tbuckley/cabot-search huggingface dataset:
Postconditioning the Human Heart
Authors: Patrick Staat, Gilles Rioufol, Christophe Piot, Yves Cottin, Thien Tri Cung, Isabelle L’Huillier, Jean-François Aupetit, Eric Bonnefoy, Gérard Finet, Xavier André-Fouët, Michel Ovize
Journal: Circulation (2005)

Background— In animal models, brief periods of ischemia performed just at the time of reperfusion can reduce infarct size, a phenomenon called postconditioning. In this prospective, randomized, controlled, multicenter study, we investigated whether postconditioning may protect the human heart during coronary angioplasty for acute myocardial infarction. Methods and Results— Thirty patients, submitted to coronary angioplasty for ongoing acute myocardial infarction, contributed to the study. Patients were randomly assigned to either a control or a postconditioning group. After reperfusion by direct stenting, control subjects underwent no further intervention, whereas postconditioning was performed within 1 minute of reflow by 4 episodes of 1-minute inflation and 1-minute deflation of the angioplasty balloon. Infarct size was assessed by measuring total creatine kinase release over 72 hours. Area at risk and collateral blood flow were estimated on left ventricular and coronary angiograms. No adverse events occurred in the postconditioning group. Determinants of infarct size, including ischemia time, size of the area at risk, and collateral flow, were comparable between the 2 groups. Area under the curve of creatine kinase release was significantly reduced in the postconditioning compared with the control group, averaging 208 984±26 576 compared with 326 095±48 779 (arbitrary units) in control subjects, ie, a 36% reduction in infarct size. Blush grade, a marker of myocardial reperfusion, was significantly increased in postconditioned compared with control subjects: 2.44±0.17 versus 1.95±0.27, respectively ( P &lt;0.05). Conclusions— This study suggests that postconditioning by coronary angioplasty protects the human heart during acute myocardial infarction.
TCT-240 Severe Renal Dysfunction In Patients Admitted With Cardiogenic Shock Complicating AMI - Early And 2-Year Outcomes From The PL-ACS Registry
Authors: Michal Hawranek, Marek Gierlotka, Mariusz Gasior, Mateusz Tajstra, Krzysztof Wilczek, Krzysztof Strojek, Zbigniew Kalarus, Marian Zembala, Lech Polonski
Journal: Journal of the American College of Cardiology (2013)
Diagnosis and management of adult coeliac disease: guidelines from the British Society of Gastroenterology
Authors: Jonas F Ludvigsson, Julio C Bai, Federico Biagi, Timothy R Card, Carolina Ciacci, Paul J Ciclitira, Peter H R Green, Marios Hadjivassiliou, Anne Holdoway, David A van Heel, Katri Kaukinen, Daniel A Leffler, Jonathan N Leonard, Knut E A Lundin, Norma McGough, Mike Davidson, Joseph A Murray, Gillian L Swift, Marjorie M Walker, Fabiana Zingone, David S Sanders
Journal: Gut (2014)

A multidisciplinary panel of 18 physicians and 3 non-physicians from eight countries (Sweden, UK, Argentina, Australia, Italy, Finland, Norway and the USA) reviewed the literature on diagnosis and management of adult coeliac disease (CD). This paper presents the recommendations of the British Society of Gastroenterology. Areas of controversies were explored through phone meetings and web surveys. Nine working groups examined the following areas of CD diagnosis and management: classification of CD; genetics and immunology; diagnostics; serology and endoscopy; follow-up; gluten-free diet; refractory CD and malignancies; quality of life; novel treatments; patient support; and screening for CD.
Novel signalling cascade for cardiac hypertrophy activation by uncoupling and internalization of 1-adrenoceptors
Authors: M. Endoh
Journal: Cardiovascular Research (2008)

This editorial refers to ‘Endocytosis machinery is required for b1-adrenergic receptor-induced hypertrophy in neonatal rat cardiac myocytes’ by Carmine Morisco et al. ,11 pp. 36–44, this issue. 

The immediate adaptation of cardiac pump function to haemodynamic stress is achieved by cardiac functional response, such as an increase in heart rate and cardiac contractility regulated through the Frank-Starling mechanism, the force-frequency relationship and adrenergic nerve stimulation. When the haemodynamic stress continues, cardiac hypertrophy develops first as the adaptive response of the myocardium that progresses to pathological (maladaptive) hypertrophy associated with fibrosis and apoptosis, and ultimately to heart failure. Maladaptive cardiac hypertrophy generally predisposes to heart failure and is an important risk factor for an increase in death of patients with heart failure, and therefore the signalling processes responsible for the development of cardiac hypertrophy have been and will be an important research target for therapies based on an understanding of the pathophysiology and development of heart failure.

During the course of cardiac hypertrophy caused by long-lasting pressure and volume overload, and after myocardial infarction, various neurohumoral factors, including catecholamines, angiotensin II (Ang II), endothelin-1 (ET-1), and cytokines, are released into the circulation to advance and/or modulate the course of cardiac hypertrophy.1,2 Activation of various protein kinases is involved in the induction of cardiac hypertrophy.3 For example, membrane receptors of Ang II (AT1 receptor), ET-1 and phenylephrine (PE; α1-adrenoceptor: α1-AR) belong to the same family and are coupled to heterotrimeric GTP binding proteins, Gq/11, resulting in the generation of 1,2-diacylglycerol (DAG) which activates protein kinase C and leads to cardiac hypertrophy. Overexpression of DAG kinase ζ, which converts DAG to inactive metabolites, suppresses the hypertrophy … 

* Corresponding author. Tel: +81 23 628 5234; fax: +81 236 28 5235. E-mail address : mendou{at}med.id.yamagata-u.ac.jp
Coordinated Functions of E-Cadherin and Transforming Growth Factor β Receptor II <i>In vitro</i> and <i>In vivo</i>
Authors: Claudia D. Andl, Brenton B. Fargnoli, Takaomi Okawa, Mark Bowser, Munenori Takaoka, Hiroshi Nakagawa, Andres Klein-Szanto, Xianxin Hua, Meenhard Herlyn, Anil K. Rustgi
Journal: Cancer Research (2006)

Abstract In epithelial cells, E-cadherin plays a key role in cell-cell adhesion, and loss of E-cadherin is a hallmark of tumor progression fostering cancer cell invasion and metastasis. To examine E-cadherin loss in squamous cell cancers, we used primary human esophageal epithelial cells (keratinocytes) as a platform and retrovirally transduced wild-type and dominant-negative forms of E-cadherin into these cells. We found decreased cell adhesion in the cells expressing dominant-negative E-cadherin, thereby resulting in enhanced migration and invasion. To analyze which molecular pathway(s) may modulate these changes, we conducted microarray analysis and found up-regulation of transforming growth factor β receptor II (TβRII) in the wild-type E-cadherin-overexpressing cells, which was confirmed by real-time PCR and Western blot analyses. To investigate the in vivo relevance of this finding, we analyzed tissue microarrays of paired esophageal squamous cell carcinomas and adjacent normal esophagus, and we could show a coordinated loss of E-cadherin and TβRII in ∼80% of tumors. To determine if there may be an E-cadherin-dependent regulation of TβRII, we show the physical interaction of E-cadherin with TβRII and that this is mediated through the extracellular domains of E-cadherin and TβRII, respectively. In addition, TβRI is recruited to this complex. When placed in the context of three-dimensional cell culture, which reflects the physiologic microenvironment, TβRII-mediated cell signaling is dependent upon intact E-cadherin function. Our results, which suggest that E-cadherin regulates TβRII function, have important implications for epithelial carcinogenesis characterized through the frequent occurrence of E-cadherin and TβRII loss. (Cancer Res 2006; 66(20): 9878-85)
Flow Microfluorometric Analysis of P3SS Murine Leukemia After Administration of Vincristine and Maytansine In Vivo
Authors: Oliver Alabaster, Mary Cassidy
Journal: JNCI Journal of the National Cancer Institute (1978)

Maytansine is a new drug undergoing clinical investigation. It has functional similarities to vincristine. Maytansine and vincristine were given to CDF1 mice with P388 leukemic ascites, and the cytokinetic response of the tumor cells was analyzed with a flow microfluorometer; mithramycin was used as the DNA fluorochrome. The results indicated a similar series of cytokinetic effects after administration of both drugs, though these effects were greater and more persistent after maytansine was given. Although both drugs produced some degree of multinucleation and endoreduplication, vincristine produced a discrete population of cells with a DNA content (fluorescence) equivalent to octoploidy (8C). Microscopy of the sorted 8C cells at 24 hours indicated 54% multinucleation and 33% mitotic figures. Most cells remained blocked in the G1-phase for at least 96 hours after administration of both drugs, which indicated that rapid DNA content distributions can be used to determine not only the effects of drugs on cell cycle distribution but also the duration of drug action.
Comparison of clinical and pharmacokinetic profiles of etanercept 25 mg twice weekly and 50 mg once weekly in patients with psoriasis
Authors: B. Elewski, C. Leonardi, A.B. Gottlieb, B.E. Strober, M.A. Simiens, M. Dunn, A. Jahreis
Journal: British Journal of Dermatology (2006)

Etanercept is a tumour necrosis factor antagonist that is approved in the U.S.A., Canada and Europe for treating adult patients with chronic moderate to severe plaque psoriasis.To assess whether clinical efficacy, safety and pharmacokinetic (PK) profiles of etanercept 50 mg once weekly are comparable to etanercept 25 mg twice weekly.Patients from a U.S. phase 3 study and a global phase 3 study were subsequently enrolled in an open-label extension study (extension study) where they all received etanercept at a dose of 50 mg once weekly for an initial 12 weeks. Patients who had received at least 24 weeks of etanercept 25 mg twice weekly in the global phase 3 study and were enrolled in the extension study (n = 265) were assessed for efficacy and safety at extension study baseline and after 12 weeks of etanercept 50 mg once weekly. Efficacy endpoints included the Psoriasis Area and Severity Index (PASI), the Dermatology Life Quality Index and the Physician's Global Assessment of psoriasis. In addition, PK profiles from patients in the U.S. phase 3 study were compared with PK profiles from another set of patients in the extension study. Comparison was made between a subset of patients receiving etanercept 25 mg twice weekly dosing in the U.S. phase 3 study (n = 13) and those receiving etanercept 50 mg once weekly in the extension study (n = 84).The mean PASI score was 5.77 at extension study baseline after treatment with etanercept 25 mg twice weekly, which was sustained at 5.82 after 12 weeks of etanercept 50 mg once weekly. Similar results were observed in other efficacy endpoints. Etanercept 50 mg once weekly was generally well tolerated. No new safety findings were reported. PK profiles overlapped extensively between the two dosing regimens.In this report, we demonstrate that efficacy, safety and PK profiles were comparable between etanercept 25 mg twice weekly and 50 mg once weekly in patients who had received at least 24 weeks of etanercept 25 mg twice weekly prior to receiving etanercept 50 mg once weekly in the extension study.
Prediction of Pharmacokinetic Alterations Caused by Drug-Drug Interactions: Metabolic Interaction in the Liver
Authors: K. Ito, T. Iwatsubo, S. Kanamitsu, K. Ueda, H. Suzuki, Y. Sugiyama
Journal: Pharmacological Reviews (1998)

Serious side-effects caused by drug interactions have attracted a great deal of attention and have become a social problem since the coadministration of ketoconazole and terfenadine was reported to cause potentially life-threatening ventricular arrhythmias ([Monahan et al., 1990][1]), and an
The Diffusion and Impact of Clean Indoor Air Laws
Authors: Michael P. Eriksen, Rebecca L. Cerak
Journal: Annual Review of Public Health (2008)

Over the past quarter century, primarily as a result of scientific discovery, citizen advocacy, and legislative action, comprehensive clean indoor air laws have spread rapidly throughout the world. Laws that establish completely smoke-free indoor environments have many relative advantages including being low cost, safe, effective, and easy to implement. The diffusion of these laws has been associated with a dramatic and rapid reduction in population levels of serum cotinine among nonsmokers and has also contributed to a reduction in overall cigarette consumption among smokers, with no adverse economic impact, except to the tobacco industry. Currently, nearly half of the U.S. population lives in jurisdictions with some combination of completely smoke-free workplaces, restaurants, or bars. The diffusion of clean indoor air laws is spreading rapidly throughout the world, stimulated by the first global health treaty, the Framework Convention on Tobacco Control.
Insulin Regulates Cleavage of Procaspase-9 via Binding of X Chromosome-Linked Inhibitor of Apoptosis Protein in HT-29 Cells
Authors: Ji-Eun Kim, Steven R. Tannenbaum
Journal: Cancer Research (2004)

Abstract Insulin significantly reduced tumor necrosis factor (TNF)-α–induced cleavage of procaspase-8, -9, and -3 and poly(ADP-ribose) polymerase when observed for up to 24 hours in a dose-dependent manner. Signaling pathways responsible for the inhibitory effects of insulin were investigated by using protein kinase inhibitors. Both phosphatidylinositol 3′-kinase (PI3K) and mitogen-activated protein kinase kinase pathways mediate the ability of insulin to decrease the TNF-α–induced cleavage of procaspase-8. In contrast, only the PI3K inhibitor reversed the effect of insulin on the TNF-α–induced cleavage of procaspase-9. Moreover, insulin decreased the apoptotic level induced by TNF-α, whereas the PI3K inhibitor enhanced it. The protein level of Apaf-1, an activator of procaspase-9, remained constant with the application of agents affecting the cleavage of procaspase-9. In examining another regulator of cleaved caspase-9, X chromosome-linked inhibitor of apoptosis protein (XIAP), we observed that TNF-α treatment induced fragmentation of XIAP, which was also enhanced by the PI3K inhibitor. In addition, XIAP was coimmunoprecipitated with procaspase-9. The treatment with TNF-α reduced the level of XIAP precipitated with procaspase-9, whereas insulin reversed this effect. Moreover, PI3K and Akt inhibitors, but not mammalian target of rapamycin inhibitor, inhibited the effect of insulin on the coprecipitation of procaspase-9 and XIAP. Our data suggest that insulin decreases the TNF-α–induced cleavage of procaspase-9 and subsequent apoptosis by regulating XIAP via the PI3K/Akt pathway.
Cargo from Tumor-Expressed Albumin Inhibits T-Cell Activation and Responses
Authors: Michael W. Graner, Anna Likhacheva, Jane Davis, Amy Raymond, Jared Brandenberger, Angela Romanoski, Sylvia Thompson, Emmanuel Akporiaye, Emmanuel Katsanis
Journal: Cancer Research (2004)

Abstract In this study, we show that rodent albumin is expressed by and cell surface localized on at least some murine tumor cells. We have been able to purify this tumor-expressed albumin from in vivo grown tumor masses. The tumor-expressed albumin, unlike normal serum albumin purified from blood, is capable of inhibiting T-cell activation, proliferation, and function in both in vitro and in vivo settings. Tumor-expressed albumin does not appear to affect antigen processing or presentation by professional antigen-presenting cells. The activity appears to lie in relatively small, lipid-like moieties that are presumably cargo for tumor-expressed albumin, and that activity can be removed from the albumin by lipid removal or treatment with lipase. Thus, we herein report of a novel form of tumor-induced immune suppression attributable to lipid-like entities, cloaked by albumin produced by tumors.
Beneficial effects of synthetic KL<sub>4</sub>surfactant in experimental lung transplantation
Authors: A. Sáenz, L. Álvarez, M. Santos, A. López-Sánchez, J.L. Castillo-Olivares, A. Varela, R. Segal, C. Casals
Journal: European Respiratory Journal (2010)

The aim of this study was to investigate whether intratracheal administration of a new synthetic surfactant that includes the cationic, hydrophobic 21-residue peptide KLLLLKLLLLKLLLLKLLLLK (KL 4 ), might be effective in reducing ischaemia–reperfusion injury after lung transplantation. Single left lung transplantation was performed in Landrace pigs 22 h post-harvest. KL 4 surfactant at a dose of 25 mg total phospholipid·kg body weight −1 (2.5 mL·kg body weight −1 ) was instilled at 37°C to the donor left lung (n = 8) prior to explantation. Saline (2.5 mL·kg body weight −1 ; 37°C) was instilled into the donor left lung of the untreated group (n = 6). Lung function in recipients was measured during 2 h of reperfusion. Recipient left lung bronchoalveolar lavage (BAL) provided native cytometric, inflammatory marker and surfactant data. KL 4 surfactant treatment recovered oxygen levels in the recipient blood (mean± sd arterial oxygen tension/inspiratory oxygen fraction 424±60 versus 263±101 mmHg in untreated group; p = 0.01) and normalised alveolar–arterial oxygen tension difference. Surfactant biophysical function was also recovered in KL 4 surfactant-treated lungs. This was associated with decreased C-reactive protein levels in BAL, and recovery of surfactant protein A content, normalised protein/phospholipid ratios, and lower levels of both lipid peroxides and protein carbonyls in large surfactant aggregates. These findings suggest an important protective role for KL 4 surfactant treatment in lung transplantation.
A Long-Branch Attraction Artifact Reveals an Adaptive Radiation in Pseudomonas
Authors: Josselin Bodilis, Sandrine Nsigue Meilo, Pierre Cornelis, Paul De Vos, Sylvie Barray
Journal: Molecular Biology and Evolution (2011)

A significant proportion of protein-encoding gene phylogenies in bacteria is inconsistent with the species phylogeny. It was usually argued that such inconsistencies resulted from lateral transfers. Here, by further studying the phylogeny of the oprF gene encoding the major surface protein in the bacterial Pseudomonas genus, we found that the incongruent tree topology observed results from a long-branch attraction (LBA) artifact and not from lateral transfers. LBA in the oprF phylogeny could be explained by the faster evolution in a lineage adapted to the rhizosphere, highlighting an unexpected adaptive radiation. We argue that analysis of such artifacts in other inconsistent bacterial phylogenies could be a valuable tool in molecular ecology to highlight cryptic adaptive radiations in microorganisms.
Controlled evaluation of primidone and diphenyllhydantoin sodium. Comparative anticonvulsant efficacy and toxicity in children
Authors: J. G. Milichap
Journal: JAMA (1968)

Primidone and diphenylhydantoin sodium were compared in a controlled study of children with major varieties of epilepsy. Records of seizures were adequate in 24 patients, and side effects were evaluated in 37. Seizures were controlled in six of 12 patients treated with primidone and four of 12 who received diphenylhydantoin. Primidone and diphenylhydantoin caused side effects in three of 20 patients, and in six of 17 patients, respectively. The drugs were found to differ only in the nature of their side effects.
Delivered Dose and Vascular Response After β-Radiation for In-Stent Restenosis
Authors: Yoshihiro Morino, Hideaki Kaneda, Tim Fox, Atsushi Takagi, Ali H.M. Hassan, Raoul Bonan, Ian Crocker, Alexandra J. Lansky, Warren K. Laskey, Mohan Suntharalingam, Heidi N. Bonneau, Paul G. Yock, Yasuhiro Honda, Peter J. Fitzgerald
Journal: Circulation (2002)

Observations from previous intracoronary radiation therapy trials noted a considerable discrepancy between the prescribed radiation dose and the dose actually delivered. The aims of this study were to investigate the effect of actual delivered dose on vascular changes and to test the appropriateness of the current dose prescription.Serial volumetric intravascular ultrasound (IVUS) analysis was performed in 30 in-stent restenosis cases treated with a 40-mm (90)Sr/Y source train. The fixed dose was prescribed at 2 mm from the centerline of the source train (18.4 Gy at 2 mm for reference diameter < or =3.35 mm and 23 Gy for diameter > or =3.36 mm). Only stent segments with full radiation coverage and device injury were enrolled and divided into 2-mm-long subsegments (n=202). D(S90)EEM (the minimum dose absorbed by 90% of the external elastic membrane surface) was calculated as the delivered dose corresponding to each segment, assuming that the radiation catheter occupied the same position in the vessel as the IVUS catheter. Mean D(S90)EEM of 23.5+/-5.82 Gy (range 12.3 to 41.7 Gy) was delivered to these subsegments. Overall, intimal hyperplasia volume remained constant from postintervention to follow-up (2.23+/-1.10 to 2.32+/-1.09 mm3/m; P=NS). Regression analysis revealed there was no correlation between delivered dose intensity and changes in intimal hyperplasia volume. No particular dose-dependent complications were appreciated in this delivered dose range.The current dose-prescription protocol of (90)Sr/Y radiation to native in-stent restenosis lesions may provide substantial inhibition of neointimal reproliferation regardless of the actual delivered dose intensity.
Bone Density and Cortical Structure after Pediatric Renal Transplantation
Authors: Anniek M. Terpstra, Heidi J. Kalkwarf, Justine Shults, Babette S. Zemel, Rachel J. Wetzsteon, Bethany J. Foster, C. Frederic Strife, Debbie L. Foerster, Mary B. Leonard
Journal: Journal of the American Society of Nephrology (2012)

The impact of renal transplantation on trabecular and cortical bone mineral density (BMD) and cortical structure is unknown. We obtained quantitative computed tomography scans of the tibia in pediatric renal transplant recipients at transplantation and 3, 6, and 12 months; 58 recipients completed at least two visits. We used more than 700 reference participants to generate Z-scores for trabecular BMD, cortical BMD, section modulus (a summary measure of cortical dimensions and strength), and muscle and fat area. At baseline, compared with reference participants, renal transplant recipients had significantly lower mean section modulus and muscle area; trabecular BMD was significantly greater than reference participants only in transplant recipients younger than 13 years. After transplantation, trabecular BMD decreased significantly in association with greater glucocorticoid exposure. Cortical BMD increased significantly in association with greater glucocorticoid exposure and greater decreases in parathyroid hormone levels. Muscle and fat area both increased significantly, but section modulus did not improve. At 12 months, transplantation associated with significantly lower section modulus and greater fat area compared with reference participants. Muscle area and cortical BMD did not differ significantly between transplant recipients and reference participants. Trabecular BMD was no longer significantly elevated in younger recipients and was low in older recipients. Pediatric renal transplant associated with persistent deficits in section modulus, despite recovery of muscle, and low trabecular BMD in older recipients. Future studies should determine the implications of these data on fracture risk and identify strategies to improve bone density and structure.