tbuckley/cabot-search huggingface dataset:
Breast cancer risk from diet, tobacco, and alcohol
Authors: M. H. Cohen
Journal: JAMA (1993)

To the Editor.  —The recently reported Nurses' Health Study found no evidence for a positive association between dietary fat intake and breast cancer incidence. 1 This study may not refute the hypothesis, however. A possible confounding factor is cigarette smoking. Approximately 22% to 25% of nurses smoke. 2 Smoking may decrease the risk for breast cancer development, an observation of some, but not all, studies. 3 Smoking has definite antiestrogenic effects decreasing the age of menopause and reducing the risk for developing endometrial cancer. 4 Another antiestrogen drug, tamoxifen, reduces the risk for developing contralateral breast cancer in patients receiving surgical adjuvant tamoxifen therapy 5 and is currently undergoing trial as a breast cancer prevention drug. These considerations suggest that the Nurses' Health Study data concerning the relationship of dietary fat to breast cancer risk be reanalyzed to include participants' smoking status. Smoking status information is available. 4
Frontal fibrosing alopecia: a clinical review of 20 black patients from South Africa
Authors: N.C. Dlova, H.F. Jordaan, A. Skenjane, N. Khoza, A. Tosti
Journal: British Journal of Dermatology (2013)

Journal Article Frontal fibrosing alopecia: a clinical review of 20 black patients from South Africa Get access N.C. Dlova, N.C. Dlova Dermatology Department Nelson R. Mandela School of Medicine University of KwaZulu‐Natal 719 Umbilo Road Durban South Africa Search for other works by this author on: Oxford Academic Google Scholar H.F. Jordaan, H.F. Jordaan Division of Dermatology Department of Medicine Faculty of Medicine and Health Sciences University of Stellenbosch PO Box 19063 Tygerberg 7505 South Africa Search for other works by this author on: Oxford Academic Google Scholar A. Skenjane, A. Skenjane Dermatology Department Nelson R. Mandela School of Medicine University of KwaZulu‐Natal 719 Umbilo Road Durban South Africa Search for other works by this author on: Oxford Academic Google Scholar N. Khoza, N. Khoza Dermatology Department Nelson R. Mandela School of Medicine University of KwaZulu‐Natal 719 Umbilo Road Durban South Africa Search for other works by this author on: Oxford Academic Google Scholar A. Tosti A. Tosti Department of Dermatology and Cutaneous Surgery University of Miami Miller School of Medicine 33136 Miami FL U.S.A Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 169, Issue 4, 1 October 2013, Pages 939–941, https://doi.org/10.1111/bjd.12424 Published: 01 October 2013
The Self-sustained sequence replication amplification system–move over, PCR
Authors: Kenneth S. Lown
Journal: Hepatology (1993)

Mutations at amino acid positions 67, 70, 215, and 219 in the human immunodeficiency virus type 1 (HIV-1) pol gene correlate with the emergence of resistance to zidovudine (AZT). These four positions were monitored in viral RNA extracted from infected peripheral blood mononuclear cells (PBMC) and viral stocks obtained after coculture with uninfected lymphocytes. Genotype determinations were made using the selfsustained sequence replication (3SR) and differential bead-based sandwich hybridization (BBSH) assay. The hybridization results obtained by 3SR and BBSH analyses were verified by dideoxynucleotide sequencing of the 3SR products. Correlation of 3SR and BBSH with the polymerase chain reaction and Southern hybridization analyses of the PBMC and corresponding viral isolates indicated that PBMC and corresponding HIV-1 isolates may differ in their genotypes at the monitored amino acid positions, variations from the wild-type nucleotide sequence may occur proximal to the codons being monitored, and viral isolates possessing the same genotypes at the four monitored amino acid positions showed a threefold variation in their ID 50 measurements.
Mutation in mitochondrial tRNA(Leu(UUR)) gene associated with progressive kidney disease.
Authors: J J Jansen, J A Maassen, F J van der Woude, H A Lemmink, J M van den Ouweland, L M t' Hart, H J Smeets, J A Bruijn, H H Lemkes
Journal: Journal of the American Society of Nephrology (1997)

Several studies show an association of a guanine for adenine substitution (A-->G) at position 3243 in mitochondrial DNA (mtDNA) with a recently recognized diabetic subtype designated maternally inherited diabetes and deafness (MIDD). This mutation shows heterogeneity in its phenotypic expression as is apparent from its association with several other syndromes. Screening for the 3243A-->G mutation in mtDNA was performed in those diabetic patients attending the Leiden University Hospital diabetics clinic who had a history of maternally inherited diabetes, sensorineural hearing loss, or both. Four individuals from three unrelated families were identified who suffered from progressive nondiabetic kidney disease in association with diabetes mellitus and hearing loss. The mode of inheritance suggested maternal transmission. The combination of renal failure and hearing loss had been misdiagnosed as Alport syndrome in three of the four individuals. Therefore, in addition to these three families, another 63 unrelated patients with possible Alport syndrome were selected at random. DNA from peripheral blood and other tissues from members of the three families and from the 63 additional Alport syndrome patients was examined for the presence of the 3243A-->G mutation in mtDNA. The mutation was detected in heteroplasmic form in the four patients and their maternal relatives. Also, one of the 63 suspected Alport syndrome patients showed heteroplasmy for the 3243 mutation. These data show the existence of a kidney disease that is characterized by the presence of the A-->G mutation at position 3243 in the mtDNA.
HLA-DR3 and DR7 in coeliac disease: immunogenetic and clinical aspects.
Authors: M Demarchi, A Carbonara, N Ansaldi, B Santini, C Barbera, I Borelli, P Rossino, S Rendine
Journal: Gut (1983)

The association of HLA-A,B,C, DR polymorphisms and of Bf and GLO with coeliac disease was analysed in 100 Italian children. Primary involvement of HLA-DR3 and DR7 is apparent, while specificities of nearby loci are probably associated secondarily, because of linkage disequilibrium. Direct assessment of D/DR genotype through family studies and mixed lymphocyte cultures led to the recognition of two high risk genotypes DR3/3 and DR3/7, and of two lower risk genotypes DR3/X and DR7/X. The different weight of the HLA-dependent genetic factors is to some extent correlated with the clinical and immunological parameters, suggesting that the low-risk genotypes induce a milder expression of coeliac disease. Furthermore, other genetic factors, such as sex, appear to contribute to the penetrance of the disease, especially in the case of DR3/X and DR7/X.
A user's guide to performance of the best shoulder physical examination tests
Authors: Cortney A Myer, Eric J Hegedus, Daniel Thomas Tarara, Daniel M Myer
Journal: British Journal of Sports Medicine (2013)

This article provides clinicians with a user's guide on the performance of the shoulder physical examination tests most supported by current evidence from a recent systematic review published in the British Journal of Sports Medicine.A description of clinical shoulder tests is provided with explanations on exact testing procedures and complimentary photographs.
A Functional Role for Hemostasis in Early Cancer Development
Authors: Carla Boccaccio, Paolo M. Comoglio
Journal: Cancer Research (2005)

Abstract Blood coagulation disorders have been known to be associated with cancer for many years. However, the mechanisms responsible for their relationship have not been understood. Recent work indicates that activation of the MET oncogene, which drives invasion and metastasis in cancer, can promote a cancer-associated thrombohemorrhagic syndrome that is mediated by transcriptional up-regulation of the procoagulation factors plasminogen activator inhibitor type-1 and cyclooxygenase-2. These findings reveal a long-sought mechanistic link between coagulation and cancer, highlighting a clinically important perspective on malignant invasion and metastasis.
Cliff-edged fitness functions and the persistence of schizophrenia
Authors: Randolph M. Nesse
Journal: Behavioral and Brain Sciences (2004)

Strong recent selection for social cognition may well explain the persistence of genes that predispose to schizophrenia. The specific mechanism responsible may be a skewed fitness function in which selection pushes the mean for advantageous mental traits perilously close to a “fitness cliff” where the system fails catastrophically in some individuals.
Stalling the Engine of Resistance: Targeting Cancer Metabolism to Overcome Therapeutic Resistance
Authors: Ethan B. Butler, Yuhua Zhao, Cristina Muñoz-Pinedo, Jianrong Lu, Ming Tan
Journal: Cancer Research (2013)

Abstract Cancer cells are markedly different from normal cells with regards to how their metabolic pathways are used to fuel cellular growth and survival. Two basic metabolites that exemplify these differences through increased uptake and altered metabolic usage are glucose and glutamine. These molecules can be catabolized to manufacture many of the building blocks required for active cell growth and proliferation. The alterations in the metabolic pathways necessary to sustain this growth have been linked to therapeutic resistance, a trait that is correlated with poor patient outcomes. By targeting the metabolic pathways that import, catabolize, and synthesize essential cellular components, drug-resistant cancer cells can often be resensitized to anticancer treatments. The specificity and efficacy of agents directed at the unique aspects of cancer metabolism are expected to be high; and may, when in used in combination with more traditional therapeutics, present a pathway to surmount resistance within tumors that no longer respond to current forms of treatment. Cancer Res; 73(9); 2709–17. ©2013 AACR.
Cathepsin S inhibition suppresses systemic lupus erythematosus and lupus nephritis because cathepsin S is essential for MHC class II-mediated CD4 T cell and B cell priming
Authors: Khader Valli Rupanagudi, Onkar P Kulkarni, Julia Lichtnekert, Murthy Narayana Darisipudi, Shrikant R Mulay, Brigitte Schott, Sabine Gruner, Wolfgang Haap, Guido Hartmann, Hans-Joachim Anders
Journal: Annals of the Rheumatic Diseases (2013)

Major histocompatibility complex (MHC) class II-mediated priming of T and B lymphocytes is a central element of autoimmunity in systemic lupus erythematosus (SLE) and lupus nephritis. The cysteine protease cathepsin S degrades the invariant peptide chain during MHC II assembly with antigenic peptide in antigen-presenting cells; therefore, we hypothesised that cathepsin S inhibition would be therapeutic in SLE.We developed a highly specific small molecule, orally available, cathepsin S antagonist, RO5461111, with suitable pharmacodynamic and pharmacokinetic properties that efficiently suppressed antigen-specific T cell and B cell priming in vitro and in vivo.When given to MRL-Fas(lpr) mice with SLE and lupus nephritis, RO5461111 significantly reduced the activation of spleen dendritic cells and the subsequent expansion and activation of CD4 T cells and CD4/CD8 double-negative T cells. Cathepsin S inhibition impaired the spatial organisation of germinal centres, suppressed follicular B cell maturation to plasma cells and Ig class switch. This reversed hypergammaglobulinemia and significantly suppressed the plasma levels of numerous IgG (but not IgM) autoantibodies below baseline, including anti-dsDNA. This effect was associated with less glomerular IgG deposits, which protected kidneys from lupus nephritis.Together, cathepsin S promotes SLE by driving MHC class II-mediated T and B cell priming, germinal centre formation and B cell maturation towards plasma cells. These afferent immune pathways can be specifically reversed with the cathepsin S antagonist RO5461111, which prevents lupus nephritis progression even when given after disease onset. This novel therapeutic strategy could correct a common pathomechanism of SLE and other immune complex-related autoimmune diseases.
Adverse Outcomes Associated With Personality Disorder Not Otherwise Specified in a Community Sample
Authors: Jeffrey G. Johnson, Michael B. First, Patricia Cohen, Andrew E. Skodol, Stephanie Kasen, Judith S. Brook
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: The authors investigated 1) whether adolescents and adults in the community diagnosed with personality disorder not otherwise specified are at elevated risk for adverse outcomes, and 2) whether this elevation in risk is comparable with that associated with the DSM-IV cluster A, B, and C personality disorders. METHOD: A community-based sample of 693 mothers and their offspring were interviewed during the offspring's childhood, adolescence, and early adulthood. Offspring psychopathology, aggressive behavior, educational and interpersonal difficulties, and suicidal behavior were assessed. RESULTS: Individuals who met DSM-IV criteria for personality disorder not otherwise specified were significantly more likely than those without personality disorders to have concurrent axis I disorders and behavioral, educational, or interpersonal problems during adolescence and early adulthood. In addition, adolescents with personality disorder not otherwise specified were at significantly elevated risk for subsequent educational failure, numerous interpersonal difficulties, psychiatric disorders, and serious acts of physical aggression by early adulthood. Adolescents with personality disorder not otherwise specified were as likely to have these adverse outcomes as those with cluster A, B, or C personality disorders or those with axis I disorders. CONCLUSIONS: Adolescents and young adults in the general population diagnosed with personality disorder not otherwise specified may be as likely as those with DSM-IV cluster A, B, or C personality disorders to have axis I psychopathology and to have behavioral, educational, or interpersonal problems that are not attributable to co-occurring psychiatric disorders. Individuals with personality disorder not otherwise specified and individuals with DSM-IV cluster A, B, or C personality disorders are likely to be at substantially elevated risk for a wide range of adverse outcomes.
A Single Nucleotide Polymorphism in the <i>MDM2</i> Gene Disrupts the Oscillation of p53 and MDM2 Levels in Cells
Authors: Wenwei Hu, Zhaohui Feng, Lan Ma, John Wagner, J. Jeremy Rice, Gustavo Stolovitzky, Arnold J. Levine
Journal: Cancer Research (2007)

Oscillations of both p53 and MDM2 proteins have been observed in cells after exposure to stress. A mathematical model describing these oscillations predicted that oscillations occur only at selected levels of p53 and MDM2 proteins. This model prediction suggests that oscillations will disappear in cells containing high levels of MDM2 as observed with a single nucleotide polymorphism in the MDM2 gene (SNP309). The effect of SNP309 upon the p53-MDM2 oscillation was examined in various human cell lines and the oscillations were observed in the cells with at least one wild-type allele for SNP309 (T/T or T/G) but not in cells homozygous for SNP309 (G/G). Furthermore, estrogen preferentially stimulated the transcription of MDM2 from SNP309 G allele and increased the levels of MDM2 protein in estrogen-responsive cells homozygous for SNP309 (G/G). These results suggest the possibility that SNP309 G allele may contribute to gender-specific tumorigenesis through further elevating the MDM2 levels and disrupting the p53-MDM2 oscillation. Furthermore, using the H1299-HW24 cells expressing wild-type p53 under a tetracycline-regulated promoter, the p53-MDM2 oscillation was observed only when p53 levels were in a specific range, and DNA damage was found to be necessary for triggering the p53-MDM2 oscillation. This study shows that higher levels of MDM2 in cells homozygous for SNP309 (G/G) do not permit coordinated p53-MDM2 oscillation after stress, which might contribute to decreased efficiency of the p53 pathway and correlates with a clinical phenotype (i.e., the development of cancers at earlier age of onset in female).
Regulatory T cells and COPD
Authors: Rachel Dancer, David M Sansom
Journal: Thorax (2013)

While the innate immune system has long been implicated in the pathogenesis of COPD, a role for the acquired immune system is less well studied. The increasing recognition that COPD shares features with autoimmune disease has led to interest in a potential role for regulatory T cells, which are intimately involved in the control of autoimmunity. The suggestion that regulatory T cell numbers are increased in patients with COPD may indicate their dysfunction or resistance to suppression by target cells. Investigation of regulatory T cells may therefore be of importance in understanding the inflammation and tissue damage that occurs in patients with COPD who cease smoking.
2-[11C]Thymidine Positron Emission Tomography as an Indicator of Thymidylate Synthase Inhibition in Patients Treated With AG337
Authors: P. Wells, E. Aboagye, R. N. Gunn, S. Osman, A. V. Boddy, G. A. Taylor, I. Rafi, A. N. Hughes, A. H. Calvert, P. M. Price, D. R. Newell
Journal: JNCI Journal of the National Cancer Institute (2003)

Some anticancer drugs inhibit thymidylate synthase (TS), a key enzyme for thymidine nucleotide biosynthesis. Cells can compensate for depleted thymidine levels by taking up extracellular thymidine via a salvage pathway. We investigated the use of 2-[11C]thymidine positron emission tomography (PET) to measure thymidine salvage kinetics in vivo in humans.Five patients with advanced gastrointestinal cancer were PET scanned both before and 1 hour after oral administration of the TS inhibitor AG337 (THYMITAQ [nolatrexed]); seven control patients were scanned twice but not treated with AG337. Thymidine salvage kinetics were measured in vivo using 2-[11C]thymidine PET and spectral analysis to obtain the standardized uptake values (SUV), the area under the time-activity curve (AUC), and the fractional retention of thymidine (FRT). Changes in PET parameters between scans in the AG337-treated and control groups were compared using the Mann-Whitney U test. The relationship between AG337 exposure and AG337-induced changes in tumor FRT and in plasma deoxyuridine levels (a conventional pharmacodynamic systemic measure of TS inhibition) was examined using Spearman's regression analysis. Statistical tests were two-sided.The between-scan change in FRT in patients treated with AG337 (38% increase, 95% confidence interval [CI] = 8% to 68%) was higher than that in control patients (3% increase, 95% CI = -11% to 17%) (P =.028). The level of AG337-induced increase in both 2-[11C]thymidine FRT and plasma deoxyuridine levels was statistically significantly correlated with AG337 exposure (r = 1.00, P =.01 for both).AG337 administration was associated with increased tumor tracer retention that was consistent with tumor cell uptake of exogenous 2-[11C]thymidine as a result of TS inhibition. 2-[11C]Thymidine PET can be used to measure thymidine salvage kinetics directly in the tissue of interest.
Neonatal, postneonatal, childhood, and under-5 mortality for 187 countries, 1970–2010: a systematic analysis of progress towards Millennium Development Goal 4
Authors: Julie Knoll Rajaratnam, Jake R Marcus, Abraham D Flaxman, Haidong Wang, Alison Levin-Rector, Laura Dwyer, Megan Costa, Alan D Lopez, Christopher JL Murray
Journal: The Lancet (2010)
Abstract 2117: The Wnt inhibitory factor 1 (WIF-1) has tumor suppressing functions in glioblastoma potentially by inducing cellular senescence
Authors: Irene Vassallo, Wanyu Lambiv, Mauro Delorenzi, Tal Shay, Annie-Claire Diserens, Anjan Misra, Burt Feuerstein, Anastasia Murat, Eugenia Migliavacca, Marie-France Hamou, Eytan Domany, Roger Stupp, Monika E. Hegi
Journal: Cancer Research (2011)

Abstract Glioblastoma multiforme is the most aggressive form of human glioma and despite recent progress in therapy the prognosis remains dismal with a median survival of 15 months. Expression based prediction of gene alterations identified Wnt inhibitory factor I (WIF1) as a new candidate tumor suppressor gene involved in glioblastoma. WIF1 encodes a secreted Wnt antagonist and it was strongly down-regulated in most glioblastoma as compared to normal brain, implying deregulation of Wnt signaling. Silencing of the WIF1 gene was found to be mediated by deletion and WIF1 promoter hypermethylation. Ectopic expression of WIF1 in glioblastoma cell lines revealed a dose dependent decrease of Wnt pathway activity. To further dissect the biological effects of WIF1 re-expression, we established WIF1 overexpressing glioblastoma cell lines. We observed that WIF1 re-expression inhibited cell proliferation in vitro and strongly reduced anchorage independent growth. The ability of forming colonies in soft agar was reduced to less than 11% of the control. Moreover, the expression of WIF1 was able to completely abolish tumorigenicity in a respective xenograft model in nude mice. Interestingly, WIF1 overexpression in glioblastoma cells induced a senescence-like phenotype characterized by the appearance of enlarged flattened and multinucleated cells positive for the presence of β-galactosidase, a late marker of senescence. These results provide evidence that WIF1 has tumor suppressing properties in glioblastoma, hence, the implication of a deregulated Wnt pathway may render glioblastoma sensitive to Wnt signaling inhibitors, potentially by diverting the tumor cells into a senescence-like state. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2117. doi:10.1158/1538-7445.AM2011-2117
Contribution of Liraglutide in the Fixed-Ratio Combination of Insulin Degludec and Liraglutide (IDegLira)
Authors: John B. Buse, Tina Vilsbøll, Jerry Thurman, Thomas C. Blevins, Irene H. Langbakke, Susanne G. Bøttcher, Helena W. Rodbard
Journal: Diabetes Care (2014)

OBJECTIVE Insulin degludec/liraglutide (IDegLira) is a novel combination of insulin degludec (IDeg) and liraglutide. This trial investigated the contribution of the liraglutide component of IDegLira versus IDeg alone on efficacy and safety in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS In a 26-week, double-blind trial, patients with type 2 diabetes (A1C 7.5–10.0% [58–86 mmol/mol]) on basal insulin (20–40 units) and metformin with or without sulfonylurea/glinides were randomized (1:1) to once-daily IDegLira + metformin or IDeg + metformin with titration aiming for fasting plasma glucose between 4 and 5 mmol/L. Maximum allowed doses were 50 dose steps (equal to 50 units IDeg plus 1.8 mg liraglutide) and 50 units for IDeg. The primary end point was change in A1C from baseline. RESULTS A total of 413 patients were randomized (mean A1C 8.8% [73 mmol/mol]; BMI 33.7 kg/m2). IDeg dose, alone or as part of IDegLira, was equivalent (45 units). A1C decreased by 1.9% (21 mmol/mol) with IDegLira and by 0.9% (10 mmol/mol) with IDeg (estimated treatment difference −1.1% [95% CI −1.3, −0.8], −12 mmol/mol [95% CI −14, −9; P &amp;lt; 0.0001). Mean weight reduction with IDegLira was 2.7 kg vs. no weight change with IDeg, P &amp;lt; 0.0001. Hypoglycemia incidence was comparable (24% for IDegLira vs. 25% for IDeg). Overall adverse events were similar, and incidence of nausea was low in both groups (IDegLira 6.5% vs. IDeg 3.5%). CONCLUSIONS IDegLira achieved glycemic control superior to that of IDeg at equivalent insulin doses without higher risk of hypoglycemia and with the benefit of weight loss. These findings establish the efficacy and safety of IDegLira and the distinct contribution of the liraglutide component.