tbuckley/cabot-search huggingface dataset:
A STAT3-inhibitory hairpin decoy oligodeoxynucleotide discriminates between STAT1 and STAT3 and induces death in a human colon carcinoma cell line
Authors: Inès Souissi, Patrick Ladam, Jean AH Cognet, Stéphanie Le Coquil, Nadine Varin-Blank, Fanny Baran-Marszak, Valeri Metelev, Remi Fagard
Journal: Molecular Cancer (2012)

Abstract Background The Signal Transducer and Activator of Transcription 3 (STAT3) is activated in tumor cells, and STAT3-inhibitors are able to induce the death of those cells. Decoy oligodeoxynucleotides (dODNs), which bind to the DNA Binding Domain (DBD) of STAT3, are efficient inhibitors. However, they also inhibit STAT1, whose activity is essential not only to resistance to pathogens, but also to cell growth inhibition and programmed cell death processes. The aim of this study was to design STAT3-specific dODNs which do not affect STAT1-mediated processes. Results New dODNs with a hairpin (hpdODNs) were designed. Modifications were introduced, based on the comparison of STAT3- and STAT1-DBD interactions with DNA using 3D structural analyses. The designed hpdODNs were tested for their ability to inhibit STAT3 but not STAT1 by determining: i) cell death in the active STAT3-dependent SW480 colon carcinoma cell line, ii) absence of inhibition of interferon (IFN) γ-dependent cell death, iii) expression of STAT1 targets, and iv) nuclear location of STAT3 and STAT1. One hpdODN was found to efficiently induce the death of SW480 cells without interfering with IFNγ-activated STAT1. This hpdODN was found in a complex with STAT3 but not with STAT1 using an original in-cell pull-down assay; this hpdODN also did not inhibit IFNγ-induced STAT1 phosphorylation, nor did it inhibit the expression of the STAT1-target IRF1. Furthermore, it prevented the nuclear transfer of STAT3 but not that of IFNγ-activated STAT1. Conclusions Comparative analyses at the atomic level revealed slight differences in STAT3 and STAT1 DBDs' interaction with their DNA target. These were sufficient to design a new discriminating hpdODN that inhibits STAT3 and not STAT1, thereby inducing tumor cell death without interfering with STAT1-dependent processes. Preferential interaction with STAT3 depends on oligodeoxynucleotide sequence modifications but might also result from DNA shape changes, known to modulate protein/DNA interactions. The finding of a STAT3-specific hpdODN establishes the first rational basis for designing STAT3 DBD-specific inhibitors.
Distribution of and Factors Associated With Serum Homocysteine Levels in Children
Authors: Stavroula K. Osganian, Meir J. Stampfer, Donna Spiegelman, Eric Rimm, Jeffrey A. Cutler, Henry A. Feldman, Deanna H. Montgomery, Larry S. Webber, Leslie A. Lytle, Linda Bausserman, Philip R. Nader
Journal: JAMA (1999)

prevention of cardiovascular disease (CVD) begins during childhood. 14][5] Recent studies suggest that plasma homocysteine concentration may be an independent and modifiable risk factor for CVD in adults. 6A meta-analysis found for every 5-µmol/L increase in homocysteine, the odds ratio for risk of coronary artery disease was 1.6 (95% confidence interval [CI], 1.4-1.7)for men and 1.8 (95% CI, 1.4-2.3)for women. 7Although conclusive evidence for a causal association with CVD in adults is lacking, 7-17 the potential for prevention provides a strong rationale for understanding the determinants of homocysteine in children.
Hypoxia–Reoxygenation Triggers Coronary Vasospasm in Isolated Bovine Coronary Arteries via Tyrosine Nitration of Prostacyclin Synthase
Authors: Ming-Hui Zou, Markus Bachschmid
Journal: The Journal of Experimental Medicine (1999)

The role of peroxynitrite in hypoxia–reoxygenation-induced coronary vasospasm was investigated in isolated bovine coronary arteries. Hypoxia–reoxygenation selectively blunted prostacyclin (PGI2)-dependent vasorelaxation and elicited a sustained vasoconstriction that was blocked by a cyclooxygenase inhibitor, indomethacin, and SQ29548, a thromboxane (Tx)A2/prostaglandin H2 receptor antagonist, but not by CGS13080, a TxA2 synthase blocker. The inactivation of PGI2 synthase, as evidenced by suppressed 6-keto-PGF1α release and a decreased conversion of 14C-prostaglandin H2 into 6-keto-PGF1α, was paralleled by an increased nitration in both vascular endothelium and smooth muscle of hypoxia–reoxygenation-exposed vessels. The administration of the nitric oxide (NO) synthase inhibitors as well as polyethylene-glycolated superoxide dismutase abolished the vasospasm by preventing the inactivation and nitration of PGI2 synthase, suggesting that peroxynitrite was implicated. Moreover, concomitant administration to the organ baths of the two precursors of peroxynitrite, superoxide, and NO mimicked the effects of hypoxia–reoxygenation, although none of them were effective when given separately. We conclude that hypoxia–reoxygenation elicits the formation of superoxide, which causes loss of the vasodilatory action of NO and at the same time yields peroxynitrite. Subsequently, peroxynitrite nitrates and inactivates PGI2 synthase, leaving unmetabolized prostaglandin H2, which causes vasospasm, platelet aggregation, and thrombus formation via the TxA2/prostaglandin H2 receptor.
THE ROLE OF THE THYMUS IN DEVELOPMENT OF IMMUNOLOGIC CAPACITY IN RABBITS AND MICE
Authors: Robert A. Good, Agustin P. Dalmasso, Carlos Martinez, Olga K. Archer, James C. Pierce, Ben W. Papermaster
Journal: The Journal of Experimental Medicine (1962)

In rabbits, complete thymectomy before the age of 5 days produced immunologic deficiency in the adult animals, as indicated by reduced antibody production to bovine serum albumin and bacteriophage T2. Homotransplantation immunity was unaffected, however. In an inbred strain of mice, complete neonatal thymectomy resulted in complete inability of the 60-day-old animals to form antibody to bacteriophage T2. Inbred mice, completely thymectomized at birth, had a deficient homograft response, indicated by acceptance of skin homografts from strains differing in both the weaker and stronger (H-2) histocompatibility antigens. Tumor transplants (mammary adenocarcinoma) were also successful across the H-2 genetic barrier in mice thymectomized at birth. Neonatal thymectomy also eliminated the Eichwald-Silmser phenomenon, rendering female mice capable of accepting isografts of male skin. Transplantation immunity in mice was also affected by later thymectomy, at 30 days of age, in certain strain combinations involving weak histocompatibility differences. Spleen and lymph node cells from mice thymectomized at birth or at 6 days of age, and sacrificed 2 months later, did not produce a graft versus host reaction in appropriate F1 hybrid recipients, indicating that such cells are immunologically inactive. Neonatal thymectomy of F1 hybrid mice, and in one strain combination thymectomy at 40 days of age, produced animals with inordinate susceptibility to runt disease (homologous disease) following injection of parent strain spleen cells 35 days (neonatal surgery) and 10 days (surgery at 40 days) later. Mice thymectomized at birth also showed growth failure and were short-lived. Studies of newborn mice indicated that they have true lymphocytes only in the thymus, and lack such cells in the spleen, lymph nodes, and gut. In normal mice, adult lymphoid structure develops gradually, beginning during the 1st week of life and continuing for the next month. In contrast, mice thymectomized at birth do not develop mature lymphoid structure: the lymph nodes and spleens tend to be small and poorly organized, and show a quantitative deficiency in lymphoid cells. It is our current working hypothesis that the thymus makes a major contribution toward the centrifugal distribution of lymphoid cells which, in turn, is essential to the full expression of immunologic capacity.
Endoscopic laser-assisted management of pediatric airway lesions: A single institution experience
Authors: Juan L. Antón-Pacheco, Carmen Luna, Gloria García-Hernández, Francisca Gómez-Acebo, Miguel A. Villafruela
Journal: European Respiratory Journal (2012)

Background:  Laser endoscopic surgery is increasingly being used in the treatment of pediatric airway disorders.   Aims:  We evaluated the outcomes of laser therapy in a selected group of patients with congenital and acquired airway lesions.   Methods:  The medical charts of patients who were treated for airway disorders with diode laser between January 2008 and December 2011 at a tertiary care children9s hospital were reviewed. All the procedures were performed endoscopically using rigid or flexible instruments. Data included relevant history and physical examination, diagnostic work-up, number of laser procedures, complications, and outcomes.   Results:  37 patients who had laser surgery were identified,13 girls and 24 boys with a mean age of 20 months (range, 3 days-12 years). 47 laser surgeries were performed, representing 1.2 procedures per patient. Indications for laser therapy were: Laryngomalacia 11 cases (29%), granulation tissue 8 (21%), vocal cord paralysis 7 (19%), laryngeal stenosis 5 (13%), vascular-lymphatic malformation 3 (8%), subglottic cyst 1 (2.7%), congenital tracheal stenosis 1, and papillomatosis 1 case. In 7 patients (19%), other concomitant endoscopic procedures were performed. Two complications were identified: Postlaser bleeding and aspiration in one patient, and subcutaneous emphysema and pneumothorax in another patient. In 89% of patients, partial or complete clinical improvement occurred after laser therapy.   Conclusions : Endoscopic laser surgery is a safe and effective technique when treating airway disorders in children. It is a good alternative to open surgery in selected patients either used alone or in combination with other endoscopic procedures.
Calculations of pulsatile flow through a branch: implications for the hemodynamics of atherogenesis.
Authors: M H Friedman, V O'Brien, L W Ehrlich
Journal: Circulation Research (1975)

Numerical simulations of pulsatile blood flow through a symmetrical branch modeling the aortic bifurcation were carried out to assess several hemodynamic theories of atherogenesis by comparing the distribution of hemodynamic variables with that of early lesions in arterial branches. Considerable spatial and temporal variations in wall shear were found when the flow was pulsatile; the highest values occurred at the convex corner on the outer wall of the branch and in the neighborhood of the flow divider tip, and the lowest shears were experienced by the outer wall of the daughter vessel a short distance distal to the corner. Transient flow reversal occurred almost everywhere in the branch, and a transient separated region was found corresponding to the low-shear region in the daughter vessel. The shear profiles and the calculated separated region were influenced to some degree by the extent of flow development at the branch inlet and markedly by the branch area ratio. All of the proposed hemodynamic promoters of atherosclerosis that were examined--high shear, low shear, and separation--were found at sites in the branch where lesions commonly develop. Comparisons with a steady-flow calculation at the same mean flow rate showed that the severity of all of these proposed hemodynamic determinants was increased by pulsatility.
Defining the effects of age and gender on clinical immune response to cancer vaccination
Authors: Adriana Ramirez, Nolan Wages, Mark E Smolkin, Craig L Slingluff
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Cancer vaccines have promise as monotherapy or as part of combination immunotherapy regimens. Age and gender implications on immune response to cancer vaccinations have not previously been well described. There is uncertainty about including elderly patients as study participants
An immunological insight into the origins of pre-eclampsia
Authors: E. Laresgoiti-Servitje, N. Gomez-Lopez, D. M. Olson
Journal: Human Reproduction Update (2010)

Pre-eclampsia is a syndrome of heterogeneous origin characterized by deficient placentation due to the inability of the cytotrophoblast to acquire an invasive phenotype and to remodel the uterine spiral arteries. One of the main problems observed early in pre-eclampsia is an altered regulation of the immune system, where the shift toward a Th2 cytokine profile observed in normal pregnancies, does not occur. In pre-eclampsia, high interferon (IFN)-gamma concentrations are present, along with transforming growth factor-beta cytokines, which retard migration of cytotrophoblasts.A review of the scientific literature was performed on the immunological factors associated with the origins of pre-eclampsia. The various components of the immune system that may be participating in the aberrant immune activation that pathologically affect early pregnancy events and inhibit cytotrophoblast invasion were identified.Cells and their signaling and regulatory molecules have been implicated in the immunological alterations found in the placental microenvironment of patients who develop pre-eclampsia. One of the main differences found in pre-eclampsia is a shift toward Th1 responses and the production of IFN-gamma. The origin of IFN-gamma is not clearly identified and could be the uterine natural killer cells, the placental dendritic cells modulating Th responses, alterations in synthesis of or response to regulatory molecules, or changes in the function of regulatory T cells in pregnancy. Aberrant immune responses promoting pre-eclampsia may also be due to an altered fetal allorecognition or to inflammatory triggers. Understanding the immunological basis for pre-eclampsia will expand knowledge regarding other adverse pregnancy outcomes.
Imiquimod: modes of action
Authors: Donna Bilu, D N Sauder
Journal: British Journal of Dermatology (2003)

Journal Article Imiquimod: modes of action Get access D.N. Sauder D.N. Sauder Daniel Sauder, Department of Dermatology, Johns Hopkins University, School of Medicine, 601 N. Caroline Street, Suite 6072, Baltimore, MD 21287, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 149, Issue s66, 1 November 2003, Pages 5–8, https://doi.org/10.1046/j.0366-077X.2003.05628.x Published: 01 November 2003
Treatment of patients with dual hepatitis B and C: a step in the right direction
Authors: Alessio Aghemo, Massimo Colombo
Journal: Gut (2013)

Several convincing lines of evidence have shown that effective antiviral treatment of patients with chronic hepatitis B (HBV) or C (HCV) can positively affect the natural course of both diseases. Indeed, maintained HBV suppression by pegylated interferon (PegIFN) or nucleos(t)ide analogue treatment has been shown to reduce the risk of hepatocellular carcinoma (HCC), eliminate the risk of liver decompensation, and improve overall survival.1 The same holds true for HCV, where viral eradication achieved by IFN or by directly acting antiviral-based therapy abolishes the risk of progression to cirrhosis and reduces, or abrogates, the risk of liver-related complications in patients with cirrhosis.1 Unfortunately, less is known about the impact of antiviral therapy in patients co-infected with both viruses. This is not a rare event, as in most countries HBV and HCV share modalities of transmission; currently it is estimated that nearly 5–20% of HBV patients and 2–10% of HCV patients have HBV–HCV co-infection.2 From a clinical standpoint, HBV–HCV co-infection has been associated with increased risk of fulminant hepatitis in the acute phase and development of cirrhosis and HCC in the long term.3 Still this has not been confirmed in all studies, probably because of significant differences in terms of ethnicity, comorbid conditions and virological profiles among the analysed cohorts.4 Patients with HBV–HCV co-infection are indeed extremely heterogeneous both in terms of infection modality—with most patients from Asia acquiring HBV infection at birth and later having HCV superinfection, whereas patients from Europe and the USA often acquire both infections concomitantly—and in terms of viral dominance of one virus over the other. …
Complete pathological response in a patient with multiple liver metastases from colon cancer treated with Folfox-6 chemotherapy plus bevacizumab: a case report
Authors: Norma Malavasi, Giovanni Ponti, Roberta Depenni, Federica Bertolini, Sandra Zironi, Gabriele Luppi, Pier Franco Conte
Journal: Journal of Hematology & Oncology (2009)

The complete pathological response after primary chemotherapy could represent an important prognostic factor in patients affected by colorectal liver metastases. In recent studies, increasing complete pathological response seems to be correlated with longer overall survival periods and it is recognized as an important prognostic factor in patients treated with pre-operative chemotherapy. The correlation of radiological information on residual neoplastic disease after neoadjuvant treatment, obtained with CT and PET, has to be evaluated; in fact the complete disappearance of liver metastasis on radiological imaging does not always mean a complete disappearance of tumor tissue on histological examination; when it is documented with surgical procedures and confirmed by pathologist's examination, we can consider the complete pathological response. In recent years the addition of monoclonal antibodies to conventional chemotherapy may further increase the proportion of patients referred for surgery; bevacizumab before surgery has been shown to be feasible and safe, although concerns still exist regarding possible post-surgical and wound healing complications or bleeding. The limitation of the radiologic assessment of response as a surrogate for pathological response is even more relevant when antiangiogenic treatments are used. Excellent responses to bevacizumab-containing regimens do occur and referral to surgical oncology is a crucial step for documentation of complete pathological response.
The Brain Renin-Angiotensin System Contributes to the Hypertension in Mice Containing Both the Human Renin and Human Angiotensinogen Transgenes
Authors: Robin L. Davisson, Gongyu Yang, Terry G. Beltz, Martin D. Cassell, Alan Kim Johnson, Curt D. Sigmund
Journal: Circulation Research (1998)

Abstract —We have previously shown that mice transgenic for both the human renin and human angiotensinogen genes (RA+) exhibit appropriate tissue- and cell-specific expression of both transgenes, have 4-fold higher plasma angiotensin II (AII) levels, and are chronically hypertensive. However, the relative contribution of circulating and tissue-derived AII in causing hypertension in these animals is not known. We hypothesized that the brain renin-angiotensin system contributes to the elevated blood pressure in this model. To address this hypothesis, mean arterial pressure (MAP) and heart rate were measured in conscious, unrestrained mice after they were instrumented with intracerebroventricular cannulae and carotid arterial and jugular vein catheters. Intracerebroventricular administration of the selective AII type 1 (AT-1) receptor antagonist losartan (10 μg, 1 μL) caused a significantly greater peak fall in MAP in RA+ mice than in nontransgenic RA− controls (−29±4 versus −4±2 mm Hg, P &lt;0.01). To explore the mechanism of a central renin-angiotensin system–dependent hypertension in RA+ mice, we determined the relative depressor responses to intravenous administration of the ganglionic blocking agent hexamethonium (5 mg/kg) or an arginine vasopressin (AVP) V 1 receptor antagonist (AVPX, 10 μg/kg). Hexamethonium caused equal lowering of MAP in RA+ mice and controls (−46±3 versus −52±3, P &gt;0.05), whereas AVPX caused a significantly greater fall in MAP in RA+ compared with RA− mice (−24±2 versus −6±1, P &lt;0.01). Consistent with this was the observation that circulating AVP was 3-fold higher in RA+ mice than in control mice. These results suggest that increased activation of central AT-1 receptors, perhaps those located at sites involved in AVP release from the posterior pituitary gland, plays a role in the hypertension in RA+ mice. Furthermore, our finding that both human transgenes are expressed in brain regions of RA+ mice known to be involved in cardiovascular regulation raises the possibility that augmented local production of AII and increased activation of AT-1 receptors at these sites is involved.
A unique autoantibody pattern of positive anti-Jo-1, anti-U1RNP, and antiproteasome antibodies in autoimmune myositis as a diagnostic challenge
Authors: E Feist
Journal: Annals of the Rheumatic Diseases (2003)

The presence of autoantibodies against tRNA synthetases is a specific serological feature of a clinically distinct entity of autoimmune myositis. This syndrome is characterised by an association of non-erosive arthritis, Raynaud’s phenomenon, and alveolitis. The most common autoimmune response of this disease is directed against the histidyl-tRNA synthetase Jo-1 and therefore also called the anti-Jo-1 syndrome.1–3 In this report we describe a patient with a unique coincidence of anti-Jo-1 antibodies with other myositis related autoantibodies directed to U1RNP typical for mixed connective tissue disease (MCTD) and proteasome.

In a 36 year old female patient, arthralgia, joint swelling, and fever led to the diagnosis of rheumatoid arthritis in 1998. Initial treatment comprised sulfasalazine and prednisolone. In February 2000, she was admitted to our department with a four month history of myalgia and weakness. Physical examination showed a tetraparesis affecting the proximal and peripheral muscles with an apparent areflexia. Gottron’s sign was positive, …
A new diagnostic algorithm for Burkitt and diffuse large B-cell lymphomas based on the expression of CSE1L and STAT3 and on MYC rearrangement predicts outcome
Authors: D. Soldini, C. Montagna, P. Schüffler, V. Martin, A. Georgis, T. Thiesler, A. Curioni-Fontecedro, P. Went, G. Bosshard, S. Dehler, L. Mazzuchelli, M. Tinguely
Journal: Annals of Oncology (2012)

BackgroundAggressive mature B-cell non-Hodgkin's lymphomas (BCL) sharing features of Burkitt's lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) (intermediate BL/DLBCL) but deviating with respect to one or more characteristics are increasingly recognized. The limited knowledge about these biologically heterogeneous lymphomas hampers their assignment to a known entity, raising incertitude about optimal treatment approaches. We therefore searched for discriminative, prognostic, and predictive factors for their better characterization.Patients and methodsWe analyzed 242 cytogenetically defined aggressive mature BCL for differential protein expression. Marker selection was based on recent gene-expression profile studies. Predictive models for diagnosis were established and validated by a different set of lymphomas.ResultsCSE1L- and inhibitor of DNA binding-3 (ID3)-overexpression was associated with the diagnosis of BL and signal transduction and transcription-3 (STAT3) with DLBCL (P<0.001 for all markers). All three markers were associated with patient outcome in DLBCL. A new algorithm discriminating BL from DLBCL emerged, including the expression of CSE1L, STAT3, and MYC translocation. This 'new classifier' enabled the identification of patients with intermediate BL/DLBCL who benefited from intensive chemotherapy regimens.ConclusionThe proposed algorithm, which is based on markers with reliable staining properties for routine diagnostics, represents a novel valid tool in separating BL from DLBCL. Most interestingly, it allows segregating intermediate BL/DLBCL into groups with different treatment requirements.