tbuckley/cabot-search huggingface dataset:
Abstract LB-154: Nuclear export of CALM-AF10 is essential for leukemogenesis
Authors: Amanda E. Conway, Paula B. Scotland, Catherine P. Lavau, Daniel S. Wechsler
Journal: Cancer Research (2012)

Abstract Background: The t(10;11) chromosomal translocation gives rise to the CALM-AF10 fusion gene and is recurrently found in patients with aggressive and difficult-to-treat hematopoietic malignancies (AML and T-ALL). CALM-AF10 leukemias are characterized by upregulation of Hoxa cluster genes and a reduction in H3K79 methylation. The native AF10 protein localizes to the nucleus, while native CALM protein is found predominantly in the cytoplasm. It has been shown that the OM-LZ domain of AF10 interacts with the histone methyltransferase, Dot1L, and that this interaction is necessary for CALM-AF10-mediated transformation. Although it is known that CALM functions as an accessory endocytic protein, the precise role of CALM in leukemogenesis is unclear. Objective: To determine the role of CALM in CALM-AF10-mediated transformation in an effort to identify novel therapeutic targets. Results: Through structure-function analyses, we determined that a minimal region of CALM (aa 520-583) is critical for CALM-AF10-mediated transformation of murine hematopoietic progenitor cells (HPCs). Further analysis of this sequence identified a nuclear export signal (NES) encoded by CALM aa 544-553. The CALM NES mediates the cytoplasmic localization of CALM-AF10; point mutation of the CALM NES (NES*) results in exclusive CALM(NES*)-AF10 accumulation in the nucleus. In contrast to CALM-AF10, transduction of primary murine HPCs with CALM(NES*)-AF10 fails to cause in vitro transformation. Fusion of an 18 aa peptide that includes the CALM NES in frame with AF10 (NESCALM-AF10) is sufficient to induce transformation in vitro and leukemogenesis in vivo. Leukemias induced by NESCALM-AF10 recapitulated the phenotype of CALM-AF10 leukemias, including aberrant Hoxa cluster upregulation and decreased H3K79 methylation. Strikingly, fusion of the NES from different proteins, such as PKI-α and APC, to AF10 also conferred cytoplasmic localization and resulted in transformation in vitro. Finally, human CALM-AF10 leukemia cell lines (U937 and P31-FUJI) display increased sensitivity to a compound that inhibits nuclear export, Leptomycin B. Conclusions: We have determined that a CALM-derived nuclear export signal is both necessary and sufficient for CALM-AF10-mediated transformation. These findings reveal a novel mechanism by which nuclear export of CALM-AF10 mediates leukemogenesis. We postulate that nuclear export inhibitor (NEI) compounds may offer new therapeutic possibilities for patients with aggressive CALM-AF10 leukemias. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-154. doi:1538-7445.AM2012-LB-154
A CASE OF IDIOPATHIC THROMBOCYTOPENIA AND AUTOIMMUNE HÆMOLYTIC ANÆMIA TREATED BY THYMIC IRRADIATION AND BY ADMINISTRATION OF IMURAN AND ACTINOMYCIN-C
Authors: J. Richmond, M.F.A. Woodruff, R.A. Cumming, K.W. Donald
Journal: The Lancet (1963)
Medical hypothesis: bifunctional genetic-hormonal pathways to breast cancer.
Authors: D L Davis, N T Telang, M P Osborne, H L Bradlow
Journal: Environmental Health Perspectives (1997)

As inherited germ line mutations, such as loss of BRCA1 or AT, account for less than 5% of all breast cancer, most cases involve acquired somatic perturbations. Cumulative lifetime exposure to bioavailable estradiol links most known risk factors (except radiation) for breast cancer. Based on a series of recent experimental and epidemiologic findings, we hypothesize that the multistep process of breast carcinogenesis results from exposure to endogenous or exogenous hormones, including phytoestrogens that directly or indirectly alter estrogen metabolism. Xenohormones are defined as xenobiotic materials that modify hormonal production; they can work bifunctionally, through genetic or hormonal paths, depending on the periods and extent of exposure. As for genetic paths, xenohormones can modify DNA structure or function. As for hormonal paths, two distinct mechanisms can influence the potential for aberrant cell growth: compounds can directly bind with endogenous hormone or growth factor receptors affecting cell proliferation or compounds can modify breast cell proliferation altering the formation of hormone metabolites that influence epithelial-stromal interaction and growth regulation. Beneficial xenohormones, such as indole-3-carbinol, genistein, and other bioflavonoids, may reduce aberrant breast cell proliferation, and influence the rate of DNA repair or apoptosis and thereby influence the genetic or hormonal microenvironments. Upon validation with appropriate in vitro and in vivo studies, biologic markers of the risk for breast cancer, such as hormone metabolites, total bioavailable estradiol, and free radical generators can enhance cancer detection and prevention.
The myeloproliferative disorder–associated JAK2 V617F mutant escapes negative regulation by suppressor of cytokine signaling 3
Authors: Michelle B. Hookham, Joanne Elliott, Yvonne Suessmuth, Judith Staerk, Alister C. Ward, William Vainchenker, Melanie J. Percy, Mary Frances McMullin, Stefan N. Constantinescu, James A. Johnston
Journal: Blood (2007)
The Metabolism and Distribution of Tritiated Quinidine.
Authors: Lamar E. Crevasse
Journal: Annals of Internal Medicine (1966)

s1 May 1966The Metabolism and Distribution of Tritiated Quinidine.Lamar E. Crevasse, M.D. (Associate), Yoshiharu Sako, M.D., Myron W. Wheat Jr., M.D.Lamar E. Crevasse, M.D. (Associate)Search for more papers by this author, Yoshiharu Sako, M.D.Search for more papers by this author, Myron W. Wheat Jr., M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-64-5-1156_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTritium-labeled quinidine (Wilzbach method), 50 mg/kg by mouth, was given to mongrel dogs. Serum, urine, bile, and myocardial radioactivity were determined simultaneously.In six acute experiments serum levels of quinidine peaked in 2 hours, were accompanied by immediate appearance of urinary radioactivity which peaked in 1 to 2 hours and accounted for the major excretory pathway. Biliary radioactivity was somewhat delayed, reaching a peak 2 to 4 hours after administration.Serum and myocardial levels of tritiated quinidine were correlated at 2, 4, 6, 12, and 24 hours, after a single dose of quinidine. Serum levels fell in linear fashion, being... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Lamar E. Crevasse, M.D. (Associate); Yoshiharu Sako, M.D.; Myron W. WheatJr., M.D.Affiliations: Gainesville, Florida PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1966Volume 64, Issue 5Page: 1156-1156KeywordsBileMouthUrine ePublished: 1 December 2008 Issue Published: 1 May 1966 PDF downloadLoading ...
Convenient Rule for Dividing Doses
Authors: Michael S. Aaronson
Journal: JAMA (1913)

To the Editor  :—I wish to submit a method which will save the doctor and nurse a good deal of time in administering drugs. If the physician wishes to divide a dose, such as a tablet containing a fraction of a certain weight (grain or gram) so as to give a smaller fraction, the following rule may prove convenient: Dissolve the larger dose in as many volumes of water (minims or cubic centimeters) as equal the denominator of the smaller fraction and give of this solution a number of volumes (minims or cubic centimeters) equal to the denominator of the larger fraction. Thus, if we have 1/8-grain tablets of morphin sulphate and wish to give 1/64 grain, we measure 64 minims of water, in which we dissolve the 1/8-grain tablet. Then by taking 8 minims for injection we give the required 1/64 grain.
The Pemberton and Maroni Signs
Authors: Kerry Siminoski
Journal: Annals of Internal Medicine (1997)

Letters1 June 1997The Pemberton and Maroni SignsKerry Siminoski, MD and Clarissa Wallace, MDKerry Siminoski, MDEndocrine Centre of Edmonton, Edmonton, Alberta T6G 2C8, CanadaSearch for more papers by this author and Clarissa Wallace, MDEndocrine Centre of Edmonton, Edmonton, Alberta T6G 2C8, CanadaSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-126-11-199706010-00017 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Norcross and colleagues point out the vagaries of photographic reproduction. The “after” picture was taken immediately after the “before” picture, and the original slides are quite faithful to the color. During the publication process, however, the “after” picture became slightly altered in darkness and color. Nevertheless, we believe it aptly demonstrates the Pemberton sign.The authors also question the sharp line of demarcation between the suffused skin and normal skin. The only reasonable explanation is that the affected vasculature happens to supply the skin in a distribution with a sharp line of demarcation. This same appearance can be ...REFERENCE1. Epstein O, Perkin GD, de Bono DP, Cookson J. Clinical Examination. New York: Gowen; 1992:621. Google Scholar Author, Article, and Disclosure InformationAffiliations: Endocrine Centre of Edmonton, Edmonton, Alberta T6G 2C8, Canada PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1997Volume 126, Issue 11Page: 916KeywordsBlood vesselsHyperthyroidismThyroidThyroid diseases Issue Published: 1 June 1997 CopyrightCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
THE TREATMENT OF INCLUSION CONJUNCTIVITIS WITH SULFATHIAZOLE OINTMENT
Authors: PHILLIPS THYGESON
Journal: JAMA (1942)

The rapid curative action of sulfanilamide in cases of inclusion conjunctivitis in infants and adults was described in two previous reports.<sup>1</sup>It was found that infants responded in the first few days of treatment and were usually cured within a week. In adults the papillary type of the disease responded equally rapidly, but in cases with predominant follicular hypertrophy several weeks were required for the conjunctiva to return completely to normal. The inclusion bodies characteristic of the disease could not be found after the first few days of treatment. There were no recurrences in cases in which the treatment was continued six days or longer. Local therapy with 0.8 per cent sulfanilamide solution produced temporary improvement in 1 of 2 cases but failed to effect a cure. In spite of the demonstrable efficacy of the administration of small doses of sulfanilamide over a comparatively short period in curing inclusion
THE ABDOMINAL REFLEX IN EPIDEMIC (LETHARGIC) ENCEPHALITIS
Authors: George E. Price
Journal: JAMA (1923)

<h3>To the Editor:</h3> —In an earlier paper (June, 1922), I mentioned the frequency of changes in the abdominal reflex in epidemic encephalitis, and stated that I felt this had not been sufficiently emphasized. With this thought in mind, the last fifty cases examined (most of them seen during the epidemic of the past winter), have been carefully studied with reference to this symptom, with these findings: The abdominal reflex was normal only eight times, or in 16 per cent, of the cases, and in the patients seen within one month of the onset of the disease only three presented normal abdominal reflexes in all quadrants. Of the remaining five patients, one had developed the infection six months previous to the examination, one eight months, two two years and one three years. To offset this, the reflex was absent in all of the abdominal quadrants in patients as late as one
Ginsenoside Rg1 protects against transient focal cerebral ischemic injury and suppresses its systemic metabolic changes in cerabral injury rats
Authors: Mingbao Lin, Wei Sun, Wan Gong, Yasi Ding, Yuanyan Zhuang, Qi Hou
Journal: Acta Pharmaceutica Sinica B (2015)

Ginsenoside Rg1 (GR), a major bioactive compound of traditional Chinese medicine, such as Panax ginseng or Radix Notoginseng, has been shown to exert neuroprotective effects against ischemic stroke. However, pharmacokinetic studies have suggested that GR could not be efficiently transported through the blood-brain barrier. The mechanism by which GR attenuates cerebral ischemic injury in vivo remains largely unknown. Therefore, this study explored potential neuro-protective effects of GR through its systemic metabolic regulating mechanism by using mass spectrometry-based metabolomic profiling. Rats with middle cerebral artery occlusion (MCAO) were treated with GR intravenously. Their metabolic profiles in serum were measured by gas chromatography coupled with mass spectrometry on 1 and 3 days after MCAO. GR exhibited a potent neuro-protective effect by significantly decreasing the neurological scores and infarct volume in the MCAO rats. Moreover, 18 differential metabolites were tentatively identified, all of which appeared to correlate well with these disease indices. Our findings suggested that GR carries a therapeutic potential in stroke possibly through a feed-back mechanism by regulating systematic metabolic mediation.
Nephrology and Bioethics
Authors: Leonard B. Berman
Journal: JAMA (1979)

Nephrology has been the battleground for some of the most bruising disputations ascribable to ethical ambiguities. Renal transplantation, for example, had to face the almost absurd question of who was dead—and thus eligible to be an organ donor—and who was not. Peace was declared only when death was redefined as brain death. We remember vividly the selection of patients who would receive dialysis at a time when there were few such facilities. Candidates were chosen by life-or-death committees until nephrologists rejected the concept of making such choices. The result was federal support of dialysis so that all might have access to it. Even this solution eventually brought back the original problem: the number of patients receiving dialysis treatment increased so rapidly that we again hear competing claims for limited resources. Thus, while problem solving is a pleasurable activity, one is soon confronted with new problems or exacerbations of old ones.
Normal Collagen and Bone Production by Gene-targeted Human Osteogenesis Imperfecta iPSCs
Authors: David R Deyle, Iram F Khan, Gaoying Ren, Pei-Rong Wang, Jordan Kho, Ulrike Schwarze, David W Russell
Journal: Molecular Therapy (2011)

Osteogenesis imperfecta (OI) is caused by dominant mutations in the type I collagen genes. In principle, the skeletal abnormalities of OI could be treated by transplantation of patient-specific, bone-forming cells that no longer express the mutant gene. Here, we develop this approach by isolating mesenchymal cells from OI patients, inactivating their mutant collagen genes by adeno-associated virus (AAV)-mediated gene targeting, and deriving induced pluripotent stem cells (iPSCs) that were expanded and differentiated into mesenchymal stem cells (iMSCs). Gene-targeted iMSCs produced normal collagen and formed bone in vivo, but were less senescent and proliferated more than bone-derived MSCs. To generate iPSCs that would be more appropriate for clinical use, the reprogramming and selectable marker transgenes were removed by Cre recombinase. These results demonstrate that the combination of gene targeting and iPSC derivation can be used to produce potentially therapeutic cells from patients with genetic disease. Osteogenesis imperfecta (OI) is caused by dominant mutations in the type I collagen genes. In principle, the skeletal abnormalities of OI could be treated by transplantation of patient-specific, bone-forming cells that no longer express the mutant gene. Here, we develop this approach by isolating mesenchymal cells from OI patients, inactivating their mutant collagen genes by adeno-associated virus (AAV)-mediated gene targeting, and deriving induced pluripotent stem cells (iPSCs) that were expanded and differentiated into mesenchymal stem cells (iMSCs). Gene-targeted iMSCs produced normal collagen and formed bone in vivo, but were less senescent and proliferated more than bone-derived MSCs. To generate iPSCs that would be more appropriate for clinical use, the reprogramming and selectable marker transgenes were removed by Cre recombinase. These results demonstrate that the combination of gene targeting and iPSC derivation can be used to produce potentially therapeutic cells from patients with genetic disease.
Diseases of the Veins: Pathology, Diagnosis and Treatment
Authors: David I. Abramson
Journal: JAMA (1988)

For reasons not entirely clear to me, diseases of the veins of the extremities have never received the exposure to scrutiny and investigative interest that the arterial side of the circulation has routinely undergone. This is so despite the fact that in the general population, the incidence of such abnormalities exceeds that for involvement of the arteries. As a consequence, a poor foundation and some ambiguity exist among physicians and surgeons regarding the proper approach to diagnosis and treatment of common venous entities in the limbs. Hence, the publication of<i>Diseases of the Veins</i>, devoted entirely to abnormalities affecting the venous circulation and written by two vascular, surgeons and a radiologist, is especially welcome. With such an authorship, it is understandable why a surgical therapeutic approach is given some prominence in the volume, although medical treatment is not neglected. The first five chapters of the book are devoted to an
EMPYEMA OF ANTRUM.
Authors: HENRY G. OHLS
Journal: JAMA (1899)

value to surgeons.Dr. Savidge diverted my effort and placed me in a contemptible position on the basis of the report, because to a high-minded, conscientious physician nothing seems more contemptible than refusing help to a suffering patient in order to advance any selfish inter¬ ests of one's own.
Hepatic intracellular distribution of tritium-labeled unconjugated and conjugated bilirubin in normal and Gunn rats.
Authors: L H Bernstein, J B Ezzer, L Gartner, I M Arias
Journal: Journal of Clinical Investigation (1966)

Relatively little is known about the mechanism, regulation, or subcellular localization of the hepatic uptake, storage, conjugation, and excretion of bilirubin.In the work here reported, the ultra- structural localization of the sites of these proc- esses was studied by determining the subcellular distribution and chemical nature of bilirubin after the injection of physiologic amounts of tritium- labeled unconjugated bilirubin (UCB-3H) and conjugated bilirubin (CB-3H) in normal and glucuronyl transferase-deficient (Gunn) rats (1, 2).Studies were also performed using bilirubin- 14C for comparison with the intracellular distri- bution of tritiated bilirubin.While these studies were in progress, Brown, Grodsky, and Carbone (3) described the subcellular distribution of in- jected UCB-3H in normal rat liver. MethodsTritium-labeled bilirubin was prepared by the Wilzbach procedure and purified and equilibrated with crystalline bovine albumin to constant specific activity as described by Grodsky, Carbone, Fanska, and Peng (4).The purity of labeled bilirubin was established by diazotization, chro-
STAT3 Is Required for the gp130-mediated Full Activation of the c-<i>myc</i> Gene
Authors: Nobuo Kiuchi, Koichi Nakajima, Makoto Ichiba, Toshiyuki Fukada, Masahiro Narimatsu, Katsunori Mizuno, Masahiko Hibi, Toshio Hirano
Journal: The Journal of Experimental Medicine (1999)

The signal transducers and activators of transcription (STAT) family members have been implicated in regulating the growth, differentiation, and death of normal and transformed cells in response to either extracellular stimuli, including cytokines and growth factors, or intracellular tyrosine kinases. c-myc expression is coordinately regulated by multiple signals in these diverse cellular responses. We show that STAT3 mostly mediates the rapid activation of the c-myc gene upon stimulation of the interleukin (IL)-6 receptor or gp130, a signal transducing subunit of the receptor complexes for the IL-6 cytokine family. STAT3 does so most likely by binding to cis-regulatory region(s) of the c-myc gene. We show that STAT3 binds to a region overlapping with the E2F site in the c-myc promoter and this site is critical for the c-myc gene promoter– driven transcriptional activation by IL-6 or gp130 signals. This is the first identification of the linkage between a member of the STAT family and the c-myc gene activation, and also explains how the IL-6 family of cytokines is capable of inducing the expression of the c-myc gene.
Medical School Admissions
Authors: Leon G. Smith
Journal: JAMA (1977)

<h3>To the Editor.—</h3> The article on the medical school admissions dilemma by Frank J. Ramsay, PhD, (237:1093, 1977) recapitulates the problems of the admissions committee in choosing the future physicians of America. As a member of admissions committees for many years, I found it an impossible task, for most of the students were too good to turn down. Most schools use the criterion that those with the best grade point averages have the best chances. Indeed, most systems are designed to review the 4.0 averages first and then move gradually down the scale, with the students having 3.3 averages rarely getting into schools on the East coast. Now it is almost up to 3.5 or 3.6, with Medical College Admissions Test scores up to 600 for some who do not make it. I believe our methods are not good. We rely a great deal on the school's evaluations and the
The Loss of Adipokine Genes in the Chicken Genome and Implications for Insulin Metabolism
Authors: Nataša Đaković, Morgane Térézol, Frédérique Pitel, Virginie Maillard, Sébastien Elis, Sophie Leroux, Sandrine Lagarrigue, Florence Gondret, Christophe Klopp, Elisabeth Baeza, Michel J. Duclos, Hugues Roest Crollius, Philippe Monget
Journal: Molecular Biology and Evolution (2014)

Gene loss is one of the main drivers in the evolution of genomes and species. The demonstration that a gene has been lost by pseudogenization is truly complete when one finds the pseudogene in the orthologous genomic region with respect to active genes in other species. In some cases, the identification of such orthologous loci is not possible because of chromosomal rearrangements or if the gene of interest has not yet been sequenced. This question is particularly important in the case of birds because the genomes of avian species possess only about 15,000 predicted genes, in comparison with 20,000 in mammals. Yet, gene loss raises the question of which functions are affected by the changes in gene counts. We describe a systematic approach that makes it possible to demonstrate gene loss in the chicken genome even if a pseudogene has not been found. By using phylogenetic and synteny analysis in vertebrates, genome-wide comparisons between the chicken genome and expressed sequence tags, RNAseq data analysis, statistical analysis of the chicken genome, and radiation hybrid mapping, we show that resistin, TNFα, and PAI-1 (SERPINE1), three genes encoding adipokines inhibiting insulin sensitivity, have been lost in chicken and zebra finch genomes. Moreover, omentin, a gene encoding an adipokine that enhances insulin sensitivity, has also been lost in the chicken genome. Overall, only one adipokine inhibiting insulin sensitivity and five adipokines enhancing insulin sensitivity are still present in the chicken genome. These genetic differences between mammals and chicken, given the functions of the genes in mammals, would have dramatic consequences on chicken endocrinology, leading to novel equilibriums especially in the regulation of energy metabolism, insulin sensitivity, as well as appetite and reproduction.