tbuckley/cabot-search huggingface dataset:
Is Cell Death a Critical End Point for Anticancer Therapies or Is Cytostasis Sufficient?
Authors: Olivier Rixe, Tito Fojo
Journal: Clinical Cancer Research (2007)

Abstract Since the discovery of conventional chemotherapy and the development of new target-based agents, the importance of cytostasis in anticancer activity has been debated. This review examines the relative importance of both cytostasis and cytotoxicity based on both preclinical data and clinical reports. Several limitations of our basic and clinical methods to evaluate cytostasis and cytotoxicity will be highlighted. Molecular mechanisms of cytostasis will be analyzed, including interference with the cell cycle as well as putative links with necrosis and autophagy. Finally, we will cite evidence that most older and newer compounds are both cytostatic and cytotoxic. The relative role of cytostasis and cytotoxicity on future drug screening and clinical development will be explored.
A Clone of Methicillin-Resistant<i>Staphylococcus aureus</i>among Professional Football Players
Authors: Sophia V. Kazakova, Jeffrey C. Hageman, Matthew Matava, Arjun Srinivasan, Larry Phelan, Bernard Garfinkel, Thomas Boo, Sigrid McAllister, Jim Anderson, Bette Jensen, Doug Dodson, David Lonsway, Linda K. McDougal, Matthew Arduino, Victoria J. Fraser, George Killgore, Fred C. Tenover, Sara Cody, Daniel B. Jernigan
Journal: New England Journal of Medicine (2005)

Methicillin-resistant Staphylococcus aureus (MRSA) is an emerging cause of infections outside of health care settings. We investigated an outbreak of abscesses due to MRSA among members of a professional football team and examined the transmission and microbiologic characteristics of the outbreak strain.We conducted a retrospective cohort study and nasal-swab survey of 84 St. Louis Rams football players and staff members. S. aureus recovered from wound, nasal, and environmental cultures was analyzed by means of pulsed-field gel electrophoresis (PFGE) and typing for resistance and toxin genes. MRSA from the team was compared with other community isolates and hospital isolates.During the 2003 football season, eight MRSA infections occurred among 5 of the 58 Rams players (9 percent); all of the infections developed at turf-abrasion sites. MRSA infection was significantly associated with the lineman or linebacker position and a higher body-mass index. No MRSA was found in nasal or environmental samples; however, methicillin-susceptible S. aureus was recovered from whirlpools and taping gel and from 35 of the 84 nasal swabs from players and staff members (42 percent). MRSA from a competing football team and from other community clusters and sporadic cases had PFGE patterns that were indistinguishable from those of the Rams' MRSA; all carried the gene for Panton-Valentine leukocidin and the gene complex for staphylococcal-cassette-chromosome mec type IVa resistance (clone USA300-0114).We describe a highly conserved, community-associated MRSA clone that caused abscesses among professional football players and that was indistinguishable from isolates from various other regions of the United States.
In Vivo Imaging of Proteolytic Activity in Atherosclerosis
Authors: Jiqiu Chen, Ching-Hsuan Tung, Umar Mahmood, Vasilis Ntziachristos, Robert Gyurko, Mark C. Fishman, Paul L. Huang, Ralph Weissleder
Journal: Circulation (2002)

Background — Atherosclerotic plaque rupture, the most important cause of acute cardiovascular incidents, has been strongly associated with vascular inflammation. On the basis of the hypothesis that the inflammatory response and proteolysis lead to plaque rupture, we have examined the role of cathepsin B as a model proteolytic enzyme. Methods and Results — Using western-type diet–fed apoE and apoE/endothelial NO synthase double knockout mice as models of atherosclerosis, we show (1) that cathepsin B is upregulated in atherosclerotic lesions characterized by high degrees of inflammation compared with normal aorta or silent lesions,(2) that intravenously injectable novel cathepsin B imaging beacons are highly activated within active atherosclerotic lesions and colocalize with cathepsin B immunoreactivity, and(3) that cathepsin B activity in atherosclerotic lesions can be imaged in whole animals by using a novel near-infrared tomographic imaging system. Conclusions — These studies indicate that cathepsin B, and potentially other proteases, may serve as a biomarker for vulnerable plaques when probed with beacons. The tomographic in vivo imaging method as well as catheter-based optical sensing methods could be readily adapted to screening and potentially to the molecular profiling of a number of proteases in vulnerable plaque in vivo.
The Circulatory Effects of Intravenous Phentolamine in Man
Authors: S. H. TAYLOR, G. R. SUTHERLAND, G. J. MACKENZIE, H. P. STAUNTON, K. W. DONALD
Journal: Circulation (1965)

Circulatory observations have been made on six normal subjects and six hypertensive patients before and after the acute intravenous injection of 5 mg. of phentolamine. The drug caused a prompt reduction in systemic vascular resistance which resulted in a rapid fall in systemic blood pressure in spite of an increase in heart rate and cardiac output. Evidence is presented that the predominant vascular activity of the drug is to cause a direct relaxation of vascular smooth muscle, an effect far more potent than its antagonism of circulating catecholamines or its very much weaker sympathetic-blocking action. This direct depressor effect on vascular smooth muscle unaccompanied by any but slight sympathetic blocking activities endows the drug with theoretically ideal antihypertensive properties. Phentolamine caused a transient but significant reduction in oxygen uptake in the majority of individuals. It is suggested that this may be due to a direct inhibition of cellular oxidative mechanisms. An appraisal of the circulatory activities of the drug with particular regard to its use as a diagnostic test for pheochromocytoma leads to serious doubts, not only with regard to the precision with which the results of such tests can be interpreted, but also to the validity of the use of the drug as a reliable screening test for excessive circulating catecholamines.
Update on Cardiovascular Outcomes at 30 Years of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study
Authors: John M. Lachin, Trevor J. Orchard, David M. Nathan
Journal: Diabetes Care (2013)

OBJECTIVE To describe the beneficial long-term effects of an average of 6.5 years of intensive diabetes therapy (INT) in type 1 diabetes on measures of atherosclerosis, cardiac structure and function, and clinical cardiovascular events observed in the Diabetes Control and Complications Trial (DCCT) and the Epidemiology of Diabetes Interventions and Complications (EDIC) study. RESEARCH DESIGN AND METHODS The DCCT was a randomized clinical trial of 1,441 participants assigned to receive INT or conventional therapy (CON). It was conducted between 1983-1993 with an average follow-up of 6.5 years. EDIC (1994-present) is an observational follow-up of the DCCT cohort. Cardiovascular events have been recorded throughout. During EDIC common carotid intima-media thickness (IMT) was measured with ultrasound, coronary artery calcification with computed tomography, and cardiac structure and function with cardiac magnetic resonance imaging. RESULTS DCCT INT and lower levels of HbA1c during DCCT/EDIC were associated with thinner carotid IMT, less coronary calcification, and a lower incidence of clinical cardiovascular events including myocardial infarction, stroke, and cardiac death. While there were no significant differences in cardiac structure and function between the former INT and CON groups, they were significantly associated with higher HbA1c during DCCT/EDIC. CONCLUSIONS DCCT INT and the attendant 6.5 years of lower HbA1c had long-term salutary effects on the development and progression of atherosclerosis and cardiovascular disease during the subsequent follow-up during EDIC.
Preoperative [18F] FDG–PET after chemotherapy in locally advanced breast cancer: prognostic value as compared with histopathology
Authors: J. Emmering, N.C. Krak, J.J.M. Van der Hoeven, M.D. Spreeuwenberg, J.W.R. Twisk, S. Meijer, H.M. Pinedo, O.S. Hoekstra
Journal: Annals of Oncology (2008)
Acid-sensing ion channels: potential therapeutic targets for neurologic diseases
Authors: Sha Liu, Xiao-Yu Cheng, Fen Wang, Chun-Feng Liu
Journal: Translational Neurodegeneration (2015)

Maintaining the physiological pH of interstitial fluid is crucial for normal cellular functions. In disease states, tissue acidosis is a common pathologic change causing abnormal activation of acid-sensing ion channels (ASICs), which according to cumulative evidence, significantly contributes to inflammation, mitochondrial dysfunction, and other pathologic mechanisms (i.e., pain, stroke, and psychiatric conditions). Thus, it has become increasingly clear that ASICs are critical in the progression of neurologic diseases. This review is focused on the importance of ASICs as potential therapeutic targets in combating neurologic diseases.
A Comprehensive Classification and Evolutionary Analysis of Plant Homeobox Genes
Authors: K. Mukherjee, L. Brocchieri, T. R. Burglin
Journal: Molecular Biology and Evolution (2009)

The full complement of homeobox transcription factor sequences, including genes and pseudogenes, was determined from the analysis of 10 complete genomes from flowering plants, moss, Selaginella, unicellular green algae, and red algae. Our exhaustive genome-wide searches resulted in the discovery in each class of a greater number of homeobox genes than previously reported. All homeobox genes can be unambiguously classified by sequence evolutionary analysis into 14 distinct classes also characterized by conserved intron–exon structure and by unique codomain architectures. We identified many new genes belonging to previously defined classes (HD-ZIP I to IV, BEL, KNOX, PLINC, WOX). Other newly identified genes allowed us to characterize PHD, DDT, NDX, and LD genes as members of four new evolutionary classes and to define two additional classes, which we named SAWADEE and PINTOX. Our comprehensive analysis allowed us to identify several newly characterized conserved motifs, including novel zinc finger motifs in SAWADEE and DDT. Members of the BEL and KNOX classes were found in Chlorobionta (green plants) and in Rhodophyta. We found representatives of the DDT, WOX, and PINTOX classes only in green plants, including unicellular green algae, moss, and vascular plants. All 14 homeobox gene classes were represented in flowering plants, Selaginella, and moss, suggesting that they had already differentiated in the last common ancestor of moss and vascular plants.
Definition, evaluation, and classification of renal osteodystrophy: A position statement from Kidney Disease: Improving Global Outcomes (KDIGO)
Authors: S. Moe, T. Drüeke, J. Cunningham, W. Goodman, K. Martin, K. Olgaard, S. Ott, S. Sprague, N. Lameire, G. Eknoyan
Journal: Kidney International (2006)
BEREAVEMENT AND LATE-LIFE DEPRESSION: Grief and Its Complications in the Elderly
Authors: Andrew Rosenzweig, MD, MPH, Holly Prigerson, PhD, Mark D. Miller, MD, Charles F. Reynolds III, MD
Journal: Annual Review of Medicine (1997)

▪ Abstract Spousal bereavement is a common event in later life and, not infrequently, an important cause of psychiatric and medical morbidity. Depression (along with suicide), anxiety, substance abuse, and symptoms of “complicated” grief are among the more important psychiatric sequelae of spousal bereavement. They may represent, in part, forms of abnormal reaction to the stress of loss and the challenges of adaption to becoming widowed. This paper summarizes current knowledge about the clinical phenomenology of the psychiatric sequelae to late-life attachment bereavment, some of the hypothesized antecedents of abnormal stress response to bereavement, psychobiologic correlates of bereavement-related depression, and the long-term course (including preliminary evidence on response to treatment with psychotherapy and antidepressant medication).
Hypoxic challenge flight assessments in patients with severe chest wall deformity or neuromuscular disease at risk for nocturnal hypoventilation
Authors: N Mestry, M Thirumaran, J M Tuggey, W Macdonald, M W Elliott
Journal: Thorax (2009)

The British Thoracic Society (BTS) recommendations for patients with respiratory disease planning air travel suggest that an oxygen saturation (SaO(2)) >95% precludes the need for any further assessment of the need for supplemental oxygen during flight. A hypoxic challenge test (HCT) is recommended for patients with a resting SaO(2) between 92% and 95% with an additional risk factor, including kyphoscoliosis (KS) or neuromuscular disease (NMD). However, this recommendation was based on very few data.HCTs were performed on 19 adult patients with KS and/or NMD (age 22-73 years, forced expiratory volume in 1 s (FEV(1)) 0.76, forced vital capacity (FVC) 0.92, SaO(2) 95%, partial pressure of arterial CO(2) (PaCO(2)) 5.7 kPa) who were at risk for nocturnal hypoventilation. 15 were home ventilator users. Arterial blood gas measurements were made before and at the end of the hypoxic challenge.The results of HCTs show that the majority (15 of 19) of this cohort of patients met the criteria suggested by the BTS Standards of Care Committee for in-flight oxygen regardless of baseline SaO(2).This finding suggests that all patients with severe extrapulmonary restrictive lung disease should undergo assessment with HCT prior to air travel. The study confirms that even patients with a resting saturation of >95% can desaturate significantly during hypoxic challenge. This study does not address the question of whether desaturation at altitude has any adverse consequences for patients. A decision as to whether it is safe for a patient to fly should be made by an experienced clinician and based on a number of factors, which should include previous travel experience, the patient's overall condition and the results of an HCT.
Costimulating aberrant T cell responses by B7-H1 autoantibodies in rheumatoid arthritis
Authors: Haidong Dong, Scott E. Strome, Eric L. Matteson, Kevin G. Moder, Dallas B. Flies, Gefeng Zhu, Hideto Tamura, Colin L.W. Driscoll, Lieping Chen
Journal: Journal of Clinical Investigation (2003)

A pathogenic hallmark of rheumatoid arthritis (RA) is persistent activation of self-reactive CD4(+) T cells. The cause of this aberrant activity remains elusive. We report here detection of autoantibodies against B7-H1, a recently described member of the B7 family, in 29% of patients with RA versus 4% of healthy donors. High-level expression of cell surface B7-H1 are found on activated human CD4(+), CD8(+), and CD45RO(+) T cells. Immobilized autoantibodies to B7-H1 are capable of costimulating the proliferation of CD4(+) T cells in vitro, and the presence of these autoantibodies correlates with active disease status. Using immobilized B7-H1 mAb's and programmed death 1Ig, we demonstrate that engagement of B7-H1 on CD4(+) T cells costimulates proliferation and secretion of IL-10, and subsequently leads to programmed cell death, accompanied with upregulated expression of TNF-related apoptosis-inducing ligand and activation of caspase-3. Taken together with our previous findings, these data indicate a bidirectional signaling role of B7-H1 in T cell costimulation and apoptosis and implicate B7-H1 autoantibodies as contributing to the progression of RA by inducing aberrant T cell responses.
Hydrogen Sulfide and Cell Signaling
Authors: Ling Li, Peter Rose, Philip K. Moore
Journal: The Annual Review of Pharmacology and Toxicology (2011)

Hydrogen sulfide (H₂S) is a gaseous mediator synthesized from cysteine by cystathionine γ lyase (CSE) and other naturally occurring enzymes. Pharmacological experiments using H₂S donors and genetic experiments using CSE knockout mice suggest important roles for this vasodilator gas in the regulation of blood vessel caliber, cardiac response to ischemia/reperfusion injury, and inflammation. That H₂S inhibits cytochrome c oxidase and reduces cell energy production has been known for many decades, but more recently, a number of additional pharmacological targets for this gas have been identified. H₂S activates K(ATP) and transient receptor potential (TRP) channels but usually inhibits big conductance Ca²(+)-sensitive K(+) (BK(Ca)) channels, T-type calcium channels, and M-type calcium channels. H₂S may inhibit or activate NF-κB nuclear translocation while affecting the activity of numerous kinases including p38 mitogen-activated protein kinase (p38 MAPK), extracellular signal-regulated kinase (ERK), and Akt. These disparate effects may be secondary to the well-known reducing activity of H₂S and/or its ability to promote sulfhydration of protein cysteine moieties within the cell.
A Reversible Jump Method for Bayesian Phylogenetic Inference with a Nonhomogeneous Substitution Model
Authors: V. Gowri-Shankar, M. Rattray
Journal: Molecular Biology and Evolution (2007)

Nonhomogeneous substitution models have been introduced for phylogenetic inference when the substitution process is nonstationary, for example, when sequence composition differs between lineages. Existing models can have many parameters, and it is then difficult and computationally expensive to learn the parameters and to select the optimal model complexity. We extend an existing nonhomogeneous substitution model by introducing a reversible jump Markov chain Monte Carlo method for efficient Bayesian inference of the model order along with other phylogenetic parameters of interest. We also introduce a new hierarchical prior which leads to more reasonable results when only a small number of lineages share a particular substitution process. The method is implemented in the PHASE software, which includes specialized substitution models for RNA genes with conserved secondary structure. We apply an RNA-specific nonhomogeneous model to a structure-based alignment of rRNA sequences spanning the entire tree of life. A previous study of the same genes from a similar set of species found robust evidence for a mesophilic last universal common ancestor (LUCA) by inference of the G+C composition at the root of the tree. In the present study, we find that the helical GC composition at the root is strongly dependent on the root position. With a bacterial rooting, we find that there is no longer strong support for either a mesophile or a thermophile LUCA, although a hyperthermophile LUCA remains unlikely. We discuss reasons why results using only RNA helices may differ from results using all aligned sites when applying nonhomogeneous models to RNA genes.
Optimal diagnosis in acute myocardial infarction. A cost-effectiveness study.
Authors: P Grande, C Christiansen, A Pedersen, M S Christensen
Journal: Circulation (1980)

The predictive value of a diagnostic test estimates the likelihood for presence or absence of disease in a patient with a positive or negative test result (PVpos or PVneg). We evaluated the predictive values of serum activities of the heart-specific creatine kinase isoenzyme MB (CK-MB), aspartate aminotransferase, lactate dehydrogenase, CK, and ECG in 401 consecutively admitted patients suspected of acute myocardial infarction (AMI). The study showed that CK-MB (PVpos = 0.98, PVneg = 1.00) was better than the other enzymes (single as well as serial) and ECG, evaluated both separately and in combinations. In all cases of AMI CK-MB was positive within 17 hours from admission. Replacement of the standard enzymes with CK-MB provides a faster and safer diagnosis of AMI and reduces hospitalization time considerably for patients without AMI.
Validation and Calibration of a Model Used to Reconstruct Historical Exposureto Polycyclic Aromatic Hydrocarbons for Use in Epidemiologic Studies
Authors: Jan Beyea, Maureen Hatch, Steven D. Stellman, Regina M. Santella, Susan L. Teitelbaum, Bogdan Prokopczyk, David Camann, Marilie D. Gammon
Journal: Environmental Health Perspectives (2006)

ObjectivesWe previously developed a historical reconstruction model to estimate exposure to airborne polycyclic aromatic hydrocarbons (PAHs) from traffic back to 1960 for use in case–control studies of breast cancer risk. Here we report the results of four exercises to validate and calibrate the model.MethodsModel predictions of benzo[a]pyrene (BaP) concentration in soil and carpet dust were tested against measurements collected at subjects' homes at interview. In addition, predictions of air intake of BaP were compared with blood PAH–DNA adducts. These same soil, carpet, and blood measurements were used for model optimization. In a separate test of the meteorological dispersion part of the model, predictions of hourly concentrations of carbon monoxide from traffic were compared with data collected at a U.S. Environmental Protection Agency monitoring station.ResultsThe data for soil, PAH–DNA adducts, and carbon monoxide concentrations were all consistent with model predictions. The carpet dust data were inconsistent, suggesting possible spatial confounding with PAH-containing contamination tracked in from outdoors or unmodeled cooking sources. BaP was found proportional to other PAHs in our soil and dust data, making it reasonable to use BaP historical data as a surrogate for other PAHs. Road intersections contributed 40–80% of both total emissions and average exposures, suggesting that the repertoire of simple markers of exposure, such as traffic counts and/or distance to nearest road, needs to be expanded to include distance to nearest intersection.
Strength and flexibility in gymnasts before and after menarche.
Authors: K. M. Haywood
Journal: British Journal of Sports Medicine (1980)

simple anthropometric measures, flexibility, and strength performance tests were conducted on 30 young gymnasts and repeated one year later. During the intervening year, 13 gymnasts, average age 14.5 at the second year, reached menarche, while the remaining 17, average age 14.1 years, did not. Multivariate analyses of covariance were calculated to test for differences between the groups at Year 2, using the Year 1 scores as covariates. No significant differences between the groups were found. Tendencies to linearity of physique and late maturation, noted in the literature among very skilled gymnasts, seemed to be confirmed among this group of local competitors.
Myocardial contractile reserve and indices of contractility
Authors: A. H. MORENO, E. A. BONFILS-ROBERTS, J. A. STEEN, R. V. REDDY
Journal: Cardiovascular Research (1976)

A close examination of several indices of contractility derived from the ventricular pressure was made using an isolated canine heart preparation. The responses to single intracoronary injections of calcium chloride as well as to increasing doses of this agent were tested. From the latter, calcium dose-transient-response curves intended to reveal the extent of myocardial/contractile reserve were constructed. Indices included various extrapolations to maximal velocity of shortening at zero load, maximal value of the quotient of the first derivative and ventricular pressure, time-tension index, energy averaged power density, and power averaged rate of generation of power density. Indices were compared over the same cardiac cycles before and after administration of calcium. Most indices showed increments from 10 to 20%, except power density functions which had increments of 40 and 70%, respectively. Calcium dose-response curves were linear for most indices, but, again, the power density functions showed the steepest slopes. After severe coronary occlusion, the curves for most indices flattened and lost linearity and, presumably, this was due to loss of myocardial contractile reserve. For milder occlusions, only the power density functions showed significant flattening. The conceptual framework of a contractile myocardial reserve appears supported by these results.