tbuckley/cabot-search huggingface dataset:
Gene networks and transcription factor motifs defining the differentiation of stem cells into hepatocyte-like cells
Authors: Patricio Godoy, Wolfgang Schmidt-Heck, Karthick Natarajan, Baltasar Lucendo-Villarin, Dagmara Szkolnicka, Annika Asplund, Petter Björquist, Agata Widera, Regina Stöber, Gisela Campos, Seddik Hammad, Agapios Sachinidis, Umesh Chaudhari, Georg Damm, Thomas S. Weiss, Andreas Nüssler, Jane Synnergren, Karolina Edlund, Barbara Küppers-Munther, David C. Hay, Jan G. Hengstler
Journal: Journal of Hepatology (2015)

The differentiation of stem cells to hepatocyte-like cells (HLC) offers the perspective of unlimited supply of human hepatocytes. However, the degree of differentiation of HLC remains controversial. To obtain an unbiased characterization, we performed a transcriptomic study with HLC derived from human embryonic and induced stem cells (ESC, hiPSC) from three different laboratories.Genome-wide gene expression profiles of ESC and HLC were compared to freshly isolated and up to 14days cultivated primary human hepatocytes. Gene networks representing successful and failed hepatocyte differentiation, and the transcription factors involved in their regulation were identified.Gene regulatory network analysis demonstrated that HLC represent a mixed cell type with features of liver, intestine, fibroblast and stem cells. The "unwanted" intestinal features were associated with KLF5 and CDX2 transcriptional networks. Cluster analysis identified highly correlated groups of genes associated with mature liver functions (n=1057) and downregulated proliferation associated genes (n=1562) that approach levels of primary hepatocytes. However, three further clusters containing 447, 101, and 505 genes failed to reach levels of hepatocytes. Key TF of two of these clusters include SOX11, FOXQ1, and YBX3. The third unsuccessful cluster, controlled by HNF1, CAR, FXR, and PXR, strongly overlaps with genes repressed in cultivated hepatocytes compared to freshly isolated hepatocytes, suggesting that current in vitro conditions lack stimuli required to maintain gene expression in hepatocytes, which consequently also explains a corresponding deficiency of HLC.The present gene regulatory network approach identifies key transcription factors which require modulation to improve HLC differentiation.
Transmembrane adaptor molecules: a new category of lymphoid-cell markers
Authors: Sara Tedoldi, Jennifer C. Paterson, Martin-Leo Hansmann, Yasodha Natkunam, Thomas Rüdiger, Pavla Angelisova, Ming Q. Du, Helen Roberton, Giovanna Roncador, Lydia Sanchez, Michela Pozzobon, Noraidah Masir, Richard Barry, Stefano Pileri, David Y. Mason, Teresa Marafioti, Václav Horejsí
Journal: Blood (2005)
USE AND ABUSE OF HUMAN GROWTH HORMONE
Authors: E. Kirk Neely, M.D, Ron G. Rosenfeld, M.D
Journal: Annual Review of Medicine (1994)

▪ Abstract Recombinant human growth hormone (hGH) has been available for nearly a decade. Side effects are rare. Its efficacy in promoting growth acceleration has been widely confirmed in children with GH deficiency (GHD), Turner syndrome, idiopathic short stature, chronic renal failure, and a variety of other conditions. The dramatic increase in height velocity in the first year of therapy partially attenuates in subsequent years in all patient groups, and convincing final height data are only available in GHD and Turner syndrome. Pediatric endocrinologists continue to be troubled by definitions of GHD. Although profound GHD is relatively obvious, other patients with severe growth failure but borderline or normal endocrine testing also respond to hGH therapy. Thus many endocrinologists use auxologic criteria [e.g. low growth velocity, height &lt;-3 standard deviation (SD), poor predicted adult height] as the de facto basis for therapy, leading to a blurred distinction between treatment of disease and enhancement of normal characteristics and, finally, raising questions about the ultimate benefit of hGH therapy. Brief clinical trials of hGH therapy in adults both with and without GHD have reported increased muscle mass, decreased fat, and improvement in quality of life. Internists may soon be faced with treatment decisions analogous to those confronting pediatricians, i.e. whether to use hGH to repair aspects of the normal aging process.
Targeted Disruption of the Mouse Caspase 8 Gene Ablates Cell Death Induction by the TNF Receptors, Fas/Apo1, and DR3 and Is Lethal Prenatally
Authors: Eugene E Varfolomeev, Marcus Schuchmann, Victor Luria, Nuchanard Chiannilkulchai, Jacques S Beckmann, Igor L Mett, Denis Rebrikov, Vadim M Brodianski, Oliver C Kemper, Orit Kollet, Tsvee Lapidot, Dror Soffer, Tama Sobe, Karen B Avraham, Tanya Goncharov, Helmut Holtmann, Peter Lonai, David Wallach
Journal: Immunity (1998)
Severe deficiency of cystic fibrosis transmembrane conductance regulator messenger RNA carrying nonsense mutations R553X and W1316X in respiratory epithelial cells of patients with cystic fibrosis.
Authors: A Hamosh, B C Trapnell, P L Zeitlin, C Montrose-Rafizadeh, B J Rosenstein, R G Crystal, G R Cutting
Journal: Journal of Clinical Investigation (1991)

Cystic fibrosis (CF) is the most common, lethal inherited disorder in the Caucasian population. We have recently reported two African-American patients with nonsense mutations in each CF gene and severe pancreatic disease, but mild pulmonary disease. In order to examine the effect of these nonsense mutations on CF gene expression, bronchial and nasal epithelial cells were obtained from one of these patients (no. 246), a compound heterozygote for nonsense mutations R553X and W1316X; a healthy normal individual; a patient (no. 528) homozygous for the common CF mutation (delta F508); and a CF patient (no. 272) who carries the R553X mutation and a missense mutation, S549N. When mRNA from bronchial cells of the normal individual, the delta F508 homozygote, and the S549N/R553X compound heterozygote was reverse transcribed and amplified by polymerase chain reaction using primers derived from the CF gene, DNA fragments of the predicted size were observed. However, patient no. 246 with nonsense mutations in each CF gene has no detectable cystic fibrosis transmembrane conductance regulator (CFTR) messenger RNA, and therefore should have severely diminished, and possibly absent, CFTR protein. Furthermore, less than 2% of the CFTR transcripts in nasal epithelial cells from patient no. 272 (S549N/R553X) were derived from the gene with the nonsense mutation. We conclude that severe reduction in CFTR mRNA causes CF, but can have different consequences in the lung and pancreas.
BULLOUS IODIDE ERUPTIONS
Authors: HARRY KEIL
Journal: British Journal of Dermatology (1938)

Journal Article BULLOUS IODIDE ERUPTIONS Get access HARRY KEIL HARRY KEIL Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 50, Issue 6, 1 June 1938, Pages 329–332, https://doi.org/10.1111/j.1365-2133.1938.tb10572.x Published: 01 June 1938
Mitochondrial Thioredoxin Reductase Is Essential for Early Postischemic Myocardial Protection
Authors: Jan Horstkotte, Tamara Perisic, Manuela Schneider, Philipp Lange, Melanie Schroeder, Claudia Kiermayer, Rabea Hinkel, Tilman Ziegler, Pankaj K. Mandal, Robert David, Sabine Schulz, Sabine Schmitt, Julian Widder, Fred Sinowatz, Bernhard F. Becker, Johann Bauersachs, Michael Naebauer, Wolfgang M. Franz, Irmela Jeremias, Markus Brielmeier, Hans Zischka, Marcus Conrad, Christian Kupatt
Journal: Circulation (2011)

Background— Excessive formation of reactive oxygen species contributes to tissue injury and functional deterioration after myocardial ischemia/reperfusion. Especially, mitochondrial reactive oxygen species are capable of opening the mitochondrial permeability transition pore, a harmful event in cardiac ischemia/reperfusion. Thioredoxins are key players in the cardiac defense against oxidative stress. Mutations in the mitochondrial thioredoxin reductase (thioredoxin reductase-2, Txnrd2) gene have been recently identified to cause dilated cardiomyopathy in patients. Here, we investigated whether mitochondrial thioredoxin reductase is protective against myocardial ischemia/reperfusion injury. Methods and Results— In mice, α-MHC-restricted Cre-mediated Txnrd2 deficiency, induced by tamoxifen ( Txnrd2-/-ic ), aggravated systolic dysfunction and cardiomyocyte cell death after ischemia (90 minutes) and reperfusion (24 hours). Txnrd2-/-ic was accompanied by a loss of mitochondrial integrity and function, which was resolved on pretreatment with the reactive oxygen species scavenger N-acetylcysteine and the mitochondrial permeability transition pore blocker cyclosporin A. Likewise, Txnrd2 deletion in embryonic endothelial precursor cells and embryonic stem cell-derived cardiomyocytes, as well as introduction of Txnrd2-shRNA into adult HL-1 cardiomyocytes, increased cell death on hypoxia and reoxygenation, unless N-acetylcysteine was coadministered. Conclusions— We report that Txnrd2 exerts a crucial function during postischemic reperfusion via thiol regeneration. The efficacy of cyclosporin A in cardiac Txnrd2 deficiency may indicate a role for Txnrd2 in reducing mitochondrial reactive oxygen species, thereby preventing opening of the mitochondrial permeability transition pore.
The Actions and Metabolic Fate of Disulfiram
Authors: D I Eneanya, J R Bianchine, D O Duran, B D Andresen
Journal: The Annual Review of Pharmacology and Toxicology (1981)

Due to the massive data sets available for drug candidates, modern drug discovery has advanced to the big data era. Central to this shift is the development of artificial intelligence approaches to implementing innovative modeling based on the dynamic, ...Read More
Skin and Soft-Tissue Infections Caused by Methicillin-Resistant<i>Staphylococcus aureus</i>
Authors: Robert S. Daum
Journal: New England Journal of Medicine (2007)

A 37-year-old man presents with localized swelling and tenderness of the left leg just below the knee; he suspects a spider bite. Examination shows a 5-by-7-cm area of erythema and warmth. A small area of necrotic skin covers a central, fluctuant 2-by-2-cm area. The temperature is 38.3°C, the pulse rate 115 beats per minute, and the blood pressure 116/78 mm Hg.
Targeting Multidrug Resistance Protein 1 (MRP1, <i>ABCC1</i>): Past, Present, and Future
Authors: Susan P.C. Cole
Journal: The Annual Review of Pharmacology and Toxicology (2013)

The human ATP-binding cassette transporter multidrug resistance protein 1 (MRP1), encoded by ABCC1, was initially identified because of its ability to confer multidrug resistance in lung cancer cells. It is now established that MRP1 plays a role in protecting certain tissues from xenobiotic insults and that it mediates the cellular efflux of the proinflammatory cysteinyl leukotriene C4 as well as a vast array of other endo- and xenobiotic organic anions. Many of these are glutathione (GSH) or glucuronide conjugates, the products of Phase II drug metabolism. MRP1 also plays a role in the cellular efflux of the reduced and oxidized forms of GSH and thus contributes to the many physiological and pathophysiological processes influenced by these small peptides, including oxidative stress. In this review, the pharmacological and physiological aspects of MRP1 are considered in the context of the current status and future prospects of pharmacological and genetic modulation of MRP1 activity.
Neuregulin in Cardiovascular Development and Disease
Authors: Oghenerukevwe Odiete, Michael F. Hill, Douglas B. Sawyer
Journal: Circulation Research (2012)

Studies in genetically modified mice have demonstrated that neuregulin-1 (NRG-1), along with the erythroblastic leukemia viral oncogene homolog (ErbB) 2, 3, and 4 receptor tyrosine kinases, is necessary for multiple aspects of cardiovascular development. These observations stimulated in vitro and in vivo animal studies, implicating NRG-1/ErbB signaling in the regulation of cardiac cell biology throughout life. Cardiovascular effects of ErbB2-targeted cancer therapies provide evidence in humans that ErbB signaling plays a role in the maintenance of cardiac function. These and other studies suggest a conceptual model in which a key function of NRG-1/ErbB signaling is to mediate adaptations of the heart to physiological and pathological stimuli through activation of intracellular kinase cascades that regulate tissue plasticity. Recent work implicates NRG-1/ErbB signaling in the regulation of multiple aspects of cardiovascular biology, including angiogenesis, blood pressure, and skeletal muscle responses to exercise. The therapeutic potential of recombinant NRG-1 as a potential treatment for heart failure has been demonstrated in animal models and is now being explored in clinical studies. NRG-1 is found in human serum and plasma, and it correlates with some clinical parameters, suggesting that it may have value as an indicator of prognosis. In this review, we bring together this growing literature on NRG-1 and its significance in cardiovascular development and disease.
Postoperative elective nodal irradiation for squamous cell carcinoma of the head and neck: outcome and prognostic factors for regional recurrence
Authors: M.R. Vergeer, P.A.H. Doornaert, R. de Bree, C.R. Leemans, B.J. Slotman, J.A. Langendijk
Journal: Annals of Oncology (2011)
An Embryonic Stem Cell–Like Signature Identifies Poorly Differentiated Lung Adenocarcinoma but not Squamous Cell Carcinoma
Authors: Khaled A. Hassan, Guoan Chen, Gregory P. Kalemkerian, Max S. Wicha, David G. Beer
Journal: Clinical Cancer Research (2009)

An embryonic stem cell (ESC) profile correlates with poorly differentiated breast, bladder, and glioma cancers. In this article, we assess the correlation between the ESC profile and clinical variables in lung cancer.Microarray gene expression analysis was done using Affymetrix Human Genome U133A on 443 samples of human lung adenocarcinoma and 130 samples of squamous cell carcinoma (SCC). To identify gene set enrichment patterns, we used the Genomica software.Our analysis showed that an increased expression of the ESC gene set and a decreased expression of the Polycomb target gene set identified poorly differentiated lung adenocarcinoma. In addition, this gene expression signature was associated with markers of poor prognosis and worse overall survival in lung adenocarcinoma. However, there was no correlation between this ESC gene signature and any histologic or clinical variable assessed in lung SCC.This work suggests that not all poorly differentiated non-small cell lung cancers exhibit a gene expression profile similar to that of ESC, and that other characteristics may play a more important role in the determination of differentiation and survival in SCC of the lung.
Remarks on Various Diseases of the Skin
Authors: S. Mackenzie
Journal: BMJ (1890)

given elsewhere,3 and it became necessary to look for some other ;dye on whiqk.thq bichloride might not exert this prejudicial in- fluence.IAi've fow,o4n 4halt tjsre are several colouring matters *hich answer tbepurpose fairly well.Thus both carmine and Prussian blue attach the cyanide salt 'to a cotton fabric perfectly so long as it is moist,but when it is thoroughly dry they are not very good as regards the question of dusting.The dye which I *have found to-comply best with all the requisite conditions is logwood, or, rather, the essential ingredient of logwood, hema-$oxylinl, which is a definite crystalline substance, and not unduly expensive.
Vascular Endothelial Growth Factor Polymorphisms and Esophageal Cancer Prognosis
Authors: Penelope A. Bradbury, Rihong Zhai, Clement Ma, Wei Xu, Jessica Hopkins, Matthew J. Kulke, Kofi Asomaning, Zhaoxi Wang, Li Su, Rebecca S. Heist, Thomas J. Lynch, John C. Wain, David Christiani, Geoffrey Liu
Journal: Clinical Cancer Research (2009)

Vascular endothelial growth factor (VEGF) promotes angiogenesis and vascular permeability. The VEGF gene is polymorphic. We investigated the prognostic significance of three VEGF single nucleotide polymorphisms (SNP) in esophageal cancer.Three hundred sixty-one patients were genotyped for three VEGF SNPs (-460T/C, 405G/C, and 936C/T) using DNA extracted from prospectively collected blood samples. The association of each individual SNP, and haplotypes of the three SNPs, on overall survival (OS) was investigated.The variant allele of 936C/T was associated with improved OS compared with the wild-type genotype (log-rank P < 0.001). This association remained significant for OS after adjustments for age, gender, performance status, and disease stage [VEGF 936C/T: adjusted hazard ratio (AHR), 0.70; 95% confidence interval (95% CI), 0.49-0.99; P = 0.04; VEGF 936T/T: AHR, 0.11; 95% CI, 0.02-0.82; P = 0.03]. No independent associations were found for VEGF -460T/C and VEGF 405G/C. The CGC haplotype of the three VEGF SNPs (-460T/C, 405G/C, and 936C/T) combined was associated with reduced OS compared with all other patients (CGC/CGC: AHR, 1.51; 95% CI, 1.00-2.30; P = 0.05).VEGF 936C/T, and a haplotype of 460T/C, 405G/C, and 936C/T combined, has potential prognostic significance in esophageal cancer.
Global deaths from TB have fallen but many cases are still missed, says WHO
Authors: A. Gulland
Journal: BMJ (2014)

Nine million people developed tuberculosis in 2013 but infection rates have been falling over the past 30 years, a report by the World Health Organization has shown.

The Global Tuberculosis Report 2014 1 showed that, although 1.5 million people died from tuberculosis in 2013, the mortality rate has fallen by 45% since 1990, when 2.7 million died from the disease. An estimated 37 million lives have been saved through effective diagnosis and treatment since 2000, and the prevalence of the disease has fallen by 41% in 23 years—from 275 in 100 000 of the population in 1990 to around 150 in …
GROSS STRESS REACTION IN COMBAT—A 15-YEAR FOLLOW-UP
Authors: HERBERT C. ARCHIBALD, DOROTHY M. LONG, CHRISTINE MILLER, READ D. TUDDENHAM
Journal: American Journal of Psychiatry (1962)

While there are similarities between the combat patients and the non-combat controls, a clear-cut picture emerges of the combat veteran syndrome with a severely disabling condition involving startle reactions, sleep difficulties, dizziness, blackouts, avoidance of activities similar to combat experience, and internalization of feelings. He is not however psychotic. The achievements of the medical and allied professions especially in dealing with the acute combat cases have been valuable but less and less interest is being shown to this particular group of veterans. In many hospitals and clinics there is no official record kept as to whether a patient was ever in combat. It is suggested that if we are to continue to study this group of patients we must at least keep track of them. Particularly with the recent emphasis on "here and now" in psychotherapy a combat veteran's tendency to avoid discussing his traumatic combat experiences may easily create a tacit agreement between the therapist and the veteran to avoid the subject. We suggest that a continuing and broadening attack on the psychological aspects of these problems is indicated. Such a study will help to clarify our concept of psychoneurosis in general and contribute to the maintenance and improvement of these men.
Adjuvant docetaxel, doxorubicin, and cyclophosphamide in node-positive breast cancer: 10-year follow-up of the phase 3 randomised BCIRG 001 trial
Authors: John R Mackey, Miguel Martin, Tadeusz Pienkowski, Janusz Rolski, Jean-Paul Guastalla, Amer Sami, John Glaspy, Eva Juhos, Andrew Wardley, Tommy Fornander, John Hainsworth, Robert Coleman, Manuel R Modiano, Jeferson Vinholes, Tamas Pinter, Álvaro Rodríguez-Lescure, Bruce Colwell, Pierre Whitlock, Louise Provencher, Kara Laing, David Walde, Chris Price, Judith C Hugh, Barrett H Childs, Kimberly Bassi, Mary-Ann Lindsay, Véronique Wilson, Matthieu Rupin, Vincent Houé, Charles Vogel
Journal: The Lancet Oncology (2012)
Comment on: Riazi et al. Can Ultrasound of the Tibial Nerve Detect Diabetic Peripheral Neuropathy? A Cross-Sectional Study. Diabetes Care 2012;35:2575–2579
Authors: D. Scott Nickerson
Journal: Diabetes Care (2013)

Riazi et al. (1) report that ultrasound demonstrates a consistent enlargement of the posterior tibial nerve in the distal leg in diabetes sensorimotor polyneuropathy (DSP). They also describe an inverse relation between calculated cross-sectional area and objectively measured nerve conduction studies and a direct relationship with subjective DSP severity. Their discussion suggests ultrasound use as a point-of-care screening device for DSP and speculates as to whether a demonstrated nerve enlargement in DSP should be of concern for anesthesiologists considering the use of local or regional nerve block injections, which might hypothetically put the compromised nerve at additional risk.

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Phagocytosis of Microbes: Complexity in Action
Authors: David M. Underhill, Adrian Ozinsky
Journal: Annual Review of Immunology (2002)

The phagocytic response of innate immune cells such as macrophages is defined by the activation of complex signaling networks that are stimulated by microbial contact. Many individual proteins have been demonstrated to participate in phagocytosis, and the application of high-throughput tools has indicated that many more remain to be described. In this review, we examine this complexity and describe how during recognition, multiple receptors are simultaneously engaged to mediate internalization, activate microbial killing, and induce the production of inflammatory cytokines and chemokines. Many signaling molecules perform multiple functions during phagocytosis, and these molecules are likely to be key regulators of the process. Indeed, pathogenic microorganisms target many of these molecules in their attempts to evade destruction.
Reliability of the ica, aap and atlE genes in the discrimination between invasive, colonizing and contaminant Staphylococcus epidermidis isolates in the diagnosis of catheter—related infections
Authors: S.J. Vandecasteele, W.E. Peetermans, R.R Merckx, B.J.A. Rijnders, J. Van Eldere
Journal: Clinical Microbiology and Infection (2003)
Phase I Trial of Panitumumab in Combination with Cisplatin, Fluourouracil and Docetaxel (Mdcf) in Advanced/Metastatic Gastric Cancer
Authors: Ioannis Boukovinas, Nikolaos Kentepozidis, Lambros Vamvakas, Athanasios Karampeazis, Ioannis Varthalitis, Christos Emmanouilides, Kostas Kalbakis, Athanasios Athanasiadis, Vassilis Georgoulias, John Souglakos
Journal: Annals of Oncology (2013)
Erratum To: Cisplatin-induced epigenetic activation of miR-34a sensitizes bladder cancer cells to chemotherapy
Authors: Heng Li, Gan Yu, Runlin Shi, Bin Lang, Xianguo Chen, Ding Xia, Haibing Xiao, Xiaolin Guo, Wei Guan, Zhangqun Ye, Wei Xiao, Hua Xu
Journal: Molecular Cancer (2014)

* Correspondence: xiaowei0041@163.com; xuhua@mail.hust.edu.cn Equal contributors Translational Medicin Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China Full list of author information is available at the end of the article
Understanding and explaining real self-deception
Authors: Alfred R. Mele
Journal: Behavioral and Brain Sciences (1997)

This response addresses seven main issues: (1) alleged evidence that in some instances of self-deception an individual simultaneously possesses “contradictory beliefs”; (2) whether garden-variety self-deception is intentional; (3) whether conditions that I claimed to be conceptually sufficient for self-deception are so; (4) significant similarities and differences between self-deception and interpersonal deception; (5) how instances of self-deception are to be explained, and the roles of motivation in explaining them; (6) differences among various kinds of self- deception; (7) whether a proper conception of self-deception implies that definitive ascriptions of self-deception to individuals are impossible.