tbuckley/cabot-search huggingface dataset:
Interaction of FkpA, a peptidyl-prolyl<i>cis</i>/<i>trans</i>isomerase with EspP autotransporter protein
Authors: Fernando Ruiz-Perez, Ian R. Henderson, James P. Nataro
Journal: Gut Microbes (2010)

The serine protease autotransporters of Enterobacteriaceae (SPATEs) represent a large class of proteases with contributions to virulence. They are synthesized with a C-terminal domain that forms a β-barrel pore in the outer membrane implicated in translocation of the N-terminal 'passenger' domain across the outer membrane. The most recent model for autotransporter secretion comprises entry to the periplasm via the Sec apparatus, followed by the insertion of the C-terminus into the outer membrane as a β-barrel protein and accompanied by translocation of the passenger domain to the bacterial cell surface, all of this with the assistance of the Bam complex insertase/foldase and periplasmic chaperone proteins. We have recently observed direct involvement of periplasmic chaperones in the biogenesis of EspP, a prototypical autotransporter protein produced by Escherichia coli O157:H7. Using molecular and biophysical approaches we demonstrated for the first time, direct protein-protein interactions between the periplasmic SurA and DegP chaperones and either the EspP-β or EspP passenger domains. Such chaperone interactions took place on conserved aromatic residues on the SPATE family. In this report, we now demonstrate direct binding of the periplasmic chaperone FkpA to the EspP passanger domain in Surface Plasmon Resonance experiments with relatively high affinity. We also provide evidence of interaction between the SurA and Skp chaperones with the Bam. These findings in conjunction with newly published data support the role of chaperones in preventing misfolding of AT passenger domains before translocation throughout the Bam complex.
Patients Presenting With CNS Lesions
Authors: W.Y. Au, K.N. Hung, F. Loong, S.K. Ma
Journal: Journal of Clinical Oncology (2003)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2003.11.086 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 14581430 Patients Presenting With CNS Lesions CASE 3. SEQUENTIAL MYELOPROLIFERATIVE DISEASE AND GLIOBLASTOMA MULTIFORME IN A RENAL TRANSPLANT RECIPIENT W.Y. AuxW.Y. AuSearch for articles by this author , K.N. HungxK.N. HungSearch for articles by this author , F. LoongxF. LoongSearch for articles by this author , S.K. MaxS.K. MaSearch for articles by this author Show More Departments of Medicine, Neurosurgery, and Pathology, Queen Mary Hospital, Hong Kong https://doi.org/10.1200/JCO.2003.11.086 First Page Full Text PDF Figures and Tables © 2003 by American Society of Clinical Oncology
Brief Communication: Organ-Specific Metastasis of a Transplantable Reticulum Cell Sarcoma2
Authors: Richard C. Parks
Journal: JNCI Journal of the National Cancer Institute (1974)

The fate and distribution of a selectively metastasizing transplantable murine reticulum cell sarcoma (RCS) were examined with the radioactive DNA precursor analog 125I-5_iodo_2′-deoxyuridine used as an intracellular marker. Most intravenously injected RCS cells died or were destroyed within the host. Immediately after administration of the tumor cells, the lungs and liver had the greatest accumulation of cells. As time progressed, the quantity of RCS cells in the lungs, liver, and kidney of the inoculated mice diminished, whereas the number of tumor cells in the spleen increased significantly. Killed animals with RCS revealed only splenic and lymph node metastasis. The data show that the preferential metastasis of the RCS is in part dependent on the type of tissue in which the tumor cells are arrested.
Survival in patients with class III idiopathic pulmonary arterial hypertension treated with first line oral bosentan compared with an historical cohort of patients started on intravenous epoprostenol
Authors: O Sitbon
Journal: Thorax (2005)

The oral dual endothelin receptor antagonist bosentan improves exercise capacity and delays clinical worsening in patients with pulmonary arterial hypertension, but its use could delay starting intravenous epoprostenol, a life saving treatment.Survival in patients with functional class III idiopathic pulmonary arterial hypertension (PAH) treated with bosentan in clinical trials was compared with historical data from similar patients treated with epoprostenol in the clinic. Statistical methods were used to adjust for possible underlying differences between the two groups.Baseline factors for the 139 patients treated with bosentan and the 346 treated with epoprostenol suggested that the epoprostenol cohort had more severe disease-that is, a lower cardiac index (2.01 v 2.39 l/min/m2) and higher pressures and resistance. Kaplan-Meier survival estimates after 1 and 2 years were 97% and 91%, respectively, in the bosentan cohort and 91% and 84% in the epoprostenol cohort. Cox regression analyses adjusting for differences in baseline factors showed a greater probability of death in the epoprostenol cohort (hazard ratio 2.2 (95% confidence interval 1.2 to 4.0) in the model adjusted for haemodynamics). Alternative regression analyses and analyses to adjust for different data collection dates gave consistently similar results. When matched cohorts of 83 patients each were selected, survival estimates were similar. In the bosentan cohort 87% and 75% of patients followed for 1 and 2 years, respectively, remained on monotherapy.No evidence was found to suggest that initial treatment with oral bosentan, followed by or with the addition of other treatment if needed, adversely affected the long term outcome compared with initial intravenous epoprostenol in patients with class III idiopathic PAH.
Of mice and (wo)men: factors influencing successful implantation including endocannabinoids
Authors: S. E. Melford, A. H. Taylor, J. C. Konje
Journal: Human Reproduction Update (2013)

BACKGROUNDOne in six couples suffer from infertility problems requiring in vitro fertilization therapy; however, the average birth rates in the past decade per IVF–embryo transfer cycle have remained static at around 25%. Although implantation failure is considered a major cause of infertility in otherwise healthy women, inadequate uterine receptivity is considered to be responsible for only two-thirds of implantation failures and problems with the embryo itself are responsible for the other third, such that only 30% of oocytes that are contacted by sperm result in successful human term pregnancies. Due to technical and ethical considerations, most research into the factors affecting the success of embryo implantation has been performed in mice, but this may be less than ideal.
Longitudinal Changes in Estimated and Measured GFR in Type 1 Diabetes
Authors: Ian H. de Boer, Wanjie Sun, Patricia A. Cleary, John M. Lachin, Mark E. Molitch, Bernard Zinman, Michael W. Steffes
Journal: Journal of the American Society of Nephrology (2013)

Estimation of GFR from serum concentrations of creatinine and cystatin C has been refined using cross-sectional data from large numbers of people. However, the ability of the improved estimating equations to identify changes in GFR within individuals over time has not been rigorously evaluated, particularly within the normal range of GFR. In cross-sectional and longitudinal analyses of 1441 participants in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study with type 1 diabetes, we compared GFR estimated from creatinine (eGFR(Cr)), cystatin C (eGFR(Cys)), or both (eGFR(Cr+Cys)) with iothalamate GFR (iGFR), including changes in each over time. Mean (SD) iGFR was 122.7 (21.0) ml/min per 1.73 m(2). In cross-sectional analyses, eGFR(Cr+Cys) estimated iGFR with the highest correlation (r=0.48 versus 0.39-0.42), precision, and accuracy. In longitudinal analyses, change in eGFR(Cr+Cys) best estimated change in iGFR; however, differences between estimates were small, and no estimate accurately classified change in iGFR. Over a median 23 years of follow-up, mean rate of change in eGFR was similar across estimates of eGFR(Cr), eGFR(Cys), and eGFR(Cr+Cys) (-1.37, -1.11, and -1.29 ml/min per 1.73 m(2) per year, respectively). Associations of BP and hemoglobin A1c with change in eGFR were strongest for eGFR(Cys) and eGFR(Cr+Cys). Together, these results suggest that the addition of cystatin C to creatinine to estimate GFR may improve identification of the causes and consequences of GFR loss in type 1 diabetes, but may not meaningfully improve the tracking of GFR in clinical care.
AAV-1–mediated gene transfer to skeletal muscle in humans results in dose-dependent activation of capsid-specific T cells
Authors: Federico Mingozzi, Janneke J. Meulenberg, Daniel J. Hui, Etiena Basner-Tschakarjan, Nicole C. Hasbrouck, Shyrie A. Edmonson, Natalie A. Hutnick, Michael R. Betts, John J. Kastelein, Erik S. Stroes, Katherine A. High
Journal: Blood (2009)
Chest wall tenderness does not exclude pulmonary embolism
Authors: S M Menzies
Journal: Thorax (2005)

▴ Le Gal G, Testuz A, Righini M, et al . Reproduction of chest pain by palpation: diagnostic accuracy in suspected pulmonary embolism. BMJ2005;330:452–3 [OpenUrl][1][FREE Full Text][2] Pulmonary embolism (PE) is usually associated with pleuritic chest pain, and the presence of chest pain that is reproducible by palpation may lead a clinician to discard this diagnosis. This study assessed whether palpable chest pain predicted the likely absence of … [1]: {openurl}?query=rft_id%253Dinfo%253Apmid%252F15684025%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=FULL&journalCode=bmj&resid=330/7489/452&atom=%2Fthoraxjnl%2F60%2F6%2F461.atom
<i>N</i>-Methyl-<scp>d</scp>-Aspartate Receptor Expression in the Nucleus Tractus Solitarii and Maturation of Hypoxic Ventilatory Response in the Rat
Authors: PATRICIA J. OHTAKE, NARONG SIMAKAJORNBOON, MATTHEW D. FEHNIGER, YING-DAN XUE, DAVID GOZAL
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Ventilatory responses to hypoxia are critically dependent on the activation of N-methyl-d-aspartate (NMDA) glutamate receptors in adult rats. To investigate the role of NMDA receptors during development, we measured minute ventilation (V˙ e) in 5-d, 10-d, and 15-d–old intact, freely behaving rat pups, using whole-body plethy-smography during breathing of room air (RA), during hypoxia (10% O2), and during hypercapnia (5% CO2), both before and after administration of the NMDA receptor antagonist MK-801 (1 mg/kg intraperitoneally). MK-801 did not affect V˙ e in RA in the younger animals, but increased both V˙ e and respiratory frequency in the 15-d– old rats. Similarly, V˙ e responses to hypoxia were unchanged from control values in young animals, whereas V˙ e respones in 15-d–old rats showed significant attenuation under hypoxic conditions. In contrast, hypercapnic ventilatory responses were not altered by administration of MK-801 to rats at any age. To further examine the topographic distribution patterns of NMDA receptor-positive neurons in the caudal brainstem and their recruitment during hypoxia, we performed immunostaining for NMDA receptor subunit NR1 and c-fos after exposing rat pups at postnatal ages of 2 d, 5 d, 10 d, and 20 d and adult rats to either RA or 10% O2 for 3 h. With advancing postnatal age, NR1 expression increased in the nucleus tractus solitarii (nTS), whereas it decreased in the hypoglossal nucleus. Hypoxic exposure was associated with increased c-fos expression in the nTS at all postnatal ages, with a marked increase occurring in ⩾ 10-d–old animals. Similarly, the density of c-fos–NR1 double-labeled neurons during hypoxia progressively increased with maturation. We conclude that NMDA glutamate receptor expression in the caudal brainstem undergoes postnatal maturation that closely parallels the development of the hypoxic ventilatory response in the rat.
Outcome Results of the Fosinopril Versus Amlodipine Cardiovascular Events Randomized Trial (FACET) in Patients With Hypertension and NIDDM
Authors: Patrizio Tatti, Marco Pahor, Robert P Byington, Patrizia Di Mauro, Riccardo Guarisco, Giovanna Strollo, Felice Strollo
Journal: Diabetes Care (1998)

OBJECTIVE ACE inhibitors and calcium antagonists may favorably affect serum lipids and glucose metabolism. The primary aim of the Fosinopril Versus Amlodipine Cardiovascular Events Randomized Trial (FACET) was to compare the effects of fosinopril and amlodipine on serum lipids and diabetes control in NIDDM patients with hypertension. Prospectively defined cardiovascular events were assessed as secondary outcomes. RESEARCH DESIGN AND METHODS Inclusion criteria included a diagnosis of NIDDM and hypertension (systolic blood pressure of &amp;gt;140 mmHg or diastolic blood pressure of &amp;gt;90 mmHg). Exclusion criteria included a history of coronary heart disease or stroke, serum creatinine &amp;gt;1.5 mg/dl, albuminuria &amp;gt;40 μg/min, and use of lipid-lowering drugs, aspirin, or antihypertensive agents other than beta-blockers or diuretics. A total of 380 hypertensive diabetics were randomly assigned to open-label fosinopril (20 mg/day) or amlodipine (10 mg/day) and followed for up to 3.5 years. If blood pressure was not controlled, the other study drug was added. RESULTS Both treatments were effective in lowering blood pressure. At the end of followup, between the two groups there was no significant difference in total serum cholesterol, HDL cholesterol, HbA1c, fasting serum glucose, or plasma insulin. The patients receiving fosinopril had a significantly lower risk of the combined outcome of acute myocardial infarction, stroke, or hospitalized angina than those receiving amlodipine (14/189 vs. 27/191; hazards ratio = 0.49, 95% CI = 0.26–0.95). CONCLUSIONS Fosinopril and amlodipine had similar effects on biochemical measures, but the patients randomized to fosinopril had a significantly lower risk of major vascular events, compared with the patients randomized to amlodipine.
Osteoblast-Derived Factors Induce Androgen-Independent Proliferation and Expression of Prostate-Specific Antigen in Human Prostate Cancer Cells
Authors: Natalie Blaszczyk, Bassam A. Masri, Nasrin R. Mawji, Takeshi Ueda, Gavan McAlinden, Clive P. Duncan, Nicholas Bruchovsky, Hans-Udo Schweikert, Doris Schnabel, Edward C. Jones, Marianne D. Sadar
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Prostate cancer metastasizes to the skeleton to form osteoblastic lesions. Androgen ablation is the current treatment for metastatic prostate cancer. This therapy is palliative, and the disease will return in an androgen-independent form that is preceded by a rising titer of prostate-specific antigen (PSA). Here, we investigated the possibility that human osteoblasts might secrete factors that contribute to the emergence of androgen-independent prostate cancer. Experimental Design: Primary cultures of human osteoblasts were used as a source of conditioned medium (OCM). Proliferation, expression of androgen-regulated genes, and transactivation of the androgen receptor (AR) were monitored in LNCaP human prostate cancer cells in response to OCM using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Northern blot analysis, and reporter gene constructs. Levels of interleukin-6 (IL-6) present in OCM were measured, and its contribution to proliferation and expression of PSA were investigated by neutralization studies with anti IL-6 antibodies. Results: OCM increased the proliferation and expression of PSA at both the protein and RNA levels in LNCaP cells. Synergistic increases in the activities of PSA (6.1 kb)- and pARR3-tk-luciferase reporters were measured in cells cotreated with both OCM and androgen. OCM targeted the NH2-terminal domain of the AR. The effect of OCM on transcriptional activity of the AR was inhibited by an antiandrogen. Neutralizing antibodies to IL-6 blocked proliferation and expression of PSA by OCM. Conclusion: Osteoblasts secrete factors, such as IL-6, that cause androgen-independent induction of PSA gene expression and proliferation of prostate cancer cells by a mechanism that partially relies on the AR. Identifying such molecular mechanisms may lead to improved clinical management of metastatic prostate cancer.
1213 CYCLOPHILIN INHIBITOR EDP-546 IS A POTENTIAL CORNERSTONE DRUG FOR USE IN COMBINATION WITH NS5A AND PROTEASE INHIBITORS DUE TO ITS HIGH BARRIER TO HCV RESISTANCE
Authors: C.M. Owens, M.H.J. Rhodin, A. Polemeropoulos, J. Long, G. Wang, L. Jiang, Y.S. Or
Journal: Journal of Hepatology (2013)
Dream and emotion regulation: Insight from the ancient art of memory
Authors: Martin Desseilles, Catherine Duclos
Journal: Behavioral and Brain Sciences (2013)

During dreaming, as well as during wakefulness, elaborative encoding, indexing and ancient art of memory (AAOM) techniques, such as the method of loci, may coincide with emotion regulation. These techniques shed light on the link between dreaming and emotional catharsis, post-traumatic stress disorder, supermemorization during sleep as opposed to wakefulness, and the developmental role of rapid eye movement (REM) sleep in children.
Idiopathic Scoliosis in Adolescents
Authors: M. Timothy Hresko
Journal: New England Journal of Medicine (2013)

Idiopathic scoliosis affects 2% of adolescents. In adolescents with an immature skeleton, bracing is commonly recommended if there is curve progression to 25 to 45 degrees. A randomized trial comparing bracing with watchful waiting is under way.
An Expression Signature Classifies Chemotherapy-Resistant Pediatric Osteosarcoma
Authors: Michelle B. Mintz, Rebecca Sowers, Kevin M. Brown, Sara C. Hilmer, BethAnne Mazza, Andrew G. Huvos, Paul A. Meyers, Bonnie LaFleur, Wendy S. McDonough, Michael M. Henry, Keri E. Ramsey, Cristina R. Antonescu, Wen Chen, John H. Healey, Aaron Daluski, Michael E. Berens, Tobey J. MacDonald, Richard Gorlick, Dietrich A. Stephan
Journal: Cancer Research (2005)

Osteosarcoma is the most common malignant bone tumor in children. Osteosarcoma patients who respond poorly to chemotherapy are at a higher risk of relapse and adverse outcome. Therefore, it was the aim of this study to identify prognostic factors at the time of diagnosis to characterize the genes predictive of poor survival outcome and to identify potential novel therapeutic targets. Expression profiling of 30 osteosarcoma diagnostic biopsy samples, 15 with inferior necrosis following induction chemotherapy (Huvos I/II) and 15 with superior necrosis following induction chemotherapy (Huvos III/IV), was conducted using Affymetrix U95Av2 oligonucleotide microarrays. One hundred and four genes were found to be statistically significant and highly differentially expressed between Huvos I/II and III/IV patients. Statistically significant genes were validated on a small independent cohort comprised of osteosarcoma xenograft tumor samples. Markers of Huvos I/II response predominantly were gene products involved in extracellular matrix (ECM) microenvironment remodeling and osteoclast differentiation. A striking finding was the significant decrease in osteoprotegerin, an osteoclastogenesis inhibitory factor. Additional genes involved in osteoclastogenesis and bone resorption, which were statistically different, include annexin 2, SMAD, PLA2G2A, and TGFbeta1. ECM remodeling genes include desmoplakin, SPARCL1, biglycan, and PECAM. Gene expression of select genes involved in tumor progression, ECM remodeling, and osteoclastogenesis were validated via quantitative reverse transcription-PCR in an independent cohort. We propose that osteosarcoma tumor-driven changes in the bone microenvironment contribute to the chemotherapy-resistant phenotype and offer testable hypotheses to potentially enhance therapeutic response.
Recurrent SETBP1 mutations in atypical chronic myeloid leukemia
Authors: Rocco Piazza, Simona Valletta, Nils Winkelmann, Sara Redaelli, Roberta Spinelli, Alessandra Pirola, Laura Antolini, Luca Mologni, Carla Donadoni, Elli Papaemmanuil, Susanne Schnittger, Dong-Wook Kim, Jacqueline Boultwood, Fabio Rossi, Giuseppe Gaipa, Greta P De Martini, Paola Francia di Celle, Hyun Gyung Jang, Valeria Fantin, Graham R Bignell, Vera Magistroni, Torsten Haferlach, Enrico Maria Pogliani, Peter J Campbell, Andrew J Chase, William J Tapper, Nicholas C P Cross, Carlo Gambacorti-Passerini
Journal: Nature Genetics (2012)
Association between adrenergic receptor genotypes and beta‐blocker dose in heart failure patients: analysis from the HF‐ACTION DNA substudy
Authors: Mona Fiuzat, Megan L. Neely, Aijing Z. Starr, William E. Kraus, G. Michael Felker, Mark Donahue, Kirkwood Adams, Ileana L. Piña, David Whellan, Christopher M. O'Connor
Journal: European Journal of Heart Failure (2012)
Changes in Human Serum Amyloid A and C-Reactive Protein after Etiocholanolone-Induced Inflammation
Authors: Keith P. W. J. McAdam, Ronald J. Elin, Jean D. Sipe, Sheldon M. Wolff
Journal: Journal of Clinical Investigation (1978)

Secondary amyloidosis is a complication of diseases characterized by recurrent acute inflammation. In this study, a standardized stimulus which induced fever and inflammation was given to six normal subjects (19-24 yr old) to follow the fluctuation in concentration of serum amyloid A (SAA), the precursor of the secondary amyloid fibril protein. After a single intramuscular injection of etiocholanolone (0.3 mg/kg), blood samples were drawn twice a day for 12 days for determination of SAA by solid phase radioimmunoassay. From a base line of <100 mug/ml, the SAA concentration began rising within 12 h to a maximum value at about 48 h of 1,350-1,800 mug/ml in three males and 380-900 mug/ml in three females and returned to base line by 4-5 days. The SAA response showed a similar time response to C-reactive protein (CRP), a well-documented acute phase protein which was assayed semiquantitatively by capillary tube precipitin reaction. CRP, but not SAA, showed a quantitative correlation with the amount of fever induced by etiocholanolone. One subject exhibited a second rise in SAA and CRP concentrations after acute over-indulgence with alcohol, suggesting that acute liver damage may have caused an acute phase reaction. Thus, a controlled episode of fever and inflammation produced a prompt and prolonged elevation of SAA and CRP concentrations. Unlike SAA, CRP has not been implicated in the pathogenesis of amyloidosis, although its relationship to the P component of amyloid has recently been established.