularities that manifested as adult-onset glomerulosclerosis and proteinuria. Taken together, our results establish the significance of Shroom3 in mammalian kidney development and progression of kidney disease. Specifically, Shroom3 maintains normal podocyte architecture in mice via modulation of the actomyosin network, which is essential for podocyte function. Furthermore, our findings strongly support the GWASs that suggest a role for SHROOM3 in human kidney disease.
Type I Interferon Signaling Prevents IL-1β-Driven Lethal Systemic Hyperinflammation during Invasive Bacterial Infection of Soft Tissue
Authors: Virginia Castiglia, Alessandra Piersigilli, Florian Ebner, Marton Janos, Oliver Goldmann, Ursula Damböck, Andrea Kröger, Sigfried Weiss, Sylvia Knapp, Amanda M. Jamieson, Carsten Kirschning, Ulrich Kalinke, Birgit Strobl, Mathias Müller, Dagmar Stoiber, Stefan Lienenklaus, Pavel Kovarik
Journal: Cell Host & Microbe (2016)
Risk of bleeding in cancer patients treated with the angiogenesis inhibitor bevacizumab: A meta-analysis
Authors: A. F. Sher, D. Chu, S. Wu
Journal: Journal of Clinical Oncology (2009)

9584 Background: Bleeding is a serious adverse event associated with bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF) used extensively in the treatment of cancer. Currently the overall risk of bleeding remains unclear. This study was conducted to determine the overall risk of bleeding associated with bevacizumab in cancer patients by a meta-analysis of randomized controlled trials (RCT). Methods: Databases from PUBMED and the Web Science from January 1966 until July 2008 and abstracts presented at the American Society of Clinical Oncology (ASCO) conferences from January 2000 to through July 2008 were searched to identify relevant studies. Eligible studies included prospective RCTs in which standard anti-neoplastic therapy was administered with and without the use of bevacizumab with available data of bleeding. Summary incidence rate, relative risk (RR), and 95% confidence interval (CI) were calculated employing fixed- or random-effect models based upon the heterogeneity of the included studies. Results: A total of 13048 patients with a variety of solid tumors from 20 RCTs were included for analysis. Among patients receiving bevacizumab, the incidence of all-grade bleeding was 36.3% (95% CI: 28.0 - 45.5), and the RR was 3.1 (95% CI: 2.4 - 4.1) as compared to controls. The incidence of high grade (grade 3 or above) bleeding with bevacizumab was 2.7% (95% CI: 2.0 - 3.6%), and the RR was 1.8 (95% CI: 1.2 - 2.7). The risk of bleeding varied with the dose of bevacizumab, with RR of 3.0 (95% CI: 2.4 - 3.6) at 5mg/kg/week and 1.6 (95% CI: 1.3 - 2.0) at 2.5mg/kg/week. The risk of bleeding with bevacizumab may vary with tumor type, with higher risk seen in patients with colorectal cancer (RR=6.6, 95% CI: 3.6–12.2) and renal cell cancer (RR=3.7, 95% CI: 2.6–5.5). Bevacizumab is associated with different patterns of bleeding, with epistaxis being the most common. The incidence of all grade epistaxis with bevacizumab was 33.8% (95% CI 24.5–44.6) with a RR of 3.1 (95% CI 2.4 - 4.0). Conclusions: There is a significant increase in the risk of bleeding in cancer patients receiving bevacizumab. The risk may vary with the dose of bevacizumab and tumor type. No significant financial relationships to disclose.
Classification based on mutations of<i>TERT</i>promoter and<i>IDH</i>characterizes subtypes in grade II/III gliomas
Authors: Pei Yang, Jinquan Cai, Wei Yan, Wei Zhang, Yinyan Wang, Baoshi Chen, Guilin Li, Shouwei Li, Chenxing Wu, Kun Yao, Wenbin Li, Xiaoxia Peng, Yongping You, Ling Chen, Chuanlu Jiang, Xiaoguang Qiu, Tao Jiang
Journal: Neuro-Oncology (2016)

Grade II and III gliomas have variable clinical behaviors, showing the distinct molecular genetic alterations from glioblastoma (GBM), many of which eventually transform into more aggressive tumors. Since the classifications of grade II/III gliomas based on the genetic alterations have been recently emerging, it is now a trend to include molecular data into the standard diagnostic algorithm of glioma.Here we sequenced TERT promoter mutational status (TERTp-mut) in the DNA of 377 grade II/III gliomas and analyzed the clinical factors, molecular aberrations, and transcriptome profiles.We found that TERTp-mut occurred in 145 of 377 grade II and III gliomas (38.5%), mutually exclusive with a TP53 mutation (TP53-mut; P < .001) and coincident with a 1p/19q co-deletion (P = .002). TERTp-mut was an independent predictive factor of a good prognosis in all patients (P = .048). It has been an independent factor associated with a good outcome in the IDH mutation (IDH-mut) subgroup (P = .018), but it has also been associated with a poor outcome in the IDH wild-type (IDH-wt) subgroup (P = .049). Combining TERTp-mut and IDH-mut allowed the grade II/III malignancies to be reclassified into IDH-mut/TERTp-mut, IDH-mut only, TERTp-mut only, and IDH-wt/TERTp-wt. 1p/19q co-deletion, TP53-muts, Ki-67 expression differences, and p-MET expression differences characterized IDH-mut/TERTp-mut, IDH-mut only, TERTp-mut only, and IDH-wt/TERTp-wt subtypes, respectively.Our results showed that TERTp-mut combined with IDH-mut allowed simple classification of grade II/III gliomas for stratifying patients and clarifying diagnostic accuracy by supplementing standard histopathological criteria.
Abstract 18867: Multiple Pregnancy Factors and Serum Lipids at Age 40 Year in Swedish Women From the Vasterbotten Intervention Programme
Authors: Nisha Parikh, Margareta Norberg, Erik Ingelsson, Sven Cnattingius, Vasan Ramachandran, Magnus Domellöf, Anna-Karin Edstedt Bonamy
Journal: Circulation (2015)

Introduction: Pregnancy factors provide an early window into future cardiovascular disease (CVD) risk in women. It is uncertain which factors, when considered together, independently relate to later lipid levels. Methods: We used Swedish National Medical Birth Register data linked with the Vasterbotten Intervention Programme cohort. We related pregnancy factors (in any pregnancy) with serum lipid levels at age 40 years in parous women. Using linear regression analysis in crude and multivariable adjusted models, we related total parity, age at first delivery, infertility ≥ 5 years, preeclampsia, small for gestational age (SGA), preterm delivery, placental abruption and gestational diabetes to each of the four clinical lipid variables (total cholesterol, triglycerides HDL-C and LDL-C). HDL-C and LDL-C were measured in a smaller subset of women. Multivariable models were adjusted for all pregnancy factors in addition to annual income, education, smoking status, alcohol intake and body mass index. Results: In multivariable models, lower parity and younger age at first birth were related to increased total cholesterol (Table). Lower parity, younger age at first birth, gestational age &lt; 37 weeks, and infertility ≥ 5 years were related to increased triglycerides. Preeclampsia was related to increased triglyceride and lower HDL-C only in crude models. Gestational diabetes was related to total cholesterol, triglyceride and lower HDL cholesterol in crude models only. SGA was related to total cholesterol and triglycerides in crude models only. Placental abruption was not associated with any lipid measures in either crude or multivariable models. Conclusions: Lower parity, younger age at first birth, a history of prolonged infertility prior to pregnancy and preterm delivery are independently related to alterations in lipid levels at age 40 years in women. The association between preeclampsia and later CVD does not appear to be independently mediated by dyslipidemia.
Statin treatment is associated with a decreased risk of active tuberculosis: an analysis of a nationally representative cohort
Authors: Chih-Cheng Lai, Meng-tse Gabriel Lee, Shih-Hao Lee, Wan-Ting Hsu, Shy-Shin Chang, Shyr-Chyr Chen, Chien-Chang Lee
Journal: Thorax (2016)

<h3>Background</h3> Epidemiological data suggest that statins improve the clinical outcome of respiratory infections. We sought to examine whether statin therapy decreases the risk of active TB. <h3>Methods</h3> We conducted a nested case-control study on data obtained from a national health insurance claims database between 1999 and 2011. The use of statins was classified as current, recent, past or chronic use. Three conditional logistic regression models were used to estimate the incidence rate ratios (RRs). The first assessed the effect of statin use without further adjustment; the second adjusted (individually) for 75 potential confounders; and the third adjusted for the Disease Risk Score (DRS). <h3>Results</h3> A total of 8098 new TB cases and 809 800 control patients were examined. All four types of statin users showed a decreased risk of active TB. Chronic use (&gt;90 days in a calendar year) of statins was associated with the lowest unadjusted risk of TB (RR 0.74; 95% CI 0.63 to 0.87). The protective effect of active TB remained after adjusting for individual confounders (RR 0.66; 95% CI 0.56 to 0.78) and after DRS adjustment (RR 0.62; 95% CI 0.53 to 0.72). The effect estimates obtained for chronic and current use of statins were very similar. We also found that the active TB protection increased with increasing length of statin prescription. <h3>Conclusions</h3> We found that statin therapy was associated with a decreased risk of active TB, and the length of statin therapy affected the TB protection. Given the observational nature of this study, the protective effect against active TB must be confirmed in future randomised trials.
Myocardial Perfusion Reserve and Strain-Encoded CMR for Evaluation of Cardiac Allograft Microvasculopathy
Authors: Christian Erbel, Nodira Mukhammadaminova, Christian A. Gleissner, Nael F. Osman, Nina P. Hofmann, Christian Steuer, Mohammadreza Akhavanpoor, Susanne Wangler, Sultan Celik, Andreas O. Doesch, Andreas Voss, Sebastian J. Buss, Philipp A. Schnabel, Hugo A. Katus, Grigorios Korosoglou
Journal: JACC. Cardiovascular imaging (2016)
Immunochemotherapy in human hepatocellular carcinoma using the streptococcal agent OK-432.
Authors: S Imaoka, Y Sasaki, O Ishikawa, H Ouhigashi, H Koyama, T Iwanaga, S Ishiguro
Journal: Journal of Clinical Oncology (1986)

Twenty-one patients with nonresectable hepatocellular carcinoma (HCC) received intraarterial infusion chemotherapy of Adriamycin (Adria Laboratories, Columbus, Ohio) via an indwelling catheter in the hepatic artery. Additional intratumoral injection therapy of OK-432 (50 KE) was administered to ten of these 21 patients. Nine of the ten patients showed a remarkable decrease in lymphocyte count on the first day after therapy. In all of the patients with a decreased lymphocyte count, computed tomograms (CTs) demonstrated evidence of necrosis associated with a rapid decrease in alpha fetoprotein (alpha-FP). Blastogenesis of lymphocytes in peripheral blood induced by phytohemagglutinin (PHA) increased by 3.99 +/- 1.9 (mean +/- SE) times 4 weeks after therapy. On the basis of these results, we concluded that intratumoral injection therapy of OK-432 apparently produced initiation of necrosis in HCC by cell-damaging activity as well as by improvement of cell-mediated immunity.
Circulating Tumor Cell Count at Baseline is an Independent Prognostic Factor from Pathological Complete Response Among Patients Treated for Primary Inflammatory Her2-Positive Breast Cancer: Survival Results of the Beverly-2 Study
Authors: J. Pierga, T. Petit, C. Levy, J. Ferrero, M. Campone, J. Gligorov, F. Lerebours, H. Roche, T. Bachelot, E. Charafe-Jauffret, J. Bonneterre, M. Coudert, J. Hernandez, F.C. Bidard, P. Viens
Journal: Annals of Oncology (2014)