tbuckley/cabot-search huggingface dataset:
B cell receptor revision diminishes the autoreactive B cell response after antigen activation in mice
Authors: Ying-Hua Wang, Betty Diamond
Journal: Journal of Clinical Investigation (2008)

Autoreactive B cells are regulated in the BM during development through mechanisms, including editing of the B cell receptor (BCR), clonal deletion, and anergy. Peripheral B cell tolerance is also important for protection from autoimmune damage, although the mechanisms are less well defined. Here we demonstrated, using a mouse model of SLE-like serology, that during an autoimmune response, RAG was reinduced in antigen-activated early memory or preplasma B cells. Expression of RAG was specific to antigen-reactive B cells, required the function of the IL-7 receptor (IL-7R), and contributed to maintenance of humoral tolerance. We also showed that soluble antigen could diminish a non-autoreactive antibody response through induction of BCR revision. These data suggest that tolerance induction operates in B cells at a postactivation checkpoint and that BCR revision helps regulate autoreactivity generated during an ongoing immune response.
Validation of a structured interview for the assessment of diabetes self-management.
Authors: M A Harris, T Wysocki, M Sadler, K Wilkinson, L M Harvey, L M Buckloh, N Mauras, N H White
Journal: Diabetes Care (2000)

OBJECTIVE: The authors developed and validated a semi-structured interview; the Diabetes Self-Management Profile (DSMP), to measure self-management of type 1 diabetes. The DSMP includes the following regimen components: exercise, management of hypoglycemia, diet, blood glucose testing, and insulin administration and dose adjustment. RESEARCH DESIGN AND METHODS: Families of youths with type 1 diabetes (n = 105) who were entering a controlled trial of intensive therapy (IT) versus usual care (UC) were administered the DSMP Analyses assessed the reliability and validity of the DSMP, including its associations with HbA1c and quality of life. RESULTS: The DSMP total score has adequate internal consistency (Cronbach's alpha 0.76), 3-month test-retest reliability (Pearson correlation, r = 0.67), inter-interviewer agreement (r = 0.94), and parent-adolescent agreement (r = 0.61). DSMP total scores (r = -0.28) and 3 subscales correlated significantly with HbA1c (diet [r = -0.27], blood glucose testing [r = -0.37], and insulin administration and dose adjustment [r = -0.25 ]). Adolescents' reports of self-management did not differ from parental reports. Higher DSMP scores were associated with more favorable quality of life for mothers and youths. CONCLUSIONS: The DSMP is a convenient measure that yields a reliable and valid assessment of diabetes self-management. Compared with extant similar measures, the DSMP is more strongly correlated with HbA1c.
Immunophenotyping of Cerebrospinal Fluid Cells in Multiple Sclerosis
Authors: Sascha Alvermann, Christian Hennig, Olaf Stüve, Heinz Wiendl, Martin Stangel
Journal: JAMA Neurology (2014)

Cerebrospinal fluid (CSF) is the compartment in closest proximity to the central nervous system (CNS) parenchyma and might reflect immune pathology in inflammatory CNS disorders like multiple sclerosis (MS). Multiparameter flow cytometry is used to characterize immunological alterations in the CSF of patients with MS.To present a comprehensive review of the cellular alterations in CSF that distinguish MS from physiological conditions and other CNS disorders; integrate relevant findings into a model of leukocyte trafficking in the CNS; highlight treatment-related changes in leukocyte subsets; and evaluate the potential of CSF immunophenotyping in the search of novel biomarkers in MS.We searched MEDLINE articles published between 1980 and 2013 that include the flow cytometric characterization of leukocyte subsets in the CSF of patients with MS.All of the articles have shown CSF pleocytosis in MS. Interesting results include CSF enrichment of helper T cells (subtypes TH1 and TH17) and regulatory T cells, as well as intrathecal B-cell differentiation resulting in the generation of antibody-producing plasmablasts and plasma cells. Other leukocyte populations, including natural killer cells, monocytes, and dendritic cells, show alterations as well. Characterization of CSF cells increases our understanding of MS pathogenesis and may provide useful biomarkers for individual prognosis and treatment decisions. However, validation in controlled settings is lacking in most cases.With the advent of more sophisticated approaches, immunophenotyping of CSF cells in MS might become increasingly important to correlate cellular subsets with different stages of disease activity and remission. An assessment of CSF cell numbers and composition should be incorporated into clinical trials.
Long-Term Prognosis of Patients With Kawasaki Disease Complicated by Giant Coronary Aneurysms
Authors: Kenji Suda, Motofumi Iemura, Hiroshi Nishiono, Yozo Teramachi, Yusuke Koteda, Shintaro Kishimoto, Yoshiyuki Kudo, Shinichi Itoh, Haruka Ishii, Takafumi Ueno, Tadashi Tashiro, Masakiyo Nobuyoshi, Hirohisa Kato, Toyojiro Matsuishi
Journal: Circulation (2011)

Background— Some patients with Kawasaki disease develop giant coronary aneurysms and coronary stenosis, leading to ischemic heart disease. The aim of this study was to determine the long-term prognosis of patients with Kawasaki disease with giant aneurysms. Methods and Results— From our institutional database, 76 patients (57 men and 19 women) who developed giant aneurysms after January 1, 1972, were identified. Information on patient demographics, catheter and surgical interventions, and most recent status was collected from medical charts and patients' contacts. From these data, we calculated the survival rate and cumulative coronary intervention rate. The average age at onset was 2.9±2.9 years, and the median observational period was 19 years. During this period, 7 patients died and 1 patient underwent a heart transplantation, resulting in 95%, 88%, and 88% survival rates at 10, 20, and 30 years after the onset of KD, respectively. On the other hand, catheter and surgical coronary interventions (median, 1 intervention; range, 1 to 7 interventions) were performed to alleviate coronary ischemia in 46 patients (61%) at 1 month to 21 years (mode at 1 month) after onset, resulting in 28%, 43%, and 59% cumulative coronary intervention rates at 5, 15, and 25 years after onset, respectively. Conclusions— The long-term survival of patients with Kawasaki disease complicated by giant coronary aneurysms is moderately good with multiple catheter and surgical interventions. Further research should focus on the prevention of coronary vascular remodeling and on the indications for and effectiveness of percutaneous and surgical coronary interventions.
Effect of intensive exercise on patients with active rheumatoid arthritis: a randomised clinical trial
Authors: C H M van den Ende
Journal: Annals of the Rheumatic Diseases (2000)

To investigate the effects of a dynamic, intensive exercise regimen on pain, disease activity, and physical functioning in active rheumatoid arthritis (RA).64 patients with RA with a mean age of 60 (13) years and mean disease duration of 8 (8) years, admitted to hospital because of active disease, were randomly assigned to an intensive exercise programme or to a conservative exercise programme during their period in hospital with a mean length of 30 (14) days. The intensive exercise programme consisted of knee and shoulder dynamic and isometric muscle strengthening exercises against resistance five times a week and conditioning bicycle training three times a week and was supplemental to the conservative exercise programme of range of motion and isometric exercises. Indices of disease activity, pain, muscle strength, and functional ability were assessed at 0, 3, 6, 12, and 24 weeks by a blinded observer.The medical treatment during the study was the same in both groups. Both groups improved in measures of disease activity, differences between groups were not statistically significant. The mean improvement in disease activity score at 24 weeks in the intensive and conservative exercise group was -1.4 (1. 5) and -0.7 (1.4), respectively. Measures of physical functioning improved significantly for patients in the intensive exercise group, and differences between groups were statistically significant for measures of muscle strength.A short term intensive exercise programme in active RA is more effective in improving muscle strength than a conservative exercise programme and does not have deleterious effects on disease activity.
IMPAIRED HEART RATE RECOVERY INDEX IN PATIENTS WITH SARCOIDOSIS
Authors: Idris Ardic, Mehmet G. Kaya, Mikail Yarlioglues, Orhan Dogdu, Hakan Buyukoglan, Nihat Kalay, Asiye Kanbay, Cemil Zencir, Ali Ergin
Journal: Journal of the American College of Cardiology (2011)
Major histocompatibility complex conformational epitopes are peptide specific.
Authors: B Catipović, J Dal Porto, M Mage, T E Johansen, J P Schneck
Journal: The Journal of Experimental Medicine (1992)

Serologically distinct forms of H-2Kb are stabilized by loading cells expressing "empty" class I major histocompatibility complex (MHC) molecules with different H-2Kb binding peptides. The H-2Kb epitope recognized by monoclonal antibody (mAb) 28.8.6 was stabilized by ovalbumin (OVA) (257-264) and murine cytomegalovirus (MCMV) pp89 (168-176) peptides, but not by vesicular stomatic virus nucleoprotein (VSV NP) (52-59) and influenza NP (Y345-360) peptides. The H-2Kb epitope recognized by mAb 34.4.20 was stabilized by VSV NP (52-59) peptide but not by OVA (257-264), MCMV pp89 (168-176), or influenza NP (Y345-360) peptides. Immunoprecipitation of H-2Kb molecules from normal cells showed that 28.8.6 and 34.4.20 epitopes were only present on a subset of all conformationally reactive H-2Kb molecules. Using alanine-substituted derivatives of the VSV peptide, the 28.8.6 epitope was completely stabilized by substitution of the first residue and partially stabilized by substitution of the third or the fifth residues in the peptides. These results indicate that distinct conformational MHC epitopes are dependent on the specific peptide that occupies the antigenic peptide binding groove on individual MHC molecules. The changes in MHC epitopes observed may also be important in understanding the diversity of T cell receptors used in an immune response and the influence of peptides on development of the T cell repertoire.
ACTIVATION OF T AND B LYMPHOCYTES IN VITRO
Authors: Dieter Armerding, David H. Katz
Journal: The Journal of Experimental Medicine (1974)

The present studies were undertaken to analyze the nature of the effect of bacterial lipopolysaccharide (LPS) on antibody production in vitro. We have done this by making comparative studies of the effects of LPS on in vitro primary and secondary antibody responses to soluble hapten-protein conjugates and to particulate and soluble sheep erythrocyte antigens. The results obtained demonstrate that the biological action of LPS in vitro may be predominantly manifested on the function of B lymphocytes or T lymphocytes depending on the conditions employed. In the absence of antigen, LPS appears to act primarily on B lymphocytes. In the presence of antigen, however, the data presented here show that LPS significantly influences specific helper T-cell function and it is this latter influence that is predominantly responsible for the adjuvant effects of LPS on antigen-specific antibody responses.
Death in Patients With Recurrent Prostate Cancer After Radical Prostatectomy: Prostate-Specific Antigen Doubling Time Subgroups and Their Associated Contributions to All-Cause Mortality
Authors: Stephen J. Freedland, Elizabeth B. Humphreys, Leslie A. Mangold, Mario Eisenberger, Frederick J. Dorey, Patrick C. Walsh, Alan W. Partin
Journal: Journal of Clinical Oncology (2007)

Among patients with biochemical recurrence after radical prostatectomy, we found previously that postoperative prostate-specific antigen doubling time (PSADT) was associated with risk of prostate cancer death. However, given the small number of patients in the highest risk PSADT subgroup, it is unclear which PSADT subgroups contribute the greatest to prostate cancer-specific death and how this influences all-cause mortality.This study was a retrospective analysis of 379 patients treated with radical prostatectomy between 1982 and 2000 who had a biochemical recurrence and PSADT data available. Mean and median follow-up after surgery was 11.4 (standard deviation, 5.4) and 11.0 years, respectively (range, 1.6 to 23.0 years).Shorter PSADT was significantly associated with prostate cancer-specific and all-cause mortality (P < .001). Although patients with a PSADT less than 3 months were at the greatest risk of death, because of the limited number of patients in this group, they accounted for only 13% of prostate cancer deaths at 15 years after biochemical recurrence, whereas patients with an intermediate PSADT (3.0 to 8.9 months) accounted for 58% of all prostate cancer deaths. Among patients with a PSADT less than 15 months, prostate cancer accounted for 90% of all deaths. Only patients in the slowest PSADT subgroup (> or = 15 months) had a greater risk of competing-causes mortality compared with that from prostate cancer.Among a select cohort of young, healthy patients with PSA recurrence after radical prostatectomy and a PSADT less than 15 months, prostate cancer accounted for an estimated 90% of all deaths by 15 years after recurrence. The majority of prostate cancer deaths occurred among patients with an intermediate PSADT (3.0 to 8.9 months).
Why Do Paralogs Persist? Molecular Evolution of CYCLOIDEA and Related Floral Symmetry Genes in Antirrhineae (Veronicaceae)
Authors: Lena C Hileman, David A Baum
Journal: Molecular Biology and Evolution (2003)

CYCLOIDEA (CYC) and DICHOTOMA (DICH) are paralogous genes that determine adaxial (dorsal) flower identity in the bilaterally symmetric flowers of Antirrhinum majus (snapdragon). We show here that the duplication leading to the existence of both CYC and DICH in Antirrhinum occurred before the radiation of the Antirrhineae (the tribe to which snapdragon belongs). We find no additional gene duplications within Antirrhineae. Using explicit codon-based models of evolution in a likelihood framework, we show that patterns of molecular evolution after the duplication that gave rise to CYC and DICH are consistent with purifying selection acting at both loci, despite their known functional redundancy in snapdragon. However, for specific gene regions, purifying selection is significantly relaxed across DICH lineages, relative to CYC lineages. In addition, we find evidence for relaxed purifying selection along the lineage leading to snapdragon in one of two putative functional domains of DICH. A model of selection accounting for the persistence of paralogous genes in the absence of diversifying selection is presented. This model takes into account differences in the degree of purifying selection acting at the two loci and is consistent with subfunctionalization models of paralogous gene evolution.
A Recipe for Perioperative Cardioprotection
Authors: Judy R. Kersten
Journal: Circulation (2012)

T he question of what is the ideal anesthetic for patients with cardiovascular disease has been debated for nearly 3 decades, and, similar to the case for the use of perioperative ␤-blockers, the answer appears to be increasingly enigmatic.In the current issue of Circulation, Buse et al 1 report the results of a randomized clinical trial to evaluate the effects of the volatile anesthetic sevoflurane versus the intravenous anesthetic propofol on the incidence of myocardial ischemia in 385 patients with known coronary artery disease or with Ն2 risk factors for coronary artery disease undergoing noncardiac surgery.Using continuous electrocardiography and troponin T plasma concentrations as the composite primary end point of the study, the incidence of myocardial ischemia was similar in both groups (sevoflurane, 40.8%; propofol, 40.3%), calling into question the current American College of Cardiology/American Heart Association guidelines recommending the use of volatile anesthetics for patients at cardiovascular risk who are undergoing noncardiac surgery. 2
Lnk controls mouse hematopoietic stem cell self-renewal and quiescence through direct interactions with JAK2
Authors: Alexey Bersenev, Chao Wu, Joanna Balcerek, Wei Tong
Journal: Journal of Clinical Investigation (2008)

In addition to its role in megakaryocyte production, signaling initiated by thrombopoietin (TPO) activation of its receptor, myeloproliferative leukemia virus protooncogene (c-Mpl, or Mpl), controls HSC homeostasis and self-renewal. Under steady-state conditions, mice lacking the inhibitory adaptor protein Lnk harbor an expanded HSC pool with enhanced self-renewal. We found that HSCs from Lnk–/– mice have an increased quiescent fraction, decelerated cell cycle kinetics, and enhanced resistance to repeat treatments with cytoablative 5-fluorouracil in vivo compared with WT HSCs. We further provide genetic evidence demonstrating that Lnk controls HSC quiescence and self-renewal, predominantly through Mpl. Consistent with this observation, Lnk–/– HSCs displayed potentiated activation of JAK2 specifically in response to TPO. Biochemical experiments revealed that Lnk directly binds to phosphorylated tyrosine residues in JAK2 following TPO stimulation. Of note, the JAK2 V617F mutant, found at high frequencies in myeloproliferative diseases, retains the ability to bind Lnk. Therefore, we identified Lnk as a physiological negative regulator of JAK2 in stem cells and TPO/Mpl/JAK2/Lnk as a major regulatory pathway in controlling stem cell self-renewal and quiescence.
Integration of a virus membrane protein intothe lipid bilayer of target cells as a prerequisite for immune cytolysis. Specific cytolysis after virosome- target cell fusion
Authors: B Morein, D Barz, U Koszinowski, V Schirrmacher
Journal: The Journal of Experimental Medicine (1978)

Structural requirements for membrane antigens on target cells to mediate immune cytolysis were studied in a model system with purified membrane proteins from Semliki Forest virus (SFV). These SFV spike proteins were isolated in the form of detergent- and lipid-free protein micelles (29S complexes) or, after reconstitution into lipid vesicles, in the form of virosomes. Both the 29S complexes and the virosomes were found to bind well to murine tumor cells (P815 or Eb). When these cells, however, were used as target cells in complement-dependent lysis or in antibody-dependent cell- mediated cytotoxicity assays in the presence of anti-SFV serum, they were not lysed, although they effectively bound the antibody and consumed complement. The same tumor cells infected with SFV served as positive controls in both assays. Different results were obtained when inactivated Sendai virus was added as a fusion reagent to the cells coated with either virosomes or 29S complexes. Under these conditions the virosome-coated cells became susceptible to SFV- specific lysis, whereas the 29S complex-coated cells remained resistant. Evidence that the susceptibility to lysis ofvirosome-coated cells was dependent on active fusion and, therefore, integration of the viral antigens into the lipid bilayer of the target cells was derived from control experiments with enzyme-treated Sendai virus preparations. The 29S complexes and the virosomes partially and selectively blocked the target cell lysis by anti-H-2 sera but not by anti-non-H-2 sera confirming our previous finding that major histocompatibility antigens serve as receptors for SFV. The general significance of these findings for mechanisms of immune cytolysis is dicussed.
In Vivo, In Vitro and Transplacental Immune Effects of a Probiotic Bacterium Lactobacillus rhamnosus GG in Humans
Authors: R.J. Boyle, L. Mah, S. Kivivuori, A. Chen, S.J. Lahtinen, R.M. Robins-Browne, M.L. Tang
Journal: Journal of Allergy and Clinical Immunology (2009)
Physical activity reduces cigarette cravings
Authors: Timothy W Glass, Christopher G Maher
Journal: British Journal of Sports Medicine (2013)

In the UK, over one-fifth of the adult population smokes. Many smokers (63%) wish to stop, but only 3–5% of unaided attempts are successful after 6–12 months and most people who stop smoking relapse within the first 8 days. Even with the best available pharmacological and behavioural support, lesser than 30% of smokers successfully stop.1–3 Physical activity (PA) is recommended as a smoking cessation aid.4 However, the evidence for the efficacy of PA in aiding cessation is limited.5

The aim of this systematic review and individual patient data (IPD) meta-analysis was to investigate the acute effects of short bouts of PA on cigarette craving.

Six electronic databases (SPORTDiscus, MEDLINE, PubMed, Web of Science, EMBASE and PsycINFO) were searched. The Cochrane Tobacco Addiction Group specialised register, electronic theses and dissertations (ETD), Digital Library—Network Digital Library of Theses and Dissertations (NDLTD) and ProQuest Digital Dissertations were also searched. Search terms used were ‘smoking’ or ‘smoking cessation’, ‘exercise’ or ‘physical activity’ and ‘craving$’ or ‘withdrawal’. Relevant reference lists and meeting abstracts were hand searched. Eligible studies examined the acute effects of PA on the desire to smoke and/or strength of desire to smoke and included randomised crossover or parallel arm trials with a minimum abstinence period of 2 h prior to …
A phase I–II study of gemcitabine and paclitaxel in advanced non-small-cell lung cancer patients
Authors: G. Giaccone, E.F. Smit, J.P. van Meerbeeck, T. Splinter, R.P. Golding, H.M. Pinedo, D. Laan, H. van Tinteren, P.E. Postmus
Journal: Annals of Oncology (2000)
Low-dose cytosine arabinoside (LD-AraC) vs LD-AraC plus granulocyte/macrophage colony stimulating factor vs LD-AraC plus Interleukin-3 for myelodysplastic syndrome patients with a high risk of developing acute leukemia: final results of a randomized phase III study (06903) of the EORTC Leukemia Cooperative Group
Authors: H Zwierzina, S Suciu, J Loeffler-Ragg, R Neuwirtova, P Fenaux, M Beksac, J Harousseau, V Nuessler, J Cermak, G Solbu, R Willemze, T de Witte, S Amadori
Journal: Leukemia (2005)