tbuckley/cabot-search huggingface dataset:
Does oxidative stress modulate limb muscle atrophy in severe COPD patients?
Authors: Clara Fermoselle, Roberto Rabinovich, Pilar Ausín, Ester Puig-Vilanova, Carlos Coronell, Francisco Sanchez, Josep Roca, Joaquim Gea, Esther Barreiro
Journal: European Respiratory Journal (2012)

Oxidative stress may differentially regulate protein loss within peripheral muscles of severe chronic obstructive pulmonary disease (COPD) patients exhibiting different body composition. Oxidation levels of proteins, myosin heavy chain (MyHC) and myonuclei, superoxide anion, antioxidants, actin, creatine kinase, carbonic anhydrase-3, ubiquitin–proteasome system, redox-signalling pathways, inflammation and muscle structure, and damage were quantified in limb muscles of severe COPD patients with and without muscle wasting, and in sedentary controls. Compared with controls, in the quadriceps of muscle-wasted COPD patients, levels of protein carbonylation, oxidation of MyHC and myonuclei, superoxide anion production, superoxide dismutase, total protein ubiquinitation, E2 14k , atrogin-1, FoxO1 and p65 were higher, while content of MyHC, creatine kinase, carbonic anhydrase-3, myogenin, and fast-twitch fibre size were decreased. Importantly, in nonwasted COPD patients, where MyHC was more oxidised than in controls, its content was preserved. Muscle inflammation and glutathione levels did not differ between patients and controls. In all patients, muscle structure abnormalities were increased, while muscle force and exercise capacity were reduced. In severe COPD, while muscle oxidative stress increases regardless of their body composition, protein ubiquitination and loss of MyHC were enhanced only in patients exhibiting muscle atrophy. Oxidative stress does not seem to directly modulate muscle protein loss in these patients.
Enhanced <i>In vitro</i> and <i>In vivo</i> Cytotoxicity of Combined Reovirus and Radiotherapy
Authors: Katie Twigger, Laura Vidal, Christine L. White, Johann S. De Bono, Shreerang Bhide, Matt Coffey, Brad Thompson, Richard G. Vile, Lucy Heinemann, Hardev S. Pandha, Fiona Errington, Alan A. Melcher, Kevin J. Harrington
Journal: Clinical Cancer Research (2008)

To test combination treatment schedules of reovirus and radiation in human and murine tumor cells in vitro and in vivo.In vitro cytotoxicity and cell cycle effects of reovirus given alone and combined with radiotherapy were assessed by colorimetric, tissue culture infectious dose 50, and fluorescence-activated cell sorting-based assays. Interactions between the agents were evaluated using combination index analysis. The effect of different schedules of reovirus and radiotherapy on viral replication and cytotoxicity was tested in vitro and the combination was assessed in three tumor models in vivo.Characterization of reovirus cytotoxicity in a panel of cell lines yielded a range of sensitivities. Combined reovirus and radiotherapy yielded statistically significantly increased cytotoxicity, particularly in cell lines with moderate susceptibility to reovirus alone. The enhanced cytotoxicity of the combination occurred independently of treatment sequence or schedule. Radiation did not affect viral replication and only reduced reoviral cytotoxicity after clinically irrelevant single doses (>50 Gy). Combination index analysis revealed synergy between radiation (3-10 Gy) and reovirus at multiplicities of infection between 0.001 and 1. Combination treatment significantly increased apoptosis in tumor cells relative to either single-agent treatment. In vivo studies using xenograft and syngeneic tumors showed enhanced activity of the combination relative to reovirus or radiation alone (P < 0.001).Combining reovirus and radiotherapy synergistically enhances cytotoxicity in a variety of tumor cells in vitro and in vivo. These results offer strong support for translational clinical trials of reovirus plus radiotherapy that have been initiated in the clinic.
The effect of membrane biocompatibility on plasma beta 2-microglobulin levels in chronic hemodialysis patients.
Authors: R M Hakim, R L Wingard, L Husni, R A Parker, T F Parker
Journal: Journal of the American Society of Nephrology (1996)

Several studies have shown that patients who have been dialyzed with high-flux biocompatible membranes have a lower plasma level of beta 2-microglobulin and a lower incidence of amyloid disease compared with patients who have been dialyzed with low-flux bioincompatible membranes. However, because high-flux membranes are associated with significant dialytic removal of beta 2-microglobulin, the specific role of membrane biocompatibility in influencing the rate of increase of beta 2-microglobulin has not been previously determined. This study investigated the effect of biocompatibility on the rate of increase of plasma levels of beta 2-microglobulin in 159 new hemodialysis patients from 13 dialysis centers (ten centers affiliated with Dallas Nephrology Associates and three with Vanderbilt University Medical Center) by using two low-flux membranes with widely different biocompatibilities. These patients were prospectively randomized to be dialyzed with either a low-flux biocompatible membrane or a low-flux bioincompatible membrane. Plasma beta 2-microglobulin levels were measured at 0, 3, 6, 9, 12, and 18 months. Sixty-six patients completed the 18-month study. Plasma beta 2-microglobulin increased in all patients; however, the increase was not significantly different from baseline at any time point in the group that used the biocompatible membrane. In this group, beta 2-microglobulin increased from (mean +/- SD) 27.8 +/- 14.8 mg/L to 34.0 +/- 10.0 mg/L at 18 months (P = not significant), and the mean increase at 18 months was 2.6 +/- 14.7 mg/L. In contrast, the increase in plasma beta 2-microglobulin level in the bioincompatible membrane group became significant in Month 6 when the levels had increased from a baseline of 24.8 +/- 9.6 mg/L to 29.5 +/- 12.2 mg/L (P < 0.001); these increases continued to be significant until Month 18, when serum beta 2-microglobulin reached 36.8 +/- 13.9 mg/L with an average increase of 11.8 +/- 11.2 mg/L (P < 0.0001). The higher rate of plasma B2-microglobulin increase in the group that had been dialyzed with the bioincompatible membrane was also evident when only patients who had completed the study were analyzed. There were no significant differences in the actual level of beta 2-microglobulin or in residual renal function between the two groups during the 18 months of the study. It was concluded that over a period of 18 months, the use of biocompatible membranes, even in the low-flux configuration, is associated with a significantly slower increase in plasma beta 2-microglobulin, independent of the influence of residual renal function.
Chronic Kidney Disease Adversely Influences Patient Safety
Authors: Stephen L. Seliger, Min Zhan, Van Doren Hsu, Lori D. Walker, Jeffrey C. Fink
Journal: Journal of the American Society of Nephrology (2008)

Reducing medical errors and improving patient safety have become a national priority. Patients with chronic kidney disease (CKD) may be at higher risk for adverse consequences of medical care, but few studies have evaluated this question. Here, data for patients hospitalized in the Veteran's Health Administration during 2004 to 2005 was analyzed to conduct a cross-sectional study of CKD and adverse safety events. Outcomes included 13 patient safety indicators (PSI) defined by the Agency for Healthcare Research and Quality and six experimental PSI relevant to CKD. The 71,666 (29%) hospitalized veterans with CKD had a higher risk for several PSI, even after case-mix adjustment. Among surgical hospitalizations, CKD was associated with increased risk for hip fracture, physiologic/metabolic derangements, and complications of anesthesia. Among all acute hospitalizations, the PSI with the highest risk in patients with CKD were infection as a result of medical care and death among those in diagnosis-related groups normally associated with low mortality. Furthermore, as preadmission estimated GFR decreased, a significant trend of increasing risk for all PSI was observed (P = 0.001). In conclusion, hospitalized patients with CKD are at increased risk for adverse safety events, measured by established PSI. Further investigation is needed to develop and test interventions to reduce this risk.
Efferent Vagal Fibre Stimulation Blunts Nuclear Factor-κB Activation and Protects Against Hypovolemic Hemorrhagic Shock
Authors: Salvatore Guarini, Domenica Altavilla, Maria-Michela Cainazzo, Daniela Giuliani, Albertino Bigiani, Herbert Marini, Giovanni Squadrito, Letteria Minutoli, Alfio Bertolini, Rolando Marini, Elena B. Adamo, Francesco S. Venuti, Francesco Squadrito
Journal: Circulation (2003)

Background— We investigated whether electrical stimulation (STIM) of efferent vagus nerves may suppress nuclear factor (NF)-κB activation and the inflammatory cascade in hemorrhagic (Hem) shock. Methods and Results— Rats were subjected to bilateral cervical vagotomy (VGX) or sham surgical procedures. Hem shock was induced by intermittent withdrawing of blood until mean arterial pressure stabilized within the range of 35 to 40 mm Hg. Application of constant voltage pulses to the caudal vagus ends (STIM; 5 V, 2 ms, 1 Hz for 12 minutes, 5 minutes after mean arterial pressure stabilization) increased survival time (VGX+Hem+Sham STIM=38±3 minutes; VGX+Hem+STIM &gt;180 minutes), reverted the marked hypotension (VGX+Hem+Sham STIM=33±3 mm Hg; VGX+Hem+STIM=66±5 mm Hg), inhibited IκBα liver loss, and blunted the augmented NF-κB activity, decreased hepatic tumor necrosis factor (TNF)-α mRNA (VGX+Hem+Sham STIM=1.42±0.5 amount of TNF-α m-RNA; VGX+Hem+STIM=0.51±0.2 amount of TNF-α mRNA), and reduced plasma TNF-α (VGX+Hem+Sham STIM=190±24 pg/mL; VGX+Hem+STIM=87±15 pg/mL). Chlorisondamine, a nicotinic receptor antagonist, abated the effects of vagal stimulation. Conclusions— Our results show a parasympathetic inhibition of NF-κB by which the brain opposes NF-κB activation in the liver and modulates the inflammatory response during acute hypovolemic hemorrhagic shock.
Short-Term Hyperglycemic Dysregulation in Patients With Type 1 Diabetes Does Not Change Myocardial Triglyceride Content or Myocardial Function
Authors: Sebastiaan Hammer, Jacqueline T. Jonker, Hildo J. Lamb, Rutger W. van der Meer, Wendy Zondag, Jan M. Sepers, Albert de Roos, Johannes W.A. Smit, Johannes A. Romijn
Journal: Diabetes Care (2008)

To evaluate the effects of hyperglycemia due to partial insulin deprivation on myocardial triglyceride (TG) content and myocardial function in patients with type 1 diabetes.Myocardial and hepatic TG content and left ventricular (LV) function were measured by magnetic resonance (MR) spectroscopy and MR imaging during optimal glucoregulation and after 24 h of partial insulin deprivation (n = 10).Mean insulin infusion rate was 45 +/- 5 units at baseline, whereas it was 27 +/- 5 units during hyperglycemia (per 24 h, P < 0.001). Plasma glucose levels increased from 8.4 +/- 0.6 to 15.9 +/- 0.8 mmol/l (P < 0.001), and plasma levels of nonesterified fatty acids from 0.31 +/- 0.05 to 0.46 +/- 0.07 mmol/l (P = 0.015). Hyperglycemia had no effects on myocardial or hepatic TG content and LV function.Short-term hyperglycemic dysregulation does not modulate myocardial or hepatic TG content or myocardial function, despite considerable metabolic adaptations.
Glycemic Variability in Patients With Early Type 2 Diabetes: The Impact of Improvement in β-Cell Function
Authors: Caroline K. Kramer, Haysook Choi, Bernard Zinman, Ravi Retnakaran
Journal: Diabetes Care (2014)

OBJECTIVE Increased glycemic variability has been reported to be associated with the risk of hypoglycemia and possibly diabetes complications and is believed to be due to β-cell dysfunction. However, it is not known whether improvement in β-cell function can reduce glycemic variability. Because short-term intensive insulin therapy (IIT) can improve β-cell function in early type 2 diabetes (T2DM), our objective was to determine whether the β-cell functional recovery induced by this therapy is associated with decreased glycemic variability. RESEARCH DESIGN AND METHODS Sixty-one patients with T2DM of 3.0 years mean duration underwent 4 weeks of IIT, which consisted of basal insulin detemir and premeal insulin aspart. Glucose variability was assessed in both the first and the last week by the coefficient of variation of capillary glucose on daily 6-point self-monitoring profiles. β-Cell function before and after IIT was assessed with the Insulin Secretion-Sensitivity Index-2 (ISSI-2). RESULTS Between the first and the last week on IIT, 55.7% of patients had a reduction in glucose variability. Change in glucose variability was negatively correlated with the change in β-cell function (ISSI-2) (r = -0.34, P = 0.008). On multiple linear regression analyses, percentage change in ISSI-2 emerged as the only factor independently associated with the change in glucose variability (standardized β = -0.42, P = 0.03). Moreover, patients with an increase in ISSI-2 ≥25% experienced a reduction in glucose variability compared with their peers who had almost no change (-0.041 ± 0.06 vs. -0.0002 ± 0.04, respectively; P = 0.006). CONCLUSIONS In early T2DM, glycemic variability is a modifiable parameter that can be reduced by improving β-cell function with short-term IIT.
Surgery versus Physical Therapy for a Meniscal Tear and Osteoarthritis
Authors: Jeffrey N. Katz, Robert H. Brophy, Christine E. Chaisson, Leigh de Chaves, Brian J. Cole, Diane L. Dahm, Laurel A. Donnell-Fink, Ali Guermazi, Amanda K. Haas, Morgan H. Jones, Bruce A. Levy, Lisa A. Mandl, Scott D. Martin, Robert G. Marx, Anthony Miniaci, Matthew J. Matava, Joseph Palmisano, Emily K. Reinke, Brian E. Richardson, Benjamin N. Rome, Clare E. Safran-Norton, Debra J. Skoniecki, Daniel H. Solomon, Matthew V. Smith, Kurt P. Spindler, Michael J. Stuart, John Wright, Rick W. Wright, Elena Losina
Journal: New England Journal of Medicine (2013)

Whether arthroscopic partial meniscectomy for symptomatic patients with a meniscal tear and knee osteoarthritis results in better functional outcomes than nonoperative therapy is uncertain.We conducted a multicenter, randomized, controlled trial involving symptomatic patients 45 years of age or older with a meniscal tear and evidence of mild-to-moderate osteoarthritis on imaging. We randomly assigned 351 patients to surgery and postoperative physical therapy or to a standardized physical-therapy regimen (with the option to cross over to surgery at the discretion of the patient and surgeon). The patients were evaluated at 6 and 12 months. The primary outcome was the difference between the groups with respect to the change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) physical-function score (ranging from 0 to 100, with higher scores indicating more severe symptoms) 6 months after randomization.In the intention-to-treat analysis, the mean improvement in the WOMAC score after 6 months was 20.9 points (95% confidence interval [CI], 17.9 to 23.9) in the surgical group and 18.5 (95% CI, 15.6 to 21.5) in the physical-therapy group (mean difference, 2.4 points; 95% CI, -1.8 to 6.5). At 6 months, 51 active participants in the study who were assigned to physical therapy alone (30%) had undergone surgery, and 9 patients assigned to surgery (6%) had not undergone surgery. The results at 12 months were similar to those at 6 months. The frequency of adverse events did not differ significantly between the groups.In the intention-to-treat analysis, we did not find significant differences between the study groups in functional improvement 6 months after randomization; however, 30% of the patients who were assigned to physical therapy alone underwent surgery within 6 months. (Funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases; METEOR ClinicalTrials.gov number, NCT00597012.).
Protein interactions in human genetic diseases
Authors: Benjamin Schuster-Böckler, Alex Bateman
Journal: Genome biology (2008)

Abstract We present a novel method that combines protein structure information with protein interaction data to identify residues that form part of an interaction interface. Our prediction method can retrieve interaction hotspots with an accuracy of 60% (at a 20% false positive rate). The method was applied to all mutations in the Online Mendelian Inheritance in Man (OMIM) database, predicting 1,428 mutations to be related to an interaction defect. Combining predicted and hand-curated sets, we discuss how mutations affect protein interactions in general.
Deterministic and Stochastic Elements of Axonal Guidance
Authors: Susan Maskery, Troy Shinbrot
Journal: Annual Review of Biomedical Engineering (2005)

An enormous literature has been developed on investigations of the growth and guidance of axons during development and after injury. In this review, we provide a guide to this literature as a resource for biomedical investigators. We first review briefly the molecular biology that is known to regulate migration of the growth cone and branching of axonal arbors. We then outline some important fundamental considerations that are important to the modeling of the phenomenology of these guidance effects and of what is known of their underlying internal mechanisms. We conclude by providing some thoughts on the outlook for future biomedical modeling in the field.
High-Sensitivity C-Reactive Protein
Authors: Paul M. Ridker
Journal: Circulation (2001)

Abstract —Inflammation plays a major role in atherothrombosis, and measurement of inflammatory markers such as high-sensitivity C-reactive protein (HSCRP) may provide a novel method for detecting individuals at high risk of plaque rupture. Several large-scale prospective studies demonstrate that HSCRP is a strong independent predictor of future myocardial infarction and stroke among apparently healthy men and women and that the addition of HSCRP to standard lipid screening may improve global risk prediction among those with high as well as low cholesterol levels. Because agents such as aspirin and statins seem to attenuate inflammatory risk, HSCRP may also have utility in targeting proven therapies for primary prevention. Inexpensive commercial assays for HSCRP are now available; they have shown variability and classification accuracy similar to that of cholesterol screening. Risk prediction algorithms using a simple quintile approach to HSCRP evaluation have been developed for outpatient use. Thus, although limitations inherent to inflammatory screening remain, available data suggest that HSCRP has the potential to play an important role as an adjunct for global risk assessment in the primary prevention of cardiovascular disease.
Urinary crystalloid excretion in patients with inflammatory bowel disease
Authors: R. I. Breuer, E. A. Gelzayd, J. K. Kirsner
Journal: Gut (1970)

Because of the potential relationship of increased urinary crystalloid excretion and concentration to stone formation, urinary calcium and uric acid excretion patterns were studied prospectively in 65 patients with inflammatory bowel disease and compared with excretion patterns in patients with functional bowel disease (controls) receiving similar dietary prescriptions. Mean 24-hr urinary calcium excretion was higher in both ulcerative colitis (212 mg, p &lt;0·02) and granulomatous bowel disease (168 mg, p = n.s.) than in controls (118 mg). Urinary calcium excretion exceeded 250 mg/24 hr in 11 of 34 patients with inflammatory bowel disease but in none of the controls. Eight of these 34 patients compared with one of 10 controls excreted urine with calcium concentrations greater than 20 mg/100 ml. Mean 24-hr uric acid excretion was slightly higher in granulomatous bowel disease (520 mg) than in ulcerative colitis (450 mg) or functional bowel disease (451 mg). Eight patients with inflammatory bowel disease but no control subject excreted &gt; 700 mg. The mean urinary uric acid concentration was significantly higher in ulcerative colitis (538 μg/ml, p &lt;0·05) and granulomatous bowel disease (558 μg/ml, p &lt;0·02) than in controls (338 μg/ml). The mean morning urine <i>p</i>H was lower (5·5, p &lt;0·01) in ulcerative colitis than in the other groups. These results indicate increased excretion and higher concentration of calcium and uric acid in some patients with inflammatory bowel disease on the usual treatment programmes. Only very long-term prospective studies of such patients can help to document the true contribution of increased crystalloid concentration and excretion to kidney stone formation in inflammatory bowel disease patients.
Chromium Supplementation Does Not Improve Glucose Tolerance, Insulin Sensitivity, or Lipid Profile: A Randomized, Placebo-Controlled, Double-Blind Trial of Supplementation in Subjects With Impaired Glucose Tolerance
Authors: Jenny E. Gunton, N. Wah Cheung, Rosemary Hitchman, Graham Hams, Christine Sullivan, Kaye Foster-Powell, Aidan McElduff
Journal: Diabetes Care (2005)

We thank Komorowski and Juturu (1) for their interest in our study, and we agree that it is possible that higher doses of chromium may show some effects. The subjects in this study received 100 μg of elemental chromium daily, administered as 800 μg of chromium picolinate, for 3 months. The small increase in serum chromium in the active group is probably appropriate …
Studies in B7-Deficient Mice Reveal a Critical Role for B7 Costimulation in Both Induction and Effector Phases of Experimental Autoimmune Encephalomyelitis
Authors: Tammy T. Chang, Claudia Jabs, Raymond A. Sobel, Vijay K. Kuchroo, Arlene H. Sharpe
Journal: The Journal of Experimental Medicine (1999)

The importance of B7 costimulation in regulating T cell expansion and peripheral tolerance suggests that it may also play a significant regulatory role in the development of autoimmune disease. It is unclear whether B7 costimulation is involved only in the expansion of autoreactive T cells in the periphery, or if it is also required for effector activation of autoreactive T cells in the target organ for mediating tissue injury and propagating autoimmune disease. In this study, the role of B7–CD28 costimulation and the relative importance of B7 costimulators for the induction and effector phases of experimental autoimmune encephalomyelitis (EAE) induced by myelin oligodendrocyte glycoprotein (MOG) peptide were examined. Wild-type, B7-1/B7-2–deficient mice, or CD28-deficient C57BL/6 mice were immunized with MOG 35-55 peptide. Mice lacking both B7-1 and B7-2 or CD28 showed no or minimal clinical signs of EAE and markedly reduced inflammatory infiltrates in the brain and spinal cord. However, mice lacking either B7-1 or B7-2 alone developed clinical and pathologic EAE that was comparable to EAE in wild-type mice, indicating overlapping functions for B7-1 and B7-2. Resistance to EAE was not due to a lack of induction of T helper type 1 (Th1) cytokines, since T cells from B7-1/B7-2−/− mice show reduced proliferative responses, but greater interferon γ production compared with T cells from wild-type mice. To study the role of B7 molecules in the effector phase of the disease, MOG 35-55–specific T lines were adoptively transferred into the B7-1/B7-2−/− and wild-type mice. Clinical and histologic EAE were markedly reduced in B7-1/B7-2−/− compared with wild-type recipient mice. These results demonstrate that B7 costimulation has critical roles not only in the initial activation and expansion of MOG-reactive T cells, but also in the effector phase of encephalitogenic T cell activation within the central nervous system.