tbuckley/cabot-search huggingface dataset:
Fructose Induces the Inflammatory Molecule ICAM-1 in Endothelial Cells
Authors: Olena Glushakova, Tomoki Kosugi, Carlos Roncal, Wei Mu, Marcelo Heinig, Pietro Cirillo, Laura G. Sa[Combining Acute Accent]nchez-Lozada, Richard J. Johnson, Takahiko Nakagawa
Journal: Journal of the American Society of Nephrology (2008)

Epidemiologic studies have linked fructose intake with the metabolic syndrome, and it was recently reported that fructose induces an inflammatory response in the rat kidney. Here, we examined whether fructose directly stimulates endothelial inflammatory processes by upregulating the inflammatory molecule intercellular adhesion molecule-1 (ICAM-1). When human aortic endothelial cells were stimulated with physiologic concentrations of fructose, ICAM-1 mRNA and protein expression increased in a time- and dosage-dependent manner, which was independent of NF-κB activation. Fructose reduced endothelial nitric oxide (NO) levels and caused a transient reduction in endothelial NO synthase expression. The administration of an NO donor inhibited fructose-induced ICAM-1 expression, whereas blocking NO synthase enhanced it, suggesting that NO inhibits endothelial ICAM-1 expression. Furthermore, fructose resulted in decreased intracellular ATP; administration of exogenous ATP blocked fructose-induced ICAM-1 expression and increased NO levels. Consistent with the in vitro studies, dietary intake of fructose at physiologic dosages increased both serum ICAM-1 concentration and endothelial ICAM-1 expression in the rat kidney. These data suggest that fructose induces inflammatory changes in vascular cells at physiologic concentrations.
Weekly docetaxel, cisplatin, and irinotecan (TPC): results of a multicenter phase II trial in patients with metastatic esophagogastric cancer
Authors: P.C. Enzinger, D.P. Ryan, J.W. Clark, A. Muzikansky, C.C. Earle, M.H. Kulke, J.A. Meyerhardt, L.S. Blaszkowsky, A.X. Zhu, P. Fidias, M.M. Vincitore, R.J. Mayer, C.S. Fuchs
Journal: Annals of Oncology (2009)
Bone marrow mesenchymal stem cells from infants with MLL-AF4+ acute leukemia harbor and express the MLL-AF4 fusion gene
Authors: Pablo Menendez, Purificación Catalina, René Rodríguez, Gustavo J. Melen, Clara Bueno, Mar Arriero, Félix García-Sánchez, Alvaro Lassaletta, Ramón García-Sanz, Javier García-Castro
Journal: The Journal of Experimental Medicine (2009)

MLL-AF4 fusion is a hallmark genetic abnormality in infant B-acute lymphoblastic leukemia (B-ALL) known to arise in utero. The cellular origin of leukemic fusion genes during human development is difficult to ascertain. The bone marrow (BM) microenvironment plays an important role in the pathogenesis of several hematological malignances. BM mesenchymal stem cells (BM-MSC) from 38 children diagnosed with cytogenetically different acute leukemias were screened for leukemic fusion genes. Fusion genes were absent in BM-MSCs of childhood leukemias carrying TEL-AML1, BCR-ABL, AML1-ETO, MLL-AF9, MLL-AF10, MLL-ENL or hyperdiploidy. However, MLL-AF4 was detected and expressed in BM-MSCs from all cases of MLL-AF4(+) B-ALL. Unlike leukemic blasts, MLL-AF4(+) BM-MSCs did not display monoclonal Ig gene rearrangements. Endogenous or ectopic expression of MLL-AF4 exerted no effect on MSC culture homeostasis. These findings suggest that MSCs may be in part tumor-related, highlighting an unrecognized role of the BM milieu on the pathogenesis of MLL-AF4(+) B-ALL. MLL-AF4 itself is not sufficient for MSC transformation and the expression of MLL-AF4 in MSCs is compatible with a mesenchymal phenotype, suggesting a differential impact in the hematopoietic system and mesenchyme. The absence of monoclonal rearrangements in MLL-AF4(+) BM-MSCs precludes the possibility of cellular plasticity or de-differentiation of B-ALL blasts and suggests that MLL-AF4 might arise in a population of prehematopoietic precursors.
Death, Dying, and Denial in the Aged
Authors: LARRY R. KIMSEY, JEAN L. ROBERTS, DANIEL L. LOGAN
Journal: American Journal of Psychiatry (1972)

In response to direct questioning, two dissimilar groups of elderly subjects reported little fear of death or dying. In producing Thematic Apperception Test stories, however, respondents who were well and autonomous used less denial and expressed more affect than did those who were sick and dependent. The authors conclude that aging per se does not result in psychological regression. But denial and constriction of affect are used by the elderly when awareness of their deterioration and dependency compels them to face the dying process.
Birth mode and gut microbiota influence the risk of allergies and asthma – The KOALA birth cohort study
Authors: John Penders, Rianne van Nimwegen, Ellen Stobberingh, Dirkje Postma, Gerard Koppelman, Marjan Kerkhof, Naomi Reijmerink, Edward Dompeling, Piet van den Brandt, Monique Mommers, Carel Thijs
Journal: European Respiratory Journal (2011)

Background:  Gut microbiota (GM) composition and birth mode have been linked to allergies. However, results are inconsistent and the hypothesized intermediate role of GM in the association between birth mode and allergies has not been studied yet.   Aim:  To study the relationship between GM composition, birth mode and allergic manifestations.   Methods:  The KOALA-study includes data on birth mode and on allergic symptoms from birth untill age 6 years. Faecal samples were collected at age 1 month (n=1176) to determine GM composition using qPCR. Blood samples were collected at ages 1, 2, and 6 years to determine specific IgE levels against common allergens.   Results:  Infants born by caesarean (C-)section had lower numbers of bacteroides.  C. difficile  prevalence was highest in infants born by C-section (42%), followed by infants born vaginally in the hospital (26%) and at home (19%). Colonisation by  C.difficile  was associated with an increased risk of eczema, wheeze and sensitisation throughout the first 6 years of life and with asthma (OR: 2.02, 95%CI: 1.15-3.56) at 6 years. Regarding mode and place of delivery, only children with atopic parents had an increased risk of asthma (2.06, 1.27-3.35) and sensitisation to food allergens (1.91, 1.29-2.84) when they had been vaginally delivered in hospital, when compared to vaginal delivery at home. C-section also increased the risk of sensitisation to food allergens (2.16, 1.21-3.86) compared to infants delivered at home.   Conclusion:  Birth mode strongly influences the GM composition and both are associated with allergic manifestations, including asthma. More extensive microbial profiling is needed to examine whether  C.difficile  reflects other shifts in GM.
The Prevalence of Metabolic Syndrome and Determination of the Optimal Waist Circumference Cutoff Points in a Rural South African Community
Authors: Ayesha A. Motala, Tonya Esterhuizen, Fraser J. Pirie, Mahomed A.K. Omar
Journal: Diabetes Care (2011)

To determine the prevalence of metabolic syndrome and to define optimal ethnic-specific waist-circumference cutoff points in a rural South African black community.This was a cross-sectional survey conducted by random-cluster sampling of adults aged >15 years. Participants had demographic, anthropometric, and biochemical measurements taken, including a 75-g oral glucose tolerance test. Metabolic syndrome was defined using the 2009 Joint Interim Statement (JIS) definition.Of 947 subjects (758 women) studied, the age-adjusted prevalence of metabolic syndrome was 22.1%, with a higher prevalence in women (25.0%) than in men (10.5%). Peak prevalence was in the oldest age-group (≥65 years) in women (44.2%) and in the 45- to 54-year age-group in men (25.0%). The optimal waist circumference cutoff point to predict the presence of at least two other components of the metabolic syndrome was 86 cm for men and 92 cm for women. The crude prevalence of metabolic syndrome was higher with the JIS definition (26.5%) than with the International Diabetes Federation (IDF) (23.3%) or the modified Third Report of the National Cholesterol Education Program Adult Treatment Panel (ATPIII) (18.5%) criteria; there was very good agreement with the IDF definition (κ = 0.90 [95% CI 0.87-0.94]) and good concordance with ATPIII criteria (0.77 [0.72-0.82]).There is a high prevalence of metabolic syndrome, especially in women, suggesting that this community, unlike other rural communities in Africa, already has entered the epidemic of metabolic syndrome. Waist circumference cutoff points differ from those currently recommended for Africans.
A phase I and pharmacokinetic study of lapatinib in combination with infusional 5-fluorouracil, leucovorin and irinotecan
Authors: R.S. Midgley, D.J. Kerr, K.T. Flaherty, J.P. Stevenson, S.E. Pratap, K.M. Koch, D.A. Smith, M. Versola, R.A. Fleming, C. Ward, P.J. O'Dwyer, M.R. Middleton
Journal: Annals of Oncology (2007)
Depression and Diabetes Treatment Nonadherence: A Meta-Analysis
Authors: Jeffrey S. Gonzalez, Mark Peyrot, Lauren A. McCarl, Erin Marie Collins, Luis Serpa, Matthew J. Mimiaga, Steven A. Safren
Journal: Diabetes Care (2008)

Depression is common in patients with diabetes and is associated with worse treatment outcomes. Its relationship to treatment adherence, however, has not been systematically reviewed. We used meta-analysis to examine the relationship between depression and treatment nonadherence in patients with type 1 and type 2 diabetes.We searched MEDLINE and PsycINFO databases for all studies published by June 2007 and reviewed references of published articles. Meta-analytic procedures were used to estimate the effect size r in a random effects model. Significance values, weighted effect sizes, 95% CIs, and tests of homogeneity of variance were calculated.Results from 47 independent samples showed that depression was significantly associated with nonadherence to the diabetes treatment regimen (z = 9.97, P < 0.0001). The weighted effect size was near the medium range (r = 0.21, 95% CI 0.17-0.25). Moderator analyses showed that the effect was significantly larger in studies that measured self-care as a continuous versus categorical variable (P = 0.001). Effect sizes were largest for missed medical appointments and composite measures of self-care (r values = 0.31, 0.29). Moderation analyses suggest that effects for most other types of self-care are also near the medium range, especially in studies with stronger methodologies.These findings demonstrate a significant association between depression and treatment nonadherence in patients with diabetes. Studies that used stronger methodologies had larger effects. Treatment nonadherence may represent an important pathway between depression and worse diabetes clinical outcomes.
Long-Acting Insulin Analogs and the Risk of Diabetic Ketoacidosis in Children and Adolescents With Type 1 Diabetes
Authors: Beate Karges, Thomas Kapellen, Andreas Neu, Sabine E. Hofer, Tilman Rohrer, Joachim Rosenbauer, Johannes Wolf, Reinhard W. Holl
Journal: Diabetes Care (2010)

OBJECTIVE To investigate if long-acting insulin analogs decrease the risk of diabetic ketoacidosis (DKA) in young individuals with type 1 diabetes. RESEARCH DESIGN AND METHODS Of 48,110 type 1 diabetic patients prospectively studied between 2001 and 2008, the incidence of DKA requiring hospitalization was analyzed in 10,682 individuals aged ≤20 years with a diabetes duration of ≥2 years. RESULTS The overall rate of DKA was 5.1 (SE ± 0.2)/100 patient-years. Patients using insulin glargine or detemir (n = 5,317) had a higher DKA incidence than individuals using NPH insulin (n = 5,365, 6.6 ± 0.4 vs. 3.6 ± 0.3, P &amp;lt; 0.001). The risk for DKA remained significantly different after adjustment for age at diabetes onset, diabetes duration, A1C, insulin dose, sex, and migration background (P = 0.015, odds ratio 1.357 [1.062–1.734]). CONCLUSIONS Despite their long-acting pharmacokinetics, the use of insulin glargine or detemir is not associated with a lower incidence of DKA compared with NPH insulin.
Prospective, randomised, double blind trial of prophylaxis with single dose of co-amoxiclav before percutaneous endoscopic gastrostomy
Authors: G Preclik, S Grune, H G Leser, J Lebherz, W Heldwein, K Machka, A Holstege, W V Kern
Journal: BMJ (1999)

<h3>Abstract</h3> <b>Objective:</b> To determine the efficacy of antibacterial prophylaxis in preventing infectious complications after percutaneous endoscopic gastrostomy. <b>Design:</b> Prospective, randomised, placebo controlled, double blind, multicentre study. <b>Setting:</b> Departments of internal medicine at six German hospitals. <b>Subjects:</b> Of 106 randomised adult patients with dysphagia, 97 received study medication, and 84 completed the study. The median age of the patients was 65 years. Most had dysphagia due to malignant disease (65%), and many (76%) had serious comorbidity. <b>Interventions:</b> A single intravenous 2.2 g dose of co-amoxiclav or identical appearing saline was given 30 min before percutaneous endoscopic gastrostomy performed by the thread pull method. <b>Main outcome measures:</b> Occurrence of peristomal wound infections and other infections within one week after percutaneous endoscopic gastrostomy. <b>Results:</b> The incidence of peristomal and other infections within one week after percutaneous endoscopic gastrostomy was significantly reduced in the antibiotic group (8/41 (20%) <i>v</i> 28/43 (65%), P&lt;0.001). Similar results were obtained in an intention to treat analysis. Several peristomal wound infections were of minor clinical significance. After wound infections that required no or only local treatment were excluded from the analysis, antibiotic prophylaxis remained highly effective in reducing clinically important wound infections (1/41 (2%) <i>v</i> 11/43 (26%), P&lt;0.01) and non-wound infections (2 (5%) <i>v</i> 9 (21%), P&lt;0.05). <b>Conclusions:</b> Antibiotic prophylaxis with a single dose of co-amoxiclav significantly reduces the risk of infectious complications after percutaneous endoscopic gastrostomy and should be recommended. <h3>Key messages</h3> Percutaneous endoscopic gastrostomy for enteral feeding can be associated with substantial rates of infectious complications, notably peristomal wound infection Small, single centre studies on prevention of wound infection by antibiotic prophylaxis have given conflicting results This prospective, randomised, placebo controlled, double blind, multicentre study showed that a single dose of 2.2 g co-amoxiclav significantly reduced the rate of infection The favourable effect of antibiotic prophylaxis included a reduction in the rate of clinically important peristomal wound infection Intention to treat analysis indicated a significant reduction in the need for therapeutic antibiotics
917 INHIBITION OF MONOCYTE SUBSETS DIFFERENTIATION WAS A NOVEL MARKER OF IMMUNOSUPPRESSION AND AN OUTCOME PREDICTOR FOR HBV ACUTE LIVER FAILURE PATIENTS
Authors: Y. Gong, J. Wang, L. Shen, Z. Zhang, Z. Hui, Y. Zhou, P. Zhang, H. Zeng, H. Li
Journal: Journal of Hepatology (2011)
The analysis of the monoclonal immune response to influenza virus. II. The antigenicity of the viral hemagglutinin.
Authors: W Gerhard
Journal: The Journal of Experimental Medicine (1976)

The antigenicity of the hemagglutinins (HA) of five influenza viruses of the A0 and A1 subtypes has been analyzed by means of monoclonal antibodies of murine origin produced in vitro. Secondary monoclonal anti-HA(PR8) antibodies were able to differentiate 14 antigenic determinants (or groups of determinants) on the HA of five influenza virus strains of the A0 and A1 subtypes. Taking into account that certain pairs of determinants delineated on heterologous HA may reflect the heterogeneity of the humoral immune response to a single homologous determinant, the presence of at least eight determinants (host cell-derived determinants not included) on the homologous HA of PR8 and probably on the HA of influenza viruses in general is postulated. Three types of HA-determinants of A0 and A1 influenza virus strains could be distinguished: strain-specific, partially shared, and determinant(s) common to all five virus strains tested. Roughly 40, 55, and 5%, respectively, of the secondary anti-PR8 antibodies of BALB/c mice were directed against determinants belonging to either of the three types.
Diabetes Antibody Standardization Program: Table 1
Authors: Michael Schlosser, Patricia W. Mueller, Peter Achenbach, Vito Lampasona, Polly J. Bingley
Journal: Diabetes Care (2011)

Autoantibodies to IA-2β (IA-2βA) are important risk markers of type 1 diabetes. We report the first Diabetes Antibody Standardization Program (DASP) evaluation of IA-2βA assays.
Learning from cricket other great clinical stories
Authors: Gavan L White
Journal: British Journal of Sports Medicine (2013)

Australian cricket has a long and glorious history in the sport, but on-field success is currently at an all-time low. Despite that current embarrassment, this BJSM member society, Sports Doctors Australia (SDrA), highlights four cricket papers. Injury surveillance is so important that on-field failure is overlooked for the greater good of clinical education!

If you are working with any team where injury surveillance may be useful, please read Dr John Orchard's editorial which details three key elements to take into account of in injury surveillance see page 605 . Also in this issue, former England cricket physiotherapist, Dr Craig Ranson, shares the first multicountry injury data from the ICC Cricket World Cup in 2011 see page 637 . This paper gives a great review of the injury rate at elite-level cricket. The paper by Prof David Mann discusses the risk …
The LIM-Homeodomain Protein Islet Dictates Motor Neuron Electrical Properties by Regulating K+ Channel Expression
Authors: Verena Wolfram, Tony D. Southall, Andrea H. Brand, Richard A. Baines
Journal: Neuron (2012)

<h2>Summary</h2> Neuron electrical properties are critical to function and generally subtype specific, as are patterns of axonal and dendritic projections. Specification of motoneuron morphology and axon pathfinding has been studied extensively, implicating the combinatorial action of Lim-homeodomain transcription factors. However, the specification of electrical properties is not understood. Here, we address the key issues of whether the same transcription factors that specify morphology also determine subtype specific electrical properties. We show that <i>Drosophila</i> motoneuron subtypes express different K<sup>+</sup> currents and that these are regulated by the conserved Lim-homeodomain transcription factor Islet. Specifically, Islet is sufficient to repress a Shaker-mediated A-type K<sup>+</sup> current, most likely due to a direct transcriptional effect. A reduction in Shaker increases the frequency of action potential firing. Our results demonstrate the deterministic role of Islet on the excitability patterns characteristic of motoneuron subtypes.
Structural Heterogeneity in the Ventricular Wall Plays a Significant Role in the Initiation of Stretch-Induced Arrhythmias in Perfused Rabbit Right Ventricular Tissues and Whole Heart Preparations
Authors: Kinya Seo, Masashi Inagaki, Satoshi Nishimura, Ichiro Hidaka, Masaru Sugimachi, Toshiaki Hisada, Seiryo Sugiura
Journal: Circulation Research (2009)

Mechanical stress is known to alter the electrophysiological properties of the myocardium and may trigger fatal arrhythmias when an abnormal load is applied to the heart.We tested the hypothesis that the structural heterogeneity of the ventricular wall modulates globally applied stretches to create heterogeneous strain distributions that lead to the initiation of arrhythmias.We applied global stretches to arterially perfused rabbit right ventricular tissue preparations. The distribution of strain (determined by marker tracking) and the transmembrane potential (measured by optical mapping) were simultaneously recorded while accounting for motion artifacts. The 3D structure of the preparations was also examined using a laser displacement meter. To examine whether such observations can be translated to the physiological condition, we performed similar measurements in whole heart preparations while applying volume pulses to the right ventricle. At the tissue level, larger stretches (> or = 20%) caused synchronous excitation of the entire preparation, whereas medium stretches (10% and 15%) induced focal excitation. We found a significant correlation between the local strain and the local thickness, and the probability for focal excitation was highest for medium stretches. In the whole heart preparations, we observed that such focal excitations developed into reentrant arrhythmias.Global stretches of intermediate strength, rather than intense stretches, created heterogeneous strain (excitation) distributions in the ventricular wall, which can trigger fatal arrhythmias.
Activation of the respiratory burst enzyme in human polymorphonuclear leukocytes by chemoattractants and other soluble stimuli. Evidence that the same oxidase is activated by different transductional mechanisms.
Authors: L C McPhail, R Snyderman
Journal: Journal of Clinical Investigation (1983)

Chemoattractant-receptor coupling triggers several biologic responses in phagocytic cells including activation of the respiratory burst. Prior evidence in intact cells implied that stimulation of the respiratory burst by chemoattractants was by a mechanism different from other soluble agents suggesting the possibility that different oxidative enzymes were responsible. We now show that the chemoattractants N-formyl-methionyl-leucyl-phenylalanine and a split fragment of the fifth component of complement (C5a) stimulate an NADPH oxidase activity, measured in the 50,000-g particulate fraction from human polymorphonuclear leukocytes (PMN). Levels of oxidase activity stimulated by the chemoattractants were both time and dose dependent and required the presence of cytochalasin B during stimulation. In contrast, activation by two nonchemotactic stimuli, the ionophore A23187 and phorbol myristate acetate (PMA), did not require cytochalasin B. Temporal patterns of oxidase activation suggested that different stimuli follow different transductional pathways. Chemoattractant-mediated activation was immediate (no lag); peaked by 45 s and declined rapidly to approximately 50% of maximal by 2 min. In contrast, activation by A23187 or PMA had a 15-30-s lag and increased more slowly. Stimulation by A23187 peaked at 5 min, then declined. Stimulation by PMA plateaued at 20 min and did not decline by 90 min. Comparison of Km values for NADPH and NADH obtained by Lineweaver-Burk analysis of the oxidase activity stimulated by N-formyl-methionyl-leucyl-phenylalanine, A23187, and PMA suggested that the same enzyme was activated by all stimuli. Thus, chemoattractants and other soluble stimuli appear to activate the same respiratory burst enzyme in PMN but they utilize different transductional mechanisms and are regulated differently.