bluuebunny/crossref_metadata_2025_split huggingface dataset:
ORIGINAL RESEARCH – BASIC SCIENCE: Primary dermal fibroblasts derived from sdc‐1 deficient mice migrate faster and have altered αv integrin function
Authors: Jurjus Rosalyn A. , Liu Yueyuan , Pal‐Ghosh Sonali , Tadvalkar Gauri , Stepp Mary Ann 
Published: September 2008

ABSTRACTThe goal of this study is to determine whether dermal fibroblasts lacking syndecan‐1 (sdc1) show differences in integrin expression and function that could contribute to the delayed skin and corneal wound healing phenotypes seen in sdc‐1 null mice. Using primary dermal fibroblasts, we show that after 3 days in culture no differences in α‐smooth muscle actin were detected but sdc‐1 null cells expressed significantly more αv and β1 integrin than wildtype (wt) cells. Transforming growth factor β1 (TGFβ1) treatment at day 3 increased αv‐ and β1‐integrin expression in sdc‐1 null cells at day 5 whereas wt cells showed increased expression only of αv‐integrin. Using time‐lapse studies, we showed that the sdc‐1 null fibroblasts migrate faster than wt fibroblasts, treatment with TGFβ1 increased these migration differences, and treatment with a TGFβ1 antagonist caused sdc‐1 null fibroblasts to slow down and migrate at the same rate as untreated wt cells. Cell spreading studies on replated fibroblasts showed altered cell spreading and focal adhesion formation on vitronectin and fibronectin‐coated surfaces. Additional time lapse studies with β1‐ and αv‐integrin antibody antagonists, showed that wt fibroblasts expressing sdc‐1 had activated integrins on their surface that impeded their migration whereas the null cells expressed αv‐containing integrins which were less adhesive and enhanced cell migration. Surface expression studies showed increased surface expression of α2β1 and α3β1 on the sdc‐1 null fibroblasts compared with wt fibroblasts but no significant differences in surface expression of α5β1, αvβ3, or αvβ5. Taken together, our data indicates that sdc‐1 functions in the activation of αv‐containing integrins and support the hypothesis that impaired wound healing phenotypes seen in sdc‐1 null mice could be due to integrin‐mediated defects in fibroblast migration after injury.
Physiological Complexity Underlying Heart Rate Dynamics and Frailty Status in Community‐Dwelling Older Women
Authors: Chaves Paulo H. M. , Varadhan Ravi , Lipsitz Lewis A. , Stein Phyllis K. , Windham B. Gwen , Tian Jing , Fleisher Lee A. , Guralnik Jack M. , Fried Linda P. 
Published: September 2008

OBJECTIVES: To assess whether less physiological complexity underlying regulation of heart rate dynamics, as indicated by lower approximate entropy for heart rate (ApEnHR), is associated with frailty. For supporting validity, relationships between frailty and traditional linear indices of heart rate variability (HRV) were also assessed.DESIGN: Cross‐sectional.SETTING: Women's Health and Aging Study I, a community‐based observational study, 1992 to 1995.PARTICIPANTS: Subset of 389 community‐dwelling women aged years and older with moderate to severe disability with ApEnHR data (convenience sampling).MEASUREMENTS: Electrocardiographic Holter recordings obtained over 2‐ to 3‐hour periods were processed for ApEnHR and HRV measures. ApEnHR is a nonlinear statistic that quantifies the regularity of heart rate fluctuations over time. Lower ApEnHR is characteristic of heart rate time series containing a high proportion of repetitive patterns. Frailty was defined according to validated phenotype criteria.RESULTS: Median ApEnHR was lower in frail than in nonfrail subjects (P=.02). Lower ApEnHR (top quartile) was associated with lower likelihood of frailty than higher ApEnHR (bottom three quartiles) (odds ratio=0.47, 95% confidence interval=0.26–0.86), even after adjustment for major confounders. Frailty was consistently associated with lower HRV as assessed using time‐ and frequency‐domain indices.CONCLUSION: This study supports the notion that less physiological complexity marks frailty and provides an empirical basis to the concept of frailty as a syndrome of homeostatic impairment. Future research will determine whether noninvasive measures of physiological complexity underlying heart rate dynamics might be useful for screening and monitoring of clinical vulnerability in older adults.
End‐of‐Life Decision‐Making, Decisional Conflict, and Enhanced Information: Race Effects
Authors: Allen Rebecca S. , Allen Jessica Y. , Hilgeman Michelle M. , DeCoster Jamie 
Published: September 2008

OBJECTIVES: To examine the effect of enhanced information regarding the risks, benefits, and life‐sustaining treatment alternatives on hypothetical medical decisions and decisional conflict in older, community‐dwelling Caucasian and African‐American adults.DESIGN: Two‐group (enhanced information; no information) between‐subjects design.SETTING: Community‐based dwellings, two assisted living facilities, and one senior citizen center.PARTICIPANTS: Seventy‐eight adults (aged 74.5±7.18) with a mean Telephone Interview for Cognitive Status—Modified (TICS‐m) score of 31.5±4.7 were recruited through personal contacts and informational talks held at the recruitment sites.MEASUREMENTS: Measures included the Life Support Preferences/Predictions Questionnaire—modified (LSPQ‐m); the Decisional Conflict Scale; and enhanced information, including detailed descriptions of life‐sustaining treatment options for each LSPQ‐m illness scenario, risks of the treatment, benefits of the treatment, and alternatives for each treatment (called medical information stimuli).RESULTS: Enhanced information (e.g., medical information stimuli) reduced decisional conflict (P=.049, d=0.47) for hypothetical life‐sustaining treatment decisions. A mixed analysis of variance with group and race as between‐subjects variables and illness and treatment as within‐subjects variables revealed significant main effects of race, illness, and treatment, as well as a significant race‐by‐illness‐by‐group interaction (Wilk's lambda=0.923, F(2, 73)=3.05, P=.05, partial η2=0.08). Enhanced information produced different patterns of desire for life‐sustaining treatments in African Americans and Caucasians.CONCLUSION: Physicians and other healthcare professionals can reduce decisional conflict in patients by providing enhanced information regarding treatment risks, benefits, and alternatives. Such decision aids may provide new information or knowledge and thus reduce desire for treatment in African Americans.
A nationwide survey for hepatitis E virus prevalence in Japanese blood donors with elevated alanine aminotransferase
Authors: Sakata Hidekatsu , Matsubayashi Keiji , Takeda Hiromi , Sato Shinichiro , Kato Toshiaki , Hino Satoru , Tadokoro Kenji , Ikeda Hisami 
Published: September 2008

BACKGROUND: Although we reported two cases of transfusion‐transmitted hepatitis E in Japan, the prevalence of hepatitis E virus (HEV) in Japanese blood donors is not very clear.STUDY DESIGN AND METHODS: Blood samples of donors who were deferred from donation because of elevated alanine aminotransferase (ALT) levels were collected from all Japanese Red Cross Blood Centers and subjected to HEV tests.RESULTS: Among the 41 donors with elevated ALT levels higher than 500 IU per L in Hokkaido, HEV RNA was detected in 8 (19.5%) samples. In 1389 donor samples with ALT levels of higher than 200 IU per L in nationwide Japan, the numbers of positive HEV RNA, immunoglobulin M (IgM) anti‐HEV, and immunoglobulin G (IgG) anti‐HEV samples were 15 (1.1%), 14 (1.0%), and 45 (3.2%), respectively. Although RNA‐positive donors were predominantly male and found in any geographic area of Japan, they tended to be higher in number in eastern Japan including Hokkaido and lower in number in western Japan. Of the 23 HEV‐positive samples, 19 were Genotype 3 and 4 were Genotype 4. DNA sequences of the 9 isolates showed more than 98.5 percent homology with the known swine HEV isolates. In 1062 donor samples with ALT levels of 61 to 199 IU per L, the percentages of IgM and IgG anti‐HEV–positive samples were 0.1 and 2.7 percent, respectively, although there was no HEV RNA–positive sample.CONCLUSION: HEV markers (HEV RNA and anti‐HEV) were detected in donors with elevated ALT levels who were widely distributed over Japan. The prevalence and incidence were higher in eastern Japan than in western Japan.
Membrane Time Constant During Internal Defibrillation Strength Shocks in Intact Heart: Effects of Na+ and Ca2+ Channel Blockers
Authors: MOWREY KENT A. , EFIMOV IGOR R. , CHENG YUANNA 
Published: September 2008

Introduction:
We assessed defibrillation strength shock‐induced changes of the membrane time constant (τ) and membrane potential (ΔVm) in intact rabbit hearts after administration of lidocaine, a sodium (Na+) channel blocker, or nifedipine, a L‐type calcium (Ca2+) channel blocker.
Methods and Results:
We optically mapped anterior, epicardial, electrical activity during monophasic shocks (±100, ±130, ±160, ±190, and ±220 V; 150 μF; 8 ms) applied at 25%, 50%, and 75% of the action potential duration via a shock lead system in Langendorff‐perfused hearts. The protocol was run twice for each heart under control and after lidocaine (15 μM, n = 6) or nifedipine (2μM, n = 6) addition. τ in the virtual electrode area away from the shock lead was approximated with single‐exponential fits from a total of 121,125 recordings. The same data set was used to calculate ΔVm. We found (1) Under all conditions, there is inverse relationship between τ and ΔVm with respect to changes of shock strength, regardless of shock polarity and phase of application: a stronger shock resulted in a larger ΔVm, which corresponded to a smaller τ (faster cellular response); (2) Lidocaine did not cause appreciable changes in either τ or ΔVm versus control, and (3) Nifedipine significantly increased both τ and ΔVm in the virtual cathode area; in contrast, in the virtual anode area, this effect depended on the phase of shock application.
Conclusion:
τ and ΔVm are inversely related. Na+ channel blocker has minimal impact on either τ or ΔVm. Ca2+ blocker caused polarity and phase‐dependent significant changes in τ and ΔVm.
Catheter Ablation of Atrial Fibrillation in Patients with Diabetes Mellitus Type 2: Results from a Randomized Study Comparing Pulmonary Vein Isolation Versus Antiarrhythmic Drug Therapy
Authors: FORLEO GIOVANNI B. , MANTICA MASSIMO , DE LUCA LUCIA , LEO ROBERTO , SANTINI LUCA , PANIGADA STEFANIA , DE SANCTIS VALERIO , PAPPALARDO AUGUSTO , LAURENZI FRANCESCO , AVELLA ANDREA , CASELLA MICHELA , RUSSO ANTONIO DELLO , ROMEO FRANCESCO , PELARGONIO GEMMA , TONDO CLAUDIO 
Published: September 2008

Introduction:
Atrial fibrillation (AF) and diabetes mellitus type 2 (DM2) often coexist; however, a small number of patients with DM2 undergoing catheter ablation (CA) of AF have been included in previous studies. The aim of this study was to evaluate safety and efficacy of ablation therapy in DM2 patients with drug refractory AF.
Methods and Results:
From January 2005 to September 2006, 70 patients with a diagnosis of DM2 and paroxysmal (n = 29) or persistent (n = 41) AF were randomized to receive either pulmonary vein isolation or a new antiarrhythmic drug treatment (ADT) with a 1‐year follow‐up. The primary endpoint was the time to first AF recurrence. By Kaplan‐Meier analysis, at the end of follow‐up, 42.9% of patients in the ADT group and 80% of patients who received a single ablation procedure and were without medications were free of AF (P = 0.001). In the ablation group, a significant improvement in quality‐of‐life (QoL) scores as compared with ADT group was observed. Six patients in the ADT group (17.1%) developed significant adverse drug effects. Hospitalization rate during follow‐up was higher in the ADT group (P = 0.01). The only complication attributable to ablation was one significant access‐site hematoma.
Conclusion:
In patients with DM2, CA of AF provides significant clinical benefits over the ADT and appears to be a reasonable approach regarding feasibility, effectiveness, and low procedural risk.
Successful Targeted Ablation of the Pathway Potential in the Noncoronary Cusp of the Aortic Valve in an Infant with Incessant Orthodromic Atrioventricular Reentrant Tachycardia
Authors: BALASUNDARAM RAMPRAKASH , RAO HYGRIV , ASIRVATHAM SAMUEL J. , NARASIMHAN CALAMBUR 
Published: September 2008

A 4‐month‐old infant presented with incessant SVT and severe failure to thrive. At EP study, orthodromic‐reciprocating tachycardia using an anteroseptal accessory pathway was identified. Detailed mapping on the right atrial septum failed to disclose a distinctly early site of atrial activation or a near‐field pathway potential. Mapping in the noncoronary cusp of the aortic valve identified a discrete pathway potential that was successfully targeted for ablation. At 12‐month follow‐up after the procedure, there had been no recurrence of tachycardia.
Conclusion:
Myocardial fibers above the aortic valve cusps may constitute the atrioventricular bypass connection and can be identified and targeted for successful ablation even in infants.
Safe and Effective Ablation of Atrial Fibrillation: Importance of Esophageal Temperature Monitoring to Avoid Periesophageal Nerve Injury as a Complication of Pulmonary Vein Isolation
Authors: KUWAHARA TAISHI , TAKAHASHI ATSUSHI , KOBORI ATSUSHI , MIYAZAKI SHINSUKE , TAKAHASHI YOSHIHIDE , TAKEI ASUMI , NOZATO TOSHIHIRO , HIKITA HIROYUKI , SATO AKIRA , AONUMA KAZUTAKA 
Published: September 2008

Introduction:
Catheter ablation on the left atrial posterior wall has been reported to potentially damage the esophagus or periesophageal vagal nerve. The aim of this study was to evaluate the efficacy of esophageal temperature monitoring (ETM) in preventing esophageal or periesophageal vagal nerve injury in patients with atrial fibrillation (AF) undergoing pulmonary vein (PV) isolation.
Methods:
This study included 359 patients with drug‐refractory AF who underwent extensive PV isolation. The first 152 patients were treated without ETM (non‐ETM) and the last 207 with ETM. In the ETM group, the esophageal temperature (ET) was measured with a deflectable temperature probe that was placed close to the ablation electrode, and the radiofrequency energy applications were stopped when the ET reached 42°C.
Results:
In all patients in the ETM group, the ET increased to 42°C in at least one site by 28 ± 14 seconds, mostly along the right side of the left PVs, especially near the left inferior PV. Less energy (6.3 ± 1.9 × 104 J) was required for PV isolation in the ETM group than that in the non‐ETM (6.8 ± 1.9 ×104 J, P = 0.03). Gastric hypomotility owing to periesophageal nerve damage was observed in three patients in the non‐ETM group, but in none in the ETM (P = 0.02). The recurrence rates of AF did not differ between the two groups (non‐ETM, 29%; ETM, 27%).
Conclusion:
Titration of the duration of the ablation energy delivery while monitoring the ET could prevent periesophageal nerve injury due to the AF ablation, without decreasing the success rate of maintaining sinus rhythm.
Fluvastatin Reduces Pulmonary Vein Spontaneous Activity Through Nitric Oxide Pathway
Authors: HU YU‐FENG , CHEN YAO‐CHANG , CHENG CHEN‐CHUAN , HIGA SATOSHI , CHEN YI‐JEN , CHEN SHIH‐ANN 
Published: September 2008

Introduction:
Pulmonary veins (PVs) are the most important focus for the generation of atrial fibrillation. The HMG‐CoA reductase inhibitors (statins) can reduce the occurrence of atrial fibrillation. The purposes of this study were to evaluate whether statins may inhibit the PV arrhythmogenic activity to prevent atrial arrhythmias from PVs and to investigate the link between fluvastatin, nitric oxide synthase (NOS) activity, mechanical activity, and electrical activity.
Methods:
Conventional microelectrodes and Western blot were used to record the electrical activity, diastolic tension, contractility and expression of Akt, endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), and phosphorylated Akt and eNOS before and after the administration of fluvastatin in rabbit PVs or atria.
Results:
Fluvastatin decreased the PV spontaneous activity, diastolic tension, and contractility, but did not change the action potential duration or resting membrane potential. The effects of fluvastatin on the PV firing rate and diastolic tension were attenuated in the presence of L‐NAME (100 μM), wortmannin (100 nM), and ODQ (3 μM). Fluvastatin (1 μM) increased the phosphorylated Akt and eNOS, but did not change the total Akt or eNOS in the PVs and atria. In contrast, fluvastatin (1 μM) decreased the total nNOS in the PVs and atria.
Conclusions and implications:
Fluvastatin produced nitric oxide through the PI3kinase/Akt pathway, thus reducing the PV vascular diastolic tension and PV spontaneous activity. These results may contribute to the beneficial effects of statins.
Variability of the Diagnostic ECG Pattern in an ICD Patient Population with Brugada Syndrome
Authors: RICHTER SERGIO , SARKOZY ANDREA , VELTMANN CHRISTIAN , CHIERCHIA GIAN‐BATTISTA , BOUSSY TIM , WOLPERT CHRISTIAN , SCHIMPF RAINER , BRUGADA JOSEP , BRUGADA RAMON , BORGGREFE MARTIN , BRUGADA PEDRO 
Published: September 2008

Introduction:
The spontaneous presence of a coved‐type ECG is considered as an important risk factor in Brugada syndrome. However, diagnosis making and risk stratification may be hampered by the dynamic nature of the ECG abnormalities. The objective of this study was to determine the variability and predictive value of the electrocardiogram in Brugada patients implanted with a cardioverter‐defibrillator (ICD).
Methods and Results:
We analyzed consecutive 12‐lead ECGs from 89 ICD patients (44 ± 14 years, 69 males) with Brugada syndrome. A total of 1,161 ECGs were included for analysis (13 ± 8 ECGs/patient). Twenty‐four percent of the ECGs/patient were coved‐type I, 25% saddleback‐type II or III, and 51% normal. Fifty‐seven patients had a diagnostic coved‐type ECG spontaneously (group A), 32 patients only after drug challenge (group B). In group A, 38% of the ECGs/patient were diagnostic, 25% saddleback‐type, and 37% normal. Fifty‐five group A patients (96%) had transient normalization and/or conversion to saddleback‐type ECGs. During a mean follow‐up of 48 ± 35 months, 16 patients (18%) experienced appropriate shocks. All patients with appropriate shocks had spontaneous diagnostic ECGs. They tended to have more coved‐type ECGs (36 vs 22%, respectively, P = 0.05) than patients without appropriate shocks.
Conclusions:
Analysis of serial ECG recordings in an ICD patient population shows that the Brugada‐ECG pattern is highly variable over time. In patients with spontaneous coved‐type ECG, only every third ECG is diagnostic and every third ECG normal. Patients with spontaneous coved‐type ST‐segment elevation have a high incidence of appropriate shocks. Spontaneous saddleback‐type electrocardiograms are not helpful for risk stratification.
Statin Use and Ventricular Arrhythmias During Clinical Treadmill Testing
Authors: DEWEY FREDERICK E. , PEREZ MARCO , HADLEY DAVID , FREEMAN JAMES V. , WANG PAUL , ASHLEY EUAN A. , MYERS JONATHAN , FROELICHER VICTOR F. 
Published: September 2008

Background:
Premature ventricular complexes (PVCs) during exercise are associated with adverse prognosis, particularly in patients with intermediate treadmill test findings. Statin use reduces the incidence of resting ventricular arrhythmias in patients with coronary artery disease; however, the relationship between statin use and exercise‐induced ventricular arrhythmias has not been investigated.
Methods and Results:
We evaluated the association between statin use and PVCs in 1,847 heart‐failure‐free patients (mean age 58, 95% male) undergoing clinical exercise treadmill testing between 1997 and 2004 in the VA Palo Alto Health Care System. PVCs were quantified in beats per minute and frequent PVCs were defined as PVC rates greater than the median value (0.43 and 0.60 PVCs per minute for exercise and recovery, respectively). Propensity‐adjusted logistic regression was used to evaluate the odds of developing PVCs during exercise and recovery periods associated with statin use. There were 431 subjects who developed frequent PVCs during exercise and 284 subjects had frequent recovery PVCs. After propensity score adjustment, subjects treated with statins (n = 145) had 42% lower odds of developing frequent PVCs during exercise (odds ratio [OR] 0.58, 95% confidence interval [CI] 0.37–0.93) and 44% lower odds of developing frequent PVCs during recovery (OR 0.56, 95% CI 0.30–0.94). These effects were not modified by age, prior coronary disease, hypercholesterolemia, exercise‐induced angina, or exercise capacity.
Conclusions:
Statin use was associated with reduced odds of frequent PVCs during and after clinical exercise testing in a manner independent of associations with coronary disease or ischemia in our study population.
ADAM15 modulates outside‐in signalling in chondrocyte–matrix interactions
Authors: Böhm Beate B. , Schirner Andrea , Burkhardt Harald 
Published: September 2008

AbstractADAM15 belongs to a family of transmembrane multi‐domain proteins implicated in proteolysis, cell–cell and cell–matrix interactions in various disease conditions. In osteoarthritis (OA), ADAM15 is up‐regulated in the chondrocytes already at early stages of cartilage degeneration where it seems to exert homeostatic effects likely associated with its ability to enhance integrin‐mediated chondrocyte adhesion to the surrounding collagen matrix. The aim of our present study was, therefore, to characterize functional domains of ADAM15 involved in collagen II (CII) interaction and to analyse associated outside‐in signalling events. Accordingly, ADAM15 and respective deletion mutants were stably transfected into the chondrocyte cell line T/C28a4. Transfected cells were adhered to CII and phosphoproteins analysed by Western blotting. Co‐immunoprecipitation served to identify protein binding to ADAM15. Our results elucidate the prodomain as critical for the capacity of ADAM15 to enhance CII adhesion, thereby identifying for the first time a cell‐adhesive role of a metalloproteinase prodomain. Moreover, the cytoplasmic tail of ADAM15 confers a modulatory effect on the autophosphorylation site Y397 of the focal adhesion kinase (FAK) during chondrocyte–collagen interaction. In conclusion, the newly uncovered impact of ADAM15 on signalling events that arise from chondrocyte interactions with its collagen matrix might contribute to the elucidation of the mechanism underlying its proposed chondroprotective role in degenerative cartilage disease.
Hypoxia induces a hedgehog response mediated by HIF‐1α
Authors: Bijlsma Maarten F. , Groot Angelique P. , Oduro Jeremiah P. , Franken Rutger J. , Schoenmakers Saskia H. H. F. , Peppelenbosch Maikel P. , Spek C. Arnold 
Published: September 2008

AbstractRecently, it has become clear that the developmental hedgehog pathway is activated in ischaemic adult tissue where it aids in salvaging damaged tissue. The exact driving force for the initial hedgehog response is unclear and as most physiological and cellular processes are disturbed in ischaemic tissue, hedgehog‐activating signals are hard to dissect. Here, we demonstrate that hypoxia per se is able to induce a rapid systemic hedgehog response in adult mice, as evident from expression of the pathway ligand, Sonic hedgehog, as well as the pathway activity marker Patched1 in various organs. Using in vitro models of hypoxia, we showed that the hedgehog response was transient and preceded by the accumulation of HIF‐1α, which we hypothesized to communicate between hypoxia and hedgehog expression. Indeed, pharmacological inhibition, knockdown or genetic ablation of HIF‐1α abolished hedgehog pathway activation. In conclusion, we have established that hypoxia is translated into a hedgehog response through HIF‐1α and this mechanism is likely to be responsible for the hedgehog response observed in various ischaemia models.