tbuckley/cabot-search huggingface dataset:
Adenosine Generation and Signaling during Acute Kidney Injury
Authors: Jessica D. Bauerle, Almut Grenz, Jae-Hwan Kim, H. Thomas Lee, Holger K. Eltzschig
Journal: Journal of the American Society of Nephrology (2011)

Acute kidney injury (AKI) is among the leading causes of morbidity and mortality in hospitalized patients. Particularly in the perioperative period, the most common cause of AKI is renal ischemia. At present, therapeutic modalities to prevent or treat AKI are extremely limited and the search for novel therapeutic interventions for ischemic AKI is an area of intense investigation. Recent studies implicate the endogenous signaling molecule, adenosine, in kidney protection from ischemia. As such, enzymatic production of adenosine from its precursor molecules ATP and AMP, and signaling events through adenosine receptors, play a critical role in attenuating renal inflammation and preserving kidney function during episodes of renal ischemia. Utilizing genetic mouse models with defects in adenosine generation or signaling provide strong evidence for the key role of extracellular adenosine in adapting renal tissues to limited oxygen availability and attenuating hypoxia-driven inflammation of the kidneys. Moreover, experimental therapeutics targeting individual adenosine receptors demonstrate strong prophylactic or therapeutic effects during murine AKI. If these experimental strategies can be translated into a clinical setting, adenosine receptor therapeutics may become an integral part in the prevention or treatment of AKI from renal ischemia.
Cellular Mechanisms of Altered Contractility in the Hypertrophied Heart
Authors: Stephen R. Shorofsky, Rajesh Aggarwal, Mary Corretti, Jeanne M. Baffa, Judy M. Strum, Badr A. Al-Seikhan, Yvonne M. Kobayashi, Larry R. Jones, W. Gil Wier, C. William Balke
Journal: Circulation Research (1999)

Abstract —To investigate the cellular mechanisms for altered Ca 2+ homeostasis and contractility in cardiac hypertrophy, we measured whole-cell L-type Ca 2+ currents ( I Ca,L ), whole-cell Ca 2+ transients ([Ca 2+ ] i ), and Ca 2+ sparks in ventricular cells from 6-month-old spontaneously hypertensive rats (SHRs) and from age- and sex-matched Wistar-Kyoto and Sprague-Dawley control rats. By echocardiography, SHR hearts had cardiac hypertrophy and enhanced contractility (increased fractional shortening) and no signs of heart failure. SHR cells had a voltage-dependent increase in peak [Ca 2+ ] i amplitude (at 0 mV, 1330±62 nmol/L [SHRs] versus 836±48 nmol/L [controls], P &lt;0.05) that was not associated with changes in I Ca,L density or kinetics, resting [Ca 2+ ] i , or Ca 2+ content of the sarcoplasmic reticulum (SR). SHR cells had increased time of relaxation. Ca 2+ sparks from SHR cells had larger average amplitudes (173±192 nmol/L [SHRs] versus 109±64 nmol/L [control]; P &lt;0.05), which was due to redistribution of Ca 2+ sparks to a larger amplitude population. This change in Ca 2+ spark amplitude distribution was not associated with any change in the density of ryanodine receptors, calsequestrin, junctin, triadin 1, Ca 2+ -ATPase, or phospholamban. Therefore, SHRs with cardiac hypertrophy have increased contractility, [Ca 2+ ] i amplitude, time to relaxation, and average Ca 2+ spark amplitude (“big sparks”). Importantly, big sparks occurred without alteration in the trigger for SR Ca 2+ release ( I Ca,L ), SR Ca 2+ content, or the expression of several SR Ca 2+ -cycling proteins. Thus, cardiac hypertrophy in SHRs is linked with an alteration in the coupling of Ca 2+ entry through L-type Ca 2+ channels and the release of Ca 2+ from the SR, leading to big sparks and enhanced contractility. Alterations in the microdomain between L-type Ca 2+ channels and SR Ca 2+ release channels may underlie the changes in Ca 2+ homeostasis observed in cardiac hypertrophy. Modulation of SR Ca 2+ release may provide a new therapeutic strategy for cardiac hypertrophy and for its progression to heart failure and sudden death.
The female athlete
Authors: C Doyle
Journal: British Journal of Sports Medicine (2004)

Mary Lloyd Ireland and Aurelia Nattiv. London: Harcourt Publishers Limited, 2002, £48.00, pp 803, hardcover. ISBN 0721680291

This book is a very informative source, both from a practical point of view with its sports medicine content, and also from an educational angle with information on the psychosocial aspects of the female athlete, which are very relevant and are not often included in general sports medicine texts.

The book presents sex differences in injury occurrence and gives effective advice on prevention and injury management. It is targeted mainly at sports medicine professionals, but also significant sections are relevant to coaches, trainers, administrators, and, in some part, the athletes themselves and their families.

The organisation is logical, with the content divided into sections including firstly historical, psychosocial, and performance issues followed by chapters on female specific and general medical conditions, and finally sections dealing with orthopaedic, rehabilitation, and …
Anal ulceration in a young man
Authors: J D Zeitoun, R Kaci, T Homsi, O Hermine, V de Parades
Journal: Gut (2009)

A 22-year-old man presented at our outpatient clinic with longstanding intermittent rectal bleeding; he was known to have chronic granulomatous disease (CGD) revealed by a hip osteitis in childhood. The diagnosis of CGD had been established …
Abnormal liver function
Authors: Y.-Y. Chen, H.-H. Yen, C.-W. Yang, C.-D. Yao, M.-S. Soon
Journal: Gut (2007)

A 58-year-old man was found lying beside his motorcycle in February 2006. A brain CT scan was performed in the hospital because of unsteady gait and one-sided weakness. Left occipital intracranial haemorrhage and cerebellar infarction were diagnosed, …
Inhibition of vascular smooth muscle cell adhesion and migration by c7E3 Fab (abciximab): a possible mechanism for influencing restenosis
Authors: J Baron
Journal: Cardiovascular Research (2000)

Objectives: Brief intravenous administration of chimeric antibody c7E3 Fab during coronary angioplasty has been shown in some studies to provide long term protection against coronary events. Smooth muscle cell (SMC) adhesion and migration are key initial steps in the development of restenosis. The purpose of this study was to investigate the effect of c7E3 Fab on adhesion and migration of SMC to the extracellular matrix (ECM) proteins osteopontin (Opn) and vitronectin (Vn). Methods: Adhesion of human vascular SMCs to ECM proteins was quantified using a CyQUANT assay kit. Migration of SMCs to Vn, Opn and PDGF was studied using a modified Boyden's chamber migration assay. Integrin expression was determined by immunoprecipitation. Results: c7E3 Fab reduced SMC adhesion on Vn and Opn to 69.2±3.3% (P<0.001) and 52.5±4.8% (P<0.001) respectively, compared to adhesion without antibody present. This reduction was the same as that for anti-αvβ3 integrin antibody LM609 (P = 0.5). The combination of anti-αvβ5 integrin antibody and c7E3 Fab had a greater effect than either antibody alone (P<0.001). c7E3 Fab reduced SMC migration to Vn and Opn to 51.6±8.9% (P<0.001) and 20.3±6.1% (P<0.001) respectively, compared to migration in the absence of antibodies. Again, similar results were seen with LM609. PDGF-induced SMC migration was also inhibited by c7E3 Fab (P = 0.004) and LM609 (P = 0.001), but to much less an extent. The migration SMCs from a culture found not to express the αvβ3 integrin was unaffected by these antibodies, strengthening the argument that c7E3 Fab inhibits SMC function via this integrin. Conclusions: c7E3 Fab inhibits the adhesion and migration of SMCs via the αvβ3 integrin. The inhibition, however, is partial, and varied depending on type of ECM protein and αvβ3 integrin expression. Some of the clinical benefits of c7E3 Fab may be due to its effect on SMCs.
Spinophilin Loss Correlates with Poor Patient Prognosis in Advanced Stages of Colon Carcinoma
Authors: Purificacion Estevez-Garcia, Iker Lopez-Calderero, Sonia Molina-Pinelo, Sandra Muñoz-Galvan, Ana Salinas, Lourdes Gomez-Izquierdo, Antonio Lucena-Cacace, Blanca Felipe-Abrio, Luis Paz-Ares, Rocio Garcia-Carbonero, Amancio Carnero
Journal: Clinical Cancer Research (2013)

The genomic region 17q21 is frequently associated with microsatellite instability and LOH in cancer, including gastric and colorectal carcinomas. This region contains several putative tumor suppressor genes, including Brca1, NM23, prohibitin, and spinophilin (Spn, PPP1R9B, neurabin II). The scaffold protein Spn is one of the regulatory subunits of phosphatase-1 (PP1) that targets PP1 to distinct subcellular locations and couples PP1 to its target. Thus, Spn may alter cell-cycle progression via the regulation of the phosphorylation status of the retinoblastoma protein, a direct target of PP1. Therefore, we analyzed whether Spn levels were reduced in colorectal carcinomas and whether Spn levels correlated with prognosis or response to therapy.By means of immunohistochemistry or quantitative PCR, we studied the levels of Spn in stages II, III, and IV colorectal carcinoma tumors and correlated to other clinicopathologic features as well as prognosis or response to therapy.Spn was lost in a percentage of human gastric, small intestine, and colorectal carcinomas. In patients with colorectal carcinoma, tumoral Spn downregulation correlated with a more aggressive histologic phenotype (poorer tumor differentiation and higher proliferative Ki67 index). Consistent with this observation, lower Spn protein expression levels were associated with faster relapse and poorer survival in patients with stage III colorectal carcinoma, particularly among those receiving adjuvant fluoropyrimidine therapy. We validated this result in an independent cohort of patients with metastatic colorectal carcinoma treated with standard chemotherapy. Although patients that achieved an objective tumor response exhibited Spn levels similar to nontumoral tissue, nonresponding patients showed a significant reduction in Spn mRNA levels.Our data suggest that Spn downregulation contributes to a more aggressive biologic behavior, induces chemoresistance, and is associated with a poorer survival in patients with advanced stages of colorectal carcinoma.
Lymphoid and non-lymphoid cells in the epithelium and lamina propria of intestinal mucosa of pigs.
Authors: H J Rothkotter, T Kirchhoff, R Pabst
Journal: Gut (1994)

The jejunum and ileum of 5 day old and adult normal pigs and of 45 day old germ free pigs were used to study the lymphocyte pools in the epithelium and lamina propria by sequential treatments with EDTA, four hours, and 12 hours of collagenase treatment. In adult animals the incubation of the jejunal wall with EDTA resulted in mean (SD) 26.8 (10.9) x 10(6) intraepithelial lymphocytes per g of tissue. The ileal wall gave lower cell yields. After complete digestion of the lamina propria by collagenase a further yield of 35.2 (10.2) x 10(6)/g lymphocytes was achieved. The separation of the gut wall from 5 day old pigs resulted in a 10-fold lower total lymphocyte yield, and the tissue was totally digested after four hours of collagenase treatment. Many eosinophils and mast cells were found in the suspensions from adult animal tissues after the collagenase treatment; 4.7 x 10(6)/g and 4.8 x 10(6)/g, respectively. The suspensions after 12 hour collagenase incubation contained up to 30% plasma cells. Almost all cells isolated by EDTA incubation were CD8+ T cells. After collagenase incubation CD4+ and CD8+ T lymphocytes were found in all animal groups, and in adult animals up to 20% surface Ig+ cells were harvested. When the incorporation of the thymidine analogue bromodesoxyuridine was used to study the lymphocyte production in vivo 3 to 7% lymphocytes in the epithelium were labelled 24 hours later (lamina propria T lymphocytes about 1%). In this study lymphoid as well as non-lymphoid cells have been analysed in mucosal cell suspensions. The absolute cell yield per gram of mucosal tissue is a basis to estimate the pool sizes of intraepithelial and lamina propria lymphocytes.
Metabolite Profiling Identifies Markers of Uremia
Authors: Eugene P. Rhee, Amanda Souza, Laurie Farrell, Martin R. Pollak, Gregory D. Lewis, David J.R. Steele, Ravi Thadhani, Clary B. Clish, Anna Greka, Robert E. Gerszten
Journal: Journal of the American Society of Nephrology (2010)

ESRD is a state of small-molecule disarray. We applied liquid chromatography/tandem mass spectrometry-based metabolite profiling to survey >350 small molecules in 44 fasting subjects with ESRD, before and after hemodialysis, and in 10 age-matched, at-risk fasting control subjects. At baseline, increased levels of polar analytes and decreased levels of lipid analytes characterized uremic plasma. In addition to confirming the elevation of numerous previously identified uremic toxins, we identified several additional markers of ESRD, including dicarboxylic acids (adipate, malonate, methylmalonate, and maleate), biogenic amines, nucleotide derivatives, phenols, and sphingomyelins. The pattern of lipids was notable for a universal decrease in lower-molecular-weight triacylglycerols, and an increase in several intermediate-molecular-weight triacylglycerols in ESRD compared with controls; standard measurement of total triglycerides obscured this heterogeneity. These observations suggest disturbed triglyceride catabolism and/or β-oxidation in ESRD. As expected, the hemodialysis procedure was associated with significant decreases in most polar analytes. Unexpected increases in several metabolites, however, indicated activation of a broad catabolic program, including glycolysis, lipolysis, ketosis, and nucleotide breakdown. In summary, this study demonstrates the application of metabolite profiling to identify markers of ESRD, provide perspective on uremic dyslipidemia, and broaden our understanding of the biochemical effects of hemodialysis.
Animal ethics in Cardiovascular Research
Authors: M. Ruiz-Meana, E. A. Martinson, D. Garcia-Dorado, H. M. Piper
Journal: Cardiovascular Research (2011)

More than 100 million animals are used for research purposes around the world annually, most of them in Europe and the USA. Rats, mice, and other rodents make up 85–90% of all research animals. 1–1.5% correspond to dogs and cats and less than 1% is represented by non-human primates. Despite a significant decrease in the numbers of animals used in biomedical research and testing in the last two decades, in part due to more restrictive policies and development of alternative methods ( in vitro tests, availability of human cells and tissues, computational models, and others), the magnitude of these numbers, together with an increasing social sensitivity towards animal pain and suffering, makes the debate about the use of animals in experimental research an important and indisputable ethical issue among scientists, scientific journals, regulatory committees, and local, national, and international agencies.

The use of animals in research has historically represented an irresolvable moral dilemma between the value of the expected benefits and the suffering, pain, confinement, and death to which it subjects sensitive living beings. Scientists using animals have to work on the assumption that the resulting increase in knowledge or improvement in human health outweighs all these associated costs, which in some cases has been arguable. The Cartesian view that prevailed up to the second half of the last century tried to circumvent this ethical conflict by depriving the animals of any sensitive and intellectual capacity. This view of animal status was extended throughout Europe for centuries due to the important impact the French philosopher Descartes (1596–1650) had on our concept about animal consciousness. Non-human living beings were considered to lack cognitive abilities and could not feel pain or distress but only automatic reactions in response to external stimuli. This doctrine had a pernicious effect on animal welfare and gave rise …
Smads regulate collagen gel contraction by human dermal fibroblasts
Authors: K. Sumiyoshi, A. Nakao, Y. Setoguchi, K. Okumura, R. Tsuboi, H. Ogawa
Journal: British Journal of Dermatology (2003)

Transforming growth factor (TGF)-beta induces fibroblast contraction that is implicated in efficient wound healing. The Smad family of proteins mediates signal transduction of the TGF-beta superfamily. However, its role in fibroblast contraction remains unclear.To determine whether Smad proteins regulate fibroblast contraction.We used an in vitro type I collagen gel contraction assay with human dermal fibroblasts infected with adenoviruses carrying Smads.Overexpression of Smad3, a major signal transducer in the Smad family, enhanced collagen gel contraction by fibroblasts when compared with fibroblasts overexpressing a control lacZ. Addition of a very low concentration of TGF-beta1 that did not affect the collagen gel contraction by itself enhanced the contraction by fibroblasts overexpressing Smad3. In contrast, TGF-beta1-mediated collagen gel contraction was suppressed by overexpression of Smad7, a major inhibitory regulator in the Smad family, in fibroblasts. In addition, inhibitors of the Erk and p38 pathways, PD98059 and SB203580, did not affect TGF-beta1-mediated collagen gel contraction by dermal fibroblasts.Modulation of Smad3 or Smad7 expression in dermal fibroblasts affected their contraction of collagen gels possibly by regulating TGF-beta signalling in fibroblasts.
Enhanced Ca <sup>2+</sup> -Sensing Receptor Function in Idiopathic Pulmonary Arterial Hypertension
Authors: Aya Yamamura, Qiang Guo, Hisao Yamamura, Adriana M. Zimnicka, Nicole M. Pohl, Kimberly A. Smith, Ruby A. Fernandez, Amy Zeifman, Ayako Makino, Hui Dong, Jason X.-J. Yuan
Journal: Circulation Research (2012)

Rationale: A rise in cytosolic Ca 2+ concentration ([Ca 2+ ] cyt ) in pulmonary arterial smooth muscle cells (PASMC) is an important stimulus for pulmonary vasoconstriction and vascular remodeling. Increased resting [Ca 2+ ] cyt and enhanced Ca 2+ influx have been implicated in PASMC from patients with idiopathic pulmonary arterial hypertension (IPAH). Objective: We examined whether the extracellular Ca 2+ -sensing receptor (CaSR) is involved in the enhanced Ca 2+ influx and proliferation in IPAH-PASMC and whether blockade of CaSR inhibits experimental pulmonary hypertension. Methods and Results: In normal PASMC superfused with Ca 2+ -free solution, addition of 2.2 mmol/L Ca 2+ to the perfusate had little effect on [Ca 2+ ] cyt . In IPAH-PASMC, however, restoration of extracellular Ca 2+ induced a significant increase in [Ca 2+ ] cyt . Extracellular application of spermine also markedly raised [Ca 2+ ] cyt in IPAH-PASMC but not in normal PASMC. The calcimimetic R568 enhanced, whereas the calcilytic NPS 2143 attenuated, the extracellular Ca 2+ -induced [Ca 2+ ] cyt rise in IPAH-PASMC. Furthermore, the protein expression level of CaSR in IPAH-PASMC was greater than in normal PASMC; knockdown of CaSR in IPAH-PASMC with siRNA attenuated the extracellular Ca 2+ -mediated [Ca 2+ ] cyt increase and inhibited IPAH-PASMC proliferation. Using animal models of pulmonary hypertension, our data showed that CaSR expression and function were both enhanced in PASMC, whereas intraperitoneal injection of the calcilytic NPS 2143 prevented the development of pulmonary hypertension and right ventricular hypertrophy in rats injected with monocrotaline and mice exposed to hypoxia. Conclusions: The extracellular Ca 2+ -induced increase in [Ca 2+ ] cyt due to upregulated CaSR is a novel pathogenic mechanism contributing to the augmented Ca 2+ influx and excessive PASMC proliferation in patients and animals with pulmonary arterial hypertension.
Lions, tigers, and bears, oh God!: How the ancient problem of predator detection may lie beneath the modern link between religion and horror
Authors: Timothy Ketelaar
Journal: Behavioral and Brain Sciences (2004)

Atran &amp; Norenzyan (A&amp;N) claim that an appreciation of the evolved inferential machinery underlying supernatural beliefs can greatly aid us in understanding regularities in culturally shared conceptions of religion. I explore how their model provides insight into why culturally shared tales of horror (e.g., horror movies) often combine religious and predatory content.
Prevalence of smoking in the Austrian general population
Authors: Robab Breyer-Kohansal, Marie-Kathrin Breyer, Andrea Schrott, Alexander Hartmann, Sylvia Hartl, Otto Burghuber
Journal: European Respiratory Journal (2013)

Introduction

Smoking is the main preventable cause of premature death and the main risk factor for chronic obstructive pulmonary disease. According to the Eurobarometer 2010, the prevalence of ever smoking in Austrian is higher compared to other European countries (57% vs. 51%, respectively). An underlying cause might be the failure of national smoke ban actions.

Objective and methods

We aimed to investigate the prevalence of active and second hand smoking in Austrian male and female participants of the Austrian LEAD study, an ongoing, longitudinal, observational, population based cohort study.

Results

Interim analysis (n=1.314; male 47%; age 51.9±17 years) showed that in Austrian male and female participants ever smoking (65% and 56%; respectively) as well as second hand smoking (70% and 70.8%; respectively) in childhood and/or adulthood are highly prevalent. Second hand smoke in adulthood lasts on average 17.4±13.3 years and happens predominantly at work (20.6%). Interestingly, ever-smokers have a higher prevalence of second hand smoking compared to never smokers in both, childhood and adulthood (p<0.01).

Conclusion

Active smoking and second hand smoking are highly prevalent in Austria and national smoke ban actions have to be executed more strictly in order to reduce smoking itself as well as smoking related morbidity and mortality.
Recombinant interferon-α2a hastens the rate of HBeAg clearance in children with chronic hepatitis B
Authors: Cristiana Barbera, Flavia Bortolotti, Carlo Crivellaro, Alessandra Coscia, Lucia Zancan, Paolo Cadrobbi, Gabriella Nebbia, Maria Nazarena Pillan, Loredana Lepore, Teresa Parrella, Giuseppe Dastoli, Maurizia R. Brunetto, Ferruccio Bonino
Journal: Hepatology (1994)

We conducted a prospective controlled study of the efficacy of recombinant interferon-alpha 2a in 77 children (44 boys, 33 girls, mean age 8 yr) with chronic hepatitis B. All patients had seropositive results for HBeAg and hepatitis B virus DNA; 52 had chronic persistent or nonspecific reactive hepatitis, and 25 had mild active hepatitis. Twenty-one children (group 1) received recombinant interferon-alpha 2a 7.5 megaunits/m2 three times weekly for 6 mo, 19 children (group 2) received megaunits/m2 on the same schedule and 37 (group 3) remained untreated. At 6 mo, HBe antigen-to-antibody seroconversion associated with biochemical remission was seen in 24% of patients in group 1, 5% in group 2 and 3% in group 3 (p < 0.05 vs. group 1). At 18 mo, seroconversion rates were 30% in group 1, 21% in group 2 and 13.5% in group 3. These results suggest that a course of recombinant interferon-alpha 2a accelerates HBeAg-HBe antibody seroconversion in children. High baseline ALT levels were sensitive predictors of seroconversion in both treated and untreated patients. In contrast, baseline IgM HBc antibody levels influenced the rate of anti-HBe seroconversion only in untreated patients. These findings suggest that, in children as well as in adults, recombinant interferon-alpha 2a favors the clearance of hepatitis B virus replication, enhancing the host antiviral immunoresponse.