tbuckley/cabot-search huggingface dataset:
Reliability and Validity of Cardiovascular and Vasomotor Autonomic Function Tests
Authors: Mary S Hartwig, Sergio S Cardoso, Donna K Hathaway, A Osama Gaber
Journal: Diabetes Care (1994)

OBJECTIVE To determine the reliability and validity of autonomic function tests (AFTs) as clinical tools for diagnosing diabetic autonomic dysfunction. RESEARCH DESIGN AND METHODS Twenty-one healthy control subjects and 21 insulin-dependent diabetes mellitus (IDDM) patients (11 with no symptomatology and 10 with symptomatic diabetic autonomic neuropathy [DAN]) were matched for age, and administered three standard cardiovascular tests and two new vasomotor tests of autonomic function. Each of the cardiovascular tests (change in heart rate [Δbpm], Valsalva ratio [VR], change in systolic blood pressure [ΔsBP]) and vasomotor tests (total pulse amplitude [TPA] and percent vasoconstriction [%VC]) were repeated within 1 week. Infrared photoplethysmography measured sympathetic-mediated vasomotor function. Reliability was determined by intraclass correlation coefficients. Validity was determined by analysis of variance procedures to test for differences between known groups and by computing sensitivity, specificity, and positive and negative predictive values. RESULTS All AFTs were reliable, with %VC having highest reproducibility (r = 0.90). AFT scores were not different from time 1 to time 2. After controlling for age, two cardiovascular tests had significantly different values for control subjects and asymptomatic diabetic patients. AFTs, except ΔsBP, were significantly different between symptomatic diabetic patients and asymptomatic diabetic patients after controlling for age and duration of disease simultaneously. Sensitivity, specificity, and predictive values for %VC were comparable to the values for Δbpm and VR. TPA indexes were lower but clinically acceptable. CONCLUSIONS AFTs were found to be reliable and valid tests for detecting DAN. TPA and %VC are important because they measure an aspect of sympathetic function not assessed by standard cardiovascular AFTs, and they do not depend on the patient's cooperation or ability to exert effort.
High Frequency of p53/MDM2/p14ARF Pathway Abnormalities in Relapsed Neuroblastoma
Authors: Jane Carr-Wilkinson, Kieran O'Toole, Katrina M. Wood, Christine C. Challen, Angela G. Baker, Julian R. Board, Laura Evans, Michael Cole, Nai-Kong V. Cheung, Joachim Boos, Gabriele Köhler, Ivo Leuschner, Andrew D.J. Pearson, John Lunec, Deborah A. Tweddle
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Most neuroblastomas initially respond to therapy but many relapse with chemoresistant disease. p53 mutations are rare in diagnostic neuroblastomas, but we have previously reported inactivation of the p53/MDM2/p14ARF pathway in 9 of 17 (53%) neuroblastoma cell lines established at relapse. Hypothesis: Inactivation of the p53/MDM2/p14ARF pathway develops during treatment and contributes to neuroblastoma relapse. Methods: Eighty-four neuroblastomas were studied from 41 patients with relapsed neuroblastoma including 38 paired neuroblastomas at different stages of therapy. p53 mutations were detected by automated sequencing, p14ARF methylation and deletion by methylation-specific PCR and duplex PCR, respectively, and MDM2 amplification by fluorescent in situ hybridization. Results: Abnormalities in the p53 pathway were identified in 20 of 41 (49%) cases. Downstream defects due to inactivating missense p53 mutations were identified in 6 of 41 (15%) cases, 5 following chemotherapy and/or at relapse and 1 at diagnosis, postchemotherapy, and relapse. The presence of a p53 mutation was independently prognostic for overall survival (hazard ratio, 3.4; 95% confidence interval, 1.2–9.9; P = 0.02). Upstream defects were present in 35% of cases: MDM2 amplification in 3 cases, all at diagnosis and relapse and p14ARF inactivation in 12 of 41 (29%) cases: 3 had p14ARF methylation, 2 after chemotherapy, and 9 had homozygous deletions, 8 at diagnosis and relapse. Conclusions: These results show that a high proportion of neuroblastomas which relapse have an abnormality in the p53 pathway. The majority have upstream defects suggesting that agents which reactivate wild-type p53 would be beneficial, in contrast to those with downstream defects in which p53-independent therapies are indicated. Clin Cancer Res; 16(4); 1108–18
Concepts and theoretical unification
Authors: Eric Margolis, Stephen Laurence
Journal: Behavioral and Brain Sciences (2010)

Concepts are mental symbols that have semantic structure and processing structure. This approach (1) allows for different disciplines to converge on a common subject matter; (2) it promotes theoretical unification; and (3) it accommodates the varied processes that preoccupy Machery. It also avoids problems that go with his eliminativism, including the explanation of how fundamentally different types of concepts can be co-referential.
Plasticity of Human Adipose Lineage Cells Toward Endothelial Cells
Authors: Valérie Planat-Benard, Jean-Sébastien Silvestre, Béatrice Cousin, Mireille André, Maryse Nibbelink, Radia Tamarat, Michel Clergue, Carole Manneville, Corinne Saillan-Barreau, Micheline Duriez, Alain Tedgui, Bernard Levy, Luc Pénicaud, Louis Casteilla
Journal: Circulation (2004)

Background— Adipose tissue development and remodeling are closely associated with the growth of vascular network. We hypothesized that adipose tissue may contain progenitor cells with angiogenic potential and that therapy based on adipose tissue-derived progenitor cells administration may constitute a promising cell therapy in patients with ischemic disease. Methods and Results— In mice, cultured stromal-vascular fraction (SVF) cells from adipose tissue have a great proangiogenic potential, comparable to that of bone marrow mononuclear cells in the mouse ischemic hindlimb model. Similarly, cultured human SVF cells differentiate into endothelial cells, incorporate into vessels, and promote both postischemic neovascularization in nude mice and vessel-like structure formation in Matrigel plug. In vitro, these cells represent a homogeneous population of CD34- and CD13-positive cells, which can spontaneously express the endothelial cell markers CD31 and von Willebrand factor when cultured in semisolid medium. Interestingly, dedifferentiated mature human adipocytes have the potential to rapidly acquire the endothelial phenotype in vitro and to promote neovascularization in ischemic tissue and vessel-like structure formation in Matrigel plug, suggesting that cells of endothelial and adipocyte phenotypes may have a common precursor. Conclusions— This study demonstrates, for the first time, that adipocytes and endothelial cells have a common progenitor. Such adipose lineage cells participate in vascular-like structure formation in Matrigel plug and enhance the neovascularization reaction in ischemic tissue. These results also highlight the concept that adipose lineage cells represent a suitable new cell source for therapeutic angiogenesis in ischemic disease.
Intramural Myocardial Shear During the Cardiac Cycle
Authors: ERIC O. FEIGL, DONALD L. FRY
Journal: Circulation Research (1964)

Instantaneous and continuous shearing strains at various sites in the wall of the left ventricle were measured in 19 dogs with a specially designed transducer. Relatively large shearing strains occurred during the "isovolumic" and immediately prediastolic portions of systole. Shearing strain during diastole was small. Under control conditions the average shearing strain during the ejection period of systole was 0.0218 radians (1.25°) at a 6 mm depth into the myocardium. Intravenous infusion of norepinephrine (approximately 0.001 mg/kg per minute) increased myocardial shear from 0.0177 radians (1.01°) to 0.0274 radians (1.57°) during the ejection period. It is concluded that shearing strain in the myocardium during the ejection period is relatively small.
Association Between Bleeding Events and In-hospital Mortality After Percutaneous Coronary Intervention
Authors: Adnan K. Chhatriwalla, Amit P. Amin, Kevin F. Kennedy, John A. House, David J. Cohen, Sunil V. Rao, John C. Messenger, Steven P. Marso, for the National Cardiovascular Data Registry
Journal: JAMA (2013)

THE most common noncardiac complication of percutaneous coronary intervention (PCI).][3][4] Post-PCI bleeding is predictable, using tools such as the bleeding risk algorithm derived from the CathPCI Registry. 5[8][9][10] Nevertheless, determining the relationship between bleeding and post-PCI mortality is inherently challenging.2][13][14][15] It is also difficult to overcome the significant overlap between patient variables that predict
Increased Turnover of T Lymphocytes in HIV-1 Infection and Its Reduction by Antiretroviral Therapy
Authors: Hiroshi Mohri, Alan S. Perelson, Keith Tung, Ruy M. Ribeiro, Bharat Ramratnam, Martin Markowitz, Rhonda Kost, None Hurley, Leor Weinberger, Denise Cesar, Marc K. Hellerstein, David D. Ho
Journal: The Journal of Experimental Medicine (2001)

The mechanism of CD4(+) T cell depletion in human immunodeficiency virus (HIV)-1 infection remains controversial. Using deuterated glucose to label the DNA of proliferating cells in vivo, we studied T cell dynamics in four normal subjects and seven HIV-1-infected patients naive to antiretroviral drugs. The results were analyzed using a newly developed mathematical model to determine fractional rates of lymphocyte proliferation and death. In CD4(+) T cells, mean proliferation and death rates were elevated by 6.3- and 2.9-fold, respectively, in infected patients compared with normal controls. In CD8(+) T cells, the mean proliferation rate was 7.7-fold higher in HIV-1 infection, but the mean death rate was not significantly increased. Five of the infected patients underwent subsequent deuterated glucose labeling studies after initiating antiretroviral therapy. The lymphocyte proliferation and death rates in both CD4(+) and CD8(+) cell populations were substantially reduced by 5-11 weeks and nearly normal by one year. Taken together, these new findings strongly indicate that CD4(+) lymphocyte depletion seen in AIDS is primarily a consequence of increased cellular destruction, not decreased cellular production.
Year in review in Intensive Care Medicine, 2008: I. Brain injury and neurology, renal failure and endocrinology, metabolism and nutrition, sepsis, infections and pneumonia
Authors: Massimo Antonelli, Elie Azoulay, Marc Bonten, Jean Chastre, Giuseppe Citerio, Giorgio Conti, Daniel De Backer, François Lemaire, Herwig Gerlach, Johan Groeneveld, Goran Hedenstierna, Duncan Macrae, Jordi Mancebo, Salvatore M. Maggiore, Alexandre Mebazaa, Philipp Metnitz, Jerôme Pugin, Jan Wernerman, Haibo Zhang
Journal: Intensive Care Medicine (2008)
Inhibition of receptor-localized PI3K preserves cardiac β-adrenergic receptor function and ameliorates pressure overload heart failure
Authors: Jeffrey J. Nienaber, Hideo Tachibana, Sathyamangla V. Naga Prasad, Giovanni Esposito, Dianqing Wu, Lan Mao, Howard A. Rockman
Journal: Journal of Clinical Investigation (2003)

β-Adrenergic receptor (βAR) downregulation and desensitization are hallmarks of the failing heart. However, whether abnormalities in βAR function are mechanistically linked to the cause of heart failure is not known. We hypothesized that downregulation of cardiac βARs can be prevented through inhibition of PI3K activity within the receptor complex, because PI3K is necessary for βAR internalization. Here we show that in genetically modified mice, disrupting the recruitment of PI3K to agonist-activated βARs in vivo prevents receptor downregulation in response to chronic catecholamine administration and ameliorates the development of heart failure with pressure overload. Disruption of PI3K/βAR colocalization is required to preserve βAR signaling, since deletion of a single PI3K isoform (PI3Kγ knockout) is insufficient to prevent the recruitment of other PI3K isoforms and subsequent βAR downregulation with catecholamine stress. These data demonstrate a specific role for receptor-localized PI3K in the regulation of βAR turnover and show that abnormalities in βAR function are associated with the development of heart failure. Thus, a strategy that blocks the membrane translocation of PI3K and leads to the inhibition of βAR-localized PI3K activity represents a novel therapeutic approach to restore normal βAR signaling and preserve cardiac function in the pressure overloaded failing heart.
Plaque Rupture After Short Periods of Fat Feeding in the Apolipoprotein E–Knockout Mouse
Authors: Jason Johnson, Kevin Carson, Helen Williams, Sharada Karanam, Andrew Newby, Gianni Angelini, Sarah George, Christopher Jackson
Journal: Circulation (2005)

These studies examined the early time course of plaque development and destabilization in the brachiocephalic artery of the apolipoprotein E-knockout mouse, the effects of pravastatin thereon, and the effects of pravastatin on established unstable plaques.Male apolipoprotein E-knockout mice were fed a high-fat, cholesterol-enriched diet from the age of 8 weeks. Animals were euthanized at 1-week intervals between 4 and 9 weeks of fat feeding. Acutely ruptured plaques were observed in the brachiocephalic arteries of 3% of animals up to and including 7 weeks of fat feeding but in 62% of animals after 8 weeks, which suggests that there is a sharp increase in the number of plaque ruptures at 8 weeks. These acute plaque ruptures then appear to heal and form buried fibrous caps; after 9 weeks of fat feeding, mice had 1.05+/-0.15 buried fibrous caps at a single site in the brachiocephalic artery. Pravastatin (40 mg/kg of body weight per day for 9 weeks; resultant plasma concentration 16+/-4 nmol/L) had no effect on plasma cholesterol concentration in fat-fed apolipoprotein E-knockout mice but reduced the number of buried fibrous caps by 43% (P<0.0001). In longer-term experiments, the delay of pravastatin treatment until unstable plaques had developed reduced the incidence of acute plaque rupture by 36% (P<0.0001).Plaque rupture occurs at high frequency in the brachiocephalic arteries of male apolipoprotein E-knockout mice after 8 weeks of fat feeding. Pravastatin treatment inhibits early plaque rupture and is also effective when begun after unstable plaques have developed.
Adiponectin modulates inflammatory reactions via calreticulin receptor–dependent clearance of early apoptotic bodies
Authors: Yukihiro Takemura, Noriyuki Ouchi, Rei Shibata, Tamar Aprahamian, Michael T. Kirber, Ross S. Summer, Shinji Kihara, Kenneth Walsh
Journal: Journal of Clinical Investigation (2007)

Obesity and type 2 diabetes are associated with chronic inflammation. Adiponectin is an adipocyte-derived hormone with antidiabetic and antiinflammatory actions. Here, we demonstrate what we believe to be a previously undocumented activity of adiponectin, facilitating the uptake of early apoptotic cells by macrophages, an essential feature of immune system function. Adiponectin-deficient (APN-KO) mice were impaired in their ability to clear apoptotic thymocytes in response to dexamethasone treatment, and these animals displayed a reduced ability to clear early apoptotic cells that were injected into their intraperitoneal cavities. Conversely, adiponectin administration promoted the clearance of apoptotic cells by macrophages in both APN-KO and wild-type mice. Adiponectin overexpression also promoted apoptotic cell clearance and reduced features of autoimmunity in lpr mice whereas adiponectin deficiency in lpr mice led to a further reduction in apoptotic cell clearance, which was accompanied by exacerbated systemic inflammation. Adiponectin was capable of opsonizing apoptotic cells, and phagocytosis of cell corpses was mediated by the binding of adiponectin to calreticulin on the macrophage cell surface. We propose that adiponectin protects the organism from systemic inflammation by promoting the clearance of early apoptotic cells by macrophages through a receptor-dependent pathway involving calreticulin.
Selective uptake of intact parathyroid hormone by the liver: differences between hepatic and renal uptake.
Authors: K Martin, K Hruska, A Greenwalt, S Klahr, E Slatopolsky
Journal: Journal of Clinical Investigation (1976)

Hepatic and renal extraction of immunoreactive parathyroid hormone (i-PTH) was studied in awake dogs with explanted kidneys and chronic indwelling hepatic vein catheters. After a single injection of bovine PTH 1-84 (b-PTH 1-84), hepatic arteriovenous (A-V) differences for immunoreactive PTH (i-PTH) was 39% at 2 min after injection but decreased to 0% by 25 min, despite high levels of i-PTH in the arterial circulation. Gel filtration of arterila and hepatic venous samples obtained when hepatic A-V differences for i-PTH were demonstrable revealed hepatic uptake of the intact hormone and addition of a smaller COOH-terminal fragment, eluting just after the intact hormone, to the hepatic venous blood. Gel filtration of samples obtained 20-30 min after injection of b-PTH was demonstrable) revealed no detectable intact hormone in the circulation. Levels of COOH-terminal fragments of the hormone at the time were identical in arterial and hepatic venous samples. In additional experiemtns no hepatic A-V difference was observed after the injection of the synthetic bovine PTH 1-34 (syn b-PTH 1-34). By comparison there was a demonstrable A-V difference of 20% across the kidney for both intact PTH and COOH-terminal fragments that persisted until i-PTH disappeared from the circulation. The kidney also demonstrated an A-V difference of 22% after injection of syn b-PTH 1-34. These studies demonstrate selective extraction of intact PTH but not of its fragments by the liver. The kidney, on the other hand, extracted the intact hormone and both COOH and NH2 terminal fragments. The studies demonstrate that the kidney was the only organ of those examined that detectably removed the fragments of PTH from the circulation.
Recommendations for Biomarker Identification and Qualification in Clinical Proteomics
Authors: Harald Mischak, Günter Allmaier, Rolf Apweiler, Teresa Attwood, Marc Baumann, Ariela Benigni, Samuel E. Bennett, Rainer Bischoff, Erik Bongcam-Rudloff, Giovambattista Capasso, Joshua J. Coon, Patrick D’Haese, Anna F. Dominiczak, Mohammed Dakna, Hassan Dihazi, Jochen H. Ehrich, Patricia Fernandez-Llama, Danilo Fliser, Jorgen Frokiaer, Jerome Garin, Mark Girolami, William S. Hancock, Marion Haubitz, Denis Hochstrasser, Rury R. Holman, John P. A. Ioannidis, Joachim Jankowski, Bruce A. Julian, Jon B. Klein, Walter Kolch, Theo Luider, Ziad Massy, William B. Mattes, Franck Molina, Bernard Monsarrat, Jan Novak, Karlheinz Peter, Peter Rossing, Marta Sánchez-Carbayo, Joost P. Schanstra, O. John Semmes, Goce Spasovski, Dan Theodorescu, Visith Thongboonkerd, Raymond Vanholder, Timothy D. Veenstra, Eva Weissinger, Tadashi Yamamoto, Antonia Vlahou
Journal: Science Translational Medicine (2010)

Recommendations about structuring proteomic biomarker studies should increase the probability that such markers will be clinically useful.
George Malcolm Ross Smith
Authors: J. MacFie
Journal: BMJ (2008)

George Malcolm Ross Smith—George, as he was known to all—was born in Naini Tal in the foothills of the Himalayas in 1936. His father was a civil engineer with the Indian Service of Engineers. His mother was a dentist who had graduated from Edinburgh Dental School in the early 1930s.

George attended the Woodstock School in Mussoorie, India, between 1943 and 1944. In 1945 he went to Edinburgh Academy as a boarder, where he excelled academically and won a cup for the best junior piper. In 1954 he won the Palmer Anatomy Scholarship to St Mary’s, Paddington, and subsequently was awarded a first class honours BSc. He entered medical school at St Mary’s, Paddington, subsequently completing his clinical studies at the John Radcliffe, Oxford. He qualified in …
Diagnostic evaluation of classification criteria for rheumatoid arthritis and reactive arthritis in an early synovitis outpatient clinic
Authors: J L Hulsemann, H Zeidler
Journal: Annals of the Rheumatic Diseases (1999)

<h3>OBJECTIVE</h3> To evaluate the diagnostic performance of classification criteria for rheumatoid arthritis (RA) and reactive arthritis (ReA) in an early synovitis outpatient clinic. <h3>METHODS</h3> In a prospective two year survey consecutive patients with early synovitis of less than one year duration were documented using a standardised registry and were classified after an expert diagnosis. Of a total of 320 patients 39 (19%) were diagnosed as having RA, 24 (11%) patients had ReA, 117 (54%) patients did not have an unequivocal diagnosis, and were considered as undifferentiated arthritis. <h3>RESULTS</h3> The retrospective application of the revised 1987 ACR criteria for the classification of RA in this data set revealed a sensitivity of 90% and a specificity of 90%. The positive predictive value was 0.67, the negative predictive value 0.98. Similarly, the criteria for ReA of the French Society of Rheumatology (FSR) showed a sensitivity of 80% and a specificity of 90% with a positive predictive value of 0.55 and a negative predictive value of 0.97. Both criteria sets had a satisfying likelihood ratio of 9 and 10, respectively. <h3>CONCLUSION</h3> Both the 1987 ACR criteria for RA and the criteria of the FSR for ReA have a reasonable diagnostic validity in patients with early synovitis, including a large portion of undifferentiated arthritis.
Identifiability of DNA Data: The Need for Consistent Federal Policy
Authors: Amy L. McGuire
Journal: The American Journal of Bioethics (2008)

"Identifiability of DNA Data: The Need for Consistent Federal Policy." The American Journal of Bioethics, 8(10), pp. 75–76 Acknowledgments This publication was made possible by the Greenwall Foundation Faculty Scholars Program in Bioethics and NIH/NHGRI-ELSI R01 HG004333. Disclosures: Amy McGuire is a member of the NIH 1000 Genomes Project, Samples/ELSI Workgroup; International Human Microbiome Consortium, Data Release Working Group; NIH Electronic Medical Records in Genomics Network (eMERGE), ELSI Consent and Community Participation Workgroup; NIH Advisory Committee to the Director (ACD), Working Group on Participant and Data Protection (PDP) for the Genetic Association Information Network (GAIN); and the Personalized Health Care Working Group (PHC), American Health Information Community (AHIC), Office of the National Coordinator for Health Information Technology (ONC HIT), Secretary of the Department of Health and Human Services (DHHS). This commentary reflects the views of Dr. McGuire and may not reflect the views of the NIH, DHHS, or other members of these committees.