tbuckley/cabot-search huggingface dataset:
Overcoming Immune Tolerance Against Multiple Myeloma With Lentiviral Calnexin-engineered Dendritic Cells
Authors: Shuhong Han, Bei Wang, Matthew J Cotter, Li-Jun Yang, James Zucali, Jan S Moreb, Lung-Ji Chang
Journal: Molecular Therapy (2007)

The key to successful cancer immunotherapy is to induce an effective anticancer immunity that will overcome the acquired cancer-specific immune tolerance. In this study, we found that dendritic cells (DCs) from multiple myeloma (MM) patients suppressed rather than induced a cancer cell-specific immune response. We demonstrated that CD4+CD25high T cells from MM patients suppressed the proliferation of activated peripheral blood lymphocytes. Further analysis illustrated that MM cell lysates or MM-specific idiotype immunoglobulins (MM Id-Ig) specifically induced the expansion of peripheral CD4+CD25highFoxP3high T regulatory (Treg) cells in vitro. Supraphysiological expression of calnexin (CNX) using lentiviral (LV) vectors in DCs of MM patients overcame the immune suppression and enhanced MM-specific CD4 and CD8 T-cell responses. However, overexpression of CNX did not affect the peripheral expansion of Treg cells stimulated by MM antigens. Thus, the immune suppression effect of Treg cells in cancer patients may be overcome by improving antigen processing in DCs, which in turn may lower the activation threshold of the immune effector cells. This concept of modulating anticancer immunity by genetically engineering cancer patients' DCs may improve immunotherapeutic regimens in cancer treatment. The key to successful cancer immunotherapy is to induce an effective anticancer immunity that will overcome the acquired cancer-specific immune tolerance. In this study, we found that dendritic cells (DCs) from multiple myeloma (MM) patients suppressed rather than induced a cancer cell-specific immune response. We demonstrated that CD4+CD25high T cells from MM patients suppressed the proliferation of activated peripheral blood lymphocytes. Further analysis illustrated that MM cell lysates or MM-specific idiotype immunoglobulins (MM Id-Ig) specifically induced the expansion of peripheral CD4+CD25highFoxP3high T regulatory (Treg) cells in vitro. Supraphysiological expression of calnexin (CNX) using lentiviral (LV) vectors in DCs of MM patients overcame the immune suppression and enhanced MM-specific CD4 and CD8 T-cell responses. However, overexpression of CNX did not affect the peripheral expansion of Treg cells stimulated by MM antigens. Thus, the immune suppression effect of Treg cells in cancer patients may be overcome by improving antigen processing in DCs, which in turn may lower the activation threshold of the immune effector cells. This concept of modulating anticancer immunity by genetically engineering cancer patients' DCs may improve immunotherapeutic regimens in cancer treatment.
The emergence of ringing vertigo
Authors: Trevor Jackson
Journal: BMJ (2005)

The emergence of ringing vertigoTrevor Jackson Reports from bell ringers show how increased awareness can lead to the creation of a new condition Ding dong merrily on high, goes the famous Christmas carol, but for some of the United Kingdom's 40 000 campanologists the bells have not been ringing so merrily.Instead, church bell ringers have this year been complaining of a disorder that has been forcing them to abandon their towers and steeples and seek out hypnotherapists and counsellors in search of a cure.Symptoms include vertigo, a sensation of the world caving in, anxiety, and a loss of feeling in the hands and feet.In some cases these have been so severe that ringers have taken to their beds."I was unable to do anything for more than a week, apart from lie in bed with my eyes shut," said one campanologist.Reports of the condition first surfaced earlier this year in the letters pages of the Ringing World, the official weekly journal of the Central Council of Church Bell Ringers.The Ringing World more usually carries news of church restorations, peal reports, and details of various campanological festivals and meetings, but from May it began to attract a series of self submitted clinical case studies.The first came in a letter from Julie Mottershead of Ashtead, Surrey, who coined the term "ringing vertigo" by which the condition has since been known. 1She said, "I found that over a few sessions I was feeling increasingly uncomfortable ringing up [using an increasing angle of swing to turn the bells through nearly 180°to the ringing position], and then suddenly I could not ring at all-it was as if the world was caving in around me.This was all the more surprising as I am not in the least a 'nervy' person."I went to my GP who prescribed anti-anxiety medication.And it worked-but I fear the effect is starting to wear off.I can still ring, but the fear that the 'cave in' will occur is still there-and this in itself makes me anxious." 1 Ms Mottershead asked if any readers of the Ringing World were doctors, hypnotherapists, or practitioners of cognitive behavioural therapy, explaining, "It would be lovely to get some advice on how to proceed from someone who is familiar both with these symptoms and with ringing."Her appeal triggered off months of correspondence from other affected ringers, psychiatrists, and counsellors.One bell ringer, quoting from the Diagnostic and Statistical Manual of Mental Disorders, described Ms Mottershead's experiences as a panic attack, for which bell ringing provided numerous potential triggers: "It may be a fear of heights or of falling through the floor, of falling off a box, or a bell falling on you or a rope catching round your neck, of being unable to escape from the tower if there's a fire."
Circulating tumour cells in non-metastatic breast cancer: a prospective study
Authors: Anthony Lucci, Carolyn S Hall, Ashutosh K Lodhi, Anirban Bhattacharyya, Amber E Anderson, Lianchun Xiao, Isabelle Bedrosian, Henry M Kuerer, Savitri Krishnamurthy
Journal: The Lancet Oncology (2012)
Salt Intake, Oxidative Stress, and Renal Expression of NADPH Oxidase and Superoxide Dismutase
Authors: Chagriya Kitiyakara, Tina Chabrashvili, Yifan Chen, Jonathan Blau, Alex Karber, Shakil Aslam, William J. Welch, Christopher S. Wilcox
Journal: Journal of the American Society of Nephrology (2003)

The hypothesis that a high salt (HS) intake increases oxidative stress was investigated and was related to renal cortical expression of NAD(P)H oxidase and superoxide dismutase (SOD). 8-Isoprostane PGF(2alpha) and malonyldialdehyde were measured in groups (n = 6 to 8) of conscious rats during low-salt, normal-salt, or HS diets. NADPH- and NADH-stimulated superoxide anion (O(2)(.-)) generation was assessed by chemiluminescence, and expression of NAD(P)H oxidase and SOD were assessed with real-time PCR. Excretion of 8-isoprostane and malonyldialdehyde increased incrementally two- to threefold with salt intake (P < 0.001), whereas prostaglandin E(2) was unchanged. Renal cortical NADH- and NADPH-stimulable O(2)(.-) generation increased (P < 0.05) 30 to 40% with salt intake. Compared with low-salt diet, HS significantly (P < 0.005) increased renal cortical mRNA expression of gp91(phox) and p47(phox) and decreased expression of intracellular CuZn (IC)-SOD and mitochondrial (Mn)-SOD. Despite suppression of the renin-angiotensin system, salt loading enhances oxidative stress. This is accompanied by increased renal cortical NADH and NADPH oxidase activity and increased expression of gp91(phox) and p47(phox) and decreased IC- and Mn-SOD. Thus, salt intake enhances generation of O(2)(.-) accompanied by enhanced renal expression and activity of NAD(P)H oxidase with diminished renal expression of IC- and Mn-SOD.
Serodiagnosis of Syphilis
Authors: William J. Brown
Journal: JAMA (1968)

<h3>To the Editor:—</h3> We are in general agreement with the answer of your consultant regarding the handling of a 54-year-old housewife having a weekly reactive venereal disease research laboratory (VDRL) slide test and a reactive fluorescent treponemal antibody-absorption procedure with serum (FTA-ABS) test (<b>203</b>: 996, 1968). Evidence available to me indicates that in the serodiagnosis of syphilis the FTA-ABS test is as specific as the<i>Treponema pallidum</i>immobilization (TPI) test, yet more sensitive. Of course, patients having yaws or pinta, or other treponematoses closley related to syphilis, may also be expected to react; but these diseases would not usually be considered in the United States unless the patient has lived or traveled in countries where the diseases are endemic. A subsequent correspondent (<b>204</b>: 833, 1968) agreed with your consultant's emphasis on the possibility or probability of syphilis, but also urged that efforts be made to identify factors which might be
Complete Prevention of Cerebral Accidents in Malignant Hypertension
Authors: ANDRÉ ROBERT
Journal: Circulation Research (1956)

Ligation of the common carotid arteries was found to prevent the development of cerebral lesions (edema, hemorrhage, softening) in animals rendered hypertensive by daily injections of desoxycorticosterone acetate. The protection was complete when both carotids were ligated, and limited to the homolateral side in the case of unilateral ligation.
Phylogenetic Comparison of Huntingtin Homologues Reveals the Appearance of a Primitive polyQ in Sea Urchin
Authors: M. Tartari, C. Gissi, V. Lo Sardo, C. Zuccato, E. Picardi, G. Pesole, E. Cattaneo
Journal: Molecular Biology and Evolution (2007)

Huntingtin is a completely soluble 3,144 amino acid (aa) protein characterized by the presence of an amino-terminal polymorphic polyglutamine (polyQ) tract, whose aberrant expansion causes the progressively neurodegenerative Huntington's disease (HD). Biological evidence indicates that huntingtin (htt) is beneficial to cells (particularly to brain neurons) and that loss of its neuronal function may contribute to HD. The exact protein domains involved in its neuroprotective function are unknown. Evolutionary analyses of htt primary aa have so far been limited to a few species, but its thorough assessment may help to clarify the functions emerging during evolution. We made an extensive comparative analysis of the available htt protein homologues from different organisms along the metazoan phylogenetic tree and defined the presence of 3 different conservative blocks corresponding to human htt aa 1-386 (htt1), 683-1,586 (htt2), and 2,437-3,078 (htt3), in which HEAT (Huntingtin, Elongator factor3, the regulatory A subunit of protein phosphatase 2A, and TOR1) repeats are well conserved. We also describe the cloning and sequencing of sea urchin htt mRNA, the oldest deuterostome homologue so far available. Multiple alignment shows the first appearance of a primitive polyQ in sea urchin, which predates an ancestral polyQ sequence in a nonchordate environment and defines the polyQ characteristic as being typical of the deuterostome branch. The fact that glutamines have conserved positions in deuterostomes and the polyQ size increases during evolution suggests that the protein has a possibly Q-dependent role. Finally, we report an evident relaxing constraint of the N-terminal block in Ciona and drosophilids that correlates with the absence of polyQ and which may indicate that the N-terminal portion of htt has evolved different functions in Ciona and protostomes.
Guidance for Evidence-Informed Policies about Health Systems: Assessing How Much Confidence to Place in the Research Evidence
Authors: Simon Lewin, Xavier Bosch-Capblanch, Sandy Oliver, Elie A. Akl, Gunn E. Vist, John N. Lavis, Davina Ghersi, John-Arne Røttingen, Peter Steinmann, Metin Gulmezoglu, Peter Tugwell, Fadi El-Jardali, Andy Haines
Journal: PLoS Medicine (2012)

In the third paper in a three-part series on health systems guidance, Simon Lewin and colleagues explore the challenge of assessing how much confidence to place in evidence on health systems interventions.
Breast Cancer Index Identifies Early-Stage Estrogen Receptor–Positive Breast Cancer Patients at Risk for Early- and Late-Distant Recurrence
Authors: Yi Zhang, Catherine A. Schnabel, Brock E. Schroeder, Piiha-Lotta Jerevall, Rachel C. Jankowitz, Tommy Fornander, Olle Stål, Adam M. Brufsky, Dennis Sgroi, Mark G. Erlander
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Residual risk of relapse remains a substantial concern for patients with hormone receptor–positive breast cancer, with approximately half of all disease recurrences occurring after five years of adjuvant antiestrogen therapy. Experimental Design: The objective of this study was to examine the prognostic performance of an optimized model of Breast Cancer Index (BCI), an algorithmic gene expression–based signature, for prediction of early (0–5 years) and late (&amp;gt;5 years) risk of distant recurrence in patients with estrogen receptor–positive (ER+), lymph node–negative (LN−) tumors. The BCI model was validated by retrospective analyses of tumor samples from tamoxifen-treated patients from a randomized prospective trial (Stockholm TAM, n = 317) and a multi-institutional cohort (n = 358). Results: Within the Stockholm TAM cohort, BCI risk groups stratified the majority (∼65%) of patients as low risk with less than 3% distant recurrence rate for 0 to 5 years and 5 to 10 years. In the multi-institutional cohort, which had larger tumors, 55% of patients were classified as BCI low risk with less than 5% distant recurrence rate for 0 to 5 years and 5 to 10 years. For both cohorts, continuous BCI was the most significant prognostic factor beyond standard clinicopathologic factors for 0 to 5 years and more than five years. Conclusions: The prognostic sustainability of BCI to assess early- and late-distant recurrence risk at diagnosis has clinical use for decisions of chemotherapy at diagnosis and for decisions for extended adjuvant endocrine therapy beyond five years. Clin Cancer Res; 19(15); 4196–205. ©2013 AACR.
Mouse Carotid Artery Ligation Induces Platelet-Leukocyte–Dependent Luminal Fibrin, Required for Neointima Development
Authors: Tomihisa Kawasaki, Mieke Dewerchin, H. Roger Lijnen, I. Vreys, Jos Vermylen, Marc F. Hoylaerts
Journal: Circulation Research (2001)

Abstract —The relationship between platelet and leukocyte activation, coagulation, and neointima development was investigated in noninjured murine blood vessels subjected to blood stasis. The left common carotid artery of C57BL/6J mice was ligated proximal to the bifurcation. Tissue-factor expression in luminal leukocytes progressively increased over 2 weeks. On day 3 after ligation, in addition to infiltrated granulocytes, platelet microthrombi and platelet-covered leukocytes as well as tissue-factor–positive fibrin deposits lined the endothelium. Maximal neointima formation in carotid artery cross sections of control mice equaled 28±3.7% (n=11) and 42±5.1% (n=8) of the internal elastic lamina cross-sectional area 1 and 2 weeks after ligation. In FVIII −/− mice, stenosis was significantly lower 1 (11±3.6%, n=8) and 2 (21±4.7%, n=7) weeks after ligation (both P &lt;0.01 versus background-matched controls). In u-PA −/− mice, luminal stenosis was significantly higher 1 (38±7.0%, n=7) and 2 (77±5.6%, n=6) weeks after ligation ( P &lt;0.05 and P &lt;0.01, respectively, versus matched controls). In α 2 -AP −/− mice, stenosis was lower at 1 week (14±2.6%, n=7, P &lt;0.01) but not at 2 weeks. Responses in tissue-type plasminogen activator or plasminogen activator inhibitor-1 gene–deficient mice equaled that in controls. Reducing plasma fibrinogen levels in controls with ancrod or inducing partial thrombocytopenia with busulfan resulted in significantly less neointima, but inflammation was inhibited only in busulfan-treated mice. We conclude that stasis induces platelet activation, leading to microthrombosis and platelet-leukocyte conjugate formation, triggering inflammation and tissue-factor accumulation on the carotid artery endothelium. Delayed coagulation then results in formation of a fibrin matrix, which is used by smooth muscle cells to migrate into the lumen.
Childhood Chemotherapy and Later Drug Abuse and Growth Curve: A Follow-Up Study of 30 Adolescents
Authors: LEAH BECK, WILLIAM S. LANGFORD, MARY MACKAY, GRACE SUM
Journal: American Journal of Psychiatry (1975)

The authors studies the correlation of methylphenidate medication in childhood with later drug abuse and growth in height. Thirty adolescents with histories of minimal brain dysfunction who had been treated for at least six months with chemotherapy were compared with 30 adolescents who had not been so treated. The findings do not indicate that methylphenidate prescribed in childhood contributed to later drug abuse or seriously interfered with growth in height.
Emerging Therapeutic Strategies for Obesity
Authors: Karen E. Foster-Schubert, David E. Cummings
Journal: Endocrine Reviews (2006)

The rising tide of obesity is one of the most pressing health issues of our time, yet existing medicines to combat the problem are disappointingly limited in number and effectiveness. Fortunately, a recent burgeoning of mechanistic insights into the neuroendocrine regulation of body weight provides an expanding list of molecular targets for novel, rationally designed antiobesity pharmaceuticals. In this review, we articulate a set of conceptual principles that we feel could help prioritize among these molecules in the development of obesity therapeutics, based on an understanding of energy homeostasis. We focus primarily on central targets, highlighting selected strategies to stimulate endogenous catabolic signals or inhibit anabolic signals. Examples of the former approach include methods to enhance central leptin signaling through intranasal leptin delivery, use of superpotent leptin-receptor agonists, and mechanisms to increase leptin sensitivity by manipulating SOCS-3, PTP-1B, ciliary neurotrophic factor, or simply by first losing weight with traditional interventions. Techniques to augment signaling by neurochemical mediators of leptin action that lie downstream of at least some levels of obesity-associated leptin resistance include activation of melanocortin receptors or 5-HT2C and 5-HT1B receptors. We also describe strategies to inhibit anabolic molecules, such as neuropeptide Y, melanin-concentrating hormone, ghrelin, and endocannabinoids. Modulation of gastrointestinal satiation and hunger signals is discussed as well. As scientists continue to provide fundamental insights into the mechanisms governing body weight, the future looks bright for development of new and better antiobesity medications to be used with diet and exercise to facilitate substantial weight loss.
RhoC GTPase Expression as a Potential Marker of Lymph Node Metastasis in Squamous Cell Carcinomas of the Head and Neck
Authors: Celina G. Kleer, Theodoros N. Teknos, Mozaffarul Islam, Benjamin Marcus, Julia Shin-Jung Lee, Quintin Pan, Sofia D. Merajver
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Survival rates for squamous cell carcinoma of the head and neck (SCCHN) have remained unchanged for several decades due to local tumor recurrences as well as regional and distant metastases. Recent evidence has shown that RhoC GTPase is overexpressed in stages III and IV regionally metastatic SCCHN compared with stages I and II localized disease. This study evaluated the expression of RhoC in head and neck carcinoma and investigated the prognostic use of this marker on a large cohort of previously untreated patients with SCCHN. Experimental Design: Standard Western blot techniques were used to evaluate RhoC protein expression in nine established head and neck cancer cell lines and in normal oral epithelium. In vivo expression of RhoC in metastatic and nonmetastatic SCCHN was investigated using immunohistochemical analysis on a tissue microarray composed of 113 independent tumor samples. RhoC expression was analyzed as it related to clinical and pathologic variables of interest. Results: Levels of RhoC protein were increased in the SCCHN cell lines compared with normal oral epithelium. The in vivo expression of RhoC correlated with advanced clinical stage and lymph node metastases for the entire patient cohort as well as in small primary tumors (T1 and T2). Conclusions: This study is the first to examine the expression of RhoC GTPase protein in SCCHN and normal squamous epithelium. It is clear from the results that RhoC is a specific marker of lymph node metastases in patients with this challenging form of carcinoma. RhoC levels seem to identify a subset of patients with early tumor stage primary tumors and high metastatic potential that might benefit from more aggressive therapy. Through continued investigation, blockade of RhoC activity may be a potential target in the development of novel strategies for treating metastases of head and neck cancer.
European Birth Cohorts for Environmental Health Research
Authors: Martine Vrijheid, Maribel Casas, Anna Bergström, Amanda Carmichael, Sylvaine Cordier, Merete Eggesbø, Esben Eller, Maria P. Fantini, Mariana F. Fernández, Ana Fernández-Somoano, Ulrike Gehring, Regina Grazuleviciene, Cynthia Hohmann, Anne M. Karvonen, Thomas Keil, Manolis Kogevinas, Gudrun Koppen, Ursula Krämer, Claudia E. Kuehni, Per Magnus, Renata Majewska, Anne-Marie Nybo Andersen, Evridiki Patelarou, Maria Skaalum Petersen, Frank H. Pierik, Kinga Polanska, Daniela Porta, Lorenzo Richiardi, Ana Cristina Santos, Rémy Slama, Radim J. Sram, Carel Thijs, Christina Tischer, Gunnar Toft, Tomáš Trnovec, Stephanie Vandentorren, Tanja G.M. Vrijkotte, Michael Wilhelm, John Wright, Mark Nieuwenhuijsen
Journal: Environmental Health Perspectives (2011)

Background: Many pregnancy and birth cohort studies investigate the health effects of early-life environmental contaminant exposure. An overview of existing studies and their data is needed to improve collaboration, harmonization, and future project planning.Objectives: Our goal was to create a comprehensive overview of European birth cohorts with environmental exposure data.Methods: Birth cohort studies were included if they a) collected data on at least one environmental exposure, b) started enrollment during pregnancy or at birth, c) included at least one follow-up point after birth, d) included at least 200 mother–child pairs, and e) were based in a European country. A questionnaire collected information on basic protocol details and exposure and health outcome assessments, including specific contaminants, methods and samples, timing, and number of subjects. A full inventory can be searched on www.birthcohortsenrieco.net.Results: Questionnaires were completed by 37 cohort studies of > 350,000 mother–child pairs in 19 European countries. Only three cohorts did not participate. All cohorts collected biological specimens of children or parents. Many cohorts collected information on passive smoking (n = 36), maternal occupation (n = 33), outdoor air pollution (n = 27), and allergens/biological organisms (n = 27). Fewer cohorts (n = 12–19) collected information on water contamination, ionizing or nonionizing radiation exposures, noise, metals, persistent organic pollutants, or other pollutants. All cohorts have information on birth outcomes; nearly all on asthma, allergies, childhood growth and obesity; and 26 collected information on child neurodevelopment.Conclusion: Combining forces in this field will yield more efficient and conclusive studies and ultimately improve causal inference. This impressive resource of existing birth cohort data could form the basis for longer-term and worldwide coordination of research on environment and child health.
Generation of bcr-abl specific cytotoxic T-lymphocytes by using dendritic cells pulsed with bcr-abl (b3a2) peptide: its applicability for donor leukocyte transfusions in marrow grafted CML patients
Authors: Y Osman, M Takahashi, Z Zheng, T Koike, K Toba, A Liu, T Furukawa, S Aoki, Y Aizawa
Journal: Leukemia (1999)