tbuckley/cabot-search huggingface dataset:
GPR56 Regulates VEGF Production and Angiogenesis during Melanoma Progression
Authors: Liquan Yang, Guangchun Chen, Sonali Mohanty, Glynis Scott, Fabeha Fazal, Arshad Rahman, Shahinoor Begum, Richard O. Hynes, Lei Xu
Journal: Cancer Research (2011)

Angiogenesis is a critical step during cancer progression. The VEGF is a major stimulator for angiogenesis and is predominantly contributed by cancer cells in tumors. Inhibition of the VEGF signaling pathway has shown promising therapeutic benefits for cancer patients, but adaptive tumor responses are often observed, indicating the need for further understanding of VEGF regulation. We report that a novel G protein-coupled receptor, GPR56, inhibits VEGF production from the melanoma cell lines and impedes melanoma angiogenesis and growth, through the serine threonine proline-rich segment in its N-terminus and a signaling pathway involving protein kinase Cα. We also present evidence that the two fragments of GPR56, which are generated by autocatalyzed cleavage, played distinct roles in regulating VEGF production and melanoma progression. Finally, consistent with its suppressive roles in melanoma progression, the expression levels of GPR56 are inversely correlated with the malignancy of melanomas in human subjects. We propose that components of the GPR56-mediated signaling pathway may serve as new targets for antiangiogenic treatment of melanoma.
Long-Term Follow-Up of Biopsy-Proven Viral Myocarditis
Authors: Stefan Grün, Julia Schumm, Simon Greulich, Anja Wagner, Steffen Schneider, Oliver Bruder, Eva-Maria Kispert, Stephan Hill, Peter Ong, Karin Klingel, Reinhardt Kandolf, Udo Sechtem, Heiko Mahrholdt
Journal: Journal of the American College of Cardiology (2012)
New Zealand adult respiratory nursing knowledge and skills framework: A platform for competence development
Authors: Victoria Perry
Journal: European Respiratory Journal (2012)

Respiratory nurses in New Zealand (NZ) are required by the Nursing Council of NZ and national legislation to provide evidence of competence however, there has been an absence of an agreed articulation of the respiratory specific knowledge and skills required to demonstrate this. A national working group of respiratory nurses therefore undertook to develop a national respiratory knowledge and skills framework that offers a mechanism for the development of a range of transferable clinical skills, seeks to minimise risk to patients, nurses and employers, provides a reference point for curricula and a mechanism for nurses to measure effectiveness of their practice. This presentation will describe the aims of the framework, process of development, scope for application, implementation to date, and initial evaluation.
Cooking birch pollen–related food: Divergent consequences for IgE- and T cell–mediated reactivity in vitro and in vivo
Authors: Barbara Bohle, Bettina Zwölfer, Annice Heratizadeh, Beatrice Jahn-Schmid, Yuliya Dall Antonia, Mareike Alter, Walter Keller, Laurian Zuidmeer, Ronald van Ree, Thomas Werfel, Christof Ebner
Journal: Journal of Allergy and Clinical Immunology (2006)
Bβ<sub>15–42</sub> Protects against Acid-induced Acute Lung Injury and Secondary <i>Pseudomonas</i> Pneumonia <i>In Vivo</i>
Authors: Ulrich Matt, Joanna Maria Warszawska, Michael Bauer, Wolfgang Dietl, Ildiko Mesteri, Bianca Doninger, Isabella Haslinger, Gernot Schabbauer, Thomas Perkmann, Christoph J. Binder, Sonja Reingruber, Peter Petzelbauer, Sylvia Knapp
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Rationale: Acute lung injury (ALI) is a serious condition in critically ill patients that predisposes to secondary bacterial pneumonia. Vascular leak is a hallmark in the pathogenesis of ALI. The fibrin-derived peptide Bβ15–42 was shown to preserve endothelial barriers, thereby reducing vascular leak. The potential therapeutic role of Bβ15–42 in ALI has not been addressed so far.Objectives: To investigate the therapeutic potential of Bβ15–42 in ALI and secondary pneumonia induced by Pseudomonas aeruginosa.Methods: The effect of the fibrin-derived peptide Bβ15–42 was studied in models of ALI, induced either by pulmonary administration of LPS or hydrochloric acid. Lung inflammation was analyzed by quantifying cell influx, cytokine levels, and oxidized lipids. Vascular leak was determined by Evans Blue extravasations and alveolar protein content. In subsequent two-hit studies, mice were infected with P. aeruginosa 24 hours after induction of aspiration pneumonitis and effects of Bβ15–42 on inflammation, bacterial clearance, and survival were evaluated.Measurements and Main Results: After LPS or acid inhalation, proinflammatory cytokine levels, neutrophil influx, and vascular leak were found diminished in mice treated with Bβ15–42. Acid aspiration impaired macrophage functions and rendered mice more susceptible to subsequent P. aeruginosa infection, whereas mice that received Bβ15–42 during acid aspiration and were subsequently challenged with bacteria displayed reduced inflammation, enhanced bacterial clearance, and ultimately improved survival.Conclusions: The fibrin-derived peptide Bβ15–42 exerted protective effects during ALI, resulting in diminished lung injury and preserved antibacterial properties of macrophages, which improved outcome during subsequent P. aeruginosa pneumonia.
Genetic and Clinical Predictors for Breast Cancer Risk Assessment and Stratification Among Chinese Women
Authors: Wei Zheng, Wanqing Wen, Yu-Tang Gao, Yu Shyr, Ying Zheng, Jirong Long, Guoliang Li, Chun Li, Kai Gu, Qiuyin Cai, Xiao-Ou Shu, Wei Lu
Journal: JNCI Journal of the National Cancer Institute (2010)

Most of the genetic variants identified from genome-wide association studies of breast cancer have not been validated in Asian women. No risk assessment model that incorporates both genetic and clinical predictors is currently available to predict breast cancer risk in this population. We analyzed 12 single-nucleotide polymorphisms (SNPs) identified in recent genome-wide association studies mostly of women of European ancestry as being associated with the risk of breast cancer in 3039 case patients and 3082 control subjects who participated in the Shanghai Breast Cancer Study. All participants were interviewed in person to obtain information regarding known and suspected risk factors for breast cancer. The c statistic, a measure of discrimination ability with a value ranging from 0.5 (random classification) to 1.0 (perfect classification), was estimated to evaluate the contribution of genetic and established clinical predictors of breast cancer to a newly established risk assessment model for Chinese women. Clinical predictors included in the model were age at menarche, age at first live birth, waist-to-hip ratio, family history of breast cancer, and a previous diagnosis of benign breast disease. The utility of the models in risk stratification was evaluated by estimating the proportion of breast cancer patients in the general population that could be accounted for above a given risk threshold as predicted by the models. All statistical tests were two-sided. Eight SNPs (rs2046210, rs1219648, rs3817198, rs8051542, rs3803662, rs889312, rs10941679, and rs13281615), each of which reflected a genetically independent locus, were found to be associated with the risk of breast cancer. A dose–response association was observed between the risk of breast cancer and the genetic risk score, which is an aggregate measure of the effect of these eight SNPs (odds ratio for women in the highest quintile of genetic risk score vs those in the lowest = 1.85, 95% confidence interval = 1.58 to 2.18, Ptrend = 2.5 × 10−15). The genetic risk score, the waist-to-hip ratio, and a previous diagnosis of benign breast disease were the top three predictors of the risk of breast cancer, each contributing statistically significantly (P < .001) to the full risk assessment model. The model, with a c statistic of 0.6295 after adjustment for overfitting, showed promise for stratifying women into different risk groups; women in the top 30% risk group accounted for nearly 50% of the breast cancers diagnosed in the general population. A risk assessment model that includes both genetic markers and clinical predictors may be useful to classify Asian women into relevant risk groups for cost-efficient screening and other prevention programs.
Interpretations. Cardiovascular disease and combined oral contraceptives: reviewing the evidence and balancing the risks
Authors: T. Farley
Journal: Human Reproduction Update (1999)

Cardiovascular risks have been a concern since combined oral contraceptives (OCs) were first introduced. In the past four years new, mostly reassuring information on the safety of modern, low oestrogen dose OCs has become available. However, in 1995 the new information showed higher venous thromboembolism (VTE) risk for OCs containing desogestrel and gestodene compared with levonorgestrel-or norethindrone-containing OCs. The controversial responses by national authorities, their scientific and public health merits were hotly debated and many considered the differences in risk small and resulted from bias and/or confounding. We discuss these arguments and conclude they lack empirical support or cannot account for the 2-fold increased risk. The risk of ischaemic stroke and myocardial infarction (MI) associated with low oestrogen dose OCs are very small in women without cardiovascular risk factors, while increased risk of haemorrhagic stroke is confined to women >35 years of age. Applying the most recent risks to models of OC-attributable events and deaths, OC-attributable mortality in women <35 years is estimated to be <3 per million users annually, rising to about 10 per million users annually among smokers. In the context of external cause mortality (about 90 per million women of reproductive age annually in the UK) such risks appear small. Over the age of 35 years, OC-attributable mortality is a more important concern, particularly among smokers. In the absence of any appreciable OC-attributable mortality in young healthy women, the additional VTE risk for third compared with second generation OCs should be considered when women choose which OC to use.
Activation of p38 Mitogen-Activated Protein Kinase Drives Dendritic Cells to Become Tolerogenic in <i>Ret</i> Transgenic Mice Spontaneously Developing Melanoma
Authors: Fang Zhao, Christine Falk, Wolfram Osen, Masashi Kato, Dirk Schadendorf, Viktor Umansky
Journal: Clinical Cancer Research (2009)

The purpose of the study was to investigate signaling molecules involved in the acquisition of tolerogenic properties by dendritic cells (DC) in ret transgenic mice with spontaneous melanoma progression and to target these molecules to overcome the barrier for effective melanoma immunotherapy.DC functions and expression patterns of p38 mitogen-activated protein kinase (MAPK) in DCs were evaluated in a ret transgenic murine cutaneous melanoma model, which shows high similarity to human cutaneous melanoma with respect to clinical development. In contrast to transplantation melanoma models (like B16), this model allows the study of melanoma progression under conditions of natural interactions between tumor and host cells over time.We showed a strong tumor infiltration with immature DCs and a reduction in the number of mature DCs in lymphoid organs during melanoma progression. DCs from melanoma-bearing mice secreted significantly more interleukin 10 and less interleukin 12p70, and showed a decreased capacity to activate T cells compared with DCs from tumor-free animals. Observed DC dysfunction was linked to considerable activation of p38 MAPK. Inhibition of its activity in spleen DCs from tumor-bearing mice led to normalization of their cytokine secretion pattern and T-cell stimulation capacity.Our data show a critical role of constitutively activated p38 MAPK in the acquirement of tolerogenic pattern by DCs during melanoma progression that contributes to the suppression of antitumor T-cell immune responses. We suggest that new strategies of melanoma immunotherapy can include inhibitors of p38 MAPK activity in DCs.
CARNITINE METABOLISM AND ITS REGULATION IN MICROORGANISMS AND MAMMALS
Authors: Charles J. Rebouche, Hermann Seim
Journal: Annual Review of Nutrition (1998)

▪ Abstract In procaryotes, l-carnitine may be used as both a carbon and nitrogen source for aerobic growth, or the carbon chain may be used selectively following cleavage of trimethylamine. Under anaerobic conditions and in the absence of preferred substrates, some bacteria use carnitine, via crotonobetaine, as an electron acceptor. Formation of trimethylamine and γ-butyrobetaine (from reduction of crotonobetaine) from l-carnitine by enteric bacteria has been demonstrated in rats and humans. Carnitine is not degraded by enzymes of eukaryotic origin. In higher organisms, carnitine has specific functions in intermediary metabolism. Concentrations of carnitine and its esters in cells of eukaryotes are rigorously maintained to provide optimal function. Carnitine homeostasis in mammals is preserved by a modest rate of endogenous synthesis, absorption from dietary sources, efficient reabsorption, and mechanisms present in most tissues that establish and maintain substantial concentration gradients between intracellular and extracellular carnitine pools.
Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria
Authors: Bruno Dubois, Howard H Feldman, Claudia Jacova, Harald Hampel, José Luis Molinuevo, Kaj Blennow, Steven T DeKosky, Serge Gauthier, Dennis Selkoe, Randall Bateman, Stefano Cappa, Sebastian Crutch, Sebastiaan Engelborghs, Giovanni B Frisoni, Nick C Fox, Douglas Galasko, Marie-Odile Habert, Gregory A Jicha, Agneta Nordberg, Florence Pasquier, Gil Rabinovici, Philippe Robert, Christopher Rowe, Stephen Salloway, Marie Sarazin, Stéphane Epelbaum, Leonardo C de Souza, Bruno Vellas, Pieter J Visser, Lon Schneider, Yaakov Stern, Philip Scheltens, Jeffrey L Cummings
Journal: The Lancet Neurology (2014)
LRRK2 knockout mice have an intact dopaminergic system but display alterations in exploratory and motor co-ordination behaviors
Authors: Kelly M Hinkle, Mei Yue, Bahareh Behrouz, Justus C Dächsel, Sarah J Lincoln, Erin E Bowles, Joel E Beevers, Brittany Dugger, Beate Winner, Iryna Prots, Caroline B Kent, Kenya Nishioka, Wen-Lang Lin, Dennis W Dickson, Christopher J Janus, Matthew J Farrer, Heather L Melrose
Journal: Molecular Neurodegeneration (2012)

Abstract Mutations in the LRRK2 gene are the most common cause of genetic Parkinson’s disease. Although the mechanisms behind the pathogenic effects of LRRK2 mutations are still not clear, data emerging from in vitro and in vivo models suggests roles in regulating neuronal polarity, neurotransmission, membrane and cytoskeletal dynamics and protein degradation. We created mice lacking exon 41 that encodes the activation hinge of the kinase domain of LRRK2. We have performed a comprehensive analysis of these mice up to 20 months of age, including evaluation of dopamine storage, release, uptake and synthesis, behavioral testing, dendritic spine and proliferation/neurogenesis analysis. Our results show that the dopaminergic system was not functionally comprised in LRRK2 knockout mice. However, LRRK2 knockout mice displayed abnormal exploratory activity in the open-field test. Moreover, LRRK2 knockout mice stayed longer than their wild type littermates on the accelerated rod during rotarod testing. Finally, we confirm that loss of LRRK2 caused degeneration in the kidney, accompanied by a progressive enhancement of autophagic activity and accumulation of autofluorescent material, but without evidence of biphasic changes.
Physical inactivity – getting Scotland on the move
Authors: Andrew Murray
Journal: British Journal of Sports Medicine (2012)

It is believed that Scotland has been inhabited for over 12 000 years. These early settlers were hunter-gatherers, sustaining regular physical activity in their search for food. Scots take pride in their proud history of innovation and invention. To medicine, we have contributed penicillin, insulin and the ECG. Scots also contributed the three best friends of the couch potato; the telephone, the refrigerator and the television, unwittingly sowing the seeds for one of the biggest public health challenges of the 21st century: physical inactivity.

Steven Blair's research has shown that low cardiorespiratory fitness is responsible for the largest attributable fraction of all-cause mortality.1 Karim Khan framed these data to emphasise that deaths attributable to low fitness exceeded those due to obesity, diabetes and smoking (‘smokadiabesity’) combined.2 The WHO looked at global health risks and found that over 3 million people each year die due to physical inactivity making physical inactivity the fourth leading cause of preventable death.3 It is accepted that increasing physical activity levels is beneficial both to preventing and managing cardiovascular conditions, diabetes, cancer and depression as well as promoting a better quality of life.

Is this global problem relevant to Scotland, or do we have bigger fish to fry in our infamous deep fat fryers? WHO data from 2008 show that the UK is one of only seven countries worldwide, where fewer than 40% of adults reach minimum recommendations for physical activity.4 The 2010 Scottish Health Survey found that 39% of adults achieved a minimum of 30 min activity five times per week, while 72% of children reached 60 min of activity daily.5 These figures were based on self-reported activity levels. Scottish …
Stability of Body Weight in Type 2 Diabetes
Authors: Zoobia W. Chaudhry, Mary C. Gannon, Frank Q. Nuttall
Journal: Diabetes Care (2006)

OBJECTIVE—There is a concern that an “epidemic of obesity” is occurring in Western societies. One consequence of obesity is that type 2 diabetes may develop. Presumably, a great increase in body weight would continue in people with diabetes and may be accelerated due to pharmacological treatment. In this retrospective study, we tested the hypothesis that the weight gain in a diabetic population is greater than that in the general population. RESEARCH DESIGN AND METHODS—Data were obtained from the records of 205 adult men who have attended a diabetes clinic for ≥5 years. Their weight and glycohemoglobin at the last visit were compared with the initial visit data. The subjects were categorized according to treatment modalities. The mean follow-up was 9.4 years (range 5–23). RESULTS—For the group as a whole, the mean increase in body weight was 0.23 ± 0.2 kg/year. BMI or initial age had little effect on the rate of weight gain. Treatment regimen used did have an effect on weight change. In subjects treated with insulin, with or without oral agents, body weight increased at a rate of 0.44 ± 0.1 kg/year. In subjects treated with metformin or metformin and a sulfonylurea, there was a mean loss in weight, i.e., −0.24 ± 0.09 kg/year, and with sulfonylureas alone weight increased by 0.42 ± 0.2 kg/year. CONCLUSIONS—The men treated with insulin alone or insulin combined with oral agents gained weight at a rate comparable with that reported for the general population, i.e., the weight gain was not extraordinary. Metformin treatment resulted in a modest loss of weight.
Association Between Bipolar Disorder and Monoamine Oxidase A Gene Polymorphisms: Results of a Multicenter Study
Authors: Martin Preisig, Frank Bellivier, Brenda T. Fenton, Patrick Baud, Alexandre Berney, Philippe Courtet, Patrick Hardy, Jean Golaz, Marion Leboyer, Jacques Mallet, Marie-Louise Matthey, Dominique Mouthon, Elisabeth Neidhart, Marika Nosten-Bertrand, Emmanuelle Stadelmann-Dubuis, Jose Guimon, Franæ®©s Ferrero, Catherine Buresi, Alain Malafosse
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: Although genetic factors have been implicated in the etiology of bipolar disorder, no specific gene has been conclusively identified. Given the link between abnormalities in serotonergic neurotransmission and bipolar disorder, a candidate gene association approach was applied to study the involvement of the monoamine oxidase A (MAOA) gene, which codes for a catabolic enzyme of serotonin, in the susceptibility to bipolar disorder.METHOD: In France and Switzerland, 272 patients with bipolar disorder and 122 healthy subjects were typed for three polymorphic markers of the MAOA gene: the MAOA-CA repeat, the MAOA restriction fragment length polymorphism (RFLP), and a repeat directly adjacent to the variable number of tandem repeats (VNTR) locus.RESULTS: A significant difference in the distribution of the alleles for the MAOA-CA repeat was observed between the female bipolar patients and comparison group.CONCLUSIONS: The results obtained in the French and Swiss population confirm findings from two studies conducted in the United Kingdom.
Regulation of low-density lipoprotein receptors: implications for pathogenesis and therapy of hypercholesterolemia and atherosclerosis.
Authors: J L Goldstein, M S Brown
Journal: Circulation (1987)

Low-density lipoprotein (LDL) is the most abundant and the most atherogenic class of cholesterol-carrying lipoproteins in human plasma. The level of plasma LDL is regulated by the LDL receptor, a cell surface glycoprotein that removes LDL from plasma by receptor-mediated endocytosis. Defects in the gene encoding the LDL receptor, which occur in patients with familial hypercholesterolemia, elevate the plasma LDL level and produce premature coronary atherosclerosis. The physiologically important LDL receptors are located primarily in the liver, where their number is regulated by the cholesterol content of the hepatocyte. When the cholesterol content of hepatocytes is raised by ingestion of diets high in saturated fat and cholesterol, LDL receptors fall and plasma LDL levels rise. Conversely, maneuvers that lower the cholesterol content of hepatocytes, such as ingestion of drugs that inhibit cholesterol synthesis (mevinolin or compactin) or prevent the reutilization of bile acids (cholestyramine or colestipol), stimulate LDL receptor production and lower plasma LDL levels. The normal process of receptor regulation can therefore be exploited in powerful and novel ways so as to reverse hypercholesterolemia and prevent atherosclerosis.
A comparison of the in vivo kinetics of Plasmodium falciparum ring–infected erythrocyte surface antigen–positive and –negative erythrocytes
Authors: Paul N. Newton, Kesinee Chotivanich, Wirongrong Chierakul, Ronatrai Ruangveerayuth, Pramote Teerapong, Kamolrat Silamut, Sornchai Looareesuwan, Nicholas J. White
Journal: Blood (2001)