tbuckley/cabot-search huggingface dataset:
Fluorescent cobalamin analogs for molecular imaging
Authors: Charles Grissom, Manfai Lee, Shawn Owen
Journal: Cancer Research (2008)

3173  Two new types of optical molecular imaging agents that incorporate the structure of vitamin B12 (cobalamin) have been designed, synthesized, and evaluated. Type-I cobalamin analogs are highly fluorescent in spite of the potential for severe singlet quenching by the corrin ring of cobalamin, whereas type-II cobalamin analogs are designed to fluoresce only after the molecule enters a cancer cell and is processed by a lysosomal protease. In general, cancer cells show an increased avidity for cobalamin and its analogs, as compared to normal cells. The increased uptake of cobalamin by cancer cells can be used to target the delivery of optical markers to cancer cells for in-vivo and ex-vivo diagnostic purposes, and to facilitate the intraoperative identification of tumor micromargins. In type-I fluorescent cobalamin analogs, a rigid linker has been placed between cobalamin and the fluorophore to prevent through-space quenching of the excited singlet state of the pendant fluorophore by the corrin ring of cobalamin. Type-I fluorescent cobalamin conjugates exhibit a higher fluorescent quantum yield than the corresponding conjugate that is constructed by tethering the fluorophore to cobalamin with a flexible linker. Type-II fluorescent cobalamin conjugates feature a flexible dipeptide linker between the corrin ring and the fluorophore. This construct takes advantage of the efficient singlet quenching afforded by the corrin ring to mask the fluorophore until the dipeptide linker is cleaved by a lysosomal protease within the cell, thereby separating the cobalamin and fluorophore moieties and unmasking the fluorophore. Type-I fluorescent cobalamin conjugates with fluorescein, Rhodamine-6G and Cy5 fluorophores have been synthesized, chemically characterized, and tested in vitro and in vivo. Type-II fluorescent cobalamin conjugates have been constructed with Cascade Blue and Cy5 as pendant fluorophores, and a dipeptide linker that is recognized by the intralysosomal enzyme, cathepsin B. Type-I and Type-II fluorescent cobalamin analogs represent two novel classes of optical tumor markers. Each class overcomes the problem of severe fluorescence quenching that limited the investigation of clinical applications of earlier fluorescent cobalamin conjugates.
The Smile
Authors: Megan A. Freeman
Journal: Annals of Internal Medicine (2015)

On Being a Doctor15 December 2015The SmileMegan A. Freeman, MDMegan A. Freeman, MDFrom The University of Texas Health Science Center at San Antonio, San Antonio, Texas.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M15-1331 Audio Reading - “The Smile” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "The Smile," by M.A. Freeman. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail I heard his little grunts and squeaks resonating down the winding acoustics of our upstairs hallway. I walked briskly to the bedside of the chubby, dimpled, squeezable little man a few doors down. As I looked in on him, he did not at first see me. His pale, blue eyes stared longingly at the sleepy air before him, his face tranquil and soft in the peaceful memory of the slumber he had so recently departed. I breathed heavily and watched him, transfixed. He was so little, so innocent, so precious. He saw me, and, amidst the fading darkness and growing ... Author, Article, and Disclosure InformationAffiliations: From The University of Texas Health Science Center at San Antonio, San Antonio, Texas.Corresponding Author: Megan A. Freeman, MD, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229; e-mail, [email protected]edu. PreviousarticleNextarticle Advertisement Audio Reading - “The Smile” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "The Smile," by M.A. Freeman. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 15 December 2015Volume 163, Issue 12Page: 958KeywordsEmotionsFoodHeartInfantsLesionsMemoryPatientsPersonal protective equipmentSmellTicks ePublished: 15 December 2015 Issue Published: 15 December 2015 Copyright & PermissionsCopyright © 2015 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Niche-Based Screening Identifies Novel Small Molecules That Overcome Stromal Effects in Multiple Myeloma
Authors: Shrikanta Chattopadhyay, Alison L. Stewart, Siddhartha Mukherjee, Cherrie Huang, Kimberly A. Hartwell, Peter G. Miller, Leigh Carmody, Rushdia Z. Yusuf, David B. Sykes, Sonia Vallet, Loredana Santo, Diana D. Cirstea, Teru Hideshima, Vladimir Dancik, Jaime Cheah, Edmund Price, Abigail Bracha, Max Majireck, Mahmud Hussain, Shambhavi Singh, Nicola Tolliday, Malcolm A.S. Moore, Andrew M. Stern, Alykhan F Shamji, Benjamin L. Ebert, Todd R. Golub, Noopur Raje, David T. Scadden, Stuart L. Schreiber
Journal: Blood (2012)
A Phase 2 Study of INCB018424, An Oral, Selective JAK1/JAK2 Inhibitor, in Patients with Advanced Polycythemia Vera (PV) and Essential Thrombocythemia (ET) Refractory to Hydroxyurea.
Authors: Srdan Verstovsek, Francesco Passamonti, Alessandro Rambaldi, Giovanni Barosi, Peter Rosen, Richard Levy, Edward C Bradley, Lee Schacter, William M Garrett, Kris Vaddi, Nancy Contel, Elisa Rumi, Elisabetta Gattoni, Mario Cazzola, Hagop Kantarjian, Tiziano Barbui, Alessandro Vannucchi
Journal: Blood (2009)
SP0097 Intracellular MTX Polyglutamates and Clinical Response
Authors: R. de Jonge
Journal: Annals of the Rheumatic Diseases (2016)

Low-dose methotrexate is the cornerstone disease-modifying anti-rheumatic drug in the treatment of patients with rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA). Although MTX levels can be measured easily in plasma, low-dose MTX is rapidly cleared from plasma and is therefore not routinely measured. In contrast, MTX is transported into and retained in cells long after it has been eliminated from plasma. We have developed an LC-MS/MS assay to measure MTX-polyglutamates (MTX-PG) in erythrocytes and measured drug concentrations in three prospective cohort studies in RA and JIA patients. Erythrocyte MTX-PG levels were related to clinical response in all cohorts and hence, could be used for therapeutic drug monitoring of low-dose MTX therapy. Moreover, higher baseline erythrocyte folate was associated with higher erythrocyte MTX-PG accumulation and improved clinical response. Determinants of MTX-PG concentrations were age, polymorphisms in ABC transporters, erythrocyte folate and dosing. <h3>Disclosure of Interest</h3> None declared
Ocular Toxicity of Mitogen-Activated Protein Kinase Inhibitors
Authors: Robert M. J. Purbrick, Olaoluwakitan A. Osunkunle, Denis C. Talbot, Susan M. Downes
Journal: JAMA Oncology (2016)

The Oxford Eye Hospital and the Oxford Experimental Cancer Centre collaborate in monitoring patients in a number of early-phase clinical trials.In this study, we report the ocular toxic effects of 3 different mitogen-activated protein kinase inhibitors (MEKIs) currently at independent stages of clinical development, including ongoing studies.Methods | Forty clinical records of patients enrolled in clinical trials of 3 different MEKIs (including 11, 19, and 10 patients in MEKI trials A, B, and C, respectively) were reviewed from March 16, 2011, to April 25, 2013.Baseline visual acuity and ophthalmic imaging data, including macular optical coherence tomography, relevant ophthalmic and general medical history, evidence of ocular toxic effects in addition to the clinical course, and relevant interventions, were recorded and analyzed.This study was approved by the Oxford Research Ethics Committee.Appropriate written informed consent was obtained from all patients, and data were deidientified.Results | Seven of 40 patients (18%) developed ocular adverse effects.In the MEKI A group, 3 of 11 patients (27%) developed bilateral central serous chorioretinopathy (CSC) (Figure, A and B), which was multifocal in 1 case.In the MEKI B group, 2 of 19 patients (11%) developed ocular adverse effects; 1 patient had a left central retinal vein occlusion (Figure, C), and 1 patient had bilateral, multifocal CSC-like changes.In the MEKI C group, 2 of 10 patients (20%) developed problems; 1 had bilateral, multifocal CSC-like changes (Figure, D), and 1 had a severe increase in intraocular pressure.Figure.Clinical Images From Patients 1, 4, and 6 Normal OCT in both eyes A Left central retinal vein occlusion C Bilateral central serous chorioretinopathy B Bilateral, multifocal central serous chorioretinopathy D A and B, Patient 1 (upper image is the right eye).A, Baseline (normal) macular optical coherence tomogram (OCT); B, 1 day after starting mitogen-activated protein kinase inhibitor (MEKI), the macular OCT shows bilateral central serous chorioretinopathy (CSC)-like changes.C, Patient 4. Color fundus photograph of left eye showing central retinal vein occlusion with dilated, tortuous retinal veins, hemorrhagic optic disc swelling, widespread deep retinal hemorrhages, and macular edema.D, Patient 6 (upper image is the right eye).Macular OCT showing multifocal CSC-like changes.
Association of Liver Iron Concentration Levels with Myocardial T2* Responses in Transfusion-Dependent Thalassemia Major Patients Treated with Deferasirox and Deferoxamine- Extension of Cordelia Study
Authors: Dudley J Pennell, John B Porter, Antonio Piga, Jackie Han, Alexander Vorog, Yesim Aydinok
Journal: Blood (2015)
Multicenter Study Evaluating the Impact of Hypomethylating Agents As Bridging Therapy to Hematopoietic Stem Cell Transplantation in Myelodysplastic Syndromes
Authors: Yundeok Kim, Lee Je Hwang, Inho Kim, Jang Joon Ho, Hyeoung Joon Kim, Soo Jeong Kim, Min Yoo Hong
Journal: Blood (2012)
The Hematopoietic Cell Transplantation Comorbidity Index: No Effect on Outcome of Reduced-Intensity Allografts.
Authors: O. Frankfurt, J. Altman, J. Krishnamurthy, Andrew M Evens, L. Gordon, S. Singhal, M. Tallman, S. Williams, J. Winter, S. Duffey, V. Singh, R. Meagher, J. Mehta
Journal: Blood (2008)
Dissecting the Hematopoietic Niche to Improve Transplant: Hedgehog and Wnt Pathways Activation in Fetal Mesenchymal Cells (MSC) Are Associated with Better Support to Hematopoietic Progenitors and Higher Proliferative Capacity Compared to Adult MSC
Authors: Marina Podestà, Daniela Cilloni, Elena Ponomareva, Clara Cassanelli, Claudia Cossu, Federica Benvenuto, Paola Anserini, Ezio Fulcheri, Katia Mareschi, Giuseppe Saglio, Franca Fagioli, Francesco Frassoni
Journal: Blood (2011)
Prognostic Significance of Minimal Residual Disease in Adult Patients with B-Lineage Acute Lymphoblastic Leukemia by 8-Color Flow Cytometry
Authors: Xiang-Qin Weng, Yang Shen, Yan Sheng, Bing Chen, Jing-han Wang, Jun-ming Li, Yong-Mei Zhu, Sai-Juan Chen
Journal: Blood (2012)
Erythroid Specific RhoA Deficiency Causes Dysplastic and Inefficient Fetal Erythropoiesis with Lethal Embryonic Anemia Due to Defects in Erythroblast Cytokinesis and Enucleation
Authors: Diamantis Konstantinidis, Suvarnamala Pushkaran, Ursula Klingmuller, James Palis, Yi Zheng, Theodosia A Kalfa
Journal: Blood (2012)
Upfront Autologous Stem Cell Transplantation Overcome the poor Prognosis of Non-Germinal Center Subtype of diffuse Large B-Cell Lymphoma in Patients with Advanced Stage and Elevated Serum Lactate Dehydrogenase
Authors: Yu Ri Kim, Soo-Jeong Kim, June-Won Cheong, Yundeok Kim, Ji Eun Jang, Jung Yeon Lee, Deok-Hwan Yang, Hyewon Lee, Hyeon-Seok Eom, Yoo Hong Min, Jin Seok Kim
Journal: Blood (2014)
Bronchiectasis
Authors: N. H. T. t. Hacken, T. v. d. Molen
Journal: BMJ (2010)

Anterolateral system (AS) neurons transmit pain signals from the spinal cord to the brain. Their morphology, anatomy and physiological properties have been extensively characterised and suggest that specific AS neurons and their brain targets are concerned with the discriminatory aspects of noxious stimuli, such as their location or intensity, and their motivational/emotive dimension. Among the recently unravelled molecular markers of AS neurons is the developmentally-expressed transcription factor Phox2a, affording us the opportunity to selectively disrupt the embryonic wiring of AS neurons to gain insights into the logic of their adult function. Since mice with a spinal cord-specific loss of the netrin-1 receptor DCC have increased AS neuron innervation of ipsilateral brain targets and defective noxious stimulus localisation or topognosis, we generated mice of either sex carrying a deletion of <i>Dcc</i> in Phox2a neurons. Such <i>Dcc<sup>Phox2a</sup></i>mice displayed impaired topognosis along the rostrocaudal axis, but with little effect on left-right discrimination, and normal aversive responses. Anatomical tracing experiments in <i>Dcc<sup>Phox2a</sup></i> mice revealed defective targeting of cervical and lumbar AS axons within the thalamus. Furthermore, genetic labelling of AS axons revealed their expression of DCC upon their arrival in the brain, at a time when many of their target neurons are being born and express <i>Ntn1</i>. Our experiments suggest a post-commissural crossing function for netrin-1:DCC signalling during the formation of somatotopically-ordered maps and are consistent with a discriminatory function of some of the Phox2a AS neurons. <b>SIGNIFICANCE STATEMENT</b> How nociceptive (pain) signals are relayed from the body to the brain remains an important question relevant to our understanding of the basic physiology of pain perception. Previous studies have demonstrated that the anterolateral system (AS) is a main effector of this function. It is composed of AS neurons located in the spinal cord that receive signals from nociceptive sensory neurons that detect noxious stimuli. In this study, we generate a genetic miswiring of mouse AS neurons that results in a decreased ability to perceive the location of a painful stimulus. The precise nature of this defect sheds light on the function of different kinds of AS neurons, and how pain information may be organised.
Phenotypic and Functional Features of Vγ9/Vδ2 T Cells in Chronic Lymphocytic Leukemia Are Strongly Correlated with the Mutational Status of the Immunoglobulin Heavy Chain Variable Region (IgVH) and Metabolic Activity of the Mevalonate Pathway in Tumor Cells.
Authors: Marta Coscia, Silvia Peola, Giorgia Matta, Francesca Pantaleoni, Myriam Foglietta, Daniela Angelini, Sabina Chiaretti, Chiara Riganti, Anna Guarini, Daniela Drandi, Marco Ladetto, Amalia Bosia, Robin Foà, Luca Battistini, Mario Boccadoro, Jean Jacques Fournie, Massimo Massaia
Journal: Blood (2007)
Allogeneic Hematopoietic Stem Cells Transplantation for Non-Hodgkin’s Lymphoma. The Swiss Experience 1985-2014
Authors: Ekaterina Chigrinova, Sara Fertani, Helen Baldomero, Eddy Roosnek, Gayathri Nair, Johanna Schep, Stavroula Masouridi-Levrat, Urs Schanz, Jakob Passweg, Yves Chalandon
Journal: Blood (2014)
Loss of Pigh Expression Frequently Results in a GPI-Negative Subclone Lacking CD52 Membrane Expression, Conferring Alemtuzumab Resistance to B Cell Acute Lymphoblastic Leukemia
Authors: Floris C. Loeff, Kevin Rijs, Willem H. Zoutman, Esther H.M. Egmond, Maarten H. Vermeer, J.H. Frederik Falkenburg, Constantijn J.M. Halkes, Inge Jedema
Journal: Blood (2015)
Imaging Nanotherapeutics in Inflamed Vasculature by Intravital Microscopy
Authors: Zhenjia Wang
Journal: Theranostics (2016)

Intravital microscopy (IVM) is the application of light microscopy to real time study biology of live animal tissues in intact and physiological conditions with the high spatial and temporal resolution.Advances in imaging systems, genetic animal models and imaging probes, IVM has offered quantitative and dynamic insight into cell biology, immunology, neurobiology and cancer.In this review, we will focus on the targeting of nanotherapeutics to inflamed vasculature.We will introduce the basic concept and principle of IVM and demonstrate that IVM is a powerful tool used to quantitatively determine the molecular mechanisms of interactions between nanotherapeutics and neutrophils or endothelium in living mice.In the future, it is needed to develop new imaging systems and novel imaging contrast agents to better understand molecular mechanisms of tissue processing of nanotherapeutics in vivo.
NUP98 Fusion Proteins Interact with the NSL and MLL1 Complexes to Drive Leukemogenesis
Authors: Haiming Xu, Daria G. Valerio, Meghan E. Eisold, Amit Sinha, Richard P. Koche, Wenhuo Hu, Chun-Wei Chen, S. Haihua Chu, Gerard L. Brien, Christopher Y. Park, James J. Hsieh, Patricia Ernst, Scott A. Armstrong
Journal: Cancer Cell (2016)
A Phase 1 Study of Lenalidomide in Combination with Mitoxantrone, Etoposide, and Ara-C in Patients with Relapsed or Refractory Acute Myeloid Leukemia
Authors: Daniel J. DeAngelo, Amir T. Fathi, Lillian Werner, David Avigan, Katarina Luptakova, Martha Wadleigh, David P. Steensma, Gabriela Soriano Hobbs, Eyal C. Attar, Philip C. Amrein, Richard M. Stone, Karen K. Ballen
Journal: Blood (2015)
OC-018 Audit of Helicobacter Pylori Testing in Microbiology Laboratories in England: In Line with Nice Guidance? Is There Scope for Routine Surveillance of Antibiotic Resistance?
Authors: R Allison, DM Lecky, M Bull, K Turner, G Godbole, CA McNulty
Journal: Gut (2016)

<h3>Introduction</h3> Current guidance from the National Institute for Health and Clinical Excellence (NICE) recommends that clinicians test for <i>Helicobacter pylori</i> using a carbon-13 urea breath test or a stool antigen test, or laboratory-based serology where its performance has been locally validated. Recommended first-line treatment suggests a proton pump inhibitor (PPI) with dual antibiotic therapy. <h3>Aims</h3> To assess: microbiology laboratory compliance with NICE guidance; and to determine the number of laboratories performing culture and antibiotic susceptibility testing which will inform decisions on future national <i>H. pylori </i>antibiotic resistance surveillance strategies. <h3>Methods</h3> In 2015, questionnaires were sent by e-mail to 170 Clinical Pathology Accreditation (CPA) labs in England. All non-responding labs were contacted and requested to complete the questionnaire by e-mail or telephone. <h3>Results</h3> Of the 121/170 (71%) labs that responded, 96% provide a <i>H. pylori</i> testing service: 78% perform on site and 13% refer elsewhere. <h3>In line with NICE guidance</h3> 95% of labs comply by testing with stool antigen or urea breath test for <i>H. pylori</i>. Five labs do not comply as they perform serology or biopsy urease tests first line (4/5 encourage urea breath tests in their acute trusts). <h3>Cultures and antibiotic susceptibility performed</h3> 23% of labs perform <i>H. pylori </i>cultures on site; 46% refer biopsy specimens to another lab (39/43 (91%) refer to the Helicobacter Reference Unit (HRU)). Of the 22 labs undertaking <i>H. pylori </i>cultures; two processed ten specimens/week; others ≤1 specimen/week. Nine labs undertake antibiotic susceptibility on site; nine refer elsewhere (8/9 to the HRU). Eight of nine labs that reported testing for antibiotic susceptibility in-house commented on the antibiotics tested: metronidazole-7/8 labs (88%); clarithromycin-6/8 labs (75%); amoxicillin-7/8 labs (88%); tetracycline-5/8 labs (63%); levofloxacin-2/8 labs (25%). <h3>Conclusion</h3> The majority of labs are complying with NICE guidance. However, the four labs still performing serology and one performing biopsy urease tests as their first line diagnostic test for <i>H. pylori </i>should be followed up and have the current guidance reinforced. As very few laboratories are routinely performing culture of biopsy specimens to investigate antibiotic susceptibility, an English culture based surveillance system would probably need centralised culture. However, a PCR based stool specimen surveillance system would be very possible, but thus far, does not give metronidazole susceptibility. <h3>Disclosure of Interest</h3> R. Allison: None Declared, D. Lecky: None Declared, M. Bull: None Declared, K. Turner: None Declared, G. Godbole: None Declared, C. McNulty Consultant for: PHE diagnostic guidance for H. pylori and PHE antibiotic guidance
AB0950 Leucine-Rich Alpha-2 Glycoprotein (LRG) as A Possible Urinary Marker for Lupus Nephritis
Authors: H. Lee, M. Fujimoto, Y. Hosono, K. Suzuki, H. Honda, H. Urushima, T. Ohkawara, S. Serada, T. Takeuchi, T. Mimori, T. Naka
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE). Its accurate evaluation is dependent on renal biopsy. A search for other non-invasive methods such as urinalysis is warranted. Recently, we identified a novel acute phase protein, LRG<sup>1,2</sup> whose expression is induced at the site of inflammation by various inflammatory cytokines. <h3>Objectives</h3> To investigate whether LRG can be a new urinary biomarker of LN. <h3>Methods</h3> We determined LRG levels in serum and urine of SLE patients (n=46, M:F=3:43, age: 37.1 (22–66)) with or without LN by ELISA. We divided SLE patients into four groups according to the results of renal biopsy (group 1: no LN [n =19], group 2: LN class 5 [n =3], group 3: LN class 1 or 2 [n =4], group 4: LN class 3 or 4 [n =20] (ISN/RPS)), and analyzed the relationship between urinary LRG levels and renal pathology. Also, we analyzed NZ B/W F1 mice, a lupus model, to study the mechanism of LRG expression in LN. Mouse urinary LRG levels were determined by western blot. Also, we evaluated the expression of LRG and several cytokines in kidney by real-time PCR, immunohistochemistry (IHC) and immunofluorescence (IF). In vitro, we investigated the expression and secretion of LRG in primary tubular epithelial cells (PTEC) obtained from NZ B/W F1. <h3>Results</h3> Urinary LRG levels were significantly higher in group 4 patients, and tend to be high in group 2 and 3 patients compared with group 1. In kidney of NZ B/W F1 mice with LN-like alteration, mRNA expression of LRG and IL-1 beta was significantly up-regulated, compared with NZ B/W F1 mice without LN-like alteration and B6 mice. By IHC and IF analysis, LRG protein was detected in renal tubular epithelia of NZ B/W F1 mice with nephritis. Additionally, macrophage infiltration and IL-1beta production was detectable around of the LRG-positive tubules in NZ B/W F1 mice. In vitro, LRG expression and secretion was induced by IL-1beta in PTEC of NZ B/W F1 mice. <h3>Conclusions</h3> Urinary LRG may be a useful biomarker which reflects the active inflammation of LN. <h3>References</h3> Serada S, Fujimoto M et al. iTRAQ-based proteomic identification of leucine-rich alpha-2 glycoprotein as a novel inflammatory biomarker in autoimmune diseases. Ann Rheum Dis. 69(4):770–4 (2010) Fujimoto M, Serada S et al. Leucine-rich α2 -glycoprotein as a potential biomarker for joint inflammation during anti-interleukin-6 biologic therapy in rheumatoid arthritis. Arthritis Rheumatol. 67(8):2056–60 (2015) <h3>Disclosure of Interest</h3> None declared