tbuckley/cabot-search huggingface dataset:
Silencing of B Cell Receptor Signals in Human Naive B Cells
Authors: Niklas Feldhahn, Ines Schwering, Sanggyu Lee, Maria Wartenberg, Florian Klein, Hui Wang, Guolin Zhou, San Ming Wang, Janet D. Rowley, Jürgen Hescheler, Martin Krönke, Klaus Rajewsky, Ralf Küppers, Markus Müschen
Journal: The Journal of Experimental Medicine (2002)

To identify changes in the regulation of B cell receptor (BCR) signals during the development of human B cells, we generated genome-wide gene expression profiles using the serial analysis of gene expression (SAGE) technique for CD34+ hematopoietic stem cells (HSCs), pre-B cells, naive, germinal center (GC), and memory B cells. Comparing these SAGE profiles, genes encoding positive regulators of BCR signaling were expressed at consistently lower levels in naive B cells than in all other B cell subsets. Conversely, a large group of inhibitory signaling molecules, mostly belonging to the immunoglobulin superfamily (IgSF), were specifically or predominantly expressed in naive B cells. The quantitative differences observed by SAGE were corroborated by semiquantitative reverse transcription–polymerase chain reaction (RT-PCR) and flow cytometry. In a functional assay, we show that down-regulation of inhibitory IgSF receptors and increased responsiveness to BCR stimulation in memory as compared with naive B cells at least partly results from interleukin (IL)-4 receptor signaling. Conversely, activation or impairment of the inhibitory IgSF receptor LIRB1 affected BCR-dependent Ca2+ mobilization only in naive but not memory B cells. Thus, LIRB1 and IL-4 may represent components of two nonoverlapping gene expression programs in naive and memory B cells, respectively: in naive B cells, a large group of inhibitory IgSF receptors can elevate the BCR signaling threshold to prevent these cells from premature activation and clonal expansion before GC-dependent affinity maturation. In memory B cells, facilitated responsiveness upon reencounter of the immunizing antigen may result from amplification of BCR signals at virtually all levels of signal transduction.
Home-Based Physical Activity Intervention for Breast Cancer Patients
Authors: Bernardine M. Pinto, Georita M. Frierson, Carolyn Rabin, Joseph J. Trunzo, Bess H. Marcus
Journal: Journal of Clinical Oncology (2005)

Purpose The efficacy of a home-based physical activity (PA) intervention for early-stage breast cancer patients was evaluated in a randomized controlled trial. Patients and Methods Eighty-six sedentary women (mean age, 53.14 years; standard deviation, 9.70 years) who had completed treatment for stage 0 to II breast cancer were randomly assigned to a PA or contact control group. Participants in the PA group received 12 weeks of PA counseling (based on the Transtheoretical Model) delivered via telephone, as well as weekly exercise tip sheets. Assessments were conducted at baseline, after treatment (12 weeks), and 6 and 9 month after baseline follow-ups. The post-treatment outcomes are reported here. Results Analyses showed that, after treatment, the PA group reported significantly more total minutes of PA, more minutes of moderate-intensity PA, and higher energy expenditure per week than controls. The PA group also out-performed controls on a field test of fitness. Changes in PA were not reflected in objective activity monitoring. The PA group was more likely than controls to progress in motivational readiness for PA and to meet PA guidelines. No significant group differences were found in body mass index and percent body fat. Post-treatment group comparisons revealed significant improvements in vigor and a reduction in fatigue in the PA group. There was a positive trend in intervention effects on overall mood and body esteem. Conclusion The intervention successfully increased PA and improved fitness and specific aspects of psychological well-being among early-stage breast cancer patients. The success of a home-based PA intervention has important implications for promoting recovery in this population.
Local therapeutic efficacy with reduced systemic side effects by rapamycin-loaded subcapsular microspheres
Authors: Lucas L. Falke, Stefan H. van Vuuren, Filis Kazazi-Hyseni, Farshad Ramazani, Tri Q. Nguyen, Gert J. Veldhuis, Erik M. Maarseveen, Jurjen Zandstra, Johan Zuidema, Luisa F. Duque, Rob Steendam, Eliane R. Popa, Robbert Jan Kok, Roel Goldschmeding
Journal: Biomaterials (2014)
Drag Addicts in a Therapeutic Community
Authors: V.S. Fischmann
Journal: Psychotherapy and Psychosomatics (1968)

Research Articles| February 12 2010 Drug Addicts in a Therapeutic Community: Outline on the California Rehabilitation Center Program, Corona Subject Area: Psychiatry and Psychology V.S. Fischmann V.S. Fischmann Corona, Cal. Search for other works by this author on: This Site PubMed Google Scholar Psychother Psychosom (1968) 16 (1-3): 109–118. https://doi.org/10.1159/000285923 Article history Published Online: February 12 2010 Content Tools Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation V.S. Fischmann; Drug Addicts in a Therapeutic Community: Outline on the California Rehabilitation Center Program, Corona. Psychother Psychosom 31 December 1968; 16 (1-3): 109–118. https://doi.org/10.1159/000285923 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsPsychotherapy and Psychosomatics Search Advanced Search This content is only available via PDF. 1968Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements. Article PDF first page preview Close Modal You do not currently have access to this content.
Allogeneic bone marrow transplantation for hematological malignancies following etoposide, cyclophosphamide, and fractionated total body irradiation
Authors: Jonathan C. Yau, Susan D. Huan, Charles F. Lemaistre, Carole M. Meneghetti, Borje S. Andersson, Ralph O. Wallerstein, Shiao Y. Woo, Lane J. Brunner, Meletios A. Dimopoulos, Sundar Jagannath, Albert B. Deisseroth, Gary Spitzer, Verneeda Spencer, Jorge A. Spinolo, Karel A. Dicke, Sergio Giralt
Journal: American Journal of Hematology (1992)

Forty-three patients received etoposide, cyclophosphamide, and fractionated total body irradiation before allogeneic marrow transplantation. Fifteen patients had chronic myelogenous leukemia in chronic phase or acute leukemia in first remission (standard risk) and twenty-eight patients with more advanced disease (high risk). All patients received etoposide 1,500 mg/m2 intravenously on day -8, cyclophosphamide 60 mg/kg/day intravenously on days -7 and -6, and total body irradiation at 170 cGy twice a day on days -3, -2, and -1. During the first 100 days 12 high risk patients (43%) died from causes unrelated to relapse while none of the standard risk patients died. Renal and hepatic dysfunction were also significantly increased during the first 14 days in the high risk group. The addition of 1,500 mg/m2 of etoposide to the cyclophosphamide and total body irradiation was well tolerated for patients with standard risk. However, the regimen was poorly tolerated with high mortality in patients with more advanced disease.
Surgical treatment in lumbar disc protrusion.
Authors: A Naylor
Journal: BMJ (1977)

Disorders of the lumbar intervertebral discs are a major source of disability and economic loss. They usually occur in the 35-45 age groups, men being affected marginally more than women. They are less often seen in adolescence, when there is an in creased incidence in boys, and the condition tends to run a more protracted course. Analysis of numerous reports indicates that injury is a prime factor in the onset of lumbar disc prolapse in only 12-14?o of patients. Injury is usually only a precipitating factor, as a biochemical defect is the underlying basic cause on which mechanical stresses are superimposed. Thus many closed methods of treatment are likely to be beneficial in view of the self-limiting nature and expected propensity of the lesion to resolve spontaneously if additional stress or strains on the lumbar spine are removed or minimised. These may take the form of bed rest, an efficient method if applied seriously, or immobilisation of the lumbar spine in a plaster jacket or Gold thwait type of belt. Alternatively, the stress on the lumbar spine may be relieved by traction, especially if combined with continuous bed rest. Epidural hydrocortisone also helps. Goldthwait in 191 11 first described the syndrome of lumbar disc herniation, diagnosing the presence of a disc protrusion to account for the development of paraplegia in a patient under going manipulative treatment for sciatica. No operation was performed, and the diagnosis was confirmed at necropsy. Belated recognition of this important lesion followed the description by Mixter and Barr2 of the results of surgery for lumbar disc prolapse. As the diagnosis was made with increasing frequency, surgical invervention became extensively and often unnecessarily employed, but with further experience of the spontaneous resolution that occurs in the syndrome in most cases and the relief produced by conservative measures in many patients, there is now a more balanced view of the need for surgical treatment. There is a wide variation of symptoms and signs from minor degrees of backache to the fully developed picture of lumbo sacral nerve root radiation, with neurological and orthopaedic signs (see figure). In many cases, the disc disorder is contained within the annulus-that is, there is a disturbance in the nucleus, biochemical in nature, which results in an increased intradisc pressure or minor incomplete annular ruptures, and these produce defective function of the disc and its segmental spinal joint. This is associated with backache, which may radiate to the buttock and as far distally as the greater trochanter of the femur. This limited radiation of pain posterolaterally should a b c d
Prospective Study of Breast Cancer Incidence in Women With a <i>BRCA1</i> or <i>BRCA2</i> Mutation Under Surveillance With and Without Magnetic Resonance Imaging
Authors: Ellen Warner, Kimberley Hill, Petrina Causer, Donald Plewes, Roberta Jong, Martin Yaffe, William D. Foulkes, Parviz Ghadirian, Henry Lynch, Fergus Couch, John Wong, Frances Wright, Ping Sun, Steven A. Narod
Journal: Journal of Clinical Oncology (2011)

The sensitivity of magnetic resonance imaging (MRI) for breast cancer screening exceeds that of mammography. If MRI screening reduces mortality in women with a BRCA1 or BRCA2 mutation, it is expected that the incidence of advanced-stage breast cancers should be reduced in women undergoing MRI screening compared with those undergoing conventional screening.We followed 1,275 women with a BRCA1 or BRCA2 mutation for a mean of 3.2 years. In total, 445 women were enrolled in an MRI screening trial in Toronto, Ontario, Canada, and 830 were in the comparison group. The cumulative incidences of ductal carcinoma in situ (DCIS), early-stage, and late-stage breast cancers were estimated at 6 years in the cohorts.There were 41 cases of breast cancer in the MRI-screened cohort (9.2%) and 76 cases in the comparison group (9.2%). The cumulative incidence of DCIS or stage I breast cancer at 6 years was 13.8% (95% CI, 9.1% to 18.5%) in the MRI-screened cohort and 7.2% (95% CI, 4.5% to 9.9%) in the comparison group (P = .01). The cumulative incidence of stages II to IV breast cancers was 1.9% (95% CI, 0.2% to 3.7%) in the MRI-screened cohort and 6.6% (95% CI, 3.8% to 9.3%) in the comparison group (P = .02). The adjusted hazard ratio for the development of stages II to IV breast cancer associated with MRI screening was 0.30 (95% CI, 0.12 to 0.72; P = .008).Annual surveillance with MRI is associated with a significant reduction in the incidence of advanced-stage breast cancer in BRCA1 and BRCA2 carriers.
Decreased prevalence of atopy in paediatric patients with familial Mediterranean fever
Authors: C Sackesen
Journal: Annals of the Rheumatic Diseases (2004)

A number of inflammatory diseases, including familial Mediterranean fever (FMF), have been shown to be driven by a strongly dominated Th1 response, whereas the pathogenesis of atopic diseases is associated with a Th2 response.Because dominance of interferon gamma has the potential of inhibiting Th2 type responses-that is, development of allergic disorders, to investigate whether FMF, or mutations of the MEFV gene, have an effect on allergic diseases and atopy that are associated with an increased Th2 activity.Sixty children with FMF were questioned about allergic diseases such as asthma, allergic rhinitis, and atopic dermatitis, as were first degree relatives, using the ISAAC Study phase II questionnaire. The ISAAC Study phase II was performed in a similar ethnic group recruited from central Anatolia among 3041 children. The same skin prick test panel used for the ISAAC Study was used to investigate the presence of atopy in patients with FMF and included common allergens.The prevalences of doctor diagnosed asthma, allergic rhinitis, and eczema were 3.3, 1.7, and 3.3%, respectively, in children with FMF, whereas the corresponding prevalences in the ISAAC study were 6.9, 8.2, and 2.2%, respectively. Only the prevalence of allergic rhinitis was significantly different between the two groups (p<0.001). The prevalence of atopy in these patients with FMF (4/60 (7%)) was significantly lower than in the children of the population based study (20.6%) (p<0.001).Family Mediterranean fever seems to be protective against development of atopic sensitisation and allergic rhinitis.
Cells with intense EGFR staining and a high nuclear to cytoplasmic ratio are specific for infiltrative glioma: a useful marker in neuropathological practice
Authors: F. Burel-Vandenbos, L. Turchi, M. Benchetrit, E. Fontas, Z. Pedeutour, V. Rigau, F. Almairac, D. Ambrosetti, J.-F. Michiels, T. Virolle
Journal: Neuro-Oncology (2013)

The differential diagnosis between infiltrative glioma (IG) and benign or curable glial lesions, such as gliosis, pilocytic astrocytoma, dysembryoplastic neuroepithelial tumor, ganglioglioma, or demyelinating disease, may be challenging for the pathologist because specific markers are lacking. Recently, we described a strong EGFR immunolabelling pattern in cells with a high nuclear to cytoplasmic ratio that enables the discrimination of low-grade IG from gliosis. The aim of this study was to extend our observation to high-grade glioma to assess whether EGFR expression pattern is of value in the discrimination of all IG from noninfiltrative glial lesions (NIG), including gliosis, benign tumors, and demyelinating disease. One hundred one IG and 58 NIG were compared for immunohistochemical expression of EGFR with use of an antibody that recognizes an epitope in the extracellular domain of both EGFRwt and EGFRvIII. Highly EGFR-positive cells with a high nuclear to cytoplasmic ratio were isolated and further characterized. Cells with intense EGFR staining and a high nuclear to cytoplasmic ratio were significantly associated with the diagnosis of IG (P < .0001). The sensitivity and specificity of this staining pattern for the diagnosis of IG were 95% and 100%, respectively. EGFR expression was independent of IDH1 mutations and EGFR amplification. Finally, we showed that these particular cells displayed the phenotype and properties of glial progenitors and coexpressed CXCR4, a marker of invasiveness. We demonstrate that cells with intense EGFR staining and a high nuclear to cytoplasmic ratio are specific criteria for the diagnosis of IG, irrespective of grade, histological subtype, and progression pathway, and their identification represents a tool to discriminate IG from benign or curable glial lesions.
Distinct Structural Domains within C19ORF5 Support Association with Stabilized Microtubules and Mitochondrial Aggregation and Genome Destruction
Authors: Leyuan Liu, Amy Vo, Guoqin Liu, Wallace L. McKeehan
Journal: Cancer Research (2005)

Abstract C19ORF5 is a sequence homologue of microtubule-associated proteins MAP1A/MAP1B of unknown function, except for its association with mitochondria-associated proteins and the paclitaxel-like microtubule stabilizer and candidate tumor suppressor RASSF1A. Here, we show that when overexpressed in mammalian cells the recombinant 393–amino acid residue COOH terminus of C19ORF5 (C19ORF5C) exhibited four types of distribution patterns proportional to expression level. Although normally distributed throughout the cytosol without microtubular association, C19ORF5C specifically accumulated on stabilized microtubules in paclitaxel-treated cells and interacted directly with paclitaxel-stabilized microtubules in vitro. The native 113-kDa full-length C19ORF5 and a shorter 56-kDa form similarly associated with stabilized microtubules in liver cells and stabilized microtubules from their lysates. As C19ORF5 accumulated, it appeared on mitochondria and progressively induced distinct perinuclear aggregates of mitochondria. C19ORF5 overlapped with cytochrome c–deficient mitochondria with reduced membrane potential. Mitochondrial aggregation resulted in gross degradation of DNA, a cell death–related process we refer to as mitochondrial aggregation and genome destruction (MAGD). Deletion mutagenesis revealed that the C19ORF5 hyperstabilized microtubule-binding domain resides in a highly basic sequence of &amp;lt;100 residues, whereas the MAGD activity resides further downstream in a distinct 25-residue sequence (F967-A991). Our results suggest that C19ORF5 mediates communication between the microtubular cytoskeleton and mitochondria in control of cell death and defective genome destruction through distinct bifunctional structural domains. The accumulation of C19ORF5 and resultant MAGD signaled by hyperstabilized microtubules may be involved in the tumor suppression activity of RASSF1A, a natural microtubule stabilizer and interaction partner with C19ORF5, and the taxoid drug family.
FDA regulation of tobacco advertising and youth smoking. Historical, social, and constitutional perspectives
Authors: L. O. Gostin
Journal: JAMA (1997)

Perspectives on tobacco control in American society have shifted markedly. As the view that smoking as a voluntarily assumed health risk has declined, the social and political environment has become more conducive to industry regulation. This transformation can be traced to the mounting evidence of the health risks of secondary smoke; the addictive quality of nicotine; the vulnerability and exploitation of young people; and industry knowledge of the harmful effects of tobacco. Regulation of tobacco advertising and promotions by the Food and Drug Administration (FDA) raises serious concerns about constitutional protection for commercial speech. However, the minimal informational value of tobacco advertising suggests that it should be afforded a low level of constitutional protection. The FDA regulations impose reasonable "time, place, and manner" restrictions, leave open alternative channels of communication, restrict messages that are harmful to the public health, do not restrict political speech, prevent misleading messages, and help deter the unlawful sale of tobacco products to minors. The regulations meet the traditional criteria for regulating commercial speech, in that the government's asserted interest is strong, the agency's regulations directly advance that interest, and the regulations are no more extensive than necessary. Thus, the judiciary should defend the FDA's historical social and legislative mission to protect the public health.
Hospice care for children.
Authors: S R Burne
Journal: BMJ (1982)

Ed Ann Armstrong-Dailey, Sarah Zarbock Goltzer Oxford University Press, pounds sterling 30, pp 294 ISBN 0-19-507312-6

Hospice care for children has developed rapidly over the past decade. As hospice care for adults has matured and become more widely available it is not surprising that similar ideas have been applied to the care of children with life threatening and terminal illnesses. In the United Kingdom this development has resulted in the opening of six hospice units providing respite and terminal care to children with a wide range of diagnoses.

Hospice Care for Children offers an account of the parallel developments in the United States in a series of essays from varied …
Type I IFN controls chikungunya virus via its action on nonhematopoietic cells
Authors: Clémentine Schilte, Thérèse Couderc, Fabrice Chretien, Marion Sourisseau, Nicolas Gangneux, Florence Guivel-Benhassine, Anton Kraxner, Jürg Tschopp, Stephen Higgs, Alain Michault, Fernando Arenzana-Seisdedos, Marco Colonna, Lucie Peduto, Olivier Schwartz, Marc Lecuit, Matthew L. Albert
Journal: The Journal of Experimental Medicine (2010)

Chikungunya virus (CHIKV) is the causative agent of an outbreak that began in La Réunion in 2005 and remains a major public health concern in India, Southeast Asia, and southern Europe. CHIKV is transmitted to humans by mosquitoes and the associated disease is characterized by fever, myalgia, arthralgia, and rash. As viral load in infected patients declines before the appearance of neutralizing antibodies, we studied the role of type I interferon (IFN) in CHIKV pathogenesis. Based on human studies and mouse experimentation, we show that CHIKV does not directly stimulate type I IFN production in immune cells. Instead, infected nonhematopoietic cells sense viral RNA in a Cardif-dependent manner and participate in the control of infection through their production of type I IFNs. Although the Cardif signaling pathway contributes to the immune response, we also find evidence for a MyD88-dependent sensor that is critical for preventing viral dissemination. Moreover, we demonstrate that IFN-α/β receptor (IFNAR) expression is required in the periphery but not on immune cells, as IFNAR−/−→WT bone marrow chimeras are capable of clearing the infection, whereas WT→IFNAR−/− chimeras succumb. This study defines an essential role for type I IFN, produced via cooperation between multiple host sensors and acting directly on nonhematopoietic cells, in the control of CHIKV.