tbuckley/cabot-search huggingface dataset:
2-Deoxyglucose as an Energy Restriction Mimetic Agent: Effects on Mammary Carcinogenesis and on Mammary Tumor Cell Growth <i>In vitro</i>
Authors: Zongjian Zhu, Weiqin Jiang, John N. McGinley, Henry J. Thompson
Journal: Cancer Research (2005)

Abstract Dietary energy restriction (DER) is a potent inhibitor of carcinogenesis, but chronic DER in human populations is difficult to sustain. Consequently, interest exists in identifying energy restriction mimetic agents (ERMAs), agents that provide the health benefits of DER without reducing caloric intake. The selection of a candidate ERMAs for this study was based on evidence that DER inhibits carcinogenesis by limiting glucose availability. The study objective was to determine if 2-deoxyglucose (2-DG), a glucose analogue that blocks its metabolism, would inhibit mammary carcinogenesis. Pilot studies were done to establish a dietary concentration of 2-DG that would not affect growth. For the carcinogenesis study, ninety 21-day-old female Sprague-Dawley rats were injected i.p. with 50 mg of 1-methyl-1-nitrosourea per kilogram of body weight. Following injection, animals were ad libitum fed AIN-93G diet containing 0.00%, 0.02%, or 0.03% (w/w) 2-DG for 5 weeks. 2-DG decreased the incidence and multiplicity of mammary carcinomas and prolonged cancer latency (P &amp;lt; 0.05). The 0.02% dose of 2-DG had no effect on circulating levels of glucose, insulin, insulin-like growth factor-I, IGF binding protein-3, leptin, or body weight gain. Using MCF-7 human breast cancer cells to investigate the signaling pathways perturbed by disruption of glucose metabolism, 2-DG reduced cell growth and intracellular ATP in a dose- and time-dependent manner (P &amp;lt; 0.01). Treatment with 2-DG increased levels of phosphorylated AMP-activated protein kinase and Sirt-1 and reduced phosphorylated Akt (P &amp;lt; 0.05). These studies support the hypothesis that DER inhibits carcinogenesis, in part, by limiting glucose availability and that energy metabolism is a target for the development of ERMA for chemoprevention.
Therapeutic Abortion and a Prior Psychiatric History
Authors: JOHN A. EWING, BEATRICE A. ROUSE
Journal: American Journal of Psychiatry (1973)

A follow-up study of 126 women who received abortions on psychiatric grounds revealed that the 52 women with a history of prior psychiatric illness did not experience significantly more post-abortion emotional reactions than the others. Ninety-six percent of the psychiatric group and 92 percent of the others reported that their emotional health was better or normal afterward.
SOCIOLOGICAL FACTORS IN PATIENTS IN ARMY NEUROSIS CENTER AND THEIR RELATION TO DISCIPLINARY ACTIONS
Authors: PAUL V. LEMKAU, FREDRICK E. KENT
Journal: American Journal of Psychiatry (1945)

1. Nine-hundred and sixty-eight cases admitted to an army neurosis center are analyzed according to certain sociological factors. The age distribution of cases is given. 2. Normal homes produce a significantly smaller proportion of military delinquents than broken homes. 3. A rough gradation of financial status of the parental home of patient-soldiers is presented. While there is an apparent tendency for the homes with inadequate finances to produce a larger proportion of military delinquents than do homes with more adequate financial status, this is statistically not significant. 4. Urban-rural background is given for the 968 patients. Patients with urban background are somewhat more likely to be military delinquents than those from rural background. 5. The marital status by three year age groups is presented. Military delinquency is not significantly related to marital status in this group of patients. 6. Men who have held but one job before entering the service are less likely to become military delinquents than men who have badly disorganized work histories.
Disrupting SUMOylation enhances transcriptional function and ameliorates polyglutamine androgen receptor–mediated disease
Authors: Jason P. Chua, Satya L. Reddy, Zhigang Yu, Elisa Giorgetti, Heather L. Montie, Sarmistha Mukherjee, Jake Higgins, Richard C. McEachin, Diane M. Robins, Diane E. Merry, Jorge A. Iñiguez-Lluhí, Andrew P. Lieberman
Journal: Journal of Clinical Investigation (2015)

Expansion of the polyglutamine (polyQ) tract within the androgen receptor (AR) causes neuromuscular degeneration in individuals with spinobulbar muscular atrophy (SBMA). PolyQ AR has diminished transcriptional function and exhibits ligand-dependent proteotoxicity, features that have both been implicated in SBMA; however, the extent to which altered AR transcriptional function contributes to pathogenesis remains controversial. Here, we sought to dissociate effects of diminished AR function from polyQ-mediated proteotoxicity by enhancing the transcriptional activity of polyQ AR. To accomplish this, we bypassed the inhibitory effect of AR SUMOylation (where SUMO indicates small ubiquitin-like modifier) by mutating conserved lysines in the polyQ AR that are sites of SUMOylation. We determined that replacement of these residues by arginine enhances polyQ AR activity as a hormone-dependent transcriptional regulator. In a murine model, disruption of polyQ AR SUMOylation rescued exercise endurance and type I muscle fiber atrophy; it also prolonged survival. These changes occurred without overt alterations in polyQ AR expression or aggregation, revealing the favorable trophic support exerted by the ligand-activated receptor. Our findings demonstrate beneficial effects of enhancing the transcriptional function of the ligand-activated polyQ AR and indicate that the SUMOylation pathway may be a potential target for therapeutic intervention in SBMA.
Delayed catabolism of high density lipoprotein apolipoproteins A-I and A-II in human cholesteryl ester transfer protein deficiency.
Authors: K Ikewaki, D J Rader, T Sakamoto, M Nishiwaki, N Wakimoto, J R Schaefer, T Ishikawa, T Fairwell, L A Zech, H Nakamura
Journal: Journal of Clinical Investigation (1993)

Deficiency of the cholesteryl ester transfer protein (CETP) in humans is characterized by markedly elevated plasma concentrations of HDL cholesterol and apoA-I. To assess the metabolism of HDL apolipoproteins in CETP deficiency, in vivo apolipoprotein kinetic studies were performed using endogenous and exogenous labeling techniques in two unrelated homozygotes with CETP deficiency, one heterozygote, and four control subjects. All study subjects were administered 13C6-labeled phenylalanine by primed constant infusion for up to 16 h. The fractional synthetic rates (FSRs) of apoA-I in two homozygotes with CETP deficiency (0.135, 0.134/d) were found to be significantly lower than those in controls (0.196 +/- 0.041/d, P < 0.01). Delayed apoA-I catabolism was confirmed by an exogenous radiotracer study in one CETP-deficient homozygote, in whom the fractional catabolic rate of 125I-apoA-I was 0.139/d (normal 0.216 +/- 0.018/d). The FSRs of apoA-II were also significantly lower in the homozygous CETP-deficient subjects (0.104, 0.112/d) than in the controls (0.170 +/- 0.023/d, P < 0.01). The production rates of apoA-I and apoA-II were normal in both homozygous CETP-deficient subjects. The turnover of apoA-I and apoA-II was substantially slower in both HDL2 and HDL3 in the CETP-deficient homozygotes than in controls. The kinetics of apoA-I and apoA-II in the CETP-deficient heterozygote were not different from those in controls. These data establish that homozygous CETP deficiency causes markedly delayed catabolism of apoA-I and apoA-II without affecting the production rates of these apolipoproteins.
Proteomics and Comparative Genomic Investigations Reveal Heterogeneity in Evolutionary Rate of Male Reproductive Proteins in Mice (Mus domesticus)
Authors: M. D. Dean, N. L. Clark, G. D. Findlay, R. C. Karn, X. Yi, W. J. Swanson, M. J. MacCoss, M. W. Nachman
Journal: Molecular Biology and Evolution (2009)

Male reproductive fitness is strongly affected by seminal fluid. In addition to interacting with the female environment, seminal fluid mediates important physiological characteristics of sperm, including capacitation and motility. In mammals, the male reproductive tract shows a striking degree of compartmentalization, with at least six distinct tissue types contributing material that is combined with sperm in an ejaculate. Although studies of whole ejaculates have been undertaken in some species, we lack a comprehensive picture of the specific proteins produced by different accessory tissues. Here, we perform proteomic investigations of six regions of the male reproductive tract in mice—seminal vesicles, anterior prostate, dorsolateral prostate, ventral prostate, bulbourethral gland, and bulbourethral diverticulum. We identify 766 proteins that could be mapped to 506 unique genes and compare them with a high-quality human seminal fluid data set. We find that Gene Ontology functions of seminal proteins are largely conserved between mice and humans. By placing these data in an evolutionary framework, we show that seminal vesicle proteins have experienced a significantly higher rate of nonsynonymous substitution compared with the genome, which could be the result of adaptive evolution. In contrast, proteins from the other five tissues showed significantly lower nonsynonymous substitution, revealing a previously unappreciated level of evolutionary constraint acting on the majority of male reproductive proteins.
Abnormal Cytology Predicts Poor Prognosis in Cancer Patients With Pericardial Effusion
Authors: Heather L. Gornik, Marie Gerhard-Herman, Joshua A. Beckman
Journal: Journal of Clinical Oncology (2005)

Pericardial tamponade is a life-threatening disorder caused by varying medical conditions. Malignancy and complications of its treatment are a common cause of pericardial effusion. The natural history of pericardial effusion remains largely unknown. We investigated the association of malignancy with adverse outcomes after pericardiocentesis.Consecutive patients undergoing pericardiocentesis at a single institution between January 1, 1999, and January 31, 2003, were included. Death was confirmed with the Social Security Death Index. Survival estimates were obtained by the Kaplan-Meier method. Cox regression was performed to determine the clinical characteristics associated with death.Two hundred nineteen patients underwent pericardiocentesis during the study period. The effusion was cancer-related in 43.8% of cases. Median survival was 59.6 weeks (95% CI, 24.3 to 94.8 weeks). During the follow-up period, 47.9% of patients died. Cancer-related pericardial effusion was associated with decreased survival (median, 15.1 weeks). Abnormal fluid cytology was further associated with poor prognosis among patients with malignancy (median survival, 7.3 v 29.7 weeks; P = .022). Patients with cancer-related pericardial effusion were more likely to require repeat pericardiocentesis (OR = 6.0; P = .001) and pericardial surgery (odds ratio [OR] OR = 5.7; P < .001). Cancer-related effusion and abnormal cytology were independent predictors of death in a multivariate model.Malignancy is the most common cause of pericardial effusion in a tertiary care center. Cancer-related pericardial effusion is associated with adverse outcomes, and abnormal cytology further worsens prognosis. The poor survival among cancer patients with pericardial effusion and abnormal fluid cytology may have important implications for management.
No primary association between LMP2 polymorphisms and extraspinal manifestations in spondyloarthropathies
Authors: T. Hohler, T. Schaper, P. M Schneider, F. Krummenauer, C. Rittner, K.-H M. zum Buschenfelde, E. Marker-Hermann
Journal: Annals of the Rheumatic Diseases (1997)

To investigate the potential role of the HLA-linked LMP2 (low molecular weight protein) gene polymorphisms in conjunction with DR4 and DR7 on extraspinal disease manifestations in HLA-B27 positive patients with spondyloarthropathy.172 patients with spondyloarthropathy, 46 healthy, HLA-B27 positive blood donors, and 99 unrelated controls were typed for HLA-class I and II antigens. LMP2 alleles were determined by polymerase chain reaction and subsequent restriction enzyme digestion.There were statistically non-significant increases of DR4 and DR7 in spondyloarthropathy subjects. However these differences did not relate to specific extraspinal manifestations. There were no significant differences in the LMP2 genotype distribution in the disease groups. All differences in LMP2 genotype frequencies disappeared when correcting for DR4, which was in linkage disequilibrium with the LMP2B allele.There is no independent association between LMP2 genotypes and the occurrence of uveitis or peripheral arthritis in HLA-B27 positive subjects with spondyloarthropathy. DR4 and DR7 do not contribute to these disease manifestations.
Electrogram polarity reversal as an additional indicator of breakthroughs from the left atrium to the pulmonary veins
Authors: Teiichi Yamane, Dipen C Shah, Pierre Jaïs, M.élèze Hocini, Isabel Deisenhofer, Kee-Joon Choi, Laurent Macle, Jacques Clémenty, Michel Haïssaguerre
Journal: Journal of the American College of Cardiology (2002)
PML/RARA Oxidation and Arsenic Binding Initiate the Antileukemia Response of As2O3
Authors: Marion Jeanne, Valérie Lallemand-Breitenbach, Omar Ferhi, Marcel Koken, Morgane Le Bras, Stéphanie Duffort, Laurent Peres, Caroline Berthier, Hassane Soilihi, Brian Raught, Hugues de Thé
Journal: Cancer Cell (2010)
AUSTRALIAN MULTICENTRE TRIAL OF STREPTOKINASE IN ACUTE MYOCARDIAL INFARCTION
Authors: J.H.N. Bett, P.A. Castaldi, G.S. Hale, J.P. Isbister, K.H. Mclean, E.F. O'Sullivan, J.C. Biggs, C.N. Chesterman, J. Hirsh, I.G. Mcdonald, J.J. Morgan, M. Rosenbaum
Journal: The Lancet (1973)
Notch is active in Langerhans cell histiocytosis and confers pathognomonic features on dendritic cells
Authors: Caroline Hutter, Max Kauer, Ingrid Simonitsch-Klupp, Gunhild Jug, Raphaela Schwentner, Judith Leitner, Peter Bock, Peter Steinberger, Wolfgang Bauer, Nadia Carlesso, Milen Minkov, Helmut Gadner, Georg Stingl, Heinrich Kovar, Ernst Kriehuber
Journal: Blood (2012)
cIAP1, cIAP2, and XIAP Act Cooperatively via Nonredundant Pathways to Regulate Genotoxic Stress–Induced Nuclear Factor-κB Activation
Authors: Hyung-Seung Jin, Dong-Hee Lee, Dong-Hwan Kim, Ji-Hye Chung, Seul-Ji Lee, Tae H. Lee
Journal: Cancer Research (2009)

Various genotoxic agents cause monoubiquitination of NEMO/IKKgamma-the regulatory subunit of IkappaB kinase (IKK) complex-in the nucleus. Ubiquitinated NEMO exits from the nucleus and forms a complex with the IKK catalytic subunits IKKalpha and IKKbeta, resulting in IKK activation and, ultimately, nuclear factor-kappaB (NF-kappaB) activation. Thus, NEMO ubiquitination is a prerequisite for IKK-dependent activation of NF-kappaB. However, the IKK activation mechanism is unknown and the NEMO-ubiquitinating E3 enzyme has not been identified. We found that inhibitors of apoptosis protein (IAP) regulate genotoxic stress-induced NF-kappaB activation at different levels. XIAP mediates activation of the upstream IKK kinase, TAK1, and couples activated TAK1 to the IKK complex. This XIAP-dependent event occurs in response to camptotechin or etoposide/VP16; however, XIAP is dispensable for activation of NF-kappaB by doxorubicin, which engages a MEK-ERK pathway to activate IKK. We also show that cIAP1 mediates NEMO ubiquitination and cIAP2 regulates an event downstream of NEMO ubiquitination. Our study highlights nonredundant cooperative contributions of IAPs to antiapoptotic NF-kappaB activation by genotoxic signals beyond their classic caspase inhibitory functions.
14-3-3η Amplifies Androgen Receptor Actions in Prostate Cancer
Authors: Mark A. Titus, Jiann-an Tan, Christopher W. Gregory, O. Harris Ford, Romesh R. Subramanian, Haian Fu, Elizabeth M. Wilson, James L. Mohler, Frank S. French
Journal: Clinical Cancer Research (2009)

PURPOSE: Androgen receptor abundance and androgen receptor-regulated gene expression in castration-recurrent prostate cancer are indicative of androgen receptor activation in the absence of testicular androgen. Androgen receptor transactivation of target genes in castration-recurrent prostate cancer occurs in part through mitogen signaling that amplifies the actions of androgen receptor and its coregulators. Herein we report on the role of 14-3-3eta in androgen receptor action. Experimental Design and RESULTS: Androgen receptor and 14-3-3eta colocalized in COS cell nuclei with and without androgen, and 14-3-3eta promoted androgen receptor nuclear localization in the absence of androgen. 14-3-3eta interacted with androgen receptor in cell-free binding and coimmunoprecipitation assays. In the recurrent human prostate cancer cell line, CWR-R1, native endogenous androgen receptor transcriptional activation was stimulated by 14-3-3eta at low dihydrotestosterone concentrations and was increased by epidermal growth factor. Moreover, the dihydrotestosterone- and epidermal growth factor-dependent increase in androgen receptor transactivation was inhibited by a dominant negative 14-3-3eta. In the CWR22 prostate cancer xenograft model, 14-3-3eta expression was increased by androgen, suggesting a feed-forward mechanism that potentiates both 14-3-3eta and androgen receptor actions. 14-3-3eta mRNA and protein decreased following castration of tumor-bearing mice and increased in tumors of castrate mice after treatment with testosterone. CWR22 tumors that recurred 5 months after castration contained 14-3-3eta levels similar to the androgen-stimulated tumors removed before castration. In a human prostate tissue microarray of clinical specimens, 14-3-3eta localized with androgen receptor in nuclei, and the similar amounts expressed in castration-recurrent prostate cancer, androgen-stimulated prostate cancer, and benign prostatic hyperplasia were consistent with androgen receptor activation in recurrent prostate cancer. CONCLUSION: 14-3-3eta enhances androgen- and mitogen-induced androgen receptor transcriptional activity in castration-recurrent prostate cancer. (Clin Cancer Res 2009;15(24):7571-81).
Inefficient Reprogramming of Fibroblasts into Cardiomyocytes Using Gata4, Mef2c, and Tbx5
Authors: Jenny X. Chen, Markus Krane, Marcus-Andre Deutsch, Li Wang, Moshe Rav-Acha, Serge Gregoire, Marc C. Engels, Kuppusamy Rajarajan, Ravi Karra, E. Dale Abel, Joe C. Wu, David Milan, Sean M. Wu
Journal: Circulation Research (2012)

Direct reprogramming of fibroblasts into cardiomyocytes is a novel strategy for cardiac regeneration. However, the key determinants involved in this process are unknown.To assess the efficiency of direct fibroblast reprogramming via viral overexpression of GATA4, Mef2c, and Tbx5 (GMT).We induced GMT overexpression in murine tail tip fibroblasts (TTFs) and cardiac fibroblasts (CFs) from multiple lines of transgenic mice carrying different cardiomyocyte lineage reporters. We found that the induction of GMT overexpression in TTFs and CFs is inefficient at inducing molecular and electrophysiological phenotypes of mature cardiomyocytes. In addition, transplantation of GMT infected CFs into injured mouse hearts resulted in decreased cell survival with minimal induction of cardiomyocyte genes.Significant challenges remain in our ability to convert fibroblasts into cardiomyocyte-like cells and a greater understanding of cardiovascular epigenetics is needed to increase the translational potential of this strategy.
The impact of weight gain and obesity on development of sleep problems in a population-based sample
Authors: Andreas Palm, Christer Janson, Eva Lindberg
Journal: European Respiratory Journal (2014)

Objectives:To investigate the role of obesity and weight gain on development of sleep problems in a population-based cohort.  Method: A population-based sample of men (n=1,896, aged 40-79 years) and women (n=5,116, age g20years) responded to questionnaires at baseline and follow-up after 10-13 years. Sleep problems were assessed by questions of difficulties in inducing sleep (DIS), difficulties maintaining sleep (DMS), excessive daytime sleepiness (EDS) and insomnia. Body mass index (BMI) was calculated from self-reported weight and height at both baseline and follow-up while confounding factors (physical activity, tobacco and alcohol use, somatic disease and snoring) were based on responses at baseline.  Results: Subjects in the quartile with the highest rise in BMI with a weight gain exceeding 2.06 kg/m 2 , had a higher risk to develop DMS (Adj. OR, 95% CI) (1.57, 1.24-1.98), EDS (2.23, 1.64-3.02) and insomnia (2.51, 1.48-4.27). Weight gain was not associated with development of DIS. Overweight and obese subjects reported more DIS, DMS and EDS at baseline but there was no independent association between BMI-level at baseline and development of new sleep problems.  Increasing age was independently associated with an increased risk of developing DIS (adj. OR 95% CI /10 years) (1.17, 1.07-1.29 but a reduced risk of developing DMS (0.92, 0.85-0.98), EDS (0.79, 0.72-0.87) and insomnia (0.80, 0.69-0.94).  Conclusions: Weight gain is an independent risk factor for development of several sleep problems and daytime sleepiness. The presence of overweight and weight gain should be taken into account when treating patients with sleep problems.
Cyclooxygenase Isozymes: The Biology of Prostaglandin Synthesis and Inhibition
Authors: Daniel L. Simmons, Regina M. Botting, Timothy Hla
Journal: Pharmacological Reviews (2004)

Nonsteroidal anti-inflammatory drugs (NSAIDs) represent one of the most highly utilized classes of pharmaceutical agents in medicine. All NSAIDs act through inhibiting prostaglandin synthesis, a catalytic activity possessed by two distinct cyclooxygenase (COX) isozymes encoded by separate genes. The discovery of COX-2 launched a new era in NSAID pharmacology, resulting in the synthesis, marketing, and widespread use of COX-2 selective drugs. These pharmaceutical agents have quickly become established as important therapeutic medications with potentially fewer side effects than traditional NSAIDs. Additionally, characterization of the two COX isozymes is allowing the discrimination of the roles each play in physiological processes such as homeostatic maintenance of the gastrointestinal tract, renal function, blood clotting, embryonic implantation, parturition, pain, and fever. Of particular importance has been the investigation of COX-1 and -2 isozymic functions in cancer, dysregulation of inflammation, and Alzheimer9s disease. More recently, additional heterogeneity in COX-related proteins has been described, with the finding of variants of COX-1 and COX-2 enzymes. These variants may function in tissue-specific physiological and pathophysiological processes and may represent important new targets for drug therapy.