tbuckley/cabot-search huggingface dataset:
Ascites Specific Inhibition of CD1d-Mediated Activation of Natural Killer T Cells
Authors: Tonya J. Webb, Robert L. Giuntoli, Ophelia Rogers, Jonathan Schneck, Mathias Oelke
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Natural killer T (NKT) cells recognize lipid antigen presented by CD1 molecules. NKT cells can both directly, through cytotoxicity, and indirectly, through activation of other effector cells, mediate antitumor immunity. It has been shown, however, that tumor-associated lipids are frequently shed into the tumor microenvironment, which can mediate immunosuppressive activity. Given that ovarian cancer–associated ascites has been reported to have increased levels of gangliosides, we examined the effect of tumor-associated and other ascites on CD1d-mediated antigen presentation to NKT cells. Experimental Design: To investigate the effects of ascites on NKT cell activation, we pretreated CD1d-expressing cells with the ascites and measured their ability to stimulate cytokine production in NKT cells. To determine whether antigen processing or editing was necessary, CD1d-immunoglobulin–based artificial antigen presenting cells (aAPC) were also incubated with ascites. In addition, to examine specificity, we analyzed whether ascites fluid could influence the activation of classic CD8+ T cells. Results: Pretreatment of CD1d-expressing cells with ascites from the majority of patients inhibited the ability of the cells to stimulate/activate NKT cells in a dose-dependent manner. Ascites treatment also partially blocked the ability of α-galactosylceramide–loaded CD1d-immunoglobulin–based aAPC to activate NKT cells. In addition, our data show that treatment with ascites does not inhibit HLA-A2–mediated activation of classic CD8+ T cells. Conclusions: Together, these data suggest that ovarian and other cancers may have developed immune evasion mechanisms specifically targeting the CD1/NKT cell system.
LAZ3 rearrangements in non-Hodgkin's lymphoma: correlation with histology, immunophenotype, karyotype, and clinical outcome in 217 patients
Authors: C Bastard, C Deweindt, JP Kerckaert, B Lenormand, A Rossi, F Pezzella, C Fruchart, C Duval, M Monconduit, H Tilly
Journal: Blood (1994)
Autoimmunity and Susceptibility to Hodgkin Lymphoma: A Population-Based Case–Control Study in Scandinavia
Authors: Ola Landgren, Eric A. Engels, Ruth M. Pfeiffer, Gloria Gridley, Lene Mellemkjaer, Jørgen H. Olsen, Kimberly F. Kerstann, William Wheeler, Kari Hemminki, Martha S. Linet, Lynn R. Goldin
Journal: JNCI Journal of the National Cancer Institute (2006)

Background: Personal history of autoimmune diseases is consistently associated with increased risk of non-Hodgkin lymphoma. In contrast, there are limited data on risk of Hodgkin lymphoma following autoimmune diseases and almost no data addressing whether there is a familial association between the conditions. Methods: Using population-based linked registry data from Sweden and Denmark, 32 separate autoimmune and related conditions were identified from hospital diagnoses in 7476 case subjects with Hodgkin lymphoma, 18 573 matched control subjects, and more than 86 000 first-degree relatives of case and control subjects. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) as measures of relative risks for each condition using logistic regression and also applied multivariable hierarchical regression models. All P values are two-sided. Results: We found statistically significantly increased risks of Hodgkin lymphoma associated with personal histories of several autoimmune conditions, including rheumatoid arthritis (OR = 2.7, 95% CI = 1.9 to 4.0), systemic lupus erythematosus (OR = 5.8, 95% CI = 2.2 to 15.1), sarcoidosis (OR = 14.1, 95% CI = 5.4 to 36.8), and immune thrombocytopenic purpura (OR = ∞, P = .002). A statistically significant increase in risk of Hodgkin lymphoma was associated with family histories of sarcoidosis (OR = 1.8, 95% CI = 1.01 to 3.1) and ulcerative colitis (OR = 1.6, 95% CI = 1.02 to 2.6). Conclusions: Personal or family history of certain autoimmune conditions was strongly associated with increased risk of Hodgkin lymphoma. The association between both personal and family histories of sarcoidosis and a statistically significantly increased risk of Hodgkin lymphoma suggests shared susceptibility for these conditions.
Relative contribution of Prevotella intermedia and Pseudomonas aeruginosa to lung pathology in airways of patients with cystic fibrosis
Authors: M. Ulrich, I. Beer, P. Braitmaier, M. Dierkes, F. Kummer, B. Krismer, U. Schumacher, U. Grapler-Mainka, J. Riethmuller, P. O. Jensen, T. Bjarnsholt, N. Hoiby, G. Bellon, G. Doring
Journal: Thorax (2010)

<h3>Background</h3> Patients with cystic fibrosis (CF) with <i>Pseudomonas aeruginosa</i> lung infections produce endobronchial mucus plugs allowing growth of obligate anaerobes including <i>Prevotella</i> spp. Whether obligate anaerobes contribute to the pathophysiology of CF lung disease is unknown. <h3>Methods</h3> The virulence of <i>Prevotella intermedia</i> and <i>Ps aeruginosa</i> was investigated in vitro and in mice, antibodies against <i>P intermedia</i> in CF sera were assessed and a culture-independent detection method for <i>P intermedia/P nigrescens</i> in CF sputum was tested. <h3>Results</h3> <i>P intermedia</i> reached cell numbers of &gt;10<sup>5</sup>–&gt;10<sup>7</sup> colony-forming units (CFU)/ml sputum. The majority of patients with CF (16/17; 94.1%) produced antibodies against two immunoreactive antigens of <i>P intermedia</i>. Culture supernatant fluids, collected from 10<sup>9</sup><i>P intermedia</i> cells, were more cytotoxic to respiratory epithelial cells in vitro and inflammatory in mouse lungs than respective fluids from anaerobically grown <i>Ps aeruginosa</i>, while fluids from aerobically grown <i>Ps aeruginosa</i> had the highest cytotoxicity and inflammation. Both pathological effects were largely reduced when culture supernatant fluids from 10<sup>7</sup> cells of either species were used. <i>P intermedia</i> cells (∼10<sup>6</sup>CFU/lung) did not induce mortality in the agar beads lung infection mouse model, while <i>Ps aeruginosa</i> cells caused death in 30% of mice due to rapid multiplication. A <i>P intermedia/P nigrescens</i>-specific PNA probe was significantly more sensitive than culture-dependent diagnostic assays to detect these strict anaerobes. <h3>Conclusion</h3> <i>Ps aeruginosa</i> and <i>P intermedia</i> become significantly virulent in vitro and in vivo when cell numbers exceed 10<sup>8</sup> CFU/lung.
The role of arterial baroreceptors in the regulation of arterial pressure in conscious dogs.
Authors: R J McRitchie, S F Vatner, G R Heyndrickx, E Braunwald
Journal: Circulation Research (1976)

To elucidate the role of arterial baroreceptors in the acute regulation of arterial pressure in the conscious animal, arterial pressure was lowered and raised in intact, conscious dogs, and in dogs after bilateral section of both carotid sinus and aortic nerves (total arterial baroreceptor denervation, TABD). Pressure was altered by intravenous bolus injections and continuous infusions of nitroglycerin and methoxamine and also by hemorrhage. TABD resulted in a change in peak mean arterial pressure 2-4 times as great as that seen in intact dogs following injection of nitroglycerin or methoxamine. However, when the time taken for the arterial pressure disturbance to return to control levels, as well as the absolute change in arterial pressure, was considered (the pressure-time product), responses of dogs with TABD were far greater for nitroglycerin (7-9 times that seen in intact dogs) and methoxamine (11-15 times). Arterial pressure responses of dogs with selective section of the carotid sinus nerves were intermediate but closer to those of intact dogs than to dogs with TABD. With infusion of drugs or following hemorrhage, responses of mean arterial pressure were 3- to 5-fold greater in dogs with TABD than in intact dogs, indicating that the static open loop gain of the arterial baroreceptor system ranged from 2 to 4.
Immunopathogenesis and therapy of cutaneous T cell lymphoma
Authors: Ellen J. Kim, Stephen Hess, Stephen K. Richardson, Sara Newton, Louise C. Showe, Bernice M. Benoit, Ravi Ubriani, Carmela C. Vittorio, Jacqueline M. Junkins-Hopkins, Maria Wysocka, Alain H. Rook
Journal: Journal of Clinical Investigation (2005)

Cutaneous T cell lymphomas (CTCLs) are a heterogenous group of lymphoproliferative disorders caused by clonally derived, skin-invasive T cells. Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common types of CTCLs and are characterized by malignant CD4+/CLA+/CCR4+ T cells that also lack the usual T cell surface markers CD7 and/or CD26. As MF/SS advances, the clonal dominance of the malignant cells results in the expression of predominantly Th2 cytokines, progressive immune dysregulation in patients, and further tumor cell growth. This review summarizes recent insights into the pathogenesis and immunobiology of MF/SS and how these have shaped current therapeutic approaches, in particular the growing emphasis on enhancement of host antitumor immune responses as the key to successful therapy.
Diverse Effects of Heparin on Mitogen-Activated Protein Kinase–Dependent Signal Transduction in Vascular Smooth Muscle Cells
Authors: Günter Daum, Ulf Hedin, Yunxia Wang, Trevina Wang, Alexander W. Clowes
Journal: Circulation Research (1997)

Abstract Proliferation of vascular smooth muscle cells (SMCs) is implicated in pathological events, including atherosclerosis and intimal hyperplasia following angioplasty. The glycosaminoglycan heparin is a growth inhibitor of SMCs in vitro and in vivo. The underlying mechanism, however, is still poorly understood. In the present study, we report that heparin inhibited the activation of the mitogen-activated protein kinase (MAPK) in baboon SMCs by serum but not by platelet-derived growth factor (PDGF). When fibroblast growth factor was used, heparin had a stimulatory effect on MAPK. The only MAPK-activating kinase found in SMCs was MAPK kinase (MAPKK)-1, although MAPKK-2 was present in comparable amounts. Activation of MAPKK-1 and DNA synthesis were affected by heparin in a similar fashion. Heparin does not appear to exert its effects through members of the protein kinase C family, which are downregulated by phorbol esters, because it was still capable of inhibiting MAPK/MAPKK-1 stimulation by FCS in phorbol ester–pretreated cells. The present findings support the conclusions that the effects of heparin depend on the nature of the mitogen and that heparin inhibits SMC proliferation by preventing activation of MAPKK-1.
Usefulness of consecutive C-reactive protein measurements in follow-up of severe community-acquired pneumonia
Authors: A. H. W. Bruns, J. J. Oosterheert, E. Hak, A. I. M. Hoepelman
Journal: European Respiratory Journal (2008)

Despite the introduction of new inflammatory markers, C-reactive protein (CRP) remains commonly used in patients hospitalised with severe infections. However, evidence on the usefulness of consecutive CRP measurements is still unclear. The clinical relevance of consecutive CRP measurements was studied in follow-up of antibiotic treatment in patients with severe community-acquired pneumonia (CAP). In a prospective multicentre trial, CRP levels were measured on admission, and on days 3 and 7. Patients were followed clinically for 28 days. Aetiology could be determined in 137 (47.4%) out of the 289 patients included. In 122 (38.8%) patients, initial antibiotic therapy was appropriate. A decline of <60% in CRP levels in 3 days and a decline of <90% in CRP levels in 7 days were both associated with an increased risk of having received inappropriate empiric antibiotic treatment (day 0-3, odds ratio (OR) 6.98, 95% confidence interval (CI) 1.56-31.33 and day 0-7, OR 3.74, 95% CI 1.12-13.77). In conclusion, consecutive C-reactive protein measurements are useful in the first week in follow-up of antibiotic treatment for severe community-acquired pneumonia when taking the causative microorganism and use of steroids into account. A delayed normalisation of C-reactive protein levels is associated with a higher risk of having received inappropriate antibiotic treatment.
Improving Phylogenetic Inference with a Semiempirical Amino Acid Substitution Model
Authors: S. Zoller, A. Schneider
Journal: Molecular Biology and Evolution (2012)

Amino acid substitution matrices describe the rates by which amino acids are replaced during evolution. In contrast to nucleotide or codon models, amino acid substitution matrices are in general parameterless and empirically estimated, probably because there is no obvious parametrization for amino acid substitutions. Principal component analysis has previously been used to improve codon substitution models by empirically finding the most relevant parameters. Here, we apply the same method to amino acid substitution matrices, leading to a semiempirical substitution model that can adjust the transition rates to the protein sequences under investigation. Our new model almost invariably achieves the best likelihood values in large-scale comparisons with established amino acid substitution models (JTT, WAG, and LG). In particular for longer alignments, these likelihood gains are considerably larger than what could be expected from simply having more parameters. The application of our model differs from that of mixture models (such as UL2 or UL3), as we optimize one rate matrix per alignment, whereas mixture models apply the variation per alignments site. This makes our model computationally more efficient, while the performance is comparable to that of UL3. Applied to the phylogenetic problem of the origin of placental mammals, our new model and the UL3 mixed model are the only ones of the tested models that cluster Afrotheria and Xenarthra into a clade called Atlantogenata, which would be in correspondence with recent findings using more sophisticated phylogenetic methods.
Post-op Tonic
Authors: Molly O’Dell
Journal: JAMA (2010)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abundance of Aβ5-xlike immunoreactivity in transgenic 5XFAD, APP/PS1KI and 3xTG mice, sporadic and familial Alzheimer’s disease
Authors: Erika Avendaño Guzmán, Yvonne Bouter, Bernhard C Richard, Lars Lannfelt, Martin Ingelsson, Anders Paetau, Auli Verkkoniemi-Ahola, Oliver Wirths, Thomas A Bayer
Journal: Molecular Neurodegeneration (2014)

According to the modified amyloid hypothesis the main event in the pathogenesis of Alzheimer's disease (AD) is the deposition of neurotoxic amyloid β-peptide (Aβ) within neurons. Additionally to full-length peptides, a great diversity of N-truncated Aβ variants is derived from the larger amyloid precursor protein (APP). Vast evidence suggests that Aβx₋₄₂ isoforms play an important role triggering neurodegeneration due to its high abundance, amyloidogenic propensity and toxicity. Although N-truncated and Aβx₋₄₂ species have been pointed as crucial players in AD etiology, the Aβ₅-x isoforms have not received much attention.The present study is the first to show immunohistochemical evidence of Aβ₅-x in familial cases of AD (FAD) and its distribution in APP/PS1KI, 5XFAD and 3xTG transgenic mouse models. In order to probe Aβ₅-x peptides we generated the AB5-3 antibody. Positive plaques and congophilic amyloid angiopathy (CAA) were observed among all the FAD cases tested carrying either APP or presenilin 1 (PS1) mutations and most of the sporadic cases of AD (SAD). Different patterns of Aβ5-x distribution were found in the mouse models carrying different combinations of autosomal mutations in the APP, PS1 and Tau genes. All of them showed extracellular Aβ deposits but none CAA. Additionally, they were all affected by a severe amyloid pathology in the hippocampus among other areas. Interestingly, neither 5XFAD nor APP/PS1KI showed any evidence for intraneuronal Aβ₅-x.Different degrees of Aβ₅-x accumulations can be found in the transgenic AD mouse models and human cases expressing the sporadic or the familial form of the disease. Due to the lack of intracellular Aβ₅-x, these isoforms might not be contributing to early mechanisms in the cascade of events triggering AD pathology. Brain sections obtained from SAD cases showed higher Aβ₅-x-immunoreactivity in vascular deposits than in extracellular plaques, while both are equally important in the FAD cases. The difference may rely on alternative mechanisms involving Aβ₅-x peptides and operating in a divergent way in the late and early onset forms of the disease.
Mortality after bilateral salpingo-oophorectomy in BRCA1 and BRCA2 mutation carriers: a prospective cohort study
Authors: Susan M Domchek, Tara M Friebel, Susan L Neuhausen, Theresa Wagner, Gareth Evans, Claudine Isaacs, Judy E Garber, Mary B Daly, Rosalind Eeles, Ellen Matloff, Gail E Tomlinson, Laura Van't Veer, Henry T Lynch, Olufunmilayo I Olopade, Barbara L Weber, Timothy R Rebbeck
Journal: The Lancet Oncology (2006)
An Intrinsic Adrenergic Vasodilator Mechanism in the Coronary Vascular Bed of the Dog
Authors: FRANCIS J. KLOCKE, GERARD A. KAISER, JOHN ROSS, EUGENE BRAUNWALD
Journal: Circulation Research (1965)

The question of whether the coronary blood vessels contain an intrinsic adrenergic mechanism for vasodilatation has been examined by studying the response of the coronary vessels of the dog to isoproterenol. Initially, coronary blood flow, coronary sinus P O O 2 , mean arterial pressure, and heart rate were measured continuously in anesthetized, open-chest animals. When isoproterenol, 0.1 to 0.3 µg/kg/min, was given intravenously, coronary flow and coronary sinus P O O 2 always increased in spite of tachycardia and a reduced or unchanged arterial pressure. Although this response suggested a primary vasodilating effect of isoproterenol, a vasodilatation consequent to increased myocardial activity or an extracardiac factor could not be eliminated. Accordingly, additional studies were performed in an isolated heart arrested with potassium and perfused with whole blood at constant rates of flow. Isoproterenol was given by single injections and constant infusions and always produced a decrease of perfusion pressure. These decreases could be blocked by nethalide and, as indicated by measurements of myocardial oxygen uptake and coronary venous P O O 2 , did not depend upon increased myocardial metabolism or decreased myocardial oxygenation. With injections of 0.01, 0.1, 1.0, and 10.0 µg of isoproterenol, the decreases averaged respectively 3, 8, 14, and 26% of the control pressures. It is concluded that the coronary vessels of the dog do contain an intrinsic adrenergic mechanism for vasodilatation.
Ia molecule-associated selectivity in T cell recognition of a 23-amino-acid peptide of lysozyme.
Authors: N Shastri, G Gammon, A Miller, E E Sercarz
Journal: The Journal of Experimental Medicine (1986)

Ak- or Ek-restricted T cells, generated by immunization with a 23-amino-acid peptide of hen egg-white lysozyme (amino acid 74-96), showed a strict correlation between the minimal peptide determinant recognized and the Ia molecule restricting recognition. All Ak-restricted clones obtained from six independently derived lines recognized determinants contained within peptides 74-86, while Ek-restricted clones recognized determinants within 85-96. This correlation was true whether B10.A mice (Ak, Ek) were immunized with peptide 74-96 or with each of the two smaller peptides (74-86 or 85-96). Furthermore, a T cell response could be obtained to peptide 74-86, but not to peptide 85-96 in B10.A (4R) mice, which express only the Ak molecule. Thus, an Ia molecule-associated selectivity exists in the choice of T cell determinants even within this small 23-amino-acid peptide antigen. Significant differences were noted, however, in the boundaries of the minimal peptide determinants recognized within peptide 74-96 by Ak- or Ek-restricted T cells, in comparison to those recognized by Ab-restricted T cells. These results indicate that interaction of the same peptide with distinct Ia molecules results in recognition of unique aspects of the antigenic determinants by the T cell receptor.
MicroRNA-145 Suppresses Cell Invasion and Metastasis by Directly Targeting Mucin 1
Authors: Mohit Sachdeva, Yin-Yuan Mo
Journal: Cancer Research (2009)

Abstract MicroRNAs are important gene regulators that could play a profound role in tumorigenesis. Our previous studies indicate that miR-145 is a tumor suppressor capable of inhibiting tumor cell growth both in vitro and in vivo. In this study, we show that miR-145 exerts its function in a cell-specific manner. Although miR-145 inhibits cell growth in MCF-7 and HCT-116 cells, it has no significant effect on cell growth in metastatic breast cancer cell lines. However, miR-145 significantly suppresses cell invasion in these cells; in contrast, the antisense oligo against miR-145 increases cell invasion. miR-145 is also able to suppress lung metastasis in an experimental metastasis animal model. This miR-145–mediated suppression of cell invasion is in part due to the silencing of the metastasis gene mucin 1 (MUC1). Using luciferase reporters carrying the 3′-untranslated region of MUC1 combined with Western blot and immunofluorescence staining, we identify MUC1 as a direct target of miR-145. Moreover, ectopic expression of MUC1 enhances cell invasion, which can be blocked by miR-145. Of interest, suppression of MUC1 by miR-145 causes a reduction of β-catenin as well as the oncogenic cadherin 11. Finally, suppression of MUC1 by RNAi mimics the miR-145 action in suppression of invasion, which is associated with downregulation of β-catenin and cadherin 11. Taken together, these results suggest that as a tumor suppressor, miR-145 inhibits not only tumor growth but also cell invasion and metastasis. Cancer Res; 70(1); 378–87