tbuckley/cabot-search huggingface dataset:
Live high-train low associated with increased haemoglobin mass as preparation for the 2003 World Championships in two native European world class runners
Authors: J P Wehrlin, B Marti
Journal: British Journal of Sports Medicine (2006)

Background: It is unclear whether world class endurance athletes, in contrast with less well trained subjects, increase their haemoglobin mass on a regimen of living high and training low (LHTL). Objective: To assess whether haemoglobin mass increases in world class athletes on LHTL and whether this increase is associated with peak performance at a subsequent important competition. Methods: Two Swiss world class runners (one 5000 m and one marathon) lived for 26 days (18 hours a day) at an altitude of 2456 m and trained at 1800 m. This LHTL camp was the preparation for the World Athletic Championships taking place 27–29 days after the end of the camp. Haemoglobin mass and other haematological variables were measured before and after the LHTL camp. The performance parameter was the race times during that period. Results: Haemoglobin mass increased by 3.9% and 7.6%, and erythrocyte volume by 5.8% and 6.3%. The race times, as well as the ranking at the World Championships, indicated clearly improved performance after the LHTL camp. Conclusions: The results suggest that LHTL with an adequate dose of hypoxia can increase haemoglobin mass even in world class athletes, which may translate into improved performance at important competitions at sea level.
Regulation of WNK1 Expression by miR-192 and Aldosterone
Authors: Emilie Elvira-Matelot, Xiao-ou Zhou, Nicolette Farman, Geneviève Beaurain, Alexandra Henrion-Caude, Juliette Hadchouel, Xavier Jeunemaitre
Journal: Journal of the American Society of Nephrology (2010)

WNK1 and WNK4 encode two members of the WNK serine-threonine kinase subfamily. Greater WNK1 expression associates with higher BP. A combination of promoters, enhancers, repressors, and insulators regulate WNK1 expression, but whether microRNAs also modulate WNK1 expression is unknown. Here, computational analysis revealed the presence of a target sequence for miR-192 and miR-215 at the same site in the 3′ untranslated region of the ubiquitous L- and the kidney-specific KS-WNK1. We functionally validated this target sequence by transient transfection and reporter assays. Although we observed expression of both miRs along the distal nephron, only miR-192 regulated endogenous WNK1 ex vivo. Furthermore, a potassium load, sodium depletion, and aldosterone infusion each significantly reduced miR-192 expression in the kidney. Taken together, these results suggest a miR-driven mechanism of gene regulation by aldosterone and a role for miR-192 in the regulation of sodium and potassium balance in the kidney.
Vaccination with DNA Encoding the Immunodominant LACK Parasite Antigen Confers Protective Immunity to Mice Infected with <i>Leishmania major </i>
Authors: Sanjay Gurunathan, David L. Sacks, Daniel R. Brown, Steven L. Reiner, Hughes Charest, Nicolas Glaichenhaus, Robert A. Seder
Journal: The Journal of Experimental Medicine (1997)

To determine whether DNA immunization could elicit protective immunity to Leishmania major in susceptible BALB/c mice, cDNA for the cloned Leishmania antigen LACK was inserted into a euykaryotic expression vector downstream to the cytomegalovirus promoter. Susceptible BALB/c mice were then vaccinated subcutaneously with LACK DNA and challenged with L. major promastigotes. We compared the protective efficacy of LACK DNA vaccination with that of recombinant LACK protein in the presence or absence of recombinant interleukin (rIL)-12 protein. Protection induced by LACK DNA was similar to that achieved by LACK protein and rIL-12, but superior to LACK protein without rIL-12. The immunity conferred by LACK DNA was durable insofar as mice challenged 5 wk after vaccination were still protected, and the infection was controlled for at least 20 wk after challenge. In addition, the ability of mice to control infection at sites distant to the site of vaccination suggests that systemic protection was achieved by LACK DNA vaccination. The control of disease progression and parasitic burden in mice vaccinated with LACK DNA was associated with enhancement of antigen-specific interferon-γ (IFN-γ) production. Moreover, both the enhancement of IFN-γ production and the protective immune response induced by LACK DNA vaccination was IL-12 dependent. Unexpectedly, depletion of CD8+ T cells at the time of vaccination or infection also abolished the protective response induced by LACK DNA vaccination, suggesting a role for CD8+ T cells in DNA vaccine induced protection to L. major. Thus, DNA immunization may offer an attractive alternative vaccination strategy against intracellular pathogens, as compared with conventional vaccination with antigens combined with adjuvants.
Lymphatic Vessels as Targets of Tumor Therapy?
Authors: Terhi Karpanen, Kari Alitalo
Journal: The Journal of Experimental Medicine (2001)

Recent evidence on the association of lymphangiogenic growth factors with intralymphatic growth and metastasis of cancers ([1][1])([2][2])([3][3])([4][4]) has raised hopes that lymphatic vessels could be used as an additional target for tumor therapy. Cancer cells spread within the body by direct
Distinct outcome of stage I lung adenocarcinoma with ACTN4 cell motility gene amplification
Authors: R. Noro, K. Honda, K. Tsuta, G. Ishii, A.M. Maeshima, N. Miura, K. Furuta, T. Shibata, H. Tsuda, A. Ochiai, T. Sakuma, N. Nishijima, A. Gemma, H. Asamura, K. Nagai, T. Yamada
Journal: Annals of Oncology (2013)
Caffeinated Coffee, Decaffeinated Coffee, and Caffeine in Relation to Plasma C-Peptide Levels, a Marker of Insulin Secretion, in U.S. Women
Authors: Tianying Wu, Walter C. Willett, Susan E. Hankinson, Edward Giovannucci
Journal: Diabetes Care (2005)

OBJECTIVE—Coffee consumption is associated with reduced risk of type 2 diabetes, but the mechanism is not clearly understood. Elevated C-peptide, as a marker of insulin secretion, has been linked to insulin-resistant type 2 diabetes. In this study, we examined consumption of caffeinated and decaffeinated coffee and total caffeine in relation to concentrations of plasma C-peptide. RESEARCH DESIGN AND METHODS—Plasma C-peptide concentrations were measured in a cross-sectional setting among 2,112 healthy women from the Nurses’ Health Study I who provided blood samples in 1989–1990. Consumption of caffeinated and decaffeinated coffee and total caffeine was assessed using a semiquantitative food-frequency questionnaire in 1990. RESULTS—Intakes of caffeinated and decaffeinated coffee and caffeine in 1990 were each inversely associated with C-peptide concentration in age-adjusted, BMI-adjusted, and multivariable-adjusted analyses. In multivariable analysis, concentrations of C-peptide were 16% less in women who drank &amp;gt;4 cups/day of caffeinated or decaffeinated coffee compared with nondrinkers (P &amp;lt; 0.005 for each). Women in the highest quintile compared with the lowest quintile of caffeine intake had 10% lower C-peptide levels (P = 0.02). We did not find any association between tea and C-peptide. The inverse association between caffeinated coffee and C-peptide was considerably stronger in obese (27% reduction) and overweight women (20% reduction) than in normal weight women (11% reduction) (P = 0.005). CONCLUSIONS—Our findings suggest a potential reduction of insulin secretion by coffee in women. This reduction may be related to other components in coffee rather than caffeine.
A cytokine and angiogenic factor (CAF) analysis in plasma for selection of sorafenib therapy in patients with metastatic renal cell carcinoma
Authors: A J Zurita, E Jonasch, X Wang, M Khajavi, S Yan, D Z Du, L Xu, M H Herynk, K S McKee, H T Tran, C J Logothetis, N M Tannir, J V Heymach
Journal: Annals of Oncology (2011)
Oxmetidine: clinical pharmacological studies with a new H2-receptor antagonist.
Authors: J G Mills, P L Brunet, R Griffiths, R H Hunt, D Vincent, G J Milton-Thompson, W L Burland
Journal: Gut (1982)

The gastric antisecretory effects of oxmetidine, a new H2-receptor antagonist, have been studied in 33 healthy subjects. The relative potency of oxmetidine compared with that of cimetidine depended on the route of administration and the experimental conditions. Oxmetidine intravenously infused was approximately four times as potent as cimetidine, weight for weight, in inhibiting impromidine stimulated gastric acid secretion but was twice as potent when food was used as a stimulus. After oral administration there were no differences in the weight-for-weight potency of oxmetidine and cimetidine, although oxmetidine was twice as potent on a molar basis. These apparent differences according to the route of drug administration are probably due to first pass metabolism of oxmetidine. There were no differences in the duration of action of oxmetidine and cimetidine. Twenty-four hour monitoring of intragastric pH showed that oxmetidine 400 mg twice daily reduced mean hourly 24 hour intragastric pH by 59%, suggesting that a twice daily dosage regimen should be evaluated in the treatment of duodenal ulceration.
CXCL12 Mediates CCR7-independent Homing of Central Memory Cells, But Not Naive T Cells, in Peripheral Lymph Nodes
Authors: M. Lucila Scimone, Thomas W. Felbinger, Irina B. Mazo, Jens V. Stein, Ulrich H. von Andrian, Wolfgang Weninger
Journal: The Journal of Experimental Medicine (2004)

Central memory CD8(+) T cells (T(CM)) confer superior protective immunity against infections compared with other T cell subsets. T(CM) recirculate mainly through secondary lymphoid organs, including peripheral lymph nodes (PLNs). Here, we report that T(CM), unlike naive T cells, can home to PLNs in both a CCR7-dependent and -independent manner. Homing experiments in paucity of lymph node T cells (plt/plt) mice, which do not express CCR7 ligands in secondary lymphoid organs, revealed that T(CM) migrate to PLNs at approximately 20% of wild-type (WT) levels, whereas homing of naive T cells was reduced by 95%. Accordingly, a large fraction of endogenous CD8(+) T cells in plt/plt PLNs displayed a T(CM) phenotype. Intravital microscopy of plt/plt subiliac lymph nodes showed that T(CM) rolled and firmly adhered (sticking) in high endothelial venules (HEVs), whereas naive T cells were incapable of sticking. Sticking of T(CM) in plt/plt HEVs was pertussis toxin sensitive and was blocked by anti-CXCL12 (SDF-1alpha). Anti-CXCL12 also reduced homing of T(CM) to PLNs in WT animals by 20%, indicating a nonredundant role for this chemokine in the presence of physiologic CCR7 agonists. Together, these data distinguish naive T cells from T(CM), whereby only the latter display greater migratory flexibility by virtue of their increased responsiveness to both CCR7 ligands and CXCL12 during homing to PLN.
B Cell Development Pathways
Authors: Richard R. Hardy, Kyoko Hayakawa
Journal: Annual Review of Immunology (2001)

B cell development is a highly regulated process whereby functional peripheral subsets are produced from hematopoietic stem cells, in the fetal liver before birth and in the bone marrow afterward. Here we review progress in understanding some aspects of this process in the mouse bone marrow, focusing on delineation of the earliest stages of commitment, on pre-B cell receptor selection, and B cell tolerance during the immature-to-mature B cell transition. Then we note some of the distinctions in hematopoiesis and pre-B selection between fetal liver and adult bone marrow, drawing a connection from fetal development to B-1/CD5 + B cells. Finally, focusing on CD5 + cells, we consider the forces that influence the generation and maintenance of this distinctive peripheral B cell population, enriched for natural autoreactive specificities that are encoded by particular germline V H -V L combinations.
The prevalence of aspirin intolerant asthma (AIA) in Australian asthmatic patients
Authors: H Vally
Journal: Thorax (2002)

Aspirin intolerant asthma (AIA) is a clinically distinct syndrome characterised by the precipitation of asthma attacks following the ingestion of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs). The prevalence of AIA among Australian asthmatic patients has not previously been reported.Three populations were surveyed to establish the prevalence of AIA among Australian asthmatics. Two surveys were completed in patients recruited from the metropolitan area in Perth, Western Australia, one comprising 150 recruited from hospital based sources (hospital cohort) and the second comprising 366 from the membership of the Asthma Foundation of Western Australia (Asthma Foundation cohort). In a third study 1298 individuals were randomly selected from the rural community of Busselton in Western Australia.The prevalence of AIA in the hospital and Asthma Foundation cohorts was found to be 10.7% and 10.4%, respectively. Univariate analyses in the Asthma Foundation cohort indicated that AIA was associated with more severe asthma (OR = 2.4, 95% CI 1.18 to 4.86), nasal polyposis (OR=3.19, 95% CI 1.52 to 6.68), atopy (OR=2.96, 95% CI 1.48 to 5.89), sulfite sensitivity (OR=3.97, 95% CI 1.87 to 8.41), and sensitivity to wine (OR=3.27, 95% CI 1.65 to 6.47). Multivariate analyses indicated that atopy (OR=2.80, 95% CI 1.38 to 5.70), nasal polyposis (OR=3.39, 95% CI 1.57 to 7.29), and the number of asthma attacks in the previous 12 months (OR=1.20, 95% CI 1.02 to 1.42) were independent predictors for AIA, as was wine sensitivity (OR=2.20, 95% CI 1.02 to 4.72). The prevalence of AIA among asthmatic patients in the Busselton cohort was 10.9%. In addition, 2.5% of non-diagnosed asthmatics in this cohort reported asthma symptoms following aspirin ingestion.The prevalence of respiratory symptoms triggered by aspirin/NSAID use was found to be 10-11% in patients with asthma and 2.5% in non-asthmatics. Aspirin sensitivity appears to be a significant problem in the community and further investigations of the mechanisms of these responses and the possible link between this syndrome and other food and chemical sensitivities are required.
Effect of a second-generation 2 ligand (pregabalin) on visceral sensation in hypersensitive patients with irritable bowel syndrome
Authors: L A Houghton, C Fell, P J Whorwell, I Jones, D P Sudworth, J D Gale
Journal: Gut (2007)

<b>Background:</b> Visceral hypersensitivity is an important pathophysiological factor in irritable bowel syndrome (IBS). Pre-clinical studies suggest that the α<sub>2</sub>δ ligand pregabalin reduces both visceral allodynia and hyperalgesia, but is inactive on basal sensitivity. <b>Aim:</b> To assess the effect of pregabalin on the perception of rectal distension in hypersensitive IBS patients. <b>Methods:</b> Twenty-six patients with Rome-II-defined IBS (aged 18–46 years, 7 male) were included in a randomized, double-blind, placebo-controlled, parallel-group study in which they received either 3 weeks oral pregabalin (titrated: 50 mg tid days 1–3, 100 mg tid days 4–7, 150 mg tid days 8–11; fixed 200 mg tid days 12–21 ±4) or placebo control. Rectal sensitivity was assessed using a barostat technique, in which sensory thresholds were determined using the ascending method of limits, followed by tracking both before and after treatment. Only patients with a pain threshold of ⩽28 mmHg were included in the study. <b>Results:</b> Pregabalin significantly increased the sensory thresholds from baseline for first sensation (p = 0.045), desire to defecate (p = 0.008) and pain (p = 0.048) compared with placebo control. In addition, pregabalin significantly increased rectal compliance (p&lt;0.0001), although this appeared to be unrelated to the changes in sensitivity. Despite the occurrence of mild dizziness and somnolence, pregabalin was generally well tolerated. <b>Conclusions:</b> Pregabalin increased distension sensory thresholds to normal levels in IBS patients with rectal hypersensitivity. A concomitant increase in rectal compliance appeared to be unrelated to the reduction in sensitivity. These data suggest that α<sub>2</sub>δ ligands are worthy of further investigation in the treatment of visceral pain disorders, including IBS.
THE RELATIONSHIP BETWEEN 2D KNEE VALGUS ANGLE DURING SINGLE LEG SQUAT (SLS), SINGLE LEG LANDING (SLL), AND FORWARD RUNNING
Authors: K Atkin, L Herrington, F Alenezi, P Jones, R Jones
Journal: British Journal of Sports Medicine (2014)

Background Two-dimensional (2D) analysis of knee valgus during common athletic screening tasks such as SLS has been purported to identify individuals who may be at a high-risk of ACL injury. There is limited literature exploring the relationships between joint motion during SLS and other athletic tasks associated with knee joint injuries, in order to evaluate the effectiveness of the SLS to identify athletes with hazardous knee motion in a range of athletic tasks. Objective To assess the relationship between the 2D knee valgus angle among three tasks (SLS, SLL, and Running). Design A correlational study. Setting Undertaken in the Human Performance Laboratory at the University of Salford. Participants 15 recreational athletes, 7 males and 8 females, were recruited (age 25.2±5.1 years; height 1.6±7.38 m; and mass 67.6±10.93 kg). Intervention Participants performed a series of SLS, SLL from a 31-cm step, and forward running at percieved maximum speed whilst being videotaped with a 2D digital camera. Main outcome measurements Maximum right knee valgus angle was quantified by measuring the frontal plane projection angle (FPPA) using Quintic Biomechanics v21 software package. Results A moderate correlation was shown between FPPA during SLS and SLL when the whole participant group was analysed (r=0.35). When split by gender female statistics showed good correlations between the majority of tasks; SLS and SLL (r=0.87), SLS and Run (r=0.59) but weaker between SLL and Run (0.26). Conclusions In females the FPPA during SLS correlates with FPPA during SLL and running. This indicates that if a female patient has increased FPPA during SLS they are likely to have increased FPPA across all the tasks. This could potentially reduce the time and tasks required for screening, as only one task would need to be assessed. In males there is little correlation between tasks so the same would not apply in male subjects.
Aspirin for the Primary Prevention of Cardiovascular Events: A Summary of the Evidence for the U.S. Preventive Services Task Force
Authors: Michael Hayden, Michael Pignone, Christopher Phillips, Cynthia Mulrow
Journal: Annals of Internal Medicine (2002)

Background: The use of aspirin to prevent cardiovascular disease events in patients without a history of cardiovascular disease is controversial. Purpose: To examine the benefits and harms of aspirin chemoprevention. Data Sources: MEDLINE (1966 to May 2001). Study Selection: 1] Randomized trials at least 1 year in duration that examined aspirin chemoprevention in patients without previously known cardiovascular disease and 2) systematic reviews, recent trials, and observational studies that examined rates of hemorrhagic strokes and gastrointestinal bleeding secondary to aspirin use. Data Extraction: One reviewer read and extracted data from each included article and constructed evidence tables. A second reviewer checked the accuracy of the data extraction. Discrepancies were resolved by consensus. Data Synthesis: Meta-analysis was performed, and the quantitative results of the review were then used to model the consequences of treating patients with different levels of baseline risk for coronary heart disease. Five trials examined the effect of aspirin on cardiovascular events in patients with no previous cardiovascular disease. For patients similar to those enrolled in the trials, aspirin reduces the risk for the combined end point of nonfatal myocardial infarction and fatal coronary heart disease (summary odds ratio, 0.72 [95% CI, 0.60 to 0.87]). Aspirin increased the risk for hemorrhagic strokes (summary odds ratio, 1.4 [CI, 0.9 to 2.0]) and major gastrointestinal bleeding (summary odds ratio, 1.7 [CI, 1.4 to 2.1]). All-cause mortality (summary odds ratio, 0.93 [CI, 0.84 to 1.02]) was not significantly affected. For 1000 patients with a 5% risk for coronary heart disease events over 5 years, aspirin would prevent 6 to 20 myocardial infarctions but would cause 0 to 2 hemorrhagic strokes and 2 to 4 major gastrointestinal bleeding events. For patients with a risk of 1% over 5 years, aspirin would prevent 1 to 4 myocardial infarctions but would cause 0 to 2 hemorrhagic strokes and 2 to 4 major gastrointestinal bleeding events. Conclusions: The net benefit of aspirin increases with increasing cardiovascular risk. In the decision to use aspirin chemoprevention, the patient's cardiovascular risk and relative utility for the different clinical outcomes prevented or caused by aspirin use must be considered.
A Predictor Based on the Somatic Genomic Changes of the BRCA1/BRCA2 Breast Cancer Tumors Identifies the Non-BRCA1/BRCA2 Tumors with BRCA1 Promoter Hypermethylation
Authors: Sara Alvarez, Ramon Diaz-Uriarte, Ana Osorio, Alicia Barroso, Lorenzo Melchor, Maria Fe Paz, Emiliano Honrado, Raquel Rodríguez, Miguel Urioste, Laura Valle, Orland Díez, Juan Cruz Cigudosa, Joaquin Dopazo, Manel Esteller, Javier Benitez
Journal: Clinical Cancer Research (2005)

Abstract The genetic changes underlying in the development and progression of familial breast cancer are poorly understood. To identify a somatic genetic signature of tumor progression for each familial group, BRCA1, BRCA2, and non-BRCA1/BRCA2 (BRCAX) tumors, by high-resolution comparative genomic hybridization, we have analyzed 77 tumors previously characterized for BRCA1 and BRCA2 germ line mutations. Based on a combination of the somatic genetic changes observed at the six most different chromosomal regions and the status of the estrogen receptor, we developed using random forests a molecular classifier, which assigns to a given tumor a probability to belong either to the BRCA1 or to the BRCA2 class. Because 76.5% (26 of 34) of the BRCAX cases were classified with our predictor to the BRCA1 class with a probability of &amp;gt;50%, we analyzed the BRCA1 promoter region for aberrant methylation in all the BRCAX cases. We found that 15 of the 34 BRCAX analyzed tumors had hypermethylation of the BRCA1 gene. When we considered the predictor, we observed that all the cases with this epigenetic event were assigned to the BRCA1 class with a probability of &amp;gt;50%. Interestingly, 84.6% of the cases (11 of 13) assigned to the BRCA1 class with a probability &amp;gt;80% had an aberrant methylation of the BRCA1 promoter. This fact suggests that somatic BRCA1 inactivation could modify the profile of tumor progression in most of the BRCAX cases.