tbuckley/cabot-search huggingface dataset:
The Use of Magnetic Resonance to Evaluate Tissue Oxygenation in Renal Artery Stenosis
Authors: Stephen C. Textor, James F. Glockner, Lilach O. Lerman, Sanjay Misra, Michael A. McKusick, Stephen J. Riederer, Joseph P. Grande, S. Ivan Gomez, J. Carlos Romero
Journal: Journal of the American Society of Nephrology (2008)

Vascular occlusive disease poses a threat to kidney viability, but whether the events leading to injury and eventual fibrosis actually entail reduced oxygenation and regional tissue ischemia is unknown. Answering this question has been difficult because of the lack of an adequate method to assess tissue oxygenation in humans. BOLD (blood oxygen-level-dependent) magnetic resonance imaging detects changes in tissue deoxyhemoglobin during maneuvers that affect oxygen consumption, therefore this technique was used to image and analyze cortical and medullary segments of 50 kidneys in 25 subjects undergoing magnetic resonance (MR) angiography to diagnose renal artery stenosis (RAS). Magnetic rate of relaxation (R2*) positively correlates with deoxyhemoglobin levels and was therefore used as a surrogate measure of tissue oxygenation. Furosemide was administered to examine the effect of inhibiting energy-dependent electrolyte transport on tissue oxygenation in subjects with renovascular disease. In 21 kidneys with normal nephrograms, administration of furosemide led to a 20% decrease in medullary R2* (P < 0.01) and an 11.2% decrease in cortical R2*. In normal-size kidneys downstream of high-grade renal arterial stenoses, R2* was elevated at baseline, but fell after furosemide. In contrast, atrophic kidneys beyond totally occluded renal arteries demonstrated low levels of R2* that did not change after furosemide. In kidneys with multiple arteries, localized renal artery stenoses produced focal elevations of R2*, suggesting areas of deoxyhemoglobin accumulation. These results suggest that BOLD MR coupled with a method to suppress tubular oxygen consumption can be used to evaluate regional tissue oxygenation in the human kidney affected by vascular occlusive disease.
Regulation of cardiac gene expression during development
Authors: J. Robbins
Journal: Cardiovascular Research (1996)

In the last five years, significant new insights have been made into the mechanistic bases that underlie controlled gene expression in the developing heart. Because different phenomena at a number of levels need to be understood before the process can be defined fully, these insights stem from a body of studies that have been carried out in both non mammalian and mammalian systems. These include: (1) the molecular basis for positional information in the temporal path of gestation; (2) determination of the mesoderm via the combination of positional information and inductive influences; (3) restriction of a mesoderm subset to the cardiac muscle cell lineage; and (4) the activation of those genes which encode the proteins whose functions are responsible for the heart’s action as a pump. The ultimate control for each of these processes rests upon the genomic apparatus and its timed response to a variety of internal and external influences. Although each facet of determination/differentiation depends upon both unique and overlapping genetic complements, a genera1 regulatory paradigm holds for all of these processes: diffusible factors act in fruns with specific sequences on the DNA (gene) to regulate transcription. The factors bind to short recognition sites either within or adjacent (in cis) to the gene and it is these cis-fruns interactions that control transcription. This review’s purpose is to outline what is known about these processes as they apply to the genes that are expressed in the heart during development and differentiation, from the establishment of positional value to the production of the proteins characteristic of the terminally differentiated state. Cardiac organogenesis occurs early in mammalian development. In the human, the cardiac primordium is appar
Deficiency or inhibition of oxygen sensor Phd1 induces hypoxia tolerance by reprogramming basal metabolism
Authors: Julián Aragonés, Martin Schneider, Katie Van Geyte, Peter Fraisl, Tom Dresselaers, Massimiliano Mazzone, Ruud Dirkx, Serena Zacchigna, Hélène Lemieux, Nam Ho Jeoung, Diether Lambrechts, Tammie Bishop, Peggy Lafuste, Antonio Diez-Juan, Sarah K Harten, Pieter Van Noten, Katrien De Bock, Carsten Willam, Marc Tjwa, Alexandra Grosfeld, Rachel Navet, Lieve Moons, Thierry Vandendriessche, Christophe Deroose, Bhathiya Wijeyekoon, Johan Nuyts, Benedicte Jordan, Robert Silasi-Mansat, Florea Lupu, Mieke Dewerchin, Chris Pugh, Phil Salmon, Luc Mortelmans, Bernard Gallez, Frans Gorus, Johan Buyse, Francis Sluse, Robert A Harris, Erich Gnaiger, Peter Hespel, Paul Van Hecke, Frans Schuit, Paul Van Veldhoven, Peter Ratcliffe, Myriam Baes, Patrick Maxwell, Peter Carmeliet
Journal: Nature Genetics (2008)
Rheumatism and Orthopaedics
Authors: A. G. T. Fisher
Journal: BMJ (1945)

<h3>Abstract</h3> Anthracyclines are among the most used and effective anticancer drugs. Their activity has been attributed to DNA double-strand breaks resulting from topoisomerase II poisoning and to eviction of histones from select sites in the genome. Here we show that the extensively used anthracyclines Doxorubicin, Daunorubicin and Epirubicin, decrease the transcription of nuclear factor kappa B (NF-κB)-dependent gene targets, but not interferon responsive genes. Using an NMR-based structural approach, we demonstrate that anthracyclines disturb the complexes formed between the NF-κB subunit RelA and its DNA binding sites. The variant anthracyclines Aclarubicin, Doxorubicinone and the newly developed Dimethyl-doxorubicin, which share anticancer properties with the other anthracyclines but do not induce DNA damage, also suppressed inflammation, thus uncoupling DNA damage from the effects on inflammation. These findings have implications for anticancer therapy and for the development of novel anti-inflammatory drugs with limited side effects for life-threatening conditions such as sepsis.
ACCF/ACR/AHA/NASCI/SAIP/SCAI/SCCT 2010 Expert Consensus Document on Coronary Computed Tomographic Angiography
Authors: Daniel B. Mark, Daniel S. Berman, Matthew J. Budoff, J. Jeffrey Carr, Thomas C. Gerber, Harvey S. Hecht, Mark A. Hlatky, John McB. Hodgson, Michael S. Lauer, Julie M. Miller, Richard L. Morin, Debabrata Mukherjee, Michael Poon, Geoffrey D. Rubin, Robert S. Schwartz
Journal: Circulation (2010)
Targeting of αv integrin identifies a core molecular pathway that regulates fibrosis in several organs
Authors: Neil C Henderson, Thomas D Arnold, Yoshio Katamura, Marilyn M Giacomini, Juan D Rodriguez, Joseph H McCarty, Antonella Pellicoro, Elisabeth Raschperger, Christer Betsholtz, Peter G Ruminski, David W Griggs, Michael J Prinsen, Jacquelyn J Maher, John P Iredale, Adam Lacy-Hulbert, Ralf H Adams, Dean Sheppard
Journal: Nature Medicine (2013)
Involvement of two different pathways in the motor effects of erythromycin on the gastric antrum in humans
Authors: B Coulie, J Tack, T Peeters, J Janssens
Journal: Gut (1998)

During the interdigestive state in humans, erythromycin 40 mg induces a premature activity front that starts in the stomach, while erythromycin 200 mg induces a prolonged period of enhanced antral contractile activity.To study the involvement of a cholinergic pathway in the motor effects of erythromycin using the muscarinic antagonist atropine and the neural 5-HT1 receptor agonist sumatriptan.In 30 healthy volunteers, fasted antroduodenojejunal motor activity was studied by stationary manometry. Placebo (n = 10), atropine (15 micrograms/kg intravenous bolus plus 15 micrograms/kg/h over 30 minutes; n = 10), or sumatriptan (6 mg subcutaneously; n = 10) was administered, followed by infusion of erythromycin 40 mg or 200 mg.After placebo, erythromycin 40 mg induced a premature activity front with gastric onset after 19.1 (1.7) minutes in all volunteers. After atropine, erythromycin 40 mg failed to induce a premature activity front during a 60 minute period in all volunteers (p < 0.001), while sumatriptan prevented the induction of a premature activity front during a 60 minute period in all but one volunteer (p < 0.005). The number of antral contractions and their mean amplitude in the 60 minutes after erythromycin 200 mg did not differ significantly after atropine or sumatriptan versus placebo.The antral motor effects of erythromycin in humans are mediated via different pathways. The induction of a premature activity front is mediated through activation of an intrinsic cholinergic pathway, while the induction of enhanced antral contractile activity may be mediated via a pathway potentially involving activation of a muscular receptor.
Staged heart transplantation and chemotherapy as a treatment option in patients with severe cardiac light‐chain amyloidosis
Authors: Arnt V. Kristen, Falk‐Udo Sack, Stefan O. Schonland, Ute Hegenbart, Burkhard M. Helmke, Achim Koch, Philipp A. Schnabel, Christoph Röcken, Stefan Hardt, Andrew Remppis, Hartmut Goldschmidt, Matthias Karck, Anthony D. Ho, Hugo A. Katus, Thomas J. Dengler
Journal: European Journal of Heart Failure (2009)
Evi1 is essential for hematopoietic stem cell self-renewal, and its expression marks hematopoietic cells with long-term multilineage repopulating activity
Authors: Keisuke Kataoka, Tomohiko Sato, Akihide Yoshimi, Susumu Goyama, Takako Tsuruta, Hiroshi Kobayashi, Munetake Shimabe, Shunya Arai, Masahiro Nakagawa, Yoichi Imai, Keiki Kumano, Katsuyoshi Kumagai, Naoto Kubota, Takashi Kadowaki, Mineo Kurokawa
Journal: The Journal of Experimental Medicine (2011)

Ecotropic viral integration site 1 (Evi1), a transcription factor of the SET/PR domain protein family, is essential for the maintenance of hematopoietic stem cells (HSCs) in mice and is overexpressed in several myeloid malignancies. Here, we generate reporter mice in which an internal ribosome entry site (IRES)-GFP cassette is knocked-in to the Evi1 locus. Using these mice, we find that Evi1 is predominantly expressed in long-term HSCs (LT-HSCs) in adult bone marrow, and in the hematopoietic stem/progenitor fraction in the aorta-gonad-mesonephros, placenta, and fetal liver of embryos. In both fetal and adult hematopoietic systems, Evi1 expression marks cells with long-term multilineage repopulating activity. When combined with conventional HSC surface markers, sorting according to Evi1 expression markedly enhances purification of cells with HSC activity. Evi1 heterozygosity leads to marked impairment of the self-renewal capacity of LT-HSCs, whereas overexpression of Evi1 suppresses differentiation and boosts self-renewal activity. Reintroduction of Evi1, but not Mds1-Evi1, rescues the HSC defects caused by Evi1 heterozygosity. Thus, in addition to documenting a specific relationship between Evi1 expression and HSC self-renewal activity, these findings highlight the utility of Evi1-IRES-GFP reporter mice for the identification and sorting of functional HSCs.
Lack of evidence for an increased microchimerism in the circulation of patients with Sjogren's syndrome
Authors: I Toda
Journal: Annals of the Rheumatic Diseases (2001)

OBJECTIVE To examine the hypothesis that fetal microchimerism plays a part in the pathogenic process of Sjögren's syndrome (SS). METHODS Genomic DNA samples were extracted from peripheral blood whole nucleated cells and the CD34+ cell enriched fraction of patients with SS and healthy women who had male offspring as well as nulliparous women. A Y chromosome-specific sequence was detected as a marker for fetal cells by a nested polymerase chain reaction (PCR) and by DNA hybridisation combined with PCR using specific primers and probes. All procedures were performed with great care to avoid the contamination of male DNA. RESULTS A nested PCR and DNA hybridisation combined with PCR was established that can detect a single male cell out of 1.67×105 female cells. It was not possible to increase the sensitivity further because the amount of template DNA held in the PCR was limited. When these methods were used, no fetal cells were detected in any samples from patients with SS, though they were detected in whole nucleated cells from two healthy women who had delivered sons previously. CONCLUSIONS The findings indicate that circulating fetal cells in patients with SS are uncommon ( < 1 in 1.67×105), if they exist. With the conventional PCR based methods that were used, it is difficult to evaluate the quantitative difference in circulating fetal cells between patients with SS and healthy women.
Development of nevirapine resistance in infants is reduced by use of infant-only single-dose nevirapine plus zidovudine postexposure prophylaxis for the prevention of mother-to-child transmission of HIV-1
Authors: S.H. Eshleman, D.R. Hoover, S.E. Hudelson, S. Chen, S.A. Fiscus, E. Piwowar-Manning, J.B. Jackson, N.I. Kumwenda, T.E. Taha
Journal: Journal of Infection (2006)
Binding of Cryptococcus neoformans by human cultured macrophages. Requirements for multiple complement receptors and actin.
Authors: S M Levitz, A Tabuni
Journal: Journal of Clinical Investigation (1991)

We studied the receptors on human cultured macrophages (MO-M phi) responsible for binding encapsulated and isogenic mutant acapsular strains of Cryptococcus neoformans, and whether such binding leads to a phagocytic event. Both strains required opsonization with complement components in normal human serum in order for binding to occur. Binding of the acapsular, but not the encapsulated, strain led to phagocytosis. MAb directed against any of the three defined complement receptors (CR) on MO-M phi (CR1, CR3, and CR4) profoundly inhibited binding of serum-opsonized encapsulated (and to a lesser extent acapsular) organisms to MO-M phi. Immunofluorescence studies demonstrated migration of CR to the area of the cryptococcal binding site. Trypsin and elastase inhibited binding of encapsulated and, to a lesser extent, acapsular yeasts to MO-M phi. Binding of encapsulated C. neoformans was profoundly inhibited by incubation in the cold or by inhibitors of receptor capping and actin microfilaments. Thus, multiple CR appear to contribute to binding of serum-opsonized encapsulated C. neoformans by MO-M phi. Binding is an energy-dependent process that requires conformational changes in actin yet does not lead to phagocytosis of the organism. In contrast, energy is not required for binding of acapsular yeasts by MO-M phi and binding triggers phagocytosis.
Fine mapping of the human <i>AR/EDA2R</i> locus in androgenetic alopecia
Authors: F.F. Brockschmidt, A.M. Hillmer, S. Eigelshoven, S. Hanneken, S. Heilmann, S. Barth, C. Herold, T. Becker, R. Kruse, M.M. Nöthen
Journal: British Journal of Dermatology (2010)

Table S1. Haplotype analyses for rs12558842 and rs5918801 for the case–control and family-based datasets. Please note: Wiley-Blackwell are not responsible for the content or functionality of any supporting materials supplied by the authors. Any queries (other than missing material) should be directed to the corresponding author for the article. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Frequency Of Grass Pollen-specific Il-4, Il-10 And Dual Il-4 And Il10 Positive Cells In Atopic And Non-atopic Individuals In And Out Of The Pollen Season
Authors: M.H. Shamji, A. Chaker, D. Cheung, M. Poon, C. Schmidt-Weber, S.R. Durham, S.R. Durham
Journal: Journal of Allergy and Clinical Immunology (2011)
Induction and Suppression of Collagen-Induced Arthritis Is Dependent on Distinct Fcγ Receptors
Authors: Sandra Kleinau, Pernilla Martinsson, Birgitta Heyman
Journal: The Journal of Experimental Medicine (2000)

Receptors for immunoglobulin (Ig)G (FcγRs) are important for the antibody-mediated effector functions of the immune system. FcγRI and FcγRIII trigger cell activation through a common γ chain, whereas FcγRII acts as a negative regulator of antibody production and immune complex–triggered activation. Here we describe the in vivo consequences of FcγR deficiency in a mouse model of human rheumatoid arthritis. FcRγ chain–deficient mice on arthritis-susceptible DBA/1 background were immunized with collagen for induction of collagen-induced arthritis. The DBA/1 mice lacking FcRγ chain were protected from collagen-induced arthritis in contrast to wild-type mice, although both groups produced similar levels of IgG anticollagen antibodies. In comparison, DBA/1 mice lacking FcγRII developed an augmented IgG anticollagen response and arthritis. These observations suggest a crucial role of FcγRI and FcγRIII in triggering autoimmune arthritis.
Endogenous galectin-1 enforces class I–restricted TCR functional fate decisions in thymocytes
Authors: Scot D. Liu, Chan C. Whiting, Tamar Tomassian, Mabel Pang, Stephanie J. Bissel, Linda G. Baum, Valeri V. Mossine, Françoise Poirier, Margaret E. Huflejt, M. Carrie Miceli
Journal: Blood (2008)
Synaptojanin-2 Binding Protein Stabilizes the Notch Ligands DLL1 and DLL4 and Inhibits Sprouting Angiogenesis
Authors: M. Gordian Adam, Caroline Berger, Anja Feldner, Wan-Jen Yang, Joycelyn Wüstehube-Lausch, Stefanie E. Herberich, Marcel Pinder, Sabine Gesierich, Hans-Peter Hammes, Hellmut G. Augustin, Andreas Fischer
Journal: Circulation Research (2013)

The formation of novel blood vessels is initiated by vascular endothelial growth factor. Subsequently, DLL4-Notch signaling controls the selection of tip cells, which guide new sprouts, and trailing stalk cells. Notch signaling in stalk cells is induced by DLL4 on the tip cells. Moreover, DLL4 and DLL1 are expressed in the stalk cell plexus to maintain Notch signaling. Notch loss-of-function causes formation of a hyperdense vascular network with disturbed blood flow.This study was aimed at identifying novel modifiers of Notch signaling that interact with the intracellular domains of DLL1 and DLL4.Synaptojanin-2 binding protein (SYNJ2BP, also known as ARIP2) interacted with the PDZ binding motif of DLL1 and DLL4, but not with the Notch ligand Jagged-1. SYNJ2BP was preferentially expressed in stalk cells, enhanced DLL1 and DLL4 protein stability, and promoted Notch signaling in endothelial cells. SYNJ2BP induced expression of the Notch target genes HEY1, lunatic fringe (LFNG), and ephrin-B2, reduced phosphorylation of ERK1/2, and decreased expression of the angiogenic factor vascular endothelial growth factor (VEGF)-C. It inhibited the expression of genes enriched in tip cells, such as angiopoietin-2, ESM1, and Apelin, and impaired tip cell formation. SYNJ2BP inhibited endothelial cell migration, proliferation, and VEGF-induced angiogenesis. This could be rescued by blockade of Notch signaling or application of angiopoietin-2. SYNJ2BP-silenced human endothelial cells formed a functional vascular network in immunocompromised mice with significantly increased vascular density.These data identify SYNJ2BP as a novel inhibitor of tip cell formation, executing its functions predominately by promoting Delta-Notch signaling.
Clinical management and outcome of refractory asthma in the UK from the British Thoracic Society Difficult Asthma Registry: Table 1
Authors: Joan Sweeney, Chris E Brightling, Andrew Menzies-Gow, Robert Niven, Chris C Patterson, Liam G Heaney
Journal: Thorax (2012)

Refractory asthma represents a significant unmet clinical need. Data from a national online registry audited clinical outcome in 349 adults with refractory asthma from four UK specialist centres in the British Thoracic Society Difficult Asthma Network. At follow-up, lung function improved, with a reduction in important healthcare outcomes, specifically hospital admission, unscheduled healthcare visits and rescue courses of oral steroids. The most frequent therapeutic intervention was maintenance oral corticosteroids and most steroid sparing agents (apart from omalizumab) demonstrated minimal steroid sparing benefit. A significant unmet clinical need remains in this group, specifically a requirement for therapies which reduce systemic steroid exposure.
Survival outcomes by tumor human papillomavirus (HPV) status in stage III-IV oropharyngeal cancer (OPC) in RTOG 0129
Authors: M. L. Gillison, J. Harris, W. Westra, C. Chung, R. Jordan, D. Rosenthal, P. Nguyen-Tan, W. J. Spanos, K. P. Redmond, K. Ang
Journal: Journal of Clinical Oncology (2009)

6003 Background: The favorable prognosis for HPV-positive (pos) OPC requires confirmation in a clinical trial of sufficient size to account for confounding variables including smoking. Methods: A correlative study was performed to evaluate the association of tumor HPV status (THS) and survival in a randomized phase 3 trial comparing standard fractionation (FX) radiotherapy (RT) and cisplatin (cis) (100 mg/m 2 , days 1, 22, 43) to accelerated FX-RT and cis (100 mg/m 2 , days 1, 22). THS for OPC cases was determined by HPV16 in situ hybridization (ISH). Two-year overall (OS, death) and progression-free survival (PFS, progression, salvage surgery, death) for patients with HPV-pos and HPV-negative [neg] OPC were estimated along with 95% confidence intervals (CIs) by Kaplan-Meier method and compared by log-rank test. Hazard ratios (HR) for OS/PFS comparing HPV-pos to HPV-neg OPC after adjustment for treatment assignment, age, race, T and N stage, and smoking (&lt; or ≥ 20 pack-years [p-y]) were estimated by use of Cox models along with 95% CIs with multiple imputation for cases with undetermined THS and/or missing p-y. Results: THS was evaluable for 73% (317/433) of OPC cases and 60.6% (55.2–65.9) were HPV16-positive. OS/PFS outcomes were similar for cases with and without HPV determination. After median follow-up of 4.4 years, cases with HPV-pos OPC had better OS (p &lt; 0.0001; 2-year 87.5% [82.8–92.2] vs 67.2% [58.9–75.4]) and PFS (p &lt; 0.0001; 2-year 71.9% [65.5–78.2] vs 51.2% [42.4–59.9]). Patients with HPV-pos OPC had a 59% reduction in risk of death (HR 0.41 [0.27–0.64]) and a 46% reduction in risk of progression or death (HR 0.54 [0.37–0.78]). Results with and without imputation were consistent. The hazard of death was elevated for HPV-neg OPC with ≥ 20 p-y (HR 4.33), HPV-neg OPC with &lt; 20 p-y (HR 2.41), and HPV-pos OPC with ≥ 20 p-y (HR 1.79), relative to HPV-pos OPC with &lt;20 p-y. Second primary tumors were less common among HPV-pos cases and patterns of first failure were similar. Conclusions: Tumor HPV status is strongly associated with OS/PFS among OPC patients receiving standard of care chemo-radiation, and should now be a stratification factor for all clinical trials including OPC cases, and separate trials based on THS should be considered. No significant financial relationships to disclose.