tbuckley/cabot-search huggingface dataset:
Adenosinetriphosphatase Activity of Cardiac Myosin
Authors: ARNOLD M. KATZ, DORIS I. REPKE, BONNIE B. RUBIN
Journal: Circulation Research (1966)

Examination of the ATPase activities of rabbit cardiac, rabbit red skeletal and rabbit white skeletal muscle myosins has demonstrated the existence of two types of myosin. One type, characterized by the higher ATPase activity, is present in white skeletal muscle; the other is found in red skeletal and cardiac muscle. The differences between myosin preparations could not be attributed to varying degrees of actin contamination nor to changes occurring in the myosins during the preparative procedure. Chromatography of dog cardiac myosin on DEAE-cellulose showed a single component. No differences were observed between the cardiac myosins of the dog and rabbit. Activation of the ATPase activity of cardiac myosin by Ca ++ was less than that of white skeletal myosin while the extent of inhibition by Mg ++ was similar for both. The stoichiometry of the interaction with actin of both cardiac and white skeletal myosins was similar but actin caused less activation of the cardiac myosin ATPase. Cardiac and white skeletal actins showed no differences in their abilities to activate myosin ATPase activity, which is in accord with previously documented similarities in the structures of these actins. Comparison of the present findings with previously reported mechanical measurements made with intact muscles does not indicate that the intrinsic level of myosin ATPase activity determines the maximal tension developed during the active state. On the other hand, there may be a direct relationship between shortening velocity and myosin ATPase activity.
Peripancreatic fat necrosis worsens acute pancreatitis independent of pancreatic necrosis via unsaturated fatty acids increased in human pancreatic necrosis collections
Authors: Pawan Noel, Krutika Patel, Chandra Durgampudi, Ram N Trivedi, Cristiane de Oliveira, Michael D Crowell, Rahul Pannala, Kenneth Lee, Randall Brand, Jennifer Chennat, Adam Slivka, Georgios I Papachristou, Asif Khalid, David C Whitcomb, James P DeLany, Rachel A Cline, Chathur Acharya, Deepthi Jaligama, Faris M Murad, Dhiraj Yadav, Sarah Navina, Vijay P Singh
Journal: Gut (2014)

Peripancreatic fat necrosis occurs frequently in necrotising pancreatitis. Distinguishing markers from mediators of severe acute pancreatitis (SAP) is important since targeting mediators may improve outcomes. We evaluated potential agents in human pancreatic necrotic collections (NCs), pseudocysts (PCs) and pancreatic cystic neoplasms and used pancreatic acini, peripheral blood mononuclear cells (PBMC) and an acute pancreatitis (AP) model to determine SAP mediators.We measured acinar and PBMC injury induced by agents increased in NCs and PCs. Outcomes of caerulein pancreatitis were studied in lean rats coadministered interleukin (IL)-1β and keratinocyte chemoattractant/growth-regulated oncogene, triolein alone or with the lipase inhibitor orlistat.NCs had higher fatty acids, IL-8 and IL-1β versus other fluids. Lipolysis of unsaturated triglyceride and resulting unsaturated fatty acids (UFA) oleic and linoleic acids induced necro-apoptosis at less than half the concentration in NCs but other agents did not do so at more than two times these concentrations. Cytokine coadministration resulted in higher pancreatic and lung inflammation than caerulein alone, but only triolein coadministration caused peripancreatic fat stranding, higher cytokines, UFAs, multisystem organ failure (MSOF) and mortality in 97% animals, which were prevented by orlistat.UFAs, IL-1β and IL-8 are elevated in NCs. However, UFAs generated via peripancreatic fat lipolysis causes worse inflammation and MSOF, converting mild AP to SAP.
Host and environmental determinants of polychlorinated aromatic hydrocarbons in serum of adolescents.
Authors: Tim S Nawrot, Jan A Staessen, Elly M Den Hond, Gudrun Koppen, Greet Schoeters, Robert Fagard, Lutgarde Thijs, Gerhard Winneke, Harry A Roels
Journal: Environmental Health Perspectives (2002)

This study investigated host factors and environmental factors as potential determinants of polychlorinated aromatic hydrocarbons (PCAHs) in serum of adolescents. We recruited 200 participants (80 boys and 120 girls), with a mean age of 17.4 years (SD, 0.8), in Belgium from a rural control area (Peer) and from two polluted suburbs of Antwerp where a nonferrous smelter (Hoboken) and waste incinerators (Wilrijk) are located. We quantified polychlorinated biphenyls (PCBs; congeners 138, 153, and 180) in serum by gas chromatography and obtained the toxic equivalents (TEQs) of PCAHs in serum with the chemically activated luciferase gene expression bioassay (CALUX). Serum PCB concentration was higher in boys than in girls (1.67 vs. 1.02 nmol/L or 377 vs. 210 pmol/g serum lipids; p&lt; 0.001). In the whole adolescent group, multiple regression showed that serum PCB concentration decreased 0.06 nmol/L per 1% increase in body fat content (p&lt; 0.001) and increased 0.39 nmol/L and 0.14 nmol/L per 1 mmol/L increase in serum concentrations of triglycerides (p &lt; 0.001) and cholesterol (p = 0.002), respectively. Host factors explained 44% of the serum PCB variance. In the same model, serum PCB concentration increased 0.14 nmol/L with 10 weeks of breast-feeding (p&lt; 0.001) and 0.06 nmol/L with intake of 10 g animal fat per day (p &lt; 0.001), and was associated with residence in the waste incinerator area (9% higher; p = 0.04); 11% of the variance could be explained by these environmental factors. The geometric mean of the serum TEQ value was similar in boys and girls (0.15 TEQ ng/L or 33.0 pg/g serum lipids). In multiple regression, TEQ in serum decreased 0.03 ng/L per centimeter increase in triceps skinfold (p = 0.006) and was 29% higher in subjects living close to the nonferrous smelter (p &lt; 0.001). This study showed that in 16- to 18-year-old teenagers host factors are important determinants of serum concentrations of PCAHs, whereas environmentally related determinants may to some extent contribute independently to human exposure to these persistent chemicals in the environment.
A Parental History of Asthma Is a Risk Factor for Wheezing and Nonwheezing Respiratory Illnesses in Infants Younger than 18 Months of Age
Authors: CAROL H. BOSKEN, WILLIAM C. HUNT, WILLIAM E. LAMBERT, JONATHAN M. SAMET
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

The relationship between respiratory infection and allergy as risk factors for the development of wheezing illnesses in infants has been in dispute. We hypothesized that a parental history of allergic diseases would be associated with an increased rate of respiratory infections as well as an increased rate of wheezing during infectious episodes. We prospectively evaluated 1,193 infants from birth to 18 mo of age, using bi-weekly telephone surveillance to document all respiratory events. The overall rate of respiratory illness (all RI) increased to a maximum of 10.6 illnesses/infant/year in the 7- to 9-mo age group and then leveled off in the older infants. Multivariable models adjusting for demographic variables, breast feeding, month of illness, number of siblings, and attendance at day care showed an increase in the rate of all RI in infants older than 7 mo of age who had a parental history of asthma (OR = 1.24, CI = 1.09 to 1.41) or a parental history of atopy (OR = 1.14, CI = 1.03 to 1.26). The rate of lower respiratory illnesses accompanied by wheezing was related only to a parental history of asthma (OR = 2.06, CI = 1.36 to 3.11). We conclude that all RI, most of which represent viral infections, are increased in otherwise normal infants with a parental history of asthma or atopy, whereas wheezing is related only to a parental history of asthma.
Muscle Diseases: The Muscular Dystrophies
Authors: Elizabeth M. McNally, Peter Pytel
Journal: Annual Review of Pathology Mechanisms of Disease (2007)

Dystrophic muscle disease can occur at any age. Early- or childhood-onset muscular dystrophies may be associated with profound loss of muscle function, affecting ambulation, posture, and cardiac and respiratory function. Late-onset muscular dystrophies or myopathies may be mild and associated with slight weakness and an inability to increase muscle mass. The phenotype of muscular dystrophy is an endpoint that arises from a diverse set of genetic pathways. Genes associated with muscular dystrophies encode proteins of the plasma membrane and extracellular matrix, and the sarcomere and Z band, as well as nuclear membrane components. Because muscle has such distinctive structural and regenerative properties, many of the genes implicated in these disorders target pathways unique to muscle or more highly expressed in muscle. This chapter reviews the basic structural properties of muscle and genetic mechanisms that lead to myopathy and muscular dystrophies that affect all age groups.
Chemotherapy (CT) and hormonotherapy (HT) as neoadjuvant treatment in luminal breast cancer patients: results from the GEICAM/2006-03, a multicenter, randomized, phase-II study
Authors: E. Alba, L. Calvo, J. Albanell, J.R. De la Haba, A. Arcusa Lanza, J.I. Chacon, P. Sanchez-Rovira, A. Plazaola, J.A. Lopez Garcia-Asenjo, B. Bermejo, E. Carrasco, A. Lluch
Journal: Annals of Oncology (2012)
Developmental and Regenerative Biology of Multipotent Cardiovascular Progenitor Cells
Authors: Anthony C. Sturzu, Sean M. Wu
Journal: Circulation Research (2011)

Our limited ability to improve the survival of patients with heart failure is attributable, in part, to the inability of the mammalian heart to meaningfully regenerate itself. The recent identification of distinct families of multipotent cardiovascular progenitor cells from endogenous, as well as exogenous, sources, such as embryonic and induced pluripotent stem cells, has raised much hope that therapeutic manipulation of these cells may lead to regression of many forms of cardiovascular disease. Although the exact source and cell type remains to be clarified, our greater understanding of the scientific underpinning behind developmental cardiovascular progenitor cell biology has helped to clarify the origin and properties of diverse cells with putative cardiogenic potential. In this review, we highlight recent advances in the understanding of cardiovascular progenitor cell biology from embryogenesis to adulthood and their implications for therapeutic cardiac regeneration. We believe that a detailed understanding of cardiogenesis will inform future applications of cardiovascular progenitor cells in heart failure therapy and regenerative medicine.
Transcriptome and methylome profiling reveals relics of genome dominance in the mesopolyploid Brassica oleracea
Authors: Isobel AP Parkin, Chushin Koh, Haibao Tang, Stephen J Robinson, Sateesh Kagale, Wayne E Clarke, Chris D Town, John Nixon, Vivek Krishnakumar, Shelby L Bidwell, France Denoeud, Harry Belcram, Matthew G Links, Jérémy Just, Carling Clarke, Tricia Bender, Terry Huebert, Annaliese S Mason, J Chris Pires, Guy Barker, Jonathan Moore, Peter G Walley, Sahana Manoli, Jacqueline Batley, David Edwards, Matthew N Nelson, Xiyin Wang, Andrew H Paterson, Graham King, Ian Bancroft, Boulos Chalhoub, Andrew G Sharpe
Journal: Genome biology (2014)

Abstract Background Brassica oleracea is a valuable vegetable species that has contributed to human health and nutrition for hundreds of years and comprises multiple distinct cultivar groups with diverse morphological and phytochemical attributes. In addition to this phenotypic wealth, B. oleracea offers unique insights into polyploid evolution, as it results from multiple ancestral polyploidy events and a final Brassiceae-specific triplication event. Further, B. oleracea represents one of the diploid genomes that formed the economically important allopolyploid oilseed, Brassica napus . A deeper understanding of B. oleracea genome architecture provides a foundation for crop improvement strategies throughout the Brassica genus. Results We generate an assembly representing 75% of the predicted B. oleracea genome using a hybrid Illumina/Roche 454 approach. Two dense genetic maps are generated to anchor almost 92% of the assembled scaffolds to nine pseudo-chromosomes. Over 50,000 genes are annotated and 40% of the genome predicted to be repetitive, thus contributing to the increased genome size of B. oleracea compared to its close relative B. rapa . A snapshot of both the leaf transcriptome and methylome allows comparisons to be made across the triplicated sub-genomes, which resulted from the most recent Brassiceae-specific polyploidy event. Conclusions Differential expression of the triplicated syntelogs and cytosine methylation levels across the sub-genomes suggest residual marks of the genome dominance that led to the current genome architecture. Although cytosine methylation does not correlate with individual gene dominance, the independent methylation patterns of triplicated copies suggest epigenetic mechanisms play a role in the functional diversification of duplicate genes.
NOTES ON A CASE OF TETANIC SPASM: WITH REFERENCE TO THE DIFFERENTIAL DIAGNOSIS BETWEEN TETANUS AND STRYCHNINE POISONING
Authors: W. S. Stevenson
Journal: BMJ (1909)

TETANIC SPASM.LTu a not in a position to sav, but one cannot help feeling that there is some connexion between the lesion in the bowel and the condition of the kidneys.With a powerful heart and diseased arteries we expect cerebral and retinal haemorrhages and epistaxis as a matter of course.Why, then, should the vessels of the stomach and intestine remain intact?I beg to thank Dr. Douglas Stanley and Dr. Foxwell, of Queen's Hospital, for
Phase II trial of 131I-B1 (anti-CD20) antibody therapy with autologous stem cell transplantation for relapsed B cell lymphomas
Authors: O.W Press, F Appelbaum, P.J Martin, D.C Matthews, I.D Bernstein, J.F Eary, W.B Nelp, T Gooley, S Glenn, B Porter, D.R Fisher
Journal: The Lancet (1995)
Tuberculosis among health care workers during three recent decades
Authors: M. Raitio, E. Tala
Journal: European Respiratory Journal (2000)

Some studies have found that health care workers have an increased risk of tuberculosis, whereas other studies have reported the opposite. This study examined data of Finnish health care workers (HCWs) for the incidence of tuberculosis disease. Cases of occupational tuberculosis in Finland were analysed over a period of 30 yrs (1966-1995). Control subjects were all other incident tuberculosis cases at working age. The material thus obtained included 658 people with notified occupational tuberculosis, and 56,146 control cases. The authors studied incidence, and age specific rate, as well as their trends. The incidence of tuberculosis among health care workers decreased from 57.9 to 6.1 per 100,000 and the corresponding figures among control subjects decreased from 156.8 to 9.1 per 100,000. The overall risk in health care workers was lower than in the general population throughout the study period. Analysis of age specific rates revealed no age group at increased risk. The reasons are multifactorial, among them the successful tuberculosis programme, and the lack of impact of such risk factors as immigration, human immunodeficiency virus infection and drug resistance; high coverage of bacille Calmette-Guerin vaccination may also be a factor, although it is difficult to assess.
Guidelines for the management of oesophageal and gastric cancer
Authors: W. H. Allum, J. M. Blazeby, S. M. Griffin, D. Cunningham, J. A. Jankowski, R. Wong
Journal: Gut (2011)

Over the past decade the Improving Outcomes Guidance (IOG) document has led to service re-configuration in the NHS and there are now 41 specialist centres providing oesophageal and gastric cancer care in England and Wales. The National Oesophago-Gastric Cancer Audit, which was supported by the British Society of Gastroenterology, the Association of Upper Gastrointestinal Surgeons (AUGIS) and the Royal College of Surgeons of England Clinical Effectiveness Unit, and sponsored by the Department of Health, has been completed and has established benchmarks for the service as well as identifying areas for future improvements.1–3 The past decade has also seen changes in the epidemiology of oesophageal and gastric cancer. The incidence of lower third and oesophago-gastric junctional adenocarcinomas has increased further, and these tumours form the most common oesophago-gastric tumour, probably reflecting the effect of chronic gastro-oesophageal reflux disease (GORD) and the epidemic of obesity. The increase in the elderly population with significant co-morbidities is presenting significant clinical management challenges. Advances in understanding of the natural history of the disease have increased interest in primary and secondary prevention strategies. Technology has improved the options for diagnostic and therapeutic endoscopy and staging with cross-sectional imaging. Results from medical and clinical oncology trials have established new standards of practice for both curative and palliative interventions. The quality of patient experience has become a significant component of patient care, and the role of the specialist nurse is fully intergrated. These many changes in practice and patient management are now routinely controlled by established multidisciplinary teams (MDTs) which are based in all hospitals managing these patients.

The original guidelines described the management of oesophageal and gastric cancer within existing practice. This paper updates the guidance to include new evidence and to embed it within the framework of the current UK National Health Service (NHS) Cancer …
Expanding the Roles for Pregnane X Receptor in Cancer: Proliferation and Drug Resistance in Ovarian Cancer
Authors: Divya Gupta, Madhukumar Venkatesh, Hongwei Wang, Sean Kim, Michael Sinz, Gary L. Goldberg, Kathleen Whitney, Clifford Longley, Sridhar Mani
Journal: Clinical Cancer Research (2008)

Abstract Purpose: We examined the presence of the pregnane X receptor (PXR) and its effects on ovarian cancer cells after activation by its cognate ligand. Experimental Design: SKOV-3 and OVCAR-8 ovarian carcinoma cells were analyzed for expression of PXR by quantitative reverse transcription-PCR and Western blot. Human ovarian cancer tissue was also analyzed for PXR expression by immunochemistry. Ligand (agonist)–induced PXR target genes were analyzed in SKOV-3 cells by quantitative reverse transcription-PCR. SKOV-3 cell proliferation was assessed by MTT assay. In vivo confirmation of in vitro effects of PXR ligands were done in NOD.SCID mice carrying SKOV-3 xenografts. Results: PXR is expressed in ovarian cancer cells. In SKOV-3 cells, PXR is functional and its activation by cognate ligands induces PXR target genes (CYP2B6, CYP3A4, and UGT1A1) but not MDR1 and MRP2. PXR activation in SKOV-3 cells induces cell proliferation and drug resistance. In mice harboring SKOV-3 xenografts, rifampicin (PXR agonist) induces cell proliferation and tumor growth. Conclusion: PXR activation, regardless of the type of ligand agonist present, promotes the “malignant” phenotype of cancer cells. These data serve as the basis for finding novel nontoxic inhibitors of PXR activation as a method to control cell growth and prevent induction of drug resistance.
ET-71 * THE ANTITUMOR EFFECTS OF WITHAFERIN A IN GLIOBLASTOMA STEM CELLS
Authors: B. Zhang, S. Shah, J. Prince, W. Walters, A. Bregy, Y. Guo, R. J Komatar, R. M. Graham
Journal: Neuro-Oncology (2014)

INTRODUCTION: Glioblastoma Multiforme (GBM) is the most common and malignant primary brain tumors. Recent studies indicate that GBM stem cells (GSCs), are chemotherapy and radiotherapy resistant and are responsible for tumor cell invasion into normal brain, tumor growth and tumor reoccurrence following treatment. Withaferin A (WA), a steroidal lactone isolated from Withania somnifera, has demonstrated anti-tumor potential including inhibiting tumor growth, metastasis and angiogenesis. However, effects of WA in GSCs have not been previously explored. METHODS: GSCs were generated from patient's tumors and analyzed for stem cell markers CD133, CD44, GFAP, Nestin, Musashi, SOX2 and BMi1 by immunocytochemistry. Effect of WA on GSC viability was determined by MTS and/or LDH assay. Morphological effects of WA were evaluated by transmission electron microscopy. Effect of WA on cell signaling pathways was evaluated with flow cytometry, western blot analysis and fluorescent microscopy. ROS was detected using MitoSOX Red. RESULTS: WA induced both dose and time dependent increase in cell death in GSC lines (IC50 average 1.27+ 0.12uM for 6 GSC lines). In contrast, primary neurons were not affected by these concentrations and had a much higher IC50 (5.78uM). Treatment of GSCs with WA significantly increased the diameter of endoplasmic reticulum (ER) and western blot analysis confirmed ER stress demonstrating increased grp78, IRE1, and CHOP protein levels. WA treatment increased mitochondrial ROS production and induced apoptosis as indicated by increased levels of cleaved PARP, caspase 4/3/7/12, Bax, and bak. Pre-treatment with the antioxidant N-acetyl-L-cysteine (NAC) or caspase inhibitor (z-vad-fmk) attenuated WA-induced apoptosis. Lastly WA increased both velcade and NVP-BEZ235 induced cell death. CONCLUSION: Our data indicates that WA mediates anti-tumor effects via ROS generation, ER stress activation, and apoptosis induction in GSCs and potentially sensitizes these cells to additional chemotherapy. These findings warrant further investigation of WA as an adjuvant therapy for GBM.
Podocytes Respond to Mechanical Stress In Vitro
Authors: NICOLE ENDLICH, KAI R. KRESS, JOCHEN REISER, DIETMAR UTTENWEILER, WILHELM KRIZ, PETER MUNDEL, KARLHANS ENDLICH
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Glomerular capillary pressure is thought to affect the structure and function of glomerular cells. However, it is unknown whether podocytes are intrinsically sensitive to mechanical forces. In the present study, differentiated mouse podocytes were cultured on flexible silicone membranes. Biaxial cyclic stress (0.5 Hz and 5% linear strain) was applied to the membranes for up to 3 d. Mechanical stress reduced the size of podocyte cell bodies, and processes became thin and elongated. Podocytes did not align in the inhomogeneous force field. Whereas the network of microtubules and that of the intermediate filament vimentin exhibited no major changes, mechanical stress induced a reversible reorganization of the actin cytoskeleton: transversal stress fibers (SF) disappeared and radial SF that were connected to an actin-rich center (ARC) formed. Epithelial and fibroblast cell lines did not exhibit a comparable stress-induced reorganization of the F-actin. Confocal and electron microscopy revealed an ellipsoidal and dense filamentous structure of the ARC. Myosin II, α-actinin, and the podocyte-specific protein synaptopodin were present in radial SF, but, opposite to F-actin, they were not enriched in the ARC. The formation of the ARC and of radial SF in response to mechanical stress was inhibited by nonspecific blockade of Ca 2+ influx with Ni 2+ (1 mM), by Rho kinase inhibition with Y-27632 (10 μM), but not by inhibition of stretch-activated cation channels with Gd 3+ (50 μM). In summary, mechanical stress induces a unique reorganization of the actin cytoskeleton in podocytes, featuring radial SF and an ARC, which differ in protein composition. The F-actin reorganization in response to mechanical stress depends on Ca 2+ influx and Rho kinase. The present study provides the first direct evidence that podocytes are mechanosensitive.