bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protein Kinase C-α Mediates Cigarette Smoke Extract- and Complement Factor 5a-Stimulated Interleukin-8 Release in Human Bronchial Epithelial Cells
Authors: Kashyap Ravindra , Floreani Anthony A. , Heires Arthur J. , Sanderson Sam D. , Wyatt Todd A. 
Published: August 2007

Background Cigarette smoke extract (CSE) activates protein kinase C (PKC) and augments complement factor 5a (C5a)-stimulated release of the proinflammatory cytokine IL-8 in human bronchial epithelial cells (HBEC). We hypothesized that PKC activation by alternative PKC activators will also mediate C5a-stimulated IL-8 release in HBEC. Methods HBEC were treated with phorbol myristate acetate (100 ng/mL), calcium ionophore A23187 (2 nM), or 10 nM cholesterol-3-sulfate in the presence or absence of C5a. Interleukin-8 (IL-8) release was measured by enzyme-linked immunoadsorbent assay. Results IL-8 release by PKC activators alone was significantly higher than in unstimulated cells and was further augmented in the presence of C5a. Preincubation with the PKC inhibitor calphostin C (1 μM) significantly suppressed IL-8 release in HBEC treated with CSE and C5a. Preincubation with 10 μM TMB-8 (an intracellular calcium sequester) also significantly suppressed IL-8 release in CSE- and C5a-treated HBEC, suggesting that intracellular calcium is required for CSE- and C5a-mediated IL-8 release. When HBEC were preincubated with 30 nM of the PKCβ-specific inhibitor LY363196, CSE- and C5a-mediated IL-8 release was not inhibited. However, with higher concentrations of LY363196 (>600 nM), which exceeds the IC50 for PKCβ greater than 100 fold, CSE- and C5a-mediated IL-8 release was significantly suppressed. Preincubation of HBEC with 100 nM of Gö 6976, a specific PKCα inhibitor, significantly inhibited CSE- and C5a-mediated stimulation of IL-8 release. Conclusions Collectively, these data suggest that PKC activators in addition to CSE augment C5a-stimulated IL-8 release from HBEC and that CSE and C5a stimulate IL-8 release in HBEC by activating the calcium-dependent PKCα isoform.
Recombinant Plasma Gelsolin Diminishes the Acute Inflammatory Response to Hyperoxia in Mice
Authors: Christofidou-Solomidou Melpo , Scherpereel Arnaud , Solomides Charalambos C , Christie Jason D , Stossel Thomas P , Goelz Susan , DiNubile Mark J 
Published: August 2007

Background The acute respiratory distress syndrome remains a common and poorly understood complication of a variety of insults. Ventilation with high concentrations of inspired oxygen may further damage already compromised lungs. By scavenging extracellular actin and modulating the effects of lysophosphatidic acid, plasma gelsolin could serve a critical protective role against oxidant injury. Methods Mice exposed to >95% O2 for a total of 72 hours were treated with gelsolin or albumin after 24 and 48 hours. Results Neutrophil counts in bronchoalveolar fluid rose ( P=0.0002) and gelsolin levels dropped ( P<0.00001) in mice with acute hyperoxic lung injury. The acute inflammatory response to hyperoxia was significantly reduced in the gelsolin-compared with the bovine serum albumin-treated mice ( P=0.03). Conclusions These data imply that i) gelsolin depletion contributes to the pathogenesis of oxygen toxicity and ii) repletion of gelsolin can partially abrogate the resultant exudative response.
Differing Effects of Inotropic Agents on Length Change Deactivation of Isolated Rat Myocardium
Authors: Leach John K. , Ford Lincoln E. , Perea John M. , Grimes Laura A. , Skipper Betty J. 
Published: August 2007

Background A rapid change in length of cardiac muscle during isometric contraction is followed by developed force that is less than appropriate for the new length because of deactivation of the contractile system. Length change deactivation may have favorable or unfavorable effects on cardiac function, depending on the circumstances under which it is produced. Methods Left ventricular papillary muscles from male Sprague-Dawley rats were arranged for recording of isometric force. After each control or reference isometric contraction, a quick release-quick stretch V-step was applied to the following contraction. For each repetition of control and experimental contractions, the time of application of V-steps was increased by 20 ms until peak force was reached. Effects of these V-steps were assessed from ratios of peak redeveloped force to peak force in an isometric reference contraction. Slopes of plots of these ratios versus time after the onset of the contraction were used to quantify the effects of inotropic agents on deactivation. Results Increasing calcium from 2.5 to 5.0 or 7.5 mM increased force by 12±4% (mean±SEM), did not change time to peak, and did not significantly alter the deactivation slope. Adding 5 mM epinephrine increased force by 16±5%, decreased time to peak by 34±3%, and increased the deactivation slope by 106±9% ( P<0.001). Caffeine had variable effects on peak force, increased time to peak by 47±4%, and decreased the deactivation slope by 71±5% ( P<0.001). Conclusions The quantitatively different effects of the three agents on length change deactivation slopes and time to peak force suggest a common mechanism, probably involving thin-filament cooperativity.
Tumor Necrosis Factor-α -308 Gene Polymorphism is Associated with Synthetic Hemodialysis Graft Failure
Authors: Ram Sunanda , Bass Kristen , Abreo Ken , Baier John R. , Kruger Thomas E. 
Published: August 2007

Background Progressive venous stenosis mediated, in part, by inflammatory cytokines is a major cause of synthetic hemodialysis graft failure. A tumor necrosis factor-α (TNF-α) gene polymorphism (G to A, position -308) has been shown to increase plasma cytokine levels and severity of diseases with an underlying inflammatory component. Methods We genotyped 67 patients with synthetic polytetrafluoroethylene (PTFE) grafts and examined the association of the high- (AA or GA) and low- (GG) production TNF-α -308 genotypes with the rate of graft failures/thrombosis and graft survival. Results Hemodialysis patients with the high-production TNF-α genotypes had a significantly increased rate of PTFE graft failure at 90 days (37.2% versus 14%) and 1 year (62.8% versus 34.4%) after graft placement compared with patients with the low-production genotype (respectively). Hemodialysis patients with the high-production TNF-α genotypes had significantly lower cumulative PTFE graft survival at 1 year (29.4% ± 11.1% versus 71.2 ± 6.8%) and 2 years (22.1% ± 10.5% versus 48.2 ± 8.1%) compared with patients with the low-production genotype (respectively). Patients with the A allele had approximately twice the mean thrombosis rate compared with those who had the low-production TNF-α genotype (3.3 ± 0.8 versus 1.7 ± 0.4 thromboses/patient/year, respectively; mean ± SEM, p < .05). Conclusions These data suggest that the TNF-α -308 A allele is associated with increased PTFE graft thrombosis and failure in hemodialysis patients.
Effect of Apolipoprotein E Polymorphism on Serum Uric Acid Levels in Healthy Subjects
Authors: Liberopoulos Evagelos N. , Miltiadous George A. , Athyros Vasilios G. , Ganotakis Manolis , Cariolou Marios , Bairaktari Eleni , Elisaf Moses S. 
Published: August 2007

Background We have previously shown that apolipoprotein E (apo E-) polymorphism may affect serum creatinine concentration and predicted glomerular filtration rate in healthy individuals. On the other hand, there are limited data regarding the possible influence of apo E- polymorphism on serum uric acid (SUA) levels. Methods Two hundred ninety (148 male, 142 female) apparently healthy white individuals were studied. apo E- genotypes, serum lipid parameters including apolipoproteins, insulin resistance using the homeostasis model assessment (HOMA) as a marker, serum and urine creatinine levels, and serum and urine uric acid concentration were determined in all participants. Results The apo E-2 allele was associated with lower serum levels of total cholesterol, higher levels of triglycerides and apo E-, and increased serum creatinine concentration compared with the apo E-3 and apo E-4 alleles in our population. Furthermore, the apo E-2 allele was associated with higher SUA levels (321.3 ± 101.1 μmol/L [5.4 ± 1.7 mg/dL]) compared with the apo E-3 allele (261.8 ± 89.2 μmol/L [4.4 ± 1.5 mg/dL]; p = .012) and the apo E-4 allele (243.9 ± 65.4 μmol/L [4.1 ± 1.1 mg/dL]; p = .010), whereas the apo E-2 allele was associated with a nonsignificant decrease in the fractional renal excretion of uric acid (FEUA) compared with the apo E-3 and apo E-4 alleles (7.9 ± 2.2% vs 8.7 ± 4.2% vs 8.9 ± 5.1%, respectively; p = .53). These observations remained statistically significant when the effect of apo E- polymorphism on SUA levels was adjusted for gender, age, systolic and diastolic blood pressure, body mass index, serum creatinine, and triglyceride and apo E- levels, as well as for HOMA index and FEUA. Conclusions Our data provide evidence, for the first time, that the apo E-2 allele is independently associated with increased SUA levels in healthy individuals.
Survey of the Impact of National Institutes of Health Clinical Research Curriculum Awards (K30) between 1999 and 2004
Authors: Bakken Lori L. , Lichtenstein Michael ,   ACRTPD Evaluation Committee
Published: August 2007

Background This report summarizes a survey conducted in 2004 by the Association of Clinical Research Training Program Directors’ Evaluation Committee. The purpose of this survey was to determine the early capacity of the 59 National Institutes of Health (NIH) K30 programs (funded between 1999 and 2004) to produce clinical investigators trained in core skills required in clinical research. Methods In July 2004, a 37-item Web-based survey was distributed to institutions funded by the NIH K30 award mechanism. Frequencies and proportions were computed for each categorical response, and means were calculated for nominal responses using SPSS, version 11.5 (SPSS, Chicago, IL). Items 7 (funding year) and 8 (recruitment year) were cross-tabulated to ascertain the tempo at which programs were able to establish their enrolment processes. Results Forty-five of the 59 programs funded by the K30 award (76%) responded to this survey. The average number of active trainees in each program is 32. Women constitute 53% of active trainees, and 22% of them are underrepresented minorities. Ninety-six percent of active trainees have medical degrees. The average number of graduates over the 5-year funding period is 18. Of the graduates, 50% are women and 17% are underrepresented minorities. Fifty-six percent of them earned certificates, 44% earned master of science degrees, and 13% earned other degrees. Sixty-one percent of K30 program graduates have some extramural funding to support their research. The average number of publications per trainee for all trainees (active and graduate) is 2.3. Conclusion The K30 program has been a catalyst at multiple US institutions for improving the pedagogy for clinical research training. It has successfully fulfilled the mandate set forth by the 1998 NIH Director's Panel on Clinical Research (Nathan Report).
Insulin-Like Growth Factor I-Mediated Skeletal Muscle Hypertrophy is Characterized by Increased mTOR-p70S6K Signaling without Increased Akt Phosphorylation
Authors: Song Yao-Hua , Godard Michael , Li Yangxin , Richmond Scott R. , Rosenthal Nadia , Delafontaine Patrick 
Published: August 2007

Background Insulin-like growth factor I (IGF-I) is an anabolic hormone that is known to induce skeletal muscle hypertrophy. However, the signaling pathways mediating IGF-I's hypertrophic effect in vivo are unknown. Method The phosphorylation of 46 proteins was investigated by Kinetworks proteomic analysis in the gastrocnemius muscle of transgenic mice overexpressing IGF-I myosin light chain/muscle specific IGF-I (MLC/mIgf-I) and wild-type littermates. Results In the hypertrophic muscle of MLC/mIgf-I mice, we observed increased phosphorylation of phosphoinositide-dependent protein kinase 1 (PDK1; 53% increase), the mammalian target of rapamycin (mTOR; 112% increase), and p70 S6 kinase (p70S6K) (254% increase) but no significant change in Akt phosphorylation (4% decrease). Furthermore, we found reduced phosphorylation of MAP kinase kinase 1 and 2 (MEK1/2) (60% decrease) and of mitogen-activated protein kinase kinases 3 and 6 (MKK3/6) (50% decrease) in muscle from transgenic mice, suggesting that the hypertrophic and mitogenic effects of IGF-I are mediated via distinct signaling pathways in skeletal muscle and that inhibition of the mitogen-activated protein (MAP) kinase pathway may be required for the IGF-I-induced hypertrophic effect. Single-fiber analysis revealed a trend toward a higher percentage of the fast twitch fibers (IIb and IIx) in the transgenic mice. Conclusion Persistent overexpression of IGF-I in mice skeletal muscle results in hypertrophy, which is likely mediated via the mTOR/p70S6K pathway, potentially via an Akt-independent signaling pathway.
Exercise, Caloric Restriction, and Systemic Oxidative Stress
Authors: Galassetti Pietro R. , Nemet Dan , Pescatello Andria , Rose-Gottron Christie , Larson Jennifer , Cooper Dan M. 
Published: August 2007

Background In humans, the main sources of reactive oxygen species (ROS), the molecules causing oxidative stress, are mitochondrial superoxide ions and neutrophil-derived oxidative radicals. Circulating antioxidants contribute to the protection against oxidative stress. Although the formation of ROS and secretion of antioxidants are independently regulated by exercise and diet, little is known about their combined effect. We hypothesized that relatively brief, intense exercise training may reduce systemic oxidation via an intrinsic mechanism, independent of changes in circulating antioxidants and of neutrophil-derived enzymes (as may be caused by concomitant caloric restriction). Methods Nineteen volunteers exercised for 7 days, 3 hours/day at 75% of oxygen uptake. Caloric intake was either 110% of caloric expenditure (high calorie, n = 10) or 75% of caloric expenditure (low calorie, n = 9). Blood samples for F2-isoprostanes, catalase, myeloperoxidase (MPO), interleukin-x (IL-x), white blood cells (WBCs), and other metabolic variables were taken at baseline, at the end of training, and 1 week after completion of the study. Results Serum F2-isoprostanes (μg/mL), markers of lipid peroxidation, were similarly reduced after 7 days of exercise in the high-calorie (from 35 ± 4 to 27 ± 2) and low-calorie (from 35 ± 3 to 24 ± 2) groups. Similar reductions were observed in IL-x concentrations. Conversely, no change was observed in circulating concentrations of the antioxidant catalase. Whereas total WBCs and neutrophil counts were significantly reduced in the low-calorie group only, no difference in neutrophil-derived MPO was measured between groups. Conclusion A significant reduction in systemic oxidation may occur relatively early during intense exercise training in healthy young men, independent of caloric intake. The potential contribution to these effects of circulating antioxidants and neutrophil-derived oxidative enzymes will require further investigation.
Differences in Triage Thresholds for Patients Presenting with Possible Acute Coronary Syndromes: More than Meets the Eye
Authors: Milch Catherine E. , Kent David M. , Ruthazer Robin , Pope Hector J. , Aufderheide Thomas P. , McNutt Robert A. , Selker Harry P. 
Published: August 2007

Background Many studies have shown differences in cardiac care by racial/ethnic groups without accounting for institutional factors at the location of care. Objective Exploratory analysis of the effect of hospital funding status (public vs private) on emergency department (ED) triage decision making for patients with symptoms suggestive of acute coronary syndromes (ACSs) and on the likelihood of ED discharge for patients with confirmed ACS. Study Design and Setting Secondary analysis of data from a randomized controlled trial of 10,659 ED patients with possible ACS in five urban academic public and five private hospitals. The main outcome measures were the sensitivity and specificity of hospital admission for the presence of ACS at public and private hospitals and the adjusted odds of a patient with ACS not being hospitalized at public versus private hospitals. Results Of 10,659 ED patients, 1,856 had confirmed ACS. For patients with suspected ACS, triage decisions at private hospitals were considerably more sensitive (99 vs 96%; p < .001) but less specific (30 vs 48%; p < .001) than at public hospitals. The difference between hospital types persisted after adjustment for multiple patient-level and hospital-level characteristics. Conclusion Significant differences in triage for patients with suspected ACS exist between public and private hospital EDs, even after adjustment for multiple patient demographic, clinical, and institutional factors. Further studies are needed to clarify the causes of the differences.
Research Ethics, Science Policy, and Four Contexts for the Stem Cell Debate
Authors: Cameron Nigel M. de S. 
Published: August 2007

There are plainly conscientious differences of opinion among scientists, politicians, and the public in respect of both the ethics of embryonic stem cell research and the more general question of the role of public policy in setting parameters for what is legal and what is funded in the biosciences. Although professional discussion of embryonic stem cell research is not hampered by the often misleading oversimplifications of the press, it remains true that the wide range of ethical options is rarely explored. These varied positions arise from a series of at least six logically distinct policy options, which we may summarize in these terms: (a) All use of human embryos for research is wrong. (b) Excess in vitro embryos may be used, but others should not be created for the purpose. (c) In vitro embryos, but not clonal embryos, may be created with the intent of using them for research. (d) Clonal embryos, but not in vitro embryos, may be created with the intent of using them for research. (e) Only certain excess embryos destroyed before a certain date should be used. (f) Only certain excess embryos created before a certain date should be used. Moreover, in any policy permitting research use of the embryo, two further sets of issues are raised. First is the question of consent. Second is the question of time limits. As advancements in biotechnology shape the possibilities of the twenty-first century and hold out both promise and threat to the human future, it is crucial that we develop a national and global conversation that both encourages science and its potential and takes wider social responsibility for the purposes for which science is engaged.
Impaired Lung Vascular Endothelial Growth Factor in Extremely Premature Baboons Developing Bronchopulmonary Dysplasia/Chronic Lung Disease
Authors: Tambunting Francis , Beharry Kay D. A. , Waltzman Joshua , Modanlou Houchang D. 
Published: August 2007

Background Preterm infants exposed to O2 with mechanical ventilation often develop bronchopulmonary dysplasia (BPD), a form of chronic lung disease (CLD). The pathogenesis of BPD/CLD involves dysmorphic microvasculature and disrupted alveolarization. This may be due to impaired vascular endothelial growth factor (VEGF) and VEGF receptor expression. Methods To examine the ontogeny of VEGF and VEGF receptors in baboon lungs from 125 to 185 (term) days gestation and to determine whether exposure to O2 and mechanical ventilation alter these ontogenic profiles, we examined lung specimens from three O2-exposed groups: (1) animals delivered at 125 days gestation and exposed to O2 for 14 days as needed; (2) animals delivered at 140 days gestation and exposed to O2 for 10 days as needed; and (3) animals delivered at 140 days gestation and exposed to 100% O2 for 10 days. Lungs from gestational age-matched controls were also examined at 125, 140, 160, 175, and 185 (term) days. Results VEGF189 was the most abundant splice variant in the lungs at all stages of development. Extremely premature baboons developing BPD/CLD had higher lung VEGF121 messenger ribonucleic acid (mRNA) expression. However, transcripts for VEGF189, VEGF165, and VEGF receptors (Fms-like tyrosine kinase-1 [Flt-1], kinase-insert domain receptor [KDR]/fetal liver kinase-1 [Flk-1], and neuropilin 1) were suppressed in the BPD models. Conclusions We conclude that impaired VEGF and VEGF receptor mRNA expression in lungs from extremely premature baboons developing BPD/CLD may contribute to dysmorphic microvasculature and disrupted alveolarization.
Patient Knowledge Improves Glycemic Control: Is it Time to Go Back to the Classroom?
Authors: Panja Srinivas , Starr Brian , Colleran Kathleen M. 
Published: August 2007

Background Over the last two decades, pharmaceutical intervention for the treatment of type 2 diabetes has expanded. Studies over this same time demonstrated the benefits of tight glycemic control. Unfortunately, despite the availability of novel therapies, glycemic control remains problematic. Nonpharmacologic interventions need to be explored, including patient empowerment. Improving patient knowledge of diabetes may ultimately improve glycemic control. To test this hypothesis, we compared patients’ diabetes knowledge with their glycemic control. Methods The Michigan Diabetes Knowledge Test, designed by the University of Michigan, was administered to patients with type 2 diabetes at three University of New Mexico primary care clinics. Patient records were reviewed. The most recent hemoglobin A1c (HbA1c) value was recorded. The data were analyzed using linear regression analysis. Results Seventy-seven patients completed surveys and had HbA1c values available. Only questions 1 to 14 of the 23-question survey were used because they pertained specifically to type 2 diabetes. HbA1c was inversely correlated with the number of questions answered correctly on the test (r = -.337, p < .003). Using “all subsets” regression, a correct response to questions 1, 3, and 9 specifically correlated with a lower HbA1c (p < .0001). Conclusions These results demonstrate that an inverse linear relationship exists between performance on this diabetes test and HbA1c values. Improvement in patient knowledge of diabetes and the importance of treatment may indeed improve glycemic control and ultimately decrease complications. Studies aimed at empowering patients with disease knowledge may help control the ramifications of the growing diabetes epidemic.
Effect of Diclofenac on Experimental Pleurodesis Induced by Tetracycline in Rabbits
Authors: Kaya Seyda Ors , Bir Ferda , Atalay Habip , Onem Gokhan , Aytekin Faruk Onder , Saçar Mustafa 
Published: August 2007

Background and Objective Pleurodesis is a frequently preferred procedure in thoracic surgery, and many factors may affect the process. We aimed to determine whether the administration of systemic diclofenac sodium diminishes the effectiveness of the pleurodesis induced by intrapleural tetracycline in rabbits. Methods Twelve male New Zealand rabbits that received tetracycline 35 mg/kg intrapleurally were allocated into two groups. The first group (diclofenac group, n = 6) received 2 mg/kg diclofenac sodium intramuscularly for 10 days, and the second group (control group, n = 6) received acetaminophen 30 mg/kg orally for 10 days after the pleurodesis procedure. The rabbits were sacrificed after 28 days, and the pleural spaces were assessed grossly for evidence of pleurodesis and microscopically for evidence of fibrosis, inflammation, and collagenization. Results The mean macroscopic pleurodesis score of the diclofenac group was 2.16 ± 0.40 compared with 2.83 ± 0.40 in the control group (p = .027). The mean microscopic pleurodesis score of the diclofenac group was 2. 3 ± 1.03, whereas it was 3.5 ± 0.54 in the control group (p = .045). Conclusion The administration of diclofenac sodium for 10 days following tetracycline pleurodesis reduces the effectiveness of pleurodesis in rabbits.