tbuckley/cabot-search huggingface dataset:
Unethical research relating to Helicobacter pylori?
Authors: D Y Graham, M F Go
Journal: Gut (1995)

<h3>Abstract</h3> Spike and wave discharges (SWDs) of absence epilepsy are considered as pathologic alterations of sleep spindles; however, their network-level relationship has never been convincingly revealed. In order to observe the development and generalization of the thalamocortical SWDs and the concomitant alterations of sleep related oscillations, we performed local field potential and single unit recordings in rats for 3 months during their maturation. We found that while SWDs and spindles look similar in young, they become different with maturation and shift to appear in different brain states. Thus, despite being generated by the same network, they are likely two distinct manifestations of the thalamocortical activity. We show that while spindles are already mainly global oscillations, SWDs appear mainly only focally in young. They become capable to generalize later with maturation, when the out-of-focus brain regions develop a decreased inhibitory/excitatory balance. These results suggest that a hyperexcitable focus is not sufficient alone to drive generalized absence seizures. Importantly, we also found the gradual age dependent disappearance of sleep spindles coinciding with the simultaneous gradual emergence of spike-and-waves, which both could be reversed by the proper dosing of ethosuximide. Based on these observations we conclude that the absence seizure development might be a multi-step process, which might involve the functional impairment of cortical interneurons and network-level changes that negatively affect sleep quality. <b>Significance statement</b> Absence seizure development parallels with the deterioration of slow wave sleep, which might be reversible with ethosuximide in a narrow therapeutic range, but not with early electrical seizure abruption. Thus, by proper dosing, spindles can be pharmaceutically recovered while epileptic activity is suppressed and absence related sleep and learning disturbances may be counterbalanced. We further found that despite the characteristic high voltage rhythmic global ictal EEG patterns the absence seizures are not accompanied with widespread phase-locking of neuronal activities.
Lack of functional assembly in mitochondrial supercomplexes: a new insight into impaired mitochondrial function?
Authors: F. J. Garcia-Palmer
Journal: Cardiovascular Research (2008)

A new mitochondrial disorder in heart failure that fits in the category of mitochondrial cytopathies is the exciting finding in the paper by Rosca et al. 1 presented in this issue of Cardiovascular Research , which also explores a new insight into the functionality of mitochondria in the heart.

The function of heart muscle is highly dependent on the energy generated by mitochondria by oxidation of fatty acids and carbohydrates through the tricarboxylic acid cycle, which is the direct source of electrons for the respiratory electron chain where oxidative phosphorylation and associated ATP synthesis takes place. Defects in mitochondrial structure and function have been found in association with cardiovascular diseases such as dilated and hypertrophic cardiomyopathy, cardiac conduction defects and sudden death, ischaemic and alcoholic cardiomyopathy, as well as myocarditis. While a subset of these mitochondrial abnormalities has a defined genetic basis, other abnormalities appear to be due to a more sporadic or environmental cardiotoxic insult or have not yet been characterized.2,3

A major function of mitochondria is the conversion of energy released by metabolic processes in the mitochondrial matrix into the energy currency of the cell—ATP—a process mediated by the oxidative phosphorylation system (OXPHOS), a group of transmembrane protein complexes which constitute the … 

*Corresponding author. Tel: + 34 971 173 187; fax: + 34 971 173 184. E-mail address : paco.garcia-palmer{at}uib.es
Region- and Type-Specific Induction of Matrix Metalloproteinases in Post–Myocardial Infarction Remodeling
Authors: Eric M. Wilson, Sina L. Moainie, Julia M. Baskin, Abigail S. Lowry, Anne M. Deschamps, Rupak Mukherjee, T. Sloane Guy, Martin G. St John-Sutton, Joseph H. Gorman, L. Henry Edmunds, Robert C. Gorman, Francis G. Spinale
Journal: Circulation (2003)

Induction of matrix metalloproteinases (MMPs) contributes to adverse remodeling after myocardial infarction (MI). Whether a region- and type-specific distribution of MMPs occurs within the post-MI myocardium remained unknown.Ten sheep were instrumented with a sonomicrometry array to measure dimensions in 7 distinct regions corresponding to the remote, transition, and MI regions. Eight sheep served as reference controls. The relative abundance of representative MMP types and the tissue inhibitors of the MMPs (TIMPs) was quantified by immunoblotting. Segment length increased from baseline in the remote (24.9+/-5.4%), transition (18.0+/-2.9%), and MI (53.8+/-11.0%) regions at 8 weeks after MI (P<0.05) and was greatest in the MI region (P<0.05). Region- and type-specific changes in MMPs occurred after MI. For example, MMP-1 and MMP-9 abundance was unchanged in the remote, fell to 3+/-2% in the transition, and was undetectable in the MI region (P<0.05). MMP-13, MMP-8, and MT1-MMP increased by >300% in the transition and MI regions (P<0.05). TIMP abundance decreased significantly in the transition region after MI and fell to undetectable levels within the MI region.The unique findings of this study were 2-fold. First, changes in regional geometry after MI were associated with changes in MMP levels. Second, a region-specific portfolio of MMPs was induced after MI and was accompanied by a decline in TIMP levels, indicative of a loss of MMP inhibitory control. Targeting the regional imbalance between specific MMPs and TIMPs within the post-MI myocardium holds therapeutic potential.
STUDIES ON GONOCOCCUS INFECTION
Authors: John Swanson
Journal: The Journal of Experimental Medicine (1973)

Attachment of Neisseria gonorrhoeae to amnion cells in tissue culture is facilitated if the gonococci bear pili. This has been determined by studying the number of pilated, colony type 2 gonococci associated with amnion cells after incubation in vitro as compared with the number of nonpilated, colony type 4 gonococci present with amnion cells under the same conditions. These data are supported by light microscope findings. Electron microscope studies provide visualization of fine structure of gonococcal attachment. Gonococci are also found within amnion cells in this in vitro system.
Autonomic Control of Cardiac Action Potentials
Authors: Cecile Terrenoire, Colleen E. Clancy, Joseph W. Cormier, Kevin J. Sampson, Robert S. Kass
Journal: Circulation Research (2005)

I(Ks), the slowly activating component of the delayed rectifier current, plays a major role in repolarization of the cardiac action potential (AP). Genetic mutations in the alpha- (KCNQ1) and beta- (KCNE1) subunits of I(Ks) underlie Long QT Syndrome type 1 and 5 (LQT-1 and LQT-5), respectively, and predispose carriers to the development of polymorphic ventricular arrhythmias and sudden cardiac death. beta-adrenergic stimulation increases I(Ks) and results in rate dependent AP shortening, a control system that can be disrupted by some mutations linked to LQT-1 and LQT-5. The mechanisms by which I(Ks) regulates action potential duration (APD) during beta-adrenergic stimulation at different heart rates are not known, nor are the consequences of mutation induced disruption of this regulation. Here we develop a complementary experimental and theoretical approach to address these questions. We reconstituted I(Ks) in CHO cells (ie, KCNQ1 coexpressed with KCNE1 and the adaptator protein Yotiao) and quantitatively examined the effects of beta-adrenergic stimulation on channel kinetics. We then developed theoretical models of I(Ks) in the absence and presence of beta-adrenergic stimulation. We simulated the effects of sympathetic stimulation on channel activation (speeding) and deactivation (slowing) kinetics on the whole cell action potential under different pacing conditions. The model suggests these kinetic effects are critically important in rate-dependent control of action potential duration. We also investigate the effects of two LQT-5 mutations that alter kinetics and impair sympathetic stimulation of I(Ks) and show the likely mechanism by which they lead to tachyarrhythmias and indicate a distinct role of I(KS) kinetics in this electrical dysfunction. The full text of this article is available online at http://circres.ahajournals.org.
Patients with chronic hepatitis B treated with oral antiviral therapy retain a higher risk for HCC compared with patients with inactive stage disease
Authors: Ju-Yeon Cho, Yong-Han Paik, Won Sohn, Hyun Chin Cho, Geum-Youn Gwak, Moon Seok Choi, Joon Hyeok Lee, Kwang Cheol Koh, Seung Woon Paik, Byung Chul Yoo
Journal: Gut (2014)

<h3>Background</h3> It is generally stated that oral antiviral therapy in patients with chronic hepatitis B (CHB) decreases the risk of developing hepatocellular carcinoma (HCC). Although oral nucleos(t)ide analogues (NUCs) may induce a state similar to inactive stage CHB, the long-term risk for HCC in patients treated with NUCs compared with inactive CHB is unclear. <h3>Methods</h3> A total of 1378 patients who were treatment naïve and started NUC therapy and 1014 patients with inactive stage CHB who were HBeAg-negative and continuously had hepatitis B DNA &lt;2000 IU/mL during follow-up were enrolled. The NUC group was divided into two groups by continuous viral suppression: NUC complete responder (CR) group and NUC incomplete responder (IR) group. Cumulative HCC incidence rates were compared between the groups. <h3>Results</h3> The risk of developing HCC was significantly higher in the NUC CR group compared with the inactive CHB group, regardless of the presence of baseline liver cirrhosis (p&lt;0.001). Risk factors associated with the development of HCC were treatment groups (p&lt;0.001), age (p&lt;0.001), sex (p&lt;0.001) and the presence of liver cirrhosis at baseline (p=0.005). Of the NUC group, the cumulative incidence of HCC in the NUC IR group was significantly higher compared with the NUC CR group (p=0.028). <h3>Conclusions</h3> The use of potent oral antiviral therapy can effectively suppress HBV replication in patients with CHB. However, the risk of HCC development in patients treated with oral antiviral agent is still significantly higher than patients with inactive stage CHB.
Phosphorylation of Nox1 Regulates Association With NoxA1 Activation Domain
Authors: Jennifer Streeter, Brandon M. Schickling, Shuxia Jiang, Bojana Stanic, William H. Thiel, Lokesh Gakhar, Jon C.D. Houtman, Francis J. Miller
Journal: Circulation Research (2014)

Activation of Nox1 initiates redox-dependent signaling events crucial in the pathogenesis of vascular disease. Selective targeting of Nox1 is an attractive potential therapy, but requires a better understanding of the molecular modifications controlling its activation.To determine whether posttranslational modifications of Nox1 regulate its activity in vascular cells.We first found evidence that Nox1 is phosphorylated in multiple models of vascular disease. Next, studies using mass spectroscopy and a pharmacological inhibitor demonstrated that protein kinase C-beta1 mediates phosphorylation of Nox1 in response to tumor necrosis factor-α. siRNA-mediated silencing of protein kinase C-beta1 abolished tumor necrosis factor-α-mediated reactive oxygen species production and vascular smooth muscle cell migration. Site-directed mutagenesis and isothermal titration calorimetry indicated that protein kinase C-beta1 phosphorylates Nox1 at threonine 429. Moreover, Nox1 threonine 429 phosphorylation facilitated the association of Nox1 with the NoxA1 activation domain and was necessary for NADPH oxidase complex assembly, reactive oxygen species production, and vascular smooth muscle cell migration.We conclude that protein kinase C-beta1 phosphorylation of threonine 429 regulates activation of Nox1 NADPH oxidase.
The Catechol Amine Content of Various Organs of the Cat After Injections and Infusions of Adrenaline and Noradrenaline
Authors: U. S. VON EULER
Journal: Circulation Research (1956)

Infusions of 2.5-7.8 µg. noradrenaline/Kg./min. over 30 min. and intraperitoneal injections of noradrenaline and adrenaline up to 2000 µg/Kg, in the cat had no effect on the catechol amine content of the heart, spleen, liver, kidney and skeletal muscle, except for a slight increase in the adrenaline content. It is concluded that these organs lack the ability to accumulate circulating catechol amines administered in physiologic dosage.
Behavioral and Social Outcomes in Adolescent Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study
Authors: Kris Ann P. Schultz, Kirsten K. Ness, John Whitton, Christopher Recklitis, Brad Zebrack, Leslie L. Robison, Lonnie Zeltzer, Ann C. Mertens
Journal: Journal of Clinical Oncology (2007)

Purpose Adolescents, regardless of medical history, may face behavioral and social challenges. Cancer and related treatments represent additional challenges for teens navigating the transition from childhood to adulthood. This study was conducted to evaluate behavioral and social outcomes of adolescent childhood cancer survivors using data from the Childhood Cancer Survivor Study. Patients and Methods We evaluated 2,979 survivors and 649 siblings of cancer survivors to determine the incidence of difficulty in six behavioral and social domains (depression/anxiety, headstrong, attention deficit, peer conflict/social withdrawal, antisocial behaviors, and social competence). Outcomes were determined by calculating parent-reported scores to questions from the behavior problem index. Results Survivors and siblings were similar in age at the time of interview (mean: 14.8, survivors; 14.9, siblings; range, 12 to 17 years). Overall, multivariate analyses showed that survivors were 1.5 times (99% CI, 1.1 to 2.1) more likely than siblings to have symptoms of depression/anxiety and 1.7 times (99% CI, 1.3 to 2.2) more likely to have antisocial behaviors. Scores in the depression/anxiety, attention deficit, and antisocial domains were significantly elevated in adolescents treated for leukemia or CNS tumors when compared with siblings. In addition, survivors of neuroblastoma had difficulty in the depression/anxiety and antisocial domains. Treatments with cranial radiation and/or intrathecal methotrexate were specific risk factors. Conclusion Adolescent survivors of childhood cancer, especially those with a history of leukemia, CNS tumors, or neuroblastoma, may be at increased risk for adverse behavioral and social outcomes. Increased surveillance of this population, in combination with development of interventional strategies, should be a priority.
Association of the 5-aminoimidazole-4-carboxamide ribonucleotide transformylase gene with response to methotrexate in juvenile idiopathic arthritis
Authors: A. Hinks, H. Moncrieffe, P. Martin, S. Ursu, S. Lal, L. Kassoumeri, T. Weiler, D. N. Glass, S. D. Thompson, L. R. Wedderburn, W. Thomson
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objectives</h3> Methotrexate (MTX) is the mainstay treatment for juvenile idiopathic arthritis (JIA), however approximately 30% of children will fail to respond to the drug. Identification of genetic predictors of response to MTX would be invaluable in developing optimal treatment strategies for JIA. Using a candidate gene approach, single nucleotide polymorphisms (SNPs) within genes in the metabolic pathway of MTX, were investigated for association with response to treatment in JIA cases. <h3>Methods</h3> Tagging SNPs were selected across 13 MTX metabolic pathway genes and were genotyped using Sequenom genotyping technology in subjects recruited from the Sparks Childhood Arthritis Response to Medication Study. Response to MTX was defined using the American College of Rheumatology (ACR) paediatric response criteria and SNP genotype frequencies were compared between the worst and best responders (ACR-Ped70) to MTX. An independent cohort of US JIA cases was available for validation of initial findings. <h3>Results</h3> One SNP within the inosine triphosphate pyrophosphatase gene (<i>ITPA</i>) and two SNPs within 5-aminoimidazole-4-carboxamide ribonucleotide transformylase gene (<i>ATIC</i>) were significantly associated with a poor response to MTX. One of the <i>ATIC</i> SNPs showed a trend towards association with MTX response in an independent cohort of US JIA cases. Meta-analysis of the two studies strengthened this association (combined p value=0.002). <h3>Conclusions</h3> This study presents association of a SNP in the <i>ATIC</i> gene with response to MTX in JIA. There is now growing evidence to support a role of the <i>ATIC</i> gene with response to MTX treatment. These results could contribute towards a better understanding of and ability to predict MTX response in JIA.
Methotrexate effect on anti-cyclic citrullinated peptide antibody levels in rheumatoid arthritis
Authors: A Spadaro
Journal: Annals of the Rheumatic Diseases (2005)

We read with interest the recent reports1–3 focusing on the changes of rheumatoid factor and anti-citrullinated peptide antibodies (anti-CCP) during infliximab treatment in refractory rheumatoid arthritis (RA), unresponsive to conventional disease modifying antirheumatic drugs.

Alessandri et al 3 reported that 24 weeks’ infliximab treatment reduced anti-CCP levels according to the study of Bobbio-Pallavicini et al .2 These results are in contrast with the findings of De Rycke et al , which showed no change of this autoantibody serum level after …
Role of cholecystokinin in the regulation of liquid gastric emptying and gastric motility in humans: studies with the CCK antagonist loxiglumide
Authors: W Schwizer, J Borovicka, P Kunz, R Fraser, C Kreiss, M D’Amato, G Crelier, P Boesiger, M Fried
Journal: Gut (1997)

Background —Exogenous cholecystokinin (CCK) inhibits antral motility and slows gastric emptying (GE) but the effect of endogenous CCK on the gastric motor mechanisms responsible for GE remains unclear. Methods —The effect of the CCK-A antagonist loxiglumide (LOX) on GE and motility was studied using magnetic resonance imaging in six healthy volunteers after ingestion of 500 ml Intralipid 10% (550 kcal). Subjects were studied in the supine position on two occasions during intravenous infusion of LOX (66 μmol/kg/h for 10 min followed by 22 μmol/kg/h) or placebo. GE was determined every 15 minutes using transaxial abdominal scans and motility was studied by means of 120 coronal scans, 1.2 seconds apart. For each coronal image the proximal and distal (antral) diameters were measured at a fixed point in the stomach to determine contraction frequency (ACF) and amplitude (AMP). Results —GE was faster during LOX infusion than placebo (t 1/2 31 (22) versus 115 (67) minutes, p&lt;0.03). There was little variation in the diameter of the proximal stomach with either LOX or placebo. In the distal stomach marked contractile activity was observed during LOX (ACF 2.9 (0.2) versus 1.5 (2.9) during placebo, p&lt;0.01). AMP also increased during LOX compared with placebo (56 (22)% versus 27 (16)%, p&lt;0.001). Conclusion —The increases in antral motility are likely to contribute to the acceleration of GE and suggest that CCK may regulate GE by acting on the distal stomach although an effect on the proximal stomach cannot be excluded.
A6.1 Antibody Response Against<i>Porphyromonas Gingivalis</i>and Matrix Metalloproteinase-3 are Associated with Anti-Citrullinated Protein Antibody in Rheumatoid Arthritis, but only Matrix Metalloproteinase-3 is a Predictive Factor of Response to Infliximab
Authors: M Rinaudo-Gaujous, P Miossec, V Blasco-Baque, P Gaudin, T Thomas, A Moreau, C Genin, S Paul, H Marotte
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background and Objectives</h3> This study evaluates clinical and biological markers of rheumatoid arthritis (RA) severity including matrix metalloproteinase (MMP-3) and <i>Porphyromonas gingivalis (P. gingivalis)</i> serology during infliximab treatment and highlights predictive factors of response to infliximab. <h3>Materials and Methods</h3> Joint damage and severe periodontal disease were assessed in 101 RA patients included in this study. DAS28, anti-citrullinated protein antibodies (ACPA), anti-<i>P. gingivalis</i> antibody, and MMP-3 were monitored before and at 6 months of infliximab therapy. ACPA, anti-<i>P. gingivalis</i> antibody, and MMP-3 were determined by ELISA. <h3>Results</h3> At baseline, ACPA titers were associated with anti-<i>P. gingivalis</i> LPS-specific antibodies titers (P &lt; 0.05). Anti-<i>P. gingivalis</i> antibodies were not significantly correlated with clinical, biological, or destruction parameters of RA disease. At 6 months of infliximab therapy, MMP-3 level decreased (from 119 ± 103 ng/ml to 62.44 ± 52 ng/ml; P &lt; 0.0001), whereas <i>P. gingivalis</i> antibody levels remained at the same level. DAS28 and inflammation markers (CRP and ESR) also decreased significantly during infliximab therapy (P &lt; 0.05) as ACPA levels (P &lt; 0.001). Only high MMP-3 level at baseline was associated with infliximab efficacy (P &lt; 0.01). <h3>Conclusions</h3> MMP-3 level can be a useful marker of the efficacy of infliximab in RA patients. The treatment did not affect anti- <i>P. gingivalis</i> antibodies.
Electrophysiological and Beta-Receptor Blocking Effects of MJ 1999 on Dog and Rabbit Cardiac Tissue
Authors: HAROLD C. STRAUSS, J. THOMAS BIGGER, BRIAN F. HOFFMAN
Journal: Circulation Research (1970)

Effects of MJ 1999 (1 x 10 -9 M to 1 x10 -2 M) on rabbit right atrial and canine Purkinje fiber preparations were studied. MJ 1999 had a pA 2 of 6.1 against the chronotropic effect of isoproterenol on rabbit SA node. Significant slowing first occurred with MJ 1999 at 1 x 10 -4 M. The spontaneous firing rate of Purkinje fibers in vitro did not change significantly after exposure to MJ 1999 1 x 10 -4 M. Idioventricular rate was slowed and idioventricular escape time was prolonged in dogs with atrioventricular block after MJ 1999, 2.0 mg/kg. MJ 1999, 1 x 10 -7 M to 5 x 10 -4 M, had no effect on resting potential, overshoot and amplitude of phase 0 of transmembrane potentials (TMP) recorded from canine ventricular muscle, canine Purkinje fibers or rabbit atrial fibers nor did it affect phase 0 V · max of TMP recorded from the Purkinje or atrial fibers. Similar concentrations of MJ 1999 had no effect on membrane responsiveness in Purkinje fibers. In Purkinje fibers, control action potential duration (APD) was 325 msec and the effective refractory period (ERP) 277 msec. MJ 1999, 1 x 10 -3 M, increased the APD to 470 msec and ERP to 404 msec. In ventricular muscle fibers, APD was 230 msec and the ERP was 223 msec, under control conditions. MJ 1999, 1 x 10 -3 M, increased the APD to 281 msec and ERP to 267 msec. Changes in APD and ERP induced by MJ 1999 were magnified at slower rates of stimulation. The effects of MJ 1999 on both APD and ERP were more marked in Purkinje fibers than in ventricular muscle fibers. The effects of MJ 1999 on phase 0 of the TMP and on repolarization and refractoriness of the TMP differ markedly from those seen with quinidine, procainamide, and lidocaine.