tbuckley/cabot-search huggingface dataset:
Metabolic biomarker signature to differentiate pancreatic ductal adenocarcinoma from chronic pancreatitis
Authors: Julia Mayerle, Holger Kalthoff, Regina Reszka, Beate Kamlage, Erik Peter, Bodo Schniewind, Sandra González Maldonado, Christian Pilarsky, Claus-Dieter Heidecke, Philipp Schatz, Marius Distler, Jonas A Scheiber, Ujjwal M Mahajan, F Ulrich Weiss, Robert Grützmann, Markus M Lerch
Journal: Gut (2017)

Objective Current non-invasive diagnostic tests can distinguish between pancreatic cancer (pancreatic ductal adenocarcinoma (PDAC)) and chronic pancreatitis (CP) in only about two thirds of patients. We have searched for blood-derived metabolite biomarkers for this diagnostic purpose. Design For a case–control study in three tertiary referral centres, 914 subjects were prospectively recruited with PDAC (n=271), CP (n=282), liver cirrhosis (n=100) or healthy as well as non-pancreatic disease controls (n=261) in three consecutive studies. Metabolomic profiles of plasma and serum samples were generated from 477 metabolites identified by gas chromatography–mass spectrometry and liquid chromatography–tandem mass spectrometry. Results A biomarker signature (nine metabolites and additionally CA19-9) was identified for the differential diagnosis between PDAC and CP. The biomarker signature distinguished PDAC from CP in the training set with an area under the curve (AUC) of 0.96 (95% CI 0.93–0.98). The biomarker signature cut-off of 0.384 at 85% fixed specificity showed a sensitivity of 94.9% (95% CI 87.0%–97.0%). In the test set, an AUC of 0.94 (95% CI 0.91–0.97) and, using the same cut-off, a sensitivity of 89.9% (95% CI 81.0%–95.5%) and a specificity of 91.3% (95% CI 82.8%–96.4%) were achieved, successfully validating the biomarker signature. Conclusions In patients with CP with an increased risk for pancreatic cancer (cumulative incidence 1.95%), the performance of this biomarker signature results in a negative predictive value of 99.9% (95% CI 99.7%–99.9%) (training set) and 99.8% (95% CI 99.6%–99.9%) (test set). In one third of our patients, the clinical use of this biomarker signature would have improved diagnosis and treatment stratification in comparison to CA19-9.
Distinctive Integration Profile of Avian Sarcoma Leukosis Virus Vectors in Rhesus Long-Term Repopulating Cells.
Authors: Jingqiong Hu, Theotonius Gomes, Andrea Ferris, Gabriel Renaud, Paul C. Hendrie, Allen E. Krouse, Robert E. Donahue, Tyra G. Wolfsberg, Stephen H. Hughes, David W. Russell, Cynthia E. Dunbar
Journal: Blood (2007)
Profound Hyperbilirubinemia during Induction of Adult Acute Lymphoblastic Leukemia: Capping L-Asparaginase Dose to 10,000 Units Attenuates It without Compromising Remission Rate.
Authors: Amish D. Vora, Vasnat R. Pai, Prabhash Kumar, Shripad Banavali, Reena Nair, Purna Kurkure, Purvish M. Parikh
Journal: Blood (2006)
<i>N</i>‐Acetylgalactosamine‐Targeted Delivery of Dendrimer‐Doxorubicin Conjugates Influences Doxorubicin Cytotoxicity and Metabolic Profile in Hepatic Cancer Cells
Authors: Sibu P. Kuruvilla, Gopinath Tiruchinapally, Mahmoud ElAzzouny, Mohamed E. H. ElSayed
Journal: Advanced Healthcare Materials (2017)

This study describes the development of targeted, doxorubicin (DOX)-loaded generation 5 (G5) polyamidoamine dendrimers able to achieve cell-specific DOX delivery and release into the cytoplasm of hepatic cancer cells. G5 is functionalized with poly(ethylene glycol) (PEG) brushes displaying N-acetylgalactosamine (NAcGal) ligands to target hepatic cancer cells. DOX is attached to G5 through one of two aromatic azo-linkages, L3 or L4, achieving either P1 ((NAcGalβ -PEGc)16.6 -G5-(L3-DOX)11.6 ) or P2 ((NAcGalβ -PEGc)16.6 -G5-(L4-DOX)13.4 ) conjugates. After confirming the conjugates' biocompatibility, flow cytometry studies show P1/P2 achieve 100% uptake into hepatic cancer cells at 30-60 × 10-9 m particle concentration. This internalization correlates with cytotoxicity against HepG2 cells with 50% inhibitory concentration (IC50 ) values of 24.8, 1414.0, and 237.8 × 10-9 m for free DOX, P1, and P2, respectively. Differences in cytotoxicity prompted metabolomics analysis to identify the intracellular release behavior of DOX. Results show that P1/P2 release alternative DOX metabolites than free DOX. Stable isotope tracer studies show that the different metabolites induce different effects on metabolic cycles. Namely, free DOX reduces glycolysis and increases fatty acid oxidation, while P1/P2 increase glycolysis, likely as a response to high oxidative stress. Overall, P1/P2 conjugates offer a platform drug delivery technology for improving hepatic cancer therapy.
Allogeneic hematopoietic stem cell transplantation for MDS and CMML: recommendations from an international expert panel
Authors: Theo de Witte, David Bowen, Marie Robin, Luca Malcovati, Dietger Niederwieser, Ibrahim Yakoub-Agha, Ghulam J. Mufti, Pierre Fenaux, Guillermo Sanz, Rodrigo Martino, Emilio Paolo Alessandrino, Francesco Onida, Argiris Symeonidis, Jakob Passweg, Guido Kobbe, Arnold Ganser, Uwe Platzbecker, Jürgen Finke, Michel van Gelder, Arjan A. van de Loosdrecht, Per Ljungman, Reinhard Stauder, Liisa Volin, H. Joachim Deeg, Corey Cutler, Wael Saber, Richard Champlin, Sergio Giralt, Claudio Anasetti, Nicolaus Kröger
Journal: Blood (2017)
OPTICAL COHERENCE TOMOGRAPHY–BASED EVALUATION OF IN–STENT NEOATHEROSCLEROSIS IN LESIONS WITH MORE THAN 50% OF PERCENT NEOINTIMAL CROSS–SECTIONAL AREA STENOSIS
Authors: Seung–Yul Lee, Byeong–Keuk Kim, Jung–Sun Kim, Dong–Ho Shin, Young–Guk Ko, Donghoon Choi, Yangsoo Jang, Myeong–Ki Hong
Journal: Journal of the American College of Cardiology (2013)
Clonal T Cell Large Granular Lymphocyte Leukaemia of Recipient Origin after Related Mismatched Allogeneic Haematopoietic Stem Cell Transplantation for Acute Myeloid Leukaemia as a Possible Consequence of Anti-Thymocyte Globulin in Conditioning Regimen
Authors: Loïc Fouillard, Christophe Marzac, Monique Lagrange, Stéphanie Huguet-Jacquot, Betina Fabiani, Frederic Davi, Christelle Mazurier, Elisabeth Soreau, jean-Philippe Laporte, Francoise Isnard, norbert-Claude Gorin, Dominique Bories
Journal: Blood (2008)
Reasons for Decreasing Early Mortality in Acute Myeloid Leukemia: An Epidemiological Study from the Swedish Acute Leukemia Registry
Authors: Stefan Deneberg, Ebba Lundin, Vladimir Lazarevic, Lina Benson, Bertil Uggla, Petar Antunovic, Lars Mollgard, Sören Lehmann, Gunnar Juliusson, Martin Höglund, Asa Rangert Derolf
Journal: Blood (2015)
Weight Adjusted Low-Dose Warfarin Decreases the Incidence of Thalidomide (T) Associated Venous Thromboembolism (VTE) in Patients (pts) with Multiple Myeloma (MM) and Waldenstroms Macroglobulinemia (WM).
Authors: Kena C. Miller, Rami Manochakian, Swaminathan Padmanabhan, Jean-Gabriel Coignet, Laurie Musial, Dawn DePaolo, Asher Alban Chanan-Khan
Journal: Blood (2006)
Imaging Protocols in Clinical Studies in Advanced Age-Related Macular Degeneration
Authors: Frank G. Holz, SriniVas R. Sadda, Giovanni Staurenghi, Moritz Lindner, Alan C. Bird, Barbara A. Blodi, Ferdinando Bottoni, Usha Chakravarthy, Emily Y. Chew, Karl Csaky, Christine A. Curcio, Ron Danis, Monika Fleckenstein, K. Bailey Freund, Juan Grunwald, Robyn Guymer, Carel B. Hoyng, Glenn J. Jaffe, Sandra Liakopoulos, Jordi M. Monés, Akio Oishi, Daniel Pauleikhoff, Philip J. Rosenfeld, David Sarraf, Richard F. Spaide, Ramin Tadayoni, Adnan Tufail, Sebastian Wolf, Steffen Schmitz-Valckenberg
Journal: Ophthalmology (2017)
Methylenetetrahydrofolate Reductase and Methionine Synthase Polymorphism and Risk of Non-Hodgkin’s Lymphoma.
Authors: Hee Nam, Yeo-Kyeoung Kim, Il-Kwon Lee, Deok-Hwan Yang, Kyeong-Soo Park, Je-Jung Lee, Hyeoung-Joon Kim
Journal: Blood (2005)
Microenvironment Induced Myelodysplastic Syndrome (MDS) in S100A9 Transgenic Mice Caused by Myeloid-Derived Suppressor Cells (MDSC)
Authors: Sheng Wei, Xianghong Chen, Junmin Zhou, Ling Zhang, Nicole R. Fortenbery, Sarah S Rasche, Kathy McGraw, Erika A. Eksioglu, P.K. Epling-Burnette, Julie Y. Djeu, Dmitry I. Gabrilovich, Alan F. List
Journal: Blood (2011)
Current Multistage Drug Delivery Systems Based on the Tumor Microenvironment
Authors: Binlong Chen, Wenbing Dai, Bing He, Hua Zhang, Xueqing Wang, Yiguang Wang, Qiang Zhang
Journal: Theranostics (2017)

The development of traditional tumor-targeted drug delivery systems based on EPR effect and receptor-mediated endocytosis is very challenging probably because of the biological complexity of tumors as well as the limitations in the design of the functional nano-sized delivery systems. Recently, multistage drug delivery systems (Ms-DDS) triggered by various specific tumor microenvironment stimuli have emerged for tumor therapy and imaging. In response to the differences in the physiological blood circulation, tumor microenvironment, and intracellular environment, Ms-DDS can change their physicochemical properties (such as size, hydrophobicity, or zeta potential) to achieve deeper tumor penetration, enhanced cellular uptake, timely drug release, as well as effective endosomal escape. Based on these mechanisms, Ms-DDS could deliver maximum quantity of drugs to the therapeutic targets including tumor tissues, cells, and subcellular organelles and eventually exhibit the highest therapeutic efficacy. In this review, we expatiate on various responsive modes triggered by the tumor microenvironment stimuli, introduce recent advances in multistage nanoparticle systems, especially the multi-stimuli responsive delivery systems, and discuss their functions, effects, and prospects.
Allogeneic Stem Cell Transplantation with Reduced-Intensity, Fludarabine-Based Conditioning in Relapsed and Refractory Hodgkin’s Disease: Low Transplant-Related Mortality and Impact of Intensity of Conditioning Regimen on Survival.
Authors: Paolo Anderlini, Rima Saliba, Michele Donato, Sergio Giralt, Borje Andersson, Nato T. Ueno, Issa F. Khouri, Marcos de Lima, Cindy Ippoliti, Richard E. Champlin
Journal: Blood (2004)
An Evaluation of Estrogenic Substances in the Treatment of Cerebral Vascular Disease
Journal: Circulation (1966)

A cooperative clinical investigation was undertaken in 17 Veterans Administration Hospitals to determine the effects of long-term therapy with conjugated equine estrogens (Premarin) in prevention of recurrent cerebral infarction or death due to atherosclerotic vascular disease. To date, 582 men with cerebral infarction have been assigned on a random basis to either the treatment or control groups and observed for periods as long as 34 months. Initial treatment consisted of 1.25 mg. of Premarin daily and was increased to 2.5 mg. after the first year. Estrogenic therapy failed to reduce the incidence of either cerebral or myocardial infarction developing during the period of follow-up observation. There was likewise no significant change in the mortality rate following onset of therapy. Of the 63 deaths in the study, 34 occurred in patients receiving treatment and 29 among those receiving the placebo preparation. Approximately 40 per cent of patients developed mild side reactions to the estrogenic agent, usually consisting of breast tenderness or enlargement, or both. These preliminary observations failed to demonstrate that treatment with conjugated equine estrogenic hormones in small and moderate dosages for an average period of 16.7 months had any value in lowering the recurrence of cerebral infarction or reducing the mortality rate subsequent to this disorder.
Poor adherence to management guidelines in nontuberculous mycobacterial pulmonary diseases
Authors: Jakko van Ingen, Dirk Wagner, Jack Gallagher, Kozo Morimoto, Christoph Lange, Charles S. Haworth, R. Andres Floto, Jennifer Adjemian, D. Rebecca Prevots, David E. Griffith
Journal: European Respiratory Journal (2016)

Nontuberculous mycobacterial pulmonary diseases (NTM-PD) are increasingly recognised as opportunistic infections of humans. Nodular/bronchiectatic disease and fibrocavitary disease are the most frequent manifestations [1]. Although guidelines have been published [1], there are few data on diagnostic and treatment practices outside of reference clinics. A recent survey in the USA suggested limited adherence to guidelines for diagnosis and treatment of NTM-PD [2]. Poor adherence to diagnosis and treatment guidelines for nontuberculous mycobacterial lung disease in EU and Japan <http://ow.ly/EVYl306vVcN>
Unmutated IGHV1-69/D3-16/J3 Stereotyped HCDR3 Rearrangements (Subset 6) Are Associated with Indolent Disease Course and Have Outcome Independent of Mutational Status In Early Stage CLL (Rai 0)
Authors: Francesco Forconi, Emanuele Cencini, Davide Rossi, Riccardo Bomben, Elisa Sozzi, Marta Coscia, Massimo Massaia, Silvio Veronese, Alessandra Tedeschi, Marco Montillo, Rita Fazzi, Mario Petrini, Stefania Ciolli, Alberto Bosi, Roberto Dottori, Maria Teresa Pirrotta, Alessandra Caremani, Giovanni Del Poeta, Ilaria Del Giudice, Simona Santangelo, Luca Laurenti, Dimitar G Efremov, Livio Trentin, Luca Arcaini, Ester Orlandi, Francesco Bertoni, Rossana Maffei, Robin Foà, Roberto Marasca, Valter Gattei, Gianluca Gaidano, Francesco Lauria
Journal: Blood (2010)
Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) Transformation From Essential Thrombocythemia (ET) In Patients Treated with Hydroxyurea or Anagrelide: A Single Center Series of 17 Cases
Authors: Jeremy W Bowers, Jijun Liu, Kenneth S. Zuckerman, Mojdeh Naghashpour, Jeffrey Lancet, Rami S. Komrokji, Lynn C. Moscinski, Ling Zhang
Journal: Blood (2010)
Reversal of Acquired von Willebrand Disease after Allogeneic Hematopoietic Stem Cell Transplantation in a Patient with High Risk Chronic Lymphocytic Leukemia.
Authors: Christian Langer, Martin Griesshammer, Donald Bunjes, Ulrich Budde, Martin Gruenewald, Hartmut Dohner, Heimo Beneke
Journal: Blood (2004)
Defibrotide (DF) for the Treatment of Severe Veno-Occlusive Disease (sVOD) and Multi-Organ Failure (MOF) Post SCT: Final Results of a Multi-Center, Randomized, Dose-Finding Trial.
Authors: Paul Richardson, R.J. Soiffer, J.H. Antin, Z. Jin, J. Kurtzberg, P.L. Martin, G. Steinbach, K.F. Murray, G.B. Vogelsang, A. Chen, A. Krishnan, N.A. Kernan, D. Avigan, T.R. Spitzer, D. Warren, C. Revta, L.J. Wei, M. Iacobelli, G.B. McDonald, E.C. Guinan
Journal: Blood (2006)
Campath-1H-Based Reduced-Intensity Conditioning Followed by Allogeneic Blood Stem-Cell Transplantation and Preemptive CD8-Depleted Donor Lymphocyte Infusions.
Authors: Ralf G. Meyer, Daniela Wehler, Thomas C. Wehler, Cedrik M. Britten, Alexander Burchardt, Udo Hartwig, Christoph Huber, Karin Kolbe, Wolfgang Herr
Journal: Blood (2004)
Outcomes of Allogeneic Blood or Marrow Transplantation for Peripheral T-Cell Lymphoma.
Authors: Jennifer A. Kanakry, Yvette L. Kasamon, Christopher D. Gocke, Hua-Ling Tsai, Janice M. Davis-Sproul, Nilanjan Ghosh, Heather J. Symons, Javier Bolaños-Meade, Douglas E. Gladstone, Lode J. Swinnen, Leo Luznik, Ephraim J. Fuchs, Richard J. Jones, Richard F. Ambinder
Journal: Blood (2012)
Implication of the Distinct Differentiation Pathway of Megakaryocytes From Hematopoietic Stem Cells in the Mouse Bone Marrow
Authors: Hidekazu Nishikii, Kenji Matsushita, Yosuke Kanazawa, Yasuhisa Yokoyama, Takayasu Kato, Naoshi Obara, Mamiko Sakata-Yanagimoto, Shigeru Chiba
Journal: Blood (2012)
Change in circulating endothelial cells (CEC) and tumor cells (CTC) in patients (pts) receiving bevacizumab and erlotinib for metastatic breast cancer (MBC) predicts stable disease at first evaluation
Authors: H. S. Rugo, M. N. Dickler, J. H. Scott, D. H. Moore, M. Melisko, B. M. Yeh, J. Caravelli, E. Brogi, C. Hudis, J. W. Park
Journal: Journal of Clinical Oncology (2005)

525 Background: The antivascular effects of antiangiogenic therapy for cancer are not well understood. Identifying clinically relevant intermediate markers for angiogenesis that might predict response has been difficult; CECs have been proposed as a marker of tumor progression and/or response to antiangiogenic therapy with bevacizumab. We performed a phase II study of erlotinib and bevacizumab in pts with MBC based on preclinical data suggesting that EGFR blockade may inhibit angiogenesis, and that combined blockade may increase anti-tumor activity. To explore markers of activity and response, we assayed CECs and CTCs at weeks 0 (baseline), 3, 9, and then Q 9 weeks. Methods: CECs were defined as CD34/31+, CD45-. Progenitor (CD133+) (CECp) and activation markers (CD106+) were also measured. For CECs, 50 ul of blood was stained with the indicated MAbs; after RBC lysis, flow cytometry (FC) was performed for total CEC and CECp. For CTCs, 20 ml of blood was subjected to immunomagnetic capture using anti-EpCAM ferrofluid, followed by FC for EpCAM, CD45, and nucleic acid content. The log rank test was used to test for significant differences related to response. Results: 35 of 37 pts have been enrolled. Prelim response data has been reported (Dickler, ASCO 2004). One pt has an ongoing PR at > 72 wks, 4 pts have SD (290, 254, 196, 193d). 27 pts have at least baseline and wk 3 CEC and CTC along with clinical response data. Median CEC level at baseline was 16 CEC/ul (range, 3.7–48.2); CTC levels were 3x less frequent with a median of 0.80 CTC/ml (range, 0–89.2). The magnitude of change in CECs from wk 0 to wk 3 predicted response at first assessment (9 wks) (p = 0.018), as did the magnitude of change in CTCs between the same time points (p=0.01). An increase in CECs over the last two measurements of treatment was associated with PFS (p=0.06). Conclusions: CECs and CTCs may serve as surrogate markers of response and progression, and changes in CEC levels may reflect angiogenic activity. Updated data on the complete study population, as well as serum and tissue markers of angiogenesis will be presented. Supported in part by CTEP and Genentech. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Biooncology
Evaluation of Minimal Residual Disease (MRD) by Quantification of TEL-AML1 Transcripts Is a Powerful Prognostic Tool in Children with T(12;21) Positive Acute Lymphoblastic Leukemia (ALL).
Authors: Jean-Michel Cayuela, Paola Ballerini, Marina Romeo, Vahid Asnafi, Marie-Francoise Auclerc, Xavier Fund, Eric Delabesse, Christian Bastard, Jean Gabert, Jean-Pierre Vanier, Odile Lejars, Mariane Debre, Brigitte Pautard, Gerard Michel, Thierry Leblanc, Guy Leverger, Sylvie Chevret, Elisabeth Macintyre, Andre Baruchel
Journal: Blood (2004)
First Interim Analysis of HOVON 76: Lenalidomide Maintenance Following Non Myeloablative Allogeneic Stem Cell Transplantation in Patients with Multiple Myeloma.
Authors: Monique C. Minnema, Bronno van der Holt, Marie Jose Kersten, Sonja Zweegman, Ellen Meijer, Edo Vellenga, Evelien Kneppers, Mark Zijlmans, Petra Cornelisse, Henk Lokhorst
Journal: Blood (2009)
Reduction of Mitochondrial Superoxide By Carbon Nanotube Scaffolds Enhances Ex Vivo Expansion of Human Cord Blood Progenitor Cells
Authors: Sudipto Bari, Pat PY Chu, Sujoy Ghosh, Andrea Lim, Xiubo Fan, Li Shang, Gigi NC Chiu, William YK Hwang
Journal: Blood (2014)
Brain-Derived Neurotrophic Factor Enhances Osteoclastogenesis in Multiple Myeloma via Upregulation of RANKL/OPG Ratio Both in Vitro and in a Murine Model of Myeloma Bone Disease
Authors: Li-Sha Ai, Chun-Yan Sun, Tao Guo, Ya-Dan Wang, Lu Zhang, You Qin, Lei Chen, Han Yan, Wei Zeng, Jun Fang, Yu Hu
Journal: Blood (2012)
Polymorphisms of NOD2/CARD15 Are Associated with Clinical Outcome in T-Cell Depleted HLA-Identical Sibling Allogeneic Stem Cell Transplantation.
Authors: Miquel Granell, Alvaro Urbano-Ispizua, Juan Ignacio Arostegui, Francesc Fernandez-Aviles, Carmen Martinez, Montserrat Rovira, Anna Gaya, Alfons Navarro, Carme Talarn, Enric Carreras, Mariano Monzo, Jordi Yague, Emili Montserrat
Journal: Blood (2005)
JAK1 gain-of-function causes an autosomal dominant immune dysregulatory and hypereosinophilic syndrome
Authors: Kate L. Del Bel, Robert J. Ragotte, Aabida Saferali, Susan Lee, Suzanne M. Vercauteren, Sara A. Mostafavi, Richard A. Schreiber, Julie S. Prendiville, Min S. Phang, Jessica Halparin, Nicholas Au, John M. Dean, John J. Priatel, Emily Jewels, Anne K. Junker, Paul C. Rogers, Michael Seear, Margaret L. McKinnon, Stuart E. Turvey
Journal: Journal of Allergy and Clinical Immunology (2017)
CoCoA/CCAR1 Pair-Mediated Recruitment of Mediator Complex Indicates Novel Pathway for the Function of GATA1 in Erythroid Differentiation
Authors: Chihiro Kaminaga, Shumpei Mizuta, Tomoya Minami, Kasumi Oda, Haruka Fujita, Keiji Matsui, Ruri Ishino, Akiko Sumitomo, Norinaga Urahama, Mitsuhiro Ito
Journal: Blood (2011)
A Recombinant HLA Class I-Specific Single-Chain Fv Diabody Can Target Cancer Stem Cell-Like Side Population Cells in Multiple Myeloma.
Authors: Akishige Ikegame, Shuji Ozaki, Daisuke Tsuji, Takeshi Harada, Shingen Nakamura, Hirokazu Miki, Ayako Nakano, Kumiko Kagawa, Kyoko Takeuchi, Kenichiro Yata, Masahiro Abe, Kohji Itoh, Toshio Matsumoto
Journal: Blood (2009)
Imexon (AOP 99.0001) for Treatment of Relapsed or Refractory Multiple Myeloma: A Phase I/II Study
Authors: Thomas M. Moehler, Anatoli Golenkov, Heinz Ludwig, Martin H Kropff, Nuriet K Khuageva, E. A Osmanov, I. Broen, H. Goldschmidt
Journal: Blood (2008)
Complex Evolutionary History of the Mammalian Histone H1.1–H1.5 Gene Family
Authors: Inma Ponte, Devani Romero, Daniel Yero, Pedro Suau, Alicia Roque
Journal: Molecular Biology and Evolution (2016)

H1 is involved in chromatin higher-order structure and gene regulation. H1 has a tripartite structure. The central domain is stably folded in solution, while the N- and C-terminal domains are intrinsically disordered. The terminal domains are encoded by DNA of low sequence complexity, and are thus prone to short insertions/deletions (indels). We have examined the evolution of the H1.1–H1.5 gene family from 27 mammalian species. Multiple sequence alignment has revealed a strong preferential conservation of the number and position of basic residues among paralogs, suggesting that overall H1 basicity is under a strong purifying selection. The presence of a conserved pattern of indels, ancestral to the splitting of mammalian orders, in the N- and C-terminal domains of the paralogs, suggests that slippage may have favored the rapid divergence of the subtypes and that purifying selection has maintained this pattern because it is associated with function. Evolutionary analyses have found evidences of positive selection events in H1.1, both before and after the radiation of mammalian orders. Positive selection ancestral to mammalian radiation involved changes at specific sites that may have contributed to the low relative affinity of H1.1 for chromatin. More recent episodes of positive selection were detected at codon positions encoding amino acids of the C-terminal domain of H1.1, which may modulate the folding of the CTD. The detection of putative recombination points in H1.1–H1.5 subtypes suggests that this process may has been involved in the acquisition of the tripartite H1 structure.
Long-Term and Sustained Correction of the α-Galactosidase A Deficiency in Fabry Mice and Patient Cells Receiving Lentivirally Transduced Hematopoietic Stem/Progenitor Cells.
Authors: Makoto Yoshimitsu, Christopher Siatskas, Sheng-Ben Liang, Vanessa I. Rasaiah, Koji Higuchi, Gary J. Murray, Toshihiro Takenaka, Chuwa Tei, Roscoe O. Brady, Jeffrey A. Medin
Journal: Blood (2005)
Hemostatic Disorders and Thrombotic Events in Multiple Myeloma Patients during Peripheral Blood Stem Cell Mobilization
Authors: Evdokia S. Urnova, Larisa P. Mendeleeva, Olga S. Pokrovskaya, Marina A. Gracheva, Eduard G. Gemdzhian, Ivan D. Tarandovsky, Maiia V. Firsova, Mariya V. Nareiko, Sergei A. Vasil'ev, Valeri G. Savchenko
Journal: Blood (2014)
Superiority of First-Line Thalidomide-Dexamethasone over Vincristine-Doxorubicin-Dexamethasone in Preparation for Autologous Stem Cell Transplantation for Multiple Myeloma.
Authors: Michele Cavo, Paola Tacchetti, Elena Zamagni, Patrizia Tosi, Delia Cangini, Claudia Cellini, Nicoletta Testoni, Antonio De Vivo, Giulia Perrone, Sante Tura, Michele Baccarani
Journal: Blood (2004)