tbuckley/cabot-search huggingface dataset:
Oxaliplatin resistant cells possess a mutant p53 that is confined to the cytoplasm
Authors: Edina Komlodi-Pasztor, Shana Trostel, Bob Murphy, Tito Fojo
Journal: Cancer Research (2008)

2785   Cancer cells often possess an impaired p53 signaling pathway and either a  de novo  or an acquired drug resistance. Translocation of p53 to the nucleus is known to occur following DNA damage and is thought to be mediated by at least one of three putative nuclear localization signals designated NLSI, NLSII, NLSIII. NLSI mediates p53 translocation while NLSII and NLSIII appear to be optimal for formation of a fully functional complex. KB-3.1 human cervical carcinoma cells selected for resistance to oxaliplatin (KB-OX20 and KB-OX60 and KB-OX80) were found to have increased levels of p53 protein and a deletion of a single nucleotide in the sequence encoding for amino acid 382, part of the NLSIII region. This mutation resulted in a frame-shift and a protein of 420 amino acids detectable by immunoblot (p53 420 ). We determined by fractionation of nuclear and cytoplasmic compartments that the p53 420  in the oxaliplatin resistant cells remained in the cytoplasm even after treatment with adriamycin. We sought to investigate possible explanations for the cytoplasmic accumulation of p53 420  by examining cytoplasmic trafficking, nuclear import and nuclear export. We found that p53 420  could tetramerize and associate with dynein, two requirements for the trafficking of p53 on microtubules prior to nuclear translocation. We next showed that blocking the function of Exportin1 by treatment of the oxaliplatin resistant cells with Leptomycin B had no effect on the cytoplasmic levels of p53 420  making it unlikely that augmented export explains the cytoplasmic accumulation. To clarify the role of the NLSIII in the cytoplasmic preference of p53 420 , we engineered seven p53 mutants: K381T, K382T, K381T/K382T, p53 frame shift 382-393 , p53 420 , NLSIIe (p53 K372T/K373T ), NLSII-IIIe(p53 K372T/K373T,K381T/K382T ) and compared their behavior to wild type p53 in transfected cells which are p53 null (PC3, H1299). Subcellular fractionation showed physiological distribution of the mutated proteins between the cytoplasm and the nucleus. We conclude that 1) mutation of amino acid 382 results in cytoplasmic localization of p53 and a non-functional p53 status, 2) p53 420  is able to tetramerize and bind to dynein, 3) Neither NSL II nor NLSIII are essential for p53 nuclear localization. Ongoing studies will examine the interaction between p53 and importin as an explanation for the cytoplasmic retention of p53.
USE OF THIOURACIL IN THE PREOPERATIVE PREPARATION OF PATIENTS WITH SEVERE HYPERTHYROIDISM
Authors: Elmer C. Bartels
Journal: Annals of Internal Medicine (1945)

Article1 March 1945USE OF THIOURACIL IN THE PREOPERATIVE PREPARATION OF PATIENTS WITH SEVERE HYPERTHYROIDISMELMER C. BARTELS, M.D., F.A.C.P.ELMER C. BARTELS, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-22-3-365 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptA preliminary report on the use of thiouracil in the preoperative management of 12 toxic hyperthyroid patients at the Lahey Clinic was published in May 1944.1We were convinced of the effectiveness of this drug and since then we have continued to use thiouracil as a preoperative therapeutic agent in a total of 64 patients. The patients treated were severely toxic and would have incurred more than the average surgical risk if they had been prepared in the usual manner by administration of Lugol's solution. Most of these patients would have required multiple stage operations, but with thiouracil most went...Bibliography1. BARTELS EC: Thiouracil: Its use in the preoperative management of severe hyperthyroidism. Preliminary report, Jr. Am. Med. Assoc., 1944, cxxv, 24-26. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: The Lahey Clinic Boston, Massachusetts*Received for publication December 12, 1944.†The thiouracil was supplied by Dr. B. W. Carey, Lederle Laboratories, Inc., Pearl River, New York. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byPerioperative management of the thyrotoxic patientThe Management of HyperthyroidismTreatment of hyperthyroidism and heart failure with methylthiouracilTHIOURACIL AND THYROTOXICOSISThiouracil: Remission or relapse of hyperthyroidism after discontinuing its useSurgery of the Thyroid GlandThe Biology of Antithyroid AgentsTHIOURACIL IN GOITRE 1 March 1945Volume 22, Issue 3Page: 365-372KeywordsDrugsHyperthyroidismRivers ePublished: 1 December 2008 Issue Published: 1 March 1945 PDF downloadLoading ...
Abstract 15985: Liver Transplantation Does Not Reverse Cirrhotic Cardiomyopathy
Authors: Ahmed Ibrahim, Andres Schuster, Abraham Sonny, Jacek B Cywinski, Wael A Jaber
Journal: Circulation (2014)

Background: Cirrhotic cardiomyopathy (CCM), a frequent finding in patients with end stage liver disease (ESLD), presents with diastolic dysfunction (DD), hyperdynamic state, and prolonged corrected QT interval (QTc). Liver transplantation (LT) is thought to be the only treatment for CCM. The aim of our study is to assess the reversibility of CCM after LT. Methods: We retrospectively assessed the data of 82 patients collected from the Cleveland Clinic LT database between the years 2007 to 2008 that had an echocardiogram (TTE) and an EKG pre and post-LT. The clinical characteristics were obtained from the electronic record and all EKG and TTE were analyzed by 2 independent observers in the standard manner. The frequency of CCM criteria in ESLD patients was compared with 74 matched controls with no history of liver disease. Results: The median age of patients was 57 years (IQR 19 to 72), 72% were males and 85% were Caucasian. The median time between LT and post-LT testing was 4 years (IQR 0.1 to 6). Compared to controls, patients with ESLD had a longer QTc (449 ±25 vs. 430 ±23 msec; p&lt;0.001) and higher cardiac output (CO) (5.9 ±1.8 vs. 4.8 ±1.1 L/min; p=0.001), left atrial (LA) volume index (33 ±10 vs. 25 ±7 ml/m 2 ; p&lt;0.001), left ventricular (LV) end diastolic volume index (60±14 vs. 49±12 ml/m 2 ; p=0.001 and mitral valve inflow velocity (E) (85 ±23 vs. 75 ±20 cm/sec; p=0.003). Post-LT, there was significant increase in LV mass index (LVMI) (107±38 vs 91±24 gm/ m 2 ; p=0.002) and prevalence of DD (75% vs. 47%; p&lt;0.001) but no difference in CO, LA and LV volumes. In contrast, there was a significant reduction of QTc (449 ±25 to 440 ±28 msec; p=0.04). Conclusions: In our study, patients with ESLD had a higher QTc and CO than matched controls. Post-LT, only QTc showed a significant improvement.
Psychotherapy in community methadone programs: a validation study
Authors: G E Woody, A T McLellan, L Luborsky, C P O'Brien
Journal: American Journal of Psychiatry (1995)

The authors tested the efficacy of individual psychotherapy in the rehabilitation counseling of psychiatrically symptomatic opiate-dependent patients during methadone maintenance treatment in community programs.Volunteers in three community programs were randomly assigned to 24 weeks of counseling plus supplemental drug counseling or to counseling plus supportive-expressive psychotherapy. Follow-ups were done 1 and 6 months after treatment ended. A total of 84 subjects were evaluated at both follow-up points.During the study the patients receiving supportive-expressive psychotherapy and those receiving drug counseling had similar proportions of opiate-positive urine samples, but the patients receiving supportive-expressive psychotherapy had fewer cocaine-positive urine samples and required lower doses of methadone. One month after the extra therapy ended both groups had made significant gains, but there were no significant differences between groups. By 6-month follow-up many of the gains made by the drug counseling patients had diminished, whereas most of the gains made by the patients who received supportive-expressive psychotherapy remained or were still evident; many significant differences emerged, all favoring supportive-expressive psychotherapy.Psychotherapy can be delivered to psychiatrically impaired patients in community methadone programs. Additional counseling is associated with early benefits comparable to those from psychotherapy, but these gains are not sustained. The gains associated with psychotherapy persist and in some cases strengthen for at least 6 months after the end of therapy.
Headaches after diagnostic dural punctures
Authors: M G Serpell
Journal: BMJ (2000)

<h3>Abstract</h3> We have analyzed gene transcription, protein expression, and enzymatic activity of the Ca<sup>2+</sup>-transporting ATPase (SERCA) in horse gluteal muscle. Horses are bred for peak athletic performance but exhibit a high incidence of exertional rhabdomyolysis, with myosolic Ca<sup>2+</sup> suggested as a correlative linkage. To assess Ca<sup>2+</sup> regulation in horse gluteus, we developed an improved protocol for isolating horse sarcoplasmic reticulum (SR) vesicles. RNA-seq and immunoblotting determined that the <i>ATP2A1</i> gene (protein product SERCA1) is the predominant Ca<sup>2+</sup>-ATPase expressed in horse gluteus, as in rabbit muscle. Gene expression was assessed for four regulatory peptides of SERCA, finding that sarcolipin (<i>SLN</i>) is the predominant regulatory peptide transcript expressed in horse gluteus, as in rabbit muscle. Surprisingly, the RNA transcription ratio of <i>SLN</i>-to-<i>ATP2A1</i> in horse gluteus is an order of magnitude higher than in rabbit muscle, but conversely, the protein expression ratio of SLN-to-SERCA1 in horse gluteus is an order of magnitude lower than in rabbit. Thus, the <i>SLN</i> gene is not translated to a stable protein in horse gluteus, yet the supra-high level of <i>SLN</i> RNA suggests a non-coding role. Gel-stain analysis revealed that horse SR expresses calsequestrin (CASQ) protein abundantly, with a CASQ-to-SERCA ratio ∼3-fold greater than rabbit SR. The Ca<sup>2+</sup> transport rate of horse SR vesicles is ∼2-fold greater than rabbit SR, suggesting horse myocytes have enhanced luminal Ca<sup>2+</sup> stores that increase intracellular Ca<sup>2+</sup> release and muscular performance. The absence of SLN inhibition of SERCA and the abundant expression of CASQ may potentiate horse muscle contractility and susceptibility to exertional rhabdomyolysis.
Cutaneous lymphangioma as a diagnostic clue for thoracic lymphangiomatosis
Authors: B.G. Bae, J.E. Do, Y.J. Kim, S. Noh, S.H. Oh
Journal: British Journal of Dermatology (2010)

Journal Article Cutaneous lymphangioma as a diagnostic clue for thoracic lymphangiomatosis Get access B.G. Bae, B.G. Bae Department of Dermatology and Cutaneous Biology Research Institute and Search for other works by this author on: Oxford Academic Google Scholar J.E. Do, J.E. Do Department of Dermatology and Cutaneous Biology Research Institute and Search for other works by this author on: Oxford Academic Google Scholar Y.J. Kim, Y.J. Kim Department of Radiology, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, Korea Search for other works by this author on: Oxford Academic Google Scholar S. Noh, S. Noh Department of Dermatology and Cutaneous Biology Research Institute and Search for other works by this author on: Oxford Academic Google Scholar S.H. Oh S.H. Oh Department of Dermatology and Cutaneous Biology Research Institute and Correspondence: Sang Ho Oh. E‐mail: oddung93@yuhs.ac Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 163, Issue 4, 1 October 2010, Pages 875–877, https://doi.org/10.1111/j.1365-2133.2010.09869.x Published: 01 October 2010
Normal Is a Place I Visit
Authors: Suzanne J Fiala
Journal: JAMA (2004)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
TUBERCULOID LEPROSY: A CASE REPORT
Authors: Tibor J. Greenwalt
Journal: Annals of Internal Medicine (1945)

Case Reports1 February 1945TUBERCULOID LEPROSY: A CASE REPORTTIBOR J. GREENWALTTIBOR J. GREENWALTSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-22-2-282 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAt the present time, there seems to be a likelihood that we shall see more cases of leprosy in this country than ever before. It is important to be on the alert for such cases at all times and more so during these times of global warfare and travel. Contrary to what is commonly believed, this disease is not uncommon in the United States. Most of the cases have been seen in the Gulf Coast area, namely, Florida, Louisiana, and Texas, although sporadic examples of the disease have been reported from the whole country.1, 2There is a general misconception...Bibliography1. FRAZIER CN: Leprosy: epidemiology and natural history, Jr. Am. Med. Assoc., 1943, cxxiii, 466. CrossrefGoogle Scholar2. SUTTONSUTTON RLRL: Diseases of the skin, 1939, The C. V. Mosby Company, St. Louis, p. 1015. Google Scholar3. PARDO-CASTELLOTIANT VFR: Leprosy: the correlation of its clinical, pathologic, immunologic and bacteriologic aspects, Jr. Am. Med. Assoc., 1943, cxxi, 1264. CrossrefGoogle Scholar4. MANSON-BAHR PH: Manson's tropical diseases, 1943, The Williams and Wilkins Company, Baltimore, p. 598. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: M. C. A. U. S. Fort Leavenworth, Kansas*Received for publication April 15, 1944. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byTibor Jack Greenwalt: Father of Transfusion MedicineAntibodies, antigens, and anticoagulants: a historical review of a lifetime in transfusion medicine—the Landsteiner Lecture 2004 1 February 1945Volume 22, Issue 2Page: 282-287KeywordsLeprosy ePublished: 1 December 2008 Issue Published: 1 February 1945 PDF downloadLoading ...
Identification of raw and cooked snow crab proteins that elicit IgE reactivity in snow crab processing workers*1
Authors: P. Venkatesh, A. Cartier, L. Horth-Susin, M. Jong, M. Swanson, D. Currie, B.V. Gill, G. Reese, B. Neis, S.B. Lehrer
Journal: Journal of Allergy and Clinical Immunology (2004)
Personal paper: A case of murder and the BMJ
Authors: R. Meadow
Journal: BMJ (2002)

Sally Clark, a 34 year old mother, was convicted in 1999 of the murder of her two sons Christopher, who died at the age of 11 weeks in December 1996, and Harry, who died at the age of 8 weeks in January 1998. Both the children had been previously healthy; they died suddenly in her care, in the evening, at home. Postmortem examinations of both children showed multiple abnormal findings.

After the verdict, the media reported the family's claim that both children had “died of cot death” and that incorrect statistical evidence given at the trial had greatly underestimated the likelihood of recurrence of cot death. The BMJ published an editorial as deficient in its sources as it was sensational in its title.1 It was called “Conviction by mathematical error?” and it ignored the fact that at the trial neither the defence nor any of the expert witnesses advanced the claim that the children's deaths were examples of sudden infant death syndrome. The risk of recurrent sudden infant death syndrome was irrelevant to the conviction.

#### Summary points

Sally Clark appealed against her conviction for murdering her two infant sons

Her appeal was partly based on a claim that misleading evidence was given about the likelihood of two cases of sudden infant death syndrome occurring in the same family

The BMJ published an editorial questioning the statistic and therefore the conviction

None of the medical experts believed the two boys' deaths were examples of sudden infant death syndrome

Statistics about the syndrome were therefore irrelevant to the case

The appeal court upheld the conviction

The trial, at Chester Crown Court, was long, and the fact that both parents were solicitors led to more publicity than usual. Many medical experts were called by both prosecution and defence, including eight pathologists with …
Abstract IA05: Small RNAs reveal nuclear hormone receptor targeting as a novel therapy for melanoma
Authors: Sohail Tavazoie
Journal: Cancer Research (2015)

Abstract In recent years, numerous genes that drive melanoma metastasis or progression of established metastatic melanoma have been identified. The identification of such genes and their associated pathways have revealed insights into the cellular processes involved in these clinically important events. Our laboratory has found that deregulated expression of microRNAs is a major mechanism by which such gene-expression states that enable metastatic progression are achieved in various solid cancers. In melanoma, we have identified 3 microRNAs (miR-1908, miR-199a5p, and miR-199a3p) to be over-expressed in metastatic sub-populations of human melanoma cells. The expression levels of these microRNAs predict metastatic relapse in primary cutaneous melanomas. These microRNAs convergently target the gene ApoE, which through genetic, molecular, pharmacological, and clinical association analyses, we have identified as a robust suppressor of melanoma metastasis and metastatic progression. We have demonstrated pre-clinical proof-of-concept for the therapeutic activation of ApoE through transcriptional engagement of the Liver-X nuclear hormone receptor (LXR). Oral administration of multiple LXR agonists suppressed the growth of primary and metastatic melanoma in mice. Genetic studies revealed that the effects of LXR agonists are mediated through LXRβ, which elicits these effects through ApoE induction in the stromal and tumoral compartments. LXRβ; agonism suppressed progression in immunocompetent, xenograft, patient-derived xenograft, and genetically initiated melanomas. Moreover, LXRβ agonism exhibited combinatorial efficacy with B-Raf inhibitors and anti-CTLA4 immunotherapy. We provide pre-clinical proof-of-concept for therapeutic activation of nuclear hormone receptors in melanoma. Citation Format: Sohail Tavazoie. Small RNAs reveal nuclear hormone receptor targeting as a novel therapy for melanoma. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Melanoma: From Biology to Therapy; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(14 Suppl):Abstract nr IA05.
Abstract 2629: Nintedanib (BIBF-1120) inhibits hepatocellular carcinoma growth independent of angiokinase activity
Authors: Wei-Tien Tai, Chung-Wai Shiau, Yong-Shi Li, Chun-Wei Chang, Jui-Wen Huang, Ting-Ting Hsueh, Kuen-Feng Chen
Journal: Cancer Research (2014)

Abstract Background &amp; Aims: Nintedanib, a triple angiokinase inhibitor, is currently being evaluated against advanced HCC in phase I/II clinical trials. Here, we report the underlying molecular mechanism by which nintedanib (BIBF-1120) induces an anti-HCC effect. Methods: HCC cell lines were treated with nintedanib or its derivative (ΔN) and apoptosis, signal transduction, and phosphatase activity were analyzed. Purified SHP-1 proteins or HCC cells expressing deletion N-SH2 domain or D61A point mutants were used to investigate the potential effect of nintedanib on SHP-1. In vivo efficacy was determined in nude mice with HCC subcutaneous xenografts (n ≥ 8 mice). Results: Nintedanib induced anti-proliferation in HCC cell lines by targeting STAT3. Ectopic STAT3 abolished nintedanib-mediated apoptosis in HCC cells. Nintedanib further activated SHP-1 in purified SHP-1 proteins suggesting that nintedanib directly affects SHP-1 for STAT3 inhibition. HCC cells or recombinant SHP-1 proteins expressing deletion of N-SH2 domain or D61A mutants restored the activity of nintedanib suggesting that the auto-inhibition structure of SHP-1 was relieved by nintedanib. To further elucidate whether the effect of nintedanib on SHP-1 is dependent on its angiokinase inhibition activity, we developed a novel kinase-independent derivative of nintedanib, ΔN. Although ΔN only retained the backbone of nintedanib without kinase activity, ΔN still induced substantial anti-HCC activity in vitro and in vivo by targeting STAT3. Conclusions: Nintedanib induced significant anti-HCC activity independent of angiokinase inhibition activity in a preclinical HCC model by relieving autoinhibition of SHP-1. Our findings provide new mechanistic insight into the inhibition of HCC growth by nintedanib. Citation Format: Wei-Tien Tai, Chung-Wai Shiau, Yong-Shi Li, Chun-Wei Chang, Jui-Wen Huang, Ting-Ting Hsueh, Kuen-Feng Chen. Nintedanib (BIBF-1120) inhibits hepatocellular carcinoma growth independent of angiokinase activity. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2629. doi:10.1158/1538-7445.AM2014-2629
Lesson of the Week: Allopurinol, erythema multiforme, and renal insufficiency
Authors: A Kumar, N Edward, M I White, P W Johnston, G R D Catto
Journal: BMJ (1996)

Allopurinol, a xanthine oxidase inhibitor, has become established as the drug of choice for preventing and treating conditions where there is overproduction of uric acid, such as occurs in gout, uric acid nephro- lithiasis, and polycythaemia vera; during chemotherapy for lymphomas; and in the Lesch-Nyhan syndrome.'Allopurinol may, however, cause a severe, and sometimes fatal, hypersensitivity reaction in patients with pre-existing renal disease.We describe two patients with severe hypersensitivity.In both the syndrome was relapsing and in one ultimately fatal.