tbuckley/cabot-search huggingface dataset:
Immunogenetics of human haptoglobins
Authors: Jamshid Javid, Wendy Yingling
Journal: Journal of Clinical Investigation (1968)

Using a radioimmunoassay method in conjunction with double diffusion studies, we characterized the antigenic determinants of the three Hp Bellevue phenotypes. An antigenic model based on these data indicates that each phenotype comprises a heterogeneous group of proteins with properties depending on their content of normal (hpβ) and of mutant (hpβ-Bellevue) chains of haptoglobin. The loss of the hemoglobin binding capacity and of a specific Hb-sensitive antigenic determinant is a consequence of the structural alteration in hpβ-Bellevue and is expressed to various extents by the populations of proteins containing this chain. It is suggested that those molecules with a preponderance of mutant β-chains are without significant hemoglobin binding capacity and are degraded more slowly in vivo than the ones capable of hemoglobin binding.
Risk Factors for Acute Graft-Versus-Host Disease After Allogeneic Blood Stem Cell Transplantation
Authors: Donna Przepiorka, Terry L. Smith, Jody Folloder, Issa Khouri, Naoto T. Ueno, Rakesh Mehra, Martin Körbling, Yang O. Huh, Sergio Giralt, James Gajewski, Michele Donato, Karen Cleary, David Claxton, Ira Braunschweig, Koen van Besien, Borje S. Andersson, Paolo Anderlini, Richard Champlin
Journal: Blood (1999)
Abstract P139: Duration of Childhood Obesity and Relation to Middle-Age Obstructive Sleep Apnea Risk: The Bogalusa Heart Study
Authors: Tian Hu, Suzie Bertisch, Wei Chen, Emily Harville, Susan Redline, Lydia Bazzano
Journal: Circulation (2015)

Background: Persons with obesity have a high risk of obstructive sleep apnea (OSA); however, the risk duration of childhood obesity confers on later OSA is not clear. Methods: We prospectively examined the association between duration of overweight and obesity (OW) in childhood and subsequent risk of OSA in 844 middle-aged adults with ≥ 2 measures of body mass index (BMI) between 4 and 18 yrs of age. Childhood OW was defined using age and gender specific BMI ≥85th percentile based on 2000 CDC Growth Charts. Duration of OW was calculated using the presence or absence of OW at each follow-up examination: For participants normal weight at baseline who then became and remained OW through the last examination, or participants who were OW throughout, duration was calculated as the cumulative number of consecutive OW yrs. If participants were OW then ever became normal weight during childhood (N=84), duration was not calculated. After an mean follow-up period of 35 years (in 2010; Interquartile: 1yr), high-risk ...
Task force 2: Investigator participation in clinical research
Authors: Robert M. Califf, Steven E. Nissen, Anthony N. DeMaria, Erik Magnus Ohman, Bertram Pitt, James T. Willerson, David W. Bilheimer, Jay N. Cohn, David W. Feigal, Lindsay Hampson, Beverly H. Lorell, Carl J. Pepine, Richard L. Popp
Journal: Journal of the American College of Cardiology (2004)
Aspergillus-PCR in bronchoalveolar lavage for detection of invasive fungal disease in immunocompromised patients
Authors: Michael Buess, Gieri Cathomas, Jörg Halter, Lilian Junker, Peter Grendelmeier, Michael Tamm, Daiana Stolz
Journal: European Respiratory Journal (2011)

Introduction:  Invasive fungal disease (IFD) is a frequent and serious infectious complication in neutropenic patients. We evaluated the diagnostic accuracy of conventional nested PCR in the bronchoalveolar fluid to diagnose IFD in severe immunocompromised patients.   Methods:  191 consecutive patients undergoing bronchoscopy for suspected pulmonary infection were included. The probability of IFD was estimated according to the standard EORTC/NIAID classification and on clinical grounds as independently assessed by a pulmonary specialist and hematologist. Conventional nested PCR to detect aspergillus fumigatus, flavus, niger, glaucus, terreus and tomarrii were applied to 2 ml bronchoalveolar fluid.   Results:  Mean age was 50.5 y (19-80), 116 were male. There were 129 patients with hematological conditions, 26 solid organ transplant recipients, 24 auto-immune disorders, and 12 HIV. A total of 111 (58.1%) of the patients were on anti-fungal therapy at the time of bronchoscopy. According to the EORTC/NIAID classification, 2 (1%) had proven, 8 (4.2%) probable, 43 (22.5%) possible and 138 (72.3%) no IFD. Nested PCR for Aspergillus was positive in 55 cases (28.8%) - 0/2 in proven, 4/8 in probable, 10/43 in possible and 41/138 in no IFD. Anti-fungal therapy did not significantly influenced PCR results (p=0.749). Irrespective of the EORT/NIAID criteria, there was a strong clinical suspicion of IFD in 53 (27.7%) cases. From those, only 15 (28.3%) had a positive nested PCR.   Conclusion:  Conventional nested aspergillus PCR in the bronchoalveolar lavage seems to be of limited usefulness for detection of invasive fungal disease in immunocompromised patients.
Iron Regulatory Proteins Mediate Host Resistance to Salmonella Infection
Authors: Manfred Nairz, Dunja Ferring-Appel, Daniela Casarrubea, Thomas Sonnweber, Lydie Viatte, Andrea Schroll, David Haschka, Ferric C Fang, Matthias W Hentze, Guenter Weiss, Bruno Galy
Journal: Cell Host & Microbe (2015)
Regulation of cancer stem cells in multiple myeloma by hedgehog pathway signaling
Authors: Craig D. Peacock, Gregory Gesell, Ian Corcoran-Schwartz, Qiuju Wang, David N. Watkins, William H. Matsui
Journal: Cancer Research (2006)

3988  Cancer stem cells (CSC) represent the cellular compartment responsible for the initiation, maintenance, and progression of multiple human cancers. CSC retain the capacity to undergo self-renewal as well as produce differentiated cells that form the bulk of the tumor mass. Embryonic signaling pathways, such as Hedgehog (Hh), Wingless (Wnt), and Notch are required for somatic stem cell development. Aberrant re-activation of these pathways has been demonstrated in many human cancers, however their role in regulating CSC phenotypes has not been tested directly. We investigated the role of Hh signaling in the regulation of CSC by examining pathway activation within distinct cellular compartments that constitute the plasma cell malignancy multiple myeloma (MM), in which clonogenic progenitors resemble post-germinal center B cells. In both MM cell lines and clinical bone marrow samples, expression of the Hh signaling pathway components PATCHED (PTCH), SMOOTHENED (SMO), GLI1 as well as GLI-responsive reporter activity were markedly elevated compared to normal B cells and plasma cells. Furthermore, the expression of PTCH, SMO and GLI reporter activity was significantly higher in the CSC compartment compared to MM plasma cells. Treatment of MM CSC from cell lines or clinical specimens with the SMO antagonist cyclopamine inhibited clonal growth and induced phenotypic evidence of plasma cell differentiation. By contrast, treatment of MM CSC with Hh ligand induced marked expansion of this population without inducing plasma cell differentiation. We conclude that aberrant Hh signaling maintains the CSC population of MM. Inhibition of Hh signaling in MM may represent a novel therapeutic strategy that directly targets MM stem cells.
Regulation of Torpor in the Gray Mouse Lemur: Transcriptional and Translational Controls and Role of AMPK Signaling
Authors: Jing Zhang, Shannon N. Tessier, Kyle K. Biggar, Cheng-Wei Wu, Fabien Pifferi, Martine Perret, Kenneth B. Storey
Journal: Genomics Proteomics & Bioinformatics (2015)

Abstract The gray mouse lemur (Microcebus murinus) is one of few primate species that is able to enter daily torpor or prolonged hibernation in response to environmental stresses. With an emerging significance to human health research, lemurs present an optimal model for exploring molecular adaptations that regulate primate hypometabolism. A fundamental challenge is how to effectively regulate energy expensive cellular processes (e.g., transcription and translation) during transitions to/from torpor without disrupting cellular homeostasis. One such regulatory mechanism is reversible posttranslational modification of selected protein targets that offers fine cellular control without the energetic burden. This study investigates the role of phosphorylation and/or acetylation in regulating key factors involved in energy homeostasis (AMP-activated protein kinase, or AMPK, signaling pathway), mRNA translation (eukaryotic initiation factor 2α or eIF2α, eukaryotic initiation factor 4E or eIF4E, and initiation factor 4E binding protein or 4EBP), and gene transcription (histone H3) in six tissues of torpid and aroused gray mouse lemurs. Our results indicated selective tissue-specific changes of these regulatory proteins. The relative level of Thr172-phosphorylated AMPKα was significantly elevated in the heart but reduced in brown adipose tissue during daily torpor, as compared to the aroused lemurs, implicating the regulation of AMPK activity during daily torpor in these tissues. Interestingly, the levels of the phosphorylated eIFs were largely unaltered between aroused and torpid animals. Phosphorylation and acetylation of histone H3 were examined as a marker for transcriptional regulation. Compared to the aroused lemurs, level of Ser10-phosphorylated histone H3 decreased significantly in white adipose tissue during torpor, suggesting global suppression of gene transcription. However, a significant increase in acetyl-histone H3 in the heart of torpid lemurs indicated a possible stimulation of transcriptional activity of this tissue. Overall, our study demonstrates that AMPK signaling and posttranslational regulation of selected proteins may play crucial roles in the control of transcription/translation during daily torpor in mouse lemurs.
Contrast-Enhanced Ultrasound Imaging of the Vasa Vasorum
Authors: Daniel Staub, Arend F.L. Schinkel, Blai Coll, Stefano Coli, Antonius F.W. van der Steen, Jess D. Reed, Christian Krueger, Kai E. Thomenius, Dan Adam, Eric J. Sijbrands, Folkert J. ten Cate, Steven B. Feinstein
Journal: JACC. Cardiovascular imaging (2010)
Abstract 19598: Increased Risk of Repeat Coronary Revascularization is Reduced by Methotrexate or Tumor Necrosis Factor Inhibitor Treatments in Patients With Rheumatoid Arthritis
Authors: Marc Sintek, Christopher Sparrow, Eric Novak, Jasvindar Singh
Journal: Circulation (2014)

Background: Rheumatoid arthritis (RA) is a chronic inflammatory condition associated with an increased risk of atherosclerosis and cardiovascular mortality. Long term data on outcomes after percutaneous coronary intervention (PCI) is lacking in this population, specifically with regards to repeat revascularization. We investigated target lesion(TLR) and target vessel revascularization(TVR) in this population. Methods: We performed a single center retrospective case control study of RA patients post PCI. Each treated RA lesion was matched to 3 control lesions based upon procedure date, drug eluting stent use, age, vein graft intervention and diabetes mellitus. Patients were censored following the last encounter in the medical record. Primary endpoints were time to TLR and TVR. Kaplan-Meier analyses and shared frailty Cox proportional hazards models were performed to compare event free survival. Results: A total of 228 lesions (142 patients) were identified in the RA cohort and matched to 677 control lesions (540 patients). Both groups were followed for a mean of 3.8 years with no difference in repeat catheterizations. There was a trend towards more TLR (HR 1.32; 95% CI 0.97-1.80) and TVR (HR 1.15; 95% CI 0.82-1.62) in RA patients. In the RA group, patients treated with methotrexate or TNF inhibitors showed significantly less TVR (figure 1). This continued to be significant when adjusting for baseline procedural differences (adjusted HR 0.52, 95% CI 0.28-0.98). TLR was also significantly reduced (unadjusted HR 0.46; 95% CI 0.23-0.92) but failed to meet significance after adjustment (adjusted HR 0.69; 95% CI 0.37-1.28). Conclusions: RA, a chronic inflammatory condition, may put patients at risk for repeat revascularization after coronary stenting. This risk appears to be reduced by treatment with anti-inflammatory agents. This has implications for the management of RA patients post PCI and may have applicability to other inflammatory diseases such as diabetes.
Endovascular Brachytherapy and Late Thrombotic Occlusion
Authors: Erich Minar, Roswitha Wolfram, Boris Pokrajac
Journal: Circulation (2000)

of self-expanding stents may be useful in this situation.However, the actual incidence of late stent malapposition in the population treated with catheter-based intracoronary radiation and tubular stent implantation is as-yet undefined and awaits large prospective studies using intravascular ultrasound imaging.The documentation of the complications of any novel technique is of paramount importance to the scientific community.Such critical analysis should allow us to improve and enhance our knowledge rather than creating pessimism or skepticism.In this regard, the group form Vienna should be congratulated, for our mutual aim is the development of the best treatment for our patients.
Response to Letter Regarding Article, “ <sup>18</sup> F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Enables the Detection of Recurrent Same-Site Deep Vein Thrombosis by Illuminating Recently Formed, Neutrophil-Rich Thrombus”
Authors: Ahmed Tawakol, Tetsuya Hara, Jessica Truelove, Gregory R. Wojtkiewicz, William J. Hucker, Megan H. MacNabb, Anna-Liisa Brownell, Kimmo Jokivarsi, Chase W. Kessinger, Michael R. Jaff, Peter K. Henke, Ralph Weissleder, Farouc A. Jaffer
Journal: Circulation (2015)
Treg Cell Function in Rheumatoid Arthritis Is Compromised by CTLA‐4 Promoter Methylation Resulting in a Failure to Activate the Indoleamine 2,3‐Dioxygenase Pathway
Authors: Adam P. Cribbs, Alan Kennedy, Henry Penn, Jordan E. Read, Parisa Amjadi, Patricia Green, Khaja Syed, Szymon W. Manka, Fionula M. Brennan, Bernard Gregory, Richard O. Williams
Journal: Arthritis & Rheumatology (2014)

Functionally impaired Treg cells expressing abnormally low levels of CTLA-4 have been well documented in rheumatoid arthritis (RA). However, the molecular defect underlying this reduced expression is unknown. The aims of this study were to assess the role of DNA methylation in regulating CTLA-4 expression in Treg cells isolated from RA patients and to elucidate the mechanism of their reduced suppressor function.CTLA-4 expression in Treg cells from RA patients and healthy controls was measured by quantitative polymerase chain reaction (PCR) and flow cytometry. Methylation of the CTLA-4 gene promoter was analyzed by bisulfite-specific PCR, followed by sequencing. Methylation-dependent transcriptional activity of the CTLA-4 gene promoter was measured by luciferase assay, and NF-AT binding to the CTLA-4 gene promoter was determined by chromatin immunoprecipitation. The role of CTLA-4 expression in controlling Teff cells was analyzed using an autologous mixed lymphocyte reaction.Down-regulation of CTLA-4 expression in Treg cells from RA patients was caused by methylation of a previously unidentified NF-AT binding site within the CTLA-4 gene promoter. As a consequence, Treg cells were unable to induce expression and activation of the tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO), which in turn resulted in a failure to activate the immunomodulatory kynurenine pathway.We show for the first time that epigenetic modifications contribute to defective Treg cell function in RA through an inability to activate the IDO pathway. Therefore, this study sets a precedent for investigating potential therapeutic strategies aimed at reinforcing the IDO pathway in RA patients.
Prevalence and clinical correlates of extrapyramidal signs and spontaneous dyskinesia in never-medicated schizophrenic patients
Authors: A Chatterjee, M Chakos, A Koreen, S Geisler, B Sheitman, M Woerner, J M Kane, J Alvir, J A Lieberman
Journal: American Journal of Psychiatry (1995)

This study assessed the prevalence of extrapyramidal signs and spontaneous dyskinesia in neuroleptic-naive, first-episode schizophrenic patients and examined the clinical correlates.In a prospective study of the psychobiology of schizophrenia, the authors examined 89 neuroleptic-naive patients for the presence of extrapyramidal signs by using the Simpson-Angus Rating Scale and for dyskinesia by using the Tardive Dyskinesia Rating Scale.Fifteen patients (16.9%) had extrapyramidal signs, but only one had spontaneous dyskinesia at baseline. Presence of extrapyramidal signs was correlated with more negative symptoms and poorer treatment outcome that was reflected in a longer time to and lower level of remission. There was no correlation of spontaneous extrapyramidal signs with age of patient, age at onset of psychotic symptoms, or baseline psychopathology. There was no difference between patients with and without spontaneous extrapyramidal signs in terms of the subsequent development of persistent tardive dyskinesia, but the patients with spontaneous extrapyramidal signs were more likely to develop parkinsonian side effects after 8 weeks of antipsychotic treatment.Extrapyramidal signs are present in a proportion of neuroleptic-naive, first-episode schizophrenic patients, which suggests an involvement of these signs in the schizophrenic process that probably reflects basal ganglia pathology. The presence of spontaneous extrapyramidal signs seems to have prognostic significance insofar as it is linked to a poorer outcome and longer time to remission. Spontaneous dyskinesia appears to be a relatively rare finding.
Abstract 311: Defibrillation in Public Places. Who is Shocking the Patients?
Authors: Mattias Ringh, Jacob Hollenberg, Mårten Rosenqvist, Martin Jonsson, Per Nordberg, David Fredman, Leif Svensson
Journal: Circulation (2013)

Background: In 2003, survival from Out of Hospital Cardiac Arrest (OHCA) was 2,5 % in Stockholm county. To increase survival, a first responder system was implemented in 2005 in parallel with a structured Public Access Defibrillation (PAD) program. In addition, the number of “wild” public Automated External Defibrillators (AEDs) has rapidly increased over time. Aim: To evaluate the impact on survival from three different defibrillation strategies (EMS, first responders and PAD) in OHCA patients available for PAD in Stockholm County, Sweden. Methods: All witnessed cases of OHCA outside home of cardiac origin with shockable rhythm in Stockholm County 2006-2012 were considered subjects for PAD and were included in the study. 60 high incidence sites were initially selected for the PAD program, and security officers and lay responders were trained to respond to “on site” emergencies. The number of sites in the PAD program increased to 120 at the end of the study. 35 fire stations throughout the county were available for simultaneously dispatch to suspected OHCAs. By approximations based on wholesale numbers, around 1000 public AEDs were present outside the PAD program. Results: 469 OHCA cases were included in the study. Out of these, 66 % (n=311) were defibrillated by the EMS, 16% (n=77) by a first responder and in 17% (n=81) the first shock was delivered by a public AED. In 33% (n=27) the public AED was a part of the PAD program. Survival to 1-month was 33 % in cases were defibrillation was performed by the EMS (n=103), 33% if defibrillation was performed by a first responder (n=25) and 66 % (n=55) if a public AED was used. Defibrillation by EMS and first responders in patients suitable for PAD decreased over time[[Unable to Display Character: ]]from 93% to 73 %. Concurrently, defibrillation by public AEDs increased from 7% to 27% during the study period. Conclusion: [[Unable to Display Character: ]]Public AEDs significantly contributes to survival in OHCAs suitable for PAD in Stockholm County, demonstrated by a 1-month survival of 66%. In this patient population, a public AED is used in 30% of all cases and with increased use of AEDs, PAD might challenge the potential gain from EMS and first responder systems.
Tyrosine kinase profiling guides combined therapeutic strategies in head and neck cancer
Authors: R. Rodríguez-Barrueco, M. Ortíz-Ruiz, J. J. Cruz, A. Ocana, A. Pandiella
Journal: Journal of Clinical Oncology (2009)

6078 Background: Squamous cell carcinoma of the head and neck (SCCHN) is still an incurable disease in the metastatic setting. A particular subgroup of proteins implicated in the head and neck cancer are the tyrosine kinases (TK). Therapeutic inhibition of several of them including the EGF receptor with cetuximab in combination with radiotherapy or chemotherapy has shown to be clinically useful. Beyond EGFR, oncogenic activation of other TKs may be implicated in the genesis/progression of SCCHN. In this context, the identification of the TKs activated in SCCHN is a must in order to adequately target these kinases with already available inhibitors. Methods: Here we have investigated activated tyrosine kinases in head and neck cancer tumors derived from patients using a human phospho protein array for 42 receptor tyrosine kinases (RTK). Western-blot experiments were performed to validate each phospho RTK in tumors from patients. The same approach was followed in a series of head and neck cancer cell lines. In vivo xenografted models were used to study the antiproliferative effect of the combination of specific TK inhibitors against them. Results: TK receptors of the EGF and the VEGF family were the mostly activated in tumors derived from patients. 90% of patients revealed high pEGFR content. In addition, other EGFR/HER family receptors, such as HER3, were also activated (phosphorylated) in samples from patients. These data were corroborated in the SCCHN cell lines. In these cells, other RTK signalling intermediates were also active. Particularly, the Akt and FAK kinases. Combination of the anti-EGFR-HER2 TK inhibitor lapatinib with dasatinib (that targets FAK) was synergistic in vitro. Combination of lapatinib with the anti-VEGFR TK inhibitor pazopanib was inefficient in vitro, but resulted in a better trend in response in the in vivo xenografted models, as compared to the action of the single agents. Conclusions: Rational target drug combinations should be based on the identification of activated TK receptors or downstream signalling molecules. In head and neck cancer combination strategies using anti-EGFR/HER, anti-FAK, and anti-VEGFR compounds increases the action of individual treatments. These results open the door for future clinical development of these drug combinations. No significant financial relationships to disclose.
International Comparison of the Community Prevalence of Symptoms of Prostatism in Four Countries
Authors: Pierre-P. Sagnier, Cynthia J. Girman, Michael Garraway, Yoshiaki Kumamoto, Michael M. Lieber, François Richard, Gary MacFariane, Harry A. Guess, Steven J. Jacobsen, Taiji Tsukamoto, Peter Boyle
Journal: European Urology (1996)
Prenatal diagnosis of heart defects aids survival after surgery
Authors: David Spurgeon
Journal: BMJ (2001)

Babies in whom a heart defect was diagnosed before birth were more likely to survive initial surgery to correct the defect than those in whom a defect was diagnosed after birth, a new study has shown. Only two thirds of those with a postnatal diagnosis survived.

Dr Wayne Tworetzky, lead investigator of the study, said: “This is the first study to demonstrate that patients diagnosed prenatally with hypoplastic left heart syndrome have improved survival after the first stage of surgery compared to those diagnosed after birth” ( Circulation 2001;103:1269-73).

Dr Tworetzky is a clinical instructor in the cardiology department at Boston Children's Hospital. The study, which …