tbuckley/cabot-search huggingface dataset:
Post-infarct heart repair with granulocyte-colony stimulating factor: Is it a utopian goal?
Authors: P PAGLIARO
Journal: Cardiovascular Research (2006)

See article by Misao et al.  [16]  (pages 455–465) in this issue. 

For many years, the regeneration of the myocardium in which cells have been lost as a result of myocardial infarction (MI) and other forms of cardiac pathology has been a utopian goal of cardiologists. Recent experimental studies and early-phase clinical trials supported the possibility of enhancing cardiac repair as an achievable therapeutic target. Yet, disappointing, negative results have been reported both in experimental and clinical studies [1–3]. There can be several reasons for negative results. Certainly, the fact that we do not know the exact physiology of stem cells is one of the reasons.

We do not know yet the ideal cell type: bone marrow stem cells (BMSCs), cardiomyoplasty cardiomyocytes, skeletal myoblasts, and resident stem cells have been tested, and among BMSCs several cell lines (MSCs, EPCs, etc.) have been proposed [1–3]. We do not know the underlying mechanism of cellular regeneration (transdifferentiation, fusion, and/or paracrine effects). Finally, we do not know whether myocardial repair can be better achieved via cellular transplantation (intramyocardial, intracoronary, and/or systemic delivery) or mobilization of primitive BMSCs by cytokines. Each of these approaches may be adequate for specific patients. Undoubtedly, mobilization of BMSCs might offer a noninvasive therapeutic approach that is appealing for both physicians and patients. The bone marrow is a large reservoir of adult stem cells distal from the heart that can be enrolled for cell-mediated cardiac repair via regeneration of healthy myocardial tissue and recovery of cardiac function. These could be accomplished by neo-angiogenesis, cardiogenesis, and/or paracrine effects.

In its … 

* Tel.: +39 011 6705430; fax: +39 011 9038639. Email address: pasquale.pagliaro{at}unito.it
TEC: Integrated view of perception and action or framework for response selection?
Authors: Robert W. Proctor, Kim-Phuong L. Vu
Journal: Behavioral and Brain Sciences (2001)

The Theory of Event Coding (TEC) presented in Hommel et al. 's target article provides a useful heuristic framework for stimulating research. Although the authors present TEC as providing a more integrated view of perception and action than classical information processing, TEC is restricted to the stage often called response selection and shares many features with existing theories.
Resequencing of positional candidates identifies low frequency IL23R coding variants protecting against inflammatory bowel disease
Authors: Yukihide Momozawa, Myriam Mni, Kayo Nakamura, Wouter Coppieters, Sven Almer, Leila Amininejad, Isabelle Cleynen, Jean-Frédéric Colombel, Peter de Rijk, Olivier Dewit, Yigael Finkel, Miquel A Gassull, Dirk Goossens, Debby Laukens, Marc Lémann, Cécile Libioulle, Colm O'Morain, Catherine Reenaers, Paul Rutgeerts, Curt Tysk, Diana Zelenika, Mark Lathrop, Jurgen Del-Favero, Jean-Pierre Hugot, Martine de Vos, Denis Franchimont, Severine Vermeire, Edouard Louis, Michel Georges
Journal: Nature Genetics (2010)
Retinoic Acid–Induced Tissue Transglutaminase and Apoptosis in Vascular Smooth Muscle Cells
Authors: Hesheng Ou, Judith Haendeler, Michael R. Aebly, Louise A. Kelly, Brian C. Cholewa, George Koike, Anne Kwitek-Black, Howard J. Jacob, Bradford C. Berk, Joseph M. Miano
Journal: Circulation Research (2000)

Abstract —Retinoids exert antiproliferative and prodifferentiating effects in vascular smooth muscle cells (SMCs) and reduce neointimal mass in balloon-injured blood vessels. The mechanisms through which retinoids carry out these effects are unknown but likely involve retinoid receptor-mediated changes in gene expression. Here we report the cloning, chromosomal mapping, and biological activity of the retinoid-response gene rat tissue transglutaminase (tTG). Northern blotting studies showed that tTG is rapidly and dose-dependently induced in a protein synthesis–independent manner after stimulation with the natural retinoid all- trans retinoic acid (atRA). The induction of tTG was selective for atRA and its stereoisomers 9- cis and 13- cis RA, because little or no elevation in mRNA expression was observed with a panel of growth factors. Western blotting and immunofluorescence confocal microscopy showed an accumulation of cytosolic tTG protein after atRA stimulation. Radiolabeled cross-linking studies revealed a corresponding elevation in in vitro tTG activity. The increase in tTG activity was reduced in the presence of 2 distinct inhibitors of tTG (monodansylcadaverine and cystamine). atRA-induced tTG mRNA and protein expression were followed by a significant elevation in SMC apoptosis. Such retinoid-induced programmed cell death could be partially inhibited with each tTG inhibitor and was completely blocked when both inhibitors were used simultaneously. These results establish a role for atRA in the sequential stimulation of tTG and apoptosis in cultured SMCs. atRA-mediated apoptosis in SMCs seems to require the participation of active tTG, suggesting a potential mechanistic link between this retinoid-inducible gene and programmed cell death.
Acquired Resistance to Erlotinib in A-431 Epidermoid Cancer Cells Requires Down-regulation of MMAC1/PTEN and Up-regulation of Phosphorylated Akt
Authors: Fumiyuki Yamasaki, Mary J. Johansen, Dongwei Zhang, Savitri Krishnamurthy, Edward Felix, Chandra Bartholomeusz, Richard J. Aguilar, Kaoru Kurisu, Gordon B. Mills, Gabriel N. Hortobagyi, Naoto T. Ueno
Journal: Cancer Research (2007)

Abstract Erlotinib (Tarceva), an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has clinical activity in advanced lung cancer, but disease that initially responds to erlotinib eventually progresses. The mechanism of this acquired resistance is unclear. We established two erlotinib-resistant pools of A-431 cells, a well-characterized epidermoid cancer cell line that constitutively overexpresses EGFR and is sensitive to erlotinib, by continuous exposure to erlotinib over a 6-month period. The extent of EGFR gene amplification or mutation of the EGFR tyrosine kinase domain was not altered in the resistant cells. Intracellular erlotinib concentrations, determined by liquid chromatography-tandem mass spectrometry, were almost the same in all three cell lines. Immunoprecipitation with EGFR antibody followed by detection with phosphotyrosine antibody revealed that erlotinib effectively reduced EGFR phosphorylation in both parental cells and resistant cells. Erlotinib induced mutated in multiple advanced cancers 1/phosphatase and tensin homologue (MMAC1/PTEN) and suppressed phosphorylated Akt (Ser473) but not in the erlotinib-resistant cells. Overexpression of MMAC1/PTEN by transfection with Ad.MMAC1/PTEN or by pharmacologic suppression of Akt activity restored erlotinib sensitivity in both resistant pools. Further, transfection of parental A-431 cells with constitutively active Akt was sufficient to cause resistance to erlotinib. We propose that acquired erlotinib resistance associated with MMAC1/PTEN down-regulation and Akt activation could be overcome by inhibitors of signaling through the phosphatidylinositol 3-kinase pathway. [Cancer Res 2007;67(12):5779–88]
Highly Sensitive and Rapid Detection of <i>Pseudomonas aeruginosa</i> Based on Magnetic Enrichment and Magnetic Separation
Authors: Yongjun Tang, Jun Zou, Chao Ma, Zeeshan Ali, Zhiyang Li, Xiaolong Li, Ninging Ma, Xianbo Mou, Yan Deng, Liming Zhang, Kai Li, Guangming Lu, Haowen Yang, Nongyue He
Journal: Theranostics (2013)

A method for highly sensitive and rapid detection of Pseudomonas aeruginosa, based on magnetic enrichment and magnetic separation, is described in this paper.The magnetic nanoparticles (MNPs) were applied to adsorb genome DNA after the sample was lysed.The DNA binding MNPs were directly subjected to polymerase chain reaction (PCR) to amplify gyrB specific sequence of Pseudomonas aeruginosa.The biotin labeled PCR products were detected by chemiluminescence when they were successively incubated with the probes-modified MNPs and alkaline phosphatase (ALP) labeled streptavidin (SA).Agarose gel electrophoresis analyses approved the method of in situ PCR to be highly reliable.The factors which could affect the chemiluminiscence were studied in detail.The results showed that the MNPs of 400 nm in diameter are beneficial to the detection.The sequence length and the binding site of the probe with a target sequence have obvious effects on the detection.The optimal concentration of the probes, hybridization temperature and hybridization time were 10 μM, 60 °C and 60 mins, respectively.The method of in situ PCR based on MNPs can greatly improve the utilization rate of the DNA template ultimately enhancing the detection sensitivity.Experiment results proved that the primer and probe had high specificity, and Pseudomonas aeruginosa was successfully detected with detection limits as low as 10 cfu/mL by this method, while the detection of a single Pseudomonas aeruginosa can also be achieved.
Global SUMOylation on active chromatin is an acute heat stress response restricting transcription
Authors: Einari A. Niskanen, Marjo Malinen, Päivi Sutinen, Sari Toropainen, Ville Paakinaho, Anniina Vihervaara, Jenny Joutsen, Minna U. Kaikkonen, Lea Sistonen, Jorma J. Palvimo
Journal: Genome biology (2015)

Cells have developed many ways to cope with external stress. One distinctive feature in acute proteotoxic stresses, such as heat shock (HS), is rapid post-translational modification of proteins by SUMOs (small ubiquitin-like modifier proteins; SUMOylation). While many of the SUMO targets are chromatin proteins, there is scarce information on chromatin binding of SUMOylated proteins in HS and the role of chromatin SUMOylation in the regulation of transcription. We mapped HS-induced genome-wide changes in chromatin occupancy of SUMO-2/3-modified proteins in K562 and VCaP cells using ChIP-seq. Chromatin SUMOylation was further correlated with HS-induced global changes in transcription using GRO-seq and RNA polymerase II (Pol2) ChIP-seq along with ENCODE data for K562 cells. HS induced a rapid and massive rearrangement of chromatin SUMOylation pattern: SUMOylation was gained at active promoters and enhancers associated with multiple transcription factors, including heat shock factor 1. Concomitant loss of SUMOylation occurred at inactive intergenic chromatin regions that were associated with CTCF-cohesin complex and SETDB1 methyltransferase complex. In addition, HS triggered a dynamic chromatin binding of SUMO ligase PIAS1, especially onto promoters. The HS-induced SUMOylation on chromatin was most notable at promoters of transcribed genes where it positively correlated with active transcription and Pol2 promoter-proximal pausing. Furthermore, silencing of SUMOylation machinery either by depletion of UBC9 or PIAS1 enhanced expression of HS-induced genes. HS-triggered SUMOylation targets promoters and enhancers of actively transcribed genes where it restricts the transcriptional activity of the HS-induced genes. PIAS1-mediated promoter SUMOylation is likely to regulate Pol2-associated factors in HS.
Injuries in orienteering.
Authors: F Linde
Journal: British Journal of Sports Medicine (1986)

In a one-year prospective study of 42 elite orienteers, 73 recent injuries (1.7 per runner per year) were found. Acute injuries totalled 52% and 48% were due to overuse. Ankle sprains made up 37% of acute injuries while the remaining were mainly contusions caused by falls or bumps against branches or rocks. Medial shin pain, Achilles peritendinitis, peroneal tenosynovitis and iliotibial band friction syndrome were the most frequent overuse injuries. All overuse injuries were located in the lower extremity while 18% of acute injuries was located elsewhere. Acute injuries were most frequent in the competitive season while overuse injuries occurred most often during the continuous training period.
Ultrastructural Analysis of Vascular Calcifications in Uremia
Authors: Georg Schlieper, Anke Aretz, Steven C Verberckmoes, Thilo Krüger, Geert J Behets, Reza Ghadimi, Thomas E Weirich, Dorothea Rohrmann, Stephan Langer, Jan H Tordoir, Kerstin Amann, Ralf Westenfeld, Vincent M Brandenburg, Patrick C D'Haese, Joachim Mayer, Markus Ketteler, Marc D McKee, Jürgen Floege
Journal: Journal of the American Society of Nephrology (2010)

Accelerated intimal and medial calcification and sclerosis accompany the increased cardiovascular mortality of dialysis patients, but the pathomechanisms initiating microcalcifications of the media are largely unknown. In this study, we systematically investigated the ultrastructural properties of medial calcifications from patients with uremia. We collected iliac artery segments from 30 dialysis patients before kidney transplantation and studied them by radiography, microcomputed tomography, light microscopy, and transmission electron microscopy including electron energy loss spectrometry, energy dispersive spectroscopy, and electron diffraction. In addition, we performed synchrotron x-ray analyses and immunogold labeling to detect inhibitors of calcification. Von Kossa staining revealed calcification of 53% of the arteries. The diameter of these microcalcifications ranged from 20 to 500 nm, with a core-shell structure consisting of up to three layers (subshells). Many of the calcifications consisted of 2- to 10-nm nanocrystals and showed a hydroxyapatite and whitlockite crystalline structure and mineral phase. Immunogold labeling of calcification foci revealed the calcification inhibitors fetuin-A, osteopontin, and matrix gla protein. These observations suggest that uremic microcalcifications originate from nanocrystals, are chemically diverse, and intimately associate with proteinaceous inhibitors of calcification. Furthermore, considering the core-shell structure of the calcifications, apoptotic bodies or matrix vesicles may serve as a calcification nidus.
Interventions for Violence Against Women
Authors: C Nadine Wathen, Harriet L MacMillan
Journal: JAMA (2003)

<h3>Context</h3> Intimate partner violence is prevalent and is associated with significant impairment, yet it remains unclear which interventions, if any, reduce rates of abuse and reabuse. <h3>Objective</h3> To systematically review, from the perspective of primary health care, the available evidence on interventions aimed at preventing abuse or reabuse of women. <h3>Data Sources</h3> MEDLINE, PsycINFO, CINAHL, HealthStar, and Sociological Abstracts were searched from the database start dates to March 2001 using database-specific key words such as<i>domestic violence</i>,<i>spouse abuse</i>,<i>partner abuse</i>,<i>shelters</i>, and<i>battered women</i>. References of key articles were hand searched. The search was updated in December 2002. <h3>Study Selection</h3> Both authors reviewed all titles and abstracts using established inclusion/exclusion criteria. Twenty-two articles met the inclusion criteria for critical appraisal. <h3>Data Extraction</h3> Following the evidence-based methods of the Canadian Task Force on Preventive Health Care, both authors independently reviewed the 22 included studies using an established hierarchy of study designs and criteria for rating internal validity. Quality ratings of individual studies—good, fair, or poor—were determined based on a set of operational parameters specific to each design category developed with the US Preventive Services Task Force. <h3>Data Synthesis</h3> Screening instruments exist that can identify women who are experiencing intimate partner violence. No study has examined, in a comparative design, the effectiveness of screening when the end point is improved outcomes for women (as opposed to identification of abuse). No high-quality evidence exists to evaluate the effectiveness of shelter stays to reduce violence. Among women who have spent at least 1 night in a shelter, there is fair evidence that those who received a specific program of advocacy and counseling services reported a decreased rate of reabuse and an improved quality of life. The benefits of several other intervention strategies in treating both women and men are unclear, primarily because of a lack of suitably designed research measuring appropriate outcomes. In most cases, the potential harms of interventions are not assessed within the studies reviewed. <h3>Conclusions</h3> Much has been learned in recent years about the epidemiology of violence against women, yet information about evidence-based approaches in the primary care setting for preventing intimate partner violence is seriously lacking. The evaluation of interventions to improve the health and well-being of abused women remains a key research priority.
Selective progesterone receptor modulators and progesterone antagonists: mechanisms of action and clinical applications
Authors: Nathalie Chabbert-Buffet, Geri Meduri, Philippe Bouchard, Irving M Spitz
Journal: Human Reproduction Update (2005)

Since the discovery of the antiprogestin mifepristone, hundreds of similar compounds have been synthesized, which can be grouped in a large family of progesterone receptor ligands. This family includes pure agonists such as progesterone itself or progestins and, at the other end of the biological spectrum, pure progesterone receptor antagonists (PA). Selective progesterone receptor modulators (SPRM) have mixed agonist-antagonist properties, and occupy an intermediate position of the spectrum. These compounds have numerous applications in female health care. Mifepristone is used to terminate pregnancy, and as such is commercially available in many countries. The negative abortion-related image of mifepristone has clearly limited the involvement of the major pharmaceutical companies in the development of PA and SPRM. Many PA and SPRM display direct antiproliferative effects in the endometrium, although with variable actions which seem product- and dose-dependent. This property justifies their use in the treatment of myomas and endometriosis. PA also suppress late follicular development, block the LH surge and retard endometrial maturation, which renders them potential estrogen-free contraceptive drugs. SPRM such as asoprisnil are not as effective in blocking the LH surge and appear to target the endometrium directly and produce amenorrhoea. Interestingly, clinical data show that treatment with these compounds is not associated with hypo-estrogenism and bone loss. The potential clinical applications of these compounds cover a broad field and are very promising in major public health areas. These include emergency contraception, long-term estrogen-free contraception (administered alone, or in association with a progestin-only pill to improve bleeding patterns), myomas (where they induce a marked reduction in tumour volume and produce amenorrhoea) and endometriosis. Further developments might also include hormone replacement therapy in post-menopausal women, as well as the treatment of hormone-dependent tumours.
More than 90% of US doctors receive favours from drug companies
Authors: Bob Roehr
Journal: BMJ (2007)

Ties between American doctors and the drug and medical devices industries are ubiquitous, concludes a large national US survey of doctors.

An analysis of the 1662 responses to the survey, which was supported by the non-profit Institute on Medicine as a Profession, found that 94% of respondents reported some form of relationship with drug companies ( New England Journal of Medicine 2007;356:1742-50). The most common benefits of such relationships were receiving food in the workplace (reported by 83% of respondents) and receiving free drug samples (78%), while more than a third (35%) were reimbursed for attending professional meetings or training, and a quarter (28%) were compensated for consulting or enrolling patients in clinical trials that were beyond …
In vitro infection of primary human hepatocytes by HCV-positive sera: insights on a highly relevant model
Authors: Claire Gondeau, Philippe Briolotti, Francia Razafy, Cédric Duret, Pierre-Alain Rubbo, François Helle, Thierry Rème, Marie-Pierre Ripault, Jacques Ducos, Jean-Michel Fabre, Jeanne Ramos, Eve-Isabelle Pécheur, Dominique Larrey, Patrick Maurel, Martine Daujat-Chavanieu
Journal: Gut (2013)

Adult primary human hepatocytes (PHHs) support the complete infection cycle of natural HCV from patients' sera. The molecular details underlying sera infectivity towards these cells remain largely unknown. Therefore, we sought to gain a deeper comprehension of these features in the most physiologically relevant culture system.Using kinetic experiments, we defined the optimal conditions to infect PHH and explored the link between cell organisation and permissivity. Based on their infectivity, about 120 sera were classified in three groups. Concentration of 52 analytes was measured in 79 selected sera using multiplexed immunobead-based analyte profiling.PHH permissivity towards HCV infection negatively correlated with cell polarisation and formation of functional bile canaliculi. PHH supported HCV replication for at least 2 weeks with de novo virus production. Depending on their reactivity, sera could be classified in three groups of high, intermediate or low infectivity toward PHH. Infectivity could not be predicted based on the donors' clinical characteristics, viral load or genotype. Interestingly, highly infectious sera displayed a specific cytokine profile with low levels of most of the 52 tested analytes. Among them, 24 cytokines/growth factors could impact hepatocyte biology and infection efficiency.We identified critical factors leading to efficient PHH infection by HCV sera in vitro. Overall, we showed that this cellular model provides a useful tool for studying the mechanism of HCV infection in its natural host cell, selecting highly infectious isolates, and determining the potency of drugs towards various HCV strains.
Successful total correction of congenital interruption of the aortic arch and ventricular septal defect
Authors: M. P. Singh, H. H. Bentall, C. M. Oakley
Journal: Thorax (1970)

Successful surgical correction of the complex anomaly of interruption of the aortic arch and intracardiac ventricular septal defect is reported. The patient was a boy 5 years old when he first came under treatment. The total correction was performed in two stages. At the first operation, at the age of 7 years, continuity of the aortic arch was achieved by insertion of a Teflon graft, employing left heart bypass. The ventricular septal defect was closed at the age of 13 years on total cardiopulmonary bypass. Two and half years after the total correction the boy is alive and well. The difficulties in diagnosing the condition are discussed. The role of left heart bypass is emphasized.