tbuckley/cabot-search huggingface dataset:
Two types of dysfunctional eighth component of complement (C8) molecules in C8 deficiency in man. Reconstitution of normal C8 from the mixture of two abnormal C8 molecules.
Authors: F Tedesco, P Densen, M A Villa, B H Petersen, G Sirchia
Journal: Journal of Clinical Investigation (1983)

Restoration of hemolytic activity was examined in sera from seven unrelated eighth component of complement (C8)-deficient subjects. The sera fell into two groups, depending on whether hemolytic activity was restored by the addition of the beta-chain (group 1) or the alpha-gamma-subunit (group 2) purified from normal human C8. Antigenic analysis of these sera by double-immunodiffusion using anti-human C8 confirmed previous findings of a dysfunctional C8 in the four sera of group 1 and established the presence of a different dysfunctional C8 in one of the sera of group 2 when tested at a high concentration. Further characterization of the dysfunctional C8 molecules in the two sera by sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated that group 1 sera were missing the beta-subunit and group 2 sera were missing the alpha-gamma-subunit of the C8 molecule. Sera from either of these two groups alone did not produce hemolysis in hemolytic plates containing sheep erythrocytes coated with antibody and complement components up to C7 (EAC1-7) and C9. When sera from the two groups were added to adjacent wells in the hemolytic plates, a zone of hemolysis developed between the wells. The contribution of C8 alpha-gamma from the sera of group 1 and of C8 beta from those of group 2 to the lysis of EAC1-7 in the presence of C9 was confirmed by the inhibitory effect of specific antibodies against the two C8 subunits. In experiments in which hemolytic activity was reconstituted by mixing sera from group 1 with sera from group 2, the serum source of C8 beta (group 2) was the limiting reagent. The dysfunctional C8 molecule in this serum was able to bind to EAC1-7. Chromatographic analysis demonstrated that the generation of hemolytic activity in the mixture of the two sera resulted from the reconstitution of the C8 molecule rather than the sequential action of the two C8 subunits.
Interventions with potential to reduce sedentary time in adults: systematic review and meta-analysis
Authors: Anne Martin, Claire Fitzsimons, Ruth Jepson, David H Saunders, Hidde P van der Ploeg, Pedro J Teixeira, Cindy M Gray, Nanette Mutrie
Journal: British Journal of Sports Medicine (2015)

Context Time spent in sedentary behaviours (SB) is associated with poor health, irrespective of the level of physical activity. The aim of this study was to evaluate the effect of interventions which included SB as an outcome measure in adults. Methods Thirteen databases, including The Cochrane Library, MEDLINE and SPORTDiscus, trial registers and reference lists, were searched for randomised controlled trials until January 2014. Study selection, data extraction and quality assessment were performed independently. Primary outcomes included SB, proxy measures of SB and patterns of accumulation of SB. Secondary outcomes were cardiometabolic health, mental health and body composition. Intervention types were categorised as SB only, physical activity (PA) only, PA and SB or lifestyle interventions (PA/SB and diet). Results Of 8087 records, 51 studies met the inclusion criteria. Meta-analysis of 34/51 studies showed a reduction of 22 min/day in sedentary time in favour of the intervention group (95% CI −35 to −9 min/day, n=5868). Lifestyle interventions reduced SB by 24 min/day (95% CI −41 to −8 min/day, n=3981, moderate quality) and interventions focusing on SB only by 42 min/day (95% CI −79 to −5 min/day, n=62, low quality). There was no evidence of an effect of PA and combined PA/SB interventions on reducing sedentary time. Conclusions There was evidence that it is possible to intervene to reduce SB in adults. Lifestyle and SB only interventions may be promising approaches. More high quality research is needed to determine if SB interventions are sufficient to produce clinically meaningful and sustainable reductions in sedentary time.
High WT1 Expression Is Associated with Very Poor Survival of Patients with Osteogenic Sarcoma Metastasis
Authors: Alok Srivastava, Bruno Fuchs, Kunbo Zhang, Ming Ruan, Chandralekha Halder, Eric Mahlum, Kristin Weber, Mark E. Bolander, Gobinda Sarkar
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Although metastasis is the primary determinant of poor survival of patients with osteogenic sarcoma, some patients live much longer than others, indicating metastatic heterogeneity underlying survival outcome. The purpose of the investigation was to identify genes underlying survival outcome of patients with osteogenic sarcoma metastasis. Experimental Design: We have used microarray to first compare mRNA expression between normal bone and osteogenic sarcoma specimens, identified genes overexpressed in osteogenic sarcoma, and compared expression of the selected gene between a poorly metastatic (SAOS) and two highly metastatic cell lines (LM8 and 143B). Finally, expression of the selected gene was assessed by immunostaining of osteogenic sarcoma samples with known survival outcome. Results: Microarray analysis revealed 5.3-fold more expression of WT1 mRNA in osteogenic sarcoma compared with normal bone and &amp;gt;2-fold overexpression in 143B and LM8 cells compared with SAOS. Furthermore, WT1 mRNA was absent in normal bone (10 of 10) by reverse transcription-PCR but present in osteogenic sarcoma–derived cell lines (5 of 8). One hundred percent (42 of 42) of low-grade osteogenic sarcoma specimens expressed no WT1 as determined by immunostaining; however, 24% (12 of 49) of the high-grade specimens showed intense staining. Mean survival of patients with high-grade metastatic osteogenic sarcoma but low WT1 staining (27 of 37) was 96.5 ± 129.3 months, whereas mean survival of patients with high-grade metastatic osteogenic sarcoma having intense staining (10 of 37) was 18.3 ± 12.3 months (P &amp;gt; 0.0143). All splice variants of WT1 mRNA, including a hitherto unknown variant (lacking exons 4 and 5), were found to be expressed in osteogenic sarcoma. Conclusion: WT1 seems to be associated with very poor survival of patients with osteogenic sarcoma metastasis.
Direct Evidence of Endothelial Oxidative Stress With Aging in Humans
Authors: Anthony J. Donato, Iratxe Eskurza, Annemarie E. Silver, Adam S. Levy, Gary L. Pierce, Phillip E. Gates, Douglas R. Seals
Journal: Circulation Research (2007)

Aging is associated with impaired vascular endothelial function, as indicated in part by reduced endothelium-dependent dilation (EDD). Decreased EDD with aging is thought to be related to vascular endothelial cell oxidative stress, but direct evidence is lacking. We studied 95 healthy men: 51 young (23±1 years) and 44 older (63±1 years). EDD (brachial artery flow-mediated dilation) was ≈50% lower in older versus young men (3.9±0.3% versus 7.6±0.3%, P &lt;0.01; n=42 older/n=51 young). Abundance of nitrotyrosine (quantitative immunofluorescence), an oxidatively modified amino acid and marker of oxidative stress, was higher in endothelial cells (ECs) obtained from the brachial artery (1.25±0.12 versus 0.61±0.11 nitrotyrosine intensity/human umbilical vein EC [HUVEC] intensity, P =0.01; n=11 older/n=11 young) and antecubital veins (0.55±0.04 versus 0.34±0.03, P &lt;0.05; n=19 older/n=17 young) of older men. Flow-mediated dilation was inversely related to arterial EC nitrotyrosine expression ( r =−0.62, P =0.01; n=22). In venous samples, EC expression of the oxidant enzyme NAD(P)H oxidase-p47 phox was higher in older men (0.71±0.05 versus 0.57±0.05 NAD[P]H oxidase-p47 phox intensity/HUVEC intensity, P &lt;0.05; n=19 older/n=18 young), whereas xanthine oxidase and the antioxidant enzymes cytosolic and mitochondrial superoxide dismutase and catalase were not different between groups. Nuclear factor-κB p65, a component of the redox-sensitive nuclear transcription factor nuclear factor-κB, was elevated in both arterial (0.73±0.07 versus 0.53±0.05 NF-κB p65 intensity/HUVEC intensity, P &lt;0.05; n=9 older/n=12 young) and venous (0.65±0.07 versus 0.34±0.05, P &lt;0.01; n=13 older/n=15 young) EC samples of older men and correlated with nitrotyrosine expression ( r =0.51, P &lt;0.05 n=16). These results provide direct support for the hypothesis that endothelial oxidative stress develops with aging in healthy men and is related to reductions in EDD. Increased expression of NAD(P)H oxidase and nuclear factor-κB may contribute to endothelial oxidative stress with aging in humans.
Involved-Nodal Radiation Therapy As a Component of Combination Therapy for Limited-Stage Hodgkin's Lymphoma: A Question of Field Size
Authors: Belinda A. Campbell, Nick Voss, Tom Pickles, James Morris, Randy D. Gascoyne, Kerry J. Savage, Joseph M. Connors
Journal: Journal of Clinical Oncology (2008)

Purpose Combined-modality therapy is the standard of care for limited-stage Hodgkin's lymphoma (HL). Radiation therapy has evolved from extended-field radiation therapy (EFRT) to involved-field radiation therapy (IFRT), reducing toxicity while maintaining high cure rates. Recent publications recommend a further reduction to involved-nodal radiation therapy (INRT), however, this has not been clinically validated. Patients and Methods We identified 325 patients with limited-stage HL, diagnosed between May 1, 1989 and April 1, 2005, and treated with chemotherapy and radiation therapy following era-specific guidelines: EFRT until 1996; IFRT from 1996 to 2001; INRT ≤ 5 cm from 2001 to the present. INRT ≤ 5 cm was defined as the prechemotherapy nodal volume with margins ≤ 5 cm to account for physiological movement, set-up variation, and the limitations of conventional simulation and radiation therapy techniques. Exclusion criteria were age younger than 16, fluorine-18 fluorodeoxyglucose positron emission tomography, non–doxorubicin, bleomycin, vinblastine, and dacarbazine-like chemotherapy, and/or more than four chemotherapy cycles. Results At diagnosis, median age was 35 years; 52% male; stage IA 29%; stage IIA 71%. Ninety-five percent of patients received two chemotherapy cycles. The three radiation therapy groups were: EFRT, 39%; IFRT, 30%; and INRT ≤ 5 cm, 31%. Median follow-up of living patients was 80 months. Median time to relapse was 37 months. Twelve relapses occurred: four after EFRT (3%); five after IFRT (5%); and three after INRT ≤ 5 cm (3%; P = .9). No marginal recurrences occurred after INRT ≤ 5 cm. Locoregional relapse (LRR) occurred in five patients: three after EFRT; two with IFRT; and none with INRT ≤ 5 cm. At 5 years, progression-free survival (PFS) was 97%, and overall survival (OS) was 95%. At 10 years, PFS and OS were 95% and 90%, respectively. Conclusion Reduction in field size appears to be safe, without an increased risk of LRR in patients receiving INRT ≤ 5 cm.
The effect of acute exercise on the systemic inflammation in patients with moderate or severe asthma
Authors: Celso R.F. Carvalho, Felipe A.R. Mendes, Andrezza França-Pinto, Rafael Stelmach, Alberto Cukier, Milton Martins
Journal: European Respiratory Journal (2014)

Background : Acute exercise modulates the immune response in healthy individuals; however, it effect on asthmatic patients remains unknown.  Objective : To evaluate the effects of an acute high intensity exercise on systemic inflammatory mediators in patients.  Methods : Thirty-nine patients with moderate or severe asthma under medical treatment and clinically stable ( 1 =76.8± 21.4% predicted). All patients were submitted to one bout of at high intensity exercise (80% of VO 2 max) in a treadmill. A venous blood was collected at rest, immediately after and one hour after the exercise and serum cytokines (interleukin-5 (IL-5), IL-6, IL-8 and IL-10) were measured by using cytometric beat array method (BD Biosciences, CA, USA).  Results : Immediately after the exercise bout, asthmatic patients demonstrated a significant increase in plasma cytokines compared to rest IL-5 (246±308  vs.  95±104 fg.mL -1 ), IL-6 (449±559  vs.  194±196 fg.mL -1 ), IL-8 (3.3±1.6  vs.  1.8±1 pg.mL -1 ) and IL-10 (102±83  vs.  38±62 fg.mL -1 ) (p 0.05); however, the levels of IL-10, an anti-inflammatory cytokine, remained at higher levels compared with rest values (81±92  vs.  38±62 fg.mL -1 ,p Conclusion : One bout of high intensity exercise induced a persistent increase in the levels of anti-inflammatory cytokine and a transitory increase in the pro-inflammatory cytokines. These results reinforce the relevance of exercise to modulate inflammation in asthmatic patients.
Endoluminal surface registration for CT colonography using haustral fold matching
Authors: Thomas Hampshire, Holger R. Roth, Emma Helbren, Andrew Plumb, Darren Boone, Greg Slabaugh, Steve Halligan, David J. Hawkes
Journal: Medical Image Analysis (2013)

Computed Tomographic (CT) colonography is a technique used for the detection of bowel cancer or potentially precancerous polyps. The procedure is performed routinely with the patient both prone and supine to differentiate fixed colonic pathology from mobile faecal residue. Matching corresponding locations is difficult and time consuming for radiologists due to colonic deformations that occur during patient repositioning. We propose a novel method to establish correspondence between the two acquisitions automatically. The problem is first simplified by detecting haustral folds using a graph cut method applied to a curvature-based metric applied to a surface mesh generated from segmentation of the colonic lumen. A virtual camera is used to create a set of images that provide a metric for matching pairs of folds between the prone and supine acquisitions. Image patches are generated at the fold positions using depth map renderings of the endoluminal surface and optimised by performing a virtual camera registration over a restricted set of degrees of freedom. The intensity difference between image pairs, along with additional neighbourhood information to enforce geometric constraints over a 2D parameterisation of the 3D space, are used as unary and pair-wise costs respectively, and included in a Markov Random Field (MRF) model to estimate the maximum a posteriori fold labelling assignment. The method achieved fold matching accuracy of 96.0% and 96.1% in patient cases with and without local colonic collapse. Moreover, it improved upon an existing surface-based registration algorithm by providing an initialisation. The set of landmark correspondences is used to non-rigidly transform a 2D source image derived from a conformal mapping process on the 3D endoluminal surface mesh. This achieves full surface correspondence between prone and supine views and can be further refined with an intensity based registration showing a statistically significant improvement (p<0.001), and decreasing mean error from 11.9 mm to 6.0 mm measured at 1743 reference points from 17 CTC datasets.
Biochemical mechanisms of hibernation and stunning in the human heart
Authors: H Lüss
Journal: Cardiovascular Research (2002)

Background: Myocardial hibernation and stunning are characterized by depressed cardiac function in the presence of reduced or normal coronary blood flow. The underlying biochemical mechanisms are widely unknown and only limited data are available in human hearts. Methods and Results: Left ventricular transmural myocardial biopsies were obtained from normal and dysfunctional segments of patients undergoing coronary bypass surgery. Segments were classified as hibernating (n = 10) or stunned (n = 9) using contrast ventriculography and echocardiography, single photon emission computed tomography (SPECT), and positron emission tomography (PET). In each patient, biopsies from normal myocardial segments were used as controls (n = 19). Compared to control myocardium, levels of cAMP (3′-5′cyclic adenosine monophosphate, in fmol/mg wet weight, means±S.E.M.) were higher in hibernating (673±76 versus 518±47, P<0.05) but unchanged in stunned myocardium (513±73 versus 466±97, P>0.05). Protein expression of phospholamban, sarcoendoplasmic Ca2+-ATPase 2a, calsequestrin, the inhibitory subunit of troponin, as well as the activation of p38 MAP kinase were not different when compared to controls. However, heat shock protein 72 (Hsp72) was increased 55% in stunned (2.89±0.58 versus 1.86±0.32, P<0.05) but not in hibernating myocardium (1.68±0.34 versus 1.67±0.29, P>0.05). Conclusions: The data from the present study suggest different pathophysiological mechanisms for myocardial hibernation and stunning. Alterations in the homeostasis of cAMP might be a compensatory mechanism in myocardial hibernation, whereas expression of Hsp72 appears to be cardioprotective in human myocardial stunning. Future studies should further elucidate these mechanisms and their potential impact on future therapeutic interventions.
Reaction of resting heart rate and blood pressure to high intensity interval and modern continuous training in coronary artery diseases
Authors: Shirin Zilaei Bouri, Sajad Arshadi
Journal: British Journal of Sports Medicine (2010)

A previous study showed the importance of physical exercise in improving heart rate (HR) and blood pressure (BP) at rest. Studies have shown that resting HR is an independent predictor of cardiovascular disease, which causes mortality in men and women with and without diagnosed cardiovascular disease, and that reducing hypertension would alone reduce the risk of developing cardiovascular disease. But published guidelines did not recommend high-intensity exercise. Therefore, the purpose of this randomised study was to assess the effect and comparison of high-intensity interval training (HIIT) versus moderate intensity continuous training (MICT) representing the same total training load on resting HR and BP in coronary artery disease (CAD). Twelve CAD patients were randomised to supervise either HIIT (65–75% HR peak) for 33 min or MICT for 41 min, three times a week for 8 weeks. The result showed that HIIT decreased significantly the resting HR (p=0.03), and the systolic (p=0.006) and diastolic (p=0.03) BP; also MICT decreased these parameters but they were not significant. However, there was no significant difference between HIIT versus MICT. Therefore, HIIT was superior to MICT for improving resting HR and BP in CAD patients. The present data may be useful in designing effective training programme for improving health among CAD patients in the future.
Glucose Control and Mortality in Critically Ill Patients
Authors: Simon J. Finney
Journal: JAMA (2003)

Hyperglycemia is common in critically ill patients, even in those without diabetes mellitus. Aggressive glycemic control may reduce mortality in this population. However, the relationship between mortality, the control of hyperglycemia, and the administration of exogenous insulin is unclear.To determine whether blood glucose level or quantity of insulin administered is associated with reduced mortality in critically ill patients.Single-center, prospective, observational study of 531 patients (median age, 64 years) newly admitted over the first 6 months of 2002 to an adult intensive care unit (ICU) in a UK national referral center for cardiorespiratory surgery and medicine.The primary end point was intensive care unit (ICU) mortality. Secondary end points were hospital mortality, ICU and hospital length of stay, and predicted threshold glucose level associated with risk of death.Of 531 patients admitted to the ICU, 523 underwent analysis of their glycemic control. Twenty-four-hour control of blood glucose levels was variable. Rates of ICU and hospital mortality were 5.2% and 5.7%, respectively; median lengths of stay were 1.8 (interquartile range, 0.9-3.7) days and 6 (interquartile range, 4.5-8.3) days, respectively. Multivariable logistic regression demonstrated that increased administration of insulin was positively and significantly associated with ICU mortality (odds ratio, 1.02 [95% confidence interval, 1.01-1.04] at a prevailing glucose level of 111-144 mg/dL [6.1-8.0 mmol/L] for a 1-IU/d increase), suggesting that mortality benefits are attributable to glycemic control rather than increased administration of insulin. Also, the regression models suggest that a mortality benefit accrues below a predicted threshold glucose level of 144 to 200 mg/dL (8.0-11.1 mmol/L), with a speculative upper limit of 145 mg/dL (8.0 mmol/L) for the target blood glucose level.Increased insulin administration is positively associated with death in the ICU regardless of the prevailing blood glucose level. Thus, control of glucose levels rather than of absolute levels of exogenous insulin appear to account for the mortality benefit associated with intensive insulin therapy demonstrated by others.
Pathological role of interleukin 17 in mice subjected to repeated BCG vaccination after infection with <i>Mycobacterium tuberculosis</i>
Authors: Andrea Cruz, Alexandra G. Fraga, Jeffrey J. Fountain, Javier Rangel-Moreno, Egídio Torrado, Margarida Saraiva, Daniela R. Pereira, Troy D. Randall, Jorge Pedrosa, Andrea M. Cooper, António G. Castro
Journal: The Journal of Experimental Medicine (2010)

Infection usually leads to the development of acquired immune responses associated with clearance or control of the infecting organism. However, if not adequately regulated, immune-mediated pathology can result. Tuberculosis is a worldwide threat, and development of an effective vaccine requires that the protective immune response to Mycobacterium tuberculosis (Mtb) be dissected from the pathological immune response. This distinction is particularly important if new vaccines are to be delivered to Mtb-exposed individuals, as repeated antigenic exposure can lead to pathological complications. Using a model wherein mice are vaccinated with bacille Calmette-Guérin after Mtb infection, we show that repeated vaccination results in increased IL-17, tumor necrosis factor, IL-6, and MIP-2 expression, influx of granulocytes/neutrophils, and lung tissue damage. This pathological response is abrogated in mice deficient in the gene encoding IL-23p19 or in the presence of IL-17–blocking antibody. This finding that repeated exposure to mycobacterial antigen promotes enhanced IL-17–dependent pathological consequences has important implications for the design of effective vaccines against Mtb.
Relative Rates of Evolution in the Coding and Control Regions of African mtDNAs
Authors: N. Howell, J. L. Elson, C. Howell, D. M. Turnbull
Journal: Molecular Biology and Evolution (2007)

Reduced median networks of African haplogroup L mitochondrial DNA (mtDNA) sequences were analyzed to determine the pattern of substitutions in both the noncoding control and coding regions. In particular, we attempted to determine the causes of the previously reported (Howell et al. 2004) violation of the molecular clock during the evolution of these sequences. In the coding region, there was a significantly higher rate of substitution at synonymous sites than at nonsynonymous sites as well as in the tRNA and rRNA genes. This is further evidence for the operation of purifying selection during human mtDNA evolution. For most sites in the control region, the relative rate of substitution was similar to the rate of neutral evolution (assumed to be most closely approximated by the substitution rate at 4-fold degenerate sites). However, there are a number of mutational hot spots in the control region, ∼3% of the total sites, that have a rate of substitution greater than the neutral rate, at some sites by more than an order of magnitude. It is possible either that these sites are evolving under conditions of positive selection or that the substitution rate at some sites in the control region is strongly dependent upon sequence context. Finally, we obtained preliminary evidence for "nonideal" evolution in the control region, including haplogroup-specific substitution patterns and a decoupling between relative rates of substitution in the control and coding regions.