tbuckley/cabot-search huggingface dataset:
Serum skeletal troponin I in inflammatory muscle disease: relation to creatine kinase, CKMB and cardiac troponin I
Authors: P D W KIELY
Journal: Annals of the Rheumatic Diseases (2000)

The measurement of serum creatine kinase (CK), which is used widely in the diagnosis and management of polymyositis and dermatomyositis lacks both sensitivity1-7 and specificity,7-9 leading to potential problems if the serum total CK concentration is interpreted as a direct measure of muscle disease activity. Furthermore, in those cases where the total CK is raised reliance on an analysis of the CK isoforms is an unreliable means of determining the presence of myocardial involvement. This is because in chronic inflammatory muscle diseases, regenerating striated muscle contains up to 50% of the CKMB isoform.6 10 11This often results in an increase in the CKMB/total CK ratio by more than the 3% threshold commonly used to imply myocardial damage.6 8 9 11 12 

The need for more sensitive and specific serum markers of striated and myocardial inflammation has led us to a study of the troponins. Skeletal troponin I (sTnI) has been found to correlate with total CK in exercising athletes13 14 and to be increased in a small series of patients with polymyositis13 but has not previously been studied in detail in relation to total CK in inflammatory muscle disease. Cardiac troponin I (cTnI) is a highly specific marker of myocardial injury15 in contrast with CKMB, which is expressed both in myocardial and striated muscle. The behaviour of cTnI has not been reported in the inflammatory muscle diseases.

We report the relation between serum sTnI and total CK in patients with polymyositis and dermatomyositis. In the …
Workgroup I: criteria for screening. UICC International Workshop on Facilitating Screening for Colorectal Cancer, Oslo, Norway (29 and 30 June 2002)
Authors: P. Boyle, H. Vainio, R. Smith, R. Benamouzig, W.C. Lee, N. Segnan, K. Takima, Y. Tsubono
Journal: Annals of Oncology (2004)
Improved Blood Pressure Control Associated With a Large-Scale Hypertension Program
Authors: Marc G. Jaffe, Grace A. Lee, Joseph D. Young, Stephen Sidney, Alan S. Go
Journal: JAMA (2013)

IMPORTANCE Hypertension control for large populations remains a major challenge.OBJECTIVE To describe a large-scale hypertension program in Northern California and to compare rates of hypertension control in that program with statewide and national estimates. DESIGN, SETTING, AND PATIENTSThe Kaiser Permanente Northern California (KPNC) hypertension program included a multifaceted approach to blood pressure control.Patients identified as having hypertension within an integrated health care delivery system in Northern California from 2001-2009 were included.The comparison group comprised insured patients in California between 2006-2009 who were included in the Healthcare Effectiveness Data and Information Set (HEDIS) commercial measurement by California health insurance plans participating in the National Committee for Quality Assurance (NCQA) quality measure reporting process.A secondary comparison group was included to obtain the reported national mean NCQA HEDIS commercial rates of hypertension control between 2001-2009 from health plans that participated in the NCQA HEDIS quality measure reporting process. MAIN OUTCOMES AND MEASURES Hypertension control as defined by NCQA HEDIS. RESULTSThe KPNC hypertension registry included 349 937 patients when established in 2001 and increased to 652 763 by 2009.The NCQA HEDIS commercial measurement for hypertension control within KPNC increased from 43.6% (95% CI, 39.4%-48.6%) to 80.4% (95% CI, 75.6%-84.4%)during the study period (P < .001for trend).In contrast, the national mean NCQA HEDIS commercial measurement increased from 55.4% to 64.1%.California mean NCQA HEDIS commercial rates of hypertension were similar to those reported nationally from 2006-2009 (63.4% to 69.4%).CONCLUSIONS AND RELEVANCE Among adults diagnosed with hypertension, implementation of a large-scale hypertension program was associated with a significant increase in hypertension control compared with state and national control rates.Key elements of the program included a comprehensive hypertension registry, development and sharing of performance metrics, evidence-based guidelines, medical assistant visits for blood pressure measurement, and single-pill combination pharmacotherapy.
Direct evidence for systemic fibrinogenolysis in patients with acquired α<sub>2</sub>‐plasmin inhibitor deficiency
Authors: Kenji Okajima, Isao Kohno, Gilbu Soe, Hiroaki Okabe, Kiyoshi Takatsuki, Bernd R. Binder
Journal: American Journal of Hematology (1994)

To examine whether or not acquired alpha 2-plasmin inhibitor deficiency is associated with systemic fibrinogenolysis, we analyzed the fibrin and fibrinogen degradation products in eight patients with this condition in various disease states. The underlying disease was gastric cancer in three patients, metastatic prostatic cancer in two, acute promyelocytic leukemia in two, and abdominal aortic aneurysm in one patient. In all eight patients, the alpha 2-plasmin inhibitor level was reduced to less than 50% of normal, and plasmin-alpha 2-plasmin inhibitor complex levels were increased. Immunoblotting of serum using an antifibrinogen antibody detected a 250 kDa protein (corresponding to fragments X or DY) in all eight patients. Fragment Y and D monomer were detected in seven of the eight patients, indicating the occurrence of systemic fibrinogenolysis. However, they were not detected in one patient with metastatic prostatic cancer. To determine whether or not fibrinogen degradation was also occurring in the patient without fragment Y, we characterized the 250 kDa protein in all eight patients. The protein was found to be fragment X in the metastatic prostatic cancer patient without fragment Y, while it was fragment DY in the other seven patients. Thus, systemic fibrinogenolysis was present in all eight patients. In the two patients with metastatic prostatic cancer, the level of alpha 2-plasmin inhibitor gradually increased with the reduction of tumor size by treatment. Fragment X, fragment Y, and D monomer were not detected when the alpha 2-plasmin inhibitor level exceeded 60% of normal in both patients. In the other six patients fragment Y and D monomer also disappeared when the alpha 2-plasmin inhibitor level exceeded 60% of normal. These findings suggest that systemic fibrinogenolysis only occurs when the plasma levels of alpha 2-plasmin inhibitor falls below 60% of normal due to activation of the fibrinolytic system by various pathological conditions.
Pathogenesis of Langerhans Cell Histiocytosis
Authors: Gayane Badalian-Very, Jo-Anne Vergilio, Mark Fleming, Barrett J. Rollins
Journal: Annual Review of Pathology Mechanisms of Disease (2012)

Langerhans cell histiocytosis (LCH) combines in one nosological category a group of diseases that have widely disparate clinical manifestations but are all characterized by accumulation of proliferating cells with surface markers and ultrastructural features similar to cutaneous Langerhans cells (LCs). Despite this unified nosology, important questions about LCH remain unanswered. First, despite having phenotypic features of LCs, LCH cell gene-expression patterns differ from those in LCs. Although this observation suggests that LCH may arise from an earlier precursor, it is not necessarily inconsistent with the hypothesis that LCs are the cell of origin for LCH. Second, LCH's prominent inflammatory component and occasional benign clinical course suggest that LCH may not be a neoplasm. However, the demonstration that LCH cells are clonal, along with the recent discovery of activating BRAF mutations in LCH cells, strongly suggests that LCH is a neoplastic disease. These new observations point the way to rationally targeted therapies.
A HISTOLOGICAL STUDY OF INFECTIOUS CANINE HEPATITIS BY MEANS OF FLUORESCENT ANTIBODY
Authors: David L. Coffin, Albert H. Coons, Victor J. Cabasso
Journal: The Journal of Experimental Medicine (1953)

A study of experimental infectious canine hepatitis in dogs by means of specific fluorescent antibody indicates that the intranuclear inclusions of this disease contain high concentrations of viral antigen. The increase in virus in the nuclei, as indicated by the accumulation of specific antigenic material, begins on the nuclear membrane and spreads from there to the interior of the nucleus, with the gradual formation of larger granules. Subsequently there appear the homogeneous inclusion bodies characteristic of this infection.
Antitumor and Antiangiogenic Activities of BMS-690514, an Inhibitor of Human EGF and VEGF Receptor Kinase Families
Authors: Tai W. Wong, Francis Y. Lee, Stuart Emanuel, Craig Fairchild, Joseph Fargnoli, Brian Fink, Ashvinikumar Gavai, Amy Hammell, Benjamin Henley, Christine Hilt, John T. Hunt, Bala Krishnan, Daniel Kukral, Anne Lewin, Harold Malone, Derek Norris, Simone Oppenheimer, Gregory Vite, Chiang Yu
Journal: Clinical Cancer Research (2011)

The extensive involvement of the HER kinases in epithelial cancer suggests that kinase inhibitors targeting this receptor family have the potential for broad spectrum antitumor activity. BMS-690514 potently inhibits all three HER kinases, and the VEGF receptor kinases. This report summarizes data from biochemical and cellular pharmacology studies, as well as antitumor activity of BMS-690514.The potency and selectivity of BMS-690514 was evaluated by using an extensive array of enzymatic and binding assays, as well as cellular assays that measure proliferation and receptor signaling. Antitumor activity was evaluated by using multiple xenograft models that depend on HER kinase signaling. The antiangiogenic properties of BMS-690514 were assessed in a matrigel plug assay, and effect on tumor blood flow was measured by dynamic contrast-enhanced MRI.BMS-690514 is a potent and selective inhibitor of epidermal growth factor receptor (EGFR), HER2, and HER4, as well as the VEGF receptor kinases. It inhibits proliferation of tumor cells with potency that correlates with inhibition of receptor signaling, and induces apoptosis in lung tumor cells that have an activating mutation in EGFR. Antitumor activity was observed with BMS-690514 at multiple doses that are well tolerated in mice. There was evidence of suppression of tumor angiogenesis and endothelial function by BMS-690514, which may contribute to its efficacy.By combining inhibition of two receptor kinase families, BMS-690524 is a novel targeted agent that disrupts signaling in the tumor and its vasculature.
Dose-dense regimen of temozolomide given every other week in patients with primary central nervous system tumors
Authors: K. Vera, L. Djafari, S. Faivre, J.-S. Guillamo, K. Djazouli, M. Osorio, F. Parker, C. Cioloca, B. Abdulkarim, J.-P. Armand, E. Raymond
Journal: Annals of Oncology (2003)
Retinoic Acid Signaling Coordinates Macrophage-Dependent Injury and Repair after AKI
Authors: Takuto Chiba, Nataliya I. Skrypnyk, Lauren Brilli Skvarca, Radostin Penchev, Ke Xin Zhang, Elizabeth R. Rochon, Jessica L. Fall, Paisit Paueksakon, Haichun Yang, Catherine E. Alford, Beth L. Roman, Ming-Zhi Zhang, Raymond Harris, Neil A. Hukriede, Mark P. de Caestecker
Journal: Journal of the American Society of Nephrology (2015)

Retinoic acid (RA) has been used therapeutically to reduce injury and fibrosis in models of AKI, but little is known about the regulation of this pathway and what role it has in regulating injury and repair after AKI. In these studies, we show that RA signaling is activated in mouse and zebrafish models of AKI, and that these responses limit the extent of injury and promote normal repair. These effects were mediated through a novel mechanism by which RA signaling coordinated the dynamic equilibrium of inflammatory M1 spectrum versus alternatively activated M2 spectrum macrophages. Our data suggest that locally synthesized RA represses proinflammatory macrophages, thereby reducing macrophage-dependent injury post-AKI, and activates RA signaling in injured tubular epithelium, which in turn promotes alternatively activated M2 spectrum macrophages. Because RA signaling has an essential role in kidney development but is repressed in the adult, these findings provide evidence of an embryonic signaling pathway that is reactivated after AKI and involved in reducing injury and enhancing repair.
Stratification of Pediatric Heart Failure on the Basis of Neurohormonal and Cardiac Autonomic Nervous Activities in Patients With Congenital Heart Disease
Authors: Hideo Ohuchi, Hisashi Takasugi, Hiroyuki Ohashi, Yoko Okada, Osamu Yamada, Yasuo Ono, Toshikatsu Yagihara, Shigeyuki Echigo
Journal: Circulation (2003)

Background— Stratification of pediatric patients with congenital heart disease (CHD) has been based on their hemodynamics and/or functional capacity. Our purpose was to compare cardiac autonomic nervous activity (CANA) and neurohormonal activities (NHA) with postoperative status in stable CHD patients with biventricular physiology. Methods and Results— We divided 379 subjects (297 CHD patients, 28 dilated cardiomyopathy patient, and 54 control subjects) into 4 subgroups according to New York Heart Association (NYHA) class (1.3±0.7) and measured various CANA and NHA indices. Stepwise decreases in baroreflex sensitivity (BRS), heart rate variability (HRV), adrenergic imaging, and vital capacity (VC) were observed in proportion to functional capacity in normal to NYHA II patients ( P &lt;0.001). However, there were no differences in these indices between NYHA II and III+IV groups, whereas a stepwise proportional increase in NHA indices was observed in these groups ( P &lt;0.001). Natriuretic peptides differentiated all NYHA classes. BRS, HRV, and VC were greater in the adult patients than in the child patients ( P &lt;0.05 to 0.01), although the functional class in adult patients was lower. Cardiac surgeries resulted in low BRS and VC, and the VC reduction independently determined a small HRV. Even if functional class and ejection fraction were comparable, CANA and brain natriuretic peptide were lower in CHD patients than in dilated cardiomyopathy patients ( P &lt;0.05 to 0.001). Conclusions— CANA and NHA indices are useful to stratify mild and severe heart failure in stable postoperative CHD patients, respectively. However, careful attention should be paid to age- and surgery-related influences on these indices.
Effect of an oral potassium channel activator, BRL 38227, on airway function and responsiveness in asthmatic patients: comparison with oral salbutamol.
Authors: J C Kidney, R W Fuller, Y M Worsdell, E A Lavender, K F Chung, P J Barnes
Journal: Thorax (1993)

Potassium (K+) channel activators, such as cromakalim, open ATP sensitive K+ channels and relax airway smooth muscle in vitro and inhibit induced bronchoconstriction in vivo in animals. The prolonged half life of cromakalim gives it potential as an oral bronchodilator. The effect of orally administered BRL 38227 (the active enantiomer of cromakalim), at doses of 0.125, 0.25, and 0.5 mg, on airway function and airway responsiveness to histamine and methacholine has been investigated in asthmatic patients.Seventeen patients with asthma were studied in three separate randomised double blind, placebo controlled studies. In the first study eight patients with moderately severe asthma were given 0.125, 0.25, and 0.5 mg of BRL 38227 or placebo, and responses to histamine were assessed before and five hours after treatment. In the second study responses to methacholine were measured before and five hours after 0.125 and 0.5 mg of BRL 38227 or placebo were given to nine patients with mild asthma. In the third study the effect of 0.5 mg of BRL 38227 or placebo was assessed in eight patients with mild asthma. Responses to histamine were measured before treatment and two and five hours after treatment. To provide a positive control study eight subjects who had taken part in studies 1 and 3 were also given oral salbutamol (8 mg) in a placebo controlled, double blind study. Responses to histamine were assessed before and two hours after treatment.BRL 38227 did not cause significant bronchodilatation or changes in airway responsiveness in any of the studies. Headache was reported in 19 of 25 of patients receiving (in some cases twice) 0.5 mg of BRL 38227. By contrast, oral salbutamol gave significant protection against histamine challenge (geometric mean 2.23 doubling dilutions).After a single oral dose of BRL 38227 no beneficial effect on airway function was detected, despite a high incidence of side effects, which indicates that the orally administered K+ channel activator BRL 38227 may not be useful in the management of asthma.
Neuropsychological inference with an interactive brain: A critique of the “locality” assumption
Authors: Martha J. Farah
Journal: Behavioral and Brain Sciences (1994)

Abstract When cognitive neuropsychologists make inferences about the functional architecture of the normal mind from selective cognitive impairments they generally assume that the effects of brain damage are local, that is, that the nondamaged components of the architecture continue to function as they did before the damage. This assumption follows from the view that the components of the functional architecture are modular, in the sense of being informationally encapsulated. In this target article it is argued that this “locality” assumption is probably not correct in general. Inferences about the functional architecture can nevertheless be made from neuropsychological data with an alternative set of assumptions, according to which human information processing is graded, distributed, and interactive. These claims are supported by three examples of neuropsychological dissociations and a comparison of the inferences obtained from these impairments with and without the locality assumption. The three dissociations are: selective impairments in knowledge of living things, disengagment of visual attention, and overt face recognition. In all three cases, the neuropsychological phenomena lead to more plausible inferences about the normal functional architecture when the locality assumption is abandoned. Also discussed are the relations between the locality assumption in neuropsychology and broader issues, including Fodor's modularity hypothesis and the choice between top-down and bottom-up research approaches.
ErbB2 Increases Vascular Endothelial Growth Factor Protein Synthesis via Activation of Mammalian Target of Rapamycin/p70S6K Leading to Increased Angiogenesis and Spontaneous Metastasis of Human Breast Cancer Cells
Authors: Kristine S. Klos, Shannon L. Wyszomierski, Menghong Sun, Ming Tan, Xiaoyan Zhou, Ping Li, Wentao Yang, Guosheng Yin, Walter N. Hittelman, Dihua Yu
Journal: Cancer Research (2006)

Abstract ErbB2 overexpression in breast tumors results in increased metastasis and angiogenesis and reduced survival. To study ErbB2 signaling mechanisms in metastasis and angiogenesis, we did a spontaneous metastasis assay using MDA-MB-435 human breast cancer cells stably transfected with constitutively active ErbB2 kinase (V659E), a kinase-dead mutant of ErbB2 (K753M), or vector control (neo). Mice injected with V659E had increased metastasis incidence and tumor microvessel density than mice injected with K753M or control. Increased angiogenesis in vivo from the V659E transfectants paralleled increased angiogenic potential in vitro. V659E produced increased vascular endothelial growth factor (VEGF) through increased VEGF protein synthesis. This was mediated through signaling events involving extracellular signal-regulated kinase, phosphatidylinositol 3-kinase/Akt, mammalian target of rapamycin (mTOR), and p70S6K. The V659E xenografts also had significantly increased phosphorylated Akt, phosphorylated p70S6K, and VEGF compared with controls. To validate the clinical relevance of these findings, we examined 155 human breast tumor samples. Human tumors that overexpressed ErbB2, which have been previously shown to have higher VEGF expression, showed significantly higher p70S6K phosphorylation as well. Increased VEGF expression also significantly correlated with higher levels of Akt and mTOR phosphorylation. Additionally, patients with tumors having increased p70S6K phosphorylation showed a trend for worse disease-free survival and increased metastasis. Our findings show that ErbB2 increases VEGF protein production by activating p70S6K in cell lines, xenografts, and in human cancers and suggest that these signaling molecules may serve as targets for antiangiogenic and antimetastatic therapies. (Cancer Res 2006; 66(4): 2028-37)
Comparative biology of test species.
Authors: E J Calabrese
Journal: Environmental Health Perspectives (1988)

This paper assesses the capacity of animal models to predict human response to carcinogenic agents with consideration for the heterogeneity of humans. It is widely accepted that human susceptibility to toxic substances, including carcinogens, is highly variable. Conventional rodent models are usually highly inbred and valued for their ability to display characteristic homogeneity. Current practice assumes that the homogeneity of response to toxic agents, including carcinogens, in the rodent model will be representative of humans. The issue then becomes, To which of the broad spectrum of human responses are specific animal models likely to be related? This paper examines the extent of human heterogeneity over a broad range of biochemical characteristics (e.g., aryl hydrocarbon hydroxylase activity, epoxide hydrase activity, beta-glucuronidase activity, debrisoquine hydroxylation, DNA-adduct formation) with emphasis on those biochemical characteristics that affect responses to carcinogens. Examples are presented to compare the heterogeneity of selected animal models for these biochemical characteristics as they relate to the spectrum of human responses noted above. The paper presents a theoretical perspective for determining to which part of the human population response spectrum common animal models are most likely to be extrapolated.
A multicentre phase II gene expression profiling study of putative relationships between tumour biomarkers and clinical response with erlotinib in non-small-cell lung cancer
Authors: E.-H. Tan, R. Ramlau, A. Pluzanska, H.-P. Kuo, M. Reck, J. Milanowski, J. S.-K. Au, E. Felip, P.-C. Yang, D. Damyanov, S. Orlov, M. Akimov, P. Delmar, L. Essioux, C. Hillenbach, B. Klughammer, P. McLoughlin, J. Baselga
Journal: Annals of Oncology (2010)

BackgroundIdentification of appropriate markers for predicting clinical benefit with erlotinib in non-small-cell lung cancer (NSCLC) may be able to guide patient selection for treatment. This open-label, multicentre, phase II trial aimed to identify genes with potential use as biomarkers for clinical benefit from erlotinib therapy.MethodsAdults with stage IIIb/IV NSCLC in whom one or more chemotherapy regimen had failed were treated with erlotinib (150 mg/day). Tumour biopsies were analysed using gene expression profiling with Affymetrix GeneChip® microarrays. Differentially expressed genes were verified using quantitative RT–PCR (qRT–PCR).ResultsA total of 264 patients were enrolled in the study. Gene expression profiles found no statistically significant differentially expressed genes between patients with and without clinical benefit. In an exploratory analysis in responding versus nonresponding patients, three genes on chromosome 7 were expressed at higher levels in the responding group [epidermal growth factor receptor (EGFR), phosphoserine phosphatase (PSPH) and Rap guanine nucleotide exchange factor 5 (RAPGEF5)]. Independent quantification using qRT–PCR validated the association between EGFR and PSPH overexpression, but not RAPGEF5 overexpression, and clinical outcome.ConclusionsThis study supports the use of erlotinib as an alternative to chemotherapy for patients with relapsed advanced NSCLC. Genetic amplification of the EGFR region of chromosome 7 may be associated with response to erlotinib therapy.