tbuckley/cabot-search huggingface dataset:
Aberrant epigenetic modifications in peripheral blood mononuclear cells from patients with pemphigus vulgaris
Authors: M. Zhao, W. Huang, Q. Zhang, F. Gao, L. Wang, G. Zhang, Y. Su, R. Xiao, J. Zhang, M. Tang, W. Cheng, Y. Tan, Q. Lu
Journal: British Journal of Dermatology (2012)

Background Pemphigus vulgaris (PV) is an autoimmune blistering disorder with a complex aetiology involving genetic and environmental factors, most of which remain unknown. It has become increasingly evident that aberrant epigenetic modifications are associated with the occurrence and development of autoimmune skin disorders. However, it is not known whether epigenetic modifications play a role in the development of PV. Objectives To analyse DNA methylation and histone modification patterns in peripheral blood mononuclear cells (PBMCs) of patients with PV. Methods PBMC samples were isolated from 24 patients with PV and 20 healthy controls. Skin lesion biopsies and control skin specimens were obtained from 25 patients with PV and 15 healthy controls. Global DNA methylcytosine levels, as well as histone acetylation and methylation levels, were measured by enzyme‐linked immunosorbent assay. mRNA expression levels were determined using real‐time reverse transcription–polymerase chain reaction. Results Genomic DNA methylation in PBMCs of patients with PV was increased relative to controls. DNMT1 expression levels were significantly higher in PV PBMCs than in controls. MBD3 expression was repressed in PV PBMCs compared with healthy controls. Global histone H3/H4 acetylation and H3K4/H3K27 methylation levels were significantly decreased in patient PBMCs compared with healthy controls. These changes were accompanied by increased HDAC1, HDAC2 and SUV39H2 and decreased SUV39H1 and EZH2 in PV PBMCs. Conclusions Aberrant DNA methylation and histone modifications occur in PBMCs of patients with PV, possibly due to the deregulation of epigenetic modifier genes. These changes may contribute to the pathological immune responses in PV.
Multiple wheat flour allergens and cross-reactive carbohydrate determinants bind IgE in baker’s asthma
Authors: I. Sander, P. Rozynek, H.-P. Rihs, V. van Kampen, F. T. Chew, W. S. Lee, N. Kotschy-Lang, R. Merget, T. Brüning, M. Raulf-Heimsoth
Journal: Allergy (2011)

Several wheat flour allergens relevant to baker's asthma have been identified in the last 25 years. The aim of this study was to determine the frequency of sensitization to these allergens in German bakers.Using recombinant DNA technology, the following wheat flour allergens were cloned, expressed in Escherichia coli and purified: five subunits of the wheat α-amylase inhibitors (WTAI-CM1, WTAI-CM2, WTAI-CM3, WDAI-0.19 and WMAI-0.28), thioredoxin, thiol reductase or 1-cys-peroxiredoxin homologues, triosephosphate-isomerase, αβ-gliadin, serpin, glyceraldehyde-3-phosphate-dehydrogenase, a nonspecific lipid transfer protein (nsLTP), dehydrin, profilin and peroxidase. In addition, ImmunoCAPs with the recombinant allergen ω-5-gliadin and two cross-reactive carbohydrate determinants (CCDs), horse radish peroxidase (HRP) and the N-glycan of bromelain (MUXF), were used. Specific IgE was measured in wheat flour-positive sera from 40 German bakers with work-related asthma/rhinitis and 10 controls with pollinosis.Thirty bakers (75%) had IgE to at least one of the 19 single allergens. Most frequent was IgE to WDAI-0.19, HRP and MUXF (25% each), followed by WTAI-CM1 (20%), thiol reductase (16%), WTAI-CM3 (15%), WTAI-CM2 and thioredoxin (12.5%), WMAI-28, triosephosphate-isomerase, αβ-gliadin (10%), 1-cys-peroxiredoxin (7.5%), dehydrin, serpin, glyceraldehyde-3-phosphate-dehydrogenase (5%), ω-5-gliadin, nsLTP and profilin (2.5%). Fifteen bakers (38%) had IgE to any α-amylase inhibitor and 12 (30%) to at least one CCD. The controls reacted exclusively to CCDs (80%), profilin (60%), thioredoxin (30%), triosephosphate isomerase and nsLTP (10%).The single allergen sensitization profiles obtained with 17 recombinant wheat flour allergens and two CCDs revealed no major allergen for German bakers. The highest frequencies were found for α-amylase inhibitors and CCDs.
Abstract 13228: Nitroxyl (HNO) donated via Slow-Release Oral Pro-Drug Improves Ventriculo-Arterial Coupling in Conscious Dogs with Induced Heart Failure: Enhanced Load-Independent Mechano-Energetics
Authors: Carlos L del Rio, Robert S George, Bradley L Youngblood, Yukie Ueyama, Jonelle R May, David J Humphries, Craig Hartman, Doris F Cully, Robert L Hamlin, John E Reardon
Journal: Circulation (2014)

Introduction: Reduction of myocardial loading and energetic demand while enhancing function are primary needs for the treatment of heart failure (HF). Nitroxyl (HNO) produces cAMP-independent unloading and inotropic/lusitropic support in both laboratory animals and patients with HF. To date, however, the cardiovascular activity of HNO has only been investigated using short-acting parenteral donors. Aim: This study assessed the feasibility of non-parenteral (oral) HNO delivery, by evaluating the cardiovascular responses to a novel slow-release HNO prodrug given to conscious dogs with induced HF. Methods: Dogs were either used for pharmacokinetic assessments or chronically instrumented for arterial pressures and LV pressure-volume (LVPV) recordings; instrumented dogs had HF induced via chronic pacing (e.g., EF: 38 ± 1%, PRSW: 51.2 ± 0.9 mmHg+, EDP: 23 ± 2 mmHg and NT-proBNP &gt; 2500 pM/L). Data were obtained before/after oral (22.5 mg/kg) and/or before/during continuous IV infusion (65 μg/kg/min) treatment with a slow-release HNO prodrug (~30min in vitro t1/2 for release of HNO); load-independent systolic/diastolic function was examined by LVPV relationships obtained for up to 180min after the onset of dosing. Results: The slow-release HNO prodrug was bioavailable orally (%F: 40 ± 4), presenting rapid absortion (Tmax: 0.1 ± 0.5 hr, Cmax: 3.6 ± 1.3 ug/mL) and clearance (t1/2: 0.40 ± 0.01 hr, AUCinf: 4.1±0.8 hr·ug/mL). Oral HNO reduced LV preload (EDV: -7 ± 1%*), filling (EDP: -29 ± 7%*) and end-systolic pressures (ESP: -17 ± 2 %*), without concomitant changes in heart rate (HR: -4 ± 2%). Oral HNO increased stroke volume (SV: 14 ± 3%*) and ejection fraction (EF: 22 ± 3%*), while decreasing arterial elastance (Ea: -27 ± 2 %). Oral HNO enhanced load-independent inotropy (PRSW, +12 ± 2%*) and lusitropy (tau: -15 ± 3 %*, EDPVR: -50 ± 8%*), improved ventriculo-arterial coupling and decreased estimated myocardial demand (PVA: -66 ± 4%*). These effects were comparable to those obtained via IV administration (PRSW: +12 ± 1%*, Ea: -23 ± 3%*, and PVA: -51 ± 8%*). (*: P &lt; 0.05 vs. pre-dosing). Conclusions: These results demonstrate the feasibility of delivering HNO orally to improve myocardial loading and enhance systolic/diastolic function in the setting of HF.
Abstract 599: Id4 acts as a tumor suppressor by inducing apoptosis and senescence in p53-dependent manner
Authors: Derrick Jerone Morton
Journal: Cancer Research (2014)

Abstract The physiological mechanisms that can restore biological activity of mutant p53 is an area of high interest given that mutant p53 expression is observed in one third of prostate cancer and more than 50% of all cancers. Here we demonstrate that Id4 (inhibitor of differentiation-4) a dominant negative regulator of bHLH transcription factors can restore the mutant p53 transcriptional activity in prostate cancer cells. Id4 is highly expressed in the normal prostate and decreased in prostate cancer due to promoter hypermethylation. Prostate cancer cell lines: DU145 harbors mutant p53 also lack Id4 expression, and LNCaP cells with wild type p53 express Id4, whereas PC3 cells are null for p53 and express low levels of Id4. The p53 mutants (P223L and V274F) in DU145 cells are within the DNA binding domain and abrogate p53 transcriptional activity due structural de-stabilization and/or DNA interactions. Ectopic expression of Id4 in DU145 cells resulted in increased apoptosis and expression of BAX, PUMA and p21, the transcriptional targets of p53. DNA binding, p53 luciferase reporter studies and ChIP analysis demonstrated that mutant p53 gains Id4 dependent DNA binding and transcriptional activity in part due to CBP/p300 dependent acetylation of p53 at lysine 373. Loss of Id4 in LNCaP cells also abrogated wild type p53 DNA binding and transcriptional activity with concomitant loss of CBP/p300 requirement and decreased acetylation of p53. To further elucidate Id4 dependent restoration of biological activity of p53 we stably transfected p53-null cell line PC3, which has endogenous Id4 with mutant p53 mimicking DU145 cells. mRNA, protein levels and apoptosis assays were used to determine the effects on cell death and to determine if mutant p53 had the ability to transactivate upstream/downstream targets (MDM2, PUMA, and p21). Our results indicate that mutant p53 in PC3 cells were able to induce expression of downstream targets as well as effect biological processes such as apoptosis and cell cycle arrest. Also, post-translational modifications on residues lys320 and lys373 indicated activation of mutant p53. Collectively, based on our studies we demonstrate that Id4 promotes post-translational modifications of p53, which in turn regulates p53 transcriptional activity. NIH grant #R01CA128914 Citation Format: Derrick Jerone Morton. Id4 acts as a tumor suppressor by inducing apoptosis and senescence in p53-dependent manner. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 599. doi:10.1158/1538-7445.AM2014-599
Gastroesophageal Reflux Disease
Authors: Ian G. Harnik
Journal: Annals of Internal Medicine (2015)

This issue provides a clinical overview of gastroesophageal reflux disease, focusing on diagnosis, treatment, and practice improvement. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including ACP Smart Medicine and MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic from these primary sources in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of science writers and physician writers. Editorial consultants from ACP Smart Medicine and MKSAP provide expert review of the content. Readers who are interested in these primary resources for more detail can consult http://smartmedicine.acponline.org, http://mksap.acponline.org, and other resources referenced in each issue of In the Clinic.
Haematologist may face disciplinary action for research fraud
Authors: Annette Tuffs
Journal: BMJ (2001)

Roland Mertelsmann, the Freiburg haematologist implicated in one of Germany's most serious cases of forged research, cannot be proved to have had deliberate involvement in fraud, a new report states.

However, Wolfgang Jaeger, the president of Freiburg University, has announced that disciplinary action might still be taken against Professor Mertelsmann after a university committee found serious irregularities in several of his papers.

In 1997 Professor Mertelsmann's former coworkers Friedhelm Hermann and Marion Brach, then professors at Ulm and Lubeck universities, were discovered to have committed a series of forgeries, mainly in papers on leukaemia and …
Textbook of Internal Medicine.
Authors: William N Kelley, Vincent T DeVita, Herbert L. Dupont
Journal: Annals of Internal Medicine (1991)

This two-volume set emphasizes practicality and now includes features designed to provide authoritative answers to the questions and problems faced by students and practitioners every day. Each section includes a series of Approach to Patients chapters focusing on evaluation and work-up. Also included are complete descriptions of disease-specific entities, with Indications for Referrals and Indications for Hospitalization highlighted for quick reference. There is also a Rapid Access Guide at the front of the book summarizing key facts pertaining to the most important disease entities or clinical problems. A free diskette packaged with the single volume contains 250 questions in an interactive format and keyed to the text.
Prevention of congenital rubella and congenital varicella in Europe
Authors: E Pandolfi, G Chiaradia, M Moncada, L Rava, A  E Tozzi
Journal: Eurosurveillance (2009)

Despite the availability of safe and efficacious vaccines, cases of congenital rubella and varicella syndrome still occur in Europe. As of 2004, several countries had high proportions of women of childbearing age that were susceptible to rubella and varicella virus infection.
Role of Drugs and Alcohol in Patients with Head Injury
Authors: M J Boyle, L Vella, E Moloney
Journal: Journal of the Royal Society of Medicine (1991)

In an effort to define the role that substance abuse has to play in head injuries, a prospective study of 204 patients presenting to the Accident and Emergency (A&E) Department over a 10-week period was carried out. Urine samples were collected and assayed for the presence of common drugs of abuse and alcohol. One or other substance (drugs or alcohol) was detected in 43% of patients. The association between alcohol and head injuries has been confirmed and the importance of drugs in this area has been addressed and found to be of some significance. More rapid and accurate methods of assaying these substances may improve our management of head injury patients.
Clinical Diagnosis of Urinary Tract Infection
Authors: Alastair D. Hay, Tom Fahey
Journal: JAMA (2002)

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Abstract 2758: Development of small molecule Bax agonists for lung cancer treatment
Authors: Meiguo Xin, Rui Li, Dongkyoo Park, Taofeek K. Owonikoko, Gabriel L. Sica, Patrick E. Corsino, Jia Zhou, Chunyong Ding, Andrew T. Magis, Suresh S. Ramalingam, Walter J. Curran, Fadlo R. Khuri, Xingming Deng
Journal: Cancer Research (2014)

Abstract Bax, a central death regulator, is required at the decisional stage of apoptosis. We recently discovered that the serine(S) 184 site on Bax is a critical functional switch for controlling the proapoptotic activity of Bax. The structural pocket around the S184 residue holds great promise as an ideal target for small molecule docking. We therefore employed the S184 residue as a docking site for screening small molecule therapeutic agents using the UCSF DOCK program suite and the NCI library of small molecules. Three compounds named small molecule Bax agonists (i.e. SMBA1, SMBA2 and SMBA3) were found to induce a conformational change of Bax by blocking phosphorylation of its S184 site, facilitating Bax insertion into mitochondrial membranes and formation of Bax oligomers leading to cytochrome c release and apoptosis in human lung cancer cells. Intriguingly, SMBA1 potently suppresses lung tumor growth via apoptosis in vivo without significant normal tissue toxicity. Survival outcomes remain very poor for lung cancer patients due to resistance to standard therapeutic interventions with radiation and systemic chemotherapy. Development of novel Bax agonists as an entirely new class of anti-cancer drugs has translational value to foster novel strategies for the treatment of lung cancer and other Bax expressing malignancies. Citation Format: Meiguo Xin, Rui Li, Dongkyoo Park, Taofeek K. Owonikoko, Gabriel L. Sica, Patrick E. Corsino, Jia Zhou, Chunyong Ding, Andrew T. Magis, Suresh S. Ramalingam, Walter J. Curran, Fadlo R. Khuri, Xingming Deng. Development of small molecule Bax agonists for lung cancer treatment. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2758. doi:10.1158/1538-7445.AM2014-2758
Abstract 18046: Pim1 Kinase Overexpression Enhances ckit+ Cardiac Stem Cells Cardioreparative Ability After Intramyocardial Delivery in a Swine Model
Authors: Vasileios Karantalis, Viky Y Suncion, Frederic McCall, Bo Wang, Luiza Bagno, Samuel Golpanian, Ariel Wolf, Adam Williams, Jose Rodriguez, David Valdes, Marcos Rosado, Sadia Mohsin, Mark Sussman, Jose Da Silva, Azorides Morales, Joshua M Hare
Journal: Circulation (2014)

Introduction: Pim-1 kinase plays an important role in cell division, survival and commitment of precursor cells towards a myocardial lineage. Hypothesis: We hypothesized that overexpression of Pim1 in ckit+ cardiac stem cell (CSCs) enhances their cardioreparative effect Methods: We treated immunosuppressed Yorkshire swine (n=29) with human ckit+ CSCs (n=10), Pim1 modified human ckit+ CSCs (n=9) or PBS (n=10) two weeks after MI. Cardiac MRI and PV loops were obtained before and after cell administration. Results: Whereas both pim1- and pim1+ c-kit cells reduced MI size, the Pim1 group had a ~3-fold decrease in scar mass at 8 weeks post transplantation compared to ckit+ (–29.2±2.7% vs. –8.4±0.7%, p<0.003). Pim1+ CSC injections also produced a 2-fold increase of viable mass compared to ckit+ CSCs at 8 weeks (113.7±7.2% vs 65.6±6.8%, p<0.003; Fig. 1B), a greater increase in regional contractility (Ecc) at infarct (–10±1.1 vs. –6.1±0.3, p<0.05, Fig. 1D) and border zones (–12.3±1 vs. –8.4±0.5, p<0.05; Fig. 1E)....
Abstract MP43: Association of White Blood Cell Count and Differential with the Incidence of Atrial Fibrillation: The Atherosclerosis Risk in Communities Study
Authors: Jeffrey R Misialek, Wobo Bekwelem, Lin Y Chen, Laura R Loehr, Sunil K Agarwal, Elsayed Z Soliman, Faye L Lopez, Alvaro Alonso
Journal: Circulation (2013)

Introduction: White blood cell (WBC) count was associated with incident atrial fibrillation (AF) in a small, community-based study. To date, the association of WBC count and differential with AF in...
Short communication: Analysis of CD4+ T‐cell gene expression in allergic subjects using two different microarray platforms
Authors: N. N. Hansel, C. Cheadle, G. B. Diette, J. Wright, K. M. Thompson, K. C. Barnes, S. N. Georas
Journal: Allergy (2008)

Background: Allergic diseases are thought to involve dysregulated activation of T cells including CD4+ lymphocytes. T‐cell activation results in changes in gene expression, but the optimal method to study gene expression profiles in T cells, and how this changes over time, are not known. Methods: Circulating CD4+ T cells were obtained from subjects with atopic asthma, nonatopic asthma or nonallergic controls, and total mRNA was rapidly isolated. Atopy was defined as positive skin prick test to one of nine allergens. Gene expression was analyzed using hybridization and Affymetrix ® oligonucleotide arrays (Hu133A and Hu133B chips, n = 84), or by reverse transcription‐polymerase chain reaction (RT‐PCR) with a pathway‐targeted array (Human Th1–Th2–Th3 RT 2 Profiler TM PCR Array, Superarray, n = 16). Results: Using Affymetrix arrays, it was difficult to discern a dominant allergy‐associated profile because of heterogeneity in gene expression profiles. In contrast, a Th2‐like signature was evident using RT‐PCR arrays with increased expression of expected genes (e.g. IL‐4, 5, 9, and 13, all P &lt; 0.05) as well as unexpected gene transcripts (e.g. osteopontin). Gene expression profiles were relatively stable over time in circulating CD4+ T cells from two subjects using both platforms. Conclusions: Unstimulated CD4+ T cells isolated from allergic subjects express a characteristic profile of genes when analyzed using RT‐PCR based microarrays.
LSC 2011 Abstract: The role of lipoxin A4 in the chronic obstructive pulmonary disease
Authors: Liga Balode, Gunta Strazda, Normunds Jurka, Uldis Kopeika, Agnese Kislina, Marina Beinare, Maris Bukovskis, Immanuels Taivans
Journal: European Respiratory Journal (2011)

The aim: Chronic obstructive pulmonary disease (COPD) is characterized by persistent inflammatory reaction with a dominance of neutrophil involvement. It is established, that during a healing of acute inflammation, a switching of arachidonic acid (AA) metabolism from leukotriene (Lt) to lipoxin (LX) production occurs. Therefore we hypothesized that in COPD patients the lipoxin production could be insufficient. Hence we measured the content of LXA4 and LtB4 in induced sputum supernatant (IS) in COPD patients and healthy subjects.

Materials and methods: 17 COPD patients and 7 healthy persons were studied. The age and gender ratios were similar in both groups. Sputum induction was performed according to the ERS protocol. LXA4 and LtB4 content in sputum supernatant was assessed by ELISA.

Results: COPD patients had decreased concentration of LXA4 in induced sputum compared to healthy persons (0,514 ng/ml and 1,310 ng/ml, respectively, p=0,00784).

LtB4 content in induced sputum did not significantly differ between COPD group and healthy persons group (3,551 ng/ml and 3,754 ng/ml, respectively). The ratio LtB4/LXA4 in COPD patients was three times higher compared to healthy persons (ie. 9,816 ng/ml and 3,425 ng/ml; p=0.00982).

Conclusions: We concluded that the chronic obstructive lung disease is characterized by suppressed production of lipoxins. This insufficiency may be responsible for a persistence of neutrophilic inflammation in airways.