tbuckley/cabot-search huggingface dataset:
Abstract 195: Increases in Ca <sup>2+</sup> Influx through the L-type Ca <sup>2+</sup> Channel Induces Pathological Cardiomyocyte Hypertrophy
Authors: Xiongwen Chen, Hiroyuki Nakayama, Hongyu Zhang, Xiaoying Zhang, David M Harris, Remus M Berretta, Rachel M Wilson, Scott MacDonnell, Hajime Kubo, Jutta Weisser-Thomas, Andrea D Eckhart, Walter J Koch, Jeffery D Molkentin, Steven R Houser
Journal: Circulation (2007)

Cardiac hypertrophy (LVH) is associated with the development of arrhythmia (sudden cardiac death) and congestive heart failure. While there is a clear role for activation of calcium (Ca) regulated signaling pathways in LVH, the specific role of Ca influx (I Ca ) through the L-type calcium channel (LTCC) has not been directly examined and is the topic of this study. Methods: In vitro, Ca influx into cultured feline (F) and neonatal rat (NR) ventricular myocytes (VMs) was increased by infecting VMs with an adenovirus (Ad) containing a fusion gene encoding the β2a subunit of the LTCC (β2a)-GFP with AdGFP as the control (CTR). In vivo, we established transgenic mouse lines with inducible (Tet-off ) overexpression of the β2a subunit (β2a TG). All evaluations of mouse hearts or VMs were done with 4-month old mice. Results: Overexpression of β2a (MOI = 5) in cultured FVMs increased I Ca (111%) and cell volume (16%), protein synthesis (25%) and ANF expression; NFAT and HDAC translocations were increased in β2a FVMs (30% and 50% respectively); Blockade of the LTCC (nifedipine, NIF), intracellular Ca (BAPTA), calcineurin (cyclosporine A (CsA) and FK506) and CaMK II (KN93) prevented β2a mediated increases in cell volume, protein/DNA ratio, NFAT and HDAC translocations; The surface area of NRVMs infected with Adβ2a at 36 hours post infection was 52.4% larger than CTR, which was prevented by NIF, BAPTA, CsA, FK 506 and KN93; In TG mice, I Ca (CTR: 13.7 ± 0.7pA/pF, n=6 vs. TG: 24.3 ± 2.6pA/pF, n=6), fractional shortening (CTR: 8.0 ± 0.5%, n=16 vs. TG: 11.9 ± 1.1%, n=11) and peak Ca transient (Fluo-3) (CTR: 2.25 ± 0.08%, n=19 vs. TG: 3.37 ± 1.58, n=11) were significantly ( p&lt;0.05 ) increased in TG-VMs than in CTR-VMs; β2a TG mice had greater ejection fraction (CTR: 68.9 ± 1.3%, n=33 vs. TG: 74.4 ± 1.3%, n=34, p&lt;0.05), and posterior wall thickness (CTR: 1.10 ± 0.04mm, n=33 vs. TG: 1.22 ± 0.03mm, n=34, p&lt;0.001 ); The heart weight to body weight ratio in TG mice (6.90 ± 1.05mg/g, n=17) was greater ( p&lt;0.05 ) than in CTR (6.04 ± 0.93mg/g, n=51) with significantly larger myocyte cross-section area. Conclusion: Increases in Ca influx through the LTCC are sufficient to induce cardiomyocyte hypertrophy both in vitro and in vivo through the calcineurin/NFAT and HDAC dependent pathways.
Interactions between human immunodeficiency virus and herpes viruses within the oral mucosa
Authors: F.X. Mbopi-Keou, R.E. Mbu, H. Gonsu Kamga, G.C.M. Kalla, M. Monny Lobe, C.G. Teo, R.J. Leke, P.M. Ndumbe, L. Belec
Journal: Clinical Microbiology and Infection (2005)
The proinflammatory role of HECTD2 in innate immunity and experimental lung injury
Authors: Tiffany A. Coon, Alison C. McKelvey, Travis Lear, Shristi Rajbhandari, Sarah R. Dunn, William Connelly, Joe Y. Zhao, SeungHye Han, Yuan Liu, Nathaniel M. Weathington, Bryan J. McVerry, Yingze Zhang, Bill B. Chen
Journal: Science Translational Medicine (2015)

Invading pathogens may trigger overactivation of the innate immune system, which results in the release of large amounts of proinflammatory cytokines (cytokine storm) and leads to the development of pulmonary edema, multiorgan failure, and shock. PIAS1 is a multifunctional and potent anti-inflammatory protein that negatively regulates several key inflammatory pathways such as Janus kinase (JAK)-signal transducer and activator of transcription (STAT) and nuclear factor κB (NF-κB). We discovered a ubiquitin E3 ligase, HECTD2, which ubiquitinated and mediated the degradation of PIAS1, thus increasing inflammation in an experimental pneumonia model. We found that GSK3β phosphorylation of PIAS1 provided a phosphodegron for HECTD2 targeting. We also identified a mislocalized HECTD2 polymorphism, HECTD2(A19P), that was present in 8.5% of the population and functioned to reduce inflammation. This polymorphism prevented HECTD2/PIAS1 nuclear interaction, thus preventing PIAS1 degradation. The HECTD2(A19P) polymorphism was also protective toward acute respiratory distress syndrome (ARDS). We then developed a small-molecule inhibitor, BC-1382, that targeted HECTD2 and attenuated lipopolysaccharide (LPS)- and Pseudomonas aeruginosa-induced lung inflammation. These studies describe an unreported innate immune pathway and suggest that mutation or antagonism of the E3 ligase HECTD2 results in reduced severity of lung inflammation by selectively modulating the abundance of the anti-inflammatory protein PIAS1.
Risk-factors of negative predictive value of cardiovascular system damage in children with recurrent respiratory tract diseases
Authors: Ketevan Barabadze, Ann Tsabutashvili
Journal: European Respiratory Journal (2011)

Introduction:  Socio-economic problems in our country had a great influence on health degree of population. The myocardium disorders in early age have meaningfully risen all around in Georgia. The conventionally accepted risk-factors of cardiovascular system disorders: Smoking, obesity, low physical activity, poor nutrition, congenital load rate, and standard social and medical risk factors was taken into account in our study.   Aims:  Revealing of prognostic risk-factors of negative predictive value in cardiovascular system damages in children with recurrent respiratory tract diseases and building up the preventive strategy.   Methods:  A cross-sectional study was held. Examination involvement criteria were as follows: children9s age (from 3 to 15). Pathological recurrent progressiveness of the respiratory system pathologies (5-7 episodes within the last year). The study was carried out on the base of applications worked out by us according to American Heart Association recommendation.   Results:  The results are given in Table 1.   Conclusions:  Study revealed the prognostic risk-factors of cardiovascular system damages in children in Georgia with respiratory tract diseases. The application applied by us in the study, can be used by pediatrics as well to reveal of children of high risk group and build up the preventive strategy.
Increased baseline IL-6 is associated with health status impairment after three years in COPD patients
Authors: Renata Ferrari, Laura Caram, Suzana Tanni, Camila Correa, Irma Godoy
Journal: European Respiratory Journal (2013)

Previous study showed that Interleukin-6 (IL-6) increased significantly after 3 years and it was associated with mortality. However, the cutoff point of IL-6 associated with mortality and its association with other outcomes in COPD is unclear. Thus, the aim of this study is to evaluate association between values of IL-6 and disease outcome markers over time. A cohort of 77 outpatients with stable COPD was evaluated at baseline, and 53 (mean FEV1, 56% predicted) were included in the prospective study. We evaluated Interleukin-6 (IL-6), Modified Medical Research Council dyspnea scale (MMRC), six-minute walking distance (6MWD), body mass index (BMI), and Saint George's Respiratory Questionnaire (SGRQ) at baseline and after three years. Plasma concentration of IL-6 was measured by high sensitivity ELISA (BioSource International Inc, Ca, USA). The ROC curve showed that the cutoff for baseline IL-6, associated with mortality, in the cohort of 77 patients was ≥ 1.28 pg/ml (sensitivity 71.4%, specificity 72.3% and the area under the curve 0.70). Modifications over three years in the studied variables were included in a multiple logistic regression analysis to verify association with IL-6 ≥ 1.28 pg/ml. Modifications in SGRQ total score over three years were associated with increased values of IL-6 [Odds 0.07 (95% CI 0.01-0.14); p=0.02]. In conclusion, higher values of IL-6 at baseline were associated with the impairment of health status after three years.
Carbapenem non-susceptible Klebsiella pneumoniae from Micronet network hospitals, Italy, 2009 to 2012
Authors: A Sisto, F D'Ancona, M Meledandri, A Pantosti, G M Rossolini, A Raglio, R Serra, L Dematte, E Aiello, A Goglio, Collective Micronet network participants
Journal: Eurosurveillance (2012)

Carbapenem-resistant Klebsiella pneumoniae has recently been reported as a new, multidrug-resistant nosocomial pathogen in several hospitals from various Italian regions. Through Micronet, a new Italian sentinel laboratory-based surveillance network, we studied the trend of non-susceptibility of K. pneumoniae to selected carbapenems (imipenem and/or meropenem) in 14 of the 15 hospitals participating in the network. Analysis of data from 1 January 2009 to 30 April 2012 revealed a statistically significant increasing trend (p<0.01) in the proportion of carbapenem non-susceptible K. pneumoniae isolates from clinical specimens (from 2.2 % in 2009 to 19.4% in 2012). The increase in the proportion of non-susceptibility was very large for isolates from the respiratory tract (from 5.3% in 2009 to 38.5% in 2012) and blood (from 5.4% in 2009 to 29.2% in 2012). The results demonstrate the urgent need in Italy for infection control, guidelines, antibiotic stewardship programmes and utilisation of surveillance systems, such as Micronet, which are capable of receiving data from hospitals in real time for many pathogens and types of clinical specimens.
Synchrotron imaging of regional ventilation/perfusion- ratio after methacholine provocation in rabbit
Authors: Liisa Porra, Mathieu Guilbart, Satu Strengell, Pekka Suortti, Anssi Sovijärvi, Sam Bayat
Journal: European Respiratory Journal (2012)

Rationale: K-edge subtraction (KES) CT imaging with synchrotron radiation allows quantitative measurements of regional ventilation (V) during xenon inhalation and regional blood volume (VB) distributions during iodine infusion. In this study, we assessed the feasibility of quasi-simultaneous KES imaging of V and VB.  Methods: Experiments were performed in anaesthetized and ventilated New Zealand rabbits (n=5). Images of V and VB were obtained at baseline and after inhaled MCh (125 mg/ml). Heterogeneity of both parameters was estimated as the coefficient of variation (CV) between pixels.  Results: Images of V, VB and their ratio (V/VB) are shown in one rabbit at baseline and after MCh challenge (Figure). Mch inhalation produced clustered areas of poor ventilation; mean V decreased to 75.7±24.2%* and VB to 69.4±12.7%* of baseline. The CV of V increased to 334±186%*, CV of VB to 140±21%*, and CV of V/VB ratio to 180±50%* of baseline. Values are m±SD, *: significant change vs. baseline (P  Conclusions: KES imaging allowed quasi-simultaneous measurement of regional ventilation and blood volume. Mch challenge caused significant changes in V and VB and increased the mismatch between the parameters. This method allows quantitative assessment of changes in regional V/VB ratio induced by drugs in models of asthma.
Sputum interleukin (IL)-13 as a biomarker for the evaluation of asthma control
Authors: Zoi Tzilogianni, Petros Bakakos, Andriana I. Papaioannou, Anastasia Papaporfyriou, Georgios Hillas, Spyros Papiris, Nikolaos Koulouris, Stelios Loukides, Konstantinos Kostikas
Journal: European Respiratory Journal (2014)

Introduction: The management of patients with severe refractory asthma (SRA) is a difficult task that may benefit from the use of non-invasive assessment by biomarkers. Interleukin (IL)-13 is a cytokine with a central role in the TH2 response.  Objective: The assessment of IL-13 as a biomarker of asthma control in patients with SRA.  Methods: We recruited 170 patients (47 with SRA) from two University asthma clinics.Patients were submitted to pulmonary function testing, measurement of fractional exhaled nitric oxide (FeNO), and sputum induction with calculation of inflammatory cells and measurement of IL-13 in the supernatant. Asthma control test (ACT) was used for evaluation of asthma control (ACT values >19 identified well-controlled asthma). Severe refractory asthma was defined by the ATS criteria.  Results: IL-13 in sputum supernatant was increased in patients with SRA compared to patients with mild-to-moderate asthma [median (IQR): 156 (80-245) pg/mL vs. 78 (66-103) pg/mL, p  Conclusions: IL-13 in induced sputum may represent a useful index of disease control in patients with SRA. The better diagnostic accuracy of IL-13, compared to FeNO and sputum eosinophils, indicates a central role of this mediator in SRA.
Exhaled nitrogen oxide (FeNO) and nasal patency in adults in relation to levels of airborne fungal DNA in dwellings in Lund, Sweden
Authors: Gunilla Wieslander, Guihong Cai, Christina Isaxson, Anders Gudmundsson, Mats Bohgard, Erik Nordin, Aneta Wierzbicka, Dan Norbäck
Journal: European Respiratory Journal (2012)

Background:   Questionnaire studies have reported associations between indoor moulds and dampness, asthma and rhinitis. We investigated if levels of fungal DNA in dwellings were associated with nasal patency, tear film stability, and levels of exhaled NO.   Methods:  Totally 49 adults from 42 homes, randomly selected from a larger population survey in the city of Lund, Scania, Sweden. Exhaled NO was measured by NIOX MINO (50 ml/min). Nasal patency was measured by acoustic rhinometry. Tear film break up time (BUT) was monitored as a sign of eye irritation. FeNO was log-transformed and associations were analysed by multiple linear regression, adjusting for age, gender, pollen/furry pet allergy and smoking. Fungal DNA in airborne settled dust was measured in the living room for one weekby Petri dish method and levels of five fungal DNA-sequences were analysed by QPCR.   Results:  Three types of fungal DNA was commonly found in the homes. Exhaled NO was higher at higher concentrations of total fungal DNA (p=0.04). Mean cross-sectional area in the front part of the nasal cavity was decreased at higher levels of Aspergillus/Penicillium DNA (p=0.05), and posterior cross-sectional area was decreased at higher levels of Aspergillus versilcolor DNA (p=0.05). No associations were found between BUT and fungal DNA.   Conclusion:  Fungal DNA in settled dust in random selected ordinary homes can be a risk factor for nasal inflammation, measured as decreased nasal patency, and lower airway inflammation measured as exhaled NO.
Prednisone Response Is the Strongest Predictor of Treatment Outcome in Infant Acute Lymphoblastic Leukemia
Authors: Michael Dördelmann, Alfred Reiter, Arndt Borkhardt, Wolf-Dieter Ludwig, Nicolai Götz, Susanne Viehmann, Helmut Gadner, Hansjörg Riehm, Martin Schrappe
Journal: Blood (1999)
Feasibility of Immunotherapy of Relapsed Leukemia With Ex Vivo–Generated Cytotoxic T Lymphocytes Specific for Hematopoietic System-Restricted Minor Histocompatibility Antigens
Authors: Tuna Mutis, Rob Verdijk, Ellen Schrama, Bennie Esendam, Anneke Brand, Els Goulmy
Journal: Blood (1999)
Demographics, clinical course and outcome of children with status asthmaticus treated in a pediatric critical care unit: 8 year review
Authors: Shahid Sheikh, Nadeem Khan, Melissa Frasure, Manuel Cestari, Karen McCoy
Journal: European Respiratory Journal (2011)

Background:  This retrospective study was done to understand demographics and clinical course in children with status asthmaticus treated in a tertiary care pediatric intensive care unit (PICU).   Methods:  The medical charts of all patients above 5 years of age admitted to the PICU with status asthmaticus, at Nationwide Children9s hospital, Columbus, OH, between 2000-2007 were reviewed. Two hundred and forty seven (247) children were admitted on 281 occasions. Patients with significant co-morbidities were excluded. Final analysis was done using 222 encounters in 183 patients.   Results:  The mean age was 11 years (range, 5-20 years). The mean PICU stay was 2.1 days (range, 1-15 days) and mean hospital stay was 3.6 days. Male: Female 109:74. Eighty nine (49%) were on no asthma controller medications. Adherence to therapy was noted in 124 of whom only 41 (33%) claimed compliance. 191 were known asthmatics. Asthma severity noted in 75 patients revealed 22 (29%) had mild intermittent, mild persistent 23 (30%), moderate persistent 17 (23%) and severe persistent 13 (17%). Sixty seven (37%) had a positive family history of asthma. Smoking exposure was noted in 140 (76%). Among 222 encounters, 203 received continuous albuterol, 216 received i/v steroids, 113 receive Terbutaline, 57 received MgSO4, 8 received non-invasive ventilation (CPAP/BiPAP) and 16 received mechanical ventilation. All patients survived. Complications included bronchopneumonia in 25 and atelectasis in 29 patients.   Conclusion:  Asthmatics with any level of disease severity are at risk for asthma exacerbations requiring PICU stay especially if they are not compliant with their medications.
Reactive oxygen metabolites cause massive, reversible proteinuria and glomerular sieving defect without apparent ultrastructural abnormality.
Authors: T Yoshioka, I Ichikawa, A Fogo
Journal: Journal of the American Society of Nephrology (1991)

To identify the specific in vivo renal effect of reactive oxygen species (ROS), hydrogen peroxide (H2O2) was infused directly into the left renal artery in Munich-Wistar rats. H2O2 (5 to 50 mumol over 1 h) induced a dose-dependent increase in urine protein excretion rate in infused kidneys, reaching a maximum at the dose of 35 mumol (on average, a 60-fold increase from baseline). The H2O2 (35 mumol)-induced proteinuria peaked over 1 h and completely normalized by 24 h after the infusion. Electrophoresis revealed that the urine protein is primarily of glomerular origin. Fractional clearances of graded-size neutral dextran of larger molecular radii, an index of glomerular size selectivity, were significantly and substantially elevated immediately but normalized by 24 h after the infusion. GFR and RPF rate remained unchanged throughout the entire time course examined. The H2O2-induced proteinuria was largely prevented by pretreatment with catalase (20 mg, iv) or deferoxamine (30 mg/100 g body wt, iv). Thus, iron-dependent metabolites of hydrogen peroxide appear to be involved in this proteinuria and glomerular size-selective defect. Light and electron microscopy, including determination of anionic site density at lamina rara externa of glomerular capillary wall by polyethyleneimine staining, did not reveal any appreciable abnormality throughout the study period, including at the peak of proteinuria. Thus, ROS can cause massive, reversible proteinuria by inducing a molecular size-selectivity defect of the glomerular capillary wall without apparent ultrastructural abnormalities. The results raise the possibilities: (1) that persistent proteinuria of a variety of renal diseases may reflect persistence of pathogenic ROS acting on glomeruli because the potent proteinuric effect of ROS can be transient (2) that the light and electron microscopy abnormalities in glomeruli of ROS-induced renal injuries reported thus far may have no direct causal linkage to proteinuria; and, finally, (3) ROS-induced reversible proteinuria may relate to the mechanism of clinical functional proteinuria, which involves increased oxygen and ROS metabolism, e.g., exercise-induced proteinuria.
Costophrenic cannulation: A safe approach to ultrasound guided thoracentesis
Authors: Riccardo Inchingolo, Andrea Smargiassi, Gino Soldati, Salvatore Valente
Journal: European Respiratory Journal (2011)

Background: The use of ultrasonography allows to increase the sensitivity of the detection of pleural effusions, to perform procedures under real time visualization and, finally, to avoid ionizing energies. The aim of the study was to evaluate feasibility, safety and efficacy of a new technique to insert the needle under ultrasonic guidance along the costophrenic sinus, avoiding every accidental complication.

Methods: 56 patients with pleural effusion, referred to thoracentesis, were placed supine or opposite lateral recumbent position. After the identification of the pleural fluid in the costophrenic sinus by ultrasound evaluation, we used Veress needle assembly to cannulate the sinus under constant ultrasound guidance in order to permit the fluid to drain.

Results: 81 separate thoracenteses were performed on 56 patients. 78 thoracenteses were successfully completed (96,3%). Three were stopped because of the appearance of considered complications such as cough (2,4%) and vasovagal event (1,2%). During 24 hours patient monitoring, we encountered only one chest pain (1,3% of completed thoracenteses) and one pneumothorax (1,3% of completed thoracenteses). The mean acquisition time of the pleural space was 76 seconds (SD: ± 9).

Conclusion: This work highlights safety and efficacy of real time echo guided thoracentesis, in terms of more comfortable patient position, easier approach for the operator, very low rate of complications and short acquisition time of the pleural space. Our new technique, real time echo guided costophrenic cannulation with Veress needle, allows to broaden the field of applications of thoracentesis and might be used in patients who cannot maintain orthostatic position.
Role of TM6SF2 rs58542926 in the pathogenesis of nonalcoholic pediatric fatty liver disease: A multiethnic study
Authors: Martina Goffredo, Sonia Caprio, Ariel E. Feldstein, Ebe D'Adamo, Melissa M. Shaw, Bridget Pierpont, Mary Savoye, Hongyu Zhao, Allen E. Bale, Nicola Santoro
Journal: Hepatology (2015)

We assessed the association between the single‐nucleotide polymorphism (SNP) rs58542926 in the transmembrane 6 superfamily member 2 ( TM6SF2 ) gene and fatty liver disease in obese youth. We genotyped the TM6SF2 rs58542926 SNP in a multiethnic cohort of 957 obese children and adolescents (42% Caucasians, 28% African Americans, 30% Hispanics). All underwent an oral glucose tolerance test, a liver panel, and a lipid profile. Of them, 454 children underwent a magnetic resonance imaging study to assess hepatic fat content and 11 underwent liver biopsy to assess the degree of disease severity. The minor allele of the rs58542926 SNP was associated with high hepatic fat content in Caucasians and African Americans (all P &lt; 0.05), with high alanine aminotransferase levels in Hispanics ( P &lt; 0.05) and a more favorable lipoprotein profile (lower low‐density lipoprotein, small dense low‐density lipoprotein, and very small low‐density lipoprotein) in Caucasians and Hispanics (all P &lt; 0.05). The liver biopsy showed a higher prevalence of fibrosis ( P = 0.04) and a higher nonalcoholic fatty liver disease activity score ( P = 0.05) in subjects carrying the minor allele than in those homozygous for the common allele. Moreover, we observed a joint effect among the TM6SF2 rs58542926, the PNPLA3 rs738409, and the GCKR rs1260326 SNPs in determining intrahepatic fat accumulation ( P &lt; 0.05). Conclusion : The rs58542926 SNP in the TM6SF2 gene is associated with pediatric nonalcoholic fatty liver disease but may confer protection against cardiovascular risk. (H epatology 2016;63:117–125)