tbuckley/cabot-search huggingface dataset:
The Effect of Metformin on Adipose Tissue Metabolism and Peripheral Blood Flow in Subjects With NIDDM
Authors: Per-Anders E Jansson, H Soffia Gudbjörnsdóttir, Ove K Andersson, Peter N Lönnroth
Journal: Diabetes Care (1996)

To examine the effect of metformin on net lactate and glycerol release in NIDDM subjects, we used abdominal subcutaneous microdialysis combined with 133Xe clearance. Skeletal muscle blood flow (MBF) was assessed simultaneously both before and after metformin treatment.Nine male patients with NIDDM (age 53 +/- 2 years [mean +/- SE]; BMI 30.2 +/- 1.4 kg/m2; body fat 23.0 +/- 2.6 kg; diabetes duration 4.6 +/- 1.5 years; six of nine receiving sulfonylurea treatment) were recruited into an open study. They were studied after an overnight fast, both before and after 1 week of additional treatment with 500 mg metformin three times daily. Nine weight- and age-matched nondiabetic subjects served as a control group.Postabsorptive net subcutaneous lactate release increased (149 +/- 50 vs. 475 +/- 127 nmol.100 g-1.min-1, P < 0.05) whereas plasma lactate was unchanged after metformin treatment in the NIDDM patients. The net decrease of glycerol release 90 min after an oral glucose tolerance test was more pronounced (110 +/- 30 vs. 199 +/- 20 nmol.100 g-1.min-1, P < 0.05) after metformin treatment. Both adipose tissue blood flow (ATBF) (1.5 +/- 0.1 vs. 2.3 +/- 0.2 ml.100 g-1.min-1, P < 0.01) and MBF (3.2 +/- 0.4 vs. 4.2 +/- 0.5 ml.100 ml-1.min-1, P < 0.05) increased after metformin treatment.In this open study, postabsorptive net lactate release in abdominal subcutaneous adipose tissue was clearly increased in NIDDM patients after metformin treatment. Basal ATBF as well as MBF was improved after metformin treatment. Whether this reflects enhanced metabolic control or is a drug-specific effect remains to be established.
Protective effect of fruits, vegetables and the Mediterranean diet on asthma and allergies among children in Crete
Authors: L. Chatzi, G. Apostolaki, I. Bibakis, I. Skypala, V. Bibaki-Liakou, N. Tzanakis, M. Kogevinas, P. Cullinan
Journal: Thorax (2007)

Atopy is not uncommon among children living in rural Crete, but wheeze and rhinitis are rare. A study was undertaken to examine whether this discrepancy could be attributed to a high consumption of fresh fruit and vegetables or adherence to a traditional Mediterranean diet.A cross-sectional survey was performed in 690 children aged 7-18 years in rural Crete. Parents completed a questionnaire on their child's respiratory and allergic symptoms and a 58-item food frequency questionnaire. Adherence to a Mediterranean diet was measured using a scale with 12 dietary items. Children underwent skin prick tests with 10 common aeroallergens.80% of children ate fresh fruit (and 68% vegetables) at least twice a day. The intake of grapes, oranges, apples, and fresh tomatoes-the main local products in Crete-had no association with atopy but was protective for wheezing and rhinitis. A high consumption of nuts was found to be inversely associated with wheezing (OR 0.46; 95% CI 0.20 to 0.98), whereas margarine increased the risk of both wheeze (OR 2.19; 95% CI 1.01 to 4.82) and allergic rhinitis (OR 2.10; 95% CI 1.31 to 3.37). A high level of adherence to the Mediterranean diet was protective for allergic rhinitis (OR 0.34; 95% CI 0.18 to 0.64) while a more modest protection was observed for wheezing and atopy.The results of this study suggest a beneficial effect of commonly consumed fruits, vegetables and nuts, and of a high adherence to a traditional Mediterranean diet during childhood on symptoms of asthma and rhinitis. Diet may explain the relative lack of allergic symptoms in this population.
Induction of nitric oxide synthase by lipopolysaccharide inhalation enhances substance P-induced microvascular leakage in guinea-pigs
Authors: Y Ohuchi, M Ichinose, M Miura, N Kageyama, M Tomaki, N Endoh, Y Mashito, H Sugiura, K Shirato
Journal: European Respiratory Journal (1998)

Inducible nitric oxide (NO) synthase (iNOS)-mediated hyperproduction of NO in airways has been reported in asthmatic patients. However, the role of NO in the pathogenesis of asthma has not yet been fully elucidated. The aim of this study was to examine whether the iNOS-derived NO affects airway microvascular leakage, one of the characteristic features of asthmatic airway inflammation. Guinea-pigs were exposed to lipopolysaccharide (LPS) (1 mg x mL(-1)) by inhalation in order to induce iNOS in the airways, and the histochemical staining of reduced nicotinamide-adenine dinucleotide phosphate (NADPH)-diaphorase activity was determined 5 h after the inhalation to confirm the iNOS induction. Airway microvascular leakage to subthreshold doses of substance P (0.3 microg x kg(-1), i.v.) was also examined in the absence and presence of an iNOS inhibitor (aminoguanidine) in LPS- or saline-exposed (control) animals using Evans blue dye and Monastral blue dye. In the LPS-exposed animals, increased NADPH-diaphorase activity was observed in the airway microvasculature compared with the control animals. Substance P caused significant airway microvascular leakage assessed by Evans blue dye in all airway levels in the LPS-exposed animals but not in the control group. This was also confirmed by Monastral blue dye extravasation. Aminoguanidine abolished this LPS-induced enhancement of plasma leakage to substance P without changing the systemic blood pressure. These results may suggest that inducible nitric oxide synthase-derived nitric oxide is capable of potentiating neurogenic plasma leakage in airways.
Off-Pump Techniques Disproportionately Benefit Women and Narrow the Gender Disparity in Outcomes After Coronary Artery Bypass Surgery
Authors: John D. Puskas, Patrick D. Kilgo, Michael Kutner, Sorin V. Pusca, Omar Lattouf, Robert A. Guyton
Journal: Circulation (2007)

Background— Women experience greater morbidity and mortality than men after conventional coronary artery bypass grafting (CABG) on cardiopulmonary bypass (CPB). The objective of this study was to determine whether off-pump CABG (OPCAB) alters this gender-based disparity. Methods and Results— Retrospective review of risk factors and clinical outcomes for 11 413 consecutive patients having isolated CABG between January 1, 1997, and May 31, 2005, at a US academic center. Interventions were OPCAB or CABG/CPB, performed at the discretion of 14 faculty surgeons. Main outcome measures included in-hospital death, stroke, myocardial infarction or combined major adverse cardiac events (MACE=death or stroke or myocardial infarction). Odds ratios of adverse events, adjusted for 31 risk factors, were compared between women and men who had OPCAB versus CABG/CPB. Covariates included Propensity Score, Society of Thoracic Surgeons’ Predicted Risk, surgeon and body habitus. Female patients (n=3248) and those treated with OPCAB (n=4492) were older, had more comorbidities and higher predicted risk than male patients (n=8165) and those treated with conventional CABG/CPB (n=6921), respectively. Women treated with CABG/CPB had a risk-adjusted odds ratio of 1.60 for death ( P =0.01), 1.71 for stroke ( P =0.007), 2.26 for myocardial infarction ( P =0.008) and 1.71 for MACE ( P &lt;0.001) compared with men who had CABG/CPB. In contrast, women treated with OPCAB had outcomes statistically similar to men who had either OPCAB or CABG/CPB. Among women, OPCAB was associated with a significant reduction in death (OR 0.39, P =0.001), stroke (OR 0.43, P =0.002) and MACE (OR 0.43, P &lt;0.001). Conclusions— OPCAB is associated with fewer major adverse cardiac events and benefits women disproportionately, thereby narrowing the gender disparity in clinical outcomes after CABG.
TH2-like Chemokine Predominance in Recurrent Respiratory Papillomatotosis (RPR) Does Not Originate from Peripheral Blood Mononuclear Cells (PBMC)
Authors: D.W. Rosenthal, J.A. DeVoti, B.M. Steinberg, V.R. Bonagura
Journal: Journal of Allergy and Clinical Immunology (2010)
Patient's response to the research
Authors: D. Wilkins
Journal: BMJ (2003)

Since “personal care” is ostensibly at the heart of primary care provision, it seems extraordinary that the concept remains—as the authors here rightly say—little studied. This research suggests that there is some important common ground between patients and healthcare providers but that perceptions nevertheless differ according to viewpoint. One of the more obvious factors that might have a bearing on the nature of the experience for patient and professional alike is the gender of the participants in that experience. Bald statistics tell us that men are significantly less likely to visit their GP …
Long-term follow-up and post-relapse survival in patients with non-metastatic osteosarcoma of the extremity treated with neoadjuvant chemotherapy
Authors: S. Ferrari, G. Bacci, P. Picci, M. Mercuri, A. Briccoli, D. Pinto, A. Gasbarrini, A. Tienghi, A. Brach del Prever
Journal: Annals of Oncology (1997)
Hydrogen peroxide metabolism in human monocytes during differentiation in vitro.
Authors: A Nakagawara, C F Nathan, Z A Cohn
Journal: Journal of Clinical Investigation (1981)

The capacity of human blood monocytes to secrete hydrogen peroxide (H2O2) and superoxide (O2-) was measured as the cells differentiated during 4 wk of culture. Morphologic transformation of monocytes into macrophages, epithelioid cells, and multinucleated giant cells accompanied a steady increase in the content of protein per cell, from 0.77 mg/10(7) cells on days 0 to 11.77 mg/10(7) cells on days 20 to 29. In contrast, secretion of H2O2 by adherent monocytes was 859 +/- 73 nmol/60 min per mg protein (mean +/- SEM, n = 18) on day 0, rose 40% on day 3, and then fell rapidly, remaining below 6% of the initial values after day 10. The decline in capacity to secrete reactive oxygen intermediates was observed whether H2O2 or O2- were measured, whether the cells were challenged with phorbol myristate acetate or with opsonized zymosan, and whether the results were expressed per milligram cell protein or per cell. Superoxide dismutase activity tripled in adherent monocytes from day 0 to day 3, and thereafter remained elevated through at least day 16. In contrast, the activity of myeloperoxidase declined rapidly, catalase and glutathione peroxidase declined more gradually, and glutathione reductase and glutathione remained constant through the period of observation. Thus, the decline in capacity to secrete H2O2 could not be attributed to increases in cellular levels of these antioxidants. On the first day of culture, H2O2 release was enhanced up to fourfold by inclusion of sodium azide or potassium cyanide in the assay medium. This enhancement appeared to be due to inhibition of monocyte myeloperoxidase, rather than catalase. This conclusion was based on the kinetics and dose-response relationships for the effects of azide and cyanide on H2O2 release and on the activities of catalase and myeloperoxidase. Thus, the differentiation of human monocytes into macrophages in vitro is accompanied by an apparent reduction in the capacity to produce H2O2 and O2-. In this regard, the human monocyte-derived macrophage comes to resemble the resting tissue macrophage previously characterized in the mouse peritoneal cavity.
Connectionist modelling in psychology: A localist manifesto
Authors: Mike Page
Journal: Behavioral and Brain Sciences (2000)

Over the last decade, fully distributed models have become dominant in connectionist psychological modelling, whereas the virtues of localist models have been underestimated. This target article illustrates some of the benefits of localist modelling. Localist models are characterized by the presence of localist representations rather than the absence of distributed representations. A generalized localist model is proposed that exhibits many of the properties of fully distributed models. It can be applied to a number of problems that are difficult for fully distributed models, and its applicability can be extended through comparisons with a number of classic mathematical models of behaviour. There are reasons why localist models have been underused, though these often misconstrue the localist position. In particular, many conclusions about connectionist representation, based on neuroscientific observation, can be called into question. There are still some problems inherent in the application of fully distributed systems and some inadequacies in proposed solutions to these problems. In the domain of psychological modelling, localist modelling is to be preferred.
Platelet size in patients with chronic airflow obstruction with and without hypoxaemia.
Authors: J A Wedzicha, F E Cotter, D W Empey
Journal: Thorax (1988)

Platelet size, expressed as mean platelet volume, was estimated in 35 patients with chronic airflow obstruction and a wide range of arterial oxygen tension (PaO2) values. In these patients there was a negative correlation between MPV and PaO2 (r = -0.70). Mean platelet volume was greater (9.41 (0.86) fl) in 20 patients with an arterial PaO2 of 8 kPa (60 mm Hg) or less than in 18 normal subjects (8.21 (0.63) fl; p less than 0.001). After 24 hours of supplemental oxygen treatment there was a small fall in mean platelet volume, from 9.47 (1.06) to 8.96 (0.8) fl (p less than 0.05) in 12 hypoxaemic patients (PaO2 breathing air less than or equal to 8 kPa) but no change in nine non-hypoxaemic patients. Larger platelets are considered to be haemostatically more active, leading to abnormal platelet function, which may contribute to the development of pulmonary vascular damage in chronic hypoxaemia. Supplemental oxygen may partially reverse these changes by modifying platelet size and activity.
Lipoprotein Lipase Activity Is Associated With Severity of Angina Pectoris
Authors: John J. P. Kastelein, J. Wouter Jukema, Aeilko H. Zwinderman, Suzanne Clee, Ad J. van Boven, Hans Jansen, Ton J. Rabelink, Ron J. G. Peters, Kong I. Lie, George Liu, Albert V. G. Bruschke, Michael R. Hayden
Journal: Circulation (2000)

Background —Raised triglyceride-rich lipoproteins significantly increase the risk for cardiovascular disease. Variation in the activity of the enzyme lipoprotein lipase (LPL), which is crucial in the removal of these lipoproteins, may therefore modulate this risk. Methods and Results —Postheparin levels of LPL activity and mass were measured in a large cohort of male coronary artery disease patients participating in the Regression Growth Evaluation Statin Study (REGRESS), a lipid-lowering regression trial. In addition, the relationships between LPL activity and mass and severity of angina pectoris according to the NYHA classification and silent ischemia on 24-hour ambulatory ECG monitoring were assessed. Patients in different LPL activity quartiles and mass had different severities of angina; a total of 47% of patients in the lowest LPL quartile reported class III or IV angina. In contrast, only 29% in the highest activity quartile ( P =0.002) had severe angina. These parameters were supported by ambulatory ECG results, for which the total ischemic burden in the lowest LPL activity quartile was 36.5±104.1 mm×min compared with 14.8±38.8 mm×min in the highest quartile of LPL activity ( P =0.001). LPL activity levels were strongly correlated with LPL mass ( r =0.70, P &lt;0.0001). A significant association between the LPL protein mass and NYHA class ( P =0.012) was also demonstrated. Conclusions —We have demonstrated a significant relationship between LPL mass and activity and severity of ischemia as defined by angina class and ambulatory ECG. These results suggest that LPL influences risk for coronary artery disease by both catalytic and noncatalytic mechanisms.
Myelin-specific T cells also recognize neuronal autoantigen in a transgenic mouse model of multiple sclerosis
Authors: Gurumoorthy Krishnamoorthy, Amit Saxena, Lennart T Mars, Helena S Domingues, Reinhard Mentele, Avraham Ben-Nun, Hans Lassmann, Klaus Dornmair, Florian C Kurschus, Roland S Liblau, Hartmut Wekerle
Journal: Nature Medicine (2009)
C/EBPα: critical at the origin of leukemic transformation
Authors: Jae-Seok Roe, Christopher R. Vakoc
Journal: The Journal of Experimental Medicine (2014)

Acute myeloid leukemia (AML) is a hematopoietic malignancy characterized by clonal expansion of myeloid progenitor cells. A major mechanistic theme in AML biology is the extensive collaboration among fusion oncoproteins, transcription factors, and chromatin regulators to initiate and sustain a transformed cellular state. A new study in this issue describes how the C/EBPα transcription factor is crucial for the initiation of AML induced by MLL fusion oncoproteins, but is entirely dispensable for the maintenance of established disease. These observations provide a unique glimpse into the pioneer round of regulatory events that are critical at the origin of AML formation. Furthermore, this study implies the existence of oncogene-induced positive feedback loops capable of bypassing the continuous need for certain regulators to propagate disease.
Coarse and fine particles but not ultrafine particles in urban air trigger hospital admission for asthma in children
Authors: Amne Iskandar, Zorana Jovanovic Andersen, Klaus Bønnelykke, Thomas Ellermann, Klaus Kaae Andersen, Hans Bisgaard
Journal: Thorax (2011)

Short-term exposure to air pollution can trigger hospital admissions for asthma in children, but it is not known which components of air pollution are most important. There are no available studies on the particular effect of ultrafine particles (UFPs) on paediatric admissions for asthma.To study whether short-term exposure to air pollution is associated with hospital admissions for asthma in children. It is hypothesised that (1) the association between asthma admissions and air pollution is stronger with UFPs than with coarse (PM10) and fine (PM2.5) particles, nitrogen oxides (NOx) or nitrogen dioxide (NO2); and (2) infants are more susceptible to the effects of exposure to air pollution than older children.Daily counts of admissions for asthma in children aged 0-18 years to hospitals located within a 15 km radius of the central fixed background urban air pollution measurement station in Copenhagen between 2001 and 2008 were extracted from the Danish National Patient Registry. A time-stratified case crossover design was applied and data were analysed using conditional logistic regression to estimate the effect of air pollution on asthma admissions.A significant association was found between hospital admissions for asthma in children aged 0-18 years and NOx (OR 1.11; 95% CI 1.05 to 1.17), NO2 (1.10; 95% CI 1.04 to 1.16), PM10 (1.07; 95% CI 1.03 to 1.12) and PM2.5 (1.09; 95% CI 1.04 to 1.13); there was no association with UFPs. The association was stronger in infants than in older children for all pollutants, but no statistically significant interaction was detected.Short-term exposure to air pollution can trigger hospital admission for asthma in children, with infants possibly being most susceptible. These effects seemed to be mediated by larger particles and traffic-related gases, whereas UFPs showed no effect.
A common neoepitope is created when the reactive center of C1-inhibitor is cleaved by plasma kallikrein, activated factor XII fragment, C1 esterase, or neutrophil elastase.
Authors: A de Agostini, P A Patston, V Marottoli, S Carrel, P C Harpel, M Schapira
Journal: Journal of Clinical Investigation (1988)

The reactive center of C1-inhibitor, a plasma protease inhibitor that belongs to the serpin superfamily, is located on a peptide loop which is highly susceptible to proteolytic cleavage. With plasma kallikrein, C1s and beta-Factor XIIa, this cleavage occurs at the reactive site residue P1 (Arg444); with neutrophil elastase, it takes place near P1, probably at residue P3 (Val442). After these cleavages, C1-inhibitor is inactivated and its conformation is modified. Moreover, in vivo, cleaved C1-inhibitor is removed from the blood stream more rapidly than the intact serpin, which suggests that proteolysis unmasks sites responsible for cellular recognition and the uptake of the cleaved inhibitor. In the study reported here, we show, using an MAb, that an identical neoepitope is created on C1-inhibitor after the cleavage of its exposed loop by plasma kallikrein, C1s, beta-Factor XIIa, and by neutrophil elastase.
Regulation of Erk1/2 activation by osteopontin in PC3 human prostate cancer cells
Authors: Brian W Robertson, Lauren Bonsal, Meenakshi A Chellaiah
Journal: Molecular Cancer (2010)

Abstract Background Osteopontin (OPN) has been shown to play many roles in the progression of cancer. We have recently demonstrated the activation of Akt by OPN. Integrin-linked kinase and PI3-kinase are integral proteins in OPN/AKT pathway in PC3 cells. To investigate the role of the extracellular receptors in OPN signaling, we have examined the spatio-temporal regulation of CD44 and integrin αvβ3 receptor in OPN-induced Akt activation in PC3 cells. Results Here, our studies demonstrate that OPN can activate Akt either through the α V β 3 integrin or the CD44 cell surface receptor. Members of the Mitogen Activated Protein Kinase (MAPK) family have been shown to be up-regulated in a variety of human cancers and have been implicated in the metastatic behavior. Our studies have demonstrated an increase in the phosphorylation of c-Raf at Ser259 and Ser338 in PC3 cells over-expressing OPN. This increase matches up with the Erk1/2 phosphorylation at Thr202/204 and activation. However, the inhibition of Akt activity augments the phosphorylation state of ERK1/2 to two to three fold with a concomitant reduction in the phosphorylation state of c-Raf at Ser259. Conclusions Regulation c-Raf phosphorylation at Ser259 has a role in the anti-apoptotic pathways mediated by Akt or Raf/MEK/ERK proteins. OPN may have dual effects in the activation of Erk1/2. We propose this based on the observations that while OPN activates c-Raf and Erk1/2; it also acts to inhibit c-Raf and Erk1/2 activation through Akt pathway. Our observations suggest that the activation of c-Raf-ERK cascade may promote cell cycle arrest in prostate cancer cells and OPN signaling has a role in the anti-apoptotic mechanism.
Premetazoan Ancestry of the Myc–Max Network
Authors: Susan L. Young, Daniel Diolaiti, Maralice Conacci-Sorrell, Iñaki Ruiz-Trillo, Robert N. Eisenman, Nicole King
Journal: Molecular Biology and Evolution (2011)

The origin of metazoans required the evolution of mechanisms for maintaining differentiated cell types within a multicellular individual, in part through spatially differentiated patterns of gene transcription. The unicellular ancestor of metazoans was presumably capable of regulating gene expression temporally in response to changing environmental conditions, and spatial cell differentiation in metazoans may represent a co-option of preexisting regulatory mechanisms. Myc is a critical regulator of cell growth, proliferation, and death that is found in all metazoans but absent in other multicellular lineages, including fungi and plants. Homologs of Myc and its binding partner, Max, exist in two of the closest living relatives of animals, the choanoflagellate Monosiga brevicollis (Mb) and Capsaspora owczarzaki, a unicellular opisthokont that is closely related to metazoans and choanoflagellates. We find that Myc and Max from M. brevicollis heterodimerize and bind to both canonical and noncanonical E-boxes, the DNA-binding sites through which metazoan Myc proteins act. Moreover, in M. brevicollis, MbMyc protein can be detected in nuclear and flagellar regions. Like metazoan Max proteins, MbMax can form homodimers that bind to E-boxes. However, cross-species dimerization between Mb and human Myc and Max proteins was not observed, suggesting that the binding interface has diverged. Our results reveal that the Myc/Max network arose before the divergence of the choanoflagellate and metazoan lineages. Furthermore, core features of metazoan Myc function, including heterodimerization with Max, binding to E-box sequences in DNA, and localization to the nucleus, predate the origin of metazoans.