tbuckley/cabot-search huggingface dataset:
<i>DEAR1</i> Is a Chromosome 1p35 Tumor Suppressor and Master Regulator of TGF-β–Driven Epithelial–Mesenchymal Transition
Authors: Nanyue Chen, Seetharaman Balasenthil, Jacquelyn Reuther, Aileen Frayna, Ying Wang, Dawn S. Chandler, Lynne V. Abruzzo, Asif Rashid, Jaime Rodriguez, Guillermina Lozano, Yu Cao, Erica Lokken, Jinyun Chen, Marsha L. Frazier, Aysegul A. Sahin, Ignacio I. Wistuba, Subrata Sen, Steven T. Lott, Ann McNeill Killary
Journal: Cancer Discovery (2013)

Abstract Deletion of chromosome 1p35 is a common event in epithelial malignancies. We report that DEAR1 (annotated as TRIM62) is a chromosome 1p35 tumor suppressor that undergoes mutation, copy number variation, and loss of expression in human tumors. Targeted disruption in the mouse recapitulates this human tumor spectrum, with both Dear1−/− and Dear1+/− mice developing primarily epithelial adenocarcinomas and lymphoma with evidence of metastasis in a subset of mice. DEAR1 loss of function in the presence of TGF-β results in failure of acinar morphogenesis, upregulation of epithelial–mesenchymal transition (EMT) markers, anoikis resistance, migration, and invasion. Furthermore, DEAR1 blocks TGF-β–SMAD3 signaling, resulting in decreased nuclear phosphorylated SMAD3 by binding to and promoting the ubiquitination of SMAD3, the major effector of TGF-β–induced EMT. Moreover, DEAR1 loss increases levels of SMAD3 downstream effectors SNAIL1 and SNAIL2, with genetic alteration of DEAR1/SNAIL2 serving as prognostic markers of overall poor survival in a cohort of 889 cases of invasive breast cancer. Significance: Cumulative results provide compelling evidence that DEAR1 is a critical tumor suppressor involved in multiple human cancers and provide a novel paradigm for regulation of TGF-β–induced EMT through DEAR1′s regulation of SMAD3 protein levels. DEAR1 loss of function has important therapeutic implications for targeted therapies aimed at the TGF-β–SMAD3 pathway. Cancer Discov; 3(10); 1172–89. ©2013 AACR. This article is highlighted in the In This Issue feature, p. 1083
Cytoplasmic Processing Is a Prerequisite for Presentation of an Endogenous Antigen by Major Histocompatibility Complex Class II Proteins
Authors: John D. Lich, John F. Elliott, Janice S. Blum
Journal: The Journal of Experimental Medicine (2000)

Biochemical and functional studies have demonstrated major histocompatibility complex (MHC) class II-restricted presentation of select epitopes derived from cytoplasmic antigens, with few insights into the processing reactions necessary for this alternate pathway. Efficient presentation of an immunodominant epitope derived from glutamate decarboxylase (GAD) was observed regardless of whether this antigen was delivered exogenously or via a cytoplasmic route into human histocompatibility leukocyte antigen class II-DR4(+) antigen-presenting cells. Presentation of exogenous as well as cytoplasmic GAD required the intersection of GAD peptides and newly synthesized class II proteins. By contrast, proteolytic processing of this antigen was highly dependent upon the route of antigen delivery. Exogenous GAD followed the classical pathway for antigen processing, with an absolute requirement for endosomal/lysosomal acidification as well as cysteine and aspartyl proteases resident within these organelles. Presentation of endogenous GAD was dependent upon the action of cytoplasmic proteases, including the proteasome and calpain. Thus, translocation of processed antigen from the cytoplasm into membrane organelles is necessary for class II-restricted presentation via this alternate pathway. Further trimming of these peptides after translocation was mediated by acidic proteases within endosomes/lysosomes, possibly after or before class II antigen binding. These studies suggest that processing of exogenous and cytoplasmic proteins occurs through divergent but overlapping pathways. Furthermore, two cytoplasmic proteases, the proteasome and calpain, appear to play important roles in MHC class II-restricted antigen presentation.
Studies on the Antitumor Activity, Mechanism of Action, and Cell Cycle Effects of Camptothecin
Authors: Robert C. Gallo, Jacqueline Whang-Peng, Richard H. Adamson
Journal: JNCI Journal of the National Cancer Institute (1971)

Camptothecin was active in increasing survival time in mice bearing various experimental leukemias. In addition, it produced 70–90% long-term survivors in mice bearing leukemias L5178Y or K1964. It was also active against the plasma cell tumor YPC-1 but less effective against a mast cell tumor and a reticulum cell sarcoma. The alkaloid was also cytotoxic in vitro against three cell lines. Studies using human lymphocytes stimulated by phytohemagglutinin (PHA) indicated that DNA synthesis was strongly inhibited with concentrations of the drug that did not affect RNA or protein synthesis. Camptothecin not only inhibited DNA synthesis but also caused a G2 “lesion” which prevented subsequent mitosis. It did not have cytocidal effects on resting “G0” lymphocytes. However, when “G0” lymphocytes exposed to the alkaloid were subsequently stimulated to enter cycle, their division was still blocked. These observations not only imply that eventual cell proliferation is necessary for the antitumor activity of camptothecin, but also suggest that the drug may be useful for tumors with long G1 intervals.
CTCF-mediated functional chromatin interactome in pluripotent cells
Authors: Lusy Handoko, Han Xu, Guoliang Li, Chew Yee Ngan, Elaine Chew, Marie Schnapp, Charlie Wah Heng Lee, Chaopeng Ye, Joanne Lim Hui Ping, Fabianus Mulawadi, Eleanor Wong, Jianpeng Sheng, Yubo Zhang, Thompson Poh, Chee Seng Chan, Galih Kunarso, Atif Shahab, Guillaume Bourque, Valere Cacheux-Rataboul, Wing-Kin Sung, Yijun Ruan, Chia-Lin Wei
Journal: Nature Genetics (2011)
Aplastic anemia complicating orthotopic liver transplantation
Authors: J A Goss, G J Schiller, P Martin, P Seu, R Stribling, S V McDiarmid, C R Shackleton, J S Markowitz, B J Nuesse, L I Goldstein, R W Busuttil
Journal: Hepatology (1997)

The clinical characteristics and outcome of posttransplantation aplastic anemia (AA) were determined in 12 of 1,736 patients (0.007%) undergoing orthotopic liver transplantation (OLT) that were afflicted with AA. None of the affected patients had a history of hematologic disease. Median patient age was 53 years (range, 2-61 years); 10 of the affected patients were men, and 2 were women. The etiologies of AA included non-A, non-B, non-C fulminant hepatic failure (FHF) (3 patients), graft-versus-host disease (4 patients), Parvovirus-induced (1 patient), and idiopathic (4 patients). The median duration between OLT and the onset of AA was 12 days (range, 11-14 days) in the 3 patients undergoing OLT for FHF; in contrast, AA developed in the other 9 patients at 37 days (range, 27-51 days) after OLT. Eleven patients were treated with reduction of their cyclosporine or tacrolimus dosage, granulocyte colony-stimulating factor, anti-thymocyte globulin, and Solumedrol. Two of the 3 patients developing AA following OLT for FHF achieved hematologic recovery 21 and 92 days after diagnosis. In contrast, all 9 non-FHF patients developing AA after OLT died, 5 due to infectious complications and 4 following intracranial bleeding. AA is an unusual complication of OLT. In the setting of FHF, it affects young males in the early posttransplantation period, and, when infectious complications can be avoided, remission and stable allograft function can be anticipated. However, in the non-FHF patient, AA occurs in older individuals later in the posttransplantation period and has a uniformly poor outcome.
Insulin and Insulin-Like Growth Factor I in Early Development: Peptides, Receptors and Biological Events*
Authors: FLORA DE PABLO, LAURIE A. SCOTT, JESSE ROTH
Journal: Endocrine Reviews (1990)

THE goal of this paper is to sketch the present understanding of the role that insulin and insulin receptors, as well as insulin-like growth factor I (IGF-I) and its receptors, seem to play in early embryogenesis. This approach overturns ideas of previous decades which have suggested that hormones function relatively late in embryogenesis, i.e. only after the individual glands envelop (1, 2); that insulin acts largely as a regulator of metabolic events in a narrow range of metabolically important target tissues (e.g. muscle, fat, and liver); and that IGF-I is mainly a postnatal growth stimulator (3). In contrast, it is now broadly accepted that 1) insulin is expressed before there is an embryonic pancreas, 2) IGFI is expressed before liver develops, and 3) both insulin and IGF-I influence metabolic, growth, and differentiation processes in a very wide range of cell types (4). We shall begin with an overview of the receptors, essential components of the hormone action cascade. Over the last decade it has been recognized that the receptors for insulin and IGF-I have similar biochemical activities, (5, 6) both in the basal and stimulated states, and both are very widely distributed throughout tissues at all ages and stages (7).
Association of Laribacter hongkongensis in community-acquired gastroenteritis with travel and eating fish: a multicentre case-control study
Authors: Patrick CY Woo, Susanna KP Lau, Jade LL Teng, Tak-lun Que, Raymond WH Yung, Wei-kwang Luk, Raymond WM Lai, Wai-Ting Hui, Samson SY Wong, Hon-Hung Yau, Kwok-yung Yuen
Journal: The Lancet (2004)
Effects of Exercise Dose and Type During Breast Cancer Chemotherapy: Multicenter Randomized Trial
Authors: Kerry S. Courneya, Donald C. McKenzie, John R. Mackey, Karen Gelmon, Christine M. Friedenreich, Yutaka Yasui, Robert D. Reid, Diane Cook, Diana Jespersen, Carolyn Proulx, Lianne B. Dolan, Cynthia C. Forbes, Evyanne Wooding, Linda Trinh, Roanne J. Segal
Journal: JNCI Journal of the National Cancer Institute (2013)

Exercise improves physical functioning and symptom management during breast cancer chemotherapy, but the effects of different doses and types of exercise are unknown. A multicenter trial in Canada randomized 301 breast cancer patients to thrice-weekly supervised exercise during chemotherapy consisting of either a standard dose of 25 to 30 minutes of aerobic exercise (STAN; n = 96), a higher dose of 50 to 60 minutes of aerobic exercise (HIGH; n = 101), or a combined dose of 50 to 60 minutes of aerobic and resistance exercise (COMB; n = 104). The primary endpoint was physical functioning assessed by the Medical Outcomes Survey-Short Form (SF)–36. Secondary endpoints were other physical functioning scales, symptoms, fitness, and chemotherapy completion. All statistical tests were linear mixed model analyses, and the P values were two-sided. Follow-up assessment of patient-reported outcomes was 99.0%. Adjusted linear mixed-model analyses showed that neither HIGH (+0.8; 95% confidence interval [CI] = −0.8 to 2.4; P = .30) nor COMB (+0.5; 95% CI = −1.1 to 2.1; P = .52] were superior to STAN for the primary outcome. In secondary analyses not adjusted for multiple comparisons, HIGH was superior to STAN for the SF-36 physical component summary (P = .04), SF-36 bodily pain (P = .02), and endocrine symptoms (P = .02). COMB was superior to STAN for endocrine symptoms (P = .009) and superior to STAN (P < .001) and HIGH (P < .001) for muscular strength. HIGH was superior to COMB for the SF-36 bodily pain (P = .04) and aerobic fitness (P = .03). No differences emerged for body composition or chemotherapy completion. A higher volume of aerobic or combined exercise is achievable and safe during breast cancer chemotherapy and may manage declines in physical functioning and worsening symptoms better than standard volumes.
MARKED HYPERGLYCAEMIA WITHOUT GLYCOSURIA
Authors: G. H. C. St. G. Griffiths
Journal: BMJ (1930)

DIABETIC RETINITIS.[Tn BRit 559 1040 F. anid a rapid pulse.Sle was removed to lhospital, anid recovered after proloniged conivalescence.The oily vpatienit iloW in the lhollme was sent to her own homi-le, andil the l)lace was closed to futrtlher admiissionis for a week and thoroughly disinfected a(lle airedl.Thie tlllats of the milatron alnd a!ssistaniit n-ur se w-ere examiined, but no evident signs of inflatinimmationi were present.A swalb from the throat of the assistant niurse w-as taken, anlil the bacteriological report stated: " Streptococci pr-esci'it on-
Treatment With the Radiolabeled Somatostatin Analog [<sup>177</sup>Lu-DOTA<sup>0</sup>,Tyr<sup>3</sup>]Octreotate: Toxicity, Efficacy, and Survival
Authors: Dik J. Kwekkeboom, Wouter W. de Herder, Boen L. Kam, Casper H. van Eijck, Martijn van Essen, Peter P. Kooij, Richard A. Feelders, Maarten O. van Aken, Eric P. Krenning
Journal: Journal of Clinical Oncology (2008)

Despite the fact that most gastroenteropancreatic neuroendocrine tumors (GEPNETs) are slow-growing, median overall survival (OS) in patients with liver metastases is 2 to 4 years. In metastatic disease, cytoreductive therapeutic options are limited. A relatively new therapy is peptide receptor radionuclide therapy with the radiolabeled somatostatin analog [(177)Lu-DOTA(0),Tyr(3)]octreotate. Here we report on the toxicity and efficacy of this treatment, performed in over 500 patients.Patients were treated up to a cumulative dose of 750 to 800 mCi (27.8-29.6 GBq), usually in four treatment cycles, with treatment intervals of 6 to 10 weeks. Toxicity analysis was done in 504 patients, and efficacy analysis in 310 patients.Any hematologic toxicity grade 3 or 4 occurred after 3.6% of administrations. Serious adverse events that were likely attributable to the treatment were myelodysplastic syndrome in three patients, and temporary, nonfatal, liver toxicity in two patients. Complete and partial tumor remissions occurred in 2% and 28% of 310 GEPNET patients, respectively. Minor tumor response (decrease in size > 25% and < 50%) occurred in 16%. Median time to progression was 40 months. Median OS from start of treatment was 46 months, median OS from diagnosis was 128 months. Compared with historical controls, there was a survival benefit of 40 to 72 months from diagnosis.Treatment with [(177)Lu-DOTA(0),Tyr(3)]octreotate has few adverse effects. Tumor response rates and progression-free survival compare favorably to the limited number of alternative treatment modalities. Compared with historical controls, there is a benefit in OS from time of diagnosis of several years.
Renal effects of the angiotensin receptor neprilysin inhibitor <scp>LCZ696</scp> in patients with heart failure and preserved ejection fraction
Authors: Adriaan A. Voors, Mauro Gori, Licette C.Y. Liu, Brian Claggett, Michael R. Zile, Burkert Pieske, John J.V. McMurray, Milton Packer, Victor Shi, Martin P. Lefkowitz, Scott D. Solomon
Journal: European Journal of Heart Failure (2015)
The newborn infant is protected by an innate antimicrobial barrier: peptide antibiotics are present in the skin and vernix caseosa
Authors: G. Marchini, S. Lindow, H. Brismar, B. Stabi, V. Berggren, A-K. Ulfgren, S. Lonne-Rahm, B. Agerberth, G.H. Gudmundsson
Journal: British Journal of Dermatology (2002)

Journal Article The newborn infant is protected by an innate antimicrobial barrier: peptide antibiotics are present in the skin and vernix caseosa Get access G. Marchini, G. Marchini Departments of Woman and Child Health Giovanna Marchini, Astrid Lindgren Children's Hospital, Karolinska Hospital C4:U1, S‐171 76 Stockholm, Sweden. E‐mail: giovanna.marchini@ks.se Search for other works by this author on: Oxford Academic Google Scholar S. Lindow, S. Lindow Departments of Woman and Child Health Search for other works by this author on: Oxford Academic Google Scholar H. Brismar, H. Brismar Departments of Woman and Child Health Search for other works by this author on: Oxford Academic Google Scholar B. Ståbi, B. Ståbi Departments of Woman and Child Health Search for other works by this author on: Oxford Academic Google Scholar V. Berggren, V. Berggren Departments of Woman and Child Health Search for other works by this author on: Oxford Academic Google Scholar A‐K. Ulfgren, A‐K. Ulfgren Rheumatology Research Search for other works by this author on: Oxford Academic Google Scholar S. Lonne‐Rahm, S. Lonne‐Rahm Dermatology, and Search for other works by this author on: Oxford Academic Google Scholar B. Agerberth, B. Agerberth Medical Biochemistry and Biophysics Search for other works by this author on: Oxford Academic Google Scholar G.H. Gudmundsson G.H. Gudmundsson Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 147, Issue 6, 1 December 2002, Pages 1127–1134, https://doi.org/10.1046/j.1365-2133.2002.05014.x Published: 01 December 2002 Article history Accepted: 24 April 2002 Published: 01 December 2002
Internal mammary artery-to-pulmonary artery fistulas. Case report and review of the literature.
Authors: S F Hearne, M K Burbank
Journal: Circulation (1980)

A case of internal mammary artery-to-pulmonary artery fistula is presented, and all previously reported cases are reviewed. This represents a rare cause of a continuous precordial murmur that may be confused clinically with a patent ductus arteriosus. Patients are usually asymptomatic, and routine diagnostic tests may be of little help in establishing a diagnosis. Selective internal mammary angiography is the procedure of choice for confirmation and localization. The question of advisability of surgery for these patients remains unanswered.
Bacterial colonisation of humidifier attachments on oxygen concentrators prescribed for long term oxygen therapy: a district review.
Authors: N Pendleton, J S Cheesbrough, M J Walshaw, C R Hind
Journal: Thorax (1991)

A microbiological survey was undertaken on the eight patients in the Liverpool District who have a humidifier attachment on their oxygen concentrator. All but one of the humidifiers were contaminated with potentially pathogenic bacteria.
Accelerated Mutation Accumulation in Asexual Lineages of a Freshwater Snail
Authors: M. Neiman, G. Hehman, J. T. Miller, J. M. Logsdon, D. R. Taylor
Journal: Molecular Biology and Evolution (2009)

Sexual reproduction is both extremely costly and widespread relative to asexual reproduction, meaning that it must also confer profound advantages in order to persist. One theorized benefit of sex is that it facilitates the clearance of harmful mutations, which would accumulate more rapidly in the absence of recombination. The extent to which ineffective purifying selection and mutation accumulation are direct consequences of asexuality and whether the accelerated buildup of harmful mutations in asexuals can occur rapidly enough to maintain sex within natural populations, however, remain as open questions. We addressed key components of these questions by estimating the rate of mutation accumulation in the mitochondrial genomes of multiple sexual and asexual representatives of Potamopyrgus antipodarum, a New Zealand snail characterized by mixed sexual/asexual populations. We found that increased mutation accumulation is associated with asexuality and occurs rapidly enough to be detected in recently derived asexual lineages of P. antipodarum. Our results demonstrate that increased mutation accumulation in asexuals can differentially affect coexisting and ecologically similar sexual and asexual lineages. The accelerated rate of mutation accumulation observed in asexual P. antipodarum provides some of the most direct evidence to date for a link between asexuality and mutation accumulation and implies that mutational buildup could be rapid enough to contribute to the short-term evolutionary mechanisms that favor sexual reproduction.
The Interrelationship of Neuroticism, Sex, and Stressful Life Events in the Prediction of Episodes of Major Depression
Authors: Kenneth S. Kendler, Jonathan Kuhn, Carol A. Prescott
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: Three potent risk factors for major depression are female sex, the personality trait of neuroticism, and adversity resulting from exposure to stressful life events. Little is known about how they interrelate in the etiology of depressive illness. METHOD: In over 7,500 individual twins from a population-based sample, the authors used a Cox proportional hazard model to predict onsets of episodes of DSM-III-R major depression in the year before the latest interviews on the basis of previously assessed neuroticism, sex, and adversity during the past year; adversity was operationalized as the long-term contextual threat scored from 15 life event categories. RESULTS: In the best-fit Cox model for prediction of depressive onsets, neuroticism, female sex, and greater adversity all strongly increased risk for major depression. An interaction was seen between neuroticism and adversity such that individuals with high neuroticism were at greater overall risk for major depression and were more sensitive to the depressogenic effects of adversity. An interaction was also seen between adversity and sex, as the excess risk for major depression in women was confined to individuals with low stress exposure. CONCLUSIONS: Psychosocial adversity interacts both with neuroticism and with sex in the etiology of major depression. The impact of neuroticism on illness risk is greater at high than at low levels of adversity, while the effect of sex on probability of onset is the opposite—greater at low than at high levels of stress. Complete etiologic models for major depression should incorporate interactions between risk factor classes.
Increased heart rate prevents the isomyosin shift after cardiac transplantation in the rat.
Authors: D L Geenen, A Malhotra, P M Buttrick, J Scheuer
Journal: Circulation Research (1992)

The heterotopically transplanted rat heart undergoes significant atrophy and a shift from V1 to V3 isomyosin. The purpose of this study was to pace the cardiac isograft and determine whether an increase in heart rate would attenuate the changes in cardiac mass and isoenzyme distribution. Nonpaced transplanted hearts were compared with hearts in which pacing was initiated at 7 Hz, 24 hours after transplantation, and continued for 7 days. There was a 29% decrease in myosin ATPase activity and a 22% decrease in alpha-myosin in the nonpaced isograft; both decreases were completely prevented by pacing. The decrease in cardiac mass was also significantly attenuated. Pacing did not alter intrinsic heart rate, systolic pressure, dP/dt, or norepinephrine concentration in the isograft. These results suggest that the adaptation in both cardiac mass and isoenzymes may be related to the rate or the rate-pressure product in the transplanted paced heart independent of left ventricular pressure, tissue catecholamines, or neural activity.