tbuckley/cabot-search huggingface dataset:
Abnormal expression of TIP30 and arrested nucleocytoplasmic transport within oligodendrocyte precursor cells in multiple sclerosis
Authors: Jin Nakahara, Kohsuke Kanekura, Mikiro Nawa, Sadakazu Aiso, Norihiro Suzuki
Journal: Journal of Clinical Investigation (2008)

Oligodendrocyte precursor cells (OPCs) persist near the demyelinated axons arising in MS but inefficiently differentiate into oligodendrocytes and remyelinate these axons. The pathogenesis of differentiation failure remains elusive. We initially hypothesized that injured axons fail to present Contactin, a positive ligand for the oligodendroglial Notch1 receptor to induce myelination, and thus tracked axoglial Contactin/Notch1 signaling in situ, using immunohistochemistry in brain tissue from MS patients containing chronic demyelinated lesions. Instead, we found that Contactin was saturated on demyelinated axons, Notch1-positive OPCs accumulated in Contactin-positive lesions, and the receptor was engaged, as demonstrated by cleavage to Notch1-intracellular domain (NICD). However, nuclear translocalization of NICD, required for myelinogenesis, was virtually absent in these cells. NICD and related proteins carrying nuclear localization signals were associated with the nuclear transporter Importin but were trapped in the cytoplasm. Abnormal expression of TIP30, a direct inhibitor of Importin, was observed in these OPCs. Overexpression of TIP30 in a rat OPC cell line resulted in cytoplasmic entrapment of NICD and arrest of differentiation upon stimulation with Contactin-Fc. Our results suggest that extracellular inhibitory factors as well as an intrinsic nucleocytoplasmic transport blockade within OPCs may be involved in the pathogenesis of remyelination failure in MS.
Quality of Life in Patients With Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia on Imatinib Versus Interferon Alfa Plus Low-Dose Cytarabine: Results From the IRIS Study
Authors: Elizabeth A. Hahn, G. Alastair Glendenning, Mark V. Sorensen, Stacie A. Hudgens, Brian J. Druker, Francois Guilhot, Richard A. Larson, Stephen G. O’Brien, Deborah G. Dobrez, Martee L. Hensley, David Cella
Journal: Journal of Clinical Oncology (2003)

Purpose: Quality of life (QOL) outcomes in patients with chronic myeloid leukemia (CML) were evaluated in an international phase III study. Patients and Methods: Newly diagnosed patients with chronic phase CML were randomly assigned to imatinib or interferon alfa plus subcutaneous low-dose cytarabine (IFN+LDAC). Cross-over to the other treatment was permitted because of intolerance or lack of efficacy. Patients completed cancer-specific QOL (Functional Assessment of Cancer Therapy–Biologic Response Modifiers) and utility (Euro QoL-5D) questionnaires at baseline and during treatment (n = 1,049). The primary QOL end point was the Trial Outcome Index (TOI; a measure of physical function and well-being). Secondary end points included social and family well-being (SFWB), emotional well-being (EWB), and the utility score. Primary analyses were intention to treat with secondary analyses accounting for cross-over. Results: Patients receiving IFN+LDAC experienced a large decline in the TOI, whereas those receiving imatinib maintained their baseline level. Treatment differences at each visit were significant (P &lt; .001) and clinically relevant in favor of imatinib. Mean SFWB, EWB, and utility scores were also significantly better for those patients taking imatinib. Patients who crossed over to imatinib experienced a large increase in TOI; significant (P &lt; .001) differences were observed between patients who did and did not cross over in favor of imatinib. Conclusion: Imatinib offers clear QOL advantages compared with IFN+LDAC as first-line treatment of chronic phase CML. In addition, patients who cross over to imatinib from IFN+LDAC experience a significant improvement in QOL compared with patients who continue to take IFN+LDAC.
Presence of substance P and neurokinin 1 receptors in human sputum macrophages and U‐937 cells
Authors: P.R. Germonpre, G.R. Bullock, B.n Lambrecht, V Van De Velde, W.H.M.l Luyten, G.f Joos, R.a Pauwels
Journal: European Respiratory Journal (1999)

Tachykinins such as substance P (SP) may be involved in the pathogenesis of inflammatory airway diseases such as asthma. This study investigated the presence of SP and its receptor in the differentiated macrophage-like U-937 cell line and in macrophages from sputum induced in healthy subjects (n=8). In situ hybridization with digoxigenin-labelled sense and antisense complementary ribonucleic acid (cRNA) probes was used to determine the expression of SP and its receptor (neurokinin (NK)1 receptor). SP-immunoreactive material was detected using a rabbit anti-SP antiserum and the alkaline phosphatase anti-alkaline phosphatase technique. Beta-preprotachykinin (PPT)-I messenger ribonucleic acid (mRNA) encoding SP, was detected using in situ hybridization in differentiated U-937 cells as well as in CD45+ human leukocyte antigen (HLA) DR+ sputum macrophages. The expression of the beta-PPT-I mRNA was increased in lipopolysaccharide (LPS)-stimulated U-937 cells. SP-immunoreactive material was found in differentiated U-937 cells and in CD68+ sputum macrophages. NK1 receptor mRNA was detected in differentiated U-937 cells and sputum macrophages. Incubation of U-937 cells with SP considerably increased the expression of NK1 receptor mRNA. This study demonstrates that human monocytes/macrophages express substance P and that this expression is upregulated by lipopolysacharide. Human monocytes/macrophages also express neurokinin1 receptor messenger ribonucleic acid, suggesting an autocrine effect of substance P on these cells.
Training effects of short bouts of stair climbing on cardiorespiratory fitness, blood lipids, and homocysteine in sedentary young women
Authors: C A G Boreham, R A Kennedy, M H Murphy, M Tully, W F M Wallace, I Young
Journal: British Journal of Sports Medicine (2005)

To study the training effects of eight weeks of stair climbing on Vo2max, blood lipids, and homocysteine in sedentary, but otherwise healthy young women.Fifteen women (mean (SD) age 18.8 (0.7) years) were randomly assigned to control (n = 7) or stair climbing (n = 8) groups. Stair climbing was progressively increased from one ascent a day in week 1 to five ascents a day in weeks 7 and 8. Training took place five days a week on a public access staircase (199 steps), at a stepping rate of 90 steps a minute. Each ascent took about two minutes to complete. Subjects agreed not to change their diet or lifestyle over the experimental period.Relative to controls, the stair climbing group displayed a 17.1% increase in Vo2max and a 7.7% reduction in low density lipoprotein cholesterol (p < 0.05) over the training period. No change occurred in total cholesterol, high density lipoprotein cholesterol, triglycerides, or homocysteine.The study confirms that accumulating short bouts of stair climbing activity throughout the day can favourably alter important cardiovascular risk factors in previously sedentary young women. Such exercise may be easily incorporated into the working day and therefore should be promoted by public health guidelines.
Abstract 5124: 12-Lipoxygenase regulation of prostate cancer progression.
Authors: Elizabeth Tovar, Stephanie Tucker, Kenneth V. Honn
Journal: Cancer Research (2013)

Abstract The underlying mechanism by which elevated omega-6 fatty acids, like arachidonic acid, lead to increased prostate cancer (PCa) risk is unclear. However, it is known that the 12-Lipoxygenase (12-LOX) enzyme that metabolizes arachidonic acid, as well as the 12(S)-HETE metabolic end product together with its cognate receptor, 12-HETER1, are strongly associated with PCa. 12(S)-HETE affects many cancer phenotypes including cell migration and metastasis. It causes the disassembly of complex cellular anchors to the substrata called hemidesmosomes that are comprised of numerous proteins, including ITGB4, which we identified as an interacting partner of 12-LOX. ITGB4 also physically interacts with c-Met at the cell membrane in multiple cell lines, in a cell line and stimulus-specific manner. PCa metastases have increased levels of both 12-LOX and c-Met. Therefore we sought to determine if ITGB4, c-MET and 12-LOX comprise a signaling axis. Our findings revealed that HGF-c-Met-induced invasion could be attenuated by enzymatic inhibitors of 12LOX, but that addition of exogenous 12(S)-HETE could not overcome the block. Furthermore, the physical interaction between β4 and c-Met remained unaffected by enzymatic inhibitors in PCa cells. Likewise, LC-MS analyses, showed that HGF stimulation did not lead to increased 12(S)-HETE production, and knockdown of 12-HETER1, by shRNA had no effect on HGF-induced invasion. Therefore, we hypothesize that 12LOX has dual functions whereby its enzymatic activity leads to hemidesmosome dissociation and cell release from the substrata, and its capacity to modulate c-MET/ITGB4 signaling may be attributed to a scaffolding function. Citation Format: Elizabeth Tovar, Stephanie Tucker, Kenneth V. Honn. 12-Lipoxygenase regulation of prostate cancer progression. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5124. doi:10.1158/1538-7445.AM2013-5124
Genome-Wide SNP Analysis Reveals Population Structure and Demographic History of the Ryukyu Islanders in the Southern Part of the Japanese Archipelago
Authors: Takehiro Sato, Shigeki Nakagome, Chiaki Watanabe, Kyoko Yamaguchi, Akira Kawaguchi, Kae Koganebuchi, Kuniaki Haneji, Tetsutaro Yamaguchi, Tsunehiko Hanihara, Ken Yamamoto, Hajime Ishida, Shuhei Mano, Ryosuke Kimura, Hiroki Oota
Journal: Molecular Biology and Evolution (2014)

The Ryukyu Islands are located to the southwest of the Japanese Archipelago.Archaeological evidence has revealed the existence of prehistoric cultural differentiation between the northern Ryukyu islands of Amami and Okinawa, and the southern Ryukyu islands of Miyako and Yaeyama.To examine a genetic subdivision in the Ryukyu Islands, we conducted genome-wide SNP typing of inhabitants from the Okinawa Islands, the Miyako Islands, and the Yaeyama Islands.Principal component and cluster analyses revealed genetic differentiation between the inhabitants of the Okinawa and Miyako, as well as more recent migration from the Okinawa Islands to the Yaeyama Islands.No genetic affinity was observed between aboriginal Taiwanese and any of the Ryukyu populations.The genetic differentiation observed between the inhabitants of the Okinawa Islands and the Miyako Islands is likely to have arisen due to genetic drift rather than admixture with people from neighboring regions.Based on the observed genetic differences, the inhabitants of Okinawa and Miyako islands are considered to have separated during the Holocene.These findings suggest that the Pleistocene inhabitants, whose bones have been found on the southern Ryukyu Islands, did not make a major genetic contribution, if any, to the present-day inhabitants of the southern Ryukyu Islands.
The Composition and Optical Rotary Dispersion of Bovine Aqueous Humor
Authors: David A Cough
Journal: Diabetes Care (1982)

The concentration of over 20 biochemicals in bovine aqueous humor was determined by conventional means, and the contribution of each to the observed optical rotation was estimated. Of those studied, only glucose and the total proteins made a significant contribution. However, other unidentified chemicals apparently also contribute to the optical activity since it was not possible to reconstruct the actual aqueous humor optical rotation based on the chemicals included. Alternative experimental approaches that may yield more complete results are discussed. With further work, optical rotation might be used as the basis of a noninvasive sensor for measuring the glucose concentration of aqueous humor in the intact eye.
Two Randomized Trials of Linaclotide for Chronic Constipation
Authors: Anthony J. Lembo, Harvey A. Schneier, Steven J. Shiff, Caroline B. Kurtz, James E. MacDougall, Xinwei D. Jia, James Z. Shao, Bernard J. Lavins, Mark G. Currie, Donald A. Fitch, Brenda I. Jeglinski, Paul Eng, Susan M. Fox, Jeffrey M. Johnston
Journal: New England Journal of Medicine (2011)

Linaclotide is a minimally absorbed peptide agonist of the guanylate cyclase C receptor. In two trials, we aimed to determine the efficacy and safety of linaclotide in patients with chronic constipation.We conducted two randomized, 12-week, multicenter, double-blind, parallel-group, placebo-controlled, dual-dose trials (Trials 303 and 01) involving 1276 patients with chronic constipation. Patients received either placebo or linaclotide, 145 μg or 290 μg, once daily for 12 weeks. The primary efficacy end point was three or more complete spontaneous bowel movements (CSBMs) per week and an increase of one or more CSBMs from baseline during at least 9 of the 12 weeks. Adverse events were also monitored.For Trials 303 and 01, respectively, the primary end point was reached by 21.2% and 16.0% of the patients who received 145 μg of linaclotide and by 19.4% and 21.3% of the patients who received 290 μg of linaclotide, as compared with 3.3% and 6.0% of those who received placebo (P<0.01 for all comparisons of linaclotide with placebo). Improvements in all secondary end points were significantly greater in both linaclotide groups than in the placebo groups. The incidence of adverse events was similar among all study groups, with the exception of diarrhea, which led to discontinuation of treatment in 4.2% of patients in both linaclotide groups.In these two 12-week trials, linaclotide significantly reduced bowel and abdominal symptoms in patients with chronic constipation. Additional studies are needed to evaluate the potential long-term risks and benefits of linaclotide in chronic constipation. (Funded by Ironwood Pharmaceuticals and Forest Research Institute; ClinicalTrials.gov numbers, NCT00765882 and NCT00730015.).
Adherence to inhaled corticosteroids: An ancillary study of the Childhood Asthma Management Program clinical trial
Authors: Jerry A. Krishnan, Bruce G. Bender, Frederick S. Wamboldt, Stanley J. Szefler, N. Franklin Adkinson, Robert S. Zeiger, Robert A. Wise, Andrew L. Bilderback, Cynthia S. Rand
Journal: Journal of Allergy and Clinical Immunology (2011)
Characterization of binding and biological effects of monoclonal antibodies against a human tumor necrosis factor receptor.
Authors: T Espevik, M Brockhaus, H Loetscher, U Nonstad, R Shalaby
Journal: The Journal of Experimental Medicine (1990)

Three different antibodies against a human TNF receptor (htr-1, htr-5, and htr-9) have been examined for their binding pattern to U937 cells and ability to mimic TNF-alpha activity in U937 cells, Fs4 fibroblasts, and human endothelial cells. Flow cytometric analysis revealed that htr-5 and htr-9 bound specifically to a TNF receptor on U937 cells that could be blocked by pretreatment with rTNF-alpha. Pretreatment of U937 cells with rTNF-beta blocked the binding of htr-9, but to a lesser extent htr-5 binding. Pretreatment with htr-5 inhibited the binding of htr-9 to U937 cells while pretreatment with htr-9 did not inhibit htr-5 binding. These results indicate that htr-5 and htr-9 recognize distinct but overlapping epitopes of a human TNF receptor on U937 cells and that htr-5 may be close to a TNF-alpha-specific domain of the binding site. Pretreatment with htr-5 or htr-9 only minimally reduced binding of BrTNF-alpha to U937 cells; however, these antibodies were much more effective in inhibiting BrTNF-alpha binding to HL-60 cells. Furthermore, it was found that htr-1 and htr-9, but not htr-5, had TNF-alpha activity on U937 cells, Fs4 fibroblasts, and endothelial cells and that the TNF-alpha activity induced by htr-9 was completely inhibited by htr-5. However, the cytotoxic activity of TNF-alpha was only partially inhibited by htr-5 on U937 cells while htr-5 had no effect on TNF-alpha activity on Fs4 cells. The data suggest that a common epitope is involved in inducing TNF-alpha activity in three different cell systems.
HER-2, gp100, and MAGE-1 Are Expressed in Human Glioblastoma and Recognized by Cytotoxic T Cells
Authors: Gentao Liu, Han Ying, Gang Zeng, Christopher J. Wheeler, Keith L. Black, John S. Yu
Journal: Cancer Research (2004)

It has recently been demonstrated that malignant glioma cells express certain known tumor-associated antigens, such as HER-2, gp100, and MAGE-1. To further determine the possible utilization of these antigens for glioma immunotherapy and as surrogate markers for specific tumor antigen cytotoxicity, we characterized the presence of mRNA and protein expression in 43 primary glioblastoma multiforme (GBM) cell lines and 7 established human GBM cell lines. HER-2, gp100, and MAGE-1 mRNA expression was detected in 81.4%, 46.5%, and 39.5% of the GBM primary cell lines, respectively. Using immunoreactive staining analysis by flow cytometry, HER-2, gp100, and MAGE-1 protein expression was detected in 76%, 45%, and 38% of the GBM primary cell lines, respectively. HLA-A1-restricted epitope specific for MAGE-1 peptide (EADPTGHSY) CTL clone B07 and HLA-A2-restricted epitope specific for HER-2 peptide (KIFGSLAFL) CTL clone A05 and gp100 peptide (ITDQVPFSV) CTL clone CK3H6 were used in this study. The specificity of CTL clone was verified by HLA/peptide tetramer staining. Three CTL clones could efficiently recognize GBM tumor cells in an antigen-specific and MHC class I-restricted manner. IFN-gamma treatment can dramatically increase MHC class I expression of GBM tumor cells and significantly increase CTL recognition of tumor cells. Treatment with the DNA hypomethylating agent 5-aza-2'-deoxycytidine induced and up-regulated the mRNA expression of MAGE-1 and epitope presentation by autologous MHC. These data indicate that HER-2, gp100, and MAGE-1 could be used as tumor antigen targets for surrogate assays for antigen-specific CTLs or to develop antigen-specific active immunotherapy strategies for glioma patients.
Measurement of IgA-alpha 1-antitrypsin complex in rheumatoid arthritis: A question of specificity?
Authors: D L MATTEY, N B NIXON, P T DAWES, L J SCOTT, G I RUSSELL;, K. IWANA, S. AOTSUKA;, D. R STANWORTH
Journal: Annals of the Rheumatic Diseases (1997)

We feel we should comment on a recent article by Iwana et al 1 on the clinical value of measuring circulating IgA-αl-antitrypsin (IgA-AT) complex concentrations in patients with rheumatoid arthritis (RA) using a prototype ELISA kit. We are concerned about the specificity of the monoclonal antibody used as the capture reagent on their ELISA plates. The authors say that the antibody recognises specific epitopes on the IgA-AT complex. However no direct proof of this is provided here or in previous reports where this particular antibody has been used.2-6 Recently, in response to another study using this assay we provided data to show that the antibody recognises the complement regulatory protein, factor H.7 We have shown that replacing the ‘complex specific’ antibody with other monoclonal antibodies to factor H (OX23 and OX24) in the ELISA essentially makes no difference to measurement of ‘complex’ values. We have also shown that the ‘lgA-AT’ antibody recognises a different epitope on factor H to that recognised by OX23 and OX24, and feel that …
Graft-versus-host disease is enhanced by extracellular ATP activating P2X7R
Authors: Konrad Wilhelm, Jayanthi Ganesan, Tobias Müller, Christoph Dürr, Melanie Grimm, Andreas Beilhack, Christine D Krempl, Stephan Sorichter, Ulrike V Gerlach, Eva Jüttner, Alf Zerweck, Frank Gärtner, Patrizia Pellegatti, Francesco Di Virgilio, Davide Ferrari, Neeraja Kambham, Paul Fisch, Jürgen Finke, Marco Idzko, Robert Zeiser
Journal: Nature Medicine (2010)
Gender‐specific plasma proteomic biomarkers in patients with Anderson–Fabry disease
Authors: Zsuzsanna Hollander, Darlene L.Y. Dai, Brendan N. Putko, Haran Yogasundaram, Janet E. Wilson‐McManus, Richard B. Thompson, Aneal Khan, Michael L. West, Bruce M. McManus, Gavin Y. Oudit
Journal: European Journal of Heart Failure (2015)
SENSE AND THE SINGLE NEURON: Probing the Physiology of Perception
Authors: A. J. Parker, W. T. Newsome
Journal: Annual Review of Neuroscience (1998)

▪ Abstract The newly defined field of cognitive neuroscience attempts to draw together the study of all brain mechanisms that underlie our mental life. Historically, the major sensory pathways have provided the most trustworthy insights into how the brain supports cognitive functions such as perception, attention, and short-term memory. The links between neural activity and perception, in particular, have been studied revealingly in recent decades. Here we review the striking progress in this area, giving particular emphasis to the kinds of neural events that underlie the perceptual judgments of conscious observers.
Lack of Efficacy of Two Consecutive Treatments of Radioimmunotherapy With <sup>131</sup>I-cG250 in Patients With Metastasized Clear Cell Renal Cell Carcinoma
Authors: Adrienne H. Brouwers, Peter F.A. Mulders, Pieter H.M. de Mulder, Wim J.M. van den Broek, Wilhelmina C.A.M. Buijs, Carola Mala, Frank B.M. Joosten, Egbert Oosterwijk, Otto C. Boerman, Frans H.M. Corstens, Wim J.G. Oyen
Journal: Journal of Clinical Oncology (2005)

A previous activity dose-escalation study using 131I-labeled chimeric monoclonal antibody cG250 in patients with progressive metastatic renal cell carcinoma (RCC) resulted in occasional therapeutic responses. The present study was designed to determine the safety and therapeutic efficacy of two sequential high-dose treatments with 131I-cG250.Patients (n = 29) with progressive metastatic RCC received a low dose of (131)I-cG250 for assessment of preferential targeting of metastatic lesions, followed by the first radioimmunotherapy (RIT) with 2220 MBq/m2 131I-cG250 (n = 27) 1 week later. If no grade 4 hematologic toxicity was observed, a second low-dose 131I-cG250 (n = 20) was given 3 months later. When blood clearance was not accelerated, a second RIT of 131I-cG250 was administered at an activity-dose of 1110 MBq/m2 (n = 3) or 1665 MBq/m2 (n = 16). Patients were monitored weekly for toxicity, and tumor size was evaluated by computed tomography once every 3 months intervals.The maximum-tolerated dose (MTD) of the second RIT was 1,665 MBq/m2 because of dose-limiting hematological toxicity. Based on an intention-to-treat analysis, after two RIT treatments, the disease stabilized in five of 29 patients, whereas it remained progressive in 14 of 29 patients. Two patients received no RIT, and eight of 29 received only one 131I-cG250 RIT because of grade 4 hematologic toxicity, formation of human antichimeric antibodies, or disease progression.In patients with progressive end-stage RCC, the MTD of the second treatment was 75% of the MTD of the first RIT. In the majority of patients, two cycles of 131I-cG250 could be safely administered without severe toxicity. No objective responses were observed, but occasionally two RIT doses resulted in stabilization of previously progressive disease.