tbuckley/cabot-search huggingface dataset:
Glutathione S-transferase omega genes in Alzheimer and Parkinson disease risk, age-at-diagnosis and brain gene expression: an association study with mechanistic implications
Authors: Mariet Allen, Fanggeng Zou, High Seng Chai, Curtis S Younkin, Richard Miles, Asha A Nair, Julia E Crook, V Shane Pankratz, Minerva M Carrasquillo, Christopher N Rowley, Thuy Nguyen, Li Ma, Kimberly G Malphrus, Gina Bisceglio, Alexandra I Ortolaza, Ryan Palusak, Sumit Middha, Sooraj Maharjan, Constantin Georgescu, Debra Schultz, Fariborz Rakhshan, Christopher P Kolbert, Jin Jen, Sigrid B Sando, Jan O Aasly, Maria Barcikowska, Ryan J Uitti, Zbigniew K Wszolek, Owen A Ross, Ronald C Petersen, Neill R Graff-Radford, Dennis W Dickson, Steven G Younkin, Nilüfer Ertekin-Taner
Journal: Molecular Neurodegeneration (2012)

Abstract Background Glutathione S-transferase omega-1 and 2 genes ( GSTO1 , GSTO2 ), residing within an Alzheimer and Parkinson disease (AD and PD) linkage region, have diverse functions including mitigation of oxidative stress and may underlie the pathophysiology of both diseases. GSTO polymorphisms were previously reported to associate with risk and age-at-onset of these diseases, although inconsistent follow-up study designs make interpretation of results difficult. We assessed two previously reported SNPs, GSTO1 rs4925 and GSTO2 rs156697, in AD (3,493 ADs vs. 4,617 controls) and PD (678 PDs vs. 712 controls) for association with disease risk (case-controls), age-at-diagnosis (cases) and brain gene expression levels (autopsied subjects). Results We found that rs156697 minor allele associates with significantly increased risk (odds ratio = 1.14, p = 0.038) in the older ADs with age-at-diagnosis &gt; 80 years. The minor allele of GSTO1 rs4925 associates with decreased risk in familial PD (odds ratio = 0.78, p = 0.034). There was no other association with disease risk or age-at-diagnosis. The minor alleles of both GSTO SNPs associate with lower brain levels of GSTO2 ( p = 4.7 × 10 -11 -1.9 × 10 -27 ), but not GSTO1 . Pathway analysis of significant genes in our brain expression GWAS, identified significant enrichment for glutathione metabolism genes ( p = 0.003). Conclusion These results suggest that GSTO locus variants may lower brain GSTO2 levels and consequently confer AD risk in older age. Other glutathione metabolism genes should be assessed for their effects on AD and other chronic, neurologic diseases.
Lower limb arterial incompressibility and obstruction in rheumatoid arthritis
Authors: I del Rincón, R W Haas, S Pogosian, A Escalante
Journal: Annals of the Rheumatic Diseases (2004)

<b>Background:</b> Despite increased cardiovascular morbidity and mortality in rheumatoid arthritis, the peripheral arteries remain understudied. <b>Objective:</b> To examine the lower limb arteries in age and sex matched, non-smoking subjects with and without rheumatoid arthritis. <b>Methods:</b> The ankle-brachial index (ABI) was measured at the posterior tibial and dorsal pedal arteries. Arteries were classified as obstructed with ABI ⩽0.9, normal with ABI &gt;0.9 but ⩽1.3, and incompressible with ABI &gt;1.3. Multinomial logistic regression was used to estimate differences in ABI between patients and controls, adjusting for cardiovascular risk factors, rheumatoid arthritis manifestations, inflammation markers, and glucocorticoid dose. <b>Results:</b> 234 patients with rheumatoid arthritis and 102 controls were studied. Among the rheumatoid patients, 66 of 931 arteries (7%) were incompressible and 30 (3%) were obstructed. Among the controls, three of 408 arteries (0.7%) were incompressible (p = 0.002) and four (1%) were obstructed (p = 0.06). At the person level, one or more abnormal arteries occurred among 45 rheumatoid patients (19%), <i>v</i> five controls (5%, p = 0.001). The greater frequency of arterial incompressibility and obstruction in rheumatoid arthritis was independent of age, sex, and cardiovascular risk factors. Adjustment for inflammation markers, joint damage, rheumatoid factor, and glucocorticoid use reduced rheumatoid arthritis <i>v</i> control differences. Most arterial impairments occurred in rheumatoid patients with 20 or more deformed joints. This subgroup had more incompressible (15%, p⩽0.001) and obstructed arteries (6%, p = 0.005) than the controls, independent of covariates. <b>Conclusions:</b> Peripheral arterial incompressibility and obstruction are increased in rheumatoid arthritis. Their propensity for patients with advanced joint damage suggests shared pathogenic mechanisms.
Laser speckle contrast analysis: a new method to evaluate peripheral blood perfusion in systemic sclerosis patients
Authors: Barbara Ruaro, Alberto Sulli, Elisa Alessandri, Carmen Pizzorni, Giorgia Ferrari, Maurizio Cutolo
Journal: Annals of the Rheumatic Diseases (2013)

The aim of this pilot study was to assess peripheral blood perfusion (PBP) by a new technique, the laser speckle contrast analysis (LASCA), in systemic sclerosis (SSc) patients showing different patterns of nailfold microangiopathy. Correlations between LASCA and single laser Doppler flowmetry (LDF) analysis were also checked.Sixty-one SSc patients and 61 healthy subjects were enrolled. PBP was evaluated using LASCA and LDF. Scleroderma patterns and microangiopathy evolution score (MES) were assessed by nailfold videocapillaroscopy (NVC).As detected by LASCA and LDF, PBP was lower in SSc patients than in healthy subjects (p<0.0001), showing SSc patients with the 'Early', 'Active' or 'Late' NVC pattern a progressively lower PBP (p=0.04 and p=0.002, respectively). There was a negative correlation between PBP and MES values (p=0.006 and p=0.002 for LASCA and LDF, respectively). A positive correlation was detected between LASCA and LDF values, in all subjects (p<0.0001). However, LASCA evaluates larger skin areas, is significantly less time consuming, is more accepted by patients and shows lower intra-operator variability than LDF.LASCA detected lower PBP in SSc patients than in healthy subjects, and for the first time, LASCA perfusion values were found correlated with progression of NVC patterns of microangiopathy.
Radiation-induced, immunologically mediated regression of an established tumor as an example of successful therapeutic immunomanipulation. Preferential elimination of suppressor T cells allows sustained production of effector T cells.
Authors: R J North
Journal: The Journal of Experimental Medicine (1986)

The results of this study confirm results published by others by showing that sublethal whole-body irradiation of mice bearing immunogenic tumors can result in complete tumor regression. The results show, in addition, that irradiation-induced tumor regression can be prevented by infusion, after irradiation, of Ly-1+,2-,L3T4+ suppressor T cells from the spleens of donors bearing an established tumor, but not by infusion of normal spleen cells. This evidence, plus the demonstration that irradiation fails to cause regression of tumors growing in immunocompetent mice, is consistent with the hypothesis that irradiation-induced regression is immunologically mediated, and that it depends on the ability of irradiation to preferentially eliminate suppressor T cells. By using passive transfer assays to measure the production of effector T cells and suppressor T cells against time of tumor growth, it was shown that irradiation of tumor-bearing mice on day 5 of tumor growth resulted in a failure to generate suppressor T cells on the one hand, and in a sustained production, effector T cells on the other. In other words, irradiation prevented the concomitant antitumor immune response from being downregulated by suppressor T cells. However, giving radiation on day 1 of tumor growth, in contrast to giving it 3-6 d later, caused immunodepression and enhancement of tumor growth. This is in keeping with published evidence showing that, whereas resting effector T cells are highly radiosensitive, antigen-activated effector T cells are relatively radioresistant. It is suggested that the radioresistance of activated effector T cells, coupled with the radiosensitivity of activated suppressor T cells, is the reason for the selectivity of ionizing radiation for suppressor T cells and why a tumor needs to be palpable to undergo regression in response to radiation therapy.
Oxidative Stress Plays a Critical Role in Inactivating Mutant BRAF by Geldanamycin Derivatives
Authors: Yayoi Fukuyo, Masahiro Inoue, Takuma Nakajima, Ryuji Higashikubo, Nobuko T. Horikoshi, Clayton Hunt, Anny Usheva, Michael L. Freeman, Nobuo Horikoshi
Journal: Cancer Research (2008)

Abstract The geldanamycin derivatives 17-allylamino-17-demethoxygeldanamycin (17-AAG) and 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) are promising chemotherapeutic drugs that inhibit heat shock protein 90 (HSP90) function. Previous studies have shown that 17-AAG/DMAG treatment induces the degradation of mutant BRAF (V600E) and inhibits the activation of mitogen-activated protein/extracellular signal-regulated kinase 1/2 (MEK1/2). We have found, however, that HSP90 inhibition alone is not sufficient for efficient BRAF(V600E) degradation in some cells. HSP90 inhibitors structurally unrelated to geldanamycin, radicicol and novobiocin, while inducing the degradation of the HSP90 client protein RAF-1 fail to induce BRAF(V600E) degradation or inhibit MEK1/2 activation in HT29 human colon cancer cells. Moreover, after treatment with 17-DMAG, the kinase activity of residual, undegraded BRAF(V600E) was also lost. Incubation of cells with a reactive oxygen species (ROS) scavenger, N-acetyl cysteine, partially restored kinase activity and also partially prevented BRAF(V600E) degradation due to 17-DMAG treatment. Conversely, treatment with the ROS producing drug menadione clearly inhibited MEK1/2 and reduced BRAF(V600E). These results suggest that in addition to direct inhibition of HSP90, the antitumor effect of geldanamycin and its derivatives is also mediated though the production of ROS, which may directly inactivate tumorigenic mutant BRAF(V600E). [Cancer Res 2008;68(15):6324–30]
Anti-tumor effects of anti-PD-L1 therapy in an orthotopic bladder tumor model
Authors: Amanda Lyon, Jonathan Fallon, Benjamin Boyerinas, Robert Schmitz, Kenneth W Hance, Yan Lan, Helen Sabzevari, Kwong Tsang, Jeffrey Schlom, John Greiner
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Antibodies that block PD-1/PD-L1 interactions have shown efficacy against both lung and skin cancers in early-stage clinical trials, and may also be effective in other tumor types, particularly bladder tumors. PD-L1 expression has been previously reported to correlate with high-
The Association Between Severity of Total Eosinophilic Count and Disease Categories
Authors: Shunya Kaneshita, Mitsumasa Kishimoto, Fumio Omata, Masei Suda, Chisun Min, Yuri Ohara, Ryo Rokutanda, Hisanori Shimizu, Tokutaro Tsuda, Ken-ichi Yamaguchi, Akira Takeda, Yukio Matsui, Masato Okada
Journal: Journal of Allergy and Clinical Immunology (2015)
The impact of the 21-gene recurrence score assay on decision making about adjuvant chemotherapy in early-stage estrogen-receptor-positive breast cancer in an oncology practice with a unified treatment policy
Authors: D.B. Geffen, S. Abu-Ghanem, N. Sion-Vardy, R. Braunstein, M. Tokar, S. Ariad, B. Delgado, M. Bayme, M. Koretz
Journal: Annals of Oncology (2011)
Central Command Regulation of Circulatory Function Mediated by Descending Pontine Cholinergic Inputs to Sympathoexcitatory Rostral Ventrolateral Medulla Neurons
Authors: James R. Padley, Natasha N. Kumar, Qun Li, Thomas B.V. Nguyen, Paul M. Pilowsky, Ann K. Goodchild
Journal: Circulation Research (2007)

Central command is a feedforward neural mechanism that evokes parallel modifications of motor and cardiovascular function during arousal and exercise. The neural circuitry involved has not been elucidated. We have identified a cholinergic neural circuit that, when activated, mimics effects on tonic and reflex control of circulation similar to those evoked at the onset of and during exercise. Central muscarinic cholinergic receptor (mAChR) activation increased splanchnic sympathetic nerve activity (SNA) as well as the range and gain of the sympathetic baroreflex via activation of mAChR in the rostral ventrolateral medulla (RVLM) in anesthetized artificially ventilated Sprague-Dawley rats. RVLM mAChR activation also attenuated and inhibited the peripheral chemoreflex and somatosympathetic reflex, respectively. Cholinergic terminals made close appositions with a subpopulation of sympathoexcitatory RVLM neurons containing either preproenkephalin mRNA or tyrosine hydroxylase immunoreactivity. M2 and M3 receptor mRNA was present postsynaptically in only non-tyrosine hydroxylase neurons. Cholinergic inputs to the RVLM arise only from the pedunculopontine tegmental nucleus. Chemical activation of this region produced increases in muscle activity, SNA, and blood pressure and enhanced the SNA baroreflex; the latter effect was attenuated by mAChR blockade. These findings indicate a novel role for cholinergic input from the pedunculopontine tegmental nucleus to the RVLM in central cardiovascular command. This pathway is likely to be important during exercise where a centrally evoked facilitation of baroreflex control of the circulation is required to maintain blood flow to active muscle.
Recruitment of latent pools of high-avidity CD8+ T cells to the antitumor immune response
Authors: Anne M. Ercolini, Brian H. Ladle, Elizabeth A. Manning, Lukas W. Pfannenstiel, Todd D. Armstrong, Jean-Pascal H. Machiels, Joan G. Bieler, Leisha A. Emens, R. Todd Reilly, Elizabeth M. Jaffee
Journal: The Journal of Experimental Medicine (2005)

A major barrier to successful antitumor vaccination is tolerance of high-avidity T cells specific to tumor antigens. In keeping with this notion, HER-2/neu (neu)-targeted vaccines, which raise strong CD8+ T cell responses to a dominant peptide (RNEU420-429) in WT FVB/N mice and protect them from a neu-expressing tumor challenge, fail to do so in MMTV-neu (neu-N) transgenic mice. However, treatment of neu-N mice with vaccine and cyclophosphamide-containing chemotherapy resulted in tumor protection in a proportion of mice. This effect was specifically abrogated by the transfer of neu-N–derived CD4+CD25+ T cells. RNEU420-429-specific CD8+ T cells were identified only in neu-N mice given vaccine and cyclophosphamide chemotherapy which rejected tumor challenge. Tetramer-binding studies demonstrated that cyclophosphamide pretreatment allowed the activation of high-avidity RNEU420-429-specific CD8+ T cells comparable to those generated from vaccinated FVB/N mice. Cyclophosphamide seemed to inhibit regulatory T (T reg) cells by selectively depleting the cycling population of CD4+CD25+ T cells in neu-N mice. These findings demonstrate that neu-N mice possess latent pools of high-avidity neu-specific CD8+ T cells that can be recruited to produce an effective antitumor response if T reg cells are blocked or removed by using approaches such as administration of cyclophosphamide before vaccination.
Human Immunodeficiency Virus Test Evaluation, Performance, and Use
Authors: J. Sanford Schwartz
Journal: JAMA (1988)

Human immunodeficiency virus (HIV) tests are essential for detecting asymptomatic infection and are helpful in confirming the diagnoses of acquired immunodeficiency syndrome—related complex and acquired immunodeficiency syndrome. Nonetheless, many aspects of their use remain controversial, partly because of concerns about test accuracy. This article reviews the scientific basis for the evaluation, performance, and use of the most commonly employed HIV assays. Current test performance could be improved by better standardization of test procedures and institution of mandatory proficiency testing and licensure of clinical laboratories that perform HIV testing. Test utility could be enhanced by sequencing tests more appropriately and by interpreting test results in conjunction with the clinical purpose for which the test is being used and the characteristics of the population under study. Finally, HIV tests should be evaluated in a manner that minimizes spectrum and referral bias and inadequate reference standard confirmation, problems that have affected the evaluation of current tests. (<i>JAMA</i>1988;259:2574-2579)
MUTATION SCREENING OF SARCOMERE GENES MYH7, MYBPC3, LDB3, AND TNNT2 IN A LARGE COHORT OF DILATED CARDIOMYOPATHY FAMILIES
Authors: Luisa Mestroni, Marco Merlo, Elisa Carniel, Dobromir Slavov, Xiao Zhu, Debra Ferguson, Ernesto E. Salcedo, Jean Cavanaugh, Andrea Di Lenarda, Gianfranco Sinagra, Matthew R.G. Taylor
Journal: Journal of the American College of Cardiology (2010)
Prevention of one-year vein-graft occlusion after aortocoronary- bypass surgery: a comparison of low-dose aspirin, low-dose aspirin plus dipyridamole, and oral anticoagulants
Authors: J van der Meer, H.L Hillege, W.H van Gilst, K.I Lie, G.J Kootstra, C.A.P.L Ascoop, M Pfisterer
Journal: The Lancet (1993)
Rac1/Pak1/p38/MMP-2 Axis Regulates Angiogenesis in Ovarian Cancer
Authors: Vianey Gonzalez-Villasana, Enrique Fuentes-Mattei, Cristina Ivan, Heather J. Dalton, Cristian Rodriguez-Aguayo, Ricardo J. Fernandez-de Thomas, Burcu Aslan, Paloma del C. Monroig, Guermarie Velazquez-Torres, Rebecca A. Previs, Sunila Pradeep, Nermin Kahraman, Huamin Wang, Pinar Kanlikilicer, Bulent Ozpolat, George Calin, Anil K. Sood, Gabriel Lopez-Berestein
Journal: Clinical Cancer Research (2015)

Zoledronic acid is being increasingly recognized for its antitumor properties, but the underlying functions are not well understood. In this study, we hypothesized that zoledronic acid inhibits ovarian cancer angiogenesis preventing Rac1 activation.The biologic effects of zoledronic acid were examined using a series of in vitro [cell invasion, cytokine production, Rac1 activation, reverse-phase protein array, and in vivo (orthotopic mouse models)] experiments.There was significant inhibition of ovarian cancer (HeyA8-MDR and OVCAR-5) cell invasion as well as reduced production of proangiogenic cytokines in response to zoledronic acid treatment. Furthermore, zoledronic acid inactivated Rac1 and decreased the levels of Pak1/p38/matrix metalloproteinase-2 in ovarian cancer cells. In vivo, zoledronic acid reduced tumor growth, angiogenesis, and cell proliferation and inactivated Rac1 in both HeyA8-MDR and OVCAR-5 models. These in vivo antitumor effects were enhanced in both models when zoledronic acid was combined with nab-paclitaxel.Zoledronic acid has robust antitumor and antiangiogenic activity and merits further clinical development as ovarian cancer treatment.
How to Define Transarterial Chemoembolization Failure or Refractoriness: A European Perspective
Authors: Jean-Luc Raoul, Marine Gilabert, Gilles Piana
Journal: Liver Cancer (2014)

In Europe, trans-arterial chemoembolization (TACE) is usually given to patients with Barcelona Clinic Liver Cancer (BCLC) "intermediate stage" hepatocellular carcinoma (HCC), and is associated with a modest improvement in median overall survival. In the two positive randomized trials that have been reported, TACE was stopped in cases of severe toxicity, worsening of liver cirrhosis or performance status and tumor progression, including local progression, extrahepatic spread and portal vein thrombosis. The necessity to stop TACE leads to the concept of untreatable progression, which is characterized by massive liver involvement, extrahepatic spread, vascular invasion, impaired liver function or performance status. More recently, the assessment for re-treatment with TACE (ART) score has been developed to determine which patients will not benefit from a second or a third TACE therapy. Herein, we propose an algorithm that summarizes our experience with TACE.
A new silybin-vitamin E-phospholipid complex improves insulin resistance and liver damage in patients with non-alcoholic fatty liver disease: preliminary observations
Authors: A Federico
Journal: Gut (2006)

Non-alcoholic fatty liver disease (NAFLD) may occur as an expression of a metabolic syndrome or in association with hepatitis C virus (HCV) chronic infection. The contemporaneous presence of NAFLD in this later group of patients may negatively affect the progression of fibrosis and the response to antiviral treatment.1,2 It has been suggested that in the future a therapeutic approach to chronic liver disease would consist of a number of complementary approaches considering the multitude of pathogenic mechanisms.3 Silybin is a natural flavonoid that has been conjugated to vitamin E and phospholipids to improve its bioavailability, and antioxidant and antifibrotic activity.4

After approval of the ethics committee and informed consent, 85 outpatients were consecutively enrolled in the study: 59 were affected by primitive NAFLD (group A) …
Intra-articular triamcinolone hexacetonide in knee osteoarthritis: factors influencing the clinical response.
Authors: K Gaffney, J Ledingham, J D Perry
Journal: Annals of the Rheumatic Diseases (1995)

To assess the efficacy of a single intra-articular injection of triamcinolone hexacetonide (THA) in knee osteoarthritis (OA) and examine factors which may relate to treatment efficacy.Eighty four patients with clinical and radiographic evidence of knee OA were recruited and randomly allocated to receive either THA (20 mg in 1 ml) or placebo (0.9% normal saline, 1 ml). Follow up assessments evaluated the following outcome variables: patient opinion of overall change in the treated knee, visual analogue pain score (VAS), distance walked in one minute (WD), and Health Assessment Questionnaire modified for lower limb function (HAQ).Seventy eight percent of THA and 49% of placebo treated patients reported overall improvement at week 1 (p < 0.05). At week 6, improvement was reported in 57% and 55% of patient groups, respectively. VAS improved in both groups at week 1 (THA, p < 0.001; placebo, p < 0.05) and week 6 (both p < 0.01). Improvement in VAS was significantly greater among THA treated patients at week 1 only (p < 0.01). Subgroup analysis of THA treated patients revealed greater improvement in VAS among patients with clinical evidence of an effusion (p < 0.05), and those who had synovial fluid successfully aspirated at the time of injection (p < 0.01). WD improved in THA treated patients at week 1 (p < 0.001), and in both groups at week 6 (THA, p < 0.001; placebo, p < 0.01). Improvements in HAQ were seen in THA patients only at weeks 1 and 6 (p < 0.05). Regression analysis did not identify any additional clinical, radiographic, or synovial fluid characteristics which influenced the response.THA provided short term pain relief in knee OA. Increased benefit was associated with both clinical evidence of joint effusion and successful aspiration of synovial fluid at the time of injection.
Predictors of phenotypic progression and disease onset in premanifest and early-stage Huntington's disease in the TRACK-HD study: analysis of 36-month observational data
Authors: Sarah J Tabrizi, Rachael I Scahill, Gail Owen, Alexandra Durr, Blair R Leavitt, Raymund A Roos, Beth Borowsky, Bernhard Landwehrmeyer, Chris Frost, Hans Johnson, David Craufurd, Ralf Reilmann, Julie C Stout, Douglas R Langbehn
Journal: The Lancet Neurology (2013)