tbuckley/cabot-search huggingface dataset:
A <sub>1</sub> Adenosine Receptor Activation Promotes Angiogenesis and Release of VEGF From Monocytes
Authors: Adam N. Clark, Rebecca Youkey, Xiaoping Liu, Liguo Jia, Rebecca Blatt, Yuan-Ji Day, Gail W. Sullivan, Joel Linden, Amy L. Tucker
Journal: Circulation Research (2007)

Adenosine is a proangiogenic purine nucleoside released from ischemic and hypoxic tissues. Of the 4 adenosine receptor (AR) subtypes (A1, A2A, A2B, and A3), the A2 and A3 have been previously linked to the modulation of angiogenesis. We used the chicken chorioallantoic membrane (CAM) model to determine whether A1 AR activation affects angiogenesis. We cloned and pharmacologically characterized chicken AR subtypes to evaluate the selectivity of various agonists and antagonists. Application of the A1 AR-selective agonist N6-cyclopentyladenosine (CPA; 100 nmol/L) to the CAM resulted in a 40% increase in blood vessel number (P<0.01), which was blocked by the A1 AR-selective antagonist C8-(N-methylisopropyl)-amino-N6-(5'-endohydroxy)-endonorbornan-2-yl-9-methyladenine (WRC-0571; 1 micromol/L). Selective A2A AR agonists did not stimulate angiogenesis in the CAM. In an ex vivo rat aortic ring model of angiogenesis that includes cocultured endothelial cells, fibroblasts, and smooth muscle cells, 50 nmol/L CPA did not directly stimulate capillary formation; however, medium from human mononuclear cells pretreated with CPA, but not vehicle, increased capillary formation by 48% (P<0.05). This effect was blocked by WRC-0571 (1.5 micromol/L) or anti-VEGF antibody (1 microg/mL). CPA (5 nmol/L) stimulated a 1.7-fold increase in VEGF release from the mononuclear cells. This is the first study to show that A1 AR activation induces angiogenesis. Stimulation of A2 ARs on endothelial cells results in proliferation and tube formation, and A2 and A3 ARs on inflammatory cells modulate release of angiogenic factors. We conclude that adenosine promotes a coordinated angiogenic response through its interactions with multiple receptors on multiple cell types.
Quantitative computed tomography and aerosol morphometry in COPD and 1-antitrypsin deficiency
Authors: S. B. Shaker, N. Maltbaek, P. Brand, S. Haeussermann, A. Dirksen
Journal: European Respiratory Journal (2005)

Relative area of emphysema below -910 Hounsfield units (RA-910) and 15th percentile density (PD15) are quantitative computed tomography (CT) parameters used in the diagnosis of emphysema. New concepts for noninvasive diagnosis of emphysema are aerosol-derived airway morphometry, which measures effective airspace dimensions (EAD) and aerosol bolus dispersion (ABD). Quantitative CT, ABD and EAD were compared in 20 smokers with chronic obstructive pulmonary disease (COPD) and 22 patients with α 1 -antitrypsin deficiency (AAD) with a similar degree of airway obstruction and reduced diffusion capacity. In both groups, there was a significant correlation between RA-910 and PD15 and pulmonary function tests (PFTs). A significant correlation was also found between EAD, RA-910 and PD15 in the study population as a whole. Upon separation into two groups, the significance disappeared for the smokers with COPD and strengthened for those with AAD, where EAD correlated significantly with RA-910 and PD15. ABD was similar in the two groups and did not correlate with PFT and quantitative CT in either group. In conclusion, based on quantitative computed tomography and aerosol-derived airway morphometry, emphysema was significantly more severe in patients with α 1 -antitrypsin deficiency compared with patients with usual emphysema, despite similar measures of pulmonary function tests.
The impact of contraction velocity on amortisation and electromyographic activity during heavy-load resistance exercise
Authors: J A Sampson, D McAndrew, N A S Taylor, H Groeller
Journal: British Journal of Sports Medicine (2011)

Heavy-load resistance exercise is not normally associated with stretch shortening muscle activation. Rapid lengthening, and a decreased period of time between lengthening and shortening phases of contraction (amortisation phase) has been associated with increased energy transfer from passive muscle structures (series elastic component, SEC), and gains in muscle efficiency during stretch shortening muscle activation. In this investigation, we sought to determine the effect of limb velocity on the amortisation phase and electromyographic (EMG) activity during heavy load (85%1RM) resistance exercise. Twelve healthy males performed 6RM unilateral elbow flexion-extension exercise during; rapid lengthening-shortening, rapid shortening and slow lengthening-shortening muscle activation. The amortisation phase and velocity of lengthening and shortening were determined using a shaft encoder and muscle activity was recorded at the biceps brachii using intramuscular and surface EMG. A decrease (P&lt;0.05) in time spent in amortisation was observed during rapid lengthening-shortening (0.10±0.00 ms), compared to rapid shortening (0.14±0.00 ms) and slow lengthening-shortening (0.19±0.00 ms). Intramuscular EMG was ∼25% (P&lt;0.05) greater during the first, second and third repetition of rapid lengthening-shortening exercise compared to the other two conditions. A trend towards increased surface EMG activity was also noted during rapid lengthening-shortening, however significance (P&lt;0.05) was only observed in the second repetition. In this investigation, the characteristics typical of a stretch shortening muscle activation were observed alongside elevated electromyographic activity during heavy-load rapid lengthening-shortening resistance exercise.
Heterogenous Nature of Flow-Mediated Dilatation in Human Conduit Arteries In Vivo
Authors: Michael J. Mullen, Rajesh K. Kharbanda, Jenny Cross, Ann E. Donald, Mia Taylor, Patrick Vallance, John E. Deanfield, Raymond J. MacAllister
Journal: Circulation Research (2001)

Abstract —Flow-mediated dilatation (FMD) of conduit arteries is dependent on an intact endothelium, although the mechanisms are not fully understood. Using high-resolution ultrasound, we examined the role of endothelial mediators in radial artery dilatation in response to transient (short period of reactive hyperemia) and sustained (prolonged period of reactive hyperemia, hand warming, or an incremental infusion of acetylcholine into the distal radial artery) hyperemia. After short episodes of reactive hyperemia, FMD was abolished by local infusion of the nitric oxide synthesis inhibitor N G monomethyl-L-arginine (5.3±1.2% versus 0.7±0.7%, P &lt;0.001). In contrast, basal vessel diameter and dilatation after prolonged episodes of reactive hyperemia, hand warming, and distal infusion of acetylcholine were not attenuated by nitric oxide synthesis inhibition. Inhibition of cyclooxygenase or local autonomic nervous system blockade also had no effect on FMD. Patients with hypercholesterolemia exhibited reduced FMD in response to transient hyperemia, but the response to sustained hyperemia was normal. These data suggest heterogeneity of endothelial responses to blood flow that are dependent on the characteristics of the flow stimulus. Dilatation after brief episodes of hyperemia is mediated by release of nitric oxide, whereas dilatation during sustained hyperemia is unaffected by NO synthesis inhibition. Hypercholesterolemia seems to differentially affect these pathways with impairment of the nitric oxide–dependent pathway and preservation of non nitric oxide–mediated dilatation to sustained flow stimuli.
Adrenal Androgen Levels as Predictors of Outcome in Prostate Cancer Patients Treated with Ketoconazole Plus Antiandrogen Withdrawal: Results from a Cancer and Leukemia Group B Study
Authors: Charles J. Ryan, Susan Halabi, San-San Ou, Nicholas J. Vogelzang, Philip Kantoff, Eric J. Small
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Adrenal androgens activate the androgen receptor and stimulate prostate cancer growth. Ketoconazole is used as an inhibitor of adrenal androgen synthesis in men with androgen-independent prostate cancer. This study analyzes the relationship between pretreatment androgen levels and outcome following ketoconazole treatment. Experimental Design: Baseline levels of three adrenal androgens (androstenedione, dehydroepiandrostenedione, and dehydroepiandrostenedione-sulfate) and testosterone were measured. Regression models (logistic and proportional hazard) were used to assess the prognostic significance of these levels in predicting overall survival and prostate-specific antigen (PSA) response defined by Consensus Criteria. Results: In 103 patients with available levels, PSA response rate was 28% and median response duration was 4.8 months. The median baseline androstenedione level was 0.64 ng/mL and was 0.88 ng/mL versus 0.53 ng/mL for those with and without a PSA response, respectively (P = 0.034). In univariate analysis, elevation of baseline androstenedione levels was predictive of PSA response [odds ratio, 2.26; 95% confidence interval (95% CI), 1.03-4.96; P = 0.043]. In multivariate analysis, both the uppermost and the middle tertile of baseline androstenedione level were associated with an improved overall survival compared with those in the lower tertile (hazard ratio, 0.59; 95% CI, 0.36-0.98; P = 0.40; hazard ratio, 0.53; 95% CI, 0.32-0.90; P = 0.018, respectively). A linear correlation was observed among all androgen levels. Conclusions: Higher androstenedione levels predict likelihood of response to ketoconazole and improved survival compared with patients with lower levels. These data suggest that therapy with ketoconazole is less effective in patients with low levels of androgen at baseline.
Death receptor 6 negatively regulates oligodendrocyte survival, maturation and myelination
Authors: Sha Mi, Xinhua Lee, Yinghui Hu, Benxiu Ji, Zhaohui Shao, Weixing Yang, Guanrong Huang, Lee Walus, Kenneth Rhodes, Bang Jian Gong, Robert H Miller, R Blake Pepinsky
Journal: Nature Medicine (2011)
Impact of Physical Inactivity on Adipose Tissue Low-Grade Inflammation in First-Degree Relatives of Type 2 Diabetic Patients
Authors: Lise Højbjerre, Mette Paulli Sonne, Amra Ciric Alibegovic, Ninna Bo Nielsen, Flemming Dela, Allan Vaag, Jens Meldgaard Bruun, Bente Stallknecht
Journal: Diabetes Care (2011)

OBJECTIVE First-degree relatives (FDRs) of patients with type 2 diabetes may exhibit a disproportionately elevated risk of developing insulin resistance, obesity, and type 2 diabetes when exposed to physical inactivity, which to some unknown extent may involve low-grade inflammation. We investigated whether subjects who are nonobese FDRs show signs of low-grade inflammation before or after exposure to short-term physical inactivity. RESEARCH DESIGN AND METHODS We studied 13 healthy FDR subjects and 20 control (CON) subjects matched for age, sex, and BMI before and after 10 days of bed rest (BR). Insulin sensitivity was measured by the hyperinsulinemic euglycemic clamp. Key low-grade inflammation mediators were measured in arterial blood and microdialysate from subcutaneous abdominal (SCAAT) and femoral adipose tissue. Adipokine mRNA expression was determined in SCAAT. RESULTS Before BR, FDR subjects displayed insulin resistance, elevated plasma C-reactive protein, leptin, and monocyte chemoattractant protein (MCP)-1, high interleukin (IL)-6, and MCP-1 expressions, as well as low adiponectin and leptin expressions. FDR subjects responded to BR by decreasing plasma adiponectin and IL-10 expression and increasing plasma expression of IL-10 and tumor necrosis factor-α. In contrast, CON subjects responded to BR by increasing plasma adiponectin and adiponectin expression and by decreasing SCAAT microdialysate leptin. CONCLUSIONS Young and nonobese FDR of patients with type 2 diabetes exhibit low-grade inflammation, which is further and disproportionately aggravated when exposed to physical inactivity. The study provides support for the notion that people at increased risk of type 2 diabetes should avoid even short periods of physical inactivity.
Differences in telomerase activity between colon and rectal cancer
Authors: G. D. Ayiomamitis, G. Notas, A. Zaravinos, M. Georgiadou, E. Kouroumalis
Journal: Gut (2011)

<h3>Introduction</h3> Colorectal cancer is developed in a multi-step process. One of the characteristic features of cancer is telomerase activation. The aim of this study was to evaluate telomerase activity between cancerous and adjacent normal tissue and to identify differences in telomerase activity between different locations in colon and rectum. <h3>Methods</h3> Matched colon tumour samples and adjacent normal mucosa from 49 patients (28 male, 25 Dukes9 stage B, 24 stage C/D, 8 right colon, 24 left colon, 17 rectum) were collected after colectomy, snap-frozen in liquid nitrogen and stored at −80°C until evaluation. Telomerase activity was measured by real time PCR and correlated with clinical and pathological parameters of the patients. <h3>Results</h3> No association was found in relation to sex, age, smoking history, BMI, Histology grade and Dukes9 stage. Interestingly normal mucosa from stage B had higher telomerase activity compared with normal mucosa from stage C/D (p=0.005) There was a significant difference in telomerase activity levels between cancerous and normal tissue (1.14×10<sup>−2</sup> vs 6.53×10<sup>−3</sup> Units, p=0.006) Right sided cancers had higher telomerase compared to left sided cancers. Moreover colon cancers had significantly more telomerase activity compared to rectal cancers.(7.7×10<sup>−3</sup> vs 3.3×10<sup>−3</sup>, p&lt;0.003). The same was true for their adjacent normal mucosa <h3>Conclusion</h3> There is a gradient in telomerase activity across the large bowel with higher values in the right side and lower in the rectum for both normal mucosa and cancer tissue. Cancerous lesions have significantly higher values from adjacent normal tissue. These results may in part explain the different biologic and clinical behaviour of cancer according to location and confirm the idea that the large bowel is not a homogeneous organ.
X-ROS signalling is enhanced and graded by cyclic cardiomyocyte stretch
Authors: Benjamin L. Prosser, Christopher W. Ward, W. Jonathan Lederer
Journal: Cardiovascular Research (2013)

A sustained, single stretch of a cardiomyocyte activates a transient production of reactive oxygen species by membrane-located NADPH oxidase 2 (Nox2).This NoX2-dependent ROS (X-ROS) tunes cardiac Ca 2+ signalling by reversibly sensitizing sarcoplasmic reticulum Ca 2+ release channels.In contrast to static length changes, working heart cells are cyclically stretched and shortened in the living animal.Additionally, this stretch cycle is constantly varied by changes in the pre-load and heart rate.Thus, the objective of this study was (i) to characterize X-ROS signalling during stretch-shortening cycles and (ii) to evaluate how the amplitude (pre-load) and frequency (heart rate) of cell stretch affects X-ROS and Ca 2+ signalling. Methods and resultsSingle adult rat cardiomyocytes were attached to MyoTak TM -coated micro-rods and stretched, while ROS production and Ca 2+ signals were monitored optically.Although a sustained stretch led to only a transient burst of ROS, cyclic stretch-shortening cycles led to a steady-state elevation of ROS production.Importantly, this new redox state was graded by both the amplitude of stretch (3-15%) and cycle frequency (1-4 Hz).Elevated ROS production enhanced Ca 2+ signalling sensitivity as measured by the Ca 2+ spark rate. ConclusionThe steady-state level of ROS production in a cardiomyocyte is graded by the amplitude and frequency of cell stretch.Thus, mechanical changes that depend on the pre-load and heart rate regulate a dynamic redox balance that tunes cellular Ca 2+ signalling.
Laboratory monitoring of warfarin therapy in Utah
Authors: Susan B. Garr, George M. Rodgers
Journal: American Journal of Hematology (1994)

Abstract Accurate laboratory monitoring of oral anticoagulation has been emphasized as an important factor in providing safe and effective therapy for patients with thromboembolism. However, recent reports indicate that coagulation laboratories may not be providing optimal clinical information to clinicians who treat these patients. We surveyed all hospltal coagulation laboratories in Utah to determine their format for reporting prothrombin time results in patients receiving oral anticoagulants. We found that less than 50% of laboratories used the reliable reporting format, i.e., the interational Normalized Ratio (INR), and that many of the laboratories using the INR format may be reporting incorrect values. Our survey also found a significant lack of interest by physicians in requesting that their laboratories adopt reliable reporting methods. These results indicate a substantial lack of understanding by laboratories and clinicians of the importance of using reliable methods to monitor oral anticoagulation. Significant educational efforts will be required to correct this problem. © 1994 Wiley‐Liss, Inc.
Rhinocerebral Mucormycosis in IDDM: Sequential magnetic resonance imaging of long-term survival with intensive therapy
Authors: George W Moll, Frank A Raila, Gilbert C Liu, A Wallace Conerly
Journal: Diabetes Care (1994)

OBJECTIVE To describe the clinical course and the utility of computerized tomography (CT) and magnetic resonance imaging (MRI) in the successful management of an often fatal fungal infection in a 12-year-old patient with insulin-dependent diabetes mellitus (IDDM). CASE The patient was admitted to The University of Mississippi Medical Center (UMC) for the purpose of diabetic ketoacidosis (DKA) management and subsequent intensive therapy for mucormycosis according to nationally accepted standards of care. Strict diabetic control was instituted with frequent monitoring of blood glucose levels and interval assessment of HbA1c. Sequential MRI studies were obtained according to approved patient standards; the clinical and MRI course of the infection was charted. RESULTS The patient's DKA resolved within 12 h on intravenous fluid repletion and insulin therapy. His sinusitis/rhinitis noted on admission did not respond to intravenous antibiotic therapy and progressed with obvious left orbital involvement and left cranial nerve palsies by 72 h of hospitalization. CT and MRI were invaluable aids to the early diagnosis and design of appropriate surgical and antifungal management of this patient, who survived with minimal left cranial nerve palsies. CONCLUSIONS Our patient is among the youngest of IDDM patients reported to have survived rhinocerebral mucormycosis. His survival is attributed to early recognition of possible mucormycosis with diagnostic support of CT and MRI, surgical debridement and antifungal therapy, and intensive blood glucose control. Sequential MRI is invaluable to the design of therapy for this type of patient and shows the nearly 3-year recovery from mucormycosis.
Randomized Clinical Trial of Adjuvant Mitomycin Plus Tegafur in Patients With Resected Stage III Gastric Cancer
Authors: L Cirera, A Balil, E Batiste-Alentorn, I Tusquets, T Cardona, A Arcusa, L Jolis, E Saigí, I Guasch, A Badia, M Boleda
Journal: Journal of Clinical Oncology (1999)

PURPOSE: The efficacy of adjuvant chemotherapy in gastric cancer is controversial. We conducted a phase III, randomized, multicentric clinical trial with the goal of assessing the efficacy of the combination of mitomycin plus tegafur in prolonging the disease-free survival and overall survival of patients with resected stage III gastric cancer. PATIENTS AND METHODS: Patients with resected stage III gastric adenocarcinoma were randomly assigned, using sealed envelopes, to receive either chemotherapy or no further treatment. Chemotherapy was started within 28 days after surgery according to the following schedule: mitomycin 20 mg/m 2 intravenously (bolus) at day 1 of chemotherapy; 30 days later, oral tegafur at 400 mg bid daily for 3 months. Disease-free survival and overall survival were estimated using the Kaplan-Meier analysis and the Cox proportional hazards model. RESULTS: Between January 1988 and September 1994, 148 patients from 10 hospitals in Catalonia, Spain, were included in the study. The median follow-up period was 37 months. The tolerability of the treatment was excellent. The overall survival and disease-free survival were higher in the group of patients treated with chemotherapy (P = .04 for survival and P = .01 for disease-free survival in the log-rank test). The overall 5-year survival rate and the 5-year disease-free survival rate were, respectively, 56% and 51% in the treatment group and 36% and 31% in the control group. CONCLUSION: Our positive results are consistent with the results of recent studies; which conclude that there is a potential benefit from adjuvant chemotherapy in resected gastric cancer.
Tissue engineering of aortic heart valves
Authors: W Zimmermann
Journal: Cardiovascular Research (2003)

See article by Schenke-Layland et al. (pages 497–509) in this issue. 

Valve replacement is the most common surgical procedure in patients with advanced valvular heart disease [1]. Extensive experience has been gained with mechanical and decellularized biological valve prostheses since their clinical implementation in 1965 [2]. In the year 2000, 87,000 valve replacement procedures were performed in the US (www.americanheart.org). Despite its indisputable clinical value, currently employed concepts are hampered by thromboembolic complications, infections, limited durability, and lack of growth potential. Tissue engineering approaches hold the promise of generating completely biological, autologous “living” valves with functional features of their native counterparts that may overcome the present limitations [3,4].

Two main concepts are being pursued in tissue engineering of heart valves: (i) engineering of completely artificial valves from biocompatible and degradable synthetic polymers or biomaterials [5–7] and (ii) decellularization of native heart valves from xenogeneic/allogeneic donors [8–10], an extension of clinically employed biological valves. A drawback of purely (bio-)material-based approaches is the pronounced thrombogenicity of the currently employed polymers and biological matrix components. Seeding of the entire thrombogenic surfaces with endothelial cells would possibly solve this problem but is severely compromised by cell detachment, especially under high pressure aortic flow conditions. Another crucial issue in cardiac valve engineering is the design of stable, strain-resistant and at the same time pliable constructs with functional … 

*Corresponding author. Tel.: +49-40-42803-3180; fax: +49-40-42803-4876. Email address: w.zimmermann{at}uke.uni-hamburg.de