tbuckley/cabot-search huggingface dataset:
Renal Hyperfiltration as a Novel Marker of All-Cause Mortality
Authors: Minseon Park, Eunsil Yoon, Youn-Hee Lim, Ho Kim, Jinwook Choi, Hyung-Jin Yoon
Journal: Journal of the American Society of Nephrology (2014)

Although renal hyperfiltration (RHF) or an abnormal increase in GFR has been associated with many lifestyles and clinical conditions, including diabetes, its clinical consequence is not clear. RHF is frequently considered to be the result of overestimating true GFR in subjects with muscle wasting. To evaluate the association between RHF and mortality, 43,503 adult Koreans who underwent voluntary health screening at Seoul National University Hospital between March of 1995 and May of 2006 with baseline GFR≥60 ml/min per 1.73 m2 were followed up for mortality until December 31, 2012. GFR was estimated with the Chronic Kidney Disease Epidemiology Collaboration creatinine equation, and RHF was defined as GFR>95th percentile after adjustment for age, sex, muscle mass, and history of diabetes and/or hypertension medication. Muscle mass was measured with bioimpedance analysis at baseline. During the median follow-up of 12.4 years, 1743 deaths occurred. The odds ratio of RHF in participants with the highest quartile of muscle mass was 1.31 (95% confidence interval [95% CI], 1.11 to 1.54) compared with the lowest quartile after adjusting for confounding factors, including body mass index. The hazard ratio of all-cause mortality for RHF was 1.37 (95% CI, 1.11 to 1.70) by Cox proportional hazards model with adjustment for known risk factors, including smoking. These data suggest RHF may be associated with increased all-cause mortality in an apparently healthy population. The possibility of RHF as a novel marker of all-cause mortality should be confirmed.
PHYSIOLOGICAL AND PHARMACOLOGICAL REGULATION OF HUMAN SALIVARY ELECTROLYTE CONCENTRATIONS; WITH A DISCUSSION OF ELECTROLYTE CONCENTRATIONS OF SOME OTHER EXOCRINE SECRETIONS 1
Authors: Abraham G. White, Paul S. Entmacher, George Rubin, Louis Leiter
Journal: Journal of Clinical Investigation (1955)

The electrolyte content of paraffin-stimulated, whole, mixed saliva obtained from patients with congestive heart failure is characterized by lower sodium, lower chloride, and higher potassium concentrations than saliva of normal subjects (1).Since these data suggested possible increased adrenal cortical activity in patients with heart failure, desoxycorticosterone acetate (DCA) was administered to nineteen normal subjects.It also seemed of interest to study additional pharmacological and physiological mechanisms that may play a role in the regulation of salivary electrolyte concentrations.Thus, the aims of this communication are to present: 1) Data on normal salivary concentrations of sodium, chloride, and potassium; 2) data relating to physiological mechanisms regulating the concentrations of salivary electrolytes; and 3) the effects on salivary elec- trolytes of three pharmacologic agents: desoxycorticosterone acetate (DCA), pilocarpine, and Mercuhydrin@.METHODS Approximately 30 ml. of saliva were collected in the morning from fasting subjects who chewed paraffin for 15 to 20 minutes following a preliminary mouth wash with water.Where indicated, normal subjects chewed paraffin for two consecutive ten-minute periods.Whole, mixed saliva was analyzed.Sodium and potassium concentrations were measured with an internal standard Perkin 52A flame photometer; chloride concentrations,
Transthoracic Echocardiography in Models of Cardiac Disease in the Mouse
Authors: Nobuaki Tanaka, Nancy Dalton, Lan Mao, Howard A. Rockman, Kirk L. Peterson, Kim R. Gottshall, John J. Hunter, Kenneth R. Chien, John Ross
Journal: Circulation (1996)

Background Transthoracic echocardiography (M-mode and Doppler) offers a noninvasive approach for in vivo evaluation of the mouse heart. The present study examines its usefulness for assessing the morphological/functional phenotype of the left ventricle (LV) in several transgenic and surgical murine models of cardiac disease. Methods and Results Observations were made in 83 intact, anesthetized mice. In mice with a surgical arteriovenous fistula, volume overload and LV dilation were detected. In normal mice, echocardiographic indexes of increased contractility (dobutamine) were confirmed by LV dP/dt max . In transgenic mice with overexpression of the β 2 -adrenergic receptor, heart rate and mean velocity of circumferential fiber shortening were increased, indicating enhanced contractility. In colony screening of transgenic mice overexpressing the H- ras gene, 45% had increased LV wall thickness (&gt;0.9 mm), and those showing a striking increase were selected for breeding. In mice with LV hypertrophy (aortic constriction) and normal mice, the actual LV mass determined by echocardiography correlated well ( r =.93), and 95% confidence limits were determined. The maximum intraobserver and interobserver coefficients of variation for M-mode data were 0.03±0.29 mm (±2 SD), &lt;10% for LV internal dimensions but 27% to 30% for wall thickness. Conclusions These studies provide the first application of transthoracic echocardiography for morphological/functional characterization of the cardiac phenotype in transgenic and surgical murine models, including (1) high reliability for detecting LV chamber dilation and function; (2) reliability (and its limits) for determining abnormal LV wall thickness and LV mass; (3) identification of marked, sometimes asymmetrical, hypertrophy in a transgenic model of hypertrophic cardiomyopathy; and (4) usefulness for transgenic colony screening to identify markedly abnormal phenotypes.
MMP-9 regulates both positively and negatively collagen gel contractionA nonproteolytic function of MMP-9
Authors: O DEFAWE, R KENAGY, C CHOI, S WAN, C DEROANNE, B NUSGENS, N SAKALIHASAN, A COLIGE, A CLOWES
Journal: Cardiovascular Research (2004)

Objective: Constrictive remodeling accounts for lumen loss in postangioplasty restenosis. Matrix metalloproteinase-9 (MMP-9) has been shown to prevent constrictive remodeling in vivo. To investigate potential mechanisms for this observation, we investigated the role of MMP-9 in smooth muscle cell (SMC)-mediated collagen gel contraction, an in vitro model of constrictive remodeling. Methods: Fischer rat SMCs were stably transfected with a construct-expressing rat-MMP-9 under the control of a tetracycline (Tet)-off promoter. SMCs were seeded in type I collagen gels (2.4 mg/ml) in the presence or not of tetracycline (1 μg/ml), and gel contraction was defined as the percentage of retraction of the collagen gel. The depletion of MMP-9 was obtained by using siRNA targeting MMP-9 mRNA or a blocking antibody. Results: Gel contraction was significantly reduced at all times when MMP-9 was overexpressed (Tet−) as compared with the control condition (Tet+). However, MMP-9 depletion of control (Tet+) SMCs (using siRNA or antibody) also inhibited gel contraction. To resolve the apparent discrepancy and determine if MMP-9 exerts a dose-dependent biphasic effect on gel contraction, conditioned medium and purified rat-MMP-9 were prepared. Gel contraction was significantly increased by addition of 0.8 ng/ml of MMP-9, while high concentrations of MMP-9 (≥ 100 ng/ml) inhibited contraction. The addition of BB94 and TIMP-1 did not alter the inhibitory or stimulatory effect of MMP-9. Conclusions: Our data suggest that MMP-9, independent of its proteolytic function, has a biphasic effect on SMC-mediated collagen gel contraction. Understanding the different roles of MMP-9 should allow the development of better therapeutic strategies for restenotic vascular disease.
On the selection and balancing of multiple selfish goals
Authors: Catalina Kopetz, Wilhelm Hofmann, Reinout W. H. J. Wiers
Journal: Behavioral and Brain Sciences (2014)

Abstract The selfish goal metaphor is interesting and intriguing. It accounts for the idiosyncrasies and inconsistencies in peoples' goal pursuits without invoking free will, self-regulatory, or self-control failures. However, people pursue multiple goals, sometimes simultaneously. We argue that the model proposed in the target article may gain significant theoretical and practical value if the principles underlying goal selection and/or balancing on a moment-to-moment basis are clearly specified and integrated with the notion of the selfish goal.
<i>Staphylococcus aureus</i> Bacteremia After Median Sternotomy
Authors: Vance G. Fowler, Keith S. Kaye, David L. Simel, Christopher H. Cabell, Douglas McClachlan, Peter K. Smith, Scott Levin, Daniel J. Sexton, L. Barth Reller, G. Ralph Corey, Eugene Z. Oddone
Journal: Circulation (2003)

Mediastinitis is a complication of coronary artery bypass graft surgery (CABG) that can be difficult to diagnose. This study evaluated the utility of blood culture results in identifying patients with mediastinitis.All unique patients undergoing CABG at our institution over a 60-month study period (n=5500) and all blood cultures performed on these patients <or=90 days after CABG were identified. Mediastinitis was identified by prospective active infection control surveillance. Eight hundred fifty-five (15.5%) patients had >or=1 blood culture drawn within 90 days of CABG. Mediastinitis occurred in 46 of 60 (76.7%) patients with blood cultures positive for Staphylococcus aureus, 15 of 126 (11.9%) patients with blood cultures positive for other pathogens, 37 of 669 (5.5%) patients with blood cultures with no growth, and 44 of 4645 (0.9%) patients with no blood cultures obtained. The isolation of S aureus from even 1 blood culture drawn after <or=90 days of CABG was strongly associated with mediastinitis (likelihood ratio [LR], 25; 95% CI, 14.7 to 44.4). Bacteremia attributable to other organisms did not alter pretest suspicion for mediastinitis (LR, 1.0; 95% CI, 0.6 to 1.7). Patients with negative blood cultures were less likely to have mediastinitis (LR, 0.45; 95% CI, 0.35 to 0.58). The association between S aureus bacteremia and mediastinitis remained highly significant when all unique patients undergoing CABG were analyzed in a logistic regression model and when a case-control analysis was used to evaluate patients with >or=1 blood culture obtained after CABG.Among patients with blood cultures drawn after CABG, S aureus bacteremia strongly suggests the presence of mediastinitis.
Acute Effect of Nonsurgical Septal Reduction Therapy on Regional Left Ventricular Asynchrony in Patients With Hypertrophic Obstructive Cardiomyopathy
Authors: Tae-Ho Park, Nasser M. Lakkis, Katherine J. Middleton, Jennifer Franklin, William A. Zoghbi, Miguel A. Quiñones, William H. Spencer, Sherif F. Nagueh
Journal: Circulation (2002)

Background — Patients with hypertrophic obstructive cardiomyopathy have left ventricular (LV) diastolic dysfunction due, in part, to temporal heterogeneity in regional function. The acute effect of the relief of LV outflow tract obstruction is unknown. Therefore, we investigated the effects of nonsurgical septal reduction therapy (NSRT) on regional function. Methods and Results — Twenty-two patients (aged 56±17 years) underwent echocardiographic examination, including tissue Doppler imaging, simultaneously with left heart catheterization before and after NSRT. LV regional function was assessed in 12 segments from which myocardial strain was obtained. Asynchrony was calculated as the coefficient of variation of the time interval from the QRS complex to the onset of expansion and to early diastolic strain. After NSRT, a significant reduction in LV outflow tract obstruction (from 57±5 to 12±3 mm Hg) occurred with shortening of the time constant of LV relaxation (71±4 to 61±3 ms; both P &lt;0.05). The coefficient of variation of the time interval to onset of regional expansion decreased significantly and related well to the changes in the time constant of LV relaxation ( r =0.81, P &lt;0.01). Conclusions — NSRT has a favorable effect on LV regional asynchrony, which accounts for the acute changes in LV relaxation.
Abnormal erythemal response and elevated T lymphocyte HRPT mutant frequency in Cockayne's syndrome
Authors: P.G. NORRIS, C.F. ARLETT, J. COLE, A.R. LEHMANN, J.L.M. HAWK
Journal: British Journal of Dermatology (1991)

Journal Article Abnormal erythemal response and elevated T lymphocyte HRPT mutant frequency in Cockayne's syndrome Get access P.G. NORRIS, P.G. NORRIS Photobiology Unit, Institute of Dermatology St. Thomas’Hospital London, U.K. Dr P.G.Norris, Photobiology Unit. 11th Floor. North Wing. St Thomas' Hospital. London, SEI 7Eh, U.K. Search for other works by this author on: Oxford Academic Google Scholar C.F. ARLETT, C.F. ARLETT MRC Cell Mutation Unit. University of Sussex, U.K. Search for other works by this author on: Oxford Academic Google Scholar J. COLE, J. COLE MRC Cell Mutation Unit. University of Sussex, U.K.Photobiology Unit, Institute of Dermatology St. Thomas’Hospital London, U.K. Search for other works by this author on: Oxford Academic Google Scholar A.R. LEHMANN, A.R. LEHMANN MRC Cell Mutation Unit. University of Sussex, U.K. Search for other works by this author on: Oxford Academic Google Scholar J.L.M. HAWK J.L.M. HAWK Photobiology Unit, Institute of Dermatology St. Thomas’Hospital London, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 124, Issue 5, 1 May 1991, Pages 453–460, https://doi.org/10.1111/j.1365-2133.1991.tb00625.x Published: 01 May 1991
THE ELECTROPHORESIS OF THE BLOOD PLATELETS OF THE HORSE WITH REFERENCE TO THEIR ORIGIN AND TO THROMBUS FORMATION
Authors: Harold A. Abramson
Journal: The Journal of Experimental Medicine (1928)

1. The cataphoretic velocity of blood platelets (horse) in plasma has been found to be between 40 and 51 micro per sec. per volt per cm. The mean velocity obtained from five horses is . 45 micro per sec. per volt per cm. 2. The cataphoretic velocity of polymorphonuclear leucocytes in similar specimens is practically identical with that of the platelets. This is noteworthy because of the fact that lymphocytes and red cells have different speeds. 3. With spontaneous agglutination of platelets, white cells and red cells, there is no change in the cataphoretic velocity incidental to aggregation. 4. The possible surface composition of platelets and white cells is briefly discussed. 5. The bearing of these findings on the origin of blood platelets and the mechanism of thrombus formation is demonstrated.
Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial
Authors: James W. Murrough, Dan V. Iosifescu, Lee C. Chang, Rayan K. Al Jurdi, Charles E. Green, Andrew M. Perez, Syed Iqbal, Sarah Pillemer, Alexandra Foulkes, Asim Shah, Dennis S. Charney, Sanjay J. Mathew
Journal: American Journal of Psychiatry (2013)

Intravenous ketamine demonstrated rapid antidepressant effects in an optimized study design, improving depression severity in 64% of treatment-resistant patients 24 hours after a single dose. The double-blind trial provides evidence for the role of the N-methyl-d-aspartate glutamate receptor in depression, a receptor not currently activated by existing antidepressant drugs.
The role of biosimilars in the treatment of rheumatic diseases
Authors: Thomas Dörner, Vibeke Strand, Gilberto Castañeda-Hernández, Gianfranco Ferraccioli, John D Isaacs, Tore K Kvien, Emilio Martin-Mola, Thomas Mittendorf, Josef S Smolen, Gerd R Burmester
Journal: Annals of the Rheumatic Diseases (2012)

The first biological therapeutics in rheumatology are approaching patent expiration, encouraging development of 'follow-on' versions, known as 'biosimilars'. Biological agents range from simple replacement hormones to complex monoclonal antibodies and soluble receptors: large, intricate proteins with unique tertiary and quaternary structures that are inherently difficult to replicate. Post-translational modifications, such as glycosylation, may occur from changes in cell lines and/or manufacturing processes, resulting in products that are highly similar, but not identical, to approved 'reference' agents, hence, the term 'biosimilar', rather than 'bioidentical'. Even minor modifications in manufacturing processes, which iteratively occur with reference products due to improvements in efficiency, scale up to meet commercial demands or changes in manufacturing sites, may alter biological function and/or immunogenicity, potentially changing their safety and efficacy profile. As biosimilars are now in randomised controlled trials for treatment of rheumatic diseases, rheumatologists face decisions regarding equipoise and will need to consider their clinical use versus reference products. A clear understanding of the inherent differences between reference antibodies and biosimilars, their clinical implications and the processes governing regulation, approval and clinical use of biosimilars, is paramount. A panel of international experts in the field of rheumatology recently convened to evaluate and discuss these issues.
Airway resistance measured by the interrupter technique: expiration or inspiration, mean or median?
Authors: P.D. Bridge, S.A. McKenzie
Journal: European Respiratory Journal (2001)

The measurement of airway resistance by the interrupter technique (R int ) needs standardization. Should measurements be made be during the expiratory or inspiratory phase of tidal breathing? In reported studies, the measurement of R int has been calculated as the median or mean of a small number of values, is there an important difference? Subjects were 2.5–5.0 yrs (median 4.0 yrs) who had previous respiratory symptoms. The R int in expiration (R int E) and inspiration (R int I) pre and postsalbutamol, the coefficient of variation (CV) of values contributing to measurements, and bronchodilator responsiveness (BDR) in both phases were compared. Measurements using median and mean were compared. R int E was higher than R int I by 4% (p&lt;0.01). The CV of values making up R int E and R int I, and BDR measured in expiration and inspiration were similar. The median difference between means and medians of values making up measurements was 0.6% (range −6–11%). R int E has been shown to be consistently greater then R int I but the difference in this study is small. It is suggested that one or the other is chosen as the standard. In the present data the mean of a set of values contributing to a measurement was not significantly different from the median. However, the use of the median has been recommended since it is less affected by possible outlying values such as might be included by fully automated equipment.
DNA Methylation Signatures Identify Biologically Distinct Subtypes in Acute Myeloid Leukemia
Authors: Maria E. Figueroa, Sanne Lugthart, Yushan Li, Claudia Erpelinck-Verschueren, Xutao Deng, Paul J. Christos, Elizabeth Schifano, James Booth, Wim van Putten, Lucy Skrabanek, Fabien Campagne, Madhu Mazumdar, John M. Greally, Peter J.M. Valk, Bob Löwenberg, Ruud Delwel, Ari Melnick
Journal: Cancer Cell (2010)
A new era in the management of pulmonary arterial hypertension related to scleroderma: endothelin receptor antagonism
Authors: E Hachulla
Journal: Annals of the Rheumatic Diseases (2004)

Evidence suggests that endothelin may have a fundamental role in scleroderma pathogenesis, including pulmonary arterial hypertension (PAH)—a leading cause of death in patients with scleroderma. Development of a new class of drug, endothelin receptor antagonists, heralds an improved outlook for patients with scleroderma and related diseases. Heightened vigilance towards early detection of PAH in scleroderma and a multidisciplinary approach to diagnosis and treatment may improve clinical outcomes for these patients.
Maternal alloantibodies induce a postnatal immune response that limits engraftment following in utero hematopoietic cell transplantation in mice
Authors: Demetri J. Merianos, Eleonor Tiblad, Matthew T. Santore, Carlyn A. Todorow, Pablo Laje, Masayuki Endo, Philip W. Zoltick, Alan W. Flake
Journal: Journal of Clinical Investigation (2009)

The lack of fetal immune responses to foreign antigens, i.e., fetal immunologic tolerance, is the most compelling rationale for prenatal stem cell and gene therapy. However, the frequency of engraftment following in utero hematopoietic cell transplantation (IUHCT) in the murine model is reduced in allogeneic, compared with congenic, recipients. This observation supports the existence of an immune barrier to fetal transplantation and challenges the classic assumptions of fetal tolerance. Here, we present evidence that supports the presence of an adaptive immune response in murine recipients of IUHCT that failed to maintain engraftment. However, when IUHCT recipients were fostered by surrogate mothers, they all maintained long-term chimerism. Furthermore, we have demonstrated that the cells responsible for rejection of the graft were recipient in origin. Our observations suggest a mechanism by which IUHCT-dependent sensitization of the maternal immune system and the subsequent transmission of maternal alloantibodies to pups through breast milk induces a postnatal adaptive immune response in the recipient, which, in turn, results in the ablation of engraftment after IUHCT. Finally, we showed that non-fostered pups that maintained their chimerism had higher levels of Tregs as well as a more suppressive Treg phenotype than their non-chimeric, non-fostered siblings. This study resolves the apparent contradiction of induction of an adaptive immune response in the pre-immune fetus and confirms the potential of actively acquired tolerance to facilitate prenatal therapeutic applications.
Myeloid Cell 5-Lipoxygenase Activating Protein Modulates the Response to Vascular Injury
Authors: Zhou Yu, Emanuela Ricciotti, Takashi Miwa, Shulin Liu, Kaori Ihida-Stansbury, Gavin Landesberg, Peter L. Jones, Rosario Scalia, Wen-Chao Song, Richard K Assoian, Garret A. FitzGerald
Journal: Circulation Research (2012)

Human genetics have implicated the 5-lipoxygenase enzyme in the pathogenesis of cardiovascular disease, and an inhibitor of the 5-lipoxygenase activating protein (FLAP) is in clinical development for asthma.