tbuckley/cabot-search huggingface dataset:
Association of lpr gene with graft-vs.-host disease-like syndrome.
Authors: A N Theofilopoulos, R S Balderas, Y Gozes, M T Aguado, L M Hang, P R Morrow, F J Dixon
Journal: The Journal of Experimental Medicine (1985)

Hemopoietic cells have been reciprocally transferred between two lines of mice (MRL lpr/lpr and MRL +/+) that are congenic, differing only at the lpr (lymphoproliferation) and possibly closely linked genes. The lpr strain develops a significantly more severe and fast-paced lupus-like syndrome than +/+ strain, along with a substantially larger lymphoid mass. The results showed that: (a) hemopoietic cells of such mice were sufficient to induce the respective disease phenotypes in lethally irradiated syngeneic recipients; (b) cells of MRL +/+ mice maturing in an MRL lpr/lpr environment essentially retained the disease-producing characteristics of the donor, i.e., they induced late-life lupus without lymphadenopathy; but (c) MRL lpr/lpr cells transferred into irradiated MRL +/+ recipients unexpectedly failed to induce the early-life severe lupus and lymphoid hyperplasia of the donor, instead they caused a severe wasting syndrome resembling, in many respects, graft-vs.-host disease (GVHD). This GVHD-like syndrome developed after transfer of MRL lpr/lpr fetal liver, bone marrow, or spleen cells, and was not abrogated by elimination of T cells from the inocula. Thymectomy of the MRL +/+ recipients retarded, but did not prevent, the wasting disease. The unidirectional nature of this disease suggests that the lpr mutation conferred either a structural or regulatory defect that interfered, blocked, or altered the expression or structure of certain lymphocyte antigen(s). As a result, the MRL +/+ cells that did express this antigen(s) were recognized as foreign, and stimulated a graft-vs.-host reaction. These findings may allow definition of a new kind of rejection phenomenon caused by non-H-2 products, and may extend our understanding of the means by which the lpr gene adversely affects lymphocyte regulation and homeostasis.
Tamoxifen Induces Oxidative Stress and Mitochondrial Apoptosis via Stimulating Mitochondrial Nitric Oxide Synthase
Authors: Rafal R. Nazarewicz, Woineshet J. Zenebe, Arti Parihar, Sarah K. Larson, Enver Alidema, Jiho Choi, Pedram Ghafourifar
Journal: Cancer Research (2007)

Abstract Tamoxifen is an anticancer drug that induces oxidative stress and apoptosis via mitochondria-dependent and nitric oxide (NO)–dependent pathways. The present report shows that tamoxifen increases intramitochondrial ionized Ca2+ concentration and stimulates mitochondrial NO synthase (mtNOS) activity in the mitochondria from rat liver and human breast cancer MCF-7 cells. By stimulating mtNOS, tamoxifen hampers mitochondrial respiration, releases cytochrome c, elevates mitochondrial lipid peroxidation, increases protein tyrosine nitration of certain mitochondrial proteins, decreases the catalytic activity of succinyl-CoA:3-oxoacid CoA-transferase, and induces aggregation of mitochondria. The present report suggests a critical role for mtNOS in apoptosis induced by tamoxifen. [Cancer Res 2007;67(3):1282–90]
Prognostic impact of B-cell lymphoma 6 in primary CNS lymphoma
Authors: Stephan Kreher, Korinna Jöhrens, Felicitas Strehlow, Peter Martus, Kathrin Borowiec, Josefine Radke, Frank Heppner, Patrick Roth, Eckhard Thiel, Torsten Pietsch, Michael Weller, Agnieszka Korfel
Journal: Neuro-Oncology (2015)

We investigated the prognostic significance of B-cell differentiation status and common B-cell differentiation markers in a post hoc analysis of 119 patients with primary CNS lymphoma (PCNSL) homogeneously receiving high-dose methotrexate (HDMTX)–based chemotherapy within the prospective G-PCNSL-SG1 trial. We evaluated protein expression of B-cell lymphoma 2 (BCL2), BCL6, CD10, and multiple myeloma oncogene 1/interferon regulatory factor 4 (MUM1/IRF4) by immunohistochemistry and analyzed the association with survival. The median follow-up of all patients was 67.5 months. Median progression-free survival (PFS) was 10.61 months (95% CI: 4.23–17.00). Median overall survival (OS) was 28.85 months (95% CI: 17.96–39.73). Eighty-nine tumors expressed BCL2 (92.7%), 24 (20.5%) expressed CD10, 60 (54.1%) expressed BCL6, and 87 (79.0%) expressed MUM1/IRF4. On the basis of the Hans algorithm, 80 tumors (73.4%) were classified to the non–germinal center B group, suggesting a post–germinal center origin of PCNSL. Expression of BCL6 (cutoff point 30%), but none of the other markers, was associated with shorter PFS (P = .047) and OS (P = .035). On multivariate analysis, BCL6 expression was associated with shorter PFS (hazard ratio: 1.95, 95% CI: 1.22–3.12, P = .005) but not OS (hazard ratio: 1.85, 95% CI: 0.71–4.80, P = .21). Classification according to Hans algorithm and expression status of the single B-cell markers BCL2, CD10, and MUM1/IRF4 did not correlate with prognosis. The findings are limited by the fact that only 23% of all G-PCNSL-SG1 patients could be included in the analysis. If validated in an independent cohort, BCL6 may assume clinical relevance as an unfavorable prognostic biomarker in PCNSL.
HUMAN CYTOTOXIC T LYMPHOCYTE RESPONSES TO EPSTEIN-BARR VIRUS INFECTION
Authors: Alan B. Rickinson, Denis J. Moss
Journal: Annual Review of Immunology (1997)

▪ Abstract Epstein-Barr virus (EBV) provides one of the most informative systems with which to study cytotoxic T lymphocyte (CTL) responses in humans. The virus establishes a highly immunogenic growth-transforming infection of B lymphocytes, associated with the coordinate expression of six virus-coded nuclear antigens (EBNAs 1, 2, 3A, 3B, 3C, -LP) and two latent membrane proteins (LMPs 1 and 2). This elicits both primary and memory CT8 + CTL responses that are markedly skewed toward HLA allele-specific epitopes drawn from the EBNA3A, 3B, 3C subset of latent proteins, with reactivities to other antigens being generally much less frequent. This heirarchy of immunodominance among the different latent proteins may at least partly reflect their differential accessibility to the HLA class I–processing pathway. Furthermore, CTLs to some of the immunodominant epitopes involve highly conserved T cell receptor (TCR) usage, a level of focusing which evidence suggests could have immunopathological consequences from cross-reactive recognition of other target structures. EBV is associated with a range of human tumors, and there is increasing interest in the possibility of targeting such malignancies using virus-specific CTLs. The dramatic reversal of EBV-driven lymphoproliferations in bone marrow transplant patients following CTL infusion demonstrates the potential of this approach, and here we discuss prospects for its extension to other EBV-positive tumors in which the immunodominant EBNA3A, 3B, 3C proteins are not expressed.
CT-guided percutaneous drainage of an anterior mediastinal abscess with a 16 F catheter
Authors: P A Gevenois, G Sergent, M De Myttenaere, A Beernaerts, P Rocmans
Journal: European Respiratory Journal (1995)

We report a case of anterior mediastinal abscess treated by percutaneous drainage under computed tomography (CT) guidance. The relationships of the abscess to the adjacent organs were clearly delineated by an intravenous injection of contrast material, and the drain was inserted between the sternum and the vasa thoracica interna. Selection of this route and the choice of a large-bore catheter (16 F) are discussed.
Functional leukemia-associated antigen-specific memory CD8+ T cells exist in healthy individuals and in patients with chronic myelogenous leukemia before and after stem cell transplantation
Authors: Katayoun Rezvani, Matthias Grube, Jason M. Brenchley, Giuseppe Sconocchia, Hiroshi Fujiwara, David A. Price, Emma Gostick, Ko Yamada, Jan Melenhorst, Richard Childs, Nancy Hensel, Daniel C. Douek, A. John Barrett
Journal: Blood (2003)
Loss of CD4 membrane expression and CD4 mRNA during acute human immunodeficiency virus replication.
Authors: P Salmon, R Olivier, Y Riviere, E Brisson, J C Gluckman, M P Kieny, L Montagnier, D Klatzmann
Journal: The Journal of Experimental Medicine (1988)

Using mAbs and genomic probe to the CD4 molecule, the HIV receptor, we demonstrated that HIV replication induces the disappearance of its functional receptor from the cell surface by two distinct mechanisms. First, after being expressed onto the cell surface, HIV envelope gp110 will complex CD4, efficiently masking the CD4 epitope used by the virus to bind its receptor. This phenomenon occurs on the surface of each infected cell and is not due to the release of soluble gp110; infection with recombinant HIV/vaccinia viruses expressing a mutated HIV env gene designed to prevent gp110 release from the cell surface induces a similar gp/CD4 complexes formation. Second, virus replication induces a dramatic and rapid loss of CD4 mRNA transcripts, preventing new CD4 molecules from being synthesized. These two mechanisms of receptor modulation could have been developed to avoid reinfection of cells replicating the virus as well as to produce more infectious particles. These results suggest that the classical virus interference documented for other retroviruses might not only be due to receptor/envelope interaction, but might also depend on receptor gene expression.
ANTIBODY FORMATION IN A TUBERCULOUS LESION AT THE SITE OF INOCULATION
Authors: John O. Westwater
Journal: The Journal of Experimental Medicine (1940)

Complement fixing antibody in animals injected with heat killed tubercle bacilli in oil appears earlier in the lesion at the site of injection than in the blood serum. Complement fixing antibody in an extract prepared by suspending one part by weight of tissue from the local site in five parts of saline is in general in higher concentration than in the blood, for a period of approximately 3 weeks following injection. After this time the serum may show the higher titre. The titre of antibody at the site of injection tends to increase with the quantity of heat killed bacilli injected into the skin, up to a definable maximum. No evidence was found to support the opinion that local accumulation of antibody was caused by fixation of antibody contained in the serum and produced elsewhere in the body, for extracts of lesions produced by the injection of paraffin oil, old tuberculin, and cod liver oil showed no demonstrable antibody, or at most a very low titre, even when the serum titre was high. After reinjection of heat killed tubercle bacilli in oil into rabbits with antibody in the serum, antibody did not appear in the local lesion any earlier than in normal animals similarly injected. These observations give evidence that antibody is formed in the skin at the site of injection of tubercle bacilli.
A rush to judgment on Th17
Authors: Lawrence Steinman
Journal: The Journal of Experimental Medicine (2008)

Some immunologists have characterized T helper (Th)17 T cells as the master mediators of tissue damage in a variety of pathological conditions. New data now demonstrate that Th1 and Th17 T cells are independently capable of inducing disease in two established models of autoimmunity. Thus, the role of Th17 cytokines as the central mediators of pathological tissue damage seems to require clarification.
Inferring a Tumor Progression Model for Neuroblastoma From Genomic Data
Authors: Sven Bilke, Qing-Rong Chen, Frank Westerman, Manfred Schwab, Daniel Catchpoole, Javed Khan
Journal: Journal of Clinical Oncology (2005)

The knowledge of the key genomic events that are causal to cancer development and progression not only is invaluable for our understanding of cancer biology but also may have a direct clinical impact. The task of deciphering a model of tumor progression by requiring that it explains (or at least does not contradict) known clinical and molecular evidence can be very demanding, particularly for cancers with complex patterns of clinical and molecular evidence.We formalize the process of model inference and show how a progression model for neuroblastoma (NB) can be inferred from genomic data. The core idea of our method is to translate the model of clonal cancer evolution to mathematical testable rules of inheritance. Seventy-eight NB samples in stages 1, 4S, and 4 were analyzed with array-based comparative genomic hybridization.The pattern of recurrent genomic alterations in NB is strongly stage dependent and it is possible to identify traces of tumor progression in this type of data.A tumor progression model for neuroblastoma is inferred, which is in agreement with clinical evidence, explains part of the heterogeneity of the clinical behavior observed for NB, and is compatible with existing empirical models of NB progression.
Phospholipid liposomes acquire apolipoprotein E in atherogenic plasma and block cholesterol loading of cultured macrophages.
Authors: K J Williams, A R Tall, C Bisgaier, R Brocia
Journal: Journal of Clinical Investigation (1987)

A single infusion of phospholipid liposomes promptly and persistently abolished the ability of hypercholesterolemic rabbit plasma to cause cholesteryl ester loading in cultured macrophages. This phospholipid enrichment of plasma caused moderate stimulation of cellular cholesterol efflux and, unexpectedly, almost complete inhibition of cellular uptake of beta-very low density lipoprotein (beta-VLDL), the major cholesteryl ester-rich particle in hypercholesterolemic rabbit plasma. Cell viability and LDL receptor activity were unaffected. Incubation of liposomes with beta-VLDL resulted in transfer of apolipoprotein-E (apoE) to the liposomes; reisolated apoE-phospholipid liposomes then competed efficiently for cellular apoprotein receptors. Thus, a major mechanism by which phospholipid infusions result in diminished accumulation of cholesteryl ester in cultured macrophages is by blocking cellular uptake of beta-VLDL. The liposomes deplete beta-VLDL of apoE, then compete for receptor-mediated uptake. These results suggest a novel mechanism contributing to the known antiatherogenic effect of phospholipid infusions: infused liposomes acquire apoE, then block uptake of atherogenic lipoproteins by arterial wall macrophages.
Methyl Chloride Poisoning
Authors: C. A. Birch
Journal: BMJ (1963)

Syntocinon, on the other hand, is a pure polypeptide and is free from vaso- pressor activity, a fact stressed by the manufacturer's pamphlet.This claim was endorsed by a recent clinical study3 during which it was noted that in normotensive women a combination of syntocinon and ergometrine did not appear to be associated with the hypertensive response characteristic of simultaneous injections of naturally derived oxytocin and ergometrine.-We trust that this promising combina- tion of oxytocic agents, syntometrine, will receive fair and rational clinical evaluation.-Weare, etc.,
Infection with a novel human DNA virus (TTV) has no pathogenic significance in patients with liver diseases
Authors: Mireia Giménez-Barcons, Xavier Forns, Sergi Ampurdanés, Magda Guilera, Marta Soler, Carolina Soguero, Alberto Sánchez-Fueyo, Antoni Mas, Jordi Bruix, José-María Sánchez-Tapias, Juan Rodés, Juan-Carlos Saiz
Journal: Journal of Hepatology (1999)
Recovery of Hypoglycemia Awareness in Long-standing Type 1 Diabetes: A Multicenter 2 × 2 Factorial Randomized Controlled Trial Comparing Insulin Pump With Multiple Daily Injections and Continuous With Conventional Glucose Self-monitoring (HypoCOMPaSS)
Authors: Stuart A. Little, Lalantha Leelarathna, Emma Walkinshaw, Horng Kai Tan, Olivia Chapple, Alexandra Lubina-Solomon, Thomas J. Chadwick, Shalleen Barendse, Deborah D. Stocken, Catherine Brennand, Sally M. Marshall, Ruth Wood, Jane Speight, David Kerr, Daniel Flanagan, Simon R. Heller, Mark L. Evans, James A.M. Shaw
Journal: Diabetes Care (2014)

OBJECTIVE To determine whether impaired awareness of hypoglycemia (IAH) can be improved and severe hypoglycemia (SH) prevented in type 1 diabetes, we compared an insulin pump (continuous subcutaneous insulin infusion [CSII]) with multiple daily injections (MDIs) and adjuvant real-time continuous glucose monitoring (RT) with conventional self-monitoring of blood glucose (SMBG). RESEARCH DESIGN AND METHODS A 24-week 2 × 2 factorial randomized controlled trial in adults with type 1 diabetes and IAH was conducted. All received comparable education, support, and congruent therapeutic targets aimed at rigorous avoidance of biochemical hypoglycemia without relaxing overall control. Primary end point was between-intervention difference in 24-week hypoglycemia awareness (Gold score). RESULTS A total of 96 participants (mean diabetes duration 29 years) were randomized. Overall, biochemical hypoglycemia (≤3.0 mmol/L) decreased (53 ± 63 to 24 ± 56 min/24 h; P = 0.004 [t test]) without deterioration in HbA1c. Hypoglycemia awareness improved (5.1 ± 1.1 to 4.1 ± 1.6; P = 0.0001 [t test]) with decreased SH (8.9 ± 13.4 to 0.8 ± 1.8 episodes/patient-year; P = 0.0001 [t test]). At 24 weeks, there was no significant difference in awareness comparing CSII with MDI (4.1 ± 1.6 vs. 4.2 ± 1.7; difference 0.1; 95% CI −0.6 to 0.8) and RT with SMBG (4.3 ± 1.6 vs. 4.0 ± 1.7; difference −0.3; 95% CI −1.0 to 0.4). Between-group analyses demonstrated comparable reductions in SH, fear of hypoglycemia, and insulin doses with equivalent HbA1c. Treatment satisfaction was higher with CSII than MDI (32 ± 3 vs. 29 ± 6; P = 0.0003 [t test]), but comparable with SMBG and RT (30 ± 5 vs. 30 ± 5; P = 0.79 [t test]). CONCLUSIONS Hypoglycemia awareness can be improved and recurrent SH prevented in long-standing type 1 diabetes without relaxing HbA1c. Similar biomedical outcomes can be attained with conventional MDI and SMBG regimens compared with CSII/RT, although satisfaction was higher with CSII.
A decade of mycophenolate mofetil for lupus nephritis: is the glass half-empty or half-full?
Authors: Dimitrios T Boumpas, George K Bertsias, James E Balow
Journal: Annals of the Rheumatic Diseases (2010)

The treatment of proliferative lupus nephritis (LN) can be staged as a period of intensive immunosuppressive therapy aimed at halting immunological injury (induction therapy) followed by a period of less aggressive maintenance therapy to consolidate the response. Maintenance therapy should be continued into the period of disease quiescence to decrease the number of flares and renal damage accrual.1 Randomised controlled trials (RCTs) have shown that adjunctive immunosuppressive agents are more effective than glucocorticoids alone in protecting against the risk of progression to end-stage renal disease (ESRD). Long-term (>10 years) efficacy has been demonstrated only for cyclophosphamide (CY)-based regimens1,–,3; however, CY is associated with gonadal toxicity, which is both dose- and age-dependent.4 Mycophenolate mofetil (MMF), with little if any gonadal toxicity, has been examined as an alternative to CY for both induction and maintenance therapies. MMF has been shown in several RCTs to achieve comparable short-term rates of partial remission of LN, but it remains to be proved whether it will ultimately be as effective as CY in pre-empting ESRD.

Irrespective of the choice of induction therapy, there is broad consensus that maintenance therapy must be well tolerated, reasonably affordable and have intrinsically low rates of toxicity. Currently, the two most common choices for maintenance therapy are MMF and azathioprine (AZA). These two agents have distinct but similar mechanisms of action as purine antimetabolites. There is ongoing controversy about the objective evidence for the superiority of MMF over AZA as maintenance therapy in organ transplantation as well as in other immune-mediated diseases.5 As a result, some have argued that the lack of objective superiority of MMF on organ survival does not justify the 16-fold higher cost of MMF over AZA, although it is expected to be reduced after the patent expires at …
BPR0L075, a Novel Synthetic Indole Compound with Antimitotic Activity in Human Cancer Cells, Exerts Effective Antitumoral Activity<b><i>in Vivo</i></b>
Authors: Ching-Chuan Kuo, Hsing-Pang Hsieh, Wen-Yu Pan, Ching-Ping Chen, Jing-Ping Liou, Shiow-Ju Lee, Yi-Ling Chang, Li-Tzong Chen, Chiung-Tong Chen, Jang-Yang Chang
Journal: Cancer Research (2004)

Abstract BPR0L075 is a novel synthetic compound discovered through research to identify new microtubule inhibitors. BPR0L075 inhibits tubulin polymerization through binding to the colchicine-binding site of tubulin. Cytotoxic activity of BPR0L075 in a variety of human tumor cell lines has been ascertained, with IC50 values in single-digit nanomolar ranges. As determined by flow cytometry, human cervical carcinoma KB cells are arrested in G2-M phases in a time-dependent manner before cell death occurs. Terminal deoxynucleotidyl transferase-mediated nick end labeling assay indicates that cell death proceeds through an apoptotic pathway. Additional studies indicate that the effect of BPR0L075 on cell cycle arrest is associated with an increase in cyclin B1 levels and a mobility shift of Cdc2 and Cdc25C. The changes in Cdc2 and Cdc25C coincide with the appearance of phosphoepitopes recognized by a marker of mitosis, MPM-2. Furthermore, phosphorylated forms of Bcl-2, perturbed mitochondrial membrane potential, and activation of the caspase-3 cascade may be involved in BPR0L075-induced apoptosis. Notably, several KB-derived multidrug-resistant cell lines overexpressing P-gp170/MDR and MRP are resistant to vincristine, paclitaxel, and colchicine but not to BPR0L075. Moreover, BPR0L075 shows potent activity against the growth of xenograft tumors of the gastric carcinoma MKN-45, human cervical carcinoma KB, and KB-derived P-gp170/MDR-overexpressing KB-VIN10 cells at i.v. doses of 50 mg/kg in nude mice. These findings indicate BPR0L075 is a promising anticancer compound with antimitotic activity that has potential for management of various malignancies, particularly for patients with drug resistance.