tbuckley/cabot-search huggingface dataset:
Abstract 15689: Activation of PKR-Like Endoplasmic Reticulum Kinase is Required for Autophagy Stimulation and Cardiomyocyte Survival During Acute Myocardial Ischemia
Authors: Sebastiano Sciarretta, Narayani Nagarajan, Derek Yee, Peiyong Zhai, Priya Umapathi, Christopher D Brady, Massimo Volpe, Giacomo Frati, Junichi Sadoshima
Journal: Circulation (2014)

PKR-like endoplasmic reticulum (ER) kinase (PERK) is an ER-resident serine/threonine kinase that regulates the cellular response to ER stress and energy deprivation. Under stress, PERK activation can be either protective or detrimental. We studied for the first time whether PERK regulates cardiomyocyte (CM) survival and death during myocardial ischemia, which is characterized by both ER and energy stress. We found that PERK is significantly activated after 30 minutes of myocardial ischemia (2.4 ± 0.04-fold, p&lt;0.001), as shown by its increased phosphorylation status. After 3 hours of ischemia, mice with cardiac-specific overexpression of dominant-negative PERK (Tg-DN-PERK) displayed a significant increase in infarct size/area at risk with respect to non-transgenic (NTg) mice (66.4 ± 4.1% vs. 38.5 ± 6.8%, p&lt;0.05), indicating that ischemia-induced PERK activation is cardioprotective. PERK signaling regulates autophagy in cancer cells. Autophagy is an intracellular degradation mechanism that promotes CM survival during ischemia by relieving both energy and ER stress. We found that autophagy activation during ischemia is abrogated in the hearts of Tg-DN-PERK with respect to NTg, as indicated by reduced LC3-II accumulation (0.71 ± 0.05-fold, p&lt;0.01). Consistently, CMs with adenovirus-mediated overexpression of DN-PERK displayed reduced LC3-II accumulation (0.69 ± 0.1-fold vs. control CMs, p&lt;0.05) after 4 hours of glucose deprivation (GD) in vitro, a condition that mimics ischemia-induced energy stress. A similar result was also observed after bafilomycin A1 treatment to test autophagic flux. These data indicate that PERK is required for autophagy activation and flux during CM ischemia and GD. Finally, we saw that DN-PERK overexpression significantly promotes CM death after GD, as shown by propidium iodide assay (2.01 ± 0.25-fold vs. control CMs, p&lt;0.05). However, co-overexpression of Atg7, which activates autophagy, significantly reduced cell death induced by DN-PERK (-61%, p&lt;0.05). These data suggest that autophagy inhibition partly mediates the detrimental effects of PERK inhibition during energy stress. In conclusion, our study demonstrates that PERK activation is required for autophagy activation and CM survival during ischemia.
Abstract 9843: Proton Pump Inhibitors inhibit DDAH and processes underlying Idiopathic Pulmonary Fibrosis
Authors: Yohannes T. Ghebremariam, Zhou Qingtao, Lawrence Ho, Glenn D. Rosen, John P. Cooke
Journal: Circulation (2013)

Yohannes Ghebremariam, 2013 Finalist and Presenting Author
Minoxidil (Mx) as a prophylaxis of doxorubicin – induced alopecia
Authors: R. Rodriguez, M. Machiavelli, B. Leone, A. Romero, M.A. Cuevas, M. Langhi, L. Romero Acuna, J. Romero Acuna, S. Amato, M. Barbieri, C. Vallejo, M. Rabinovich, J. Perez, C. Sabatini, E. Ortiz, M. Salvadori, J. Lacava
Journal: Annals of Oncology (1994)
Alterations in glomerular proteoglycan metabolism in experimental non-insulin dependent diabetes mellitus.
Authors: P Fioretto, W F Keane, B L Kasiske, M P O'Donnell, D J Klein
Journal: Journal of the American Society of Nephrology (1993)

Glomerular proteoglycans (PG) are important in modulating extracellular matrix assembly and glomerular permselectivity. In the obese Zucker rat, an experimental model of non-insulin dependent diabetes mellitus, expansion of the mesangial matrix, and microalbuminuria occur before the development of overt renal disease. The in vivo incorporation of (35S)sulfate into glomerular PG in 12-wk-old obese Zucker rats at the onset of microalbuminuria was compared with that of 12-wk-old lean Zucker rats. Specific (35S)sulfate incorporation into glomerular PG over 8 h was increased by 57% in obese rats compared with lean rats, suggesting increased PG synthesis. However, at variance with the observation in experimental models of insulin-dependent diabetes mellitus, the proportion of total glomerular (35S)PG released by heparin treatment was unchanged. Heparan sulfate (HS)-PG constituted over 60% of radiolabeled de novo synthesized glomerular PG. Similar proportions of HS-PG were extracted from the glomeruli of obese and lean rats. Isolated glomeruli spontaneously released two HS-PG, which constituted approximately 30% of total glomerular (35S)PG. On the basis of their chromatographic and electrophoretic patterns, these PG were similar in obese and lean rats. Heparin treatment of isolated glomeruli released an additional HS-PG, which appeared to be derived primarily from the glomerular extracellular matrix compartment and not from the detergent soluble cell fraction. Heparin-releasable HS-PG from both the lean and obese Zucker rats eluted at a KAV of 0.31 from Sepharose CL-6B chromatographic columns, indicating a hydrodynamic size similar to that reported for glomerular basement membrane HS-PG. However, gel electrophoresis demonstrated faster migration of the HS-PG released by heparin from the glomeruli of obese Zucker rats, suggesting increased electronegativity. Thus, early in the course of nephropathy in the obese Zucker rat, there is increased glomerular PG synthesis with no change in the proportions of the constitutively releasable and heparin-releasable HS-PG. Whether electrophoretic abnormalities of the heparin-releasable HS-PG observed in the obese rats contribute to the development of albuminuria and/or mesangial matrix expansion remains to be established.
Duplex scanning in vascular disorders, (2nd edn.): By D E Strandness Jr. (Pp 329; $120.) New York: Raven Press, 1993. ISBN 0-7817-0014-0
Authors: R Migliacci, P Gresele
Journal: Cardiovascular Research (1995)

Journal Article Duplex scanning in vascular disorders, (2nd edn.): By D E Strandness Jr. (Pp 329; $120.) New York: Raven Press, 1993. ISBN 0-7817-0014-0 Get access Duplex Scanning in Vascular Disorders, 2nd edn. By Strandness D EJr.. (Pp 329; $120.) New York: Raven Press, 1993. ISBN 0-7817-0014-0. R Migliacci, R Migliacci Perugia, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar P Gresele P Gresele Perugia, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 29, Issue 2, February 1995, Page 294, https://doi.org/10.1016/S0008-6363(95)90020-9 Published: 01 February 1995
Application of Immunofluorescence to the Study of Human Leukemia
Authors: Mary Alexander Fink, Richard A. Malmgren, Frank J. Rauscher, Henry C. Orr, Myron Karon
Journal: JNCI Journal of the National Cancer Institute (1964)

The concentrated plasma of individuals with leukemia has been shown by several electron microscopists to contain virus-like particles. In the present study, plasmas containing similar particles were used as an antigen in the production of an antiserum in rabbits. After absorption with normal human antigens and labeling with fluorescein isothiocyanate, this serum reacted specifically with various cellular elements of the bone marrow and peripheral blood of a significant number of patients with leukemia, and failed to react with leukocytes of nonleukemic individuals. A similar antibody prepared against a murine leukemia virus (Rauscher) cross-reacted with the bone marrow and peripheral blood cells from some humans with leukemia, and especially with the cells from a patient with erythroleukemia. It is of interest that this murine leukemia resembles human erythroleukemia pathologically. Tissue culture cells of Burkitt's lymphoma reacted strongly with the antihuman leukemia fluorescent antibody, and less strongly with the antimurine. These same preparations of fluorescent antibody did not react with HeLa cells infected with either Herpes simplex or Herpes zoster viruses. These findings are interpreted as supporting the hypothesis of a viral etiology of human leukemia, and as suggesting a strong probability of antigenic similarities among strains of leukemia virus infecting various species.
Retrospective health care claims database analysis of direct medical costs of newly diagnosed patients (pts) with hepatocellular carcinoma (HCC) in the United States.
Authors: A. S. Poklepovic, A. Sanyal, E. Moyneur, S. Meyers, V. Barghout
Journal: Journal of Clinical Oncology (2010)

6078 Background: Incidence of HCC is rising in the United States. Published cost data of HCC are obsolete, as pt populations analyzed were from >10 y ago and treatment options have dramatically changed. The objective of this study was to update the literature by quantifying incremental direct medical costs and full resource use of HCC from a current U.S. perspective and using patient level data. Methods: Deidentified, individual-level healthcare claims data from MarketScan were retrospectively analyzed. Pts diagnosed 1/07-12/08 with ≥2 primary HCC claims (ICD9 155.0); continuous enrolment; ≥180 days coverage before HCC; no prior claims for secondary HCC (ICD9 197.7), transarterial chemoembolization (TACE), liver transplant, or hospice were included. Pts were followed from HCC diagnosis until healthcare coverage end or 3/31/09 and matched 5:1 to subjects without HCC by 10-y age increments, sex, health plan type, and U.S. census region. Univariate and multivariate analysis was conducted at per member per month (PMPM) level. Results: Mean age of HCC pts (n=1475) was 62.6 y and matched cohort (n=7375) was 62.1 y; 67.9% in each group were male. Incremental univariate and multivariate annualized total medical expenses of HCC pts were $87,240 and $36,996 greater, respectively, than those without HCC. HCC treatment procedures were 32.2% of outpt costs (19.6% IV chemo, 10.5% TACE). Conclusions: This retrospective U.S. database analysis quantified significantly greater costs among HCC patients than those without HCC and that older agents are still commonly used. Additional expenses were largely attributed to inpt costs, while one-third of outpt costs were attributed to procedures. Cost expenditures have increased considerably based on data from 10 y ago. These data may be useful to support future cost analyses and cost effectiveness model of HCC. Univariate costs, mean PMPM ($) HCC pts HCC-free subjects Cost ratio P value Inpt 3,745 238 15.71 < 0.0001 Procedures 231 TACE 145 RFA 39 IV chemo 46 Outpt 3,774 386 9.77 < 0.0001 Procedures 1,217 TACE 397 SIRT 56 RFA 25 IV chemo 739 Drug 529 153 3.46 < .0001 Sorafenib 280 Total 8,048 778 10.35 < 0.0001 Pt-mos (n) 12,116 119,510 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer Amylin, Astellas Pharma, Bayer, Bayer-Onyx, Exhalenz, Gilead, Ikaria, Pfizer, Salix, sanofi-aventis, Takeda, Vertex Bayer Bayer, Gilead, Intercept, Roche, Salix, sanofi-aventis Up-to-Date
Cd163 Expression in Cancer Cells is Caused By Cell Fusion and Cannot Be Explained By Paracrine Cellular Interaction- an in Vitro Study with Mcf-7 Cells and Human M2-Macrophages
Authors: A. Lindström, K. Midtbö, P. Wegman, H. Andersson, O. Stal, H. Olsson, C. Gunnarsson, I. Shabo
Journal: Annals of Oncology (2014)
Cross-species translation of the Morris maze for Alzheimer’s disease
Authors: Katherine L. Possin, Pascal E. Sanchez, Clifford Anderson-Bergman, Roland Fernandez, Geoffrey A. Kerchner, Erica T. Johnson, Allyson Davis, Iris Lo, Nicholas T. Bott, Thomas Kiely, Michelle C. Fenesy, Bruce L. Miller, Joel H. Kramer, Steven Finkbeiner
Journal: Journal of Clinical Investigation (2016)

Analogous behavioral assays are needed across animal models and human patients to improve translational research. Here, we examined the extent to which performance in the Morris water maze — the most frequently used behavioral assay of spatial learning and memory in rodents — translates to humans. We designed a virtual version of the assay for human subjects that includes the visible-target training, hidden-target learning, and probe trials that are typically administered in the mouse version. We compared transgenic mice that express human amyloid precursor protein (hAPP) and patients with mild cognitive impairment due to Alzheimer’s disease (MCI-AD) to evaluate the sensitivity of performance measures in detecting deficits. Patients performed normally during visible-target training, while hAPP mice showed procedural learning deficits. In hidden-target learning and probe trials, hAPP mice and MCI-AD patients showed similar deficits in learning and remembering the target location. In addition, we have provided recommendations for selecting performance measures and sample sizes to make these assays sensitive to learning and memory deficits in humans with MCI-AD and in mouse models. Together, our results demonstrate that with careful study design and analysis, the Morris maze is a sensitive assay for detecting AD-relevant impairments across species.
Survival on dialysis among chronic renal failure patients treated with a supplemented low-protein diet before dialysis.
Authors: J Coresh, M Walser, S Hill
Journal: Journal of the American Society of Nephrology (1995)

Concerns have been raised about the possibility of protein restriction resulting in malnutrition and poor subsequent survival on dialysis. However, no studies have examined patients treated with protein restriction to determine their subsequent survival on dialysis. This study prospectively monitored 67 patients with established chronic renal failure (mean initial serum creatinine of 4.3 mg/dL) who were treated with a very low-protein diet (0.3 g/kg per day) supplemented with either essential amino acids or a ketoacid-amino acid mixture and observed closely for clinical complications. Forty-four patients required dialysis. Once dialysis was started, dietary treatment was no longer prescribed. The cumulative mortality rate during the first 2 yr after starting dialysis was 7% (95% confidence interval, 0 to 16%). During this period, only two deaths occurred compared with 11.5 deaths expected on the basis of national mortality rates adjusted for age, sex, race, and cause of renal disease (P = 0.002). However, the protective effect was limited to the first 2 yr on dialysis. Thereafter, mortality rates increased, resulting in a total of 10 deaths during 96.4 person-years of follow-up, which was not significantly lower than the 14.9 deaths expected (P = 0.25). Extrapolation of sequential serum creatinine measurements made before dietary treatment suggests that the improved survival cannot be due to the early initiation of dialysis. Although the lack of an internal control group and data on dialysis lends uncertainty, the large difference in mortality rate between these patients and the nationwide experience indicates that protein restriction and close clinical monitoring predialysis does not worsen and may substantially improve survival during the first 2 yr on dialysis. These findings point out the importance of studying predialysis treatments as a means for lowering mortality on dialysis.
Importance of “default” intraoperative ventilator settings
Authors: Elizabeth L Whitlock
Journal: BMJ (2015)

This article is very useful for anesthesia providers, who are typically responsible for selecting intraoperative ventilator settings—an area that sometimes does not receive the attention it deserves.1 I noticed that women in the cohort were substantially less likely to receive lung protective ventilation. Such a sex imbalance has been found before in studies of acute lung injury ventilation.2 Could this be due to default ventilator settings …
Relative risk (RR) of second malignancies (SM) in patients treated by “risk” radiotherapy (RT) or “risk” RT plus chemotherapy (CT) in comparison with patients treated by CT ± “non risk RT” for Hodgkin's disease (HD)
Authors: K. Petrakova, H. Koukalová, R. Soumarová, M. Palácov', S. Blažkova, R. Vyzula
Journal: Journal of Clinical Oncology (2004)

6695 Background: Late effect, in particular second malignancies, kill more patients with HD then the disease itself. The most of published studies compare observed and expected numbers of cancers in the cohort with use of age-specific national incidence rate. Aim of our study was quantification of RR of SM in patients treated by “risk” RT ± CT (mantel field for breast cancer, and thyroid cancer, upper abdomen for stomach cancer, inverted Y or total nodal irradiation for colon cancer, inverted Y for gynecologic cancer) in comparison with patients treated by CT ± “non risk” RT. We wanted to assess if there is a reason to provide different follow up to this two different groups of patients. Methods: 851 patients (475 men and 376 women) with survival time after HD diagnosis >1 year were treated in MOÚ during 1967–1995. 337 patients were treated only by RT, 182 only by CT and 332 by RT+CT. Median age at RT was 33 years, median follow-up 11 years. 74 cases of SM developed in the cohort. To consider the exposure effect, rate ratio (RR), attributable risk (AR) and relative attributable risk (RAR) were computed for main sites of SM. The association between exposure and SM occurrence was tested by Fisher's test. Results: RR for the SM were as follows: breast cancer 5.39; lung cancer 0.77; colorectal cancer 10.3; stomach cancer 1.46; thyroid cancer 1.18; gynaecologic cancer 2.19. Rate ratio for NHL could not be established because of no case in the control group. Conclusion: The relative risk of solid tumors as second malignancies increased with the time of follow-up. Treatment by “risk RT” increases RR of breast cancer, colorectal cancer, gynecologic cancer and slightly thyroid cancer. Therefore this group of patient should be offered more intensive follow-up : yearly breast examination ( MG), yearly hemoccult ( colonoscopy every 3 years), yearly gynecologic examination according to the risk of SM. No significant financial relationships to disclose.
Abstract 68: Role of Substance P Signaling in the Pathogenesis of Murine Viral Myocarditis
Authors: Prema Robinson, Bahrom Firozgary, George Taffet, Corey Reynolds, Thuy Pham, Mitra Khumbatta, Gohar Firozgary
Journal: Circulation Research (2012)

Viral myocarditis is an important cause of heart failure in adolescents and young adults for which no specific treatment is currently available. Substance P (SP) is a neuropeptide and pain transmitter that activates RhoA, a small G-protein, shown to induce hypertrophy of neonatal rat ventricular myocytes. The current studies were performed to determine if SP signaling contributes to the pathogenesis of encephalomyocarditis virus (EMCV) infection, a well-established murine model of viral myocarditis. Aprepitant (1.2 mg/kg), a SP receptor antagonist, or fasudil (10mg/kg), a Rho A inhibitor, or saline control, was administered daily to mice orally by gavage 3 times for 3 days prior to intraperitoneal infection with 50 PFU of EMCV, and the mice monitored for 14 days. Pretreatment with aprepitant reduced mortality by 40% (25±7% vs. 65±7%), reduced heart-to-body weight ratio by 26% (0.0088±0.0001 vs. 0.0119±0.0001), reduced end systolic diameter (ESD) by 21% (3.0±0.2mm vs. 3.8±0.4mm), improved ejection fraction by 72% (57.2±4.7% vs. 33.2 ±9.3%), reduced chamber volume by 46% (34±5.0 μl vs. 62.7±30.8 μl), increased peak aortic flow velocity by 41% (87.0±24.7 vs. 61.7±20.1), and reduced cardiomyocyte diameter size by13% (11.0±0.1 μM vs. 12.7± 0.2 μM); p&lt;.05 for all, Student’s t-test). Pretreatment with fasudil reduced heart-to-body weight ratio by 18% (0.0097±0.0001 vs. 0.0119±0.0001) and reduced cardiomyocyte diameter size by 12% (11.14±0.51 μM vs. 12.7± 0.2 μM; p&lt;.05 for both), but did not significantly impact heart functional changes or mortality. These findings indicate that SP contributes to cardiac remodeling and dysfunction following ECMV infection and raises the possibility that inhibition of SP signaling may be of benefit in the treatment of patients with viral myocarditis.
P158Mangafodipir as an adjunct to percutaneous coronary intervention in patients with acute myocardial infarction
Authors: W El-Saadi, E Maret, R Andersson, W Puskar, M Ali, P Skogvard, A Koch, JE Karlsson
Journal: Cardiovascular Research (2014)

Background: Animal studies have shown that the superoxide dismutase mimetic mangafodipir (manganese dipyridoxyl diphosphate) with an active metabolite (manganese dipyridoxyl ethyldiamine) reduces reperfusion injuries and thereby infarct size in acute myocardial infarction (MI). In this small pilot trial we attempted to assess the feasibility of applying mangafodipir as a cardioprotective adjunct to Percutaneus Coronary Intervention (PCI). Methods: 20 patients with their first acute ST-elevation MI (STEMI) were assigned into two groups receiving an intravenous bolus dose of mangafodipir, 2 μmol per kilogram of body weight, or saline (control group) immediately before performing PCI. Infarct size was assessed by ST-segment changes, release of plasma biomarkers and cardiac magnetic resonance imaging (MRI) at routine follow up. Results: On cardiac MRI, the mangafodipir group revealed a smaller mean infarct size (26.2% scar vs 32.5%) and a higher mean ejection fraction (47.7 % vs 41.8 %), despite a significant prolonged ischemia time (205 min vs 144 min). ST-segment elevation also regressed more rapidly in the mangafodipir group, whereas there were no apparent differences in biomarker release. Conclusions: In this small local feasibility study with a skewed distribution of patients the administration of mangafodipir at the time of reperfusion was associated with a non-significant smaller scar tissue and better ejection fraction compared with placebo. The results give the impression that mangafodipir may reduce infarct size in STEMI patients, however this require confirmation in a larger clinical trial. No adverse effects of mangafodipir administration were detected.
Agalsidase-Beta Therapy for Advanced Fabry Disease
Authors: Maryam Banikazemi, Jan Bultas, Stephen Waldek, William R. Wilcox, Chester B. Whitley, Marie McDonald, Richard Finkel, Seymour Packman, Daniel G. Bichet, David G. Warnock, Robert J. Desnick
Journal: Annals of Internal Medicine (2020)

Fabry disease is a rare, X-linked lysosomal storage disorder that can cause early death from renal, cardiac, and cerebrovascular involvement. In this double-blind multicenter trial, 82 adults with ...