tbuckley/cabot-search huggingface dataset:
Jund is a determinant of macrophage activation and is associated with glomerulonephritis susceptibility
Authors: Jacques Behmoaras, Gurjeet Bhangal, Jennifer Smith, Kylie McDonald, Brenda Mutch, Ping Chin Lai, Jan Domin, Laurence Game, Alan Salama, Brian M Foxwell, Charles D Pusey, H Terence Cook, Timothy J Aitman
Journal: Nature Genetics (2008)
Single-cell systems-level analysis of human Toll-like receptor activation defines a chemokine signature in patients with systemic lupus erythematosus
Authors: William E. O'Gorman, Elena W.Y. Hsieh, Erica S. Savig, Pier Federico Gherardini, Joseph D. Hernandez, Leo Hansmann, Imelda M. Balboni, Paul J. Utz, Sean C. Bendall, Wendy J. Fantl, David B. Lewis, Garry P. Nolan, Mark M. Davis
Journal: Journal of Allergy and Clinical Immunology (2015)

Activation of Toll-like receptors (TLRs) induces inflammatory responses involved in immunity to pathogens and autoimmune pathogenesis, such as in patients with systemic lupus erythematosus (SLE). Although TLRs are differentially expressed across the immune system, a comprehensive analysis of how multiple immune cell subsets respond in a system-wide manner has not been described.We sought to characterize TLR activation across multiple immune cell subsets and subjects, with the goal of establishing a reference framework against which to compare pathologic processes.Peripheral whole-blood samples were stimulated with TLR ligands and analyzed by means of mass cytometry simultaneously for surface marker expression, activation states of intracellular signaling proteins, and cytokine production. We developed a novel data visualization tool to provide an integrated view of TLR signaling networks with single-cell resolution. We studied 17 healthy volunteer donors and 8 patients with newly diagnosed and untreated SLE.Our data revealed the diversity of TLR-induced responses within cell types, with TLR ligand specificity. Subsets of natural killer cells and T cells selectively induced nuclear factor κ light chain enhancer of activated B cells in response to TLR2 ligands. CD14(hi) monocytes exhibited the most polyfunctional cytokine expression patterns, with more than 80 distinct cytokine combinations. Monocytic TLR-induced cytokine patterns were shared among a group of healthy donors, with minimal intraindividual and interindividual variability. Furthermore, autoimmune disease altered baseline cytokine production; newly diagnosed untreated SLE patients shared a distinct monocytic chemokine signature, despite clinical heterogeneity.Mass cytometry defined a systems-level reference framework for human TLR activation, which can be applied to study perturbations in patients with inflammatory diseases, such as SLE.
Nanofiber-mediated inhibition of focal adhesion kinase sensitizes glioma stemlike cells to epidermal growth factor receptor inhibition
Authors: Maya Srikanth, Sunit Das, Eric J. Berns, Juno Kim, Samuel I. Stupp, John A. Kessler
Journal: Neuro-Oncology (2013)

Glioblastoma multiforme is the most common glioma in adults and carries a poor prognosis, due to tumor recurrence despite aggressive treatment. Such relapse has been attributed to the persistence of glioma stemlike cells (GSCs), a subpopulation of glioma cells with stem cell properties. Thus, targeting these cells will be critical to achieving meaningful improvement in glioblastoma multiforme survival. We investigated the role of β1-integrin signaling as one such potential target. We used GSCs isolated from primary human gliomas and maintained in stem cell conditions. We manipulated β1-integrin signaling using a self-assembling peptide amphiphile (PA) displaying the IKVAV (isoleucine-lysine-valine-alanine-valine) epitope as well as lentiviral overexpression, and we assayed the effects on downstream effectors and apoptosis using immunofluorescence. We show that β1-integrin expression correlates with decreased survival in glioma patients and that β1-integrin is highly expressed by GSCs. The IKVAV PA potently increases immobilized β1-integrin at the GSC membrane, activating integrin-linked kinase while inhibiting focal adhesion kinase (FAK). The IKVAV PA induces striking apoptosis in GSCs via this FAK inhibition, which is enhanced in combination with inhibition of epidermal growth factor receptor (EGFR). Conversely, lentiviral overexpression of β1-integrin renders GSCs resistant to EGFR inhibition, which was overcome by FAK inhibition. These observations reveal a role for β1-integrin signaling through FAK in GSC treatment resistance and introduce self-assembling PAs as a novel new therapeutic approach for overcoming this resistance.
Long-term follow-up of corticosteroid injection for traumatic olecranon bursitis.
Authors: P S Weinstein, J J Canoso, J R Wohlgethan
Journal: Annals of the Rheumatic Diseases (1984)

Forty-seven patients with traumatic olecranon bursitis were evaluated after a mean follow-up of 31 months (range 6 to 62 months). Twenty-two patients treated with bursal aspiration had delayed recovery and no complications of therapy. Twenty-five patients treated with intrabursal injection of 20 mg of triamcinolone hexacetonide had rapid recovery, usually within one week, but suffered complications such as infection (3 cases), skin atrophy (5 cases), and chronic local pain (7 cases). Since spontaneous resolution can be expected, a conservative approach is suggested in the treatment of traumatic olecranon bursitis.
Pretreatment serum levels of matrix metalloproteinase-9 and vascular endothelial growth factor in non-small-cell lung cancer
Authors: E. Laack, A. Köhler, C. Kugler, T. Dierlamm, C. Knuffmann, G. Vohwinkel, A. Niestroy, N. Dahlmann, A. Peters, J. Berger, W. Fiedler, D.K. Hossfeld
Journal: Annals of Oncology (2002)
Neuroanatomic Variation in Monozygotic Twin Pairs Discordant for the Narrow Phenotype for Autism
Authors: Wendy R Kates, Courtney P Burnette, Stephan Eliez, Leslie Abbott Strunge, Desmond Kaplan, Rebecca Landa, Allan L Reiss, Godfrey D Pearlson
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: The broader autism phenotype includes relatives of individuals with autism who display social and language deficits that are qualitatively similar to those of autism but less severe. In previous studies of monozygotic twins discordant for autism, more than 75% of the twins without autism displayed the broader phenotype. Differences in neuroanatomy between discordant monozygotic twins might be associated with the narrow and broader behavioral phenotypes. The authors examined the relationship of twin pair differences in clinical phenotype to differences in neuroanatomic phenotype. METHOD: The subjects were 16 monozygotic twin pairs between the ages of 5 and 14 years and 16 matched singleton comparison subjects. Seven twin pairs were clinically concordant and nine twin pairs were clinically discordant for strictly defined autism. After magnetic resonance imaging, a semiautomated procedure was applied to images in which the brain tissue was subdivided into neurofunctional regions and segmented into gray, white, and ventricular compartments. RESULTS: Both the concordant and discordant twin pairs exhibited concordance in cerebral gray and white matter volumes. However, only the clinically concordant pairs exhibited concordance in cerebellar gray and white matter volumes. Within the discordant twin pairs, both the twins with autism and their co-twins exhibited frontal, temporal, and occipital white matter volumes that were lower than those of the comparison subjects. CONCLUSIONS: These findings support the role and the limits of genetic liability in autism. Continuing to clarify the neuroanatomic pathways in autistic spectrum disorders could illuminate the etiology of autism and, ultimately, contribute to treatments.
Expression of C/EBPβ from the C/ebpα gene locus is sufficient for normal hematopoiesis in vivo
Authors: Letetia C. Jones, Meng-Liang Lin, Shih-Shun Chen, Utz Krug, Wolf-K. Hofmann, Stephen Lee, Ying-Hue Lee, H. Phillip Koeffler
Journal: Blood (2002)
Spironolactone Prevents Diabetic Nephropathy through an Anti-Inflammatory Mechanism in Type 2 Diabetic Rats
Authors: Sang-Youb Han, Cy-Hyun Kim, Han-Seong Kim, Yi-Hwa Jee, Hye-Kyoung Song, Mi-Hwa Lee, Kum-Hyun Han, Hyoung-Kyu Kim, Young-Sun Kang, Jee-Young Han, Young-Sik Kim, Dae-Ryong Cha
Journal: Journal of the American Society of Nephrology (2006)

Aldosterone induces myocardial fibrosis and vascular inflammation via proinflammatory and profibrotic cytokines. The effect of spironolactone on renal inflammation and renal function was investigated in type 2 diabetic rats. For define the molecular mechanism of spironolactone, the effect of spironolactone on the synthesis of monocyte chemotactic peptide-1 (MCP-1) and its upstream transcription factor, NF-kappaB, was evaluated in cultured mesangial cells and proximal tubular cells. There were no changes in blood glucose concentration or BP after spironolactone treatment. Spironolactone treatment significantly reduced urinary albumin excretion and ameliorated glomerulosclerosis. Urinary levels of MCP-1 were significantly increased concurrently with renal expression of MCP-1, macrophage migration inhibitory factor, and macrophage infiltration. Spironolactone treatment significantly inhibited urinary excretion of MCP-1 as well as renal MCP-1 and migration inhibitory factor expression and macrophage infiltration. In addition, aldosterone induced upregulation of MCP-1 expression and NF-kappaB transcriptional activity in cultured cells, and spironolactone reduced both NF-kappaB activation and MCP-1 synthesis. Furthermore, NF-kappaB inhibition abolished aldosterone-induced MCP-1 production. Overall, these findings suggest that aldosterone-induced NF-kappaB activation leads to activation of proinflammatory cytokines, ultimately leading to renal injury in this model. These data suggest that mineralocorticoid blockade may be a potential therapeutic target in diabetic nephropathy.
Nitric Oxide–Donating Aspirin Derivatives Suppress Microsatellite Instability in Mismatch Repair–Deficient and Hereditary Nonpolyposis Colorectal Cancer Cells
Authors: Michael A. McIlhatton, Jessica Tyler, Susan Burkholder, Josef Ruschoff, Basil Rigas, Levy Kopelovich, Richard Fishel
Journal: Cancer Research (2007)

Abstract Nitric oxide–donating nonsteroidal anti-inflammatory drugs (NO-NSAIDs) are an emergent class of pharmaceutical derivatives with promising utility as cancer chemopreventive agents. Aspirin and sulindac have been shown to be effective in selecting for cells with reduced microsatellite instability (MSI) that is inherent in mismatch repair (MMR)–deficient hereditary nonpolyposis colorectal cancer (HNPCC) cells. The effect of NO-NSAIDs on MSI in MMR-deficient HNPCC cells is unknown. Here, we have examined genetically defined MMR-deficient murine embryo fibroblasts, murine colonocytes, and isogenic human HNPCC tumor cell lines treated with acetylsalicylic acid (aspirin; ASA) and three isomeric derivatives of NO-aspirin (NO-ASA). The MSI profiles were determined and compared with the Bethesda Criteria. We found that the ASA- and NO-ASA–treated MMR-deficient cell lines displayed a dose-dependent suppression of MSI that appeared as early as 8 weeks and gradually increased to include up to 67% of the microsatellite sequences examined after 19 to 20 weeks of continuous treatment. Residual resistance to microsatellite stabilization was largely confined to mononucleotide repeat sequences. Control (MMR-proficient) cells showed no changes in microsatellite status with or without treatment. The relative dose-dependent stabilization selection was: ortho-NO-ASA ≈ para-NO-ASA &amp;gt; meta-NO-ASA ≫ ASA. Moreover, the doses required for stabilization by the ortho- and para-NO-ASA were 300- to 3,000-fold lower than ASA. These results suggest that NO-ASA derivatives may be more effective at suppressing MSI in MMR-deficient cell lines than ASA and should be considered for chemopreventive trials with HNPCC carriers. [Cancer Res 2007;67(22):10966–75]
Evaluation of Bilirubin in a Liver Screening Panel
Authors: Andrew N. Brown
Journal: JAMA (1992)

<h3>To the Editor.</h3> —Since 1984, the clinical laboratory at the medical center of the University of California, San Francisco, has offered a three-test "liver panel" (bilirubin, alkaline phosphatase, and aspartate aminotransferase) for screening for liver disease. A clinician could order all three tests by selecting the "liver panel" option on the clinical laboratory order form. We recently investigated the contribution of bilirubin to this panel. We used the Combined Patient Experience database (University of California, San Francisco, Department of Laboratory Medicine), which was created by linkage of computerized data from three sources: the clinical laboratory, hospital information, and medical records. The database contains diagnostic, demographic, and laboratory test information for all inpatients during the study 1986 and 1987. Forty percent (12 459/31 064) of the adults aged ≥19 years during these 2 years had all three tests performed within 48 hours of admission. These 12 459 admissions constituted our study
Postmortem inflation and fixation of human lungs: A technique for pathological and radiological correlations
Authors: B. M. Wright, G. Slavin, L. Kreel, K. Callan, B. Sandin
Journal: Thorax (1974)

<b>Wright, B. M., Slavin, G., Kreel, L., Callan, K., and Sandin, Brenda (1974).</b><i>Thorax</i>, <b>29</b>, 189-194. <b>Postmortem inflation and fixation of human lungs.</b> A method of fixing lungs by inflating them with heated formalin vapour is described. This method facilitates postmortem correlations between radiographic and histological appearances.
A novel clinical role for angiopoietin-1 in malignant pleural mesothelioma
Authors: C. Tabata, N. Hirayama, R. Tabata, A. Yasumitsu, S. Yamada, A. Murakami, S. Iida, K. Tamura, K. Fukuoka, K. Kuribayashi, T. Terada, T. Nakano
Journal: European Respiratory Journal (2010)

Malignant pleural mesothelioma (MPM) is an aggressive malignant tumour associated with asbestos exposure that has only a limited response to conventional therapy; therefore, diagnosing MPM early is very important. We have previously reported that angiopoietin (Ang)-1 was correlated with bleomycin-induced pulmonary fibrosis. Here, we investigated the association of Ang-1 with the development of MPM cells, which originate from mesenchymal cells similar to lung fibroblasts, and demonstrated that Ang-1 stimulated the growth and migration of MPM cells in vitro. We also demonstrated that patients with MPM had significantly higher serum levels of Ang-1 in comparison to a population who had been exposed to asbestos but had not developed MPM. The patients with advanced-stage MPM showed higher levels of Ang-1 than the early-stage MPM patients and the Kaplan-Meier method revealed a significant correlation between serum Ang-1 levels and survival. We propose the possibility that Ang-1 plays an important role in MPM tumour growth and our data suggest that the serum concentration of Ang-1 could be useful as prognostic factor.
A network perspective on the evolution of metabolism by gene duplication
Authors: Juan Javier Díaz-Mejía, Ernesto Pérez-Rueda, Lorenzo Segovia
Journal: Genome biology (2007)

Gene duplication followed by divergence is one of the main sources of metabolic versatility. The patchwork and stepwise models of metabolic evolution help us to understand these processes, but their assumptions are relatively simplistic. We used a network-based approach to determine the influence of metabolic constraints on the retention of duplicated genes.We detected duplicated genes by looking for enzymes sharing homologous domains and uncovered an increased retention of duplicates for enzymes catalyzing consecutive reactions, as illustrated by the ligases acting in the biosynthesis of peptidoglycan. As a consequence, metabolic networks show a high retention of duplicates within functional modules, and we found a preferential biochemical coupling of reactions that partially explains this bias. A similar situation was found in enzyme-enzyme interaction networks, but not in interaction networks of non-enzymatic proteins or gene transcriptional regulatory networks, suggesting that the retention of duplicates results from the biochemical rules governing substrate-enzyme-product relationships. We confirmed a high retention of duplicates between chemically similar reactions, as illustrated by fatty-acid metabolism. The retention of duplicates between chemically dissimilar reactions is, however, also greater than expected by chance. Finally, we detected a significant retention of duplicates as groups, instead of single pairs.Our results indicate that in silico modeling of the origin and evolution of metabolism is improved by the inclusion of specific functional constraints, such as the preferential biochemical coupling of reactions. We suggest that the stepwise and patchwork models are not independent of each other: in fact, the network perspective enables us to reconcile and combine these models.
Highly Localized Arterial Remodeling in Patients With Coronary Atherosclerosis
Authors: Hans Berglund, Huai Luo, Toshihiko Nishioka, Michael C. Fishbein, Neal L. Eigler, Steven W. Tabak, Robert J. Siegel
Journal: Circulation (1997)

Background Preservation of luminal area and symmetry in the presence of irregular plaques necessitates local expansion of the artery wall. Methods and Results Cross-sectional dimensions of coronary arteries in 65 patients were measured with the use of intravascular ultrasound. A total of 104 arterial segments were studied, of which 88 had atherosclerosis; 16 served as nonatherosclerotic control segments. Three features of atherosclerotic arterial segments were classified: (1) plaque formation, (2) lumen shape, and (3) shape of arterial external elastic lamina. With our intravascular ultrasound–based three-level classification system, we identified three patterns that accounted for 89% of all atherosclerotic arterial segments: (1) concentric plaque with a circular lumen and a circular external elastic lamina (n=17), (2) eccentric plaque with a circular lumen and an oval external elastic lamina (n=35), and (3) eccentric plaque with an oval lumen and a circular external elastic lamina (n=26). A circular lumen was preserved in 66% of all atherosclerotic arterial segments. Arterial segments with a circular lumen in the presence of an eccentric plaque had a significantly larger lumen area than the other two main groups ( P &lt;.05). Conclusions With our intravascular ultrasound–based classification, we provided information regarding the local remodeling response in the coronary artery wall. In a majority of cases, a circular lumen is maintained. Failure of this highly localized response to be operative may contribute to the development of stenotic lesions at a specific site in the artery.
C-Reactive Protein–Mediated Low Density Lipoprotein Uptake by Macrophages
Authors: Thomas P. Zwaka, Vinzenz Hombach, Jan Torzewski
Journal: Circulation (2001)

LDL and C-reactive protein (CRP) are important cardiovascular risk factors. Both LDL and CRP deposit in the arterial wall during atherogenesis. Stranded LDL is taken up by macrophages, causing foam cell formation. Because native LDL does not induce foam cell formation, we hypothesized that CRP may opsonize native LDL for macrophages.Monocytes were isolated from human blood and transformed into macrophages. CRP/LDL uptake was assessed by immunofluorescent labeling and the use of confocal laser scanning microscopy. Native LDL coincubated with CRP was taken up by macrophages by macropinocytosis. Uptake of the CRP/LDL coincubate was mediated by the CRP receptor CD32.We conclude that foam cell formation in human atherogenesis may be caused in part by uptake of CRP-opsonized native LDL.
Durations of Transmembrane Action Potentials and Functional Refractory Periods of Canine False Tendon and Ventricular Myocardium:
Authors: E. NEIL MOORE, JAMES B. PRESTON, GORDON K. MOE
Journal: Circulation Research (1965)

In vitro studies have shown that alterations in the ionic composition of the perfusion fluid, substitution of blood or plasma for Tyrode's solution, time lapse following removal of the cardiac preparation from the animal, and addition of varying amounts of acetylcholine and/or epinephrine, do not change differentially the functional refractory period and action potential duration of false tendon and papillary muscle fibers; false tendon values exceeded those of papillary muscle in all of the above conditions. Cycle length was the only variable found to influence differentially false tendon and papillary muscle functional refractory periods and action potential durations. At very short cycle lengths, produced by premature responses, the functional refractory period and action potential duration of false tendon and papillary muscle cells approached each other. In some experiments the functional refractory periods of premature false tendon responses were less than corresponding values for papillary muscle. The relationship between the action potential durations and functional refractory periods of canine epicardial and endocardial cells was investigated also. It was found that the epicardial cells had a shorter functional refractory period and action potential duration than endocardial units when studied at physiological rates.
KRAB Zinc Finger Protein ZNF382 Is a Proapoptotic Tumor Suppressor That Represses Multiple Oncogenes and Is Commonly Silenced in Multiple Carcinomas
Authors: Yingduan Cheng, Hua Geng, Suk Hang Cheng, Pei Liang, Yan Bai, Jisheng Li, Gopesh Srivastava, Margaret H.L. Ng, Tatsuo Fukagawa, Xiushan Wu, Anthony T.C. Chan, Qian Tao
Journal: Cancer Research (2010)

Zinc finger transcription factors are involved broadly in development and tumorigenesis. Here, we report that the little studied zinc finger transcription factor ZNF382 functions as a tumor suppressor in multiple carcinomas. Although broadly expressed in normal tissues, ZNF382 expression was attenuated in multiple carcinoma cell lines due to promoter CpG methylation. ZNF382 was also frequently methylated in multiple primary tumors (nasopharyngeal, esophageal, colon, gastric, and breast). Ectopic expression of ZNF382 in silenced tumor cells significantly inhibited their clonogenicity and proliferation and induced apoptosis. We further found that ZNF382 inhibited NF-kappaB and AP-1 signaling and downregulated the expression of multiple oncogenes including MYC, MITF, HMGA2, and CDK6, as well as the NF-kappaB upstream factors STAT3, STAT5B, ID1, and IKBKE, most likely through heterochromatin silencing. ZNF382 could suppress tumorigenesis through heterochromatin-mediated silencing, as ZNF382 was colocalized and interacted with heterochromatin protein HP1 and further changed the chromatin modifications of ZNF382 target oncogenes. Our data show that ZNF382 is a functional tumor suppressor frequently methylated in multiple carcinomas.