tbuckley/cabot-search huggingface dataset:
Three-Gene Prognostic Classifier for Early-Stage Non–Small-Cell Lung Cancer
Authors: Suzanne K. Lau, Paul C. Boutros, Melania Pintilie, Fiona H. Blackhall, Chang-Qi Zhu, Dan Strumpf, Michael R. Johnston, Gail Darling, Shaf Keshavjee, Thomas K. Waddell, Ni Liu, Davina Lau, Linda Z. Penn, Frances A. Shepherd, Igor Jurisica, Sandy D. Der, Ming-Sound Tsao
Journal: Journal of Clinical Oncology (2007)

Several microarray studies have reported gene expression signatures that classify non-small-cell lung carcinoma (NSCLC) patients into different prognostic groups. However, the prognostic gene lists reported to date overlap poorly across studies, and few have been validated independently using more quantitative assay methods.The expression of 158 putative prognostic genes identified in previous microarray studies was analyzed by reverse transcription quantitative polymerase chain reaction in the tumors of 147 NSCLC patients. Concordance indices and risk scores were used to identify a stage-independent set of genes that could classify patients with significantly different prognoses.We have identified a three-gene classifier (STX1A, HIF1A, and CCR7) for overall survival (hazard ratio = 3.8; 95% CI, 1.7 to 8.2; P < .001). The classifier was also able to stratify stage I and II patients and further improved the predictive ability of clinical factors such as histology and tumor stage. The predictive value of this three-gene classifier was validated in two large independent microarray data sets from Harvard and Duke Universities.We have identified a new three-gene classifier that is independent of and improves on stage to stratify early-stage NSCLC patients with significantly different prognoses. This classifier may be tested further for its potential value to improve the selection of resected NSCLC patients in adjuvant therapy.
Exochelins of Mycobacterium tuberculosis remove iron from human iron-binding proteins and donate iron to mycobactins in the M. tuberculosis cell wall.
Authors: J Gobin, M A Horwitz
Journal: The Journal of Experimental Medicine (1996)

To multiply and cause disease in the host, Mycobacterium tuberculosis must acquire iron from the extracellular environment at sites of replication. To do so, the bacterium releases high-affinity iron-binding siderophores called exochelins. In previous studies, we have described the purification and characterization of the exochelin family of molecules. These molecules share a common core structure with another type of high-affinity iron-binding molecule located in the cell wall of M. tuberculosis: the mycobactins. The water-soluble exochelins differ from each other and from water insoluble mycobactins in polarity, which is dependent primarily upon the length and modifications of an alkyl side chain. In this study, we have investigated the capacity of purified exochelins to remove iron from host high-affinity iron-binding molecules, and to transfer iron to mycobactins. Purified desferri-exochelins rapidly removed iron from human transferrin, whether it was 95 or 40% iron saturated, its approximate percent saturation in human serum, and from human lactoferrin. Desferri-exochelins also removed iron, but at a slower rate, from the iron storage protein ferritin. Purified ferri-exochelins, but not iron transferrin, transferred iron to desferri-mycobactins in the cell wall of live bacteria. To explore the possibility that the transfer iron from exochelins to mycobactins was influenced by their polarity, we investigated the influence of polarity on the iron affinity of exochelins. Exochelins of different polarity exchanged iron equally with each other. This study supports the concept that exochelins acquire iron for M. tuberculosis by removing this element from host iron-binding proteins and transferring it to desferri-mycobactins in the cell wall of the bacterium. The finding that ferri-exochelins but not iron transferrin transfer iron to mycobactins in the cell wall underscores the importance of exochelins in iron acquisition. This study also shows that the variable alkyl side chain on the core structure of exochelins and mycobactins, the principal determinant of their polarity, has little or no influence on their iron affinity.
-Glucosylceramide: a novel method for enhancement of natural killer T lymphoycte plasticity in murine models of immune-mediated disorders
Authors: E Zigmond, S Preston, O Pappo, G Lalazar, M Margalit, Z Shalev, L Zolotarov, D Friedman, R Alper, Y Ilan
Journal: Gut (2006)

<b>Background:</b> β-Glucosylceramide, a naturally occurring glycolipid, exerts modulatory effects on natural killer T (NKT) lymphocytes. <b>Aim:</b> To determine whether β-glucosylceramide can alter NKT function in opposite directions, colitis was induced by intracolonic installation of trinitrobenzenesulphonic acid, and hepatocellular carcinoma (HCC) was induced by transplantation of Hep3B cells. <b>Methods:</b> The immunological effect of β-glucosylceramide was assessed by analysis of intrahepatic and intrasplenic lymphocyte populations, serum cytokines and STAT protein expression. <b>Results:</b> Administration of β-glucosylceramide led to alleviation of colitis and to suppression of HCC, manifested by improved survival and decreased tumour volume. The beneficial effects were associated with an opposite immunological effect in the two models: the peripheral:intrahepatic CD4:CD8 lymphocyte ratio increased in the colitis model and decreased in the HCC group. The peripheral:intrahepatic NKT lymphocyte ratio decreased in β-glucosylceramide-treated mice solely in the HCC model. The effect of β-glucosylceramide was associated with decreased STAT1 and 4 expression, and with overexpression of STAT6, along with decreased interferon γ levels in the colitis model, whereas an opposite effect was noted in the HCC model. <b>Conclusions:</b> β-glucosylceramide alleviates immunologically incongruous disorders and may be associated with “fine tuning” of immune responses, by changes in plasticity of NKT lymphocytes.
Letter Regarding Article by Tsimikas et al, “High-Dose Atorvastatin Reduces Total Plasma Levels of Oxidized Phospholipids and Immune Complexes Present on Apolipoprotein B-100 in Patients With Acute Coronary Syndromes in the MIRACL Trial”
Authors: Lambertus J. van Tits, Jacqueline de Graaf, Anton F. Stalenhoef
Journal: Circulation (2005)
Prognostic factors for malignant mesothelioma in 142 patients: validation of CALGB and EORTC prognostic scoring systems
Authors: J G Edwards
Journal: Thorax (2000)

<b><i>Objective:</i></b> To test whether female gonadal hormone status and estrogen modulate the metabolism of Aβ peptides in vivo. <b><i>Background:</i></b> AD is a neurodegenerative disorder characterized by accumulation of aggregated forms of the 40- and 42-amino acid Aβ peptides (Aβ40 and Aβ42). Estrogen replacement therapy in postmenopausal women is associated with decreased risk for AD or delay in disease onset or both. The mechanism by which estrogen exerts this neuroprotective effect is elusive. 17β-estradiol (E2) was shown to reduce the release of Aβ peptides by primary neuronal cultures of murine and human origin. <b><i>Methods:</i></b> For this purpose, four experimental sets of guinea pigs were used: intact animals, ovariectomized animals (ovx), and ovariectomized animals that received E2 at two different doses (ovx+low-dose E2 and ovx+high-dose E2). Brain Aβ40 and Aβ42 levels were assessed using Aβ40 and Aβ42-specific ELISA assays. <b><i>Results:</i></b> Prolonged ovariectomy resulted in uterine atrophy and decreased serum E2 levels and was associated with a pronounced increase in brain Aβ levels. Total brain Aβ in the ovx animals was increased by 1.5-fold on average as compared to intact controls. E2 treatment of ovariectomized animals led to uterine hypertrophy and a dose-dependent increase in serum E2 levels. In addition, both doses of E2 significantly reversed the ovariectomy-induced increase in brain Aβ levels. The high-dose E2 treatment did not lead to a further decrease in brain Aβ beyond that observed with the low-dose E2 treatment. <b><i>Conclusions:</i></b> Our results infer that cessation of ovarian estrogen production in postmenopausal women might facilitate Aβ deposition by increasing the local concentrations of Aβ40 and Aβ42 peptides in brain. In addition, our finding that E2 treatment is associated with diminution of brain Aβ levels suggests that modulation of Aβ metabolism may be one of the ways by which estrogen replacement therapy prevents or delays the onset of AD or both in postmenopausal women.
Major increase in brain natriuretic peptide indicates right ventricular systolic dysfunction in patients with heart failure
Authors: Denis Mariano‐Goulart, Marie‐Claude Eberlé, Vincent Boudousq, Azadeh Hejazi‐Moughari, Christophe Piot, Charles Caderas de Kerleau, Régis Verdier, Marie‐Luce Barge, Frédéric Comte, Nicole Bressot, Michel Rossi, Pierre‐Olivier Kotzki
Journal: European Journal of Heart Failure (2003)
Surgical treatment of isolated coarctation of the aorta: 18 years' experience.
Authors: P R Behl, P Sante, A Blesovsky
Journal: Thorax (1987)

From March 1967 to February 1985 91 patients aged from 11 months to 53 years underwent surgical treatment of isolated coarctation of the aorta. The surgical procedures in descending order of frequency, were: resection with end to end anastomosis, resection with replacement by a tube graft, patch aortoplasty, and bypass graft. Resection with end to end anastomosis was achieved mainly in younger patients. The number of patients needing other procedures increased with advancing age. Eighty six patients have been followed up (mean 10 years). There were no hospital or late deaths and none of the patients suffered from spinal cord injury. There were three recurrences of the coarctation, all in patients who had had primary reconstruction below the age of one year. The patients were divided into three groups by age: group 1, 0-5 years; group 2, 6-15 years; and group 3, over 15 years. It was found that there was no late hypertension in group 1 while hypertension persisted in 7% of group 2 and in 28% of group 3. Fifty per cent of the patients with persistent hypertension were above the age of 20 years at the time of operation and had resection with replacement by a tube graft. It is recommended that elective surgery for coarctation of the aorta should be performed at the age of 3-5 years to avoid both recurrence of stenosis and persistent hypertension.
Protesting too much: Self-deception and self-signaling
Authors: Ryan McKay, Danica Mijović-Prelec, Dražen Prelec
Journal: Behavioral and Brain Sciences (2011)

Abstract Von Hippel &amp; Trivers (VH&amp;T) propose that self-deception has evolved to facilitate the deception of others. However, they ignore the subjective moral costs of deception and the crucial issue of credibility in self-deceptive speech. A self-signaling interpretation can account for the ritualistic quality of some self-deceptive affirmations and for the often-noted gap between what self-deceivers say and what they truly believe.
Antiinflammatory Action of Glucocorticoids — New Mechanisms for Old Drugs
Authors: Turk Rhen, John A. Cidlowski
Journal: New England Journal of Medicine (2005)

Glucocorticoids are among the most common therapeutic agents used in medical practice, yet their mechanisms of action are only partly understood. This review summarizes our understanding of how glucocorticoids inhibit inflammation and give rise to side effects.
Specific suppression of major histocompatibility complex class I and class II genes in astrocytes by brain-enriched gangliosides.
Authors: P T Massa
Journal: The Journal of Experimental Medicine (1993)

The effect of brain-enriched gangliosides on constitutive and cytokine-inducible expression of major histocompatibility complex (MHC) class I and II genes in cultured astrocytes was studied. Before treatment with gangliosides, astrocytes expressed constitutive MHC class I but not class II molecules, however, the expression of both MHC class I and II cell surface molecules on astrocytes was induced to high levels by interferon gamma (IFN-gamma). Constitutive and IFN-gamma-inducible expression of MHC class I and II molecules was suppressed by treatment of astrocytes with exogenous bovine brain gangliosides in a dose-dependent manner. Constitutive and induced MHC class I and II mRNA levels were also suppressed by gangliosides, indicating control through transcriptional mechanisms. This was consistent with the ability of gangliosides to suppress the binding activity of transcription factors, especially NF-kappa B-like binding activity, important for the expression of both MHC class I and II genes. These studies may be important for understanding mechanisms of central nervous system (CNS)-specific regulation of major histocompatibility molecules in neuroectodermal cells and the role of gangliosides in regulating MHC-restricted antiviral and autoimmune responses within the CNS.
Regulatory T Cells Suppress Innate Immunity in Kidney Ischemia-Reperfusion Injury
Authors: Gilbert R. Kinsey, Rahul Sharma, Liping Huang, Li Li, Amy L. Vergis, Hong Ye, Shyr-Te Ju, Mark D. Okusa
Journal: Journal of the American Society of Nephrology (2009)

Both innate and adaptive mechanisms participate in the pathogenesis of kidney ischemia-reperfusion injury (IRI), but the role of regulatory immune mechanisms is unknown. We hypothesized that the anti-inflammatory effects of CD4+CD25+FoxP3+ regulatory T cells (Tregs) protect against renal IRI. Partial depletion of Tregs with an anti-CD25 mAb potentiated kidney damage induced by IRI. Reducing the number of Tregs resulted in more neutrophils, macrophages, and innate cytokine transcription in the kidney after IRI but did not affect CD4+ T cells or B cells. We performed adoptive transfer of lymph node cells from wild-type mice or FoxP3-deficient Scurfy mice into T cell– and B cell–deficient RAG-1 knockout mice to generate mice with and without FoxP3+ Tregs, respectively. FoxP3+ Treg–deficient mice accumulated a greater number of inflammatory leukocytes after renal IRI than mice containing Tregs. To confirm that a lack of Tregs potentiated renal injury, we co-transferred isolated Tregs and Scurfy lymph node cells; Treg repletion significantly attenuated IRI-induced renal injury and leukocyte accumulation. Furthermore, although adoptive transfer of wild-type Tregs into RAG-1 knockout mice was sufficient to prevent kidney IRI, transfer of IL-10–deficient Tregs was not. Taken together, these results demonstrate that Tregs modulate injury after kidney IRI through IL-10–mediated suppression of the innate immune system.
Efficient Elimination of B-Lineage Lymphomas by Anti-CD20–Auristatin Conjugates
Authors: Che-Leung Law, Charles G. Cerveny, Kristine A. Gordon, Kerry Klussman, Bruce J. Mixan, Dana F. Chace, Damon L. Meyer, Svetlana O. Doronina, Clay B. Siegall, Joseph A. Francisco, Peter D. Senter, Alan F. Wahl
Journal: Clinical Cancer Research (2004)

Abstract The anti-CD20 antibody rituximab is useful in the treatment of certain B-cell malignancies, most notably non-Hodgkin’s lymphoma. Its efficacy has been increased when used in combination with chemotherapy, yet anti-CD20 monoclonal antibodies (mAbs) directly conjugated with drugs such as doxorubicin (Dox) have failed to deliver drug or to demonstrate antitumor activity. We have produced anti-CD20 antibody-drug conjugates that possess potent antitumor activity by using the anti-mitotic agent, monomethyl auristatin E (MMAE), linked via the lysosomally cleavable dipeptide, valine-citrulline (vc). Two anti-CD20 conjugates, rituximab-vcMMAE and 1F5-vcMMAE, were selectively cytotoxic against CD20+ B-lymphoma cell lines, with IC50 values ranging from 50 ng/mL to 1 μg/mL. Unlike rituximab, which showed diffuse surface localization, rituximab-vcMMAE capped and was internalized within 4 hours after binding to CD20+ B cells. Internalization of rituximab-vcMMAE was followed by rapid G2-M phase arrest and onset of apoptosis. Anti-CD20 antibody-drug conjugates prepared with Dox were internalized and localized as with rituximab-vcMMAE, yet these were not effective for drug delivery (IC50 &amp;gt; 50 μg/mL). Consistent with in vitro activity, rituximab-vcMMAE showed antitumor efficacy in xenograft models of CD20-positive lymphoma at doses where rituximab or rituximab-Dox conjugates were ineffective. These data indicate that anti-CD20–based antibody-drug conjugates are effective antitumor agents when prepared with a stable, enzyme-cleavable peptide linkage to highly potent cytotoxic agents such as MMAE.
Hepatitis C virus testing in primary biliary cirrhosis
Authors: Emanuela Bertolini, Pier Maria Battezzati, Paola Zermiani, Savino Bruno, Gian Alessandro Moroni, Filippo Marelli, Erica Villa, Frederico Manenti, Massimo Zuin, Andrea Crosignani, Mauro Podda
Journal: Journal of Hepatology (1992)
Differentiation of Reinfection from Relapse in Recurrent Lyme Disease
Authors: Robert B. Nadelman, Klára Hanincová, Priyanka Mukherjee, Dionysios Liveris, John Nowakowski, Donna McKenna, Dustin Brisson, Denise Cooper, Susan Bittker, Gul Madison, Diane Holmgren, Ira Schwartz, Gary P. Wormser
Journal: New England Journal of Medicine (2012)

Erythema migrans is the most common manifestation of Lyme disease. Recurrences are not uncommon, and although they are usually attributed to reinfection rather than relapse of the original infection, this remains somewhat controversial. We used molecular typing of Borrelia burgdorferi isolates obtained from patients with culture-confirmed episodes of erythema migrans to distinguish between relapse and reinfection.
A minimal binding footprint on CD1d-glycolipid is a basis for selection of the unique human NKT TCR
Authors: Kwok S. Wun, Natalie A. Borg, Lars Kjer-Nielsen, Travis Beddoe, Ruide Koh, Stewart K. Richardson, Meena Thakur, Amy R. Howell, James P. Scott-Browne, Laurent Gapin, Dale I. Godfrey, James McCluskey, Jamie Rossjohn
Journal: The Journal of Experimental Medicine (2008)

Although it has been established how CD1 binds a variety of lipid antigens (Ag), data are only now emerging that show how alphabeta T cell receptors (TCRs) interact with CD1-Ag. Using the structure of the human semiinvariant NKT TCR-CD1d-alpha-galactosylceramide (alpha-GalCer) complex as a guide, we undertook an alanine scanning mutagenesis approach to define the energetic basis of this interaction between the NKT TCR and CD1d. Moreover, we explored how analogues of alpha-GalCer affected this interaction. The data revealed that an identical energetic footprint underpinned the human and mouse NKT TCR-CD1d-alpha-GalCer cross-reactivity. Some, but not all, of the contact residues within the Jalpha18-encoded invariant CDR3alpha loop and Vbeta11-encoded CDR2beta loop were critical for recognizing CD1d. The residues within the Valpha24-encoded CDR1alpha and CDR3alpha loops that contacted the glycolipid Ag played a smaller energetic role compared with the NKT TCR residues that contacted CD1d. Collectively, our data reveal that the region distant to the protruding Ag and directly above the F' pocket of CD1d was the principal factor in the interaction with the NKT TCR. Accordingly, although the structural footprint at the NKT TCR-CD1d-alpha-GalCer is small, the energetic footprint is smaller still, and reveals the minimal requirements for CD1d restriction.
Surface properties of bacillus Calmette-Guérin-activated mouse macrophages. Reduced expression of mannose-specific endocytosis, Fc receptors, and antigen F4/80 accompanies induction of Ia.
Authors: R A Ezekowitz, J Austyn, P D Stahl, S Gordon
Journal: The Journal of Experimental Medicine (1981)

Infection of the mouse peritoneal cavity by bacillus Calmette-Guérin (BCG) markedly alters the surface properties of the macrophages induced, compared with cells obtained from uninfected control animals or after injection of thioglycollate broth. Quantitative binding assays with radiolabeled ligands or antibodies showed that BCG-activated peritoneal macrophages (BCG-PM) expressed one-fourth or less receptor activity for mannose-terminal glycoconjugates as well as reduced levels of Fc receptors and of antigen F4/80 compared with nonactivated macrophages. Endocytosis mediated by mannose-specific receptors was reduced in parallel. In contrast, surface Ia antigen was increased threefold in the same adherent cell population. Radioautographic analysis confirmed that greater than 80% of adherent cells still expressed low levels of the macrophage-specific mannosyl receptor and antigen F4/80, and that I antigens had been induced on 64% of macrophages rather than on other cells. Control experiments established that only the BCG-PM macrophages released H2O2 after stimulation with phorbol myristate acetate, whereas both BCG-PM and thioglycollate-induced macrophages produced superoxide anion and plasminogen activator. The BCG-PM were viable, secreted normal levels of lysozyme, and displayed a stable phenotype after cultivation for 60 h. Inhibitors of oxygen products, prostaglandins, and proteases did not alter reduced endocytosis by BCG-PM. These studies indicated that expression of macrophage surface markers is reversed by BCG-activation, and that their known enhanced ability to lyse target cells extracellularly is associated with decreased endocytosis via specific receptors. Whether these changes are a result of an altered cell population or of modulation of selective surface properties is not known.
The functional role of long non-coding RNA in human carcinomas
Authors: Ewan A Gibb, Carolyn J Brown, Wan L Lam
Journal: Molecular Cancer (2011)

Long non-coding RNAs (lncRNAs) are emerging as new players in the cancer paradigm demonstrating potential roles in both oncogenic and tumor suppressive pathways. These novel genes are frequently aberrantly expressed in a variety of human cancers, however the biological functions of the vast majority remain unknown. Recently, evidence has begun to accumulate describing the molecular mechanisms by which these RNA species function, providing insight into the functional roles they may play in tumorigenesis. In this review, we highlight the emerging functional role of lncRNAs in human cancer.
Therapy with imatinib mesylate (Glivec) preceding allogeneic stem cell transplantation (SCT) in relapsed or refractory Philadelphia-positive acute lymphoblastic leukemia (Ph+ALL)
Authors: B Wassmann, H Pfeifer, U Scheuring, SA Klein, N Gökbuget, A Binckebanck, H Martin, H Gschaidmeier, D Hoelzer, OG Ottmann
Journal: Leukemia (2002)