tbuckley/cabot-search huggingface dataset:
A Novel Member of the Leukocyte Receptor Complex Regulates Osteoclast Differentiation
Authors: Nacksung Kim, Masamichi Takami, Jaerang Rho, Regis Josien, Yongwon Choi
Journal: The Journal of Experimental Medicine (2002)

Osteoclasts (OCs) are multinucleated cells that resorb bone and are essential for bone homeostasis. They develop from hematopoietic cells of the myelomonocytic lineage. OC formation requires cell-to-cell interactions with osteoblasts and can be achieved by coculturing bone marrow precursor cells with osteoblasts/stromal cells. Two of the key factors mediating the osteoblast-induced osteoclastogenesis are macrophage-colony stimulating factor (M-CSF) and the tumor necrosis factor (TNF) family member TNF-related activation-induced cytokine (TRANCE) that are produced by osteoblasts/stromal cells in response to various bone resorbing hormones. In addition, other factors produced by osteoblasts/stromal cells further influence osteoclastogenesis. Here we report the identification and characterization of OC-associated receptor (OSCAR), a novel member of the leukocyte receptor complex (LRC)-encoded family expressed specifically in OCs. Genes in the LRC produce immunoglobulin (Ig)-like surface receptors and play critical roles in the regulation of both innate and adaptive immune responses. Different from the previously characterized members of the LRC complex, OSCAR expression is detected specifically in preosteoclasts or mature OCs. Its putative-ligand (OSCAR-L) is expressed primarily in osteoblasts/stromal cells. Moreover, addition of a soluble form of OSCAR in coculture with osteoblasts inhibits the formation of OCs from bone marrow precursor cells in the presence of bone-resorbing factors, indicating that OSCAR may be an important bone-specific regulator of OC differentiation. In addition, this study suggests that LRC-encoded genes may have evolved to regulate the physiology of cells beyond those of the immune system.
Anticarbamylated protein (anti-CarP) antibodies are present in sera of juvenile idiopathic arthritis (JIA) patients
Authors: P C E Hissink Muller, J Anink, J Shi, E W N Levarht, T H C M Reinards, M H Otten, M J D van Tol, C M Jol-van der Zijde, D M C Brinkman, C F Allaart, E P Hoppenreijs, Y Koopman-Keemink, S S M Kamphuis, K Dolman, J M van den Berg, M A J van Rossum, L W A van Suijlekom-Smit, M W Schilham, T W J Huizinga, R E M Toes, R ten Cate, L A Trouw
Journal: Annals of the Rheumatic Diseases (2013)

In juvenile idiopathic arthritis (JIA) patients there is a lack of markers that predict severe disease. Although anticitrullinated protein antibodies (ACPA) have contributed substantially to the understanding of rheumatoid arthritis (RA),1 their detection in JIA has not been equally useful as incidence rates in JIA patients are low2 and merely confined to the polyarticular immunoglobulin (Ig)M-rheumatoid factor (RF)-positive category resembling RA. Recently, anticarbamylated protein (anti-CarP) antibodies were detected in 45% of RA patients and importantly also in 16%–20% ACPA-negative patients.3–5 Within the ACPA-negative patients, anti-CarP antibodies were associated with more severe radiographic progression.3 Since most JIA patients are ACPA-negative we investigated whether anti-CarP antibodies are present in the sera of JIA patients and how they are related to ACPA and IgM-RF.

JIA patients from three Dutch sources were included: the BeSt for Kids trial (NTR 1574, a treatment strategy study) (n=33), a previously described cohort6 (n=48) and the Arthritis and Biologicals in Children (ABC) register7 (n=153). Healthy controls (n=107) (mean age/range 11/(2–20)) are stem-cell graft …
Fibroblast Growth Factor 23 and Left Ventricular Hypertrophy in Chronic Kidney Disease
Authors: Orlando M. Gutiérrez, James L. Januzzi, Tamara Isakova, Karen Laliberte, Kelsey Smith, Gina Collerone, Ammar Sarwar, Udo Hoffmann, Erin Coglianese, Robert Christenson, Thomas J. Wang, Christopher deFilippi, Myles Wolf
Journal: Circulation (2009)

Background— Fibroblast growth factor 23 (FGF-23) is a phosphorus-regulating hormone. In chronic kidney disease (CKD), circulating FGF-23 levels are markedly elevated and independently associated with mortality. Left ventricular hypertrophy and coronary artery calcification are potent risk factors for mortality in CKD, and FGFs have been implicated in the pathogenesis of both myocardial hypertrophy and atherosclerosis. We conducted a cross-sectional study to test the hypothesis that elevated FGF-23 concentrations are associated with left ventricular hypertrophy and coronary artery calcification in patients with CKD. Methods and Results— In this study, 162 subjects with CKD underwent echocardiograms and computed tomography scans to assess left ventricular mass index and coronary artery calcification; echocardiograms also were obtained in 58 subjects without CKD. In multivariable-adjusted regression analyses in the overall sample, increased log FGF-23 concentrations were independently associated with increased left ventricular mass index (5% increase per 1-SD increase in log FGF-23; P =0.01) and risk of left ventricular hypertrophy (odds ratio per 1-SD increase in log FGF-23, 2.1; 95% confidence interval, 1.03 to 4.2). These associations strengthened in analyses restricted to the CKD subjects (11% increase in left ventricular mass index per 1-SD increase in log FGF-23; P =0.01; odds ratio of left ventricular hypertrophy per 1-SD increase in log FGF-23, 2.3; 95% confidence interval, 1.2 to 4.2). Although the highest tertile of FGF-23 was associated with a 2.4-fold increased risk of coronary artery calcification ≥100 versus &lt;100 U compared with the lowest tertile (95% confidence interval, 1.1 to 5.5), the association was no longer significant after multivariable adjustment. Conclusions— FGF-23 is independently associated with left ventricular mass index and left ventricular hypertrophy in patients with CKD. Whether increased FGF-23 is a marker or a potential mechanism of myocardial hypertrophy in CKD requires further study.
Abstract 178: Exercise Augments Cardiac Akt Activity And Reverses Aging-related Systolic Dysfunction.
Authors: Haruya Kawase, Yasuko K Bando, Morihiko Aoyama, Akio Monji, Xieng W Cheng, Masafumi Kuzuya, Toyoaki Murohara
Journal: Circulation Research (2014)

Purpose: Aging is one of the primary factors causing left-ventricular (LV) remodeling and susceptibility to heart failure (HF). Clinical evidences demonstrate a sustained exercise (EX) ameliorates HF; however, the molecular mechanism underlying the aging-related LV remodeling remains uncertain and few data have demonstrated whether EX may be beneficial for the aging-related LV remodeling and contractility. Because preclinical studies indicate the pivotal role of protein kinase Akt in aging, we thus hypothesized whether EX may exert benefits on HF induced by aging in which Akt may play an essential role. Methods: Male aged (40 w/o) and young (14 w/o) C57BL6 mice were subjected to the EX (45-min running (10~20m/s, 5-degree) on treadmill every second day for 15 weeks; agedC57EX and agedC57CON). To elucidate the role of Akt in aging heart, age- and gender-matched Akt knockout mice were also enrolled. Results: Aging impairs both systolic and diastolic function without any changes in cardiac geometry. The systolic dysfunction of agedC57 reversed by EX with concomitant Akt activation; however, its diastolic dysfunction remained unaffected. EX enhanced cardiac Akt activity independently of aging. Aged AktKO exhibited systolic dysfunction to the more severe extent, which was reversed by EX. Conclusions: Our study demonstrates that #1 Akt is essential for adaptive cardiac contractility both to EX and aging. #2 Aging promotes diastolic dysfunction independently of Akt axis.
Elderly humans exposed to concentrated air pollution particles have decreased heart rate variability
Authors: R.B. Devlin, A.J. Ghio, H. Kehrl, G. Sanders, W. Cascio
Journal: European Respiratory Journal (2003)

Air pollution particles are thought to kill &gt;500,000 people worldwide each year. The population most at risk appears to be elderly people with respiratory and cardiovascular disease. As yet, no commonly accepted mechanism has been proposed which can explain the cause of these deaths. Heart rate variability (HRV) was assessed in healthy elderly adults between the ages of 60 and 80 who were exposed twice for 2 h: once to clean air and once to concentrated ambient air pollution particles (CAPS). Changes in HRV were measured immediately before, immediately following, and 24 h after exposure. Elderly subjects experienced significant decreases in HRV in both time and frequency domains immediately following exposure. Some of these changes persisted for at least 24 h. These data were compared with HRV data collected from young healthy volunteers exposed to CAPS in a previous study, in which no CAPS-induced changes in HRV were found. These concentrated ambient air pollution particle-induced changes in heart rate variability in a controlled human exposure study extend similar findings reported in recent panel studies and suggest potential mechanisms by which particulate matter may induce adverse cardiovascular events.
Predictors of mortality and the provision of dialysis in patients with acute tubular necrosis. The Auriculin Anaritide Acute Renal Failure Study Group.
Authors: G M Chertow, J M Lazarus, E P Paganini, R L Allgren, R A Lafayette, M H Sayegh
Journal: Journal of the American Society of Nephrology (1998)

To explore the natural history of critically ill patients with acute renal failure due to acute tubular necrosis, we evaluated 256 patients enrolled in the placebo arm of a randomized clinical trial. Death and the composite outcome, death or the provision of dialysis, were determined with follow-up to 60 d. The relative risks (RR) and 95% confidence intervals (95% CI) associated with routinely available demographic, clinical, and laboratory variables were estimated using proportional hazards regression. Ninety-three (36%) deaths were documented; an additional 52 (20%) patients who survived received dialysis. Predictors of mortality included male gender (RR, 2.01; 95% CI, 1.21 to 3.36), oliguria (RR, 2.25; 95% CI, 1.43 to 3.55), mechanical ventilation (RR, 1.86; 95% CI, 1.18 to 2.93), acute myocardial infarction (RR, 3.14; 95% CI, 1.85 to 5.31), acute stroke or seizure (RR, 3.08; 95% CI, 1.56 to 6.06), chronic immunosuppression (RR, 2.37; 95% CI, 1.16 to 4.88), hyperbilirubinemia (RR, 1.06; 95% CI, 1.03 to 1.08 per 1 mg/dl increase in total bilirubin) and metabolic acidosis (RR, 0.95; 95% CI, 0.90 to 0.99 per 1 mEq/L increase in serum bicarbonate concentration). Predictors of death or the provision of dialysis were oliguria (RR, 5.95; 95% CI, 3.96 to 8.95), mechanical ventilation (RR, 1.53; 95% CI, 1.07 to 2.21), acute myocardial infarction (RR, 1.95; 95% CI, 1.24 to 3.07), arrhythmia (RR, 1.51; 95% CI, 1.04 to 2.19), and hypoalbuminemia (RR, 0.56; 95% CI, 0.42 to 0.74 per 1 g/dl increase in serum albumin concentration). Neither mortality nor the provision of dialysis was related to patient age. These observations can be used to estimate risk early in the course of acute tubular necrosis. Furthermore, these and related models may be used to adjust for case-mix variation in quality improvement efforts, and to objectively stratify patients in future intervention trials aimed at favorably altering the course of hospital-acquired acute renal failure.
OCCURRENCE OF PSYCHOSIS AMONG OKINAWANS IN HAWAII
Authors: BRYANT M. WEDGE
Journal: American Journal of Psychiatry (1952)

This study was carried out to test a hypothesis that the mothering practices of Okinawans afford protection against psychosis in later life. It was found (1) that Okinawan immigrants to Hawaii showed a significantly high rate of psychosis, and (2) that the mothering practices of the immigrants were similar to those of native Okinawans. It is concluded that the hypothesis is disproved. The social situation of Okinawan immigrants was reviewed. It is suggested that the meaning of cultural practices for personality development should be considered in the context of the total social setting to which psychological adjustment must be made.
Comment on: Tam et al. Defining Insulin Resistance From Hyperinsulinemic-Euglycemic Clamps. Diabetes Care 2012;35:1605–1610
Authors: Kristine Færch, Dorte Vistisen
Journal: Diabetes Care (2012)

We have read with interest the article in the July issue of Diabetes Care by Tam et al. (1) in which they define a cutoff point for having insulin resistance and provide classification trees for predicting insulin resistance from clinical and biochemical markers. We appreciate the authors’ effort to translate detailed phenotypic data into clinical usefulness; however, defining a cutoff point is always challenging, and the study raises a number of questions.

Whether the overall aim of setting a cutoff point for insulin resistance is to guide treatment in patients with type 2 diabetes or to prevent or delay the development of diabetes in the general population, the rationale for determining insulin resistance should be clearly defined in order for the cutoff point to …
Fibronectin extra domain B-specific aptide conjugated nanoparticles for targeted cancer imaging
Authors: Jinho Park, Sunghyun Kim, Phei Er Saw, In-Hyun Lee, Mi Kyung Yu, Minsik Kim, Kwangyeol Lee, Yong-Chul Kim, Yong Yeon Jeong, Sangyong Jon
Journal: Journal of Controlled Release (2012)
Human monocyte-derived suppressor cells control graft-versus-host disease by inducing regulatory forkhead box protein 3–positive CD8+ T lymphocytes
Authors: Nona Janikashvili, Malika Trad, Alexandrine Gautheron, Maxime Samson, Baptiste Lamarthée, Francis Bonnefoy, Stéphanie Lemaire-Ewing, Marion Ciudad, Khatuna Rekhviashvili, Famky Seaphanh, Béatrice Gaugler, Sylvain Perruche, Andrew Bateman, Laurent Martin, Sylvain Audia, Philippe Saas, Nicolas Larmonier, Bernard Bonnotte
Journal: Journal of Allergy and Clinical Immunology (2015)
Fexofenadine Decreases Sensitivity to and Montelukast Improves Recovery from Inhaled Mannitol
Authors: JOHN D. BRANNAN, SANDRA D. ANDERSON, KERRY GOMES, GREGORY G. KING, H. KIM CHAN, J. PAUL SEALE
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

We studied, separately, the effects of the histamine antagonist, fexofenadine hydrochloride, and the leukotriene antagonist, montelukast sodium, and their placebos on airway sensitivity to and recovery from inhaled mannitol in subjects with asthma. Two 180-mg doses of fexofenadine were taken over 14 h, and three 10-mg doses of montelukast over 36 h, with the last dose 5 h before challenge. Fexofenadine reduced sensitivity to mannitol and the PD(15) was (mean [95% confidence interval] 138 [95, 201]) mg versus placebo (51 [25, 106] mg) (p < 0.001). The final percent reduction in FEV(1) with fexofenadine was 20.8 +/- 5.4% and not different from placebo (20.1 +/- 5.3%) (p = 0.7); however, recovery was slower with fexofenadine compared with placebo (p < 0.001). By contrast, montelukast had no effect on sensitivity to mannitol and the PD(15) was 71 [36, 144] mg versus placebo (87 [51, 148] mg (p = 0.35). The total dose of mannitol delivered and the final percent reduction in FEV(1) with montelukast were 171 +/- 142 mg and 21 +/- 4% and for placebo were 182 +/- 144 mg and 20 +/- 5% (p = 0.35, p = 0.59, respectively). However, recovery of FEV(1) to baseline was faster with montelukast, with the area under the percent reduction FEV(1)-versus-time curve reduced (220 +/- 121% change.min) compared with placebo (513 +/- 182% change.min) (p < 0.001). We conclude that whereas histamine is important for the initial airway response, leukotrienes are important in sustaining the airway response to inhaled mannitol.
Adverse Events Associated With Prescription Drug Cost-Sharing Among Poor and Elderly Persons
Authors: R Tamblyn, R Laprise, J A Hanley, M Abrahamowicz, S Scott, N Mayo, J Hurley, R Grad, E Latimer, R Perreault, P McLeod, A Huang, P Larochelle, L Mallet
Journal: JAMA (2001)

ContextRising costs of medications and inequities in access have sparked calls for drug policy reform in the United States and Canada. Control of drug expenditures by prescription cost-sharing for elderly persons and poor persons is a contentious issue because little is known about the health impact in these subgroups.ObjectivesTo determine (1) the impact of introducing prescription drug cost-sharing on use of essential and less essential drugs among elderly persons and welfare recipients and (2) rates of emergency department (ED) visits and serious adverse events associated with reductions in drug use before and after policy implementation.Design and SettingInterrupted time-series analysis of data from 32 months before and 17 months after introduction of a prescription coinsurance and deductible cost-sharing policy in Quebec in 1996. Separate 10-month prepolicy control and postpolicy cohort studies were conducted to estimate the impact of the drug reform on adverse events.ParticipantsA random sample of 93 950 elderly persons and 55 333 adult welfare medication recipients.Main Outcome MeasuresMean daily number of essential and less essential drugs used per month, ED visits, and serious adverse events (hospitalization, nursing home admission, and mortality) before and after policy introduction.ResultsAfter cost-sharing was introduced, use of essential drugs decreased by 9.12% (95% confidence interval [CI], 8.7%-9.6%) in elderly persons and by 14.42% (95% CI, 13.3%-15.6%) in welfare recipients; use of less essential drugs decreased by 15.14% (95% CI, 14.4%-15.9%) and 22.39% (95% CI, 20.9%-23.9%), respectively. The rate (per 10 000 person-months) of serious adverse events associated with reductions in use of essential drugs increased from 5.8 in the prepolicy control cohort to 12.6 in the postpolicy cohort in elderly persons (a net increase of 6.8 [95% CI, 5.6-8.0]) and from 14.7 to 27.6 in welfare recipients (a net increase of 12.9 [95% CI, 10.2-15.5]). Emergency department visit rates related to reductions in the use of essential drugs also increased by 14.2 (95% CI, 8.5-19.9) per 10 000 person-months in elderly persons (prepolicy control cohort, 32.9; postpolicy cohort, 47.1) and by 54.2 (95% CI, 33.5-74.8) among welfare recipients (prepolicy control cohort, 69.6; postpolicy cohort, 123.8). These increases were primarily due to an increase in the proportion of recipients who reduced their use of essential drugs. Reductions in the use of less essential drugs were not associated with an increase in risk of adverse events or ED visits.ConclusionsIn our study, increased cost-sharing for prescription drugs in elderly persons and welfare recipients was followed by reductions in use of essential drugs and a higher rate of serious adverse events and ED visits associated with these reductions.
Development and Validation of a Drug Activity Biomarker that Shows Target Inhibition in Cancer Patients Receiving Enzastaurin, a Novel Protein Kinase C-β Inhibitor
Authors: Lisa J. Green, Philip Marder, Chad Ray, Carolyn A. Cook, Susan Jaken, Luna C. Musib, Roy S. Herbst, Michael Carducci, Carolyn D. Britten, Michele Basche, S. Gail Eckhardt, Donald Thornton
Journal: Clinical Cancer Research (2006)

Abstract Purpose: To evaluate the effects of the novel protein kinase C (PKC) inhibitor enzastaurin on intracellular phosphoprotein signaling using flow cytometry and to use this approach to measure enzastaurin effects on surrogate target cells taken from cancer patients that were orally dosed with this agent. Experimental Design: The activity of PKC was assayed in intact cells using a modification of published techniques. The U937 cell line and peripheral blood mononuclear cells were stimulated with phorbol ester, fixed, permeabilized, and reacted with an antibody specific for the phosphorylated forms of PKC substrates. The processed samples were quantitatively analyzed using flow cytometry. The assay was validated for selectivity, sensitivity, and reproducibility. Finally, blood was obtained from volunteer cancer patients before and after receiving once daily oral doses of enzastaurin. These samples were stimulated ex vivo with phorbol ester and were assayed for PKC activity using this approach. Results: Assay of U937 cells confirmed the selectivity of the antibody reagent and enzastaurin for PKC. Multiparametric analysis of peripheral blood mononuclear cells showed monocytes to be the preferred surrogate target cell. Day-to-day PKC activity in normal donors was reproducible. Initial results showed that five of six cancer patients had decreased PKC activity following enzastaurin administration. In a following study, a group of nine patients displayed a significant decrease in PKC activity after receiving once daily oral doses of enzastaurin. Conclusion: An inhibition of surrogate target cell PKC activity was observed both in vitro and ex vivo after exposure to the novel kinase inhibitor, enzastaurin.
Primary Prevention of Coronary Heart Disease: Guidance From Framingham
Authors: Scott M. Grundy, Gary J. Balady, Michael H. Criqui, Gerald Fletcher, Philip Greenland, Loren F. Hiratzka, Nancy Houston-Miller, Penny Kris-Etherton, Harlan M. Krumholz, John LaRosa, Ira S. Ockene, Thomas A. Pearson, James Reed, Reginald Washington, Sidney C. Smith
Journal: Circulation (1998)

HomeCirculationVol. 97, No. 18Primary Prevention of Coronary Heart Disease: Guidance From Framingham
Circulating MicroRNAs as Novel Biomarkers for Platelet Activation
Authors: Peter Willeit, Anna Zampetaki, Katarzyna Dudek, Dorothee Kaudewitz, Alice King, Nicholas S. Kirkby, Roxanne Crosby-Nwaobi, Marianna Prokopi, Ignat Drozdov, Sarah R. Langley, Sobha Sivaprasad, Hugh S. Markus, Jane A. Mitchell, Timothy D. Warner, Stefan Kiechl, Manuel Mayr
Journal: Circulation Research (2013)

MicroRNA (miRNA) biomarkers are attracting considerable interest. Effects of medication, however, have not been investigated thus far.
Removal of Duodenum Elicits GLP-1 Secretion
Authors: Giovanna Muscogiuri, Teresa Mezza, Annamaria Prioletta, Gian Pio Sorice, Gennaro Clemente, Gerardo Sarno, Gennaro Nuzzo, Alfredo Pontecorvi, Jens J. Holst, Andrea Giaccari
Journal: Diabetes Care (2013)

To evaluate the effect of removal of the duodenum on the complex interplay between incretins, insulin, and glucagon in nondiabetic subjects.For evaluation of hormonal secretion and insulin sensitivity, 10 overweight patients without type 2 diabetes (age 61 ± 19.3 years and BMI 27.9 ± 5.3 kg/m(2)) underwent a mixed-meal test and a hyperinsulinemic-euglycemic clamp before and after pylorus-preserving pancreatoduodenectomy for ampulloma.All patients experienced a reduction in insulin (P = 0.002), C-peptide (P = 0.0002), and gastric inhibitory peptide (GIP) secretion (P = 0.0004), while both fasting and postprandial glucose levels increased (P = 0.0001); GLP-1 and glucagon responses to the mixed meal increased significantly after surgery (P = 0.02 and 0.031). While changes in GIP levels did not correlate with insulin, glucagon, and glucose levels, the increase in GLP-1 secretion was inversely related to the postsurgery decrease in insulin secretion (R(2) = 0.56; P = 0.012) but not to the increased glucagon secretion, which correlated inversely with the reduction of insulin (R(2) = 0.46; P = 0.03) and C-peptide (R(2) = 0.37; P = 0.04). Given that the remaining pancreas presumably has preserved intraislet anatomy, insulin secretory capacity, and α- and β-cell interplay, our data suggest that the increased glucagon secretion is related to decreased systemic insulin.Pylorus-preserving pancreatoduodenectomy was associated with a decrease in GIP and a remarkable increase in GLP-1 levels, which was not translated into increased insulin secretion. Rather, the hypoinsulinemia may have caused an increase in glucagon secretion.