tbuckley/cabot-search huggingface dataset:
Oxidative stress and dysfunctional NRF2 underlie pachyonychia congenita phenotypes
Authors: Michelle L. Kerns, Jill M.C. Hakim, Rosemary G. Lu, Yajuan Guo, Andreas Berroth, Roger L. Kaspar, Pierre A. Coulombe
Journal: Journal of Clinical Investigation (2016)

Palmoplantar keratoderma (PPK) are debilitating lesions that arise in individuals with pachyonychia congenita (PC) and feature upregulation of danger-associated molecular patterns and skin barrier regulators. The defining features of PC-associated PPK are reproduced in mice null for keratin 16 (Krt16), which is commonly mutated in PC patients. Here, we have shown that PPK onset is preceded by oxidative stress in footpad skin of Krt16–/– mice and correlates with an inability of keratinocytes to sustain nuclear factor erythroid–derived 2 related factor 2–dependent (NRF2-dependent) synthesis of the cellular antioxidant glutathione (GSH). Additionally, examination of plantar skin biopsies from individuals with PC confirmed the presence of high levels of hypophosphorylated NRF2 in lesional tissue. In Krt16–/– mice, genetic ablation of Nrf2 worsened spontaneous skin lesions and accelerated PPK development in footpad skin. Hypoactivity of NRF2 in Krt16–/– footpad skin correlated with decreased levels or activity of upstream NRF2 activators, including PKCδ, receptor for activated C kinase 1 (RACK1), and p21. Topical application of the NRF2 activator sulforaphane to the footpad of Krt16–/– mice prevented the development of PPK and normalized redox balance via regeneration of GSH from existing cellular pools. Together, these findings point to oxidative stress and dysfunctional NRF2 as contributors to PPK pathogenesis, identify K16 as a regulator of NRF2 activation, and suggest that pharmacological activation of NRF2 should be further explored for PC treatment.
Abstract 4713: Targeting the mitochondria for the treatment of MLH1-deficient disease
Authors: Sukaina Rashid, Gemma Bridge, Zhi Yao, Gyorgy Szabadkai, Sarah A. Martin
Journal: Cancer Research (2015)

Abstract The DNA Mismatch repair (MMR) pathway is responsible for the repair of base-base mismatches and insertion/deletion loops that arise during DNA replication. MMR deficiency is currently estimated to be present in 15-17% of colorectal cancer cases and 30% of endometrial cancers. MLH1 is one of the key proteins involved in the MMR pathway. MMR deficient tumours are often resistant to standard chemotherapies, therefore there is a critical need to identify new therapeutic strategies to treat MMR deficient disease. We have performed synthetic lethal compound and RNAi screens to identify potential therapeutic targets for the treatment of MLH1 deficient tumours. Strikingly, upon analysis, a number of the hit compounds have been shown to target mitochondrial function. Our previous work has shown that MLH1 can localize to the mitochondria and silencing of the mitochondrial genes, POLG and PINK1 are synthetically lethal with MLH1 deficiency. We demonstrate that MLH1 deficient tumours are synthetically lethal with mitochondrial targeted agents (Menadione, Parthenolide) which are known to induce reactive oxygen species and cause oxidative stress as one of their main mechanisms of action. Upon functional analysis we show that loss of MLH1 is associated with a reduction in Complex I activity, reduced basal oxygen consumption rate, reduced spare respiratory capacity and reactive mitochondrial biogenesis (upregulation of pgc1β), suggesting that mitochondrial function is deregulated upon loss of MLH1. Taken together, our results thus far suggest that targeting the mitochondria may be a potential therapeutic strategy for the treatment of MLH1 deficient disease. Citation Format: Sukaina Rashid, Gemma Bridge, Zhi Yao, Gyorgy Szabadkai, Sarah A. Martin. Targeting the mitochondria for the treatment of MLH1-deficient disease. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4713. doi:10.1158/1538-7445.AM2015-4713
Presence of Activated T-Cells With a T8+ M1+ Leu 7+ Surface Phenotype in Invaded Lymph Nodes From Patients With Solid Tumors23
Authors: Federico Cozzolino, Maria Torcia, Emanuela Castigli, Cesare Selli, Rosanna Giordani, Anna Maria Carossino, Massimo Squadrelli, Mario Cagnoni, Vito Pistoia, Manlio Ferrarini
Journal: JNCI Journal of the National Cancer Institute (1986)

Journal Article Presence of Activated T-Cells With a T8+ M1+ Leu 7+ Surface Phenotype in Invaded Lymph Nodes From Patients With Solid Tumors Get access Federico Cozzolino, Federico Cozzolino Search for other works by this author on: Oxford Academic PubMed Google Scholar Maria Torcia, Maria Torcia Search for other works by this author on: Oxford Academic PubMed Google Scholar Emanuela Castigli, Emanuela Castigli Search for other works by this author on: Oxford Academic PubMed Google Scholar Cesare Selli, Cesare Selli Search for other works by this author on: Oxford Academic PubMed Google Scholar Rosanna Giordani, Rosanna Giordani Search for other works by this author on: Oxford Academic PubMed Google Scholar Anna Maria Carossino, Anna Maria Carossino Search for other works by this author on: Oxford Academic PubMed Google Scholar Massimo Squadrelli, Massimo Squadrelli Search for other works by this author on: Oxford Academic PubMed Google Scholar Mario Cagnoni, Mario Cagnoni Search for other works by this author on: Oxford Academic PubMed Google Scholar Vito Pistoia, Vito Pistoia Search for other works by this author on: Oxford Academic PubMed Google Scholar Manlio Ferrarini Manlio Ferrarini Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 77, Issue 3, September 1986, Pages 637–641, https://doi.org/10.1093/jnci/77.3.637 Published: 01 September 1986 Article history Received: 29 July 1985 Revision received: 04 April 1986 Accepted: 28 May 1986 Published: 01 September 1986
Impairment of dendritic cell functions in patients with adaptor protein-3 complex deficiency
Authors: Alberto Prandini, Valentina Salvi, Francesca Colombo, Daniele Moratto, Luisa Lorenzi, William Vermi, Maria Antonia De Francesco, Lucia Dora Notarangelo, Fulvio Porta, Alessandro Plebani, Fabio Facchetti, Silvano Sozzani, Raffaele Badolato
Journal: Blood (2016)
Trends in the Use of Guideline-Directed Therapies Among Dialysis Patients Hospitalized With Systolic Heart Failure
Authors: Ambarish Pandey, Harsh Golwala, Adam D. DeVore, Di Lu, George Madden, Deepak L. Bhatt, Phillip J. Schulte, Paul A. Heidenreich, Clyde W. Yancy, Adrian F. Hernandez, Gregg C. Fonarow
Journal: JACC Heart Failure (2016)
Unmasking a Role for Noninvasive Ventilation in Early Acute Respiratory Distress Syndrome
Authors: Jeremy R. Beitler, Robert L. Owens, Atul Malhotra
Journal: JAMA (2016)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
Case 12-1977
Authors: George P. Canellos, John C. Long, Ann M. Dvorak
Journal: New England Journal of Medicine (1977)

Presentation of CaseA 14-year-old boy was admitted to the hospital because of fever, lymphadenopathy and skin lesions.He was in excellent health until six weeks previously, when he began to experience increasing fatigue while working after school. Four weeks before entry he became anorectic, with a rise of the temperature to 39.9°C. The fever persisted, and one week later he noticed swelling in the left cervical region. His weight had diminished by 3 kg. Three weeks before admission he entered another hospital, where examination disclosed that he appeared ill, with a cough that was occasionally productive of small amounts . . .
Many people receive suboptimal care after myocardial infarction, research shows
Authors: Jacqui Wise
Journal: BMJ (2016)

Nearly 33 000 deaths could have been avoided in England and Wales from 2003 to 2013 if patients had received better follow-up care after a myocardial infarction, say researchers.1

The findings, published in the European Heart Journal: Acute Cardiovascular Care , showed that most people hospitalised with non-ST elevation myocardial infarction (NSTEMI), the most common type, missed out on at least one recommended intervention.

Chris Gale, study leader and associate professor of cardiovascular health sciences at the Leeds Institute of Cardiovascular and Metabolic Medicine, said, “What we’ve highlighted here is the unacceptable deficit in the care being given to people after they’ve had an NSTEMI heart attack. We calculate that roughly one patient per month …
Broadly Neutralizing Antibodies to HIV and Their Role in Vaccine Design
Authors: Dennis R. Burton, Lars Hangartner
Journal: Annual Review of Immunology (2016)

HIV employs multiple means to evade the humoral immune response, particularly the elicitation of and recognition by broadly neutralizing antibodies (bnAbs). Such antibodies can act antivirally against a wide spectrum of viruses by targeting relatively conserved regions on the surface HIV envelope trimer spike. Elicitation of and recognition by bnAbs are hindered by the arrangement of spikes on virions and the relatively difficult access to bnAb epitopes on spikes, including the proximity of variable regions and a high density of glycans. Yet, in a small proportion of HIV-infected individuals, potent bnAb responses do develop, and isolation of the corresponding monoclonal antibodies has been facilitated by identification of favorable donors with potent bnAb sera and by development of improved methods for human antibody generation. Molecular studies of recombinant Env trimers, alone and in interaction with bnAbs, are providing new insights that are fueling the development and testing of promising immunogens aimed at the elicitation of bnAbs.
Partitioning-Defective 1a/b Depletion Impairs Glomerular and Proximal Tubule Development
Authors: Oleh Akchurin, Zhongfang Du, Nadira Ramkellawan, Vidhi Dalal, Seung Hyeok Han, James Pullman, Anne Müsch, Katalin Susztak, Kimberly J. Reidy
Journal: Journal of the American Society of Nephrology (2016)

The kidney is a highly polarized epithelial organ that develops from undifferentiated mesenchyme, although the mechanisms that regulate the development of renal epithelial polarity are incompletely understood. Partitioning-defective 1 (Par1) proteins have been implicated in cell polarity and epithelial morphogenesis; however, the role of these proteins in the developing kidney has not been established. Therefore, we studied the contribution of Par1a/b to renal epithelial development. We examined the renal phenotype of newborn compound mutant mice carrying only one allele of Par1a or Par1b. Loss of three out of four Par1a/b alleles resulted in severe renal hypoplasia, associated with impaired ureteric bud branching. Compared with kidneys of newborn control littermates, kidneys of newborn mutant mice exhibited dilated proximal tubules and immature glomeruli, and the renal proximal tubular epithelia lacked proper localization of adhesion complexes. Furthermore, Par1a/b mutants expressed low levels of renal Notch ligand Jag1, activated Notch2, and Notch effecter Hes1. Together, these data demonstrate that Par1a/b has a key role in glomerular and proximal tubule development, likely via modulation of Notch signaling.
IADPSG and WHO 2013 Gestational Diabetes Mellitus Criteria Identify Obese Women With Marked Insulin Resistance in Early Pregnancy
Authors: Jürgen Harreiter, David Simmons, Gernot Desoye, Rosa Corcoy, Juan M. Adelantado, Roland Devlieger, Andre van Assche, Sander Galjaard, Peter Damm, Elisabeth R. Mathiesen, Dorte M. Jensen, Lise Lotte T. Andersen, Fidelma Dunne, Annunziata Lapolla, Maria G. Dalfra, Alessandra Bertolotto, Urzula Mantaj, Ewa Wender-Ozegowska, Agnieszka Zawiejska, David Hill, Judith G.M. Jelsma, Frank J. Snoek, Christof Worda, Dagmar Bancher-Todesca, Mireille N.M. van Poppel, Alexandra Kautzky-Willer
Journal: Diabetes Care (2016)

Implementation of the International Association of Diabetes and Pregnancy Study Groups (IADPSG) and the World Health Organization 2013 (WHO 2013) recommendations leads to an increased prevalence of gestational diabetes mellitus (GDM) due to more stringent criteria and early screening of women at high risk for diabetes in pregnancy (DIP) (1,2). IADPSG members now recommend that their GDM criteria should not be used in early pregnancy but have not provided alternative criteria (3). We have compared the characteristics of overweight/obese women early in pregnancy, with and without GDM using the new criteria, to assess whether those testing positive are metabolically distinct.

Pregnant women with a BMI ≥29.0 kg/m2 underwent a 75-g oral glucose tolerance test in early pregnancy as part of enrollment into the DALI (Vitamin D And Lifestyle Intervention for GDM prevention) pilot and lifestyle Pan-European multicenter trials (4). GDM and DIP were diagnosed using WHO 2013 criteria.

A high rate of GDM (237/1,035 or 22.9%: DIP 0.5%; total hyperglycemia in early pregnancy 23.4%) was found at a …
Case 10-1971
Authors: Richard C. Cabot, Benjamin Castleman, Betty U. McNeely, William H. Baker, Benjamin Castleman
Journal: New England Journal of Medicine (1971)

Presentation of Case First admission. A 37-year-old man was admitted to the hospital for treatment of psoriasis.For six years he had had psoriasis, which had been treated with multiple medications and had occasioned five admissions to the hospital. Four months before entry there was the onset of weakness of the arms and legs, dyspnea and a chronic cough productive of yellowish-white sputum.He smoked one and a half packages of cigarettes daily and consumed seven or eight drinks of whiskey daily. Sixteen years previously he had worked in a tuberculosis sanatorium for several months; a tuberculin skin test . . .
Effect of Genetic Profiling on Prediction of Therapeutic Resistance and Survival in Adult Acute Myeloid Leukemia
Authors: Roland B. Walter, Megan Othus, Elisabeth M. Paietta, Janis Racevskis, Hugo F Fernandez, Ju-Whei Lee, Zhuoxin Sun, Martin S. Tallman, Jay P. Patel, Mithat Gönen, Omar Abdel-Wahab, Ross L Levine, Elihu H. Estey
Journal: Blood (2014)
Positron Emission Tomography Scans Can Detect Radiographically Occult Lung Cancer in the Central Airways
Authors: Gerarda J.M. Herder, Roderik H.J. Breuer, Emile F.I. Comans, Elle K.J. Risse, Johan C. van Mourik, Pieter E. Postmus, Tom G. Sutedja
Journal: Journal of Clinical Oncology (2001)

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2001.19.22.4271 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11709574 Positron Emission Tomography Scans Can Detect Radiographically Occult Lung Cancer in the Central Airways Gerarda J.M. HerderxGerarda J.M. HerderSearch for articles by this author , Roderik H.J. BreuerxRoderik H.J. BreuerSearch for articles by this author , Emile F.I. ComansxEmile F.I. ComansSearch for articles by this author , Elle K.J. RissexElle K.J. RisseSearch for articles by this author , Johan C. van MourikxJohan C. van MourikSearch for articles by this author , Pieter E. PostmusxPieter E. PostmusSearch for articles by this author , Tom G. SutedjaxTom G. SutedjaSearch for articles by this author Show More Vrije Universiteit Medical Center, Amsterdam, the Netherlands https://doi.org/10.1200/JCO.2001.19.22.4271 First Page Full Text PDF Figures and Tables © 2001 by American Society of Clinical Oncology
Isotype Matched Paired Immunoglobulin Suppression Identifies High Risk Multiple Myeloma Patients and Is Independent Of Bone Marrow Infiltration Suggesting Significant Variability In The HLC Matched Pair Suppressive Activity Of Individual Myeloma Clones
Authors: Heinz Ludwig, Dejan Milosavljevic, Philip Young, Niklas Zojer, Stephen Harding
Journal: Blood (2013)
JAK2V617F complete molecular remission in polycythemia vera/essential thrombocythemia patients treated with ruxolitinib
Authors: Lisa Pieri, Alessandro Pancrazzi, Annalisa Pacilli, Claudia Rabuzzi, Giada Rotunno, Tiziana Fanelli, Paola Guglielmelli, Rajmonda Fjerza, Chiara Paoli, Srdan Verstovsek, Alessandro M. Vannucchi
Journal: Blood (2015)
THU0182 Single Dose? Multiple Doses? Comparison of MTX-PG Concentration, Safety and Efficacy in Patients with Rheumadoid Arthritis Between Single- and Divided Dosage Regimens
Authors: A. Ihata, K. Kobayashi, A. Osada, H. Sakuma, F. Tsuji, T. Yoshimura, C. Setoguchi, M. Okamoto, S. Nagaoka
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Methotrexate (MTX) has been well-known anchor drug for rheumatoid arthritis (RA), however, dose regimen varies and it depends on countries. The divided dosage of MTX was frequently prescribed in Japan, however, the differences of safety and efficacy between divided and single dose regimens were not fully examined. <h3>Objectives</h3> We conducted a preliminary study for RA patients to compare the safety, efficacy profile and MTX-polyglutamates (PGs) concentration between single- and divided dosage regimens. <h3>Methods</h3> Single-center Random Controlled Trial was designed. Thirty-one patients who had been insufficiently controlled by MTX (8 mg/week) were randomly assigned to 2 groups (single dose regimen/week: 15 patients; three-dose regimen/week: 16 patients). MTX dose of all patients was allowed to increase up to 16 mg/week. Safety and efficacy parameters (adverse events, the elevation of liver function tests (LFTs), WBC counts and DAS28 were monitored at baseline, 4, 8, 12 and 19 weeks. MTX-PGs in red blood cells were also detected by LC-MS/MS at same interval. <h3>Results</h3> There were no significant differences in the average of age (66.3±9.2yr), disease duration (5.8yr), and baseline DAS28(CPR) (2.84±0.98) between two groups. There were also no differences in the improvement of DAS28(CPR) between two groups (-0.95±1.66 vs -0.75±1.09 respectively) and weekly MTX dose (11.5±1.6mg/week vs 11.4±1.4mg/week). Three adverse events were observed only in 3-dose regimen group (18.8%, increase in LTFs). The remarkable difference was observed in MTX-PGs, 3-dose regimen group showed significantly higher concentration of MTX-PG1+2 than single-dose group. On the other hand, 3-doses regimen group showed slight lower MTX-PG4+5 than single-dose regimen group, and there was no difference in MTX-PG3. <h3>Conclusions</h3> The efficacy did not show significant difference between two groups. Liver function may be affected by concentration of MTX-PG1+2, which elevated in divided dosage regimen group. Further investigation is required in a larger population. <h3>Acknowledgements</h3> Clinical registration: UMIN000012473 <h3>Disclosure of Interest</h3> A. Ihata: None declared, K. Kobayashi: None declared, A. Osada: None declared, H. Sakuma: None declared, F. Tsuji Employee of: Santen Pharmaceutical. CO.,Ltd., T. Yoshimura Employee of: Santen Pharmaceutical. CO.,Ltd., C. Setoguchi Employee of: Santen Pharmaceutical. CO.,Ltd., M. Okamoto Employee of: Santen Pharmaceutical. CO.,Ltd., S. Nagaoka: None declared
Thrombophilic status may predict prognosis in patients with metastatic BRAFV600-mutated melanoma who are receiving BRAF inhibitors
Authors: Anna Falanga, Marina Marchetti, Daniela Massi, Barbara Merelli, Cristina Verzeroli, Laura Russo, Eliana Rulli, Carlo Tondini, Lorenzo Legramandi, Romina Nassini, Cristian Scatena, Francesco De Logu, Laura Cattaneo, Mario Mandalà
Journal: Journal of the American Academy of Dermatology (2016)
Evaluation of Human Circulating Tumor Cells By Htert-Specific Replication-Selective Adenovirus in Soft Tissue Sarcoma
Authors: T. Matsuo, N. Hamada, H. Hachisuka, T. Hamasaki, Y. Izuta, R. Mori, S. Okawa, T. Harada, Y. Urata, T. Sugita
Journal: Annals of Oncology (2014)
Heterogeneous Contribution of Insulin Sensitivity and Secretion Defects to Gestational Diabetes Mellitus
Authors: Camille E. Powe, Catherine Allard, Marie-Claude Battista, Myriam Doyon, Luigi Bouchard, Jeffrey L. Ecker, Patrice Perron, Jose C. Florez, Ravi Thadhani, Marie-France Hivert
Journal: Diabetes Care (2016)

OBJECTIVE To characterize physiologic subtypes of gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS Insulin sensitivity and secretion were estimated in 809 women at 24–30 weeks' gestation, using oral glucose tolerance test–based indices. In women with GDM (8.3%), defects in insulin sensitivity or secretion were defined below the 25th percentile in women with normal glucose tolerance (NGT). GDM subtypes were defined based on the defect(s) present. RESULTS Relative to women with NGT, women with predominant insulin sensitivity defects (51% of GDM) had higher BMI and fasting glucose, larger infants (birth weight z score 0.57 [−0.01 to 1.37] vs. 0.03 [−0.53 to 0.52], P = 0.001), and greater risk of GDM-associated adverse outcomes (57.6 vs. 28.2%, P = 0.003); differences were independent of BMI. Women with predominant insulin secretion defects (30% of GDM) had BMI, fasting glucose, infant birth weights, and risk of adverse outcomes similar to those in women with NGT. CONCLUSIONS Heterogeneity of physiologic processes underlying hyperglycemia exists among women with GDM. GDM with impaired insulin sensitivity confers a greater risk of adverse outcomes.