tbuckley/cabot-search huggingface dataset:
Sensitivity and specificity of recombinant ω‐5 gliadin‐specific IgE measurement for the diagnosis of wheat‐dependent exercise‐induced anaphylaxis
Authors: H. Matsuo, J. Dahlström, A. Tanaka, K. Kohno, H. Takahashi, M. Furumura, E. Morita
Journal: Allergy (2008)

Background: A recent study has shown that the measurement of specific IgE antibodies to B‐cell epitope peptides of wheat ω‐5 gliadin (Pep A) and high molecular weight glutenin subunit (Pep B) are useful to diagnose wheat‐dependent exercise‐induced anaphylaxis (WDEIA). Aims of the study: We sought to compare the sensitivity and specificity of the in vitro tests for measuring the specific IgE antibodies to recombinant ω‐5 gliadin (rω‐5 gliadin) with those for wheat, gluten, Pep A, and Pep B in identification of patients with WDEIA. Methods: Fifty patients with WDEIA, 25 healthy subjects and 25 patients with atopic dermatitis with specific IgE antibodies to wheat but without experience of allergic reactions after ingestion of wheat products were enrolled in this study. The concentrations of specific IgE antibodies were measured using ImmunoCAP TM . The empirical receiver operating characteristics curves (ROC) for each test were prepared and the areas under the ROC curve ( AUC ) were compared. Results: In patients with WDEIA, the sensitivities of the allergen‐specific IgE tests for wheat, gluten, Pep A, Pep B and rω‐5 gliadin were 48%, 56%, 76%, 22%, and 80%, respectively. The seven of 10 WDEIA patients with no specific IgE antibodies to rω‐5 gliadin had specific IgE antibodies to Pep B. The highest AUC (0.850) was observed in the test for rω‐5 gliadin. Conclusions: Measuring the concentration of specific IgE antibodies to rω‐5 gliadin is more useful than to wheat, gluten, or Pep A in the identification of patients with WDEIA.
Abstract 4153: Global African ancestry is not associated with lung cancer survival
Authors: Carissa C. Iverson, Sarah Fletcher, Jeffery Blume, Holli Dilks, Heidi Chen, Stephen A. Deppen, William S. Bush, Dana C. Crawford, William J. Blot, Eric L. Grogan, Melinda C. Aldrich
Journal: Cancer Research (2014)

Abstract Lung cancer is the leading cause of cancer-related mortality among men and women in the United States, accounting for 27% of all cancer-related deaths. Blacks experience poorer 5-year survival compared to whites. We hypothesized that individuals with higher global African ancestry have poorer survival compared to individuals with lower global African ancestry. We identified incident non-small cell lung cancer cases in the Southern Community Cohort Study (SCCS), a prospective study of low-income adults recruited from across the Southeast region of the United States. Individuals who donated a biospecimen were genotyped using the Illumina Human Exome BeadChip, which contains a panel of ancestry informative markers (AIMs). After standard quality control, 398 individuals (262 self-reported black and 134 self-reported white) remained for analysis. Global ancestry was estimated from 2,604 AIMs using the software program ADMIXTURE. Self-reported blacks had a median global African ancestry of 88.12%, while the median global African ancestry in self-reported whites was less than 0.01%. We estimated hazard ratios and 95% confidence intervals using Cox proportional hazard models adjusted for age, sex, body mass index (BMI), cigarettes per day, disease stage, treatment, insurance coverage, family history of lung cancer and recruitment site. BMI, age, cigarettes per day and global African ancestry were modeled using restricted cubic splines. We estimated time dependent area under the curve (AUC) for our main effects model and a main effects model with interactions, both with and without genetic ancestry. We found that the main effects model had an average AUC of 0.81. When global African ancestry was excluded, the AUC was minimally reduced to 0.80. When interactions were added to the main effects model, the AUC increased to 0.88. Removal of global ancestry from the interactions model reduced the AUC to 0.84. In the main effects model, the two most predictive variables were stage and treatment with X2 values of 36.13 (degrees of freedom, df=2) and 15.47 (df=4), respectively. While we conclude that global African ancestry has little effect on overall survival, a relationship between global African ancestry and stage or treatment remains to be investigated. Citation Format: Carissa C. Iverson, Sarah Fletcher, Jeffery Blume, Holli Dilks, Heidi Chen, Stephen A. Deppen, William S. Bush, Dana C. Crawford, William J. Blot, Eric L. Grogan, Melinda C. Aldrich. Global African ancestry is not associated with lung cancer survival. [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 4153. doi:10.1158/1538-7445.AM2014-4153
SURF1, encoding a factor involved in the biogenesis of cytochrome c oxidase, is mutated in Leigh syndrome
Authors: Zhiqing Zhu, Jianbo Yao, Timothy Johns, Katherine Fu, Isabelle De Bie, Carol Macmillan, Andrew P. Cuthbert, Robert F. Newbold, Jia-chi Wang, Mario Chevrette, Garry K. Brown, Ruth M. Brown, Eric A. Shoubridge.
Journal: Nature Genetics (1998)
Abstract 1791: 19-Substituted benzoquinone ansamycin Hsp90 inhibitors: Effects on Hsp90 co-chaperones and Hsp90-Hsf1 complexes in cellular systems
Authors: Derek A. Drechsel, Chuan-Hsin Chang, Russell Kitson, David Siegel, Christopher J. Moody, David Ross
Journal: Cancer Research (2014)

Abstract The 19-substituted benzoquinone ansamycin (BQA) class of Hsp90 inhibitors were developed to decrease the off-target toxicity of their parent unsubstituted BQAs, geldanamcyin, 17-AAG, and 17-DMAG. We have shown that 19-BQAs do not react with thiols and show decreased toxicity to liver cell systems relative to parent BQAs. As a class, Hsp90 inhibitors exhibit anti-cancer activity by decreasing the levels of Hsp90 client proteins critical to cell growth and survival. Some Hsp90 inhibitors also disrupt interaction with Hsp90 co-chaperones, including cdc37, contributing to inhibited growth. Upon inhibition, the transcription factor heat shock factor 1 (Hsf1) dissociates from Hsp90 leading to a compensatory induction of other heat shock proteins, including Hsp70 which is commonly used as a molecular biomarker of cellular Hsp90 inhibition. We undertook a detailed study of the mechanism of action of 19-BQAs in HER2-positive breast cancer cells (BT474) using 19-phenyl- and 19-methyl-DMAG as model compounds. Their ability to disrupt association of Hsp90 with the co-chaperones p23 and cdc37, the kinetics of decreased Hsp90-Hsf1 levels, nuclear Hsf1 accumulation and increases in Hsp70 levels were defined. Both 19-phenyl- and 19-methyl -DMAG disrupted Hsp90-p23 association, confirming binding of the compounds at the N-terminal ATPase site of Hsp90. 19-Phenyl-DMAG and 19-methyl-DMAG also disrupted association of Hsp90 with cdc37, although 19-phenyl-DMAG was more potent. A detailed time course of decreased levels of Hsp90 client proteins and Hsp induction showed that increased Hsp70 was a more sensitive cellular marker as it could be detected at lower drug concentrations. Increases in Hsp70 did not appear to be a generalized stress response, since 19-substituted-BQAs caused dissociation of the Hsp90-Hsf1 dimer, nuclear translocation of Hsf-1, and subsequent increases in Hsp70 levels in a temporal manner. These data indicate that 19-substituted BQAs may exhibit their growth inhibitory effects in breast cancer cells through disruption of Hsp90 and its co-chaperones, particularly cdc37. The N-terminal ATPase site binding and Hsp90 inhibitory activity of these compounds was confirmed through disruption of Hsp90-p23 and Hsp90-Hsf1 associations, respectively (Supported by NCI grant CA51210). Citation Format: Derek A. Drechsel, Chuan-Hsin Chang, Russell Kitson, David Siegel, Christopher J. Moody, David Ross. 19-Substituted benzoquinone ansamycin Hsp90 inhibitors: Effects on Hsp90 co-chaperones and Hsp90-Hsf1 complexes in cellular systems. [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 1791. doi:10.1158/1538-7445.AM2014-1791
A new biomarker for chronic lung allograft dysfunction
Authors: Mallory Pain, Pierre-Joseph Royer, Jennifer Loy, Maxime Fieux, Adrien Tissot, Philippe Lacoste, Damien Reboulleau, Sandie Parès, Karine Botturi, Antoine Magnan
Journal: European Respiratory Journal (2014)

Introduction :  Chronic lung allograft dysfunction (CLAD) is the major limitation to lung transplantation. Bronchial epithelial cells (BEC) seem to play a key role and several studies suggest their implication through epithelial to mesenchymal transition (EMT). The aim of this study was to set up  in vitro  model of co-culture for testing the impact of allogenic context on EMT in order to discover new biomarkers predictive of CLAD.   Methods :  Primary bronchial epithelial cells (PBECs) were cultured with activated T cells and monocytes from healthy patients during 4 days. Epithelial and mesenchymal markers were assessed by qPCR and western blot and secretion of cytokines was measured in culture supernatants. Potential biomarkers were assayed in plasma from CLAD and stable lung transplant recipients from the COLT cohort.   Results : Activated T cells and monocytes co-cultured with PBECs in presence of TGF-β1 had no effect on junction expression (E-cadherin, ZO-1), but increased fibronectin expression (n=4 p   Conclusion : This new  in vitro  model suggests the implication of immune cells in airway remodeling by the induction of extracellular matrix marker and suggest a link between MCP-1 and MMP-9. It appears as a relevant tool for biomarker discovery. Plasmatic MMP-9 secretion may be a valuable biomarker for CLAD.
„Missed” Upper Gastrointestinal Tract Lesions May Explain „Occult” Bleeding
Authors: None Descamps, None Schmit, None Van Gossum
Journal: Endoscopy (1999)

Background and Study Aims: Enteroscopy has been shown to be an effective diagnostic method in patients with obscure gastrointestinal bleeding. Arteriovenous malformations (AVMs) of the small bowel are the most common lesions discovered at enteroscopy. However, bleeding lesions may still be detected in the upper gastrointestinal tract even in patients who have previously undergone esophagogastroduodenoscopy. The aim of this study was to focus on these "missed" upper gastrointestinal lesions.
Anaerobic cocci and their resistance patterns to penicillin, cefoxitin, clindamycin and metronidazole: a Bulgarian study
Authors: L. Boyanova, D. Osmanliev, D. Petrov, I. Mitov, I. Usunova, S. Petrov, T.Z. Minchev
Journal: Clinical Microbiology and Infection (2000)
Abdominal pain is common in microscopic colitis despite remission : a long-term follow-up of 203 patients
Authors: Nils Nyhlin, Johan Bohr, Scott M. Montgomery, Robert Brummer, Anna Wickbom, Curt Tysk
Journal: Gut (2008)

Abdominal pain is common in microscopic colitis despite remission : a long-term follow-up of 203 patients
Abstract B32: Responses of direct in vivo melanoma xenograft cells to targeted therapeutics
Authors: Joel Basken, Mayumi Fujita, Natalie Ahn
Journal: Cancer Research (2015)

Abstract The purpose of this study was to investigate the mechanism of resistance of a melanoma cell line generated from a direct in vivo xenograft (DIVX) model. Although BRAF and MKK1/2 inhibitors have produced positive clinical responses in melanoma patients with BRAF-V600 mutations, between 25-50% of patients show intrinsic resistance. Deciphering the mechanisms of intrinsic resistance will be critical for developing future treatment strategies. MB947P cells were established from a direct in vivo xenograft of a resected metastatic melanoma and exhibited innate resistance to apoptosis induced by MKK1/2 inhibitor (AZD6244/selumetinib). In contrast, the established metastatic melanoma cell line, WM239A, showed a strong apoptotic response, induced by inhibitor. Microarray expression profiling was carried out on MB947P and WM239A cells in the presence and absence of drug. The results showed that in MB947P cells inhibitor-dependent induction of Bim was minimal. In contrast, Bim was strongly induced by inhibitor in WM239A cells, where siRNA knockdown of Bim demonstrated its requirement for the apoptotic response. This suggests that the lack of apoptotic response in MB947P cells may be caused by a block in Bim induction through an unknown mechanism. Finally, co-culture of MB947P and WM239A cells showed partial inhibition of the apoptotic response in WM239A cells after AZD6244 treatment. This suggests the potential existence of a soluble factor in MB947P cells that confers resistance to apoptosis in WM239A cells. We propose that mechanisms for resistance to apoptosis in direct in vivo xenograft cell lines may ultimately inform mechanisms for resistance in patient tumors. Citation Format: Joel Basken, Mayumi Fujita, Natalie Ahn. Responses of direct in vivo melanoma xenograft cells to targeted therapeutics. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Melanoma: From Biology to Therapy; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(14 Suppl):Abstract nr B32.
Abstract 14426: Accuracy and Usefulness of Finger Pulse Wave Analysis during Brief Deep Breathing Exercise (Respiratory Stress Response) as a Marker of Significant Coronary Artery Disease
Authors: Arthur Shiyovich, Amos Katz, Steven J Sushinsky, Yosi Blaer, Petros Okubagzi, Jamal Jafari, Ron Waksman
Journal: Circulation (2010)
Press: Press releases on trial
Authors: A. Vass
Journal: BMJ (2002)

As the main means of communication between medical journals and the media, press releases have a pivotal role in conveying scientific accuracy. But can they do that at the same time as making the results attractive to lay journalists?

A study in last week's Journal of the American Medical Association (2002;287:2856-8) found that press releases from medical journals often present data using formats that exaggerate the importance of the findings and do not routinely highlight study limitations or conflicts of interest.

The study authors, Steven Woloshin and Lisa …
Short-term clinical prediction of assaultive behavior: artifacts of research methods
Authors: L J Apperson, E P Mulvey, C W Lidz
Journal: American Journal of Psychiatry (1993)

The apparent accuracy of predictions of assaultive behavior in psychiatric inpatients varies substantially, depending on the method used to study the prediction. The authors explored the effects of different measures and sampling strategies on short-term clinical predictions of dangerousness.The index subjects were patients who were rated by intake clinicians as potentially highly assaultive on the ward (N = 32) and patients who were involuntarily committed on grounds of danger to others (N = 32). The respective comparison groups comprised patients predicted by clinicians not to be assaultive (N = 32) and patients committed for reasons other than danger to others (N = 40). The text of unit meetings and data from chart reviews were used to determine the occurrence and dates of violent acts, seclusions for violent acts or threats, and violent threats.There was a significant difference in the rate of inpatient violence between the subjects rated at admission as potentially assaultive (75.0%) and patients rated as not potentially assaultive (12.5%), but the difference in the rates of violence between the patients who were (56.0%) and were not (42.0%) involuntarily committed as dangerous to others was not significant. Most of the violent acts occurred relatively late in the hospitalization, but seclusions occurred almost exclusively in the initial stages of hospitalization.The reported accuracy of clinical predictions of assaultive behavior is markedly affected by the choice of sampling strategy, comparison group, outcome measures, and follow-up period. Including seclusion and violent threats in the outcome variable appears to lead to deceptive findings.
Generation of T cells from adult human hematopoietic stem cells and progenitors in a fetal thymic organ culture system: stimulation by tumor necrosis factor-α
Authors: Steven F. A. Weekx, Hans W. Snoeck, Fritz Offner, Magda De Smedt, Dirk R. Van Bockstaele, Griet Nijs, Marc Lenjou, Adriaan Moulijn, Inez Rodrigus, Zwi N. Berneman, Jean Plum
Journal: Blood (2000)
Glycoprotein 2 (GP2)
Authors: Hiroshi Ohno, Koji Hase
Journal: Gut Microbes (2010)

Membranous (M) cells are specialized epithelial antigen-transporting cells scattered in the follicle-associated epithelium covering the gut lymphoid follicles such as Peyer's patches. Although the importance of M cells as a main portal for luminal antigens has long been recognized, molecular mechanisms for M-cell antigen uptake has remained largely elusive. We have recently found that glycoprotein 2 (GP2) is exclusively expressed on M cells among intestinal epithelial cells and serves as an uptake receptor for a subset of commensal and pathogenic bacteria. GP2 interacts with FimH, a major component of the type 1 pilus on the outer membrane of a subset of gram-negative enterobacilli such as E. coli and Salmonella enterica. Furthermore, GP2-FimH interaction is necessary for efficient uptake of FimH+ bacteria by M cells and subsequent bacteria-specific mucosal immune responses. Pancreatic GP2 may also be involved in innate immunity by 'opsonization' of FimH+ bacteria to facilitate their egestion in feces as well as translocation across the intestinal epithelium.
Investigating allegations of research misconduct
Authors: T. Stephenson, C. Henshall, D. Henshall, A. Wilkinson, J. Rennie, T. Wright, K. Lucking, D. Hall, P. Mellor, B. Morgan, E. Hey, E. Hey, I. Chalmers
Journal: BMJ (2000)

Investigating allegations of research misconduct Worst outcome of Griffiths report would be that research becomes increasingly difficultEditor-The Griffiths report contained a critique of two specific research projects and proposals on the regulation of research generally.Hey and Chalmers express no view on these proposals. 1However, the accompanying editorial by Smith agrees with the report's main recommendations on the need for better research governance in the NHS without citing supporting evidence.The Griffiths report made three main recommendations which could inhibit clinical research.Firstly, concern about consent for research at times of stress.Most intensive care research requires consent at times of stress and if the researchers waited this research would be impossible.The financial cost of the suggested consent from a third party would inhibit research.Secondly, the inquiry stated that brain damage could not be reliably assessed at a short period of follow up and was critical that follow up was determined by the amount of funding available.To place a requirement that all research in children involves long term follow up studies would abolish much research.The resources required are not addressed.Thirdly, trusts should ensure that arrangements are in place for active monitoring of the progress of research.There is no indication that new funding will be available for this.Furthermore, "research involving vulnerable groups should be subject to an even greater degree of independent supervision than clinical research in general."Not for the first time will there be the paradox of well-meaning discrimination against children.This has been the case for trials of new drugs, in which the perceived obstacles deter research in children. 2 The Department of Health's draft research governance "to protect participants, improve quality and stop research fraud" gives no evidence of the magnitude of these problems and does not discuss the resource implications of implementation. 3"There are already powerful incentives to adhere to many of the principles" in the framework, including the law, duty of care, and high professional standards of researchers.No evidence is quoted to assess how often these safeguards fail.Unreferenced "recent enquiries into adverse incidents relating to research" are inadequate justification.Patients must be protected from inappropriate research, and informed consent must be obtained.However, extrapolating from the Griffiths report to clinical research throughout the United Kingdom must be thought through.Currently, 40% of drugs prescribed for children are not licensed, 4 partly because of the existing deterrents to research in children.More hurdles are likely to inhibit research further, 5 and ultimately it is children particularly who will suffer.
Abstract 18964: Resveratrol Prevents Iron-overload Cardiomyopathy by up Regulating Serca2a and by Exerting Anti-oxidant Effects
Authors: Subhash K Das, Wang Wang, Pavel Zhabyeyev, Brent A McLean, Dong Fan, Ratnadeep Basu, Nirmal Parajuli, Zamaneh Kassiri, Jason R Dyck, Roger J Hajjar, Nancy C Andrews, Gavin Y Oudit
Journal: Circulation (2014)

Introduction:  Iron-overload cardiomyopathy is a world wide epidemic with high morbidity and mortality which has both acquired and genetic causes. Cardiac iron-deposition results in progressive myocardial damage and dysfunction due to increased oxidative stress.   Hypothesis:  We hypothesized that resveratrol supplementation prevents oxidative stress and iron-overload cardiomyopathy.   Methods and Results:  We developed an acquired iron-overload model by treating 10 week old male C57BL6 mice sub-acutely/chronicaly with iron-dextran (5 mg/25g) i.p. for 4 or 12 wks, and a genetic model by treating 4 wk old hemojuvelin (HJV) knockout male mice with high iron diet for 6 months. The natural antioxidant, resveratrol, was given at 190 mg/kg/day. Iron-overload hearts showed significant iron deposition. Hemodynamic (+dP/dt/-dP/dt max  =1.0 vs 1.7) and echocardiographic (E/A: 1.46±0.043 vs 1.27±0.06, p 2+  transients were slowed in iron-overloaded cardiomyocytes and normalized with resveratrol treatment. In contrast, chronic iron-overload was associated with increased myocardial fibrosis in HJVKO and chronic iron-overload models. Resveratrol treatment prevented the development of diastolic dysfunction (E/A: 1.27±0.06 vs 1.67±0.13 and E’/A’:1.2±0.05 vs 0.80±0.02, p   Conclusions:  Cardiac iron-overload resulted in abnormal Ca 2+ cycling with reduced SERCA2a levels and increased myocardial fibrosis, leading to impaired myocardial relaxation and increased stiffness. Resveratrol therapy increased SERCA2a protein, decreased myocardial fibrosis leading to protection from iron-overload induced cardiac dysfunction.