tbuckley/cabot-search huggingface dataset:
Novel mechanisms of gliadin immunotoxicity?
Authors: E. Arranz, J. A. Garrote
Journal: Gut (2010)

Coeliac disease (CoD) is a chronic inflammatory intestinal disorder caused by dietary gluten proteins (prolamines) from cereals in genetically predisposed individuals. The disease is manifested by a lesion which ranges from a complete transformation of the mucosa with villus atrophy and crypt cell hyperplasia to the infiltration by lymphocytes of the epithelium and lamina propria. Gluten is uniquely resistant to gastrointestinal digestion, and gluten fragments accumulate in the intestine where they trigger two distinct immune responses, mediated by the innate and adaptive immunity, and both contribute to the pathogenesis of CoD.1 2 Although HLA-DQ2/8 is the major predisposing factor, other non-HLA genes, some of them related to the innate response,3 and/or environmental factors might contribute to the development of the disease in a small group of DQ2+ individuals.

Immunostimulatory peptides, as assessed by using lymphocyte-based systems, have been identified in gliadin and glutenins from wheat gluten, and homologues from barley and rye. All peptides which are stimulatory when tested in vitro are also harmful in vivo. The best known is the immunogenic peptide p57-89 (33mer) from α-gliadin, which is the preferred substrate for tissue transglutaminase (TGt) and once deaminated becomes a potent activator of gluten-specific DQ2-restricted CD4+ T cells from patients with CoD, characterised by interferon γ (IFNγ) production. Other peptides, …
Response-Guided Telaprevir Combination Treatment for Hepatitis C Virus Infection
Authors: Kenneth E. Sherman, Steven L. Flamm, Nezam H. Afdhal, David R. Nelson, Mark S. Sulkowski, Gregory T. Everson, Michael W. Fried, Michael Adler, Hendrik W. Reesink, Marie Martin, Abdul J. Sankoh, Nathalie Adda, Robert S. Kauffman, Shelley George, Christopher I. Wright, Fred Poordad
Journal: New England Journal of Medicine (2011)

Patients with chronic infection with hepatitis C virus (HCV) genotype 1 often need 48 weeks of peginterferon–ribavirin treatment for a sustained virologic response. We designed a noninferiority trial (noninferiority margin, −10.5%) to compare rates of sustained virologic response among patients receiving two treatment durations.
Prevalence of HCV infection in nongastric marginal zone B-cell lymphoma of MALT
Authors: L. Arcaini, S. Burcheri, A. Rossi, M. Paulli, R. Bruno, F. Passamonti, E. Brusamolino, A. Molteni, A. Pulsoni, M.C. Cox, L. Orsucci, A. Fabbri, M. Frezzato, M.T. Voso, F. Zaja, F. Montanari, M. Merli, C. Pascutto, E. Morra, S. Cortelazzo, M. Lazzarino
Journal: Annals of Oncology (2006)
Pain Simulating Heart Disease
Authors: M. G. Good
Journal: BMJ (1950)

<h3>Objective</h3> To investigate global and lobular cerebellar volumetries in patients with progressive multiple sclerosis (MS), testing the contribution of cerebellar lobular atrophy to both motor and cognitive performances. <h3>Methods</h3> Eighty-two patients with progressive MS and 46 healthy controls (HC) were enrolled in this cross-sectional study. Clinical evaluation included motor and cognitive testing: Expanded Disability Status Scale, cerebellar Functional System score, Timed 25-Foot Walk Test, 9-Hole Peg Test (9-HPT), Symbol Digit Modalities Test (SDMT), Brief Visuospatial Memory Test–Revised (BVMT) and California Verbal Learning Test II (CVLT). Cerebellar volumes were automatically obtained using the Spatially Unbiased Infratentorial Toolbox. A hierarchical multiple linear regression analysis was performed to assess the relationship between MRI variables of supratentorial and cerebellar damage (grey matter fraction, T2 lesion volume, metrics of cerebellar atrophy and cerebellar lesion volume) and motor/cognitive scores. <h3>Results</h3> Patients with MS exhibited lower cerebellar volumes compared with HC. Regression analysis showed that cerebellar metrics accounted for extra variance in both motor and cognitive performances, with cerebellar lesion volume, cerebellar Lobules VI, Crus I and VIIIa atrophy being independent predictors of 9-HPT, SDMT, BVMT and CVLT performances. <h3>Conclusions</h3> Atrophy of specific cerebellar lobules explains different aspects of motor and cognitive disability in patients with progressive MS. Investigation of cerebellar involvement provides further insight into the pathophysiological basis of clinical disability in progressive MS.
High-mobility group box 2 is associated with prognosis of glioblastoma by promoting cell viability, invasion, and chemotherapeutic resistance
Authors: Zhe Bao Wu, Lin Cai, Shao Jian Lin, Zhen Kun Xiong, Jiang Long Lu, Ying Mao, Yu Yao, Liang Fu Zhou
Journal: Neuro-Oncology (2013)

The expression profile of high-mobility group box 2 (HMGB2) in patients with glioblastoma multiforme (GBM) and its clinical signature with underlying mechanisms were not fully explored.HMGB2 protein levels were measured in 51 GBM patients by immunohistochemical studies. To clarify the precise role of HMGB2 on cell invasion and viability of 3 GBM cell lines, we did in vitro and in vivo analyses with lentivirus vectors and small interfering RNA. Transwell invasion assays and wound-healing assays were used to analyze the invasion of GBM cells. Expression of p53 and matrix metalloproteinase 2/tissue inhibitors of metalloproteinase 2 (MMP2/TIMP2) protein was analyzed by Western blot.HMGB2 protein expression was significantly higher in GBM than in controlled brain tissues (P < .0001). HMGB2 overexpression was significantly correlated with shorter overall survival time, which was the only independent prognostic factor for overall survival in a multivariate analysis (P = .017). HMGB2 knockdown by small interfering RNA decreased cell viability and invasion in vitro and significantly decreased tumor volume in vivo, which might be involved in the change of p53 expression and the balance of MMP2/TIMP2. Moreover, silencing of HMGB2 could significantly increase the sensitivity of GBM cells to temozolomide chemotherapy.Our present data suggest that HMGB2 expression is a significant prognostic factor and might play an important role in cell invasion and temozolomide-induced chemotherapeutic sensitivity of GBM. This study highlights the importance of HMGB2 as a novel prognostic marker and an attractive therapeutic target of GBM.
The Relationship Among Homocysteine, Creatinine Clearance, and Albuminuria in Patients With Type 2 Diabetes
Authors: Linda Davies, Errol G. Wilmshurst, Aidan McElduff, Jenny Gunton, Phillip Clifton-Bligh, Gregory R. Fulcher
Journal: Diabetes Care (2001)

Although it is accepted that elevated plasma homocysteine (tHcy) levels occur in end-stage renal disease and type 2 diabetes, the changes with milder renal dysfunction (e.g., microalbuminuria) are less clearly established. This study explores the relationship among tHcy, creatinine clearance (Ccr), and albumin excretion rate (AER) in a population with type 2 diabetes.A total of 260 patients with type 2 diabetes were screened in our outpatient clinic during 10 months. Fasting blood samples were collected, and AER was calculated from an overnight timed urine sample. Ccr was calculated using the Cockroft-Gault formula.A total of 198 subjects (76%) had normoalbuminuria (<20 microg/min), 50 subjects (19%) had microalbuminuria (20-200 microg/min), and 12 subjects (5%) had macroalbuminuria (>or=200 microg/min). Those with microalbuminuria had higher levels of tHcy than those with normoalbuminuria (13.2 +/- 7.8 vs. 11.3 +/- 4.6 micromol/l, P < 0.05). Patients were then subdivided based on low Ccr (<80 ml x min(-1) x 1.73 m(-2)) and normal Ccr (>or=80 x min(-1) x 1.73 m(-2)). None of the patients with macroalbuminuria had normal Ccr. In those with normoalbuminuria, tHcy levels were higher than in those with low Ccr than in those with normal Ccr (12.0 +/- 4.6 vs. 10.0 +/- 4.4 micromol/l, P < 0.01). The same was found for those with microalbuminuria (low Ccr versus normal Ccr: 14.6 +/- 9.0 vs. 10.2 +/- 2.8 micromol/l, P < 0.02). For normal Ccr, tHcy was similar irrespective of AER (normoalbuminuria versus microalbuminuria: 10.0 +/- 4.4 vs. 10.2 +/- 2.8 micromol/l, NS). For low Ccr, tHcy was higher in those with microalbuminuria versus normoalbuminuria (14.6 +/- 9.0 vs. 12.0 +/- 4.6 micromol/l, P = 0.01). Using multivariate regression, Ccr, but neither AER nor the presence of albuminuria, was an independent predictor of tHcy.These data strongly suggest that in patients with type 2 diabetes, the relationship between plasma tHcy and AER is largely due to associated changes in renal function, as defined by Ccr.
Age, Gender, and Ethnicity Differences in Patterns of Cocaine and Ethanol Use Preceding Suicide
Authors: Steven J. Garlow
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: The goal of this study was to examine the relationship between suicide and substance use among completed suicides in Fulton County, Ga., from 1994 through 1998. METHOD: Extensive data on completed suicides were obtained from records of the Office of the Medical Examiner. Specific characteristics of the victims who had used cocaine, ethanol, or both before committing suicide were compared across demographic groups. RESULTS: There were important race, sex, and age differences among the victims who had used cocaine and ethanol before committing suicide. Almost all (94.6%) of the suicide victims in whom cocaine was detected were male, 51.4% of the cocaine-positive victims were African American men, and 43.2% were white men. Substance use by teenage victims differed dramatically across ethnic lines. The vast majority (86.7%) of African American teenagers did not use either substance before committing suicide, whereas 50.0% of the white teenage victims had used one or both substances, with 41.7% of the white teenagers having used ethanol. Overall, ethanol use was much more common among white victims of all age groups. CONCLUSIONS: Intoxicant use preceding suicide occurred in specific age-, ethnic-, and gender-based patterns.
Tumor-Localized Ligation of CD3 and CD28 with Systemic Regulatory T-Cell Depletion Induces Potent Innate and Adaptive Antitumor Responses
Authors: Chien-Hsin Lee, Yi-Hsuan Chiang, Shih-En Chang, Chin-Liew Chong, Bing-Mae Cheng, Steve R. Roffler
Journal: Clinical Cancer Research (2009)

Tumor-localized activation of immune cells by membrane-tethered anti-CD3 antibodies (CD3L) is under investigation to treat poorly immunogenic tumors. Here we sought to elucidate the mechanism of antitumor immunity elicited by CD3L.CD3L and CD86 were expressed on poorly immunogenic B16 melanoma cells (B16/3L86 cells) and the effect of various lymphocytes, including CD4(+) and CD8(+) T cells, natural killer T (NKT) cells, and regulatory T cells, on antitumor activity was investigated.B16/3L86 cells activated naïve T cells; suppressed tumor growth in subcutaneous, peritoneal, and metastasis models; and protected mice from rechallenge with B16 melanoma cells. However, in vivo antitumor activity against primary B16/3L86 tumors unexpectedly depended on NKT cells rather than CD4(+) or CD8(+) T cells. Treatment of mice with low-dose cyclophosphamide or anti-CD25 antibody to deplete regulatory T cells unmasked latent T-cell antitumor activity; the number of activated CD8(+) T cells in tumors increased and B16/3L86 tumors were completely rejected in a CD8(+) and CD4(+) T-cell-dependent fashion. Furthermore, fibroblasts expressing CD3L and CD86 suppressed the growth of neighboring B16 cancer cells in vivo, and direct intratumoral injection of adenoviral vectors expressing CD3L and CD86 or CD3L and a membrane-tethered anti-CD28 antibody significantly suppressed the growth of subcutaneous tumors.Tumor-located ligation of CD3 and CD28 can activate both innate (NKT cells) and adaptive (CD4(+) and CD8(+) T cells) responses to create a tumor-destructive environment to control tumor growth, but modulation of regulatory T cells is necessary to unmask local adaptive antitumor responses.
Neural Tissue Engineering: Strategies for Repair and Regeneration
Authors: Christine E. Schmidt, Jennie Baier Leach
Journal: Annual Review of Biomedical Engineering (2003)

▪ Abstract Nerve regeneration is a complex biological phenomenon. In the peripheral nervous system, nerves can regenerate on their own if injuries are small. Larger injuries must be surgically treated, typically with nerve grafts harvested from elsewhere in the body. Spinal cord injury is more complicated, as there are factors in the body that inhibit repair. Unfortunately, a solution to completely repair spinal cord injury has not been found. Thus, bioengineering strategies for the peripheral nervous system are focused on alternatives to the nerve graft, whereas efforts for spinal cord injury are focused on creating a permissive environment for regeneration. Fortunately, recent advances in neuroscience, cell culture, genetic techniques, and biomaterials provide optimism for new treatments for nerve injuries. This article reviews the nervous system physiology, the factors that are critical for nerve repair, and the current approaches that are being explored to aid peripheral nerve regeneration and spinal cord repair.
Intact Memory for Irrelevant Information Impairs Perception in Amnesia
Authors: Morgan D. Barense, Iris I.A. Groen, Andy C.H. Lee, Lok-Kin Yeung, Sinead M. Brady, Mariella Gregori, Narinder Kapur, Timothy J. Bussey, Lisa M. Saksida, Richard N.A. Henson
Journal: Neuron (2012)

Memory and perception have long been considered separate cognitive processes, and amnesia resulting from medial temporal lobe (MTL) damage is thought to reflect damage to a dedicated memory system. Recent work has questioned these views, suggesting that amnesia can result from impoverished perceptual representations in the MTL, causing an increased susceptibility to interference. Using a perceptual matching task for which fMRI implicated a specific MTL structure, the perirhinal cortex, we show that amnesics with MTL damage including the perirhinal cortex, but not those with damage limited to the hippocampus, were vulnerable to object-based perceptual interference. Importantly, when we controlled such interference, their performance recovered to normal levels. These findings challenge prevailing conceptions of amnesia, suggesting that effects of damage to specific MTL regions are better understood not in terms of damage to a dedicated declarative memory system, but in terms of impoverished representations of the stimuli those regions maintain.
TCE treatment pasta-bilities.
Authors: W C Holton
Journal: Environmental Health Perspectives (1999)

Monsanto's "Lasagna" process uses layers of treatment zones spaced between buried electrodes to remove trichloroethylene (TCE) from contaminated soil and groundwater. TCE is used primarily as a metal degreaser as well as in products such as dyes, printing ink, and paint. TCE can eventually make its way into the environment and is prevalent in the water and soil of industrialized nations. Although TCE breaks down in a few days when released into the atmosphere, it degrades much more slowly in soil, taking months or years. Moreover, it is often broken down by microbes into toxic substances such as vinylidene chloride (a suspected human carcinogen) and vinyl chloride (a known human carcinogen). The Lasagna process is based on the principle of electro-osmosis, in which an electric current draws water from low--permeability soils such as clays, silts, and fine sands. To remove TCE from contaminated soils, Monsanto scientists added layers of filtering media, which attack the contaminant as it is pulled from electrode to electrode. The technology has been tested at the Paducah Gaseous Diffusion Plant in western Kentucky, where it removed over 98% of TCE from contaminated soil.
Ventilation inhomogeneity in children with severe asthma and normal spirometry indicates residual airways disease
Authors: Elpis Hatziagorou, Vasiliki Avramidou, Fotis Kirvasillis, John Tsanakas
Journal: European Respiratory Journal (2013)

Background: In adults with asthma, ventilation inhomogeneity, independent of inflammation, has been hypothesized to be associated with airway remodelling. No such study is reported among children.

Objective: We investigated whether children with severe, well controlled asthma and normal lung function, were more likely to have increased ventilation inhomogeneity (LCI) and increased fraction of exhaled nitric oxide (FeNO) than healthy controls.

Methods: In 18 children with well-controlled, severe, atopic asthma of mean age 14.2 years (±3.7), FVC, FEV1, FEF, LCI, Scond and Sacin, as well as FeNO were measured. 18 healthy volunteers of mean age 13.2 years (±3.9) were used as controls.

Results: Baseline mean (SD) LCI was significantly higher in children with asthma than in controls (8.5 (1.5) vs 6.7 (0.33), p < 0.0001). There were also significant differences among asthmatics and controls, in mean (SD) FEV1 (96.2(21.2), vs. 108.9 (11.8), p=0.033, FEF 85.8(39.8), vs. 113.08 (37.6), p= 0.045) and median FeNO 31.3 (16.9) vs. 11.3 (5.2), p=0.043).

Conclusion: There is ventilation inhomogeneity in children with well controlled severe, asthma and normal FEV1. LCI is the most sensitive indicator of abnormal pulmonary function in children with severe, well controlled asthma. The role of LCI in measuring airway disease in children with severe asthma requires further exploration, possibly as a surrogate of structural remodeling.
Right ventricular dysfunction is an independent predictor for mortality in ST‐elevation myocardial infarction patients presenting with cardiogenic shock on admission
Authors: Annemarie E. Engström, Marije M. Vis, Berto J. Bouma, Renée B.A. van den Brink, Jan Baan, Bimmer E.P.M. Claessen, Wouter J. Kikkert, Krischan D. Sjauw, Martijn Meuwissen, Karel T. Koch, Robbert J. de Winter, Jan G.P. Tijssen, Jan J. Piek, José P.S. Henriques
Journal: European Journal of Heart Failure (2010)
Cyclin G1 Is a Target of miR-122a, a MicroRNA Frequently Down-regulated in Human Hepatocellular Carcinoma
Authors: Laura Gramantieri, Manuela Ferracin, Francesca Fornari, Angelo Veronese, Silvia Sabbioni, Chang-Gong Liu, George A. Calin, Catia Giovannini, Eros Ferrazzi, Gian Luca Grazi, Carlo M. Croce, Luigi Bolondi, Massimo Negrini
Journal: Cancer Research (2007)

Abstract We investigated the role of microRNAs (miRNAs) in the pathogenesis of human hepatocellular carcinoma (HCC). A genome-wide miRNA microarray was used to identify differentially expressed miRNAs in HCCs arisen on cirrhotic livers. Thirty-five miRNAs were identified. Several of these miRNAs were previously found deregulated in other human cancers, such as members of the let-7 family, mir-221, and mir-145. In addition, the hepato-specific miR-122a was found down-regulated in ∼70% of HCCs and in all HCC-derived cell lines. Microarray data for let-7a, mir-221, and mir-122a were validated by Northern blot and real-time PCR analysis. Understanding the contribution of deregulated miRNAs to cancer requires the identification of gene targets. Here, we show that miR-122a can modulate cyclin G1 expression in HCC-derived cell lines and an inverse correlation between miR-122a and cyclin G1 expression exists in primary liver carcinomas. These results indicate that cyclin G1 is a target of miR-122a and expand our knowledge of the molecular alterations involved in HCC pathogenesis and of the role of miRNAs in human cancer. [Cancer Res 2007;67(13):6092–9]
Genomic signatures to guide the use of chemotherapeutics
Authors: Anil Potti, Holly K Dressman, Andrea Bild, Richard F Riedel, Gina Chan, Robyn Sayer, Janiel Cragun, Hope Cottrill, Michael J Kelley, Rebecca Petersen, David Harpole, Jeffrey Marks, Andrew Berchuck, Geoffrey S Ginsburg, Phillip Febbo, Johnathan Lancaster, Joseph R Nevins
Journal: Nature Medicine (2006)
Impact of <i>KRAS</i> and <i>BRAF</i> Gene Mutations on Targeted Therapies in Colorectal Cancer
Authors: Adam Bass
Journal: Journal of Clinical Oncology (2011)

Article Tools UNDERSTANDING THE PATHWAY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2011.36.1816 Journal of Clinical Oncology - published online before print June 6, 2011 PMID: 21646605 Impact of KRAS and BRAF Gene Mutations on Targeted Therapies in Colorectal Cancer Adam BassxAdam BassSearch for articles by this author Show More Dana-Farber Cancer Institute, Boston, MA https://doi.org/10.1200/JCO.2011.36.1816 Full Text PDF Figures and Tables "Impact of KRAS and BRAF Gene Mutations on Targeted Therapies in Colorectal Cancer." Journal of Clinical Oncology, 29(19), pp. 2728–2729© 2011 by American Society of Clinical Oncology
Abstract 3602: Antitumor effects of epidermal growth factor (EGF) and insulin-like growth factor (IGF) inhibitors in the treatment of metastatic renal cell carcinoma
Authors: Johny E. Elkahwaji, Ralph J. Hauke
Journal: Cancer Research (2011)

Abstract Background: Renal cell carcinoma (RCC) is associated with mutation or loss of function of the von Hippel-Lindau gene resulting in hypoxia-inducible factor 1-alpha accumulation and production of growth factors involved in proliferation and angiogenesis. Radical nephrectomy remains the primary treatment option for two thirds of RCC patients who present with tumors confined to the kidney. However, approximately one half of patients will develop metastatic RCC. Treatment of RCC has been hampered by its resistance to most chemotherapy and hormonal therapy, although selected patients have long term remission from high dose of interleukin-2. Despite the recent availability of several active targeted agents in this disease, therapy is not curative. As a result, there is continued demand for improving therapy for metastatic disease to enhance both clinical benefits and patients overall survival. The EGF and IGF-1 pathways have been implicated as potential therapeutic targets in RCC. The objective of this study was to investigate the antitumor response to EGF and IGF inhibitors as a novel combination therapy in metastatic RCC. Methods: RCC cells lines (Caki-1 and Caki-2) were cultured in appropriate media supplemented with 10% FBS in a 5% CO2 incubator. Cells were treated for 24, 48, 72h, and 96h with different doses of EGFR (AG1478) and/or IGF-1R (AG1024) inhibitors (0-100 µM) given as single agent or in combination therapy. The epithelial cell proliferation was determined by AlamarBlue proliferation assay. Results: Both AG1478 and AG1024, given as single agent, decreased the epithelial cell proliferation of RCC human malignant cell lines (Caki-1 and Caki-2) (p&amp;lt;0.05). The inhibition occurred in a dose-dependent manner and was more pronounced at higher doses of AG1478 or AG1024 (100 µM), and when both agents were given as combination therapy. Conclusions: These data suggest that both inhibitors exhibit a synergistic antitumor effect when given as combination therapy. This synergistic benefit exhibits an anti-proliferative and pro-apoptotic effects on RCC cell lines in vitro and warrants further investigation as a potential therapeutic approach for metastatic RCC patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3602. doi:10.1158/1538-7445.AM2011-3602