tbuckley/cabot-search huggingface dataset:
MULTIPLEXED PROTEIN ARRAY PLATFORMS FOR ANALYSIS OF AUTOIMMUNE DISEASES
Authors: Imelda Balboni, Steven M. Chan, Michael Kattah, Jessica D. Tenenbaum, Atul J. Butte, Paul J. Utz
Journal: Annual Review of Immunology (2006)

Several proteomics platforms have emerged in the past decade that show great promise for filling in the many gaps that remain from earlier studies of the genome and from the sequencing of the human genome itself. This review describes applications of proteomics technologies to the study of autoimmune diseases. We focus largely on biased technology platforms that are capable of analyzing a large panel of known analytes, as opposed to techniques such as two-dimensional gel electrophoresis (2DIGE) or mass spectroscopy that represent unbiased approaches (as reviewed in 1). At present, the main analytes that can be systematically studied in autoimmunity include autoantibodies, cytokines and chemokines, components of signaling pathways, and cell-surface receptors. We review the most commonly used platforms for such studies, citing important discoveries and limitations that exist. We conclude by reviewing advances in biomedical informatics that will eventually allow the human proteome to be deciphered.
Elevated Homocysteine Levels in Young Male Patients With Schizophrenia
Authors: Joseph Levine, Ziva Stahl, Ben Ami Sela, Slava Gavendo, Vladimir Ruderman, Robert H Belmaker
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: Elevated plasma homocysteine has been found to be a risk factor for Alzheimer's disease as well as cerebral vascular disease, suggesting that some risk factors can accelerate or increase the severity of several CNS disease processes. The authors measured plasma homocysteine levels in patients with chronic schizophrenia in their catchment area. METHOD: A one-way analysis of covariance with age and sex as covariates was performed on the total plasma homocysteine levels of 193 patients with schizophrenia compared with 762 subjects without the diagnosis of schizophrenia who were evaluated in a screening program for employee health. RESULTS: The effect of schizophrenia was marked: the mean homocysteine level was 16.3 μM (SD=11.8) in patients with schizophrenia compared with 10.6 μM (SD=3.6) in healthy comparison subjects. The difference between groups was almost entirely attributable to the homocysteine levels of young male patients with schizophrenia. CONCLUSIONS: Elevated levels of homocysteine in young male patients with schizophrenia could be related to the pathophysiology of aspects of this illness.
Comparison of Two Types of Mechanical Assistance in Experimental Heart Failure
Authors: PETER F. SALISBURY, CECIL E. CROSS, P. ANDRE RIEBEN, RICHARD J. LEWIN
Journal: Circulation Research (1960)

In open-chest dog experiments, 7 different types of cardiac failure were produced. In each type of failure, the effect of veno-arterial pumping and of left ventricular bypass (blood pumped from the left atrium to femoral artery) was investigated. Pressures were recorded in the left ventricle, the left atrium, the right ventricle, and the femoral artery. Veno-arterial pumping reversed failure of the right ventricle. It also was beneficial when overtransfusion had aggravated failure of the right or left ventricles, except in pre-existing aortic insufficiency. Veno-arterial pumping markedly increased decompensation of the left heart in the majority of observations, even though it occasionally reduced pressures in the left atrium and the right ventricle. The experiments suggest the use of veno-arterial pumping or of partial bypass with a heart-lung machine in acute cor pulmonale and in pulmonary congestion caused by abnormalities of the mitral valve where the left ventricle remains compensated. Veno-arterial pumping appears contraindicated in true failure of the left ventricle. Left ventricular bypass always restored compensation in all types of heart failure except cor pumonale. The experiments suggest the clinical use of left ventricular bypass in left heart failure.
BIS/BTS SARS guidelines
Authors: J H Lange
Journal: Thorax (2004)

The guidelines on severe acute respiratory syndrome (SARS) published by the British Infection Society (BIS) and the British Thoracic Society (BTS) in July 2003 recommend giving adult patients with suspected or probable SARS an N95 or equivalent mask and request that they wear this continuously.1 This recommendation was apparently provided to prevent the spread of the SARS coronavirus from the patient to the surrounding environment.

An N95 respirator (mask) is a negative pressure respirator which only filters air entering the mask, not leaving it.2 Those wearing this respirator will experience an additional burden on the breathing system in moving …
NCX-1000, a nitric oxide-releasing derivative of ursodeoxycholic acid, ameliorates portal hypertension and lowers norepinephrine-induced intrahepatic resistance in the isolated and perfused rat liver
Authors: Stefano Fiorucci, Elisabetta Antonelli, Vincenzo Brancaleone, Laura Sanpaolo, Stefano Orlandi, Eleonora Distrutti, Giancarlo Acuto, Carlo Clerici, Monia Baldoni, Piero Del Soldato, Antonio Morelli
Journal: Journal of Hepatology (2003)
A Role for Focal Adhesion Kinase Signaling in Tumor Necrosis Factor-α–Dependent Matrix Metalloproteinase-9 Production in a Cholangiocarcinoma Cell Line, CCKS1
Authors: Naing Naing Mon, Hitoki Hasegawa, Aye Aye Thant, Pengyu Huang, Yoko Tanimura, Takeshi Senga, Michinari Hamaguchi
Journal: Cancer Research (2006)

Abstract We have previously reported that tumor necrosis factor-α (TNF-α) stimulation of CCKS1, a cell line established from cholangiocarcinoma with i.p. dissemination, dramatically increased matrix metalloproteinase-9 (MMP-9) production and tumor invasion. We investigated the role of focal adhesion kinase (FAK) in TNF-α–dependent production of MMP-9 in CCKS1 and FAK-null mouse fibroblast cells. TNF-α stimulation of CCKS1 or wild-type fibroblasts substantially activated FAK phosphorylation and increased MMP-9 production. In contrast, FAK-null fibroblasts could not respond well to TNF-α stimulation. Conditional expression of wild-type FAK in FAK-null cells restored the TNF-α–dependent production of MMP-9. TNF-α treatment activated the kinase activity of FAK and its phosphorylation especially at Y397 and Y925. Phosphorylated FAK accumulated at focal adhesions and formed a complex with growth factor receptor binding protein 2 and SOS. In contrast, Y397F FAK and Y925F FAK, whose Y397 and Y925 were replaced with phenylalanine, respectively, as well as KD FAK, whose kinase was inactivated, could not restore the MMP-9 production. In addition, small interfering RNA against FAK drastically suppressed the TNF-α–dependent production of MMP-9 and inhibited the TNF-α–dependent invasion of CCKS1. Taken together, our results suggest the pivotal role of FAK in TNF-α–dependent production of MMP-9 and subsequent activation of tumor invasion. (Cancer Res 2006; 66(13): 6778-84)
Posttranslational modifications of recombinant myotube-synthesized human factor IX
Authors: Valder R. Arruda, James N. Hagstrom, Jeffrey Deitch, Terry Heiman-Patterson, Rodney M. Camire, Kirk Chu, Paul A. Fields, Roland W. Herzog, Linda B. Couto, Peter J. Larson, Katherine A. High
Journal: Blood (2001)
Pre-Emptive Treatment With Rituximab of Molecular Relapse After Autologous Stem Cell Transplantation in Mantle Cell Lymphoma
Authors: Niels S. Andersen, Lone B. Pedersen, Anna Laurell, Erkki Elonen, Arne Kolstad, Anne Marie Boesen, Lars M. Pedersen, Grete F. Lauritzsen, Roald Ekanger, Herman Nilsson-Ehle, Marie Nordström, Susanne Fredén, Mats Jerkeman, Mikael Eriksson, Jaan Väärt, Beatrice Malmer, Christian H. Geisler
Journal: Journal of Clinical Oncology (2009)

Minimal residual disease (MRD) is predictive of clinical progression in mantle-cell lymphoma (MCL). According to the Nordic MCL-2 protocol we prospectively analyzed the efficacy of pre-emptive treatment using rituximab to MCL patients in molecular relapse after autologous stem cell transplantation (ASCT).MCL patients enrolled onto the study, who had polymerase chain reaction (PCR) detectable molecular markers and underwent ASCT, were followed with serial PCR assessments of MRD in consecutive bone marrow and peripheral blood samples after ASCT. In case of molecular relapse with increasing MRD levels, patients were offered pre-emptive treatment with rituximab 375 mg/m(2) weekly for 4 weeks.Of 160 MCL patients enrolled, 145 underwent ASCT, of whom 78 had a molecular marker. Of these, 74 were in complete remission (CR) and four had progressive disease after ASCT. Of the CR patients, 36 underwent a molecular relapse up to 6 years (mean, 18.5 months) after ASCT. Ten patients did not receive pre-emptive treatment mainly due to a simultaneous molecular and clinical relapse, while 26 patients underwent pre-emptive treatment leading to reinduction of molecular remission in 92%. Median molecular and clinical relapse-free survival after pre-emptive treatment were 1.5 and 3.7 years, respectively. Of the 38 patients who remain in molecular remission for now for a median of 3.3 years (range, 0.4 to 6.6 years), 33 are still in clinical CR.Molecular relapse may occur many years after ASCT in MCL, and PCR based pre-emptive treatment using rituximab is feasible, reinduce molecular remission, and may prevent clinical relapse.
The Ly-49 and NKR-P1 Gene Families Encoding Lectin-Like Receptors on Natural Killer Cells: The NK Gene Complex
Authors: W M Yokoyama, W E Seaman
Journal: Annual Review of Immunology (1993)

Natural killer cells lyse tumor and virally infected cells in a specific manner that has not been molecularly characterized. Target cell expression of major histocompatibility complex (MHC) class I molecules is correlated with target cell resistance to natural killing. A mechanism to explain this observation is that NK cells may display two types of recognition and activation molecules that have opposing functions when bound to target cell ligands. One type of surface receptor such as the NKR-P1 molecule may activate NK activity whereas the other, represented by the mouse Ly-49 molecule, may engage target cell MHC molecules and inhibit cytotoxicity by transducing "negative" signals. NKR-P1 and Ly-49 are structurally related, and they are encoded by genetically linked loci in a chromosomal region, termed the NK gene complex (NKC), on distal mouse chromosome 6. Target cell susceptibility to natural killing may be dependent upon specific ligand-receptor interaction with these activating or inhibitory NKC-encoded molecules.
The Renin–Angiotensin System Mediates EGF Receptor–Vitamin D Receptor Cross-Talk in Colitis-Associated Colon Cancer
Authors: Urszula Dougherty, Reba Mustafi, Farhana Sadiq, Anas Almoghrabi, Devkumar Mustafi, Maggi Kreisheh, Sumana Sundaramurthy, Weicheng Liu, Vani J. Konda, Joel Pekow, Sharad Khare, John Hart, Loren Joseph, Alice Wyrwicz, Gregory S. Karczmar, Yan Chun Li, Marc Bissonnette
Journal: Clinical Cancer Research (2014)

Abstract Purpose: We previously showed that EGF receptor (EGFR) promotes tumorigenesis in the azoxymethane/dextran sulfate sodium (AOM/DSS) model, whereas vitamin D suppresses tumorigenesis. EGFR–vitamin D receptor (VDR) interactions, however, are incompletely understood. Vitamin D inhibits the renin–angiotensin system (RAS), whereas RAS can activate EGFR. We aimed to elucidate EGFR–VDR cross-talk in colorectal carcinogenesis. Experimental Design: To examine VDR–RAS interactions, we treated Vdr+/+ and Vdr−/− mice with AOM/DSS. Effects of VDR on RAS and EGFR were examined by Western blotting, immunostaining, and real-time PCR. We also examined the effect of vitamin D3 on colonic RAS in Vdr+/+ mice. EGFR regulation of VDR was examined in hypomorphic EgfrWaved2 (Wa2) and Egfrwild-type mice. Angiotensin II (Ang II)–induced EGFR activation was studied in cell culture. Results: Vdr deletion significantly increased tumorigenesis, activated EGFR and β-catenin signaling, and increased colonic RAS components, including renin and angiotensin II. Dietary VD3 supplementation suppressed colonic renin. Renin was increased in human colon cancers. In studies in vitro, Ang II activated EGFR and stimulated colon cancer cell proliferation by an EGFR-mediated mechanism. Ang II also activated macrophages and colonic fibroblasts. Compared with tumors from EgfrWaved2 mice, tumors from Egfrwild-type mice showed upregulated Snail1, a suppressor of VDR, and downregulated VDR. Conclusions: VDR suppresses the colonic RAS cascade, limits EGFR signals, and inhibits colitis-associated tumorigenesis, whereas EGFR increases Snail1 and downregulates VDR in colonic tumors. Taken together, these results uncover a RAS-dependent mechanism mediating EGFR and VDR cross-talk in colon cancer. Clin Cancer Res; 20(22); 5848–59. ©2014 AACR.
Statins worse pulmonary fibrosis through enhancing NLRP3 inflammasome activation
Authors: Jin-Fu Xu, George R. Washko, Hui-Ping Li, Augustine M.K. Choi, Gary M. Hunninghake
Journal: European Respiratory Journal (2012)

The role of statins is controversial. To evaluate the association between statin use and ILD. We used regression analyses to evaluate the association between statin use and interstitial lung abnormalities (ILA) in a large cohort of smokers from COPDGene. Next, we evaluated the effect of statin pretreatment on bleomycin-induced fibrosis in mice and explored the mechanism behind these observations in vitro. In COPDGene, 38% of subjects with ILA were taking statins compared to 27% of subjects without ILA. Statin use was positively associated in ILA (odds ratio [OR] 1.60, 95% confidence interval [CI] 1.03-2.50, P=0.04) after adjustment for covariates including a history of high cholesterol or coronary artery disease. This association was modified by the hydrophilicity of statin and the age of the subject. Next, we demonstrate that statin administration aggravates lung injury and fibrosis in bleomycin-treated mice. Statin pretreatment enhances caspase-1-mediated immune responses in vivo and in vitro; the latter responses were abolished in bone marrow-derived macrophages (BMDM) isolated from Nlrp3-/- and Casp1-/- mice. Finally, we provide further insights by demonstrating that statins enhance NLRP3-inflammasome activation by increasing mitochondrial reactive oxygen species generation in macrophages. Statin use is associated with ILA among smokers in the COPDGene study and enhances bleomycin-induced lung inflammation and fibrosis in the mouse through a mechanism involving enhanced NLRP3-inflammasome activation. Our findings suggest that clinicians should be aware that radiological evidence of ILD can develop in some COPD patients treated with statins.
Plasma amino-acid patterns in liver disease.
Authors: M Y Morgan, A W Marshall, J P Milsom, S Sherlock
Journal: Gut (1982)

Plasma amino-acid concentrations were measured in 167 patients with liver disease of varying aetiology and severity, all free of encephalopathy, and the results compared with those in 57 control subjects matched for age and sex. In the four groups of patients with chronic liver disease (26 patients with chronic active hepatitis, 23 with primary biliary cirrhosis, 11 with cryptogenic cirrhosis, and 48 with alcoholic hepatitis +/- cirrhosis) plasma concentrations of methionine were significantly increased, while concentrations of the three branched chain amino-acids were significantly reduced. In the first three groups of patients plasma concentrations of aspartate, serine, and one or both of the aromatic amino-acids tyrosine and phenylalanine were also significantly increased, while in the patients with alcoholic hepatitis +/- cirrhosis plasma concentrations of glycine, alanine, and phenylalanine were significantly reduced. In the three groups of patients with minimal, potentially reversible liver disease (31 patients with alcoholic fatty liver, 10 with viral hepatitis, and 18 with biliary disease) plasma concentrations of proline and the three branched chain amino-acids were significantly reduced. Patients with alcoholic fatty liver also showed significantly reduced plasma phenylalanine values. Most changes in plasma amino-acid concentrations in patients with chronic liver disease may be explained on the basis of impaired hepatic function, portal-systemic shunting of blood, and hyperinsulinaemia and hyperglucagonaemia. The changes in patients with minimal liver disease are less easily explained.
Toward a mechanistic psychology of dialogue
Authors: Martin J. Pickering, Simon Garrod
Journal: Behavioral and Brain Sciences (2004)

Traditional mechanistic accounts of language processing derive almost entirely from the study of monologue. Yet, the most natural and basic form of language use is dialogue. As a result, these accounts may only offer limited theories of the mechanisms that underlie language processing in general. We propose a mechanistic account of dialogue, the interactive alignment account, and use it to derive a number of predictions about basic language processes. The account assumes that, in dialogue, the linguistic representations employed by the interlocutors become aligned at many levels, as a result of a largely automatic process. This process greatly simplifies production and comprehension in dialogue. After considering the evidence for the interactive alignment model, we concentrate on three aspects of processing that follow from it. It makes use of a simple interactive inference mechanism, enables the development of local dialogue routines that greatly simplify language processing, and explains the origins of self-monitoring in production. We consider the need for a grammatical framework that is designed to deal with language in dialogue rather than monologue, and discuss a range of implications of the account.
Mesenchymal stem cells enhance survival and bacterial clearance in murine<i>Escherichia coli</i>pneumonia
Authors: Naveen Gupta, Anna Krasnodembskaya, Maria Kapetanaki, Majd Mouded, Xinping Tan, Vladimir Serikov, Michael A Matthay
Journal: Thorax (2012)

<h3>Rationale</h3> Bacterial pneumonia is the most common infectious cause of death worldwide and treatment is increasingly hampered by antibiotic resistance. Mesenchymal stem cells (MSCs) have been demonstrated to provide protection against acute inflammatory lung injury; however, their potential therapeutic role in the setting of bacterial pneumonia has not been well studied. <h3>Objective</h3> This study focused on testing the therapeutic and mechanistic effects of MSCs in a mouse model of Gram-negative pneumonia. <h3>Methods and results</h3> Syngeneic MSCs from wild-type mice were isolated and administered via the intratracheal route to mice 4 h after the mice were infected with <i>Escherichia coli</i>. 3T3 fibroblasts and phosphate-buffered saline (PBS) were used as controls for all in vivo experiments. Survival, lung injury, bacterial counts and indices of inflammation were measured in each treatment group. Treatment with wild-type MSCs improved 48 h survival (MSC, 55%; 3T3, 8%; PBS, 0%; p&lt;0.05 for MSC vs 3T3 and PBS groups) and lung injury compared with control mice. In addition, wild-type MSCs enhanced bacterial clearance from the alveolar space as early as 4 h after administration, an effect that was not observed with the other treatment groups. The antibacterial effect with MSCs was due, in part, to their upregulation of the antibacterial protein lipocalin 2. <h3>Conclusions</h3> Treatment with MSCs enhanced survival and bacterial clearance in a mouse model of Gram-negative pneumonia. The bacterial clearance effect was due, in part, to the upregulation of lipocalin 2 production by MSCs.
Cortical Deficits of Glutamic Acid Decarboxylase 67 Expression in Schizophrenia: Clinical, Protein, and Cell Type-Specific Features
Authors: Allison A. Curley, Dominique Arion, David W. Volk, Josephine K. Asafu-Adjei, Allan R. Sampson, Kenneth N. Fish, David A. Lewis
Journal: American Journal of Psychiatry (2011)

Cognitive deficits in schizophrenia are associated with altered activity of the dorsolateral prefrontal cortex, which has been attributed to lower expression of the 67 kDa isoform of glutamic acid decarboxylase (GAD67), the major γ-aminobutyric acid (GABA)-synthesizing enzyme. However, little is known about the relationship of prefrontal GAD67 mRNA levels and illness severity, translation of the transcript into protein, and protein levels in axon terminals, the key site of GABA production and function.Quantitative polymerase chain reaction was used to measure GAD67 mRNA levels in postmortem specimens of dorsolateral prefrontal cortex from subjects with schizophrenia and matched comparison subjects with no known history of psychiatric or neurological disorders (N=42 pairs). In a subset of this cohort in which potential confounds of protein measures were controlled (N=19 pairs), Western blotting was used to quantify tissue levels of GAD67 protein in tissue. In five of these pairs, multilabel confocal immunofluorescence was used to quantify GAD67 protein levels in the axon terminals of parvalbumin-containing GABA neurons, which are known to have low levels of GAD67 mRNA in schizophrenia.GAD67 mRNA levels were significantly lower in schizophrenia subjects (by 15%), but transcript levels were not associated with predictors or measures of illness severity or chronicity. In schizophrenia subjects, GAD67 protein levels were significantly lower in total gray matter (by 10%) and in parvalbumin axon terminals (by 49%).The findings that lower GAD67 mRNA expression is common in schizophrenia, that it is not a consequence of having the illness, and that it leads to less translation of the protein, especially in the axon terminals of parvalbumin-containing neurons, support the hypothesis that lower GABA synthesis in parvalbumin neurons contributes to dorsolateral prefrontal cortex dysfunction and impaired cognition in schizophrenia.
Gene expression correlates of clinical prostate cancer behavior
Authors: Dinesh Singh, Phillip G. Febbo, Kenneth Ross, Donald G. Jackson, Judith Manola, Christine Ladd, Pablo Tamayo, Andrew A. Renshaw, Anthony V. D'Amico, Jerome P. Richie, Eric S. Lander, Massimo Loda, Philip W. Kantoff, Todd R. Golub, William R. Sellers
Journal: Cancer Cell (2002)
Higher Levels of CSF Homovanillic Acid in Recently Abstinent Cocaine-Dependent Patients
Authors: Alec Roy, Jeffrey Berman, Redford Williams, Cynthia Kuhn, Bienvenido Gonzalez
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: The authors examined an index of dopaminergic neurotransmission in recently abstinent cocaine-dependent patients. METHOD: CSF concentrations of the dopamine metabolite homovanillic acid (HVA) were determined in 30 recently abstinent cocaine-dependent patients and 69 healthy comparison subjects. RESULTS: The cocaine-dependent patients had a significantly higher mean concentration of CSF HVA than did the healthy comparison group. CONCLUSIONS: Recently abstinent cocaine-dependent patients may show dysregulation of the central dopaminergic system.
Inflammation-Mediated Cytosine Damage: A Mechanistic Link between Inflammation and the Epigenetic Alterations in Human Cancers
Authors: Victoria Valinluck, Lawrence C. Sowers
Journal: Cancer Research (2007)

Abstract Aberrant methylation patterns have long been known to exist in the promoter regions of key regulatory genes in the DNA of tumor cells. However, the mechanisms by which these methylation patterns become altered during the transformation of normal cells to tumor cells have remained elusive. We have recently shown in in vitro studies that inflammation-mediated halogenated cytosine damage products can mimic 5-methylcytosine in directing enzymatic DNA methylation and in enhancing the binding of methyl-binding proteins whereas certain oxidative damage products inhibit both. We have therefore proposed that cytosine damage products could potentially interfere with normal epigenetic control by altering DNA-protein interactions critical for gene regulation and the heritable transmission of methylation patterns. These inflammation-mediated cytosine damage products may provide, in some cases, a mechanistic link between inflammation and cancer. [Cancer Res 2007;67(12):5583–6]