tbuckley/cabot-search huggingface dataset:
Steroid Hormone Receptors and the Nucleus*
Authors: MARIAN R. WALTERS
Journal: Endocrine Reviews (1985)

THE CONCEPT that steroid hormone action is mediated by interaction with specific target tissue receptor proteins has become generally well accepted. Receptors that are not bound to hormone (unoccupied receptors) were initially described as residing in cytosolic/cytoplasmic1 compartments of many systems. Biochemical and autoradiographic procedures led to this conclusion. Additional evidence established that hormone binding induces receptor transformation2 and receptor movement from the cytosolic to the nuclear compartment (translocation), where the biological response is initiated. This review summarizes the evidence for steroid receptor action in the nucleus and discusses the recent controversy that unoccupied receptors themselves may be predominantly associated with nuclear components in vivo. This summary, rather than being an exhaustive review of one or two receptor systems, emphasizes the parallel development of these concepts in multiple steroid hormone receptor systems,3 in part by relying on prior reviews that focus in depth on specific areas. In spite of extensive evidence suggesting possible direct or nonnuclear effects of steroids, in particular on membrane function/components (e.g. Refs. 1 to 6), this controversial area and that of the type II binding sites (7) will not be discussed herein.
Can Inhibiting Dihydropyrimidine Dehydrogenase Limit Hand-Foot Syndrome Caused by Fluoropyrimidines?
Authors: Jane L. Yen-Revollo, Richard M. Goldberg, Howard L. McLeod
Journal: Clinical Cancer Research (2008)

Hand-foot syndrome (HFS) is a cutaneous adverse event that occurs in some patients treated with fluoropyrimidines. Although it is not life threatening, HFS can severely disrupt the daily lives of patients. HFS appears more frequently with 5-fluorouracil (5-FU) delivered by continuous infusion or with the 5-FU oral derivative capecitabine than with bolus 5-FU therapy. HFS is a leading cause of treatment interruption, dosage reduction, or, even, therapy discontinuation for patients on a capecitabine regimen. Interestingly, addition of a dihydropyrimidine dehydrogenase (DPD) inhibitor, such as uracil, 5-chloro-2,4-dihydroxypyridine, or eniluracil, to the fluoropyrimidine treatment regimen significantly diminishes the incidence of HFS. DPD inhibitors were initially combined with fluoropyrimidines to increase the efficacy of the drugs by impairing the DPD-mediated catabolism of 5-FU. However, with the accumulating findings from clinical trials that show the benefits of DPD inhibition on decreasing the risk of HFS, consideration should be given to changing the recommendations for the treatment of cancer patients with fluoropyrimidines to include DPD inhibitor components as standard therapy.
ICAM-1 expression by lung cancer cell lines: effects of upregulation by cytokines on the interaction with LAK cells
Authors: M Melis, M Spatafora, A Melodia, E Pace, M Gjomarkaj, AM Merendino, G Bonsignore
Journal: European Respiratory Journal (1996)

Intercellular adhesion molecule-1 (ICAM-1) expression by tumour cells may be involved in their interaction with defensive cells. In this study the surface ICAM-1 expression and soluble ICAM-1 (sICAM-1) production by five small cell lung cancer (SCLC) and five non-SCLC (NSCLC) cell lines was investigated. In addition, the effects of ICAM-1 upregulation by cytokines on the adhesion of lung cancer cells to allogeneic lymphokine-activated killer (LAK) cells and susceptibility to LAK cytotoxicity was also evaluated. ICAM-1 expression was assessed by flow cytometry. Soluble ICAM-1 release was measured by enzyme-linked immunosorbent assay (ELISA). Interaction with LAK cells was tested by adhesion and cytotoxicity assays. At baseline, SCLC lines did not express ICAM-1, while 4 of the 5 NSCLC lines expressed ICAM-1. ICAM-1 expression was induced by interferon-gamma (IFN-gamma) in 4 of the 5 SCLC lines and upregulated in 1 of the 5 NSCLC lines. ICAM-1 expression was induced by tumour necrosis factor-alpha (TNF-alpha) in 1 of the 5 SCLC lines (National Cancer Institute (NCI) H211), and upregulated in 2 of the 5 NSCLC lines (NCI H460 and NCI H838). Among the latter lines, one (NCI H838) released significant amounts of sICAM-1. Adhesion to LAK cells and susceptibility to LAK cytotoxicity were significantly higher in TNF-alpha-treated NCI H460 and NCI H211 cells, compared to untreated NCI H460 and NCI H211 cells. In contrast, no difference in adhesion to LAK cells and susceptibility to LAK cytotoxicity was detected between baseline and TNF-alpha-treated NCI H838 cells. Intercellular adhesion molecule-1 surface expression and soluble intercellular adhesion molecule-1 release may play an important role in interactions between lymphokine-activated killer cells and lung cancer cells.
The longer-term health outcomes for children born as a result of IVF treatment: Part I–General health outcomes
Authors: Roger Hart, Robert J. Norman
Journal: Human Reproduction Update (2013)

BACKGROUND Several million children have been born from in vitro fertilization (IVF) treatment, but limited data exist regarding their health and development beyond the first year of life. It has been alleged that IVF may lead to long-term adverse consequences, in addition to the documented worse perinatal outcome and increased risk of congenital abnormalities in children born resulting from IVF treatment. METHODS A search strategy restricted to studies relating to the medical condition of children of at least 1 year of age born as a result of IVF treatment was performed to include case series, data linkage and prospective studies published 1 January 2000-1 April 2012. RESULTS Limited long-term follow-up data suggest that there is potentially an increase in the incidence of raised blood pressure, elevated fasting glucose, increase in total body fat composition, advancement of bone age and potentially subclinical thyroid disorder in the IVF offspring. Whether these potential associations are related to the IVF treatment per se, the adverse obstetric outcomes associated with IVF treatment or are related to the genetic origin of the children is yet to be determined. CONCLUSIONS This review provides evidence to suggest that the short-term health outcome for children born from IVF treatment is positive. However, it is expected that the cardiovascular and metabolic risk factors found in childhood and tracking into adulthood could be worse in later life, and may be responsible for chronic cardiometabolic disease. These observations need to be addressed by further studies.
Efflux Kinetics and Intracellular Distribution of Daunorubicin Are Not Affected by Major Vault Protein/Lung Resistance-Related Protein (Vault) Expression
Authors: Arend van Zon, Marieke H. Mossink, Martijn Schoester, Rik J. Scheper, Pieter Sonneveld, Erik A. C. Wiemer
Journal: Cancer Research (2004)

Abstract Vaults may contribute to multidrug resistance by transporting drugs away from their subcellular targets. To study the involvement of vaults in the extrusion of anthracyclines from the nucleus, we investigated the handling of daunorubicin by drug-sensitive and drug-resistant non-small lung cancer cells, including a green fluorescent protein (GFP)-tagged major vault protein (MVP)-overexpressing transfectant (SW1573/MVP-GFP). Cells were exposed to 1 μm daunorubicin for 60 min, after which the cells were allowed to efflux the accumulated drug. No significant differences in daunorubicin efflux kinetics were observed between the sensitive SW1573 and SW1573/MVP-GFP transfectant, whereas the drug-resistant SW1573/2R120 cells clearly demonstrated an increased efflux rate. It was noted that the redistribution of daunorubicin from the nucleus into distinct vesicular structures in the cytoplasm was not accompanied by changes in the intracellular localization of vaults. Similar experiments were performed using mouse embryonic fibroblasts derived from wild-type and MVP knockout mice, which were previously shown to be devoid of vault particles. Both cell lines showed comparable drug efflux rates, and the intracellular distribution of daunorubicin in time was identical. Reintroduction of a human MVP tagged with GFP in the MVP−/− cells results in the formation of vault particles but did not give rise an altered daunorubicin handling compared with MVP−/− cells expressing GFP. Our results indicate that vaults are not directly involved in the sequestration of anthracyclines in vesicles nor in their efflux from the nucleus.
The International Neuroblastoma Risk Group (INRG) Staging System: An INRG Task Force Report
Authors: Tom Monclair, Garrett M. Brodeur, Peter F. Ambros, Hervé J. Brisse, Giovanni Cecchetto, Keith Holmes, Michio Kaneko, Wendy B. London, Katherine K. Matthay, Jed G. Nuchtern, Dietrich von Schweinitz, Thorsten Simon, Susan L. Cohn, Andrew D.J. Pearson
Journal: Journal of Clinical Oncology (2008)

The International Neuroblastoma Risk Group (INRG) classification system was developed to establish a consensus approach for pretreatment risk stratification. Because the International Neuroblastoma Staging System (INSS) is a postsurgical staging system, a new clinical staging system was required for the INRG pretreatment risk classification system.
Noncancer Pain Conditions and Risk of Suicide
Authors: Mark A. Ilgen, Felicia Kleinberg, Rosalinda V. Ignacio, Amy S. B. Bohnert, Marcia Valenstein, John F. McCarthy, Frederic C. Blow, Ira R. Katz
Journal: JAMA Psychiatry (2013)

There are limited data on the extent to which suicide mortality is associated with specific pain conditions.To examine the associations between clinical diagnoses of noncancer pain conditions and suicide among individuals receiving services in the Department of Veterans Affairs Healthcare System.Retrospective data analysis.Data were extracted from National Death Index and treatment records from the Department of Veterans Healthcare System.Individuals receiving services in fiscal year 2005 who remained alive at the start of fiscal year 2006 (N = 4 863 086).Analyses examined the association between baseline clinical diagnoses of pain-related conditions (arthritis, back pain, migraine, neuropathy, headache or tension headache, fibromyalgia, and psychogenic pain) and subsequent suicide death (assessed in fiscal years 2006-2008).Controlling for demographic and contextual factors (age, sex, and Charlson score), elevated suicide risks were observed for each pain condition except arthritis and neuropathy (hazard ratios ranging from 1.33 [99% CI, 1.22-1.45] for back pain to 2.61 [1.82-3.74] for psychogenic pain). When analyses controlled for concomitant psychiatric conditions, the associations between pain conditions and suicide death were reduced; however, significant associations remained for back pain (hazard ratio, 1.13 [99% CI, 1.03-1.24]), migraine (1.34 [1.02-1.77]), and psychogenic pain (1.58 [1.11-2.26]).There is a need for increased awareness of suicide risk in individuals with certain noncancer pain diagnoses, in particular back pain, migraine, and psychogenic pain.
Long‐term high‐level expression of human β‐globin occurs following transplantation of transgenic marrow into irradiated mice
Authors: Andrew Himelstein, Maureen Ward, Silvio Podda, Eduardo de la Flor Weiss, Frank Costantini, Arthur Bank
Journal: American Journal of Hematology (1993)

Abstract When the human β‐globin gene is transferred into the bone marrow cells of live mice, its expression is very low. To investigate the reason for this, we transferred the bone marrow of transgenic mice containing and expressing the human β‐globin into irradiated recipients. We demonstrate that long‐term high level expression of the human β‐globin gene can be maintained in the marrow and blood of irradiated recipients following transplantation. Although expression decreased over time in most animals because of host marrow reconstitution, the ratio of human β‐globin transgene expression to endogenous mouse β‐globin gene expression in donor‐derived erythroid cells remained constant over time. We conclude that there is no inherent limitation to efficient expression of an exogenous human β‐globin gene in mouse bone marrow cells following marrow transplantation. © 1993 Wiley‐Liss, Inc.
Selective digestive or oropharyngeal decontamination and topical oropharyngeal chlorhexidine for prevention of death in general intensive care: systematic review and network meta-analysis
Authors: R. Price, G. MacLennan, J. Glen
Journal: BMJ (2014)

<b>Objectives</b> To determine the effect on mortality of selective digestive decontamination, selective oropharyngeal decontamination, and topical oropharyngeal chlorhexidine in adult patients in general intensive care units and to compare these interventions with each other in a network meta-analysis. <b>Design</b> Systematic review, conventional meta-analysis, and network meta-analysis. Medline, Embase, and CENTRAL were searched to December 2012. Previous meta-analyses, conference abstracts, and key journals were also searched. We used pairwise meta-analyses to estimate direct evidence from intervention-control trials and a network meta-analysis within a Bayesian framework to combine direct and indirect evidence. <b>Inclusion criteria</b> Prospective randomised controlled trials that recruited adult patients in general intensive care units and studied selective digestive decontamination, selective oropharyngeal decontamination, or oropharyngeal chlorhexidine compared with standard care or placebo. <b>Results</b> Selective digestive decontamination had a favourable effect on mortality, with a direct evidence odds ratio of 0.73 (95% confidence interval 0.64 to 0.84). The direct evidence odds ratio for selective oropharyngeal decontamination was 0.85 (0.74 to 0.97). Chlorhexidine was associated with increased mortality (odds ratio 1.25, 1.05 to 1.50). When each intervention was compared with the other, both selective digestive decontamination and selective oropharyngeal decontamination were superior to chlorhexidine. The difference between selective digestive decontamination and selective oropharyngeal decontamination was uncertain. <b>Conclusion</b> Selective digestive decontamination has a favourable effect on mortality in adult patients in general intensive care units. In these patients, the effect of selective oropharyngeal decontamination is less certain. Both selective digestive decontamination and selective oropharyngeal decontamination are superior to chlorhexidine, and there is a possibility that chlorhexidine is associated with increased mortality.
Mitochondrial-Mediated Disregulation of Ca2+ Is a Critical Determinant of Velcade (PS-341/Bortezomib) Cytotoxicity in Myeloma Cell Lines
Authors: Terry H. Landowski, Christina J. Megli, Kevin D. Nullmeyer, Ronald M. Lynch, Robert T. Dorr
Journal: Cancer Research (2005)

Abstract The proteasome inhibitor bortezomib (also known as PS-341/Velcade) is a dipeptidyl boronic acid that has recently been approved for use in patients with multiple myeloma. Bortezomib inhibits the activity of the 26S proteasome and induces cell death in a variety of tumor cells; however, the mechanism of cytotoxicity is not well understood. In this report, oligonucleotide microarray analysis of the 8226 multiple myeloma cell line showed a predominant induction of gene products associated with the endoplasmic reticulum secretory pathway following short-term, high-dose exposure to bortezomib. Examination of mediators of endoplasmic reticulum stress–induced cell death showed specific activation of caspase 12, as well as of caspases 8, 9, 7, and 3, and cleavage of bid. Treatment of myeloma cells with bortezomib also showed disregulation of intracellular Ca2+ as a mechanism of caspase activation. Cotreatment with a panel of Ca2+-modulating agents identified the mitochondrial uniporter as a critical regulatory factor in bortezomib cytotoxicity. The uniporter inhibitors ruthenium red and Ru360 prevented caspase activation and bid cleavage, and almost entirely inhibited bortezomib-induced cell death, but had no effect on any other chemotherapeutic drug examined. Additional Ca2+-modulating agents, including 2-amino-ethoxydiphenylborate, 1,2-bis (o-aminophenoxy) ethane-tretraacetic acid (acetoxymethyl) ester, and dantrolene, did not alter bortezomib cytotoxicity. Analysis of intracellular Ca2+ showed that the ruthenium-containing compounds inhibited Ca2+ store loading and abrogated the desensitized capacitative calcium influx associated with bortezomib treatment. These data support the hypothesis that intracellular Ca2+ disregulation is a critical determinant of bortezomib cytotoxicity.
Minimal and small size invasive breast cancer with no axillary lymph node involvement: the need for tailored adjuvant therapies
Authors: M. Colleoni, N. Rotmensz, G. Peruzzotti, P. Maisonneuve, G. Viale, G. Renne, C. Casadio, P. Veronesi, M. Intra, R. Torrisi, A. Goldhirsch
Journal: Annals of Oncology (2004)
Wilson's disease: clinical presentation and use of prognostic index.
Authors: H Nazer, R J Ede, A P Mowat, R Williams
Journal: Gut (1986)

As the results of treatment in Wilson's disease are so dependent on the stage at which penicillamine therapy is started, the antecedent history in 34 patients with Wilson's disease was analysed with particular respect to the earliest manifestations of the disease. Lethargy and anorexia (70%) jaundice (56%) and abdominal pain (48%) were the commonest symptoms and less common were intellectual deterioration (22%) and recurrent epistaxes (22%). The duration of symptoms before diagnosis ranged from five days to three years (mean 10.5 months) and in only five of the patients was the diagnosis established before referral. Analysis of the physical signs at presentation showed hepatomegaly (81%) and splenomegaly (70%) to be common and the only signs which were significantly more common in the 13 fatal cases were jaundice and ascites. In three of these and in one other patient who survived the clinical course was exceptionally severe and was indistinguishable from fulminant hepatic failure. Based on the severity of abnormality of serum aspartate aminotransferase, bilirubin, and prothrombin time on admission a prognostic index was derived which enabled complete separation of fatal and nonfatal cases and when subsequently used in a further nine index cases correctly predicted the outcome. Two further cases found to have indices in the fatal category did well after liver transplantation, which needs to be considered as soon as the diagnosis is established in cases with such severe liver damage.
Effect of cigarette smoking on the specific antibody response in pigeon fanciers.
Authors: K Anderson, S M Morrison, S Bourke, G Boyd
Journal: Thorax (1988)

Titres of circulating IgG antibodies to pigeon gammaglobulin and end expired carbon monoxide concentrations were measured in 86 pigeon fanciers attending the "Show of the Year." Antibody levels were significantly higher in non-smokers and in those with end expired carbon monoxide concentrations below 10 parts per million.
Critical Role of the Programmed Death-1 (PD-1) Pathway in Regulation of Experimental Autoimmune Encephalomyelitis
Authors: Alan D. Salama, Tanuja Chitnis, Jaime Imitola, Mohammed Javeed I. Ansari, Hisaya Akiba, Fumihiko Tushima, Miyuki Azuma, Hideo Yagita, Mohamed H. Sayegh, Samia J. Khoury
Journal: The Journal of Experimental Medicine (2003)

Experimental autoimmune encephalomyelitis (EAE) is mediated by autoantigen-specific T cells dependent on critical costimulatory signals for their full activation and regulation. We report that the programmed death-1 (PD-1) costimulatory pathway plays a critical role in regulating peripheral tolerance in murine EAE and appears to be a major contributor to the resistance of disease induction in CD28-deficient mice. After immunization with myelin oligodendrocyte glycoprotein (MOG) there was a progressive increase in expression of PD-1 and its ligand PD-L1 but not PD-L2 within the central nervous system (CNS) of mice with EAE, peaking after 3 wk. In both wild-type (WT) and CD28-deficient mice, PD-1 blockade resulted in accelerated and more severe disease with increased CNS lymphocyte infiltration. Worsening of disease after PD-1 blockade was associated with a heightened autoimmune response to MOG, manifested by increased frequency of interferon γ–producing T cells, increased delayed-type hypersensitivity responses, and higher serum levels of anti-MOG antibody. In vivo blockade of PD-1 resulted in increased antigen-specific T cell expansion, activation, and cytokine production. Interestingly, PD-L2 but not PD-L1 blockade in WT animals also resulted in disease augmentation. Our data are the first demonstration that the PD-1 pathway plays a critical role in regulating EAE.
Genetic Dissection of Increased Urinary Albumin Excretion in the Munich Wistar Fro[Combining Diaeresis]mter Rat
Authors: Angela Schulz, Andre Litfin, Peter Kossmehl, Reinhold Kreutz
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. An elevated urinary albumin excretion (UAE) is a risk factor for the development of chronic nephropathy and for cardiovascular mortality. The Munich Wistar Frömter (MWF) rat represents a genetic model that develops spontaneously mild hypertension and a 142-fold increased UAE compared with normal Lewis rats at 14 wk of age. The genetic basis of UAE in male MWF was analyzed in relation to BP by using a quantitative trait (QTL) mapping strategy. F1-hybrids generated from a cross between MWF and Lewis rats showed normal UAE rates similar to Lewis. A backcross strategy including 213 animals was therefore used. To account for age-of-onset effects, UAE was determined in young backcross animals at 8 wk and in adult animals at 14 and 24 wk of age, respectively. Total genome scan analysis identified three QTL with significant linkage to UAE and one QTL with suggestive linkage to UAE. These loci showed no linkage to BP, and BP explained only 2% of the total variance of UAE. Homozygosity for the MWF allele accounted for a similar mean increase in UAE in adult backcross animals at each UAE QTL. When single gene effects were analyzed, only one UAE QTL led to a significant increase in UAE. Early onset of albuminuria and a considerable increase of UAE in adult animals required homozygosity at three loci at least. This study demonstrates the polygenetic recessive determination of increased UAE by a set of genes that are unlinked to BP.
Colorectal-Cancer Incidence and Mortality with Screening Flexible Sigmoidoscopy
Authors: Robert E. Schoen, Paul F. Pinsky, Joel L. Weissfeld, Lance A. Yokochi, Timothy Church, Adeyinka O. Laiyemo, Robert Bresalier, Gerald L. Andriole, Saundra S. Buys, E. David Crawford, Mona N. Fouad, Claudine Isaacs, Christine C. Johnson, Douglas J. Reding, Barbara O'Brien, Danielle M. Carrick, Patrick Wright, Thomas L. Riley, Mark P. Purdue, Grant Izmirlian, Barnett S. Kramer, Anthony B. Miller, John K. Gohagan, Philip C. Prorok, Christine D. Berg
Journal: New England Journal of Medicine (2012)

The benefits of endoscopic testing for colorectal-cancer screening are uncertain. We evaluated the effect of screening with flexible sigmoidoscopy on colorectal-cancer incidence and mortality.