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Sample records for depletion syndrome mds

  1. Depletion of mtDNA: syndromes and genes.

    Science.gov (United States)

    Alberio, Simona; Mineri, Rossana; Tiranti, Valeria; Zeviani, Massimo

    2007-01-01

    Maintenance of mitochondrial DNA (mtDNA) requires the concerted activity of several nuclear-encoded factors that participate in its replication, being part of the mitochondrial replisome or ensuring the balanced supply of dNTPs to mitochondria. In the past decade, a growing number of syndromes associated with dysfunction due to tissue-specific depletion of mtDNA (MDS) have been reported. This article reviews the current knowledge of the genes responsible for these disorders, the impact of different mutations in the epidemiology of MDS and their role in the pathogenic mechanisms underlying the different clinical presentations.

  2. Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy

    DEFF Research Database (Denmark)

    Grövdal, Michael; Karimi, Mohsen; Khan, Rasheed

    2010-01-01

    This prospective Phase II study is the first to assess the feasibility and efficacy of maintenance 5-azacytidine for older patients with high-risk myelodysplastic syndrome (MDS), chronic myelomonocytic leukaemia and MDS-acute myeloid leukaemia syndromes in complete remission (CR) after induction...

  3. Adult mitochondrial DNA depletion syndrome with mild manifestations

    Directory of Open Access Journals (Sweden)

    Josef Finsterer

    2013-06-01

    Full Text Available Mitochondrial DNA depletion syndrome (MDS is usually a severe disorder of infancy or childhood, due to a reduced copy number of mtDNA molecules. MDS with only mild, non-specific clinical manifestations and onset in adulthood has not been reported. A 47-year-old Caucasian female with short stature and a history of migraine, endometriosis, Crohn’s disease, C-cell carcinoma of the thyroid gland, and a family history positive for mitochondrial disorder (2 sisters, aunt, niece, developed day-time sleepiness, exercise intolerance, and myalgias in the lower-limb muscles since age 46y. She slept 9-10 hours during the night and 2 hours after lunch daily. Clinical exam revealed sore neck muscles, bilateral ptosis, and reduced Achilles tendon reflexes exclusively. Blood tests revealed hyperlipidemia exclusively. Nerve conduction studies, needle electromyography, and cerebral and spinal magnetic resonance imaging were non-informative. Muscle biopsy revealed detached lobulated fibers with subsarcolemmal accentuation of the NADH and SDH staining. Real-time polymerase chain reaction revealed depletion of the mtDNA down to 9% of normal. MDS may be associated with a mild phenotype in adults and may not significantly progress during the first year after onset. In an adult with hypersomnia, severe tiredness, exercise intolerance, and a family history positive for mitochondrial disorder, a MDS should be considered.

  4. [Lenalidomide treatment in myelodysplastic syndrome with 5q deletion--Czech MDS group experience].

    Science.gov (United States)

    Jonášová, Anna; Červinek, Libor; Bělohlávková, Petra; Čermák, Jaroslav; Beličková, Monika; Rohoň, Petr; Černá, Olga; Hochová, Ivana; Šišková, Magda; Kačmářová, Karla; Janoušová, Eva

    2015-12-01

    Myelodysplastic syndrome (MDS) is a common hematological disease in patients over sixty. Despite intensive research, the therapy of this heterogeneous blood disease is complicated. In recent years, two new therapeutic approaches have been proposed: immunomodulation and demethylation therapy. Immunomodulation therapy with lenalidomide represents a meaningful advance in the treatment of anemic patients, specifically those with 5q- aberrations. As much as 60-70% of patients respond and achieve transfusion independence. We present the initial lenalidomide experience of the Czech MDS group. We analyze Czech MDS register data of 34 (31 female; 3 male; median age 69 years) chronically transfused low risk MDS patients with 5q- aberration treated by lenalidomide. Twenty-seven (79.4%) patients were diagnosed with 5q- syndrome, 5 patients with refractory anemia with multilineage dysplasia, 1 patient with refractory anemia with excess of blasts 1, and 1 patient with myelodysplastic/myeloproliferative unclassified. Response, as represented by achieving complete transfusion independence, was achieved in 91% of patients. A true 5q- syndrome diagnosis in most our patients may be responsible for such a high response rate. Complete cytogenetic response was reached in 15% of patients and partial cytogenetic response in 67%, within a median time of 12 months. TP53 mutation was detected in 15% (3 from 18 tested) and 2 of these patients progressed to higher grade MDS. The majority of patients tolerated lenalidomide very well. Based on this albeit small study, we present our findings of high lenalidomide efficacy as well as the basic principles and problems of lenalidomide therapy.

  5. New Comprehensive Cytogenetic Scoring System for Primary Myelodysplastic Syndromes (MDS) and Oligoblastic Acute Myeloid Leukemia After MDS Derived From an International Database Merge

    Science.gov (United States)

    Schanz, Julie; Tüchler, Heinz; Solé, Francesc; Mallo, Mar; Luño, Elisa; Cervera, José; Granada, Isabel; Hildebrandt, Barbara; Slovak, Marilyn L.; Ohyashiki, Kazuma; Steidl, Christian; Fonatsch, Christa; Pfeilstöcker, Michael; Nösslinger, Thomas; Valent, Peter; Giagounidis, Aristoteles; Aul, Carlo; Lübbert, Michael; Stauder, Reinhard; Krieger, Otto; Garcia-Manero, Guillermo; Faderl, Stefan; Pierce, Sherry; Le Beau, Michelle M.; Bennett, John M.; Greenberg, Peter; Germing, Ulrich; Haase, Detlef

    2012-01-01

    Purpose The karyotype is a strong independent prognostic factor in myelodysplastic syndromes (MDS). Since the implementation of the International Prognostic Scoring System (IPSS) in 1997, knowledge concerning the prognostic impact of abnormalities has increased substantially. The present study proposes a new and comprehensive cytogenetic scoring system based on an international data collection of 2,902 patients. Patients and Methods Patients were included from the German-Austrian MDS Study Group (n = 1,193), the International MDS Risk Analysis Workshop (n = 816), the Spanish Hematological Cytogenetics Working Group (n = 849), and the International Working Group on MDS Cytogenetics (n = 44) databases. Patients with primary MDS and oligoblastic acute myeloid leukemia (AML) after MDS treated with supportive care only were evaluated for overall survival (OS) and AML evolution. Internal validation by bootstrap analysis and external validation in an independent patient cohort were performed to confirm the results. Results In total, 19 cytogenetic categories were defined, providing clear prognostic classification in 91% of all patients. The abnormalities were classified into five prognostic subgroups (P < .001): very good (median OS, 61 months; hazard ratio [HR], 0.5; n = 81); good (49 months; HR, 1.0 [reference category]; n = 1,809); intermediate (26 months; HR, 1.6; n = 529); poor (16 months; HR, 2.6; n = 148); and very poor (6 months; HR, 4.2; n = 187). The internal and external validations confirmed the results of the score. Conclusion In conclusion, these data should contribute to the ongoing efforts to update the IPSS by refining the cytogenetic risk categories. PMID:22331955

  6. Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy

    DEFF Research Database (Denmark)

    Grövdal, Michael; Karimi, Mohsen; Khan, Rasheed

    2010-01-01

    This prospective Phase II study is the first to assess the feasibility and efficacy of maintenance 5-azacytidine for older patients with high-risk myelodysplastic syndrome (MDS), chronic myelomonocytic leukaemia and MDS-acute myeloid leukaemia syndromes in complete remission (CR) after induction...... and 24 months post CR. Twenty-four (40%) patients achieved CR after induction chemotherapy and 23 started maintenance treatment with azacytidine. Median CR duration was 13.5 months, >24 months in 17% of the patients, and 18-30.5 months in the four patients with trisomy 8. CR duration was not associated......-IV thrombocytopenia and neutropenia occurred after 9.5 and 30% of the cycles, respectively, while haemoglobin levels increased during treatment. 5-azacytidine treatment is safe, feasible and may be of benefit in a subset of patients....

  7. Novel TK2 mutations as a cause of delayed muscle maturation in mtDNA depletion syndrome.

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    Termglinchan, Thanes; Hisamatsu, Seito; Ohmori, Junko; Suzumura, Hiroshi; Sumitomo, Noriko; Imataka, George; Arisaka, Osamu; Murakami, Nobuyuki; Minami, Narihiro; Akihiko, Ishiyama; Sasaki, Masayuki; Goto, Yuichi; Noguchi, Satoru; Nonaka, Ikuya; Mitsuhashi, Satomi; Nishino, Ichizo

    2016-10-01

    Recessive mutations in TK2 cause a severe mitochondrial DNA depletion syndrome (MDS),(1) characterized by severe myopathy from early infancy. Recent reports have suggested a wider clinical spectrum including encephalomyopathic form.(1,2) We report a patient with infantile-onset fatal encephalomyopathy presenting with extreme muscle fiber immaturity.

  8. Differences in Community and Academic Practice Patterns for Newly Diagnosed Myelodysplastic Syndromes (MDS) Patients

    Science.gov (United States)

    Pease, Daniel F.; Ross, Julie A.; Poynter, Jenny N.; Nguyen, Phuong L.; Hirsch, Betsy; Cioc, Adina; Roesler, Michelle A.; Warlick, Erica D.

    2015-01-01

    Purpose The heterogeneous nature of myelodysplastic syndromes (MDS) complicates therapeutic decision making, particularly for newly diagnosed disease. Factors impacting the treatment plan in this early period of disease course are poorly defined. This study determines whether therapeutic choices for newly diagnosed MDS are associated with location of treatment (community or academic), prognostic risk category, and patient age. Methods The Adults in Minnesota with Myelodysplastic Syndromes (AIMMS) database was utilized in this statewide, prospective population-based study conducted by the University of Minnesota (UMN), Mayo Clinic, and Minnesota Department of Health. Adult (age 20+ years) cases of MDS newly diagnosed starting in April 2010 were invited to participate. This analysis includes patients enrolled during the first study year with one-year follow-up data. Treatment choices (supportive, active, and transplant) were stratified by the international prognostic scoring system (IPSS) and the revised-IPSS (IPSS-R), then separated into groups by location of care and age (<65 or 65+ years). Academic-based care was any contact with the UMN and Mayo Clinic; community-based care was all other clinical sites. Results Stratification by IPSS and IPSS-R showed supportive care decreased and active care increased with advancing risk categories (p <0.0001). Comparing treatment setting, community-based care had 77% supportive and 23% active treatment; academic-based care was 36% supportive, 41% active, and 23% transplant (p <0.0001). By age groups, patients <65 years with intermediate, high, or very high risk disease by IPSS-R received 97% active care/transplant, compared to only 52% of patients age 65+. Conclusions Younger patients and those treated at academic centers had a more aggressive treatment approach. Whether these treatment differences convey improved disease control and mortality, and therefore should be extended more frequently to older and community

  9. Impact Of Mutation-derived Antigens In Immune Recognition Of Hematological Malignancies, Specifically Myeloid Dysplastic Syndromes (MDS)

    DEFF Research Database (Denmark)

    Saini, Sunil Kumar; Dorfmüller, S.; Bjerregaard, Anne-Mette

    2016-01-01

    Mutation-derived neoepitopes have been suggested as a major component for immune recognition of solid tumors with a high mutational load, e.g. Melanoma and Non-Small-Cell Lung Cancer (NSCLC). Myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid neoplasms characterized by increasing...

  10. Bilateral lung 99mTc-MDP uptake on the bone scintigraphy in the myelodysplastic syndromes (MDS).

    Science.gov (United States)

    Mogharrabi, Mehdi; Javadi, Hamid; Assadi, Majid

    2013-05-01

    We report a case of myelodysplastic syndrome (MDS) with unusual abnormal 99mTc-MDP activity throughout both lungs on whole-body bone scan. To explain the pancytopenia, bone marrow examination was carried out which showed hypocellularity in addition to large abnormal megakaryocytes indicating myelodysplastic changes. His whole-body bone scan showed increased 99mTc-MDP activity in both lungs, kidneys, and also along the proximal two thirds of the femora. It was concluded that lung uptake in addition to skeletal uptake on scintigraphic bone scanning should be kept in mind in patients with MDS.

  11. Implementation of flow cytometry in the diagnostic work-up of myelodysplastic syndromes in a multicenter approach : Report from the Dutch Working Party on Flow Cytometry in MDS

    NARCIS (Netherlands)

    Westers, Theresia M.; van der Velden, Vincent H. J.; Alhan, Canan; Bekkema, Roelof; Bijkerk, Andre; Brooimans, Rik A.; Cali, Claudia; Drager, Angelika M.; de Haas, Valerie; Homburg, Christa; Kuiper-Kramer, P. (Ellen) A.; Leenders, Marije; Lommerse, Ingrid; Marvelde, Jeroen G. te; van der Molen-Sinke, Joke K.; Moshaver, Bijan; Mulder, Andre B.; Preijers, Frank W. M. B.; Schindhelm, Roger K.; van der Sluijs, Alita; van Wering, Elisabeth R.; Westra, August H.; van de Loosdrecht, Arjan A.; de Jong, A.

    2012-01-01

    Flow cytometry (FC) is recognized as an important tool in the diagnosis of myelodysplastic syndromes (MDS) especially when standard criteria fail. A working group within the Dutch Society of Cytometry aimed to implement FC in the diagnostic work-up of MDS. Hereto, guidelines for data acquisition, an

  12. Surveying the landscape of MDS/MPN research: overlap among the overlap syndromes?

    Science.gov (United States)

    Padron, Eric

    2015-01-01

    The myelodysplastic/myeloproliferative neoplasms (MDS/MPNs) lie at the interphase of phenotypically opposing bone marrow malignancies. They are characterized by concomitant features of bone marrow failure and myeloproliferation and are generally associated with a poor prognosis. Although much is unknown with respect to the clinical course and molecular biology of MDS/MPNs, emerging research is beginning to uncover the key defining characteristics of this designation. In this review, we will discuss the features of MDS/MPN diseases that unify there clinical and molecular course and those that define distinct disease entities. We will discuss advances in genetics and MDS/MPN modeling, as well as translational discoveries that are anticipated to inform the diagnosis, prognostication, and treatment of MDS/MPNs in the near future.

  13. Cost-effectiveness of azacitidine compared with low-doses of chemotherapy (LDC in myelodysplastic syndrome (MDS

    Directory of Open Access Journals (Sweden)

    Myrna Candelaria-Hernández

    2017-05-01

    Full Text Available Introduction: Myelodysplastic syndrome (MDS comprises a group of clonal hematological disorders, characterized by ineffective hematopoiesis and progressive bone marrow failure. It increases the risk of transformation to acute myeloid leukemia (AML. Therapeutic benefit should include overall survival increase (OS, hematological improvement, transfusion dependence and time to progression to AML decrease. Objective: Assess, from a Mexican health-care perspective, the cost-effectiveness of azacitidine compared with low-doses of chemotherapy (LDC plus best supportive care (BSC for the treatment of adult patients with intermediate- 2 and high-risk MDS, who are not eligible for hematopoietic stem-cell transplantation. We developed a cost-effectiveness survival analysis model of three stages: MDS, AML, and death. OS and costs are extrapolated beyond three-year time horizon. Discount rate of 5% was applied. To estimate the model cycle probability transition to mortality state, survival curves were constructed for each treatment arm using individual patient-level data from Study AZA-001. Unitary costs are from public price list, and profiles for the management of MDS and AML were collected separately using a structured questionnaire. Probabilistic sensitivity analyses (PSA were conducted by simultaneously sampling from estimated probability distributions of model parameters. Results: Overall survival was projected to increase by 72.26 weeks with azacitidine. Incremental expected total costs for azacitidine compared to LDC was MXN$68,045. However, the cost of the drug therapy was lower with azacitidine. The incremental cost-effectiveness ratio (ICER for azacitidine compared to LDC was MXN$48,932 per life-year gained (LYG. PSA showed that azacitidine was a highly cost-effective option in 96.49% of the simulated cases in MXN$180,000/LYG willingness-to-pay. Conclusions: Compared with LDC, azacitidine represents a cost-effective treatment alternative in

  14. Treatment-related myelodysplastic syndrome (t-MDS)/acute myeloid leukemia (AML) in children with cancer: A single-center experience.

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    Tragiannidis, Athanasios; Gombakis, Nikolaos; Papageorgiou, Maria; Hatzipantelis, Emmanuel; Papageorgiou, Theodotis; Hatzistilianou, Maria

    2016-12-01

    Treatment-related myelodysplastic syndrome (t-MDS)/acute myeloid leukemia (AML) is a devastating early or late complication of treatment for childhood cancer related with a significant morbidity and mortality. We retrospectively studied survivors of childhood cancer. Overall, 287 patients were recorded in the databases and we identified three (1.04%) with t-MDS. The primary cancer diagnoses were Langerhans cell histiocytosis (one patient) and acute lymphoblastic leukemia (ALL; two patients). The mean age of patients was 12.1 years. All patients had received systemic antifungal treatment for invasive pulmonary aspergillosis successfully treated with voriconazole and liposomal amphotericin B before diagnosis of t-MDS. Two patients (66%) remain alive after a median follow-up period of 3.5 years.

  15. Therapy-Related Myelodysplastic Syndrome Following Treatment for Childhood Acute Lymphoblastic Leukemia: Outcome of Patients Registered in the EWOG-MDS 98/06 Studies

    DEFF Research Database (Denmark)

    Strahm, Birgitte; Amann, Roland; De Moerloose, Barbara

    Objective: Therapy-related myelodysplastic syndrome (tMDS) following treatment of childhood acute lymphoblastic leukemia (ALL) is one of the most frequently observed secondary malignancies in survivors of childhood cancer. Allogeneic stem cell transplantation (SCT) is the only curative treatment....... This analysis was performed to asses the outcome of patients with tMDS following treatment for childhood ALL reported to the EWOG-MDS study group. Patients and Transplant Procedure: Forty-three patients (19 male/24 female) were diagnosed with tMDS between August 1989 and August 2009. The median age at diagnosis...... was 8.9 yrs (3.4–20.5). The median interval from diagnosis of ALL to the diagnosis of tMDS was 3.3 yrs (1.7–7.0). Five patients did not receive SCT and died due to progressive disease at a median of 5.6 mo after diagnosis. Thirty-eight patients were transplanted. One patient was excluded from...

  16. Outcomes in RBC transfusion-dependent patients with Low-/Intermediate-1-risk myelodysplastic syndromes with isolated deletion 5q treated with lenalidomide: A subset analysis from the MDS-004 study

    NARCIS (Netherlands)

    A. Giagounidis (Aristoteles); G.J. Mufti (Ghulam); M. Mittelman (Moshe); G. Sanz (Guillermo); U. Platzbecker (Uwe); P. Muus (P.); D. Selleslag; O. Beyne-Rauzy (Odile); P.A.W. te Boekhorst (Peter); C. del Cañizo (Consuelo); A. Guerci-Bresler (Agnes); L. Nilsson (Lars); M. Lübbert (Michael); B. Quesnel (Bruno); A. Ganser (Arnold); D. Bowen (David); B. Schlegelberger (Brigitte); G. Göhring (Gudrun); T. Fu (Tommy); B. Benettaib (Bouchra); E. Hellström-Lindberg (Eva); P. Fenaux (Pierre)

    2014-01-01

    textabstractObjective: A subset analysis of the randomised, phase 3, MDS-004 study to evaluate outcomes in patients with International Prognostic Scoring System (IPSS)-defined Low-/Intermediate (Int)-1-risk myelodysplastic syndromes (MDS) with isolated del(5q). Methods: Patients received lenalidomid

  17. Validation of the revised international prognostic scoring system (IPSS-R) in patients with lower-risk myelodysplastic syndromes: a report from the prospective European LeukaemiaNet MDS (EUMDS) registry

    NARCIS (Netherlands)

    Swart, L. de; Smith, A.; Johnston, T.W.; Haase, D.; Droste, J.; Fenaux, P.; Symeonidis, A.; Sanz, G.; Hellstrom-Lindberg, E.; Cermak, J.; Germing, U.; Stauder, R.; Georgescu, O.; MacKenzie, M.; Malcovati, L.; Holm, M.S.; Almeida, A.M.; Madry, K.; Slama, B.; Guerci-Bresler, A.; Sanhes, L.; Beyne-Rauzy, O.; Luno, E.; Bowen, D.; Witte, T.J. de

    2015-01-01

    Baseline characteristics, disease-management and outcome of 1000 lower-risk myelodysplastic syndrome (MDS) patients within the European LeukaemiaNet MDS (EUMDS) Registry are described in conjunction with the validation of the revised International Prognostic Scoring System (IPSS-R). The EUMDS regist

  18. Advanced Myelodysplastic Syndromes (MDS) and Juvenile Myelomonocytic Leukemia (JMML) | EU Clinical Trials Register [EU Clinical Trials Register

    Lifescience Database Archive (English)

    Full Text Available trattamento con Azacitidina (Vidaza®) in pazienti pediatrici con sindrome mielodisplastica avanzata, o con leucemia...venile Myelomonocytic Leukemia (JMML) sindrome mielodisplastica avanzata (MDS) e con leucemia mielomonocitic...anomalie genetiche caratterisitche di leucemia mieloide acuta- pazienti con JMML nei quail sia sospettata un

  19. Low-dose decitabine versus best supportive care in elderly patients with intermediate- or high-risk myelodysplastic syndrome (MDS) ineligible for intensive chemotherapy: final results of the randomized phase III study of the European Organisation for Research and Treatment of Cancer Leukemia Group and the German MDS Study Group

    NARCIS (Netherlands)

    Lubbert, M.; Suciu, S.; Baila, L.; Ruter, B.H.; Platzbecker, U.; Giagounidis, A.; Selleslag, D.; Labar, B.; Germing, U.; Salih, H.R.; Beeldens, F.; Muus, P.; Pfluger, K.H.; Coens, C.; Hagemeijer, A.; Eckart Schaefer, H.; Ganser, A.; Aul, C.; Witte, T.J.M. de; Wijermans, P.W.

    2011-01-01

    PURPOSE: To compare low-dose decitabine to best supportive care (BSC) in higher-risk patients with myelodysplastic syndrome (MDS) age 60 years or older and ineligible for intensive chemotherapy. PATIENTS AND METHODS: Two-hundred thirty-three patients (median age, 70 years; range, 60 to 90 years)

  20. Low-dose decitabine versus best supportive care in elderly patients with intermediate- or high-risk myelodysplastic syndrome (MDS) ineligible for intensive chemotherapy: final results of the randomized phase III study of the European Organisation for Research and Treatment of Cancer Leukemia Group and the German MDS Study Group

    NARCIS (Netherlands)

    Lubbert, M.; Suciu, S.; Baila, L.; Ruter, B.H.; Platzbecker, U.; Giagounidis, A.; Selleslag, D.; Labar, B.; Germing, U.; Salih, H.R.; Beeldens, F.; Muus, P.; Pfluger, K.H.; Coens, C.; Hagemeijer, A.; Eckart Schaefer, H.; Ganser, A.; Aul, C.; Witte, T.J.M. de; Wijermans, P.W.

    2011-01-01

    PURPOSE: To compare low-dose decitabine to best supportive care (BSC) in higher-risk patients with myelodysplastic syndrome (MDS) age 60 years or older and ineligible for intensive chemotherapy. PATIENTS AND METHODS: Two-hundred thirty-three patients (median age, 70 years; range, 60 to 90 years) wer

  1. Electrolyte depletion in white-nose syndrome bats

    Science.gov (United States)

    Cryan, Paul M.; Meteyer, Carol Uphoff; Blehert, David S.; Lorch, Jeffrey M.; Reeder, DeeAnn M.; Turner, Gregory G.; Webb, Julie; Behr, Melissa; Verant, Michelle L.; Russell, Robin E.; Castle, Kevin T.

    2013-01-01

    The emerging wildlife disease white-nose syndrome is causing widespread mortality in hibernating North American bats. White-nose syndrome occurs when the fungus Geomyces destructans infects the living skin of bats during hibernation, but links between infection and mortality are underexplored. We analyzed blood from hibernating bats and compared blood electrolyte levels to wing damage caused by the fungus. Sodium and chloride tended to decrease as wing damage increased in severity. Depletion of these electrolytes suggests that infected bats may become hypotonically dehydrated during winter. Although bats regularly arouse from hibernation to drink during winter, water available in hibernacula may not contain sufficient electrolytes to offset winter losses caused by disease. Damage to bat wings from G. destructans may cause life-threatening electrolyte imbalances.

  2. Lessons from the atomic bomb about secondary MDS.

    Science.gov (United States)

    Hata, Tomoko; Imanishi, Daisuke; Miyazaki, Yasushi

    2014-12-01

    Myelodysplastic syndromes (MDSs) is a hematological neoplasm defined by ineffective hematopoiesis, dysplasia of hematopoietic cells, and risk of progression to acute leukemia. MDS occurs as de novo or secondary, and chemoradiotherapy for cancers is thought to increase the risk of MDS among patients. Recently, an epidemiological study for MDS among A-bomb survivors was performed, and it clearly demonstrated that the exposure to external radiation significantly increased the risk of MDS. Precise epidemiological data among survivors have revealed important clinical factors related to the risk of leukemias. In this review, by comparing data for secondary MDS and leukemia/MDS among survivors, several factors which would affect the risk of MDS, especially secondary MDS, are discussed.

  3. Specific scoring systems to predict survival of patients with high-risk myelodysplastic syndrome (MDS) and de novo acute myeloid leukemia (AML) after intensive antileukemic treatment based on results of the EORTC-GIMEMA AML-10 and intergroup CRIANT studies

    NARCIS (Netherlands)

    Oosterveld, M.; Suciu, S.; Muus, P.; Germing, U.; Delforge, M.; Belhabri, A.; Aul, C.; Selleslag, D.; Ferrant, A.; Marie, J.P.; Amadori, S.; Jehn, U.; Mandelli, F.; Hess, U.; Hellstrom-Lindberg, E.; Cakmak-Wollgast, S.; Vignetti, M.; Labar, B.; Willemze, R.; Witte, T.J. de

    2015-01-01

    High-risk myelodysplastic syndrome (MDS) patients have usually a less favorable outcome after intensive treatment compared with de novo acute myeloid leukemia (AML) patients. This may reflect different disease-related and patient-related factors. The purpose of this analysis is to identify disease-s

  4. Platelet doubling after the first azacitidine cycle is a promising predictor for response in myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML) and acute myeloid leukaemia (AML) patients in the Dutch azacitidine compassionate named patient programme

    NARCIS (Netherlands)

    van der Helm, Lieke H.; Alhan, Canan; Wijermans, Pierre W.; Kooy, Marinus van Marwijk; Schaafsma, Ron; Biemond, Bart J.; Beeker, Aart; Hoogendoorn, Mels; van Rees, Bastiaan P.; de Weerdt, Okke; Wegman, Jurgen; Libourel, Ward J.; Luykx-de Bakker, Sylvia A.; Minnema, Monique C.; Brouwer, Rolf E.; Boer, Fransien Croon-de; Eefting, Matthijs; Jie, Kon-Siong G.; de Loosdrecht, Arjan A. van; Koedam, Jan; Veeger, Nic J. G. M.; Vellenga, Edo; Huls, Gerwin

    2011-01-01

    The efficacy of azacitidine in the treatment of high-risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML) and acute myeloid leukaemia (AML) (20-30% blasts) has been demonstrated. To investigate the efficacy of azacitidine in daily clinical practice and to identify predictors

  5. Revisiting guidelines for integration of flow cytometry results in the WHO classification of myelodysplastic syndromes-proposal from the International/European LeukemiaNet Working Group for Flow Cytometry in MDS.

    Science.gov (United States)

    Porwit, A; van de Loosdrecht, A A; Bettelheim, P; Brodersen, L Eidenschink; Burbury, K; Cremers, E; Della Porta, M G; Ireland, R; Johansson, U; Matarraz, S; Ogata, K; Orfao, A; Preijers, F; Psarra, K; Subirá, D; Valent, P; van der Velden, V H J; Wells, D; Westers, T M; Kern, W; Béné, M C

    2014-09-01

    Definite progress has been made in the exploration of myelodysplastic syndromes (MDS) by flow cytometry (FCM) since the publication of the World Health Organization 2008 classification of myeloid neoplasms. An international working party initiated within the European LeukemiaNet and extended to include members from Australia, Canada, Japan, Taiwan and the United States has, through several workshops, developed and subsequently published consensus recommendations. The latter deal with preanalytical precautions, and propose small and large panels, which allow evaluating immunophenotypic anomalies and calculating myelodysplasia scores. The current paper provides guidelines that strongly recommend the integration of FCM data with other diagnostic tools in the diagnostic work-up of MDS.

  6. On Asymmetric Quantum MDS Codes

    CERN Document Server

    Ezerman, Martianus Frederic; Ling, San

    2010-01-01

    Assuming the validity of the MDS Conjecture, the weight distribution of all MDS codes is known. Using a recently-established characterization of asymmetric quantum error-correcting codes, linear MDS codes can be used to construct asymmetric quantum MDS codes with $d_{z} \\geq d_{x}\\geq 2$ for all possible values of length $n$ for which linear MDS codes over $\\F_{q}$ are known to exist.

  7. Myelodysplastic changes mimicking MDS following treatment for osteosarcoma

    DEFF Research Database (Denmark)

    Løhmann, Ditte

    Myelodysplastic changes mimicking MDS following treatment for osteosarcoma Ditte Juel Adolfsen Løhmann, Department of Pediatrics, Aarhus University Hospital, Skejby, Denmark Authors: Ditte Juel Adolfsen Løhmann and Henrik Hasle. Therapy-related myelodysplastic syndrome/acute myeloid leukaemia (t......-MDS/AML) is a feared long-term complication of paediatric cancer including osteosarcoma. Few develop t-MDS/AML, but it is not known how many have significant haematological changes after finishing treatment for osteosarcoma. In this study we reviewed biochemistry from a consecutive series of children for up to two...... for osteosarcoma developed haematological abnormalities similar to early MDS but few developed t-MDS/AML. Close monitoring of patients recovering from osteosarcoma is essential. Keywords: Osteosarcoma, t-MDS/AML, Haematological abnormalities, Children...

  8. Downregulation of MMP1 in MDS-derived mesenchymal stromal cells reduces the capacity to restrict MDS cell proliferation

    Science.gov (United States)

    Zhao, Sida; Zhao, Youshan; Guo, Juan; Fei, Chengming; Zheng, Qingqing; Li, Xiao; Chang, Chunkang

    2017-01-01

    The role of mesenchymal stromal cells (MSCs) in the pathogenesis of myelodysplastic syndromes (MDS) has been increasingly addressed, but has yet to be clearly elucidated. In this investigation, we found that MDS cells proliferated to a greater extent on MDS-derived MSCs compared to normal MSCs. Matrix metalloproteinase 1(MMP1), which was downregulated in MDS-MSCs, was identified as an inhibitory factor of MDS cell proliferation, given that treatment with an MMP1 inhibitor or knock-down of MMP1 in normal MSCs resulted in increased MDS cell proliferation. Further investigations indicated that MMP1 induced apoptosis of MDS cells by interacting with PAR1 and further activating the p38 MAPK pathway. Inhibition of either PAR1 or p38 MAPK can reverse the apoptosis-inducing effect of MMP1. Taken together, these data indicate that downregulation of MMP1 in MSCs of MDS patients may contribute to the reduced capacity of MSCs to restrict MDS cell proliferation, which may account for the malignant proliferation of MDS cells. PMID:28262842

  9. Erlotinib exhibits antineoplastic off-target effects in AML and MDS: a preclinical study.

    Science.gov (United States)

    Boehrer, Simone; Adès, Lionel; Braun, Thorsten; Galluzzi, Lorenzo; Grosjean, Jennifer; Fabre, Claire; Le Roux, Génèviève; Gardin, Claude; Martin, Antoine; de Botton, Stéphane; Fenaux, Pierre; Kroemer, Guido

    2008-02-15

    Erlotinib, an inhibitor of the epidermal growth factor receptor (EGFR), induces differentiation, cell-cycle arrest, and apoptosis of EGFR-negative myeloblasts of patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), as well as in EGFR-negative cell lines representing these diseases (P39, KG-1, and HL 60). This off-target effect can be explained by inhibitory effects on JAK2. Apoptosis induction coupled to mitochondrial membrane permeabilization occurred independently from phenotypic differentiation. In apoptosis-sensitive AML cells, erlotinib caused a rapid (within less than 1 hour) nucleocytoplasmic translocation of nucleophosmin-1 (NPM-1) and p14(ARF). Apoptosis-insensitive myeloblasts failed to manifest this translocation yet became sensitive to apoptosis induction by erlotinib when NPM-1 was depleted by RNA interference. Moreover, erlotinib reduced the growth of xenografted human AML cells in vivo. Erlotinib also killed CD34(+) bone marrow blasts from MDS and AML patients while sparing normal CD34(+) progenitors. This ex vivo therapeutic effect was once more associated with the nucleocytoplasmic translocation of NPM-1 and p14(ARF). One patient afflicted with both MDS and non-small cell lung cancer manifested hematologic improvement in response to erlotinib. In summary, we here provide novel evidence in vitro, ex vivo, and in vivo for the potential therapeutic efficacy of erlotinib in the treatment of high-risk MDS and AML.

  10. Cytogenetic findings in primary and secondary MDS.

    Science.gov (United States)

    Heim, S

    1992-01-01

    More than 1300 MDS cases with clonal cytogenetic abnormalities, 200 of them secondary MDS, have been reported. The most common aberrations in primary MDS are del(5q) (27%), trisomy 8 (19%), monosomy 7 (15%), der(11q) (7%), -5, der(12p) and -Y (5%), del(7q) (4%), and t(1;7), der(3q), del(13q), i(17q) and del(20q) in 2% or less. The 5q- is mostly, but not always, a del(5)(q13q33); it is the cytogenetic hall-mark of the "5q- syndrome" and is frequently found as the sole abnormality. The frequency of the aberrations varies among MDS subgroups: 5q- is most frequent in RA, -5, -7, and der(12p) are more common in CMML and especially in RAEB, and +8 and der(11q) are more often found in RARS. The most common aberrations in secondary MDS are -7 (41%), del(5q) (28%), -5 (11%), der(21q) (9%), 7q-, +8 and der(12p) (8%), t(1;7) and -12 (7%), der(17p) (6%), der(3p) and der(6p) (5%), and der(3q), der(11q), -17, -18 and der(19q) (4%). The average number of abnormalities per case is 5.3, compared with 2.9 in unspecified MDS. The frequency of cytogenetically unrelated clones is 5.7% in secondary and 4.3% in primary MDS. When the literature data are broken down by type of genotoxic exposure, it turns out that -5, -7, and der(17p) are over-represented in patients who have received chemotherapy, whereas 5q- is associated with no exposure or preceding radiotherapy only. The karyotypic profile is prognostically important: patients with -7 or complex karyotypes have a higher risk of progression to acute leukemia and shorter survival.

  11. Monitoring treatment efficiency in MDS at the molecular level; possibilities now and in the future.

    NARCIS (Netherlands)

    Dijk, J.P. van; Witte, T.J.M. de

    2004-01-01

    Myelodysplastic syndromes (MDS) are a heterogeneous group of bone marrow (BM) diseases. MDS patients suffer from bone marrow failure because of the expansion of a malignant clone, resulting in abnormal differentiation of blood cells and severe pancytopenias. MDS patients have a high propensity for t

  12. The Weights in MDS Codes

    CERN Document Server

    Ezerman, Martianus Frederic; Sole, Patrick

    2009-01-01

    The weights in MDS codes of length n and dimension k over the finite field GF(q) are studied. Up to some explicit exceptional cases, the MDS codes with parameters given by the MDS conjecture are shown to contain all k weights in the range n-k+1 to n. The proof uses the covering radius of the dual code

  13. Morphology, cytogenetics and classification of MDS.

    Science.gov (United States)

    Giagounidis, Aristoteles; Haase, Detlef

    2013-12-01

    Myelodysplastic syndromes are heterogeneous bone marrow diseases with a variable pathogenetic background. Cytomorphological alterations in peripheral blood films as well as bone marrow aspirates and histological findings in trephine biopsies result from cytogenetic and molecular abnormalities, epigenetic dysregulation and immune dysfunction and are key elements for setting the diagnosis of MDS. Whereas diagnosis can be made quite easily in advanced MDS this is much more difficult in early MDS, especially in cases with cytopenias or dysplasias of uncertain significance (ICUS and IDUS). Recommendations, illustrated by case reports for a stepwise annealing to the final diagnosis and exclusion of differential diagnoses are given. Furthermore, the problem of correct counting and identification of blasts is covered and features defining dysplasia in all three cell lineages are recapitulated thoroughly. Histopathology is not mandatory but has a distinct diagnostic and prognostic value especially in cases with hypoplasia or fibrosis and when the TP53 mutational status is of relevance. In up to 70% of patients with MDS clonal chromosome abnormalities can be identified which have a high impact on setting the correct diagnosis and estimation of prognosis. Incidence, type, molecular background and clinical relevance of distinct anomalies as well as cytogenetic subgroups are presented in detail and the development of the new cytogenetic prognostic scoring system as part of the IPSS-R is explained. The value of FISH-Analysis as a complementary tool for chromosome analysis in MDS is demonstrated with special emphasis on the possibility to perform frequent cytogenetic monitoring by CD34-FISH examination of peripheral blood. Finally the evolution of MDS-classification systems from FAB to WHO with a critical discussion of their shortcomings like degree of dysplasia, blast thresholds, inclusion/exclusion of CMML, and the lack of dynamic information is presented.

  14. Expression and role of CIP2A in myelodysplastic syndromes(MDS)%CIP2A在骨髓增生异常综合症中的意义探讨

    Institute of Scientific and Technical Information of China (English)

    王石松

    2013-01-01

    Objective To investigate the expression and significance of cancerous inhibitor of protein phosphatase 2A(CIP2A) in myelodysplastic syndromes(MDS). Methods The immunohistochemical SP staining was used to detect expression of CIP2A in control group and in MDS. Result Expression of CIP2A in MDS was significantly higher than that in control group(P 0.05). CIP2A in high-risk group was significantly higher than that in low-risk group(P <0.05). CIP2A in AML group was significantly higher than that in high-risk group(P <0.05). Conclusion The expression of CIP2A is significantly increased in MDS bone marrow mononuclear cells, and the positive expression of CIP2A is associated with the genesis and prognosis of MDS.%  目的探讨CIP2A在骨髓增生异常综合症(MDS)中的表达及意义.方法采用免疫组化SP法对31例MDS患者、19例急性髓系白血病(AML)患者(包括4例由MDS转变而来)和20例对照组骨髓单个核细胞中CIP2A蛋白质水平进行检测.结果 MDS组CIP2A蛋白的表达水平高于对照组,差异有统计学意义(P <0.05).MDS高危组CIP2A蛋白的表达水平显著高于MDS低危组(P <0.05),AML组CIP2A蛋白的表达水平显著高于MDS高危组(P <0.05).结论 CIP2A在MDS骨髓单个核细胞中高表达可能与MDS的疾病发展有关.

  15. Stem cell depletion in Hutchinson-Gilford progeria syndrome.

    Science.gov (United States)

    Rosengardten, Ylva; McKenna, Tomás; Grochová, Diana; Eriksson, Maria

    2011-12-01

    Hutchinson-Gilford progeria syndrome (HGPS or progeria) is a very rare genetic disorder with clinical features suggestive of premature aging. Here, we show that induced expression of the most common HGPS mutation (LMNA c.1824C>T, p.G608G) results in a decreased epidermal population of adult stem cells and impaired wound healing in mice. Isolation and growth of primary keratinocytes from these mice demonstrated a reduced proliferative potential and ability to form colonies. Downregulation of the epidermal stem cell maintenance protein p63 with accompanying activation of DNA repair and premature senescence was the probable cause of this loss of adult stem cells. Additionally, upregulation of multiple genes in major inflammatory pathways indicated an activated inflammatory response. This response has also been associated with normal aging, emphasizing the importance of studying progeria to increase the understanding of the normal aging process.

  16. Strongly-MDS convolutional codes

    NARCIS (Netherlands)

    Gluesing-Luerssen, H; Rosenthal, J; Smarandache, R

    2006-01-01

    Maximum-distance separable (MDS) convolutional codes have the property that their free distance is maximal among all codes of the same rate and the same degree. In this paper, a class of MDS convolutional codes is introduced whose column distances reach the generalized Singleton bound at the earlies

  17. Outcomes in RBC transfusion-dependent patients with Low-/Intermediate-1-risk myelodysplastic syndromes with isolated deletion 5q treated with lenalidomide: a subset analysis from the MDS-004 study

    Science.gov (United States)

    Giagounidis, Aristoteles; Mufti, Ghulam J; Mittelman, Moshe; Sanz, Guillermo; Platzbecker, Uwe; Muus, Petra; Selleslag, Dominik; Beyne-Rauzy, Odile; te Boekhorst, Peter; del Cañizo, Consuelo; Guerci-Bresler, Agnès; Nilsson, Lars; Lübbert, Michael; Quesnel, Bruno; Ganser, Arnold; Bowen, David; Schlegelberger, Brigitte; Göhring, Gudrun; Fu, Tommy; Benettaib, Bouchra; Hellström-Lindberg, Eva; Fenaux, Pierre

    2014-01-01

    Objective A subset analysis of the randomised, phase 3, MDS-004 study to evaluate outcomes in patients with International Prognostic Scoring System (IPSS)-defined Low-/Intermediate (Int)-1-risk myelodysplastic syndromes (MDS) with isolated del(5q). Methods Patients received lenalidomide 10 mg/d (days 1–21; n = 47) or 5 mg/d (days 1–28; n = 43) on 28-d cycles or placebo (n = 45). From the placebo and lenalidomide 5 mg groups, 84% and 58% of patients, respectively, crossed over to lenalidomide 5 or 10 mg at 16 wk, respectively. Results Rates of red blood cell-transfusion independence (RBC-TI) ≥182 d were higher in the lenalidomide 10 mg (57.4%; P < 0.0001) and 5 mg (37.2%; P = 0.0001) groups vs. placebo (2.2%). Cytogenetic response rates (major + minor responses) were 56.8% (P < 0.0001), 23.1% (P = 0.0299) and 0%, respectively. Two-year cumulative risk of acute myeloid leukaemia progression was 12.6%, 17.4% and 16.7% in the lenalidomide 10 mg, 5 mg, and placebo groups, respectively. In a 6-month landmark analysis, overall survival was longer in lenalidomide-treated patients with RBC-TI ≥182 d vs. non-responders (P = 0.0072). The most common grade 3–4 adverse event was myelosuppression. Conclusions These data support the clinical benefits and acceptable safety profile of lenalidomide in transfusion-dependent patients with IPSS-defined Low-/Int-1-risk MDS with isolated del(5q). PMID:24813620

  18. Specific scoring systems to predict survival of patients with high-risk myelodysplastic syndrome (MDS) and de novo acute myeloid leukemia (AML) after intensive antileukemic treatment based on results of the EORTC-GIMEMA AML-10 and intergroup CRIANT studies.

    Science.gov (United States)

    Oosterveld, Margriet; Suciu, Stefan; Muus, Petra; Germing, Ulrich; Delforge, Michel; Belhabri, Amin; Aul, Carlo; Selleslag, Dominik; Ferrant, Augustin; Marie, Jean-Pierre; Amadori, Sergio; Jehn, Ulrich; Mandelli, Franco; Hess, Uwe; Hellström-Lindberg, Eva; Cakmak-Wollgast, Songuel; Vignetti, Marco; Labar, Boris; Willemze, Roel; de Witte, Theo

    2015-01-01

    High-risk myelodysplastic syndrome (MDS) patients have usually a less favorable outcome after intensive treatment compared with de novo acute myeloid leukemia (AML) patients. This may reflect different disease-related and patient-related factors. The purpose of this analysis is to identify disease-specific prognostic factors and to develop prognostic scores for both patient groups. A total of 692 patients in the EORTC/GIMEMA AML-10 study and 289 patients in the CRIANT study received identical remission-induction and consolidation treatment. Estimated 5-year survival rate was 34 % in the AML-10 versus 27 % in the CRIANT study, and estimated disease-free survival was 40 % versus 28 %, respectively. In multivariate analysis, cytogenetic characteristics, white blood count, and age appeared prognostic for survival in both studies. French-American-British (FAB) subtype and performance status were prognostic in the AML-10 study only, whereas number of cytopenias and duration of antecedent hematologic disorder >6 months were prognostic in the CRIANT study only. The prognostic scores distinguish three groups with a 5-year survival rate of 54, 38, and 19 % in the AML-10 study versus 69, 37, and 5 % in the CRIANT study. The prognostic value of these scores has been validated on two external series. The new scoring systems form a practical tool to predict the outcome of individual MDS and AML patients treated with intensive antileukemic therapy.

  19. Outcome of Allogeneic Stem Cell Transplantation for Patients Transformed to Myelodysplastic Syndrome or Leukemia from Severe Aplastic Anemia: A Report from the MDS Subcommittee of the Chronic Malignancies Working Party and the Severe Aplastic Anemia Working Party of the European Group for Blood and Marrow Transplantation

    NARCIS (Netherlands)

    Hussein, A.A.; Halkes, C.M.; Socie, G.; Tichelli, A.; Borne, P.A. von dem; Schaap, M.N.; Foa, R.; Ganser, A.; Dufour, C.; Bacigalupo, A.; Locasciulli, A.; Aljurf, M.; Peters, C.; Robin, M.; Biezen, A.A. van; Volin, L.; Witte, T.J. de; Marsh, J.; Passweg, J.R.; Kroger, N.

    2014-01-01

    One hundred and forty patients who had undergone hematopoietic stem cell transplantation (HSCT) for myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) transformation after treatment of severe aplastic anemia (SAA) were identified in the European Group for Blood and Marrow Transplanta

  20. Depletion of cytotoxic T-cells does not protect NUP98-HOXD13 mice from myelodysplastic syndrome but reveals a modest tumor immunosurveillance effect.

    Directory of Open Access Journals (Sweden)

    Sheryl M Gough

    Full Text Available Myelodysplastic syndrome (MDS and aplastic anemia (AA patients both present with symptoms of bone marrow failure. In many AA patients, these features are thought to result from an oligoclonal expansion of cytotoxic T-cells that destroy haematopoietic stem or progenitor cells. This notion is supported by the observation that AA patients respond to immunosuppressive therapy. A fraction of MDS patients also respond well to immunosuppressive therapy suggesting a similar role for cytotoxic T-cells in the etiology of MDS, however the role of cytotoxic T-cells in MDS remains unclear. Mice that express a NUP98-HOXD13 (NHD13 transgene develop a MDS that closely mimics the human condition in terms of dysplasia, ineffective hematopoiesis, and transformation to acute myeloid leukemia (AML. We followed a cohort of NHD13 mice lacking the Rag1 protein (NHD13/Rag1KO to determine if the absence of lymphocytes might 1 delay the onset and/or diminish the severity of the MDS, or 2 effect malignant transformation and survival of the NHD13 mice. No difference was seen in the onset or severity of MDS between the NHD13 and NHD13/Rag1KO mice. However, NHD13/Rag1KO mice had decreased survival and showed a trend toward increased incidence of transformation to AML compared to the NHD13 mice, suggesting protection from AML transformation by a modest immuno-surveillance effect. In the absence of functional Tcrb signaling in the NHD13/Rag1KO T-cell tumors, Pak7 was identified as a potential Tcrb surrogate survival signal.

  1. Apoptosis-Related Gene Expression Profiling in Hematopoietic Cell Fractions of MDS Patients

    NARCIS (Netherlands)

    MC Langemeijer, Saskia; Mariani, Niccolo; Knops, Ruth; Gilissen, Christian; Woestenenk, Rob; de Witte, Theo; Huls, Gerwin; van der Reijden, Bert A.; Jansen, Joop H.

    2016-01-01

    Although the vast majority of patients with a myelodysplastic syndrome (MDS) suffer from cytopenias, the bone marrow is usually normocellular or hypercellular. Apoptosis of hematopoietic cells in the bone marrow has been implicated in this phenomenon. However, in MDS it remains only partially

  2. Whole-arm translocation of der(5;17)(p10;q10) with concurrent TP53 mutations in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS): A unique molecular-cytogenetic subgroup.

    Science.gov (United States)

    Hong, Ming; Hao, Suyang; Patel, Keyur P; Kantarjian, Hagop M; Garcia-Manero, Guillermo; Yin, C Cameron; Medeiros, L Jeffrey; Lin, Pei; Lu, Xinyan

    2016-05-01

    Der(5;17)(p10;q10) is a recurrent but rare aberration reported in myeloid neoplasms (MNs). We report 48 such patients including 19 acute myeloid leukemia (AML) and 29 myelodysplastic syndrome (MDS), to characterize their clinicopathological features. There were 29 men and 19 women, with a median age of 61 years (range, 18-80). 62.5% patients had therapy-related diseases (t-MNs), 70.8% had multilineage dysplasia and 83.3% showed complex karyotypes. In 39 patients tested, FLT3, NPM1, CEBPA, KIT were all wild type and NRAS, KRAS, IDH1, APC, TET2 mutations were detected in single case(s) respectively. TP53 mutations were identified in 8 of 10 cases (80%) tested. Median disease-free survival (DFS) and overall survival (OS) were 3 and 10 months, respectively and did not differ between AML or MDS cases, or between de novo versus therapy-related cases, or between the groups with or without complex karyotypes. In 19 patients who achieved complete remission after chemotherapy, and in 9 patients who underwent stem cell transplantation, the OS was better (14 and 17.5 months, P = 0.0128 and P = 0.0086, respectively). The der(5;17)(p10;q10) represents a unique molecular-cytogenetic subgroup in t-MNs and, associated with complex karyotypes. TP53 inactivation, resulting from 17p deletion coupled with TP53 mutation, likely contributes to the poor clinical outcome of these patients.

  3. MDS 3.0 Frequency Report

    Data.gov (United States)

    U.S. Department of Health & Human Services — The MDS 3.0 Frequency Report summarizes information for active residents currently in nursing homes. The source of these counts is the residents MDS assessment...

  4. Clinical variability in neurohepatic syndrome due to combined mitochondrial DNA depletion and Gaucher disease

    Directory of Open Access Journals (Sweden)

    Julie Harvengt

    2014-01-01

    Full Text Available A 1-year-old girl born to consanguineous parents presented with unexplained liver failure, leading to transplantation at 19 months. Subsequent partial splenectomy for persistent cytopenia showed the presence of foamy cells, and Gaucher disease was confirmed by homozygosity for the p.Leu483Pro mutation in the GBA gene. She was treated by enzyme replacement therapy (ERT. Clinical follow-up showed mild developmental delay, strabismus, nystagmus and oculomotor apraxia. Biochemical studies revealed multiple respiratory chain deficiencies and a mosaic pattern of deficient complex IV immunostaining in liver and fibroblast. Molecular analysis identified a mtDNA depletion syndrome due to the homozygous p.Pro98Leu mutation in MPV17. A younger sister unaffected by mtDNA depletion, presented with pancytopenia and hepatosplenomegaly. ERT for Gaucher disease resulted in visceral normalization without any neurological symptom. A third sister, affected by both conditions, had marked developmental delay, strabismus and ophthalmoplegia but no liver cirrhosis. In conclusion, intrafamilal variability occurs in MPV17-related disease. The combined pathological effect of Gaucher and mitochondrial diseases can negatively impact neurological and liver functions and influence the outcome in consanguineous families. The immunocytochemical staining of OXPHOS protein in tissues and cultured cells is a powerful tool revealing mosaic pattern of deficiency pointing to mtDNA-related mitochondrial disorders.

  5. Gene expression profiling in MDS and AML: potential and future avenues

    DEFF Research Database (Denmark)

    Theilgaard-Mönch, K; Boultwood, J; Ferrari, S

    2011-01-01

    Today, the classification systems for myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) already incorporate cytogenetic and molecular genetic aberrations in an attempt to better reflect disease biology. However, in many MDS/AML patients no genetic aberrations have been identified yet...... the MDS/AML classification system, incorporating as yet unknown molecular genetic and epigenetic pathomechanisms, which are likely reflected by aberrant gene expression patterns. In this study, we provide a comprehensive review on how GEP has contributed to a refined molecular taxonomy of MDS and AML...... technologies, which will continue to improve our understanding of malignant transformation in myeloid malignancies and thereby contribute to individualized risk-adapted treatment strategies for MDS and AML patients....

  6. A zebrafish model of Roberts syndrome reveals that Esco2 depletion interferes with development by disrupting the cell cycle.

    Directory of Open Access Journals (Sweden)

    Maren Mönnich

    Full Text Available The human developmental diseases Cornelia de Lange Syndrome (CdLS and Roberts Syndrome (RBS are both caused by mutations in proteins responsible for sister chromatid cohesion. Cohesion is mediated by a multi-subunit complex called cohesin, which is loaded onto chromosomes by NIPBL. Once on chromosomes, cohesin binding is stabilized in S phase upon acetylation by ESCO2. CdLS is caused by heterozygous mutations in NIPBL or cohesin subunits SMC1A and SMC3, and RBS is caused by homozygous mutations in ESCO2. The genetic cause of both CdLS and RBS reside within the chromosome cohesion apparatus, and therefore they are collectively known as "cohesinopathies". However, the two syndromes have distinct phenotypes, with differences not explained by their shared ontology. In this study, we have used the zebrafish model to distinguish between developmental pathways downstream of cohesin itself, or its acetylase ESCO2. Esco2 depleted zebrafish embryos exhibit features that resemble RBS, including mitotic defects, craniofacial abnormalities and limb truncations. A microarray analysis of Esco2-depleted embryos revealed that different subsets of genes are regulated downstream of Esco2 when compared with cohesin subunit Rad21. Genes downstream of Rad21 showed significant enrichment for transcriptional regulators, while Esco2-regulated genes were more likely to be involved the cell cycle or apoptosis. RNA in situ hybridization showed that runx1, which is spatiotemporally regulated by cohesin, is expressed normally in Esco2-depleted embryos. Furthermore, myca, which is downregulated in rad21 mutants, is upregulated in Esco2-depleted embryos. High levels of cell death contributed to the morphology of Esco2-depleted embryos without affecting specific developmental pathways. We propose that cell proliferation defects and apoptosis could be the primary cause of the features of RBS. Our results show that mutations in different elements of the cohesion apparatus have

  7. T-cell receptor Vbeta CDR3 oligoclonality frequently occurs in childhood refractory cytopenia (MDS-RC) and severe aplastic anemia

    DEFF Research Database (Denmark)

    Vries, A.C. de; Langerak, A.W.; Verhaaf, B.

    2008-01-01

    (Very) severe acquired aplastic anemia ((v)SAA) and myelodysplastic syndrome (MDS) are rare diseases in childhood. (V)SAA is a bone marrow (BM) failure syndrome characterized by immune-mediated destruction of hematopoietic progenitors. MDS is a malignant clonal stem cell disorder, of which...

  8. Low-dose rapamycin extends lifespan in a mouse model of mtDNA depletion syndrome.

    Science.gov (United States)

    Siegmund, Stephanie; Yang, Hua; Sharma, Rohit; Javors, Martin; Skinner, Owen; Mootha, Vamsi; Hirano, Michio; Schon, Eric A

    2017-09-01

    Mitochondrial disorders affecting oxidative phosphorylation (OxPhos) are caused by mutations in both the nuclear and mitochondrial genomes. One promising candidate for treatment is the drug rapamycin, which has been shown to extend lifespan in multiple animal models, and which was previously shown to ameliorate mitochondrial disease in a knock-out mouse model lacking a nuclear-encoded gene specifying an OxPhos structural subunit (Ndufs4). In that model, relatively high-dose intraperitoneal rapamycin extended lifespan and improved markers of neurological disease, via an unknown mechanism. Here, we administered low-dose oral rapamycin to a knock-in (KI) mouse model of authentic mtDNA disease, specifically, progressive mtDNA depletion syndrome, resulting from a mutation in the mitochondrial nucleotide salvage enzyme thymidine kinase 2 (TK2). Importantly, low-dose oral rapamycin was sufficient to extend Tk2KI/KI mouse lifespan significantly, and did so in the absence of detectable improvements in mitochondrial dysfunction. We found no evidence that rapamycin increased survival by acting through canonical pathways, including mitochondrial autophagy. However, transcriptomics and metabolomics analyses uncovered systemic metabolic changes pointing to a potential "rapamycin metabolic signature." These changes also implied that rapamycin may have enabled the Tk2KI/KI mice to utilize alternative energy reserves, and possibly triggered indirect signaling events that modified mortality through developmental reprogramming. From a therapeutic standpoint, our results support the possibility that low-dose rapamycin, while not targeting the underlying mtDNA defect, could represent a crucial therapy for the treatment of mtDNA-driven, and some nuclear DNA-driven, mitochondrial diseases. © The Author 2017. Published by Oxford University Press.

  9. Implementation of standardized international karyotype scoring practices is needed to provide uniform and systematic evaluation for patients with myelodysplastic syndrome using IPSS criteria: An International Working Group on MDS Cytogenetics Study.

    Science.gov (United States)

    Chun, Kathy; Hagemeijer, Anne; Iqbal, Anwar; Slovak, Marilyn L

    2010-02-01

    Karyotype status and complexity are key components of the IPSS; however, emerging data suggest the use of cytogenetics at disease presentation is not applied uniformly among MDS patients. To investigate the degree of consistency of scoring karyotypes, the International Working Group on MDS Cytogenetics (IWGMC) conducted a survey of 32 abnormal karyotype challenges carried out in two phases: (a) an initial survey without any specified karyotype counting guidelines and (b) a second survey conducted after the development of IWGMC consensus guidelines for scoring karyotype complexity. Results indicate that IWGMC guidelines were simple and clear for the cytogeneticists in scoring karyotype complexity, but not as clear for the hematologists. We propose an immediate need for standardized international karyotype counting practices and a corresponding IPSS cytogenetic risk that can be incorporated into the cytogenetics reports of all newly diagnosed MDS patients.

  10. Effect observation and mechanism of low - dose decitabine combined with modified CAG therapeutic regimen in the treatment of patients with myelodysplastic syndrome(MDS)%低剂量地西他滨序贯改良 CAG 方案对治疗骨髓增生异常综合征的临床疗效观察

    Institute of Scientific and Technical Information of China (English)

    陈喜填; 夏维林; 林东; 王楚林; 张淳嘉; 吴桂香

    2016-01-01

    目的:探究低剂量地西他滨序贯改良 CAG 方案对治疗中高危骨髓增生异常综合征(Myelodysplastic syn-drome,MDS)的临床疗效。方法:随机抽取收治的中高危 MDS 患者96例,分为观察组46例及对照组患者50例,其中观察组患者采用低剂量地西他滨序贯 CAG 方案进行治疗,而对照组患者均采用 CAG 方案进行治疗,观察两组患者的临床疗效、不良反应的发生情况及处理结果。结果:观察组比对照组患者的疾病缓解率更高、疗效更显著,且两组比较差异具有统计学意义(P ﹤0.05)。结论:低剂量地西他滨序贯改良 CAG 方案治疗高危 MDS 比单用 CAG 方案疗效更明显、确切。%Objective The objection of the study was to investigate the clinical efficiencies and adverse reactions of treating the myelodysplastic syndrome(MDS)by using low - does decitabine combined with modified CAG therapeutic regimen. Method 96 high - risk MDS patients were randomly selected,they were divided into observation group with 46 cases and control group with 50 cases. The observation group was treated with low - dose decitabine combined with modified CAG therapeutic regimen, while the control group was treated with CAG therapeutic regimen. Clinical efficacy,adverse reactions and treatment results of each group were observed and analyzed. Results The remission rate was higher and the curative effect was more significant of ob-servation group when compared with control group,the difference between two groups has statistical significance( P ﹤ 0. 05) . Conclusion The effect of high risk MDS in treatment with low dose of decitabine combined with modified CAG therapeutic regi-ment is more significance than treated with CAG therapeutic regimen.

  11. A calcium- and calpain-dependent pathway determines the response to lenalidomide in myelodysplastic syndromes.

    Science.gov (United States)

    Fang, Jing; Liu, Xiaona; Bolanos, Lyndsey; Barker, Brenden; Rigolino, Carmela; Cortelezzi, Agostino; Oliva, Esther N; Cuzzola, Maria; Grimes, H Leighton; Fontanillo, Celia; Komurov, Kakajan; MacBeth, Kyle; Starczynowski, Daniel T

    2016-07-01

    Despite the high response rates of individuals with myelodysplastic syndrome (MDS) with deletion of chromosome 5q (del(5q)) to treatment with lenalidomide (LEN) and the recent identification of cereblon (CRBN) as the molecular target of LEN, the cellular mechanism by which LEN eliminates MDS clones remains elusive. Here we performed an RNA interference screen to delineate gene regulatory networks that mediate LEN responsiveness in an MDS cell line, MDSL. We identified GPR68, which encodes a G-protein-coupled receptor that has been implicated in calcium metabolism, as the top candidate gene for modulating sensitivity to LEN. LEN induced GPR68 expression via IKAROS family zinc finger 1 (IKZF1), resulting in increased cytosolic calcium levels and activation of a calcium-dependent calpain, CAPN1, which were requisite steps for induction of apoptosis in MDS cells and in acute myeloid leukemia (AML) cells. In contrast, deletion of GPR68 or inhibition of calcium and calpain activation suppressed LEN-induced cytotoxicity. Moreover, expression of calpastatin (CAST), an endogenous CAPN1 inhibitor that is encoded by a gene (CAST) deleted in del(5q) MDS, correlated with LEN responsiveness in patients with del(5q) MDS. Depletion of CAST restored responsiveness of LEN-resistant non-del(5q) MDS cells and AML cells, providing an explanation for the superior responses of patients with del(5q) MDS to LEN treatment. Our study describes a cellular mechanism by which LEN, acting through CRBN and IKZF1, has cytotoxic effects in MDS and AML that depend on a calcium- and calpain-dependent pathway.

  12. Long Term Care Minimum Data Set (MDS)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Long-Term Care Minimum Data Set (MDS) is a standardized, primary screening and assessment tool of health status that forms the foundation of the comprehensive...

  13. Long Term Care Minimum Data Set (MDS)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Long-Term Care Minimum Data Set (MDS) is a standardized, primary screening and assessment tool of health status that forms the foundation of the comprehensive...

  14. Genetics Home Reference: RRM2B-related mitochondrial DNA depletion syndrome, encephalomyopathic form with renal ...

    Science.gov (United States)

    ... Munnich A, Rötig A. Mutation of RRM2B, encoding p53-controlled ribonucleotide reductase (p53R2), causes severe mitochondrial DNA depletion. Nat Genet. 2007 Jun;39(6):776-80. Epub 2007 May 7. Citation on PubMed GeneReview: RRM2B-Related Mitochondrial Disease Pontarin G, Ferraro P, Bee L, Reichard P, ...

  15. Hypomethylation and up-regulation of PD-1 in T cells by azacytidine in MDS/AML patients

    DEFF Research Database (Denmark)

    Ørskov, Andreas D; Treppendahl, Marianne B; Skovbo, Anni

    2015-01-01

    The hypomethylating agents (HMAs) are standard therapy for patients with higher-risk myelodysplastic syndrome (MDS); however, the majority of the patients will lose their response to HMAs over time due to unknown mechanisms. It has recently been shown that T cell expression of the immunoinhibitory......-responding patients compared to healthy controls (p = 0.023). Accordingly, in addition to their beneficial function, HMAs induce PD-1 expression on T cells in the MDS microenvironment, thereby likely hampering the immune response against the MDS blasts. Thus, we suggest that activation of the PD-1 checkpoint during...

  16. Tryptophan depletion in chronic fatigue syndrome, a pilot cross-over study

    NARCIS (Netherlands)

    The, G.K.H.; Verkes, R.J.; Fekkes, D.; Bleijenberg, G.; Meer, J.W. van der; Buitelaar, J.K.

    2014-01-01

    BACKGROUND: Chronic fatigue syndrome (CFS) is still an enigmatic disorder. CFS can be regarded as a complex disorder with tremendous impact on lives of CFS-patients. Full recovery without treatment is rare.A somatic explanation for the fatigue is lacking. There is clinical and experimental evidence

  17. Tryptophan depletion in chronic fatigue syndrome, a pilot cross-over study

    NARCIS (Netherlands)

    G.K.H. The (Gerard K.H.); R.J. Verkes (Robbert); D. Fekkes (Durk); G. Bleijenberg (G.); J.W.M. van der Meer (Jos); J.K. Buitelaar (Jan)

    2014-01-01

    textabstractBackground: Chronic fatigue syndrome (CFS) is still an enigmatic disorder. CFS can be regarded as a complex disorder with tremendous impact on lives of CFS-patients. Full recovery without treatment is rare. A somatic explanation for the fatigue is lacking. There is clinical and experimen

  18. [Epigenetic dysregulation in myelodysplastic syndrome].

    Science.gov (United States)

    Sashida, Goro; Iwama, Atsushi

    2015-02-01

    Myelodysplastic syndrome (MDS) is a clonal hematopoietic stem cell disease characterized by impaired hematopoiesis and an increased risk of transformation to acute myeloid leukemia. Various epigenetic regulators are mutated in MDS patients, indicating that accumulation of epigenetic alterations together with genetic alterations plays a crucial role in the development of MDS.

  19. Maternal uniparental disomy of chromosome 2 in a patient with a DGUOK mutation associated with hepatocerebral mitochondrial DNA depletion syndrome.

    Science.gov (United States)

    Haudry, Coralie; de Lonlay, Pascale; Malan, Valerie; Bole-Feysot, Christine; Assouline, Zahra; Pruvost, Solenn; Brassier, Anais; Bonnefont, Jean-Paul; Munnich, Arnold; Rötig, Agnès; Lebre, Anne-Sophie

    2012-12-01

    We report maternal uniparental disomy of chromosome 2 (matUPD2) in a 9-month-old girl presenting with hepatocerebral mitochondrial DNA depletion syndrome. This patient was homozygous for the c.352C>T (p.Arg118Cys) mutation in DGUOK gene. The proband's mother was heterozygous for the mutation was absent in DNA of the father. For proband, the absence of paternal contribution at the DGUOK locus prompted us to exclude intragenic DGUOK deletion of the paternal allele with Multiplex ligation-dependent probe amplification (MLPA) analysis. We also excluded non-paternity by studying various markers at different loci. Then we performed an analysis of copy number variations and absence of heterozygosity (AOH) on the proband DNA using high resolution oligonucleotides microarray. Several large regions of AOH with no copy number change were detected on chromosome 2 and one of these AOH regions encompassed DGUOK gene. These results were confirmed with haplotype analysis using polymorphic markers. Informative SNPs and microsatellites markers spanning the whole chromosome 2 showed a matUPD2 with heterodisomy and isodisomy regions, the absence of paternal allele and presence of two maternal alleles, with only one maternal allele on the region of DGUOK locus in 2p13.1. This is the first demonstration of matUPD2 with segmental isodisomy at 2p13.1 locus in hepatocerebral mitochondrial DNA depletion syndrome. The identification of UPD2 will impact genetic counseling for the proband's parents. Because the recurrence risk for UPD2 is very low, the risk for disease in further offspring for this couple is negligible.

  20. Spontaneous and Fas-induced apoptosis of low-grade MDS erythroid precursors involves the endoplasmic reticulum.

    Science.gov (United States)

    Gyan, E; Frisan, E; Beyne-Rauzy, O; Deschemin, J-C; Pierre-Eugene, C; Randriamampita, C; Dubart-Kupperschmitt, A; Garrido, C; Dreyfus, F; Mayeux, P; Lacombe, C; Solary, E; Fontenay, M

    2008-10-01

    Spontaneous apoptosis of bone marrow erythroid precursors accounts for the anemia that characterizes most low-grade myelodysplastic syndromes (MDS). We have shown that death of these precursors involved the Fas-dependent activation of caspase-8. To explore the pathway leading from caspase-8 activation to apoptosis, we transduced MDS bone marrow CD34(+) cells with a lentivirus encoding wild-type (WT) or endoplasmic reticulum (ER)-targeted Bcl-2 protein before inducing their erythroid differentiation. Both WT-Bcl-2 and ER-targeted Bcl-2 prevented spontaneous and Fas-dependent apoptosis in MDS erythroid precursors. ER-targeted Bcl-2 inhibited mitochondrial membrane depolarization and cytochrome c release in MDS erythroid precursors undergoing apoptosis, indicating a role for the ER in the death pathway, upstream of the mitochondria. MDS erythroid precursors demonstrated elevated ER Ca(2+) stores and these stores remained unaffected by ER-targeted Bcl-2. The ER-associated protein Bcl-2-associated protein (BAP) 31 was cleaved by caspase-8 in MDS erythroid precursors undergoing apoptosis. The protective effect of ER-targeted Bcl-2 toward spontaneous and Fas-induced apoptosis correlated with inhibition of BAP31 cleavage. A protective effect of erythropoietin against Fas-induced BAP31 cleavage and apoptosis was observed. We propose that apoptosis of MDS erythroid precursors involves the ER, downstream of Fas and upstream of the mitochondria, through the cleavage of the ER-associated BAP31 protein.

  1. SKY detection of chromosome rearrangements in two cases of tMDS with a complex karyotype.

    Science.gov (United States)

    Cohen, Ninette; Trakhtenbrot, Luba; Yukla, Mona; Manor, Yosef; Gaber, Elena; Yosef, Gabi; Amariglio, Ninette; Rechavi, Gideon; Amiel, Aliza

    2002-10-15

    In this study, we used spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH) as complementary techniques for the analysis of two therapy-related secondary myelodysplastic syndrome (t-MDS) cases with complex karyotypes, previously analyzed by G-banding. Different types of SKY's cytogenetic contributions include confirmation of G-banding results, identification of partially characterized rearrangements, identification of marker chromosomes unidentified by G-banding, and detection of cryptic reciprocal translocations. In particular, the ability of SKY to clarify a number of markers led to the comprehension of clonal evolution. The common aberration found in these two t-MDS cases was the fragility of chromosome 5 and monosomy of chromosome 18. We clearly present that the use of SKY combined with conventional G-banding analysis and FISH has assisted in the identification of important chromosomal events that may play a key role in the development of t-MDS.

  2. Myelodysplastic Syndrome Occurring in a Patient with Gorlin Syndrome.

    Science.gov (United States)

    Mull, Jamie L; Madden, Lisa M; Bayliss, Susan J

    2016-07-01

    We report a case of myelodysplastic syndrome (MDS) occurring in an African American boy with Gorlin syndrome with a novel PTCH1 mutation. Before developing MDS, the patient had been treated with chemotherapy and radiation for a medulloblastoma. He received a bone marrow transplant for the MDS and eventually died of treatment complications. Secondary hematologic malignancies are a known complication of certain chemotherapeutics, although whether a patient with Gorlin syndrome has a greater propensity for the development of such malignancies is unclear.

  3. TK2-related mitochondrial DNA depletion syndrome:two cases report and review of literature%TK2相关线粒体DNA耗竭综合征2例并文献复习

    Institute of Scientific and Technical Information of China (English)

    移艳红; 吴晔; 熊晖; 王朝霞; 袁云; 常杏芝

    2016-01-01

    Objective To study the clinical characteristics,muscle pathological features,diagnosis and prognosis of TK2-related mitochondrial DNA depletion syndrome(MDS).Methods Clinical and laboratory data of 2 cases of TK2-related myopathic MDS were reported.And data of previously reported 58 TK2-related MDS cases were reviewed.Results Total 60 patients consisted of 35 male and 25 female.The age of onset ranged from the birth to the age of 74 years old,and 54 of the patients were attacked at the age younger than 3 years old.Muscle weakness and hypotonia were detected in all patients,with 40 patients(including the newly diagnosed 2 cases) manifested as pure myopathic form,and 20 patients with other multiple organs involvement.Serum creatine kinase was mildly increased (211-6 500 IU/L) in 53 patients.Elevated serum lactic acid level (2.3-12.0 mmol/L)was observed in 24 patients.Muscle biopsy was available from 55 patients,and ragged red fibers and/or cytochrome C oxidase (COX)-negative fibers were detected in 48 out of them.Nine out of 11 patients received electronic microscope study showed proliferation of abnormal mitochondria.Respiratory chain enzymatic activities in skeletal muscle were reduced in 31 out of 33 patients.Marked mtDNA content reduction was observed in 36 out of 41 patients (4%-25% of age-and tissue-matched controls).A total of 42 TK2 mutations were found in 60 patients,including 2 novel mutations c.923A > G and c.619-2A > T in this study.Conclusions The most common clinical manifestations of TK2-related MDS are severely,rapidly progressing myopathy with infantile or early childhood onset.As the detection rate of characteristic pathologic features in muscle is high,muscle biopsy is important for the diagnosis of TK2-related MDS.%目的 探讨TK2相关线粒体DNA耗竭综合征的临床和病理特征、诊断及预后,提高对该病的认识.方法 报道2例基因和病理检查确诊的TK2相关肌病型线粒体DNA耗竭综合

  4. Immune Mechanisms in Myelodysplastic Syndrome

    Directory of Open Access Journals (Sweden)

    Andreas Glenthøj

    2016-06-01

    Full Text Available Myelodysplastic syndrome (MDS is a spectrum of diseases, characterized by debilitating cytopenias and a propensity of developing acute myeloid leukemia. Comprehensive sequencing efforts have revealed a range of mutations characteristic, but not specific, of MDS. Epidemiologically, autoimmune diseases are common in patients with MDS, fueling hypotheses of common etiological mechanisms. Both innate and adaptive immune pathways are overly active in the hematopoietic niche of MDS. Although supportive care, growth factors, and hypomethylating agents are the mainstay of MDS treatment, some patients—especially younger low-risk patients with HLA-DR15 tissue type—demonstrate impressive response rates after immunosuppressive therapy. This is in contrast to higher-risk MDS patients, where several immune activating treatments, such as immune checkpoint inhibitors, are in the pipeline. Thus, the dual role of immune mechanisms in MDS is challenging, and rigorous translational studies are needed to establish the value of immune manipulation as a treatment of MDS.

  5. Depletion of white adipose tissue in cancer cachexia syndrome is associated with inflammatory signaling and disrupted circadian regulation.

    Directory of Open Access Journals (Sweden)

    Maria Tsoli

    Full Text Available Involuntary weight loss in patients with cancer is the hallmark of cancer cachexia. The etiology of cachexia is multifactorial involving loss of skeletal muscle and adipose tissue associated with high systemic levels of acute phase proteins and inflammatory cytokines. While muscle wasting overtly impacts on cancer patient quality of life, loss of lipid depots represents a sustained energy imbalance. In this study fat depletion was examined in Colon-26 model of cancer cachexia, which is a widely used rodent model of this syndrome. We investigated diurnal expression of circadian rhythm regulators as well as key mediators of energy metabolism and cytokine signaling. Mice bearing the C26 tumour exhibited reduced adipose mass, elevated adipose tissue lipolysis and a 5-fold increase in plasma levels of free fatty acids. These changes were associated with activated IL-6 signaling in WAT through a 3-fold increase in phosphorylated STAT3 and high SOCS3 gene expression levels. In addition perturbations in circadian regulation of lipid metabolism were also observed. Lipid catabolism did not appear to be influenced by the classical PKA pathway activating the lipase HSL. ATGL protein levels were elevated 2-fold in cachectic mice while 4-fold increase phosphorylated ACC and a 2-fold decrease in phosphorylated 4EBP1 was observed indicating that lipid metabolism is modulated by the ATGL & AMPK/mTOR pathways. This study provides evidence for activation of cytokine signaling and concomitant alterations in circadian rhythm and regulators of lipid metabolism in WAT of cachectic animals.

  6. Depletion of white adipose tissue in cancer cachexia syndrome is associated with inflammatory signaling and disrupted circadian regulation.

    Science.gov (United States)

    Tsoli, Maria; Schweiger, Martina; Vanniasinghe, Anne S; Painter, Arran; Zechner, Rudolf; Clarke, Stephen; Robertson, Graham

    2014-01-01

    Involuntary weight loss in patients with cancer is the hallmark of cancer cachexia. The etiology of cachexia is multifactorial involving loss of skeletal muscle and adipose tissue associated with high systemic levels of acute phase proteins and inflammatory cytokines. While muscle wasting overtly impacts on cancer patient quality of life, loss of lipid depots represents a sustained energy imbalance. In this study fat depletion was examined in Colon-26 model of cancer cachexia, which is a widely used rodent model of this syndrome. We investigated diurnal expression of circadian rhythm regulators as well as key mediators of energy metabolism and cytokine signaling. Mice bearing the C26 tumour exhibited reduced adipose mass, elevated adipose tissue lipolysis and a 5-fold increase in plasma levels of free fatty acids. These changes were associated with activated IL-6 signaling in WAT through a 3-fold increase in phosphorylated STAT3 and high SOCS3 gene expression levels. In addition perturbations in circadian regulation of lipid metabolism were also observed. Lipid catabolism did not appear to be influenced by the classical PKA pathway activating the lipase HSL. ATGL protein levels were elevated 2-fold in cachectic mice while 4-fold increase phosphorylated ACC and a 2-fold decrease in phosphorylated 4EBP1 was observed indicating that lipid metabolism is modulated by the ATGL & AMPK/mTOR pathways. This study provides evidence for activation of cytokine signaling and concomitant alterations in circadian rhythm and regulators of lipid metabolism in WAT of cachectic animals.

  7. MDS Array Codes with Optimal Rebuilding

    CERN Document Server

    Tamo, Itzhak; Bruck, Jehoshua

    2011-01-01

    MDS array codes are widely used in storage systems to protect data against erasures. We address the \\emph{rebuilding ratio} problem, namely, in the case of erasures, what is the the fraction of the remaining information that needs to be accessed in order to rebuild \\emph{exactly} the lost information? It is clear that when the number of erasures equals the maximum number of erasures that an MDS code can correct then the rebuilding ratio is 1 (access all the remaining information). However, the interesting (and more practical) case is when the number of erasures is smaller than the erasure correcting capability of the code. For example, consider an MDS code that can correct two erasures: What is the smallest amount of information that one needs to access in order to correct a single erasure? Previous work showed that the rebuilding ratio is bounded between 1/2 and 3/4, however, the exact value was left as an open problem. In this paper, we solve this open problem and prove that for the case of a single erasure...

  8. Th17 Cells Exhibit Antitumor Effects in MDS Possibly through Augmenting Functions of CD8+ T Cells.

    Science.gov (United States)

    Li, Jing; Yue, Lanzhu; Wang, Huaquan; Liu, Chunyan; Liu, Hui; Tao, Jinglian; Qi, Weiwei; Wang, Yihao; Zhang, Wei; Fu, Rong; Shao, Zonghong

    2016-01-01

    Th17 cells are a newly found subset of distinct CD4+ Th effector cells' family and are found to play an important role in cancers. Myelodysplastic syndromes (MDS) are a common malignant hematological disease. Here, we showed that both the percentage and the function of Th17 cells were elevated in low-risk MDS while being decreased in high-risk MDS. Levels of upstream molecules of Th17 cells, IL-6 and IL-23, were higher in low-risk MDS but lower in high-risk MDS patients. The abnormal percentage of Th17 cells was closely related to clinical parameters including karyotype, morphologic blast percentage of bone marrow, peripheral absolute neutrophil count, and hemoglobin concentration. Furthermore, expression rates of perforin and granzyme B in BM CD3+CD8+ cells (cytotoxic T lymphocyte, CTL) positively correlated with levels of IL-17 but negatively correlated with BM blast percentage and could be significantly increased after stimulation with human recombinant IL-17 (rhIL-17). Our results suggested that Th17 cells might play an antitumor effect in the pathogenesis of MDS through IL-17/CTL pathway.

  9. Apoptosis-Related Gene Expression Profiling in Hematopoietic Cell Fractions of MDS Patients

    Science.gov (United States)

    Langemeijer, Saskia MC; Knops, Ruth; Gilissen, Christian; Woestenenk, Rob; de Witte, Theo; Huls, Gerwin; van der Reijden, Bert A; Jansen, Joop H

    2016-01-01

    Although the vast majority of patients with a myelodysplastic syndrome (MDS) suffer from cytopenias, the bone marrow is usually normocellular or hypercellular. Apoptosis of hematopoietic cells in the bone marrow has been implicated in this phenomenon. However, in MDS it remains only partially elucidated which genes are involved in this process and which hematopoietic cells are mainly affected. We employed sensitive real-time PCR technology to study 93 apoptosis-related genes and gene families in sorted immature CD34+ and the differentiating erythroid (CD71+) and monomyeloid (CD13/33+) bone marrow cells. Unsupervised cluster analysis of the expression signature readily distinguished the different cellular bone marrow fractions (CD34+, CD71+ and CD13/33+) from each other, but did not discriminate patients from healthy controls. When individual genes were regarded, several were found to be differentially expressed between patients and controls. Particularly, strong over-expression of BIK (BCL2-interacting killer) was observed in erythroid progenitor cells of low- and high-risk MDS patients (both p = 0.001) and TNFRSF4 (tumor necrosis factor receptor superfamily 4) was down-regulated in immature hematopoietic cells (p = 0.0023) of low-risk MDS patients compared to healthy bone marrow. PMID:27902785

  10. Limited clinical efficacy of azacitidine in transfusion-dependent, growth factor-resistant, low- and Int-1-risk MDS

    DEFF Research Database (Denmark)

    Dybedahl, I; Holm, Mette; Karimi, M

    2014-01-01

    This prospective phase II study evaluated the efficacy of azacitidine (Aza)+erythropoietin (Epo) in transfusion-dependent patients with lower-risk myelodysplastic syndrome (MDS). Patients ineligible for or refractory to full-dose Epo+granulocyte colony stimulation factors for >8 weeks and a trans...

  11. 线粒体DNA耗竭综合征1例临床特点和DGUOK基因突变分析%Clinical features and DGUOK mutations of an infant with mitochondrial DNA depletion syndrome

    Institute of Scientific and Technical Information of China (English)

    邓梅; 林伟霞; 郭丽; 张占会; 宋元宗

    2016-01-01

    The aim of this study was to investigate the clinical features and DGUOK gene mutations of an infant with mitochondrial DNA depletion syndrome (MDS). The patient (more than 7 months old) manifested as hepatosplenomegaly, abnormal liver function, nystagmus and psychomotor retardation. Genetic DNA was extracted from peripheral blood samples of the patient and her parents. Targeted Exome Sequencing was performed to explore the genetic causes. Sanger sequencing was carried out to confirm the detected mutations. The sequencing results showed that the patient was a compound heterozygote for c.679G>A and c.817delT in the DGUOK gene. The former was a reportedly pathogenic missense mutation of maternal origin, while the latter, a frameshift mutation from the father, has not been described yet. The findings in this study expand the mutation spectrum of DGUOK gene, and provide molecular evidence for the etiologic diagnosis of the patient as well as for the genetic counseling and prenatal diagnosis in the family.%该文报道1例线粒体DNA耗竭综合征患儿的临床特征及DGUOK基因突变特点。患儿女,婴儿期起病,表现为肝脾肿大、肝功能异常、眼球震颤和精神运动发育迟缓等。提取患儿及其父母外周血DNA标本,采用外显子组捕获测序技术检测致病突变,并对检测到的突变进行Sanger测序验证。结果显示患儿为DGUOK基因突变c.679G>A和c.817delT的复合杂合子,前一个突变来自于母亲,为已报道致病性突变;后者来自于父亲,是一个未见文献报道的新突变。该研究扩展了DGOUK基因突变谱,为患儿病因诊断及该家系的遗传咨询和产前诊断提供了分子依据。

  12. Therapeutic efficacies of decitabine application prior to hematopoietic cell transplantation in patients with myelodysplastic syndrome and acute myeloid leukemia%含地西他滨方案桥接异基因造血干细胞移植治疗MDS/AML的效果评估

    Institute of Scientific and Technical Information of China (English)

    周进; 王婧; 刘辉; 郑慧菲; 马玲; 王攀峰; 颜霜; 吴德沛; 傅琤琤

    2015-01-01

    Objective To explore the therapeutic efficacies of decitabine application prior to hematopoietic cell transplantation (HSCY) in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).Methods Retrospective reviews were conducted for 46 patients with MDS (n =14) and AML (n =32) on a therapy of decitabine prior to allo-HSCT between September 2009 and February 2013.Results In MDS patients,complete remission (CR,n =10),partial remission (PR,n =2) and stable disease (SD,n =1) were achieved prior to HSCT.And the remission rate of one course was 10/14.After decitabine dosing,17/32 patients achieved CR in 32 with AML and the remission rate of one course was 53.1% (17/32) and effective rate of one course (CR + PR) achieves 78.1% (25/32).Successful engraftment was attained in all MDS patients and 12/14 patients survived disease-free and one died of pneumonia after relapse.And 28 patients with AML attained successful engraftment after using decitabine prior to allo-HSCT and there were 20 disease-free survivors.Ten patients died and another lived with tumor.The incidences of acute and chronic graft-versus-host disease (GVHD) among evaluable patients were 4.3% (2/26) and 23.9% (11/46) respectively.After a median follow-up of 8 months for survivors,the treatment-related mortality was 23.9% (11/46).The 30-month disease-free survival (DFS) rate was 53.1% and 30-month overall survival rate after decitabine dosing 61.9%.Conclusion Thus decitabine is an effective therapy during bridge time to HSCT in patients with MDS and AML.%目的 观察骨髓增生异常综合征(MDS)及复发难治性急性髓系白血病(AML)患者造血干细胞移植前选择含地西他滨方案诱导或巩固作为过渡治疗的临床疗效,以期降低肿瘤负荷,控制疾病并为寻找供体赢取时间.方法 回顾性分析苏州大学附属第一医院2009年9月至2013年2月期间在异基因造血干细胞移植前采用地西他滨单药

  13. Childhood myelodysplastic syndrome.

    Science.gov (United States)

    Chatterjee, Tathagata; Choudhry, V P

    2013-09-01

    Myelodysplastic syndrome (MDS) comprises of a heterogeneous group of bone marrow disorders resulting from a clonal stem cell defect characterised by cytopenias despite a relatively hypercellular marrow, ineffective hematopoiesis, morphological dysplasia in the marrow elements, no response to hematinics such as iron, B12 or folic acid and risk of progression to leukemia. Myelodysplastic syndrome in childhood is extremely rare and accounts for less than 5% of all hematopoietic neoplasms in children below the age of 14 y. The primary MDS in children, also known as de novo MDS differs from secondary MDS which generally follows congenital or acquired bone marrow (BM) failure syndromes as well as from therapy related MDS, commonly resulting from cytotoxic therapy. MDS associated with Down syndrome which accounts for approximately one-fourth of cases of childhood MDS is now considered a unique biologic entity synonymous with Down syndrome-related myeloid leukemia and is biologically distinct from other cases of childhood MDS. Refractory cytopenia of childhood (RCC) is the commonest type of MDS. Genetic changes predisposing to MDS in childhood remain largely obscure. Monosomy 7 is by-far the commonest cytogenetic abnormality associated with childhood MDS; however most cases of RCC show a normal karyotype. Complex cytogenetic abnormalities and trisomy 8 and trisomy 21 are also occasionally observed. The most effective and curative treatment is Hematopoietic stem cell transplantation and this is particularly effective in children with the monosomy 7 genetic defect as well as those displaying complex karyotype abnormalities provided it is instituted early in the course of the disease.

  14. Valuation of transfusion-free living in MDS: results of health utility interviews with patients

    Directory of Open Access Journals (Sweden)

    Lübbert Michael

    2009-09-01

    Full Text Available Abstract Background This study measured how myelodysplastic syndrome (MDS patients value transfusion independence (TI, reduced transfusions (RT and transfusion-dependence (TD using health utility assessment methodology. Methods 47 MDS patients were interviewed, US (n = 8, France (n = 9, Germany (n = 9 and the UK (n = 21, to elicit the utility value of TI, RT and TD. Health states were developed based on literature; patient forum discussions; and were validated by a hematologist. Face-to-face interviews used the feeling thermometer Visual Analogue Scale (VAS and the Time Trade-Off (TTO method to value the health states on a 0 (dead to 1 (perfect health scale. Socio-demographic, clinical, and quality-of-life (EQ-5D characteristics were surveyed to describe the patient sample. Results and Discussion The mean age was 67 years (range: 29-83; 45% male, 70% retired; 40% had secondary/high school education, or higher (32%, and 79% lived with family, a partner or spouse, or friends. The mean time from MDS diagnosis was 5 years (range:1-23. Most patients (87% received previous transfusions and 49% had received a transfusion in the last 3 months. Mean EQ-5D index score was 0.78; patients reported at least some problem with mobility (45%, usual activities (40%, pain/discomfort (47%, and anxiety/depression (34%. Few patients had difficulty understanding the VAS (n = 3 and TTO (n = 4 exercises. Utility scores for TI were higher than for RT (0.84 vs. 0.77; p Conclusion Patients value TI, suggesting an important role for new treatments aiming to achieve greater TI in MDS. These results can be used in preference-based health economic evaluation of new MDS treatments, such as in future cost-utility studies.

  15. Gingival enlargement in myelodysplastic syndrome

    Directory of Open Access Journals (Sweden)

    Navia George

    2015-01-01

    Full Text Available The myelodysplastic syndrome (MDS is characterized by peripheral blood cytopenias and increased risk of transformation to acute myeloid leukemia. This syndrome affects blood cell production and behavior. MDS is difficult to diagnose because of the absence of symptoms in the early stage of the disease. Often it is accidentally discovered during a routine physical exam/blood test. Till date, only a few cases of gingival enlargement associated with MDS are reported in the literature. Here is a remarkable case of gingival enlargement heralding the presence of MDS.

  16. PP2A: The Achilles Heal in MDS with 5q Deletion

    Directory of Open Access Journals (Sweden)

    David eSallman

    2014-09-01

    Full Text Available Myelodysplastic syndromes (MDS represent a hematologically diverse group of myeloid neoplasms, however, one subtype characterized by an isolated deletion of chromosome 5q (del(5q is pathologically and clinically distinct. Patients with del(5q MDS share biological features that account for the profound hypoplastic anemia and unique sensitivity to treatment with lenalidomide. Ineffective erythropoiesis in del(5q MDS arises from allelic deletion of the ribosomal processing S-14 (RPS14 gene, which leads to MDM2 sequestration with consequent p53 activation and erythroid cell death. Since its approval in 2005, lenalidomide has changed the natural course of the disease. Patients who achieve transfusion independence and/or a cytogenetic response with lenalidomide have a decreased risk of progression to AML and an improved overall survival compared to non-responders. Elucidation of the mechanisms of action of lenalidomide in del(5q MDS has advanced therapeutic strategies for this disease. The selective cytotoxicity of lenalidomide in del(5q clones derives from inhibition of a haplodeficient phosphatase whose catalytic domain is encoded within the common deleted region on chromosome 5q, i.e., protein phosphatase 2A (PP2Acα. PP2A is a highly conserved, dual specificity phosphatase that plays an essential role in regulation of the G2/M checkpoint. Inhibition of PP2Acα results in cell cycle arrest and apoptosis in del(5q cells. Targeted knockdown of PP2Acα using siRNA is sufficient to sensitize non-del(5q clones to lenalidomide. Through its inhibitory effect on PP2A, lenalidomide stabilizes MDM2 to restore p53 degradation in erythroid precursors, with subsequent arrest in G2/M. Unfortunately, the majority of patients with del(5q MDS develop resistance to lenalidomide over time associated with PP2Acα overexpression. Targeted inhibition of PP2A with a more potent inhibitor has emerged as an attractive therapeutic approach for patients with del(5q MDS.

  17. Hypermethylation of the VTRNA1-3 Promoter is Associated with Poor Outcome in Lower Risk Myelodysplastic Syndrome Patients

    DEFF Research Database (Denmark)

    Helbo, Alexandra Søgaard; Treppendahl, Marianne; Aslan, Derya

    2015-01-01

    Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematopoietic disorders. MDS is frequently associated with deletions on chromosome 5q as well as aberrant DNA methylation patterns including hypermethylation of key tumor suppressors. We have previously shown that hypermethylation ...

  18. Downregulation but lack of promoter hypermethylation or somatic mutations of the potential tumor suppressor CXXC5 in MDS and AML with deletion 5q

    DEFF Research Database (Denmark)

    Treppendahl, Marianne Bach; Möllgård, L; Hellström-Lindberg, E

    2013-01-01

    During recent years mutations in epigenetic modulators have been identified in several human cancers, including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)[1]. CXXC5 has been found to be necessary for retinoic acid induced differentiation of myelocytic leukemia cells, identify......During recent years mutations in epigenetic modulators have been identified in several human cancers, including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)[1]. CXXC5 has been found to be necessary for retinoic acid induced differentiation of myelocytic leukemia cells...

  19. Lenalidomide induces ubiquitination and degradation of CK1α in del(5q) MDS.

    Science.gov (United States)

    Krönke, Jan; Fink, Emma C; Hollenbach, Paul W; MacBeth, Kyle J; Hurst, Slater N; Udeshi, Namrata D; Chamberlain, Philip P; Mani, D R; Man, Hon Wah; Gandhi, Anita K; Svinkina, Tanya; Schneider, Rebekka K; McConkey, Marie; Järås, Marcus; Griffiths, Elizabeth; Wetzler, Meir; Bullinger, Lars; Cathers, Brian E; Carr, Steven A; Chopra, Rajesh; Ebert, Benjamin L

    2015-07-09

    Lenalidomide is a highly effective treatment for myelodysplastic syndrome (MDS) with deletion of chromosome 5q (del(5q)). Here, we demonstrate that lenalidomide induces the ubiquitination of casein kinase 1A1 (CK1α) by the E3 ubiquitin ligase CUL4-RBX1-DDB1-CRBN (known as CRL4(CRBN)), resulting in CK1α degradation. CK1α is encoded by a gene within the common deleted region for del(5q) MDS and haploinsufficient expression sensitizes cells to lenalidomide therapy, providing a mechanistic basis for the therapeutic window of lenalidomide in del(5q) MDS. We found that mouse cells are resistant to lenalidomide but that changing a single amino acid in mouse Crbn to the corresponding human residue enables lenalidomide-dependent degradation of CK1α. We further demonstrate that minor side chain modifications in thalidomide and a novel analogue, CC-122, can modulate the spectrum of substrates targeted by CRL4(CRBN). These findings have implications for the clinical activity of lenalidomide and related compounds, and demonstrate the therapeutic potential of novel modulators of E3 ubiquitin ligases.

  20. Myelodysplastic syndrome in children and adolescents.

    Science.gov (United States)

    Niemeyer, Charlotte M; Baumann, Irith

    2008-01-01

    Myelodysplastic syndromes (MDS) are clonal disorders characterized by ineffective hematopoiesis and subsequent frequent development of acute myeloid leukemia (AML). In children and adolescents, MDS are uncommon disorders, accounting for less than 5% of hematopoietic malignancy, with great heterogeneity in presentation and clinical course. The genetic changes predisposing children to MDS are largely obscure. Monosomy 7 is the most common chromosomal abnormality, often occurring as a sole abnormality. The recent pediatric modification of the World Health Organization (WHO) classification has greatly facilitated the diagnostic process. Refractory cytopenia (RC) is the most common MDS subtype in children, occurring in about half of all MDS cases. There is consensus that the relationship between MDS with increased blast count and de novo AML is better defined by biological and clinical features than by blast count. Because monosomy 7 is the only chromosomal abnormality strongly suggestive of MDS, children presenting with a low blast count and other chromosomal aberrations or normal karyotype must be closely observed before a diagnosis of MDS can be established. With an increasing number of children surviving primary cancer with chemotherapy or radiation therapy, the incidence of secondary therapy-related MDS is rising. The MDS risk is also increased in patients with inherited bone marrow failure disorders; this relationship provides valuable insights into MDS biology. Allogeneic hematopoietic stem cell transplantation (HSCT) from a matched related or suitable unrelated donor is the choice for most children with MDS and can rescue a large proportion of patients.

  1. Provision of TCRγδ T Cells and Memory T Cells Plus Selected Use of Blinatumomab in Naïve T-cell Depleted Haploidentical Donor Hematopoietic Cell Transplantation for Hematologic Malignancies Relapsed or Refractory Despite Prior Transplantation

    Science.gov (United States)

    2017-03-29

    Acute Lymphoblastic Leukemia (ALL); Acute Myeloid Leukemia (AML); Myeloid Sarcoma; Chronic Myeloid Leukemia (CML); Juvenile Myelomonocytic Leukemia (JMML); Myelodysplastic Syndrome (MDS); Non-Hodgkin Lymphoma (NHL)

  2. MDS 2.0 Public Quality Indicator and Resident Reports

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Minimum Data Set (MDS) is part of the federally mandated process for clinical assessment of all residents in Medicare or Medicaid certified nursing homes. This...

  3. Resident Assessment Instrument/Minimum Data Set (RAI/MDS)

    Data.gov (United States)

    Department of Veterans Affairs — The Resident Assessment Instrument/Minimum Data Set (RAI/MDS) is a comprehensive assessment and care planning process used by the nursing home industry since 1990 as...

  4. Gene-Specific Demethylation as Targeted Therapy in MDS

    Science.gov (United States)

    2016-07-01

    methylation is considered a dominant mechanism for Tumor Suppressor Genes silencing during MDS evolution to AML, but the causes leading to aberrant DNA...DNA methylation is considered a dominant mechanism for Tumor Suppressor Genes silencing during MDS evolution to AML, but the causes leading to...study two tumor suppressor genes chromosomally linked and frequently methylated in cancer: the CDKN2A (aka P16 ) and CDKN2B (aka: P15). While P16 is

  5. Relationship between the non-motor items of the MDS-UPDRS and Quality of Life in patients with Parkinson's disease.

    Science.gov (United States)

    Skorvanek, Matej; Rosenberger, Jaroslav; Minar, Michal; Grofik, Milan; Han, Vladimir; Groothoff, Johan W; Valkovic, Peter; Gdovinova, Zuzana; van Dijk, Jitse P

    2015-01-01

    The Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is a newly developed comprehensive tool to assess Parkinson's disease (PD), which covers a wider range of non-motor PD manifestations than the original UPDRS scale. The aim of this study was to assess the relationship between the MDS-UPDRS and Quality of Life (QoL) and to analyze the relationship between individual MDS-UPDRS non-motor items and QoL. A total of 291 PD patients were examined in a multicenter Slovak study. Patients were assessed by the MDS-UPDRS, HY scale and PDQ39. Data were analyzed using the multiple regression analyses. The mean participant age was 68.0 ± 9.0 years, 53.5% were men, mean disease duration was 8.3 ± 5.3 years and mean HY was 2.7 ± 1.0. In a multiple regression analysis model the PDQ39 summary index was related to MDS-UPDRS parts II, I and IV respectively, but not to part III. Individual MDS-UPDRS non-motor items related to the PDQ39 summary index in the summary group and in the non-fluctuating patients subgroup were pain, fatigue and features of dopamine dysregulation syndrome (DDS). In the fluctuating PD patient subgroup, PDQ39 was related to pain and Depressed mood items. Other MDS-UPDRS non-motor items e.g. Anxious mood, Apathy, Cognitive impairment, Hallucinations and psychosis, Sleep problems, Daytime sleepiness and Urinary problems were related to some PDQ39 domains. The overall burden of NMS in PD is more important in terms of QoL than motor symptoms. Individual MDS-UPDRS non-motor items related to worse QoL are especially pain and other sensations, fatigue and features of DDS.

  6. Myelodysplastic syndromes: recent progress in diagnosis and understanding of their pathophysiology.

    Science.gov (United States)

    Ogata, Kiyoyuki

    2006-12-01

    Myelodysplastic syndromes (MDS) are common malignant disorders with a poor prognosis. MDS are a group of highly heterogeneous disorders but show certain universal findings including a high incidence in the elderly population, cytopenia, dysplastic myeloid cells, and frequent transformation to acute myeloid leukemia. Until recently, the vast majority of MDS patients were treated with supportive therapy alone, such as transfusions. Allogeneic stem cell transplantation (SCT) has the potential for cure, although due to the age and comorbidity of MDS patients, the role of allogeneic SCT in MDS has been limited. Recently, research in MDS has shown substantial advances that have deepened our understanding of MDS pathophysiology and changed our approach to MDS patients. This review touches on some recent developments in the diagnosis and pathophysiology of MDS.

  7. Hyperfibrotic myelodysplastic syndrome: a report of three cases from north India

    Directory of Open Access Journals (Sweden)

    Prasenjit Das

    2009-06-01

    Full Text Available Extensive fibrosis in myelodysplastic syndromes (MDS is distinctly infrequent. Herein, we report three rare cases of hyperfibrotic MDS. This entity should be classified separately in the chronic myeloproliferative disease (CMPD-MDS group due to variable clinical presentation and poor prognosis.

  8. Gitelman's syndrome with persistent hypokalemia - don't forget licorice, alcohol, lemon juice, iced tea and salt depletion: a case report

    Directory of Open Access Journals (Sweden)

    Schmid Christoph

    2011-07-01

    Full Text Available Abstract Introduction Chronic hypokalemia is the main finding in patients with Gitelman's syndrome. Exogenous factors can trigger deterioration of the patient's condition and provoke clinical symptoms. We discuss the pathophysiology of and therapy for Gitelman's syndrome, with a focus on dietary factors which may aggravate the disease. Case presentation We describe the case of a 31-year-old, previously apparently healthy Caucasian Swiss man who presented to our hospital with gait disturbance of subacute onset and a potassium level of 1.5 mmol/L. A detailed medical history revealed that he had been consuming large amounts of licorice (in the form of Fisherman's Friend menthol eucalyptus lozenges. Despite discontinuing the intake of glycyrrhizinic acid, his potassium level remained low. Biochemical investigations showed refractory hypokalemia and secondary hyperaldosteronism, suggestive of Gitelman's syndrome. Despite treatment with supplementation of potassium and magnesium in combination with an aldosterone antagonist, further clinically symptomatic episodes occurred. Triggers could be identified only by repeated detailed history taking. In response to the patient's dietary excesses (ingestion of relevant amounts of alcohol, lemon juice and iced tea, his hypokalemia was aggravated and provoked clinical symptoms. Finally, vomiting and failure to replace salt led to volume depletion and hypokalemic crisis, with a plasma potassium level of 1.0 mmol/L and paralysis with respiratory failure necessitating not only infusion of saline and potassium but also temporary mechanical ventilation. Conclusion Dietary preferences may have a much larger impact than any drug treatment on the symptoms of this chronic syndrome. Individual (mainly dietary preferences must be monitored closely, and patients should be given dietary advice to avoid recurrent aggravation of hypokalemia with muscular weakness.

  9. 中高危MDS与MDS/MPN患者骨髓单个核细胞凋亡及临床特征比较%Comparison of apoptosis of bone marrow mononuclear cells and clinical features in patients with advanced MDS and MDS/MPN

    Institute of Scientific and Technical Information of China (English)

    刘小柳; 邹立新; 雷坚; 张曙辉; 吴剑雄

    2016-01-01

    Objective To compare the apoptosis of bone marrow mononuclear cells (BMNCs) in myelodysplastic syn-drome (MDS) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN), and analyze the relationship between apoptosis and clinical characteristics of patients. Methods Bone marrow specimens and clinical data of 8 cases of in-termediate/high risk MDS and 5 cases of MDS/MPN patients were collected from July 2013 to July 2015 in Department of Hematology, Changsha Hospital Affiliated to Hu′nan Normal University. Acridine orange/ethidium bromide fluores-cence staining and Caspase-3 activity assay were used to detect apoptosis of BMNCs, and the correlation between apoptosis and clinical characteristics of patients was analyzed. Results The apoptotic rate in intermediate/high risk MDS and MDS/MPN patients were (10.25±1.77)%, (6.90±1.66)%respectively, the former was higher than the latter (P=0.032). Caspase-3 activity assay showed that the Caspase-3 activity of intermediate/high risk MDS BMNCs was (0.18± 0.04)%, significantly higher than that of the MDS/MPN group [(0.07 ±0.02)%], with statistically significant difference (P=0.028). Correlation analysis showed that negative correlation was found between BMNCs apoptosis and bone marrow blast cell percentage in intermediate/high risk MDS patients (r=-0.81, P=0.015), but BMNCs apoptotic rate and the proportion of bone marrow blast cells was positively correlated in MDS/MPN patients (r=0.90, P=0.037). Conclusion The apoptotic rate and Caspase-3 activity are significantly different in intermediate/high risk MDS and MDS/MPN, and there is a correlation between apoptotic rate and bone marrow blasts.%目的 比较中高危骨髓增生异常综合征(MDS)与骨髓增生异常/骨髓增殖性肿瘤(MDS/MPN)骨髓单个核细胞(BMNCs)凋亡情况及其与患者临床特征的关系. 方法 收集2013年7月~2015年7月在湖南师范大学附属长沙医院血液科就诊的8例中高危MDS及5例MDS/MPN患者的骨髓标本及

  10. Disturbance of inorganic phosphate metabolism in diabetes mellitus: clinical manifestations of phosphorus-depletion syndrome during recovery from diabetic ketoacidosis

    Directory of Open Access Journals (Sweden)

    Lervang H

    2010-09-01

    Full Text Available Jørn Ditzel, Hans-Henrik LervangDepartment of Endocrinology, and Center for Prevention of Struma and Metabolic Diseases, Aalborg University Hospital, Aarhus University, DenmarkAbstract: The acute effects of intracellular phosphate depletion and hypophosphatemia on organs and tissues in and during recovery from diabetic ketoacidosis (DKA have been reviewed. When insufficient phosphate and/or oxygen are available for high energy phosphate synthesis, cell homeostasis cannot be maintained and cell integrity may be impaired. The clinical consequences are recognized as occasional cause of morbidity and mortality. Although phosphate repletion has not been routinely recommended in the treatment of DKA, physicians should be aware of these clinical conditions and phosphate repletion in such situations should be considered.Keywords: high energy phosphates, hypoxia, fructose 1,6-diphosphate

  11. SUCLA2相关脑肌病型线粒体DNA耗竭综合征一例并文献复习%SUCLA2-related encephalomyopathic mitochondrial DNA depletion syndrome: a case report and review of literature

    Institute of Scientific and Technical Information of China (English)

    刘志梅; 方方; 丁昌红; 吴沪生; 吕俊兰; 伍妘

    2014-01-01

    丙二酸轻度升高,血C3和C4DC轻度升高.头颅MRI为基底节受累和脑萎缩样改变,以双侧尾状核、壳核对称性病变为主.25例中19例来自欧洲,其中的13例来自法罗群岛,为SUCLA2 c.534+ 1G>A纯合突变.结论 SUCLA2相关脑肌病型线粒体DNA耗竭综合征临床特征为:生后或婴儿早期出现严重肌张力低下、喂养困难、生长迟缓、发育迟滞(尤其是运动)、听力损害等;血乳酸增高,尿甲基丙二酸轻度增高,血C3和C4DC轻度升高;头颅MRI为双侧对称性尾状核、壳核受累,伴有脑萎缩样改变.发现SUCLA2致病性突变可确诊.%Objective To analyze the clinical characteristics of SUCLA2-related encephalomyopathic mitochondrial DNA depletion syndrome (MDS) in one patient,and review the latest clinical research reports.Method Clinical,laboratory and genetic data of one case of SUCLA2-related encephalomyopathic MDS diagnosed by department of Neurology,Beijing Children's Hospital in November,2013 were reported,and through taking "SUCLA2" as key words to search at CNKI,Wanfang,PubMed and the Human Gene Mutation Database (HGMD) professional to date,the clinical characteristics of 24 reported cases of SUCLA2-related encephalomyopathic MDS in international literature in combination with our case were analyzed.Result (1) The patient was 5 years and 9 months old,born as a term small for gestational age infant whose birth weight was 2 400 g,and presented since birth with severe muscular hypotonia,feeding difficulties,failure to thrive,psychomotor retardation and hearing impairment.Until now,he still showed severe developmental retardation,together with muscular atrophy,thoracocyllosis and scoliosis,and facial features.The patient is the first born from consanguineous healthy parents,whose relationship is cousins.Laboratory tests showed urinary excretion of mild methylmalonic acid (MMA),elevated plasma lactate concentration,and increased C3-carnitine and C4-dicarboxylic-carnitine in plasma carnitine ester

  12. Myelodysplastic changes mimicking MDS following treatment for osteosarcoma

    DEFF Research Database (Denmark)

    Løhmann, Ditte

    , and ANC decreased from a median of 4.64 x 109/L at diagnosis to a minimum of 2.18 at 18 months and increased slightly to 2.93 at 24 months. Haemoglobin normalized after one month and remained within the normal range. Within the study period two cases had a bone marrow examination performed. In one case...... MDS (refractory anaemia with excess blasts) with monosomy 7 was found and a hematopoietic stem cell transplant was performed. In the other case MDS without excess of blasts was found and a spontaneous normalization of the biochemistry occurred. In conclusion in our study most patients treated...

  13. Efficacy of Induction Chemotherapy on Patients with High-risk Myelodysplastic Syndrome or MDS-transformed Acute Myeloid Leukemia with CHG Regimen and the Comparison with Regimen%含羟基喜树碱的预激方案诱导治疗高危骨髓增生异常综合征及骨髓增生异常综合征转化的急性髓系白血病的疗效观察

    Institute of Scientific and Technical Information of China (English)

    王石松

    2013-01-01

    Objective To observe the efficacy and side effects of low - density regimen CHG ( Hydroxy camptothecin, Cytarabine, and granulocyte colony - stimulating factor ) as a priming induction regimen in the treatment of patients with high -risk myelodysplasia syndrome ( MDS ) or MDS - transformed acute myeloid leukemia ( AML ), and to compare the results with those of CAG regimen ( Aclacimomycin, Cytarabine and granulocyte colony - stimulating factor ). Methods Patients with high - risk MDS or MDS - transformed AML who had not undergone chemotherapy were divided into the CHG group ( n = 32; CHG regimen as induction therapy ) and the CAG group ( n = 29; CAG regimen as induction therapy ). The efficacy and side effects after one course of chemotherapy were observed and compared between the two regimens. Results After one course of treatment, the total effective rate of the CHG group was 68. 8% , with 14 patients achieving complete remission ( CR ), 7 partial remission ( PR ), and 1 with hematological response; while the total effective rate of the CAG group was 72. 4% , with 12 patients achieving CR, 6 PR and 3 with hematological response. No significant difference was found between the two groups in rate of CR, total effective rate, and side effects ( P >0. 05 ). During follow - up, 3 out of 14 cases of the CHG group who were followed by the Harringtonine + Ara - c ( HA ) or Etoposide + Ara - c ( EA ) maintenance therapy due to cardiac arrhythmia relapsed after CR. Out of the 14 cases, 11 cases were alternately treated with HA, Aclacimomycin + Ara - c ( AA ), Topotecan + Ara - c ( TA ), Mitoxantrone + Ara - c ( MA ), and Idamycin + Ara - c ( IA ) regimens, with 7 cases relapsed within 3-16 months, 3 cases transformed into AML, and 1 case lost to follow - up. Two out of 4 cases who relapsed after more than 6 months of remission achieved CR, but relapsed afterwards. Out of the 12 cases in the CAG group who reached CR, 8 patients relapsed within 2. 6 ~ 17 months, 2

  14. IER3 Expression in Childhood Myelodysplastic Syndrome

    DEFF Research Database (Denmark)

    de Vries, Andrica; Zwaan, Christian M.; Danen van Ooschot, Astrid

    Background: Childhood myelodysplastic syndrome (MDS) is a rare disease accounting for less than 5% of all hematological malignancies. In about 50% of the MDS cases an abnormal karyotype is found by conventional karyotyping, of which chromosome 6 is involved in 10%. The immediate-early-response 3 ...

  15. Depletion of the bloom syndrome helicase stimulates homology-dependent repair at double-strand breaks in human chromosomes.

    Science.gov (United States)

    Wang, Yibin; Smith, Krissy; Waldman, Barbara Criscuolo; Waldman, Alan S

    2011-04-03

    Mutation of BLM helicase causes Blooms syndrome, a disorder associated with genome instability, high levels of sister chromatid exchanges, and cancer predisposition. To study the influence of BLM on double-strand break (DSB) repair in human chromosomes, we stably transfected a normal human cell line with a DNA substrate that contained a thymidine kinase (tk)-neo fusion gene disrupted by the recognition site for endonuclease I-SceI. The substrate also contained a closely linked functional tk gene to serve as a recombination partner for the tk-neo fusion gene. We derived two cell lines each containing a single integrated copy of the DNA substrate. In these cell lines, a DSB was introduced within the tk-neo fusion gene by expression of I-SceI. DSB repair events that occurred via homologous recombination (HR) or nonhomologous end-joining (NHEJ) were recovered by selection for G418-resistant clones. DSB repair was examined under conditions of either normal BLM expression or reduced BLM expression brought about by RNA interference. We report that BLM knockdown in both cell lines specifically increased the frequency of HR events that produced deletions by crossovers or single-strand annealing while leaving the frequency of gene conversions unchanged or reduced. We observed no change in the accuracy of individual HR events and no substantial alteration of the nature of individual NHEJ events when BLM expression was reduced. Our work provides the first direct evidence that BLM influences DSB repair pathway choice in human chromosomes and suggests that BLM deficiency can engender genomic instability by provoking an increased frequency of HR events of a potentially deleterious nature.

  16. LIN7A depletion disrupts cerebral cortex development, contributing to intellectual disability in 12q21-deletion syndrome.

    Directory of Open Access Journals (Sweden)

    Ayumi Matsumoto

    Full Text Available Interstitial deletion of 12q21 has been reported in four cases, which share several common clinical features, including intellectual disability (ID, low-set ears, and minor cardiac abnormalities. Comparative genomic hybridization (CGH analysis using the Agilent Human Genome CGH 180K array was performed with the genomic DNA from a two-year-old Japanese boy with these symptoms, as well as hypoplasia of the corpus callosum. Consequently, a 14 Mb deletion at 12q21.2-q21.33 (nt. 77 203 574-91 264 613 bp, which includes 72 genes, was detected. Of these, we focused on LIN7A, which encodes a scaffold protein that is important for synaptic function, as a possible responsible gene for ID, and we analyzed its role in cerebral cortex development. Western blotting analyses revealed that Lin-7A is expressed on embryonic day (E 13.5, and gradually increases in the mouse brain during the embryonic stage. Biochemical fractionation resulted in the enrichment of Lin-7A in the presynaptic fraction. Suppression of Lin-7A expression by RNAi, using in utero electroporation on E14.5, delayed neuronal migration on postnatal day (P 2, and Lin-7A-deficient neurons remained in the lower zone of the cortical plate and the intermediate zone. In addition, when Lin-7A was silenced in cortical neurons in one hemisphere, axonal growth in the contralateral hemisphere was delayed; development of these neurons was disrupted such that one half did not extend into the contralateral hemisphere after leaving the corpus callosum. Taken together, LIN7A is a candidate gene responsible for 12q21-deletion syndrome, and abnormal neuronal migration and interhemispheric axon development may contribute to ID and corpus callosum hypoplasia, respectively.

  17. Handling missing values in the MDS-UPDRS.

    Science.gov (United States)

    Goetz, Christopher G; Luo, Sheng; Wang, Lu; Tilley, Barbara C; LaPelle, Nancy R; Stebbins, Glenn T

    2015-10-01

    This study was undertaken to define the number of missing values permissible to render valid total scores for each Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part. To handle missing values, imputation strategies serve as guidelines to reject an incomplete rating or create a surrogate score. We tested a rigorous, scale-specific, data-based approach to handling missing values for the MDS-UPDRS. From two large MDS-UPDRS datasets, we sequentially deleted item scores, either consistently (same items) or randomly (different items) across all subjects. Lin's Concordance Correlation Coefficient (CCC) compared scores calculated without missing values with prorated scores based on sequentially increasing missing values. The maximal number of missing values retaining a CCC greater than 0.95 determined the threshold for rendering a valid prorated score. A second confirmatory sample was selected from the MDS-UPDRS international translation program. To provide valid part scores applicable across all Hoehn and Yahr (H&Y) stages when the same items are consistently missing, one missing item from Part I, one from Part II, three from Part III, but none from Part IV can be allowed. To provide valid part scores applicable across all H&Y stages when random item entries are missing, one missing item from Part I, two from Part II, seven from Part III, but none from Part IV can be allowed. All cutoff values were confirmed in the validation sample. These analyses are useful for constructing valid surrogate part scores for MDS-UPDRS when missing items fall within the identified threshold and give scientific justification for rejecting partially completed ratings that fall below the threshold.

  18. Cytogenetic studies of Brazilian pediatric myelodysplastic syndrome cases: challenges and difficulties in a large and emerging country

    Directory of Open Access Journals (Sweden)

    E.D.R.P. Velloso

    2013-01-01

    Full Text Available Myelodysplastic syndromes (MDS and juvenile myelomonocytic leukemia (JMML are rare hematopoietic stem cell diseases affecting children. Cytogenetics plays an important role in the diagnosis of these diseases. We report here the experience of the Cytogenetic Subcommittee of the Brazilian Cooperative Group on Pediatric Myelodysplastic Syndromes (BCG-MDS-PED. We analyzed 168 cytogenetic studies performed in 23 different cytogenetic centers; 84 of these studies were performed in patients with confirmed MDS (primary MDS, secondary MDS, JMML, and acute myeloid leukemia/MDS+Down syndrome. Clonal abnormalities were found in 36.9% of the MDS cases and cytogenetic studies were important for the detection of constitutional diseases and for differential diagnosis with other myeloid neoplasms. These data show the importance of the Cooperative Group for continuing education in order to avoid a late or wrong diagnosis.

  19. Benefit from B-lymphocyte depletion using the anti-CD20 antibody rituximab in chronic fatigue syndrome. A double-blind and placebo-controlled study.

    Directory of Open Access Journals (Sweden)

    Øystein Fluge

    Full Text Available BACKGROUND: Chronic fatigue syndrome (CFS is a disease of unknown aetiology. Major CFS symptom relief during cancer chemotherapy in a patient with synchronous CFS and lymphoma spurred a pilot study of B-lymphocyte depletion using the anti-CD20 antibody Rituximab, which demonstrated significant clinical response in three CFS patients. METHODS AND FINDINGS: In this double-blind, placebo-controlled phase II study (NCT00848692, 30 CFS patients were randomised to either Rituximab 500 mg/m(2 or saline, given twice two weeks apart, with follow-up for 12 months. Xenotropic murine leukemia virus-related virus (XMRV was not detected in any of the patients. The responses generally affected all CFS symptoms. Major or moderate overall response, defined as lasting improvements in self-reported Fatigue score during follow-up, was seen in 10 out of 15 patients (67% in the Rituximab group and in two out of 15 patients (13% in the Placebo group (p = 0.003. Mean response duration within the follow-up period for the 10 responders to Rituximab was 25 weeks (range 8-44. Four Rituximab patients had clinical response durations past the study period. General linear models for repeated measures of Fatigue scores during follow-up showed a significant interaction between time and intervention group (p = 0.018 for self-reported, and p = 0.024 for physician-assessed, with differences between the Rituximab and Placebo groups between 6-10 months after intervention. The primary end-point, defined as effect on self-reported Fatigue score 3 months after intervention, was negative. There were no serious adverse events. Two patients in the Rituximab group with pre-existing psoriasis experienced moderate psoriasis worsening. CONCLUSION: The delayed responses starting from 2-7 months after Rituximab treatment, in spite of rapid B-cell depletion, suggests that CFS is an autoimmune disease and may be consistent with the gradual elimination of autoantibodies preceding

  20. Aplastic Anemia & MDS International Foundation (AA&MDSIF): Bone Marrow Failure Disease Scientific Symposium 2014.

    Science.gov (United States)

    Visconte, Valeria; Lindsley, R Coleman; Berlyne, Deborah

    2015-01-01

    Bone marrow failure syndromes (BMFS) are characterized by a failure of the hematopoietic stem cells to produce adequate blood cells, resulting in either cytopenia (defect in one or more blood cell lineages) or pancytopenia (defect in all blood cell lineages). BMFS can be inherited or acquired. The pathogenesis of these diseases is very heterogeneous. Research efforts have been made all over the world to improve the basic knowledge of these diseases. The Aplastic Anemia and MDS International Foundation (AA&MDSIF) is an independent nonprofit organization whose mission is to help patients and family members cope with BMFS. Here, we summarize novel scientific discoveries in several BMFS that were presented at the 4th International Bone Marrow Failure Disease Scientific Symposium 2014 that AA&MDSIF sponsored on March 27-28, 2014, in Rockville, MD.

  1. Research Progress in MDS Mouse Model%骨髓增生异常综合征小鼠模型研究进展

    Institute of Scientific and Technical Information of China (English)

    张耀

    2012-01-01

    Myelodysplastic syndromes (MDS) are hematopoietic malignancies characterized by peripheral cytopenia and dysplastic bone marrow that arise from mutations in the hematopoietic stem/progenitor cells (HSPC). Recently, significant effects have been made to develop appropriate mouse models to study this complex disease. Three general approaches have been used to establish the MDS mouse, including treatment with mutagens or carcinogene, xenotransplantation of human MDS cells, and genetic engineering of mouse hematopoietic cells. In this review, several MDS mouse models and the advances of study on the mechanisms of malignant clone and the marrow microenvironment are summarized. In addition, the progress in xenotransplantation models of MDS and the problems to be solved are discussed briefly.%骨髓增生异常综合征(MDS)是一组造血干、祖细胞发生突变造成以外周血细胞减少、骨髓病态造血为特征的恶性血液病.近年来,为了建立确切的MDS小鼠模型来研究该病,全世界的研究者们做了大量的努力.建立MDS小鼠模型大致可以归纳为3种途径:转致病基因、异种移植人MDS细胞、基因工程改造小鼠的造血细胞.本综述描述几种MDS小鼠模型,以阐述恶性克隆造成的致病机制和骨髓微环境的改变,同时,阐述异种移植人MDS细胞小鼠模型的进展和尚待解决的问题.

  2. [Successful treatment with azacitidine for myelodysplastic syndrome with large vessel vasculitis].

    Science.gov (United States)

    Mishima, Mai; Makita, Masanori; Sando, Yasuhisa; Yamamoto, Yoshikazu; Shiote, Yasuhiro; Hara, Yoshitaka; Yamamoto, Kazuhiko; Imajo, Kenji

    2015-01-01

    Paraneoplastic inflammation of the large vessels is a rare complication of myelodysplastic syndrome (MDS), and patients with MDS and systemic vasculitis have a poor prognosis. We present a 66-year-old male with MDS and large vessel vasculitis treated with azacitidine. Azacitidine administration improved his clinical symptoms, high fever and thickening of the arterial wall, and he achieved a complete bone marrow remission. However, 1 year later he showed progression of MDS. For MDS with vasculitis, intensive therapy, the same as that given to the high-risk group, should be considered and azacitidine administration may represent an efficacious treatment.

  3. Segregated Optical-NIR colour distributions of MDS galaxies

    CERN Document Server

    Ferreras, I; Martínez-González, E; Benítez, N

    1998-01-01

    We present a K survey of 29 fields covering approximately 90 arcmin^2 from the Medium Deep Survey (MDS) catalogue down to a completeness magnitude of K=18.0 (limiting magnitude K=19.0). The morphology obtained by the MDS team using high resolution images from HST/WFPC2 along with our NIR observations allow a Colour-Magnitude and Colour-Colour analysis that agrees in general with spectral evolution models (Bruzual & Charlot 1998) especially if a reasonable range of metallicities for the Simple Stellar Populations used (0.2 4.5, setting an upper limit to the number density of EROs at dn_{EROs}/dØmega < 0.011 arcmin^{-2} (K < 18.0).

  4. Abnormal expression of PACAP gene in patients with myelodysplastic syndrome%骨髓增生异常综合征患者骨髓细胞中PACAP基因的异常表达

    Institute of Scientific and Technical Information of China (English)

    Stella Aprilia Ika; Zixing Chen; Xiaofei Qi; Hongjie Shen; Jiannong Cen; Yuanyuan Wang

    2009-01-01

    Objective: To explore the expression pattern of PACAP gene in patients with myelodysplastic syndrome (MDS). Methods: The expression pattem of PACAP gene in CD34+ cells from MDS patients was determined by microarray, con-firmed in expanding samples by quantitative real-time PCR in bone marrow mononuclear cells. Results: The transcription of PACAP gene was found significantly down-regulated in patients with MDS in comparison with that in control samples, with a means of 220.1 in MDS-RA and 116.8 in MDS-RAEB (P < 0.05 ). Conclusion: PACAP gene is expressed significantly lower in patients with MDS.

  5. Study of Rpl22 in MDS and AML

    Science.gov (United States)

    2015-10-01

    usually linked with bone marrow disease , our data doesn’t support p53 is the key player in MDS/AML caused by Rpl22 defect. 3. Uncovered a pathological...our lab and others supports that ribosomal proteins play a critical role in development(1) and diseases including bone marrow disease (2) in addition...that RP play a critical but poorly understood role in development as well as disease . Mutations in RP cause a group of diseases collectively termed

  6. Zigzag Codes: MDS Array Codes with Optimal Rebuilding

    CERN Document Server

    Tamo, Itzhak; Bruck, Jehoshua

    2011-01-01

    MDS array codes are widely used in storage systems to protect data against erasures. We address the \\emph{rebuilding ratio} problem, namely, in the case of erasures, what is the fraction of the remaining information that needs to be accessed in order to rebuild \\emph{exactly} the lost information? It is clear that when the number of erasures equals the maximum number of erasures that an MDS code can correct then the rebuilding ratio is 1 (access all the remaining information). However, the interesting and more practical case is when the number of erasures is smaller than the erasure correcting capability of the code. For example, consider an MDS code that can correct two erasures: What is the smallest amount of information that one needs to access in order to correct a single erasure? Previous work showed that the rebuilding ratio is bounded between 1/2 and 3/4, however, the exact value was left as an open problem. In this paper, we solve this open problem and prove that for the case of a single erasure with ...

  7. Development and validation of the Maladaptive Daydreaming Scale (MDS).

    Science.gov (United States)

    Somer, Eli; Lehrfeld, Jonathan; Bigelsen, Jayne; Jopp, Daniela S

    2016-01-01

    This study describes the development of the Maladaptive Daydreaming Scale (MDS), a 14-item self-report instrument designed to gauge abnormal fantasizing. Our sample consisted of 447 English-speaking individuals from 45 different countries. A 3-correlated-factors model best presented the underlying dimensions Yearning, Kinesthesia and Impairment, capturing related rewarding experiences as well as psychological impairment of maladaptive daydreaming. MDS scores were associated with obsessive-compulsive behavior and thoughts, dissociative absorption, attention deficit, and high sense of presence during daydreaming, but less with psychotic symptoms. The MDS and its subscale demonstrated good validity, sound internal consistency and temporal stability and discriminated well between self-identified individuals with and without maladaptive daydreaming. Considering the instrument's high sensitivity and specificity levels, it seems an excellent measure for future investigation of MD that will, hopefully, shed light on the etiology and psycho-biological mechanisms involved in this mental condition, as well as on the development of effective MD treatment methods. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Research Progress on Mechanism of MDS Transformation into AML——Review%MDS转化为AML机制的研究进展

    Institute of Scientific and Technical Information of China (English)

    王淋淋; 高冲; 陈宝安

    2011-01-01

    骨髓增生异常综合症(MDS)是造血干细胞克隆性疾病,以无效造血和可转变为急性白血病为特征,大约有30%的病例可转变成急性白血病.这种转变则在高危的MDS患者中更为常见,故又称为继发性急性髓系白血病(sAML或MDS/AML).化疗对这类疾病-般很难奏效,唯-治愈的方法就是异基因造血干细胞移植,但是只有很少的病人适合移植.所以,对MDS发生和发展的机制研究和为临床开发其有效药物显得特别重要.本文将从染色体异常、DNA异常甲基化和AMLI/RUNXI,FLT- 3,PI-PLCβ1基因突变这三个方面进行介绍.%Myelodysplastic syndrome (MDS) is a clonal hematopoietic stem cell disorder characterized by ineffective hematopoiesis and a risk of transformation into acute leukemia. Approximately 30% of patients with MDS will progress and develop into acute myeloid leukemia ( AML), especially in the patients with high-risk MDS, which can be named as secondary acute myeloid leukemia (sAML or MDS/AML ). Generally, chemotherapy for sAML hardly has any efficacy. The only way to cure the patients with sAML is allogeneic hematopoietic stem cell transplantation, but unfortunately, only few patients are appropriate for transplantation. So it is important to study the mechanisms of progression of MDS to AML and to explore the potent drug for clinical use. This review summarizes the mechanism of MDS transformation into AML from chromosomal abnormality, aberrant DNA methylation and gene mutation, such as AML1/RUNX1 mutations, FLT3 mutations and PI-PLCβ1 mono-allelic deletion.

  9. Lenalidomide induces cell death in an MDS-derived cell line with deletion of chromosome 5q by inhibition of cytokinesis

    National Research Council Canada - National Science Library

    Matsuoka, A; Tochigi, A; Kishimoto, M; Nakahara, T; Kondo, T; Tsujioka, T; Tasaka, T; Tohyama, Y; Tohyama, K

    2010-01-01

    ... Organization classification of MDS. (4) Although the deleted area of 5q is different in case by case, del(5)(q32q33) is considered as a common deleted region. (5,6) The common deleted region expected in patients with 5q- syndrome is located distal to the region recognized in higher-risk groups with del(5q) that are susceptible to leuk...

  10. Reassessment of H&E stained clot specimens and immunohistochemistry of phosphorylated Stat5 for histological diagnosis of MDS/MPN.

    Science.gov (United States)

    Tsuruyama, Tatsuaki; Aini, Wulamujiang; Hiratsuka, Takuya

    2015-12-01

    Few studies have comprehensively analysed histopathological findings of bone marrow clots for diagnosis of haematopoietic cell dysplasia. In particular, a limited number of studies have assessed the use of haematoxylin and eosin (H&E) staining, which is generally considered less informative than May-Giemsa staining. In the current study, the utility of bone marrow clot specimens for diagnosis was examined using H&E staining and immunohistochemistry. Patients with myelodysplastic syndromes (MDS) and myelodysplastic/myeloproliferative neoplasm (MDS/MPN), including chronic myelomonocytic leukaemia (CMML), atypical chronic myeloid leukaemia (aCML) lacking Philadelphia chromosome, and juvenile myelomonocytic leukaemia (JMML), were selected for histological evaluation. H&E stained specimens were advantageous for observation of atypical basophilic staining of the cytoplasm and nucleus related to dysplasia. This finding was significantly supported for both MDS and MDS/MPN (p < 0.05 versus May-Giemsa staining); therefore, we concluded that H&E staining could be used for identification of dysplastic cells. In addition, despite the loss of tissue structure, phosphorylated Stat5 immunostaining was sufficiently useful for the observation of myelodysplastic blasts. Thus, clot specimens are useful for diagnosis of haematopoietic dysplasia by pathologists.

  11. Chidamide, a novel histone deacetylase inhibitor, inhibits the viability of MDS and AML cells by suppressing JAK2/STAT3 signaling

    Science.gov (United States)

    Zhao, Sida; Guo, Juan; Zhao, Youshan; Fei, Chengming; Zheng, Qingqing; Li, Xiao; Chang, Chunkang

    2016-01-01

    Many studies have indicated that histone deacetylase (HDAC) activity is always increased in a lot of human tumors, and inhibition of HDAC activity is a promising new strategy in the treatment of cancers. Chidamide, a novel HDAC inhibitor of the benzamide class, is currently under clinical trials. In this study, we aimed to investigate the antitumor activity of Chidamide on myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) cell lines and explore the possible mechanism. Chidamide exhibited efficient anti-proliferative activity on MDS and AML cells in a time- and dose-dependent manner, accompanied by cell cycle arrest at G0/G1 phase and cell apoptosis. Importantly, Chidamide possessed potent HDAC inhibition property, as evaluated by HDAC activity analysis and acetylation of histone H3 and H4. Moreover, Chidamide significantly increased the expression of Suppressors of cytokine signaling 3 (SOCS3), reduced the expression of Janus activated kinases 2 (JAK2) and Signal transducer and activator of transcription 3 (STAT3), and inhibited STAT3 downstream genes, including c-Myc, Bcl-xL, and Mcl-1, which are involved in cell cycle progression and anti-apoptosis. Therefore, we demonstrate that Chidamide exhibits potent inhibitory effect on cell viability of MDS and AML cells, and the possible mechanism may lie in the downregulation of JAK2/STAT3 signaling through SOCS3 upregulation. Our data provide rationale for clinical investigations of Chidamide in MDS and AML. PMID:27508038

  12. [Etiological factors of myelodysplastic syndromes].

    Science.gov (United States)

    Nisse, C

    1997-09-01

    Specific epidemiologic data on myelodysplastic syndromes are rare. Analysis of data is in fact affected by problems of terminology and classification. The link between the exposure to ionizing radiation or alkylating agents and MDS is well established. Etiologic factors of acute leukemia, or new factors such as non ionizing radiation, solvent, ethylene oxide, glycol eters, tobacco smoke, exhaust gases, agricultural work have been hypothesized but should be confirmed by other studies on MDS.

  13. Treosulfan, Fludarabine and 2 Gy Total Body Irradiation Followed by Allogeneic Hematopoietic Cell Transplantation in Patients with MDS and AML

    Science.gov (United States)

    Gyurkocza, Boglarka; Gutman, Jonathan; Nemecek, Eneida R.; Bar, Merav; Milano, Filippo; Ramakrishnan, Aravind; Scott, Bart; Fang, Min; Wood, Brent; Pagel, John M.; Baumgart, Joachim; Delaney, Colleen; Maziarz, Richard T.; Sandmaier, Brenda M.; Estey, Elihu H.; Appelbaum, Frederick R.; Storer, Barry E.; Deeg, H. Joachim

    2014-01-01

    Allogeneic hematopoietic cell transplantation (HCT) offers curative therapy for many patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). However, post-HCT relapse remains a major problem, particularly in patients with high-risk cytogenetics. In this prospective phase II trial we assessed the efficacy and toxicity of treosulfan, fludarabine and 2 Gy total body irradiation (TBI) as conditioning for allogeneic HCT in patients with MDS or AML. Ninety-six patients with MDS (n=36; 15 RMCD; 10 RAEB-1; 10 RAEB-2; 1 CMML-1) or AML (n=60; 35 CR1; 18 CR2; 3 advanced CR; 4 refractory relapse) were enrolled; median age was 51 (range: 1–60) years. Twelve patients had undergone a prior HCT with high intensity conditioning. Patients received intravenous (IV) treosulfan, 14 g/m2/day on days −6 to −4, IV fludarabine, 30 mg/m2/day on days −6 to −2, and 2 Gy TBI on day 0, followed by infusion of hematopoietic cells from related (n=27) or unrelated (n=69) donors. Graft-vs.-host disease prophylaxis consisted of tacrolimus and methotrexate. With a median follow-up of 30 months, the 2-year overall survival (OS), relapse incidence and non-relapse mortality were 73%, 27% and 8%, respectively. The incidences of grades II–IV (III–IV) acute and chronic graft-versus-host disease were 59% (10%) and 47%, respectively. Two-year OS was not significantly different between MDS patients with poor risk and good/intermediate risk cytogenetics (69% and 85%, respectively), or between AML patients with unfavorable and favorable/intermediate risk cytogenetics (64% and 76%, respectively). In AML patients, minimal residual disease (MRD; n=10) at the time of HCT predicted higher relapse incidence (70% vs. 18%) and lower OS (41% vs. 79%) at 2 years, when compared to patients without MRD. In conclusion, treosulfan, fludarabine and low-dose TBI provided effective conditioning for allogeneic HCT in patients with MDS or AML, and resulted in low relapse incidence, regardless

  14. The Mice Drawer System Tissue Sharing Program (MDS-TSP)

    Science.gov (United States)

    Biticchi, Roberta; Cancedda, Ranieri; Cilli, Michele; Cotronei, Vittorio; Costa, Delfina; Liu, Yi; Piccardi, Federica; Pignataro, Salvatore; Ruggiu, Alessandra; Tasso, Roberta; Tavella, Sara

    Several organs and apparatus are affected by weightless conditions and in particular by the weightless experienced during space flights. Therefore space missions are good opportunities to investigate in a whole organism the controlling cellular and molecular mechanisms. For this type of studies mice represent an excellent animal model for several reasons: reduced body size, relatively short time needed to reach adulthood, availability of strains with different genetic background and of different transgenic lines, etc. In line with the International Space Station (ISS) development, the Italian Space Agency (ASI) contracted Thales Alenia Space Italia, the largest Italian aerospace industry, to design and build a spaceflight payload for rodent research on ISS, the Mouse Drawer System (MDS -see abstract P. Cipparelli et al.). This payload meets NIH guideline for several physical parameters to maintain 6 animals in good health conditions in a space environment. Given the interest of our laboratory in the microgravity induced skeleton alterations, we focused our attention on transgenic mice over-expressing pleiotrophin (PTN) under the control of the human bone specific osteocalcin promoter. This protein is a heparin-binding cytokine with different functions. PTN is expressed by the cells in an early differentiation stage and is upregulated in tissue injury and wound repair. PTN is specifically involved in bone formation, neurite outgrowth and angiogenesis. As PTN-transgenic mice show an increased bone mass and mineralization, we decided to use this mouse model in the flight experiment and to study its potential role in counteracting bone loss in microgravity. Not all mouse strains are equally suitable for flight. After preliminary tests in the MDS breadboard at our animal facility on the behavior of different mouse strains, PTN-transgenic mice originally obtained in the BDF strain were backcrossed in the C57Bl/J10 strain before being used in this study. In order to

  15. WT1 vaccination in AML and MDS: A pilot trial with synthetic analog peptides.

    Science.gov (United States)

    Brayer, Jason; Lancet, Jeffrey E; Powers, John; List, Alan; Balducci, Lodovico; Komrokji, Rami; Pinilla-Ibarz, Javier

    2015-07-01

    Peptide vaccines are capable of eliciting immune responses targeting tumor-associated antigens such as the Wilms' Tumor 1 (WT1) antigen, often overexpressed in myeloid malignancies. Here, we assessed the safety, tolerability, and immunogenicity of a polyvalent WT1 peptide vaccine. Individuals with WT1-positive acute myeloid leukemia (AML) in first (CR1) or second (CR2) remission or with higher-risk myelodysplastic syndrome (MDS) following at least 1 prior line of therapy were vaccinated with a mixture of peptides derived from the WT1 protein, with sargramostim injections before vaccination to amplify immunogenicity. Six vaccinations were delivered biweekly, continuing then monthly until patients received 12 vaccinations or showed disease relapse or progression. Therapeutic efficacy was evaluated by progression-free and overall survival. Immune responses were evaluated by delayed-type hypersensitivity testing and T-cell IFNγ ELISPOT at specified intervals. In 16 patients who received at least one vaccination, 10 completed the planned course of six vaccinations and six continued for up to six additional monthly vaccinations. Vaccinations were well tolerated, with no patients discontinuing due to toxicity. One of two patients with high-risk MDS experienced a prolonged decrease in transfusion dependence. Two of 14 AML patients demonstrated relapse-free survival >1 year. Both patients were in CR2 at time of vaccination, with duration of their remission exceeding duration of their first remission, suggesting a potential benefit. Our WT1 vaccine was well-tolerated. The clinical benefit that we observed in several patients suggests engagement of a protective immune response, indicating a need for further trials.

  16. Prognostic factors in de novo myelodysplastic syndrome in young and middle-aged people

    Directory of Open Access Journals (Sweden)

    Наталья Николаевна Климкович

    2015-01-01

    Full Text Available We spent multivariate analysis of clinical and laboratory parameters for the prediction of de-novo myelodysplastic syndromes (MDS patients aged 18-60 years. The results of clinical application of prognostic systems in MDS show that there is a large variability within individual risk groups, especially at low-risk MDS. So now hematologists conduct research aimed at identifying additional adverse risk MDS. This is done so that patients with low-risk MDS embodiments and unfavorable prognosis could benefit from early therapeutic intervention, and not only be clinician monitored until disease progression. We found that additional adverse risk factors for the development of MDS are the expression of CD95 in bone marrow ≤40 % and FLT3≥60 %. The expression level of CD95 in bone marrow cells≤40 % and FLT3≥60 % can be considered as a prognostic marker progression of MDS and time start specific therapy

  17. Molecular bases of myelodysplastic syndromes: lessons from animal models.

    Science.gov (United States)

    Komeno, Yukiko; Kitaura, Jiro; Kitamura, Toshio

    2009-06-01

    Myelodysplastic syndrome (MDS) is a clonal disorder of hematopietic stem cells characterized by ineffective hematopoiesis, peripheral blood cytopenia, morphologic dysplasia, and susceptibility to acute myeloid leukemia. Several mechanisms have been suggested as causes of MDS: unbalanced chromosomal abnormalities reflecting a gain or loss of chromosomal material, point mutations of transcription factors, and inactivation of p53. However, appropriate animal models that mimic MDS have long been lacking. We recently reported a novel murine model of MDS that recapitulates trilineage dysplasia and transformation to AML. In this review, we summarize the animal models of MDS and discuss the molecular bases of MDS as well as those of leukemia and myeloproliferative disorders (MPD). J. Cell. Physiol. 219: 529-534, 2009. (c) 2009 Wiley-Liss, Inc.

  18. Paclitaxel Induced MDS and AML: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Udit Bhaskar Bhatnagar

    2016-01-01

    Full Text Available Therapy related acute myelogenous leukemia (AML and myelodysplastic syndromes (MDS have been classically linked to alkylating agents and topoisomerase inhibitors. They constitute about 1% of all AMLs. There is less evidence on association of taxanes (paclitaxel and docetaxel with these myeloid neoplasms. We present a case of paclitaxel therapy related acute myelogenous leukemia after treatment of endometrial cancer with a regimen containing paclitaxel and carboplatin. A 63-year-old female underwent surgery followed by a total of 6 cycles of chemotherapy with carboplatin and paclitaxel. Six months after last cycle of chemotherapy, she was diagnosed with myelodysplastic syndrome with refractory anemia and excess blasts. Six weeks later, she had worsening anemia and thrombocytopenia which prompted a bone marrow biopsy which revealed acute myelomonocytic leukemia. A thorough literature review revealed 12 other case reports where taxanes have been implicated in the development of therapy related myeloid neoplasm. Based on the timeline of events in our patient, paclitaxel is the likely culprit in the pathogenesis of this myeloid neoplasm. This rare but significantly grave adverse effect should be kept in consideration when deciding on treatment options for gynecological malignancies.

  19. Hematopoietic stem cell and progenitor cell mechanisms in myelodysplastic syndromes

    Science.gov (United States)

    Pang, Wendy W.; Pluvinage, John V.; Price, Elizabeth A.; Sridhar, Kunju; Arber, Daniel A.; Greenberg, Peter L.; Schrier, Stanley L.; Park, Christopher Y.; Weissman, Irving L.

    2013-01-01

    Myelodysplastic syndromes (MDS) are a group of disorders characterized by variable cytopenias and ineffective hematopoiesis. Hematopoietic stem cells (HSCs) and myeloid progenitors in MDS have not been extensively characterized. We transplanted purified human HSCs from MDS samples into immunodeficient mice and show that HSCs are the disease-initiating cells in MDS. We identify a recurrent loss of granulocyte-macrophage progenitors (GMPs) in the bone marrow of low risk MDS patients that can distinguish low risk MDS from clinical mimics, thus providing a simple diagnostic tool. The loss of GMPs is likely due to increased apoptosis and increased phagocytosis, the latter due to the up-regulation of cell surface calreticulin, a prophagocytic marker. Blocking calreticulin on low risk MDS myeloid progenitors rescues them from phagocytosis in vitro. However, in the high-risk refractory anemia with excess blasts (RAEB) stages of MDS, the GMP population is increased in frequency compared with normal, and myeloid progenitors evade phagocytosis due to up-regulation of CD47, an antiphagocytic marker. Blocking CD47 leads to the selective phagocytosis of this population. We propose that MDS HSCs compete with normal HSCs in the patients by increasing their frequency at the expense of normal hematopoiesis, that the loss of MDS myeloid progenitors by programmed cell death and programmed cell removal are, in part, responsible for the cytopenias, and that up-regulation of the “don’t eat me” signal CD47 on MDS myeloid progenitors is an important transition step leading from low risk MDS to high risk MDS and, possibly, to acute myeloid leukemia. PMID:23388639

  20. Quality of life, physical function and MRI T2* in elderly low-risk MDS patients treated to a haemoglobin level of ≥120 g/L with darbepoetin alfa ± filgrastim or erythrocyte transfusions

    DEFF Research Database (Denmark)

    Nilsson-Ehle, Herman; Birgegård, Gunnar; Samuelsson, Jan

    2011-01-01

    Anaemia in low-risk myelodysplastic syndromes (MDS) is associated with reduced quality of life (QoL). Response to treatment with erythropoietin ± granulocyte colony-stimulating factor (G-CSF) is associated with improved QoL, but whether transfusion therapy with higher haemoglobin (Hb) target levels...... has similar effects is unknown. The objective for this prospective phase II Nordic multicentre trial was to assess QoL, response rate and physical function in elderly anaemic MDS patients treated to a target Hb level of >120 g/L....

  1. Myelodysplastic syndrome: classification and prognostic systems

    Directory of Open Access Journals (Sweden)

    Rosangela Invernizzi

    2011-12-01

    Full Text Available Myelodysplastic syndromes (MDS are acquired clonal disorders of hematopoiesis, that are characterized most frequently by normocellular or hypercellular bone marrow specimens, and maturation that is morphologically and functionally dysplastic. MDS constitute a complex hematological problem: differences in disease presentation, progression and outcome have made it necessary to use classification systems to improve diagnosis, prognostication and treatment selection. On the basis of new scientific and clinical information, classification and prognostic systems have recently been updated and minimal diagnostic criteria forMDS have been proposed by expert panels. In addition, in the last few years our ability to define the prognosis of the individual patient with MDS has improved. In this paper World Health Organization (WHO classification refinements and recent prognostic scoring systems for the definition of individual risk are highlighted and current criteria are discussed. The recommendations should facilitate diagnostic and prognostic evaluations in MDS and selection of patients for new effective targeted therapies.

  2. MECP2 Duplication Syndrome

    DEFF Research Database (Denmark)

    Signorini, Cinzia; De Felice, Claudio; Leoncini, Silvia

    2016-01-01

    Rett syndrome (RTT) and MECP2 duplication syndrome (MDS) are neurodevelopmental disorders caused by alterations in the methyl-CpG binding protein 2 (MECP2) gene expression. A relationship between MECP2 loss-of-function mutations and oxidative stress has been previously documented in RTT patients...... and murine models. To date, no data on oxidative stress have been reported for the MECP2 gain-of-function mutations in patients with MDS. In the present work, the pro-oxidant status and oxidative fatty acid damage in MDS was investigated (subjects n = 6) and compared to RTT (subjects n = 24) and healthy...... condition (subjects n = 12). Patients with MECP2 gain-of-function mutations showed increased oxidative stress marker levels (plasma non-protein bound iron, intraerythrocyte non-protein bound iron, F2-isoprostanes, and F4-neuroprostanes), as compared to healthy controls (P ≤ 0.05). Such increases were...

  3. Immune-mediated complications in patients with myelodysplastic syndromes--clinical and cytogenetic features.

    Science.gov (United States)

    Billström, R; Johansson, H; Johansson, B; Mitelman, F

    1995-07-01

    It has been recognized in recent years that some patients with myelodysplastic syndromes (MDS) develop immune-mediated complications (IMC), but little is known about the correlations to MDS-specific disease features. In a retrospective study of 82 MDS patients, we identified 10 (12%) with IMC (group A) and compared them to the remaining 72 cases (group B). Group A consisted of 5 patients with biopsy-verified skin vasculitis and 1 case each with temporal arteritis/polymyalgia rheumatica, necrotising panniculitis, Hashimoto's thyroiditis, autoimmune thrombocytopenia, and Sweet's syndrome. Survival times, sex ratio and distribution of MDS subtypes were similar in the two groups. The patients in group A were younger than those in group B (median 66 vs. 76 years, p aberrations, were also observed to be more common in group A (3/9 vs. 8/53). The results indicate that IMC preferentially develop in patients with secondary MDS, in younger MDS cases, and in patients with cytogenetic abnormalities.

  4. TSUBASA (MDS-1) observations of energetic electrons and magnetic field variations in outer radiation belt

    Science.gov (United States)

    Nakamura, M.; Matsuoka, H.; Liu, H.; Koshiishi, H.; Koga, K.; Matsumoto, H.; Goka, T.

    2002-12-01

    We have investigated variations of energetic electrons (> 0.4 MeV) and magnetic field in the radiation belt obtained from the Standard DOse Monitor (SDOM) and the MAgnetoMeter (MAM) of the Space Environment Data Acquisition equipment (SEDA) onboard TSUBASA (the Mission Demonstration Test Satellite (MDS)-1) launched on February 4, 2002. Since TSUBASA is operated in the geostationary transfer orbit, it has provided rare opportunities of directly observing near-equatorial radiation belt plasma particles and magnetic field, having already included several large magnetic storms. The energetic electrons in the outer radiation belt are contributors to the total radiation dose deposited in lightly shielded spacecraft electronics for high altitude orbits and are known to have a drastic variability associated with geomagnetic storm and high speed solar wind streams. The abrupt energetic electron flux decreases in the outside of outer radiation belt show characteristic variations of in situ magnetic field. These observations have implications for the possible mechanisms of the depletion and the following recovery and/or buildup of energetic electrons in the outer radiation belt.

  5. The chimeric genes AML1/DS1 and AML1/EAP inhibit AML1B activation at the CSF1R promoter, but only AML1/MDS1 has tumor-promoter properties

    Energy Technology Data Exchange (ETDEWEB)

    Zent, C.S.; Matheiu, C.; Rowley, J.D. [Univ. of Chicago, IL (United States)] [and others

    1996-02-06

    The (3;21)(q26;q22) translocation associated with treatment-related myelodysplastic syndrome, treatment-related acute myeloid leukemia, and blast crisis of chronic myeloid leukemia results in the expression of the chimeric genes AML1/EAP, AML1MDS1, and AML1/EVI1. AML1 (CBFA2), which codes for the {alpha} subunit of the heterodimeric transcription factor CBF, is also involved in the t(8;21), and the gene coding for the {beta} subunit (CBFB) is involved in the inv(16). These are two of the most common recurring chromosomal rearrangements in acute myeloid leukemia. CBF corresponds to the murine Pebp2 factor, and CBF binding sites are found in a number of eukaryotic and viral enhancers and promoters. We studied the effects of AML1/EAP and AML1/MDS1 at the AML1 binding site of the CSF1R (macrophage-colony-stimulating factor receptor gene) promoter by using reporter gene assays, and we analyzed the consequences of the expression of both chimeric proteins in an embryonic rat fibroblast cell line (Rat1A) in culture and after injection into athymic nude mice. Unlike AML1, which is an activator of the CSF1R promoter, the chimeric proteins did not transactivate the CSF1R promoter site but acted as inhibitors of AMLI (CBFA2). AML1/EAP and AML1/MDS1 expressed in adherent Rat1A cells decreased contact inhibition of growth, and expression of AML1/MDS1 was associated with acquisition of the ability to grow in suspension culture. Expression of AML1/MDS1 increased the tumorigenicity of Rat1A cells injected into athymic nude mice, whereas AML1/EAP expression provented tumor growth. These results suggest that expression of AML1/MDS1 can interfere with normal AML1 function, and that AML1/MDS1 has tumor-promoting properties in an embryonic rat fibroblast cell line. 26 refs., 5 figs.

  6. Measuring depression in nursing home residents with the MDS and GDS: an observational psychometric study

    Directory of Open Access Journals (Sweden)

    Fries Brant E

    2005-01-01

    Full Text Available Abstract Background The objective of this study was to examine the Minimum Data Set (MDS and Geriatric Depression Scale (GDS as measures of depression among nursing home residents. Methods The data for this study were baseline, pre-intervention assessment data from a research study involving nine nursing homes and 704 residents in Massachusetts. Trained research nurses assessed residents using the MDS and the GDS 15-item version. Demographic, psychiatric, and cognitive data were obtained using the MDS. Level of depression was operationalized as: (1 a sum of the MDS Depression items; (2 the MDS Depression Rating Scale; (3 the 15-item GDS; and (4 the five-item GDS. We compared missing data, floor effects, means, internal consistency reliability, scale score correlation, and ability to identify residents with conspicuous depression (chart diagnosis or use of antidepressant across cognitive impairment strata. Results The GDS and MDS Depression scales were uncorrelated. Nevertheless, both MDS and GDS measures demonstrated adequate internal consistency reliability. The MDS suggested greater depression among those with cognitive impairment, whereas the GDS suggested a more severe depression among those with better cognitive functioning. The GDS was limited by missing data; the DRS by a larger floor effect. The DRS was more strongly correlated with conspicuous depression, but only among those with cognitive impairment. Conclusions The MDS Depression items and GDS identify different elements of depression. This may be due to differences in the manifest symptom content and/or the self-report nature of the GDS versus the observer-rated MDS. Our findings suggest that the GDS and the MDS are not interchangeable measures of depression.

  7. Incidence of ATRX mutations in myelodysplastic syndromes, the value of microcytosis.

    Science.gov (United States)

    Herbaux, Charles; Duployez, Nicolas; Badens, Catherine; Poret, Nicolas; Gardin, Claude; Decamp, Mathieu; Eclache, Virginie; Daliphard, Sylvie; Murati, Anne; Cony-Makhoul, Pascale; Cheze, Stéphane; Beve, Blandine; Lacoste, Caroline; Prebet, Thomas; Hunault-Berger, Mathilde; Maloisel, Frédéric; Renneville, Aline; Figeac, Martin; Stamatoullas-Bastard, Aspasia; Bastard, Christian; Fenaux, Pierre; Preudhomme, Claude; Rose, Christian

    2015-08-01

    Acquired α-thalassemia myelodysplastic syndrome (MDS) (ATMDS) is an acquired syndrome characterized by a somatic point mutation or splicing defect in the ATRX gene in patients with myeloid disorders, primarily MDS. In a large MDS patient series, the incidence of ATMDS was below 0.5%. But no large series has yet assessed the incidence of ATMDS in microcytic MDS. In this study, we focused on patients with MDS and unexplained microcytosis, which was defined as absence of iron deficiency, inflammatory disease, or history of inherited hemoglobinopathy. Our data confirm the low frequency of ATRX mutations in MDS: 0% in an unselected clinical trial cohort of 80 low risk MDS, 0.2-0.8% in a multicenter registry of 2,980 MDS and 43% of MDS with unexplained microcytosis in this same registry. In addition, we reported four novel mutations of the ATRX gene in ATMDS. This study further determines the frequency of ATRX mutations and highlights the importance of microcytosis to detect ATRX mutations within MDS patients.

  8. Impact of cytogenetics on outcome of de novo and therapy-related AML and MDS after allogeneic transplantation.

    Science.gov (United States)

    Armand, Philippe; Kim, Haesook T; DeAngelo, Daniel J; Ho, Vincent T; Cutler, Corey S; Stone, Richard M; Ritz, Jerome; Alyea, Edwin P; Antin, Joseph H; Soiffer, Robert J

    2007-06-01

    Cytogenetics has an important impact on the prognosis of patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) for acute myelogenous leukemia (AML) or myelodysplastic syndromes (MDS). However, it is unclear whether currently accepted cytogenetic risk groups, which were established for patients treated mostly with standard therapy, are optimally discriminating for patients undergoing HSCT. Also, the impact of cytogenetics in the growing population of patients with therapy-related disease has not been completely elucidated. In this study, we retrospectively analyzed data on 556 patients with AML or MDS transplanted at our institution. We examined, in multivariate analyses, the contribution of cytogenetics to survival, relapse, and nonrelapse mortality for the 476 patients with de novo disease. We used these results to establish an optimal cytogenetic grouping scheme. We then applied this grouping scheme to the 80 patients with therapy-related disease. Our proposed 3-group cytogenetic classification outperformed the established grouping schemes for both de novo and therapy-related disease. When classified by this new scheme, cytogenetics was the strongest prognostic factor for overall survival in our cohort, through its impact on the risk of relapse (and not on nonrelapse mortality). After accounting for cytogenetics, patients with therapy-related AML or MDS had an equivalent outcome to those with de novo disease. This study demonstrates the impact of cytogenetics on the risk of relapse and death for patients with both de novo and therapy-related disease undergoing transplantation; it also emphasizes the necessity of using cytogenetics to stratify patients entering clinical trials, and provides a system for doing so, which can be validated in a multi-institutional database.

  9. High-resolution genome-wide array-based comparative genome hybridization reveals cryptic chromosome changes in AML and MDS cases with trisomy 8 as the sole cytogenetic aberration.

    Science.gov (United States)

    Paulsson, K; Heidenblad, M; Strömbeck, B; Staaf, J; Jönsson, G; Borg, A; Fioretos, T; Johansson, B

    2006-05-01

    Although trisomy 8 as the sole chromosome aberration is the most common numerical abnormality in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), little is known about its pathogenetic effects. Considering that +8 is a frequent secondary change in AML/MDS, cryptic--possibly primary--genetic aberrations may occur in cases with trisomy 8 as the apparently single anomaly. However, no such hidden anomalies have been reported. We performed a high-resolution genome-wide array-based comparative genome hybridization (array CGH) analysis of 10 AML/MDS cases with isolated +8, utilizing a 32K bacterial artificial chromosome array set, providing >98% coverage of the genome with a resolution of 100 kb. Array CGH revealed intrachromosomal imbalances, not corresponding to known genomic copy number polymorphisms, in 4/10 cases, comprising nine duplications and hemizygous deletions ranging in size from 0.5 to 2.2 Mb. A 1.8 Mb deletion at 7p14.1, which had occurred prior to the +8, was identified in MDS transforming to AML. Furthermore, a deletion including ETV6 was present in one case. The remaining seven imbalances involved more than 40 genes. The present results show that cryptic genetic abnormalities are frequent in trisomy 8-positive AML/MDS cases and that +8 as the sole cytogenetic aberration is not always the primary genetic event.

  10. Despite differential gene expression profiles pediatric MDS derived mesenchymal stromal cells display functionality in vitro

    Directory of Open Access Journals (Sweden)

    F.G.J. Calkoen

    2015-03-01

    An altered mRNA expression profile, associated with cell survival and malignant transformation, of MSC derived from children with MDS strengthens the hypothesis that the micro-environment is of importance in this disease. Our data support the understanding that pediatric and adult MDS are two different diseases. Further evaluation of the pathways involved might reveal additional therapy targets.

  11. New q-ary quantum MDS codes with distances bigger than q/2

    Science.gov (United States)

    He, Xianmang; Xu, Liqing; Chen, Hao

    2016-07-01

    The construction of quantum MDS codes has been studied by many authors. We refer to the table in page 1482 of (IEEE Trans Inf Theory 61(3):1474-1484, 2015) for known constructions. However, there have been constructed only a few q-ary quantum MDS [[n,n-2d+2,d

  12. A DMA interface between a Biomation 8100 and an Intel MDS-800 microcomputer development system.

    Science.gov (United States)

    Lynk, E T

    1979-09-01

    An interface is described which permits high-speed data transfer between a Biomation 8100 transient recorder and an Intel MDS-800 microcomputer system equipped with an MDS-501 DMA (direct memory access) channel controller. The interface is especially useful for data acquisition situations in which many successive traces must be recorded. For example, signal averaging can be performed within the microcomputer system.

  13. Measurement of Radiation Belt Partcles by MDS-1 Onboard SEDA

    Science.gov (United States)

    Matsumoto, H.; Koshiishi, H.; Goka, T.

    The Space Environment Data Acquisition Equipment (SEDA) is on board the Mission Demonstration Test Satellite-1 (MDS-1) to measure the radiation environment, which was launched into geo-stationary transfer orbit (GTO) on February 4, 2002 with an apogee of about 35,700km, a perigee of about 500 km and an inclination of about 28.5 degrees. SEDA consists of the four instruments. Standard Dose Monitor monitors the electron and proton flux. Dosimeter measures the integrated radiation dose at fifty-six points of the satellite. Heavy Ion Telescope monitors the flux of heavy ions from He to Fe. Magnetometer measures the magnetic field in the magnetosphere. In this paper are described first results and comparison with the ISO standard model for the space environment

  14. Autoimmune diseases and myelodysplastic syndromes.

    Science.gov (United States)

    Komrokji, Rami S; Kulasekararaj, Austin; Al Ali, Najla H; Kordasti, Shahram; Bart-Smith, Emily; Craig, Benjamin M; Padron, Eric; Zhang, Ling; Lancet, Jeffrey E; Pinilla-Ibarz, Javier; List, Alan F; Mufti, Ghulam J; Epling-Burnette, Pearlie K

    2016-05-01

    Immune dysregulation and altered T-cell hemostasis play important roles in the pathogenesis of myelodysplastic syndromes (MDS). Recent studies suggest an increased risk of MDS among patients with autoimmune diseases. Here, we investigated the prevalence of autoimmune diseases among MDS patients, comparing characteristics and outcomes in those with and without autoimmune diseases. From our study group of 1408 MDS patients, 391 (28%) had autoimmune disease, with hypothyroidism being the most common type, accounting for 44% (n = 171) of patients (12% among all MDS patients analyzed). Other autoimmune diseases with ≥5% prevalence included idiopathic thrombocytopenic purpura in 12% (n = 46), rheumatoid arthritis in 10% (n = 41), and psoriasis in 7% (n = 28) of patients. Autoimmune diseases were more common in female MDS patients, those with RA or RCMD WHO subtype, and those who were less dependent on red blood cell transfusion. Median overall survival (OS) was 60 months (95% CI, 50-70) for patients with autoimmune diseases versus 45 months (95% CI, 40-49) for those without (log-rank test, P = 0.006). By multivariate analysis adjusting for revised IPSS and age >60 years, autoimmune diseases were a statistically significant independent factor for OS (HR 0.78; 95% CI, 0.66-0.92; P = 0.004). The rate of acute myeloid leukemia (AML) transformation was 23% (n = 89) in MDS patients with autoimmune disease versus 30% (n = 301) in those without (P = 0.011). Patient groups did not differ in response to azacitidine or lenalidomide treatment. Autoimmune diseases are prevalent among MDS patients. MDS patients with autoimmune diseases have better OS and less AML transformation.

  15. Azacitidine for treatment of imminent relapse in MDS or AML patients after allogeneic HSCT: results of the RELAZA trial

    Science.gov (United States)

    Platzbecker, U; Wermke, M; Radke, J; Oelschlaegel, U; Seltmann, F; Kiani, A; Klut, I-M; Knoth, H; Röllig, C; Schetelig, J; Mohr, B; Graehlert, X; Ehninger, G; Bornhäuser, M; Thiede, C

    2012-01-01

    This study evaluated azacitidine as treatment of minimal residual disease (MRD) determined by a sensitive donor chimerism analysis of CD34+ blood cells to pre-empt relapse in patients with CD34+ myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (HSCT). At a median of 169 days after HSCT, 20/59 prospectively screened patients experienced a decrease of CD34+ donor chimerism to <80% and received four azacitidine cycles (75 mg/m2/day for 7 days) while in complete hematologic remission. A total of 16 patients (80%) responded with either increasing CD34+ donor chimerism to ⩾80% (n=10; 50%) or stabilization (n=6; 30%) in the absence of relapse. Stabilized patients and those with a later drop of CD34+ donor chimerism to <80% after initial response were eligible for subsequent azacitidine cycles. A total of 11 patients (55%) received a median of 4 (range, 1–11) additional cycles. Eventually, hematologic relapse occurred in 13 patients (65%), but was delayed until a median of 231 days (range, 56–558) after initial decrease of CD34+ donor chimerism to <80%. In conclusion, pre-emptive azacitidine treatment has an acceptable safety profile and can substantially prevent or delay hematologic relapse in patients with MDS or AML and MRD after allogeneic HSCT. PMID:21886171

  16. Immune responses to WT1 in patients with AML or MDS after chemotherapy and allogeneic stem cell transplantation.

    Science.gov (United States)

    Casalegno-Garduño, Rosaely; Schmitt, Anita; Spitschak, Alf; Greiner, Jochen; Wang, Lei; Hilgendorf, Inken; Hirt, Carsten; Ho, Anthony D; Freund, Mathias; Schmitt, Michael

    2016-04-01

    Wilms' tumor gene 1 (WT1) is overexpressed in leukemia and WT1-derived CD8(+) T-cell epitopes for immunotherapies targeting WT1 have been defined. Here, we analyzed expression of WT1 in 226 peripheral blood and bone marrow samples from patients with acute myeloid leukemia or myelodysplastic syndrome (AML/MDS) before and after allogeneic stem cell transplantation (SCT). Transcripts were assessed by quantitative polymerase chain reaction, and WT1-specific CD8+ cytotoxic T cells (CTL) were monitored by tetramer staining and enzyme-linked immunospot (ELISPOT) assays. Reduction of WT1 levels correlated with a longer survival (p CTL than in patients developing a relapse were detected. These cells were effector T cells secreting interferon gamma and granzyme B. In summary, WT1 is a suitable marker for the detection of minimal residual disease after SCT or chemotherapy. A rising WT1 signal correlated with a dismal prognosis of the patients. WT1-specific CD8(+) T cells might contribute to the maintenance of a cCR. Targeting WT-1 by peptide/protein vaccination as well as adoptive transfer of genetically modified T cells are future options in the individualized therapy for AML/MDS patients. © 2015 UICC.

  17. Quantitative Detection of ID4 Gene Aberrant Methylation in the Differentiation of Myelodysplastic Syndrome from Aplastic Anemia

    Institute of Scientific and Technical Information of China (English)

    Mian-Yang Li; Yuan-Yuan Xu; Hui-Yuan Kang; Xin-Rong Wang; Li Gao; Jian Cen; Wei Wang

    2015-01-01

    Background:The diagnosis of myelodysplastic syndrome (MDS),especially hypoplastic MDS,and MDS with low blast counts or normal karyotype may be problematic.This study characterized ID4 gene methylation in patients with MDS and aplastic anemia (AA).Methods:The methylation status ofID4 was analyzed by bisulfite sequencing polymerase chain reaction (PCR) and quantitative real-time methylation-specific PCR (MethyLight PCR) in 100 patients with MDS and 31 patients with AA.Results:The MDS group had a higher ID4 gene methylation positivity rate (22.22%) and higher methylation levels (0.21 [0-3.79]) than the AA group (P < 0.05).Furthermore,there were significant differences between the hypoplastic MDS and AA groups,the MDS with low blast count and the AA groups,and the MDS with normal karyotype and the AA groups.The combination of genetic and epigenetic markers was used in much more patients with MDS (62.5% [35/56]) than the use of genetic markers only (51.79% [29/56]).Conclusions:These results showed that the detection ofID4 methylation positivity rates and levels could be a useful biomarker for MDS diagnosis.

  18. Iron overload in patients with acute leukemia or MDS undergoing myeloablative stem cell transplantation.

    Science.gov (United States)

    Armand, Philippe; Kim, Haesook T; Rhodes, Joanna; Sainvil, Marie-Michele; Cutler, Corey; Ho, Vincent T; Koreth, John; Alyea, Edwin P; Hearsey, Doreen; Neufeld, Ellis J; Fleming, Mark D; Steen, Hanno; Anderson, Damon; Kwong, Raymond Y; Soiffer, Robert J; Antin, Joseph H

    2011-06-01

    Patients with hematologic malignancies undergoing allogeneic stem cell transplantation (HSCT) commonly have an elevated serum ferritin prior to HSCT, which has been associated with increased mortality after transplantation. This has led to the suggestion that iron overload is common and deleterious in this patient population. However, the relationship between serum ferritin and parenchymal iron overload in such patients is unknown. We report a prospective study of 48 patients with acute leukemia (AL) or myelodysplastic syndromes (MDS) undergoing myeloablative HSCT, using magnetic resonance imaging (MRI) to estimate liver iron content (LIC) and cardiac iron. The median (and range) pre-HSCT value of serum ferritin was 1549 ng/mL (20-6989); serum hepcidin, 59 ng/mL (10-468); labile plasma iron, 0 LPI units (0.0-0.9). Eighty-five percent of patients had hepatic iron overload (HIO), and 42% had significant HIO (LIC ≥5.0 mg/gdw). Only 1 patient had cardiac iron overload. There was a strong correlation between pre-HSCT serum ferritin and estimated LIC (r = .75), which was mostly dependent on prior transfusion history. Serum hepcidin was appropriately elevated in patients with HIO. Labile plasma iron elevation was rare. A regression calibration analysis supported the hypothesis that elevated pre-HSCT LIC is significantly associated with inferior post-HSCT survival. These results contribute to our understanding of the prevalence, mechanism, and consequences of iron overload in HSCT.

  19. Epigenetic landscape of the TERT promoter: a potential biomarker for high risk AML/MDS.

    Science.gov (United States)

    Zhao, Xin; Tian, Xin; Kajigaya, Sachiko; Cantilena, Caroline R; Strickland, Stephen; Savani, Bipin N; Mohan, Sanjay; Feng, Xingmin; Keyvanfar, Keyvan; Dunavin, Neil; Townsley, Danielle M; Dumitriu, Bogdan; Battiwalla, Minoo; Rezvani, Katayoun; Young, Neal S; Barrett, A John; Ito, Sawa

    2016-11-01

    Although recent observations implicate the importance of telomerase activity in acute myeloid leukaemia (AML), the roles of epigenetic regulations of the TERT gene in leukaemogenesis, drug resistance and clinical prognosis in AML are not fully understood. We developed a quantitative pyrosequencing-based methylation assay covering the TERT proximal promoter and a partial exon 1 (TERTpro/Ex1) region and tested both cell lines and primary leukaemia cells derived from AML and AML with preceding myelodysplastic syndrome (AML/MDS) patients (n = 43). Prognostic impact of methylation status of the upstream TERT promoter region was assessed by the Kaplan-Meier method. The activity of the telomerase inhibitor, imetelstat, was measured using leukaemia cell lines. The TERTpro/Ex1 region was highly methylated in all cell lines and primary leukaemia cells showed diverse methylation profiles. Most cases showed hypermethylated regions at the upstream TERTpro/Ex1 region, which were associated with inferior patient survival. TERTpro/Ex1 methylation status was correlated with the cytotoxicity to imetelstat and its combination with hypomethylating agent enhanced the cytotoxicity of imetelstat. AML cell lines and primary blasts harbour distinct TERTpro/Ex1 methylation profiles that could serve as a prognostic biomarker of AML. However, validation in a large cohort of patients is necessary to confirm our findings.

  20. Temporary CD8(+) T-cell depletion in pigs does not exacerbate infection with porcine reproductive and respiratory syndrome virus (PRRSV)

    DEFF Research Database (Denmark)

    Lohse, Louise; Nielsen, Jens; Eriksen, Lis

    2004-01-01

    , confirmed the depletion effect of specific mAb therapy. Almost complete depletion of cell subsets expressing the CD8(+) antigen was obtained on day 2 and 5 post infection (PI) with nadir less than 1 % of peripheral blood mononuclear cells (PBMC). One week PI, an increase in T-cell subsets was observed...... to test this hypothesis, we examined five 5-week-old pigs, which had been depleted for CD8(+) T-cells by treatment with anti-CD8 mAb injections, starting 2 days before inoculation with PRRSV. Virus-inoculated and sham-inoculated age-matched pigs served as controls. Blood samples were collected...... continuously, together with organ material at necropsy, to study kinetics of leukocyte subpopulations, antibody production and virus persistence in individual pigs. Significant lower CD8(+) T-cell counts on day 0, that is, before virus challenge, in the anti-CD8 mAb treated pigs compared to the control pigs...

  1. Cellular immune profiling after sequential clofarabine and lenalidomide for high risk myelodysplastic syndromes and acute myeloid leukemia.

    Science.gov (United States)

    Jain, Prachi; Klotz, Jeffrey; Dunavin, Neil; Lu, Kit; Koklanaris, Eleftheria; Draper, Debbie; Superata, Jeanine; Chinian, Fariba; Yu, Quan; Keyvanfar, Keyvan; Wong, Susan; Muranski, Pawel; Barrett, A John; Ito, Sawa; Battiwalla, Minoo

    2017-01-01

    Patients with high risk myelodysplastic syndromes (MDS) and acute myelogenous leukemia (AML) are commonly older with multiple co-morbidities, rendering them unsuitable for intensive induction chemotherapy or transplantation. We report preliminary cellular immune profiling of four cases receiving sequential clofarabine and lenalidomide for high risk MDS and AML in a phase I study. Our results highlight the potential of immune profiling for monitoring immune-modifying agents in high risk MDS and AML.

  2. Cellular immune profiling after sequential clofarabine and lenalidomide for high risk myelodysplastic syndromes and acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Prachi Jain

    2017-01-01

    Full Text Available Patients with high risk myelodysplastic syndromes (MDS and acute myelogenous leukemia (AML are commonly older with multiple co-morbidities, rendering them unsuitable for intensive induction chemotherapy or transplantation. We report preliminary cellular immune profiling of four cases receiving sequential clofarabine and lenalidomide for high risk MDS and AML in a phase I study. Our results highlight the potential of immune profiling for monitoring immune-modifying agents in high risk MDS and AML.

  3. Safety and efficacy of romiplostim in patients with lower-risk myelodysplastic syndrome and thrombocytopenia.

    NARCIS (Netherlands)

    Kantarjian, H.; Fenaux, P.; Sekeres, M.A.; Becker, P.S.; Boruchov, A.; Bowen, D.; Hellstrom-Lindberg, E.; Larson, R.A.; Lyons, R.M.; Muus, P.; Shammo, J.; Siegel, R.; Hu, K.; Franklin, J.; Berger, D.P.

    2010-01-01

    PURPOSE: To assess the safety and efficacy of romiplostim, a peptibody that increases platelet production, for treatment of thrombocytopenic patients with myelodysplastic syndromes (MDS). PATIENTS AND METHODS: Eligible patients had lower-risk MDS (International Prognostic Scoring System low or inter

  4. Genomic array as compared to karyotyping in myelodysplastic syndromes in a prospective clinical trial

    NARCIS (Netherlands)

    Stevens-Kroef, Marian J; Olde Weghuis, Daniel; ElIdrissi-Zaynoun, Najat; van der Reijden, Bert; Cremers, Eline M P; Alhan, Canan; Westers, Theresia M; Visser-Wisselaar, Heleen A; Chitu, Dana A; Cunha, Sonia M; Vellenga, Edo; Klein, Saskia K; Wijermans, Pierre; de Greef, Georgine E; Schaafsma, M Ron; Muus, Petra; Ossenkoppele, Gert J; van de Loosdrecht, Arjan A; Jansen, Joop H

    2017-01-01

    Karyotyping is considered as the gold standard in the genetic subclassification of myelodysplastic syndrome (MDS). Oligo/SNP-based genomic array profiling is a high-resolution tool that also enables genome wide analysis. We compared karyotyping with oligo/SNP-based array profiling in 104 MDS patient

  5. Transformation of Myelodysplastic Syndrome to Acute Lymphoblastic Leukemia in a Child

    OpenAIRE

    2010-01-01

    Childhood myelodysplastic syndrome (MDS) is an uncommon condition. Unlike adult MDS, pediatric patients have a more progressive course and rapidly transform to acute myeloid leukemia. Evolution to acute lymphoblastic leukemia is extremely rare. We report a 5 year old female child who presented with refractory anemia with excess blasts and transformed into acute lymphoblastic leukemia 4 months after initial diagnosis.

  6. Necrotizing fasciitis in two patients with myelodysplastic syndrome treated with azacitidine.

    Science.gov (United States)

    Lai, Shiue-Wei; Huang, Tzu-Chuan; Ye, Ren-Hua; Wu, Yi-Ying

    2015-03-01

    Azacitidine is a novel agent for treating myelodysplastic syndromes (MDS). It has a relatively safe toxicity profile with very few reported skin toxicities. Patients with MDS were prone to get severe infections, especially via respiratory tract, urinary system, and bloodstream. However, necrotizing fasciitis (NF) is a relatively rare event in patients with MDS, and it is hard to diagnose early. Here, we report two MDS cases that developed NF in lower extremities while receiving azacitidine treatment. One of them survives after emergent fasciotomy along with the administration of broad-spectrum antibiotics and intravenous immunoglobulin.

  7. Severe myoclonus-dystonia syndrome associated with a novel epsilon-sarcoglycan gene truncating mutation.

    Science.gov (United States)

    Maréchal, Lucie; Raux, Grégory; Dumanchin, Cécile; Lefebvre, Guillaume; Deslandre, Emmanuelle; Girard, Carole; Campion, Dominique; Parain, Dominique; Frebourg, Thierry; Hannequin, Didier

    2003-05-15

    Myoclonus-dystonia syndrome (MDS) is an autosomal dominant disorder characterized by myoclonic and dystonic muscle contractions, associated with psychiatric manifestations. MDS is usually considered as a benign disease. In most of the families, MDS is linked to chromosome 7q21 and mutations within epsilon-sarcoglycan (SGCE) gene have been recently described. We report a MDS family with a severe and heterogeneous phenotype, including myoclonus with important functional impact and several psychiatric features, characterized by obsessive-compulsive disorder, depression, and anxiety. This phenotype was shown to be associated with a novel truncating mutation located within exon 4 of SGCE.

  8. Clinical utility of lenalidomide in the treatment of myelodysplastic syndromes

    Directory of Open Access Journals (Sweden)

    Abou Zahr A

    2014-12-01

    Full Text Available Abdallah Abou Zahr,1 Ehab Saad Aldin,2 Rami S Komrokji,3 Amer M Zeidan4 1Section of Hematology/Oncology, Department of Internal Medicine, Mount Sinai Beth Israel, New York City, New York, NY, 2Department of Internal Medicine, Medstar Good Samaritan Hospital, Baltimore, MD, 3Department of Malignant Hematology, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 4Division of Hematology, Department of Medicine, Yale University, New Haven, CT, USA Abstract: Myelodysplastic syndromes (MDS represent a heterogeneous group of acquired clonal hematopoietic disorders characterized by peripheral blood cytopenias, paradoxical BM hypercellularity, ineffective hematopoiesis, and increased risk of leukemic transformation. Risk stratification, using different prognostic scores and markers, is at the core of MDS management. Deletion 5q [del(5q] MDS is a distinct class of MDS characterized by the haploinsufficiency of specific genes, microRNAs, and proteins, which has been linked to increased sensitivity to the drug lenalidomide. Phase II and III clinical trials have demonstrated the efficacy of lenalidomide in improving clinical outcomes of patients with del(5q MDS, including reduction in red blood cell transfusion requirements and improvements in quality of life. Lenalidomide has also demonstrated some activity in non-del(5q lower-risk MDS as well as higher-risk MDS, especially in combination with other agents. In this paper, we review the pathogenesis of del(5q MDS, the proposed mechanisms of action of lenalidomide, the major clinical trials that documented the activity of lenalidomide in different MDS populations, potential predictors of benefit from the drug and suggested mechanisms of resistance, and the use of combination strategies to expand the clinical utility of lenalidomide in MDS. Keywords: deletion 5q, lenalidomide, myelodysplastic syndromes, 5q-syndrome

  9. Endothelial Progenitor Cell Dysfunction in Myelodysplastic Syndromes: Possible Contribution of a Defective Vascular Niche to Myelodysplasia

    Directory of Open Access Journals (Sweden)

    Luciana Teofili

    2015-05-01

    Full Text Available We set a model to replicate the vascular bone marrow niche by using endothelial colony forming cells (ECFCs, and we used it to explore the vascular niche function in patients with low-risk myelodysplastic syndromes (MDS. Overall, we investigated 56 patients and we observed higher levels of ECFCs in MDS than in healthy controls; moreover, MDS ECFCs were found variably hypermethylated for p15INK4b DAPK1, CDH1, or SOCS1. MDS ECFCs exhibited a marked adhesive capacity to normal mononuclear cells. When normal CD34+ cells were co-cultured with MDS ECFCs, they generated significant lower amounts of CD11b+ and CD41+ cells than in co-culture with normal ECFCs. At gene expression profile, several genes involved in cell adhesion were upregulated in MDS ECFCs, while several members of the Wingless and int (Wnt pathways were underexpressed. Furthermore, at miRNA expression profile, MDS ECFCs hypo-expressed various miRNAs involved in Wnt pathway regulation. The addition of Wnt3A reduced the expression of intercellular cell adhesion molecule-1 on MDS ECFCs and restored the defective expression of markers of differentiation. Overall, our data demonstrate that in low-risk MDS, ECFCs exhibit various primary abnormalities, including putative MDS signatures, and suggest the possible contribution of the vascular niche dysfunction to myelodysplasia.

  10. Two splice-factor mutant leukemia subgroups uncovered at the boundaries of MDS and AML using combined gene expression and DNA-methylation profiling.

    Science.gov (United States)

    Taskesen, Erdogan; Havermans, Marije; van Lom, Kirsten; Sanders, Mathijs A; van Norden, Yvette; Bindels, Eric; Hoogenboezem, Remco; Reinders, Marcel J T; Figueroa, Maria E; Valk, Peter J M; Löwenberg, Bob; Melnick, Ari; Delwel, Ruud

    2014-05-22

    Mutations in splice factor (SF) genes occur more frequently in myelodysplastic syndromes (MDS) than in acute myeloid leukemias (AML). We sequenced complementary DNA from bone marrow of 47 refractory anemia with excess blasts (RAEB) patients, 29 AML cases with low marrow blast cell count, and 325 other AML patients and determined the presence of SF-hotspot mutations in SF3B1, U2AF35, and SRSF2. SF mutations were found in 10 RAEB, 12 AML cases with low marrow blast cell count, and 25 other AML cases. Our study provides evidence that SF-mutant RAEB and SF-mutant AML are clinically, cytologically, and molecularly highly similar. An integrated analysis of genomewide messenger RNA (mRNA) expression profiling and DNA-methylation profiling data revealed 2 unique patient clusters highly enriched for SF-mutant RAEB/AML. The combined genomewide mRNA expression profiling/DNA-methylation profiling signatures revealed 1 SF-mutant patient cluster with an erythroid signature. The other SF-mutant patient cluster was enriched for NRAS/KRAS mutations and showed an inferior survival. We conclude that SF-mutant RAEB/AML constitutes a related disorder overriding the artificial separation between AML and MDS, and that SF-mutant RAEB/AML is composed of 2 molecularly and clinically distinct subgroups. We conclude that SF-mutant disorders should be considered as myeloid malignancies that transcend the boundaries of AML and MDS.

  11. 657del5 mutation of the NBS1 gene in myelodysplastic syndrome

    Directory of Open Access Journals (Sweden)

    Bunjevacki Vera

    2014-01-01

    Full Text Available Myelodysplastic syndromes (MDS are clonal hematologic stem cell disorders with an as yet unknown molecular pathology. Genetic instability has been proposed as a cause of MDS. Mutations in the NBS1 gene, whose product nibrin (p95 is involved in DNA damage repair and cell-cycle control, might be associated with an elevated predisposition to the development of MDS. The aim of the study was to examine truncating 5 bp deletion (657del5, the most frequent NBS1 gene mutation in Slavic populations, in MDS patients. Among 71 MDS patients, we found one case that was heterozygous for the NBS1 657del5 mutation. To the best of our knowledge, this is the first report of a NBS1 mutation in MDS. [Projekat Ministarstva nauke Republike Srbije, br. 175091

  12. Comprehensive scanning of somatic mitochondrial DNA alterations in acute leukemia developing from myelodysplastic syndromes.

    Science.gov (United States)

    Linnartz, Bjoern; Anglmayer, Roswitha; Zanssen, Stefanie

    2004-03-15

    Myelodysplastic syndromes (MDS) are clonal myeloid disorders characterized by ineffective hematopoiesis resulting in refractory cytopenias. Transformation resulting in acute myeloblastic leukemia is the final stage in the multistep process of MDS evolution. Functional relevant mutations of mitochondrial DNA (mtDNA) have been related to sideroblastic anemia and MDS. To investigate the role of mtDNA in malignant transformation to acute leukemia, we used high-resolution techniques such as single-strand conformational polymorphism and fluorescence sequencing for investigation of the whole mitochondrial genome from blood cells of 10 patients with MDS. Functionally relevant point mutations in mitochondrial RNA and polypeptide-encoding genes were detected in 50% of patients with MDS. Their increasing mutation load connects MDS and the developing acute myeloid leukemias. Several point mutations of mtDNA, including secondary point mutations for Leber's hereditary optic neuropathy, occur in one bone marrow and may synergically affect bone marrow stem cells by an apoptotic pathway.

  13. Myelodysplastic Syndrome and Histone Deacetylase Inhibitors: “To Be or Not to Be Acetylated”?

    Directory of Open Access Journals (Sweden)

    Sebastian Stintzing

    2011-01-01

    Full Text Available Myelodysplastic syndrome (MDS represents a heterogeneous group of diseases with clonal proliferation, bone marrow failure and increasing risk of transformation into an acute myeloid leukaemia. Structured guidelines are developed for selective therapy based on prognostic subgroups, age, and performance status. Although many driving forces of disease phenotype and biology are described, the complete and possibly interacting pathogenetic pathways still remain unclear. Epigenetic investigations of cancer and haematologic diseases like MDS give new insights into the pathogenesis of this complex disease. Modifications of DNA or histones via methylation or acetylation lead to gene silencing and altered physiology relevant for MDS. First clinical trials give evidence that patients with MDS could benefit from epigenetic treatment with, for example, DNA methyl transferase inhibitors (DNMTi or histone deacetylase inhibitors (HDACi. Nevertheless, many issues of HDACi remain incompletely understood and pose clinical and translational challenges. In this paper, major aspects of MDS, MDS-associated epigenetics and the potential use of HDACi are discussed.

  14. Non-hematologic predictors of mortality improve the prognostic value of the international prognostic scoring system for MDS in older adults†

    Science.gov (United States)

    Fega, K. Rebecca; Abel, Gregory A.; Motyckova, Gabriela; Sherman, Alexander E.; DeAngelo, Daniel J.; Steensma, David P.; Galinsky, Ilene; Wadleigh, Martha; Stone, Richard M.; Driver, Jane A.

    2016-01-01

    Objectives The International Prognostic Scoring System (IPSS) is commonly used to predict survival and assign treatment for the myelodysplastic syndromes (MDS). We explored whether self-reported and readily available non-hematologic predictors of survival add independent prognostic information to the IPSS. Materials and Methods Retrospective cohort study of consecutive MDS patients ≥age 65 who presented to Dana-Farber Cancer Institute between 2006 and 2011 and completed a baseline quality of life questionnaire. Questions corresponding to functional status and symptoms and extracted clinical-pathologic data from medical records. Kaplan–Meier and Cox proportional hazards models were used to estimate survival. Results One hundred fourteen patients consented and were available for analysis. Median age was 73 years, and the majority of patients were White, were male, and had a Charlson comorbidity score of <2. Few patients (24%) had an IPSS score consistent with lower-risk disease and the majority received chemotherapy. In addition to IPSS score and history of prior chemotherapy or radiation, significant univariate predictors of survival included low serum albumin, Charlson score, performance status, ability to take a long walk, and interference of physical symptoms in family life. The multivariate model that best predicted mortality included low serum albumin (HR = 2.3; 95% CI: 1.06–5.14), therapy-related MDS (HR = 2.1; 95% CI: 1.16–4.24), IPSS score (HR = 1.7; 95% CI: 1.14–2.49), and ease taking a long walk (HR = 0.44; 95% CI: 0.23–0.90). Conclusions In this study of older adults with MDS, we found that low serum albumin and physical function added important prognostic information to the IPSS score. Self-reported physical function was more predictive than physician-assigned performance status. PMID:26073533

  15. Phase II study of tosedostat with cytarabine or decitabine in newly diagnosed older patients with acute myeloid leukaemia or high-risk MDS.

    Science.gov (United States)

    Mawad, Raya; Becker, Pamela S; Hendrie, Paul; Scott, Bart; Wood, Brent L; Dean, Carol; Sandhu, Vicky; Deeg, Hans Joachim; Walter, Roland; Wang, Lixia; Myint, Han; Singer, Jack W; Estey, Elihu; Pagel, John M

    2016-01-01

    Tosedostat, an oral aminopeptidase inhibitor, has synergy with cytarabine and hypomethylating agents. We performed a Phase II trial to determine rates of complete remission (CR) and survival using tosedostat with cytarabine or decitabine in older patients with untreated acute myeloid leukaemia (AML) or high-risk myelodysplastic syndrome (MDS). Thirty-four patients ≥60 years old (median age 70 years; range, 60-83) were randomized to receive tosedostat (120 mg on days 1-21 or 180 mg continuously) with 5 d of either cytarabine (1 g/m2 /d) or decitabine (20 mg/m2 /d) every 35 d. Twenty-nine patients (85%) had AML, including 15 (44%) with secondary AML/MDS, and 5 (15%) had MDS-refractory anaemia with excess blasts type 2. The CR/CR with incomplete count recovery (CRi) rate was 53% [9 in each arm; 14 CR (41%) and 4 CRi (12%)], attained in 6 of 14 patients with adverse cytogenetics and 4 of 7 with FLT3-internal tandem duplication mutations. Median follow-up was 11.2 months (range, 0.5-22.3), and median survival was 11.5 months (95% confidence interval, 5.2-16.7). Twenty-three patients (67.6%) were treated as outpatients and 10 of these patients required hospitalization for febrile neutropenia. No Grade 3-4 non-haematological toxicities required withdrawal from study. Tosedostat with cytarabine or decitabine is tolerated in older patients with untreated AML/MDS, results in a CR/CRi rate of >50%, and warrants further study in larger trials.

  16. MDS-Multifunctional Dynamometer for Application in Space

    Science.gov (United States)

    Adamcik, G.; Barta, N.; Talla, R.; Angeli, T.; Kozlovskaya, I. B.; Grigoriev, A. I.; Tschan, H.; Bachl, N.

    2008-06-01

    The project MDS (Multifunctional Dynamometer for Application in Space) is an international collaboration of the University of Vienna (Faculty of Sport Science, Department of Sport and Exercise Physiology), the Russian Academy of Sciences (Institute of Biomedical Problems) and the Technical University of Vienna (Institute for Engineering Design and Logistics Engineering) with the aim to develop a training and diagnostic device that counteracts the muscle and bone loss during long term space flights. Due to the scientific results of the last years research in space medicine, it is well known, that the muscles and bones of the lower extremities and the trunk are most affected by the atrophy. Based on this knowledge a various number of resistance exercises can be done in order to train the muscles of these parts of the body and to increase the efficiency of the training by intra- and intermuscular coordination. The resisting power for the training is provided by an electric motor, thereby force, position and speed of the training can be well-regulated for different training modes.

  17. Treating 2 cases of MDS by Professor PEI Zheng-xue%裴正学教授治愈MDS 2例

    Institute of Scientific and Technical Information of China (English)

    陈光艳; 靖芳

    2014-01-01

    骨髓增生异常综合征(Myelodysplastic Syndromes,MDS)病因不明,发病机理不清,西医治疗无策。裴正学教授具有多年的临床实践经验,擅长治疗各种疑难病症,其以“兰州方”治疗MDS 2例,疗效显著。%MDS unknown etiology, pathogenesis is unclear, modern medicine is no policy. Professor PEI Zheng-xue has many years of clinical experience, specializes in treating various incurable diseases, using the “Lanzhou recipe” for treating MDS 2 cases, a significant effect.

  18. Cronkhite-Canada syndrome associated with myelodysplastic syndrome

    Institute of Scientific and Technical Information of China (English)

    Rei Suzuki; Atsushi Irisawa; Takuto Hikichi; Yuta Takahashi; Hiroko Kobayashi; Hiromi Kumakawa; Hiromasa Ohira

    2009-01-01

    We report a case of Cronkhite-Canada syndrome (CCS) associated with myelodysplastic syndrome (MDS). A 54-year-old woman, diagnosed as MDS the prior year after evaluation of anemia, visited our hospital with the chief complaint of epigastric discomfort. She also had dysgeusia, alopecia, atrophic nail change, and pigmentation of the palm, all of which began several months ago. Blood tests revealed severe hypoalbuminemia. Colonoscopy (CS) showed numerous, dense, red polyps throughout the colon and rectum. Biopsy specimens showed stromal edema, infiltration of lymphocytes, and cystic dilatation of the crypt. Her clinical manifestations and histology were consistent with CCS. We prescribed corticosteroids, which dramatically improved her physical findings, laboratory data, and endoscopic findings. This is the first report of CCS in a patient with MDS.

  19. MDS 3.0 for Nursing Homes and Swing Bed Providers

    Data.gov (United States)

    U.S. Department of Health & Human Services — The MDS is a powerful tool for implementing standardized assessment and for facilitating care management in nursing homes (NHs) and non-critical access hospital...

  20. Differential expression of ribosomal proteins in myelodysplastic syndromes.

    Science.gov (United States)

    Rinker, Elizabeth B; Dueber, Julie C; Qualtieri, Julianne; Tedesco, Jason; Erdogan, Begum; Bosompem, Amma; Kim, Annette S

    2016-02-01

    Aberrations of ribosomal biogenesis have been implicated in several congenital bone marrow failure syndromes, such as Diamond-Blackfan anaemia, Shwachman-Diamond syndrome and Dyskeratosis Congenita. Recent studies have identified haploinsufficiency of RPS14 in the acquired bone marrow disease isolated 5q minus syndrome, a subtype of myelodysplastic syndromes (MDS). However, the expression of various proteins comprising the ribosomal subunits and other proteins enzymatically involved in the synthesis of the ribosome has not been explored in non-5q minus MDS. Furthermore, differences in the effects of these expression alterations among myeloid, erythroid and megakaryocyte lineages have not been well elucidated. We examined the expression of several proteins related to ribosomal biogenesis in bone marrow biopsy specimens from patients with MDS (5q minus patients excluded) and controls with no known myeloid disease. Specifically, we found that there is overexpression of RPS24, DKC1 and SBDS in MDS. This overexpression is in contrast to the haploinsufficiency identified in the congenital bone marrow failure syndromes and in acquired 5q minus MDS. Potential mechanisms for these differences and aetiology for these findings in MDS are discussed.

  1. 支持iSCSI和FCIP两种协议Cisco MDS 9000 IP

    Institute of Scientific and Technical Information of China (English)

    张旭军

    2003-01-01

    近日,Cisco发布了MDS 9000IP存储服务模块,该模块同时支持SCSI和IFCIP(IP光纤通道)。并能通过客户现有的联网基础设施.确保经济高效和远距离的SAN连接。IP存储服务模块与Cisco MDS 9000 SAN系

  2. 骨髓增生异常综合征患者c/ebpα基因表达水平及其临床意义%Expression of c/ebpα Gene in MDS and Its Clinical Significance

    Institute of Scientific and Technical Information of China (English)

    姬文灿; 丁凯阳; 朱薇波; 汪健; 张磊; 吴竞生

    2011-01-01

    本研究探讨骨髓增生异常综合征(myelodysplastic syndrome,MDS)患者CCAAT/增强子结合蛋白α(CCAAT/enhancer binding protein alpha,C/EBPα)基因的表达及其在MDS发病、病情进展中的意义.应用Taq-man探针的实时荧光定量PCR(Real-time quantitative PCR,RQ-PCR)方法检测33例MDS患者和14例正常对照者的骨髓单个核细胞中的c/ebpα mRNA的表达,分析其在MDS中的表达水平变化.结果表明,MDS低危组和高危组c/ebpα mRNA的表达水平均显著低于对照组(分别为t=3.310,P<0.01,t=6.260,P<0.001),且c/ebpαmRNA在MDS高危组中的表达水平较低危组降低(t=2.709,P<0.05).MDS患者中c/ebpα mRNA表达水平与患者性别、年龄及血象无明显相关性,但MDS患者c/ebpα mRNA低表达组的骨髓中原始细胞比例明显高于c/ebpα mRNA高表达组(P0.01).结论:c/ebpα基因表达的下调与MDS的发病密切相关,c/ebpα基因可能是诱导MDS发病的重要分子生物学标志;c/eblα表达下调的程度与MDS的病情进展有密切关系.%This study was aimed to investigate the expression of CCAAT/enhancer binding protein alpha gene (c/ebpα) in patients with myelodysplastic syndromes (MDS) and to explore the significance of c/ebpα in pathogenesis and progression of MDS.Real time quantitative reverse transcriptase polymerase chain reaction (RQ-PCR) method was used to detect the expression level of c/ebpα mRNA in bone marrow mononuclear cells (BMMNC) of 33 patients with MDS and 14 normal controls.The results showed that the expression level of c/ebpα mRNA in low-risk and high-risk MDS was significantly lower than that of normal controls(p < 0.01, p < 0.001, respectively), moreover, high-risk MDS showed lower c/ebpα mRNA expression compared with low-risk MDS (p < 0.05 ).c/ebpα mRNA expression level in MDS was not correlated with sex, age and peripheral blood cell amount, while the ratio of blast cells in bone marrow was in the c/ebpα mRNA low expression group

  3. Influence of Decitabine on JAK2 expression in patients with MDS%地西他滨对MDS患者JAK2基因表达的影响及临床意义

    Institute of Scientific and Technical Information of China (English)

    王婷; 潘琳莉

    2016-01-01

    Objective:To study the effect of decitabine on JAK2 expression in MDS patients. Methods:To review the data of 22 patients diagnosed with myelodysplastic syndrome and 20 cases of normal control. FQ-PCR method was applied to test the peripheral blood JAK2-V617F expression. Results:The peripheral blood JAK2-V617F gene real time quantitative PCR copy number of patients with MDS-RAEB reduced from 22545. 98 ± 11084. 17 to 14654. 88 ± 7205. 41 after 2 cycles of chemotherapy by decitabine single-agent chemotherapy. The two groups before and after treatment difference was statistically significant(P<0. 01). The peripheral blood JAK2-V617F gene real time quan-titative PCR copy number reduced from 14654. 88 ± 7205. 41 to 9469. 31 ± 4655. 56 after two more cycles of chemo-therapy by decitabine single-agent chemotherapy. difference was statistically significant( P<0. 0 l). Conclusion:Decitabine can reduce JAK2 V617F gene expression significantly in patients with MDS RAEB.%目的:通过研究地西他滨对骨髓增生异常综合征(myelodysplastic syndrome,MDS)患者JAK2基因表达的影响进一步明确JAK2基因是否可作为预示地西他滨对MDS疗效的阳性分子标志物.方法:回顾2011年11月至2014年11月在门诊及住院确诊为骨髓增生异常综合征的患者共22例(其中高危MDS-RAEB型10例,低危MDS-RA型12例),抽取同期健康体检者20例作为对照组,应用FQ-PCR方法监测正常人群、MDS-RA型患者、MDS-RAEB型患者化疗前、MDS-RAEB型患者单药地西他滨化疗2周期及4周期后外周血JAK2-V617F实时定量PCR拷贝数.结果:MDS-RAEB型患者经地西他滨单药化疗2周期后外周血JAK2-V617F基因实时定量PCR拷贝数由化疗前的22545.98±11084.17下降为14654.88±7205.41,两组治疗前后比较差异有统计学意义(P<0.01).再经地西他滨单药化疗4周期后JAK2-V617F基因PCR拷贝数与化疗2周期后比,由14654.88±7205.41下降为9469.31±4655.56,比较差异有统计学意义(P<0.0l

  4. Myelodysplastic Syndrome with Myelofibrosis Transformed to a Precursor B-Cell Acute Lymphoblastic Leukemia: A Case Report with Review of the Literature

    OpenAIRE

    2012-01-01

    Myelodysplastic syndromes (MDS) comprise a group of heterogeneous clonal hematopoietic cell disorders characterized by cytopenias, bone marrow hypercellularity, and increased risk of transformation to acute leukemias. MDS usually transformed to acute myeloid leukemia, and transformation to acute lymphoblastic leukemia (ALL) is rare. Herein, we report a unique patient who presented with MDS with myelofibrosis. Two months after the initial diagnosis, she progressed to a precursor B-cell acute l...

  5. The abnormalities of microenvironment in myelodysplastic syndrome%骨髓增生异常综合征中的微环境异常

    Institute of Scientific and Technical Information of China (English)

    钱军; 陈子兴

    2003-01-01

    Myelodysplastic syndrome (MDS) is considered as a preleukemic course, characteristic of hypercellular marrow and pancytopenia. Many studies have demonstrated that defects occur in the heamtopoiet-ic cells from patients with MDS. Recently, many abnormal changes in apoptosis, proliferation, ability of hematopoietic support, cytokine secretion, clonal origin of stromal cells and angiogenesis have also been re-vealed in the bone marrow mieroenvironment of MDS patients.

  6. Epigenetic approaches in the treatment of myelodysplastic syndromes: clinical utility of azacitidine

    Directory of Open Access Journals (Sweden)

    Steven E McCormack

    2010-07-01

    Full Text Available Steven E McCormack, Erica D WarlickDepartment of Medicine, Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minneapolis, Minnesota, USAAbstract: Myelodysplastic syndromes (MDS are a varied group of diseases leading to ­significant morbidity and mortality. Therapy of MDS has been difficult, with supportive cares used to ameliorate symptoms, and hematopoietic stem cell transplantation the only curative option. Agents, such as the cytidine analog azacitidine, exert an effect on DNA methyltransferase leading to a reduction in DNA methylation, a process thought to be key to the pathogenesis of MDS. Recently, azacitidine has been shown to prolong survival and improve quality of life in patients with MDS, while maintaining a favorable adverse effect profile. This review highlights the scientific rationale for the use of azacitidine in addition to its application in current clinical practice for patients with MDS.Keywords: hypomethylation, epigenetics, myelodysplastic syndromes, azacitidine

  7. Translocation (6;15(q12;q15: A Novel Mutation in a Patient with Therapy-Related Myelodysplastic Syndrome

    Directory of Open Access Journals (Sweden)

    Saba F. Ali

    2015-01-01

    Full Text Available Most myelodysplastic syndromes (MDS present with loss or gain of chromosomal material and less commonly show translocations as a sole abnormality. In addition, certain translocations are more commonly seen in MDS than others, but to our knowledge, the presence of t(6;15 has not been reported in MDS, specifically therapy-related MDS (t-MDS cases. Patients with t-MDS, a group of heterogeneous stem cell related disorders resulting as a latent complication of cytotoxic and/or radiation therapy, generally tend to have a poorer prognosis than de novo MDS. We present a unique case of a patient who initially presented with acute myeloid leukemia (AML with a normal karyotype and FLT3-ITD and NPM1 mutations. The patient was successfully treated with chemotherapy and an autologous bone marrow transplant but subsequently developed a new FLT3-ITD negative t-MDS with a unique translocation, t(6;15(q12;q15, three years after transplant. To our knowledge, this unique sole translocation has never been reported in MDS or t-MDS and given her successful response to treatment and remission, presence of this translocation may have some prognostic value.

  8. 麦克米兰(MDS)的无纸化配送中心%An introduction to the paperless delivery center in the MDS

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    麦克米兰配送服务公司(MDS)是澳大利亚最大的图书分销商之一,为Pan Macmillan、Macmillan Education、Macmillan Academic and Reference及多家第三方出版商提供配送服务。

  9. Localization algorithm for wireless sensor networks based on MDS-MAP and nonlinear filtering%基于MDS-MAP和非线性滤波的WSN定位算法

    Institute of Scientific and Technical Information of China (English)

    陈岁生; 卢建刚; 楼晓春

    2012-01-01

    New localization algorithms for wireless sensor networks which combine multidimensional scal-ing-map (MDS-MAP) and nonlinear filtering were studied to improve the localization accuracy of sensor nodes. According to the nonlinear relationship between the sensor node distances and the node localized coordinates, the extended Kalman filter (EKF) and the unscented Kalman filter (UKF) were applied to refine the localized coordinates obtained by the MDS-MAP algorithm. The localization accuracies of these three different localization algorithms, MDS-MAP, MDS-EKF (combination of MDS-MAP and EKF) and MDS-UKF (combination of MDS-MAP and UKF), were compared. Experimental results show that the implementation of nonlinear filtering algorithms (EKF and UKF) can improve the localization accuracy. Under the same conditions, the MDS-UKF localization algorithm achieves the best accuracy and its generated network topology is the closest to the actual network topology.%为提高传感器网络节点的定位精度,对MDS-MAP结合非线性滤波方法的多种传感器网络定位算法进行研究.根据传感器节点间距离与节点定位坐标之间存在的非线性关系,在MDS-MAP定位算法的基础上,引入扩展卡尔曼滤波(EKF)求精算法和不敏卡尔曼滤波(UKF)求精算法,对MDS- MAP求得的节点坐标进行求精.对MDS-MAP定位算法、MDS-MAP和EKF相结合的定位算法(MDS-EKF)、MDS-MAP和UKF相结合的定位算法(MDS-UKF)的定位精度进行比较.实验结果表明:EKF和UKF等非线性滤波方法的应用可以提高定位精度,在相同条件下MDS-UKF定位算法的定位精度更高并且其生成的网络拓扑图最接近于实际网络拓扑图.

  10. Radiotherapy- and Chemotherapy-Induced Myelodysplasia Syndrome

    Science.gov (United States)

    Sun, Li-Min; Lin, Cheng-Li; Lin, Ming-Chia; Liang, Ji-An; Kao, Chia-Hung

    2015-01-01

    Abstract This study explored which kinds of cancer are related to a higher incidence of subsequent myelodysplastic syndrome (MDS) after radiotherapy (RT) and chemotherapy (CT). We performed a nested case–control study by using data from the Taiwanese National Health Insurance (NHI) system. The case group included cancer patients who developed MDS. For the control group, 4 cancer patients without MDS were frequency-matched with each MDS case by age, sex, year of cancer diagnosis, and MDS index year. A multivariable logistic regression analysis was conducted, and odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. Overall, cancer patients who received RT or CT exhibited secondary MDS more frequently than did those who did not (RT: OR = 1.53; 95% CI = 1.33–1.77; CT: OR = 1.51; 95% CI = 1.25–1.82). Analysis by cancer site showed that RT increased the risk of MDS for patients with stomach, colorectal, liver, breast, endometrial, prostate, and kidney cancers. By contrast, CT was more likely to increase the risk of MDS for patients with lung, endometrial, and cervical cancers. Further analysis revealed that RT and CT seemed to have a positive interaction. The major limitation of this study was the lack of certain essential data in the NHI Research Database, such as data regarding cancer stage and treatment dose details. This population-based nested case–control study determined that RT and CT predisposed patients in Taiwan to the development of MDS. This effect was more prominent when both modalities were used. PMID:25929909

  11. Molecular studies in myelodysplastic syndromes

    NARCIS (Netherlands)

    Dijk, Jeroen Peter van

    2003-01-01

    This thesis describes molecular studies of myelodysplastic syndromes (MDS). The first question was if high-dose chemotherapy could induce polyclonal remission. Disease clonality was investigated with karyotyping in patients with large chromosomal aberrations and determination of X-chromosome inactiv

  12. Study on phenotypic and cytogenetic characteristics of bone marrow mesenchymal stem cells in myelodysplastic syndromes

    Institute of Scientific and Technical Information of China (English)

    宋陆茜

    2013-01-01

    Objective To investigate phenotype,cell differentiation and cytogenetic properties of bone marrow(BM) mesenchymal stem cells(MSC)separated from the myelodysplastic syndrome(MDS) patients,and to analyze cytogenetic

  13. Current major depressive syndrome measured with the Patient Health Questionnaire-9 (PHQ-9) and the Composite International Diagnostic Interview (CIDI): results from a cross-sectional population-based study of adults in Germany.

    Science.gov (United States)

    Maske, Ulrike E; Busch, Markus A; Jacobi, Frank; Beesdo-Baum, Katja; Seiffert, Ingeburg; Wittchen, Hans-Ulrich; Riedel-Heller, Steffi; Hapke, Ulfert

    2015-04-10

    Prevalence estimates for depression vary considerably by the type of assessment instrument, and there is limited information on their overlap in population-based samples. Our aim was to compare the Patient Health Questionnaire-9 (PHQ-9) with the Composite International Diagnostic Interview (CIDI) as measures for current major depressive syndrome (MDS) in a large population-based sample. Data derived from the mental health module of the nationwide cross-sectional German Health Interview and Examination Survey for Adults (DEGS1-MH) (n = 4483; age 18-79 years). MDS in the past two weeks was assessed (a) using the PHQ-9 diagnostic algorithm (PHQ-MDS) and (b) based on CIDI information about the latest symptom occurrence (recency) (CIDI-MDS). Prevalences, overall concordance and percentages of overlap of both MDS measures were determined. Prevalences of affirmed PHQ-9 depression symptoms and the mean and median PHQ-9 sum scores were analyzed per measure. Prevalence of current MDS was 2.7% (95% CI: 2.0-3.6) for PHQ-MDS and 3.9% (95% CI: 3.1-5.0) for CIDI-MDS. The overall agreement between both measures was moderate (kappa: 0.43). Of all the participants, 1.5% (95% CI: 1.0-2.2) were classified as MDS cases by both measures, with 54.5% (95% CI: 42.7-65.9) of PHQ-MDS cases and 37.9% (95% CI: 27.8-49.1) of CIDI-MDS cases also being classified as MDS by the respective other MDS measure. However, 94.8% (95% CI: 93.6-95.8) of the participants were classified as non-MDS by both measures, with 97.5% (95% CI: 96.6-98.1) of non-PHQ-MDS and 98.7% (95% CI: 98.2-99.1) of non-CIDI-MDS being classified as non-MDS by the respective other MDS measure. The mean and median PHQ-9 sum score was higher in those with PHQ-MDS than in those with CIDI-MDS. Both measures have a high level of agreement for ruling out current MDS, but the overlap in their classification of cases is moderate. Our results indicate that they cannot be interpreted as equal measures of the same construct, suggesting

  14. Mediators of the Association of Major Depressive Syndrome and Anxiety Syndrome with Postpartum Smoking Relapse

    Science.gov (United States)

    Correa-Fernandez, Virmarie; Ji, Lingyun; Castro, Yessenia; Heppner, Whitney L.; Vidrine, Jennifer Irvin; Costello, Tracy J.; Mullen, Patricia Dolan; Cofta-Woerpel, Ludmila; Velasquez, Mary M.; Greisinger, Anthony; Cinciripini, Paul M.; Wetter, David W.

    2012-01-01

    Objective: Based on conceptual models of addiction and affect regulation, this study examined the mechanisms linking current major depressive syndrome (MDS) and anxiety syndrome (AS) to postpartum smoking relapse. Method: Data were collected in a randomized clinical trial from 251 women who quit smoking during pregnancy. Simple and multiple…

  15. Abrupt evolution of Philadelphia chromosome-positive acute myeloid leukemia in myelodysplastic syndrome.

    Science.gov (United States)

    Fukunaga, Akiko; Sakoda, Hiroto; Iwamoto, Yoshihiro; Inano, Shojiro; Sueki, Yuki; Yanagida, Soshi; Arima, Nobuyoshi

    2013-03-01

    Myelodysplastic syndrome (MDS) is a clonal disorder arising from an alteration in multipotent stem cells, which lose the ability of normal proliferation and differentiation. Disease progression occurs in approximately 30% MDS cases. Specific chromosomal alterations seem responsible for each step in the evolution of acute myeloid leukemia (AML). Multiple genetic aberrations occur during the clonal evolution of MDS; however, few studies report the presence of the Philadelphia (Ph) chromosome. We report a rare case of Ph-positive AML, which evolved during the course of low-risk MDS. The patient, a 76-year-old man with mild leukocytopenia, was diagnosed with MDS, refractory neutropenia (RN). After 1.5 yr, his peripheral blood and bone marrow were suddenly occupied by immature basophils and myeloblasts, indicating the onset of AML. A bone marrow smear showed multilineage dysplasia, consistent with MDS evolution. Chromosomal analysis showed an additional t(9;22)(q34;q11) translocation. Because progression occurred concurrently with emergence of the Ph chromosome, we diagnosed this case as Ph-positive AML with basophilia arising from the clonal evolution of MDS. The patient was initially treated with nilotinib. A hematological response was soon achieved with disappearance of the Ph chromosome in the bone marrow. Emergence of Ph-positive AML in the course of low-risk MDS has rarely been reported. We report this case as a rare clinical course of MDS.

  16. [Clinical analysis in a cohort of 102 patients with myelodysplastic syndrome characterized by erythroid hyperplasia].

    Science.gov (United States)

    Yu, Y; Sun, A N; Chen, S N; Wang, Q R; Zhang, T T; Wu, D P

    2017-01-01

    Objective: To investigate the clinical and laboratorial characteristics of patients with myelodysplastic syndrome (MDS) and erythroid hyperplasia. Methods: MDS patients whose bone marrow was hypercellular with erythroid lineage more than 50% and blasts account for less than 20% of non-erythroid cells were enrolled in this study. The ratio of mature erythrocytes to nucleated erythrocytes was no more than 20, namely MDS patients with erythroid hyperplasia(MDS-E). The retrospective analysis comprised 102 patients with MDS-E from the First Affiliated Hospital of Suzhou University. Clinical characteristics, karyotype, and the prognostic significance of erythroid hyperplasia were evaluated. Results: A total of 48 MDS-E patients (47.1%) presented a variety of cytogenetic abnormalities. The most frequently involved chromosomes were chromosome 8 (39.5% of all abnormal karyotypes), chromosome 7 (22.9%), followed by chromosome 5 (18.8%), chromosome 1 (16.7%) and chromosome 20 (16.7%). Hemoglobin (Hb) level affected the prognosis by survival analysis. The overall survival (OS) of MDS-E patients with Hb equal or more than 70 g/L was longer than that of patients less than 70 g/L (Phyperplasia in bone marrow did not impact on prognosis (P=0.187). Conclusions: Compared with previous reports of MDS patients, MDS-E patients have higher level of erythroid hyperplasia, more common erythroid dyshematopoiesis, more frequent 8 and 1 chromosome abnormalities. The degree of erythroid hyperplasia is not correlated with prognosis. Allogeneic hematopoietic stem cell transplantation improves the prognosis.

  17. ROLE AND TIMING OF HEMATOPOIETIC CELL TRANSPLANTATION FOR MYELODYSPLASTIC SYNDROME

    Directory of Open Access Journals (Sweden)

    Teresa L Field

    2010-07-01

    Full Text Available Allogeneic hematopoietic cell transplantation (HCT is the only curative treatment for patients with myelodysplastic syndromes (MDS.  Most patients with MDS are older than 60 years and age-associated morbidities limit the patients’ options for curative transplant therapy.  Since the development of conditioning regimens with reduced toxicity, the age limitations for HCT have waned for those patients with good performance status. This review will discuss the role of HCT for MDS based on prognostic features, the optimal timing of HCT, and outcomes based on patient age.

  18. Treatment of myelodysplastic syndromes: practical tools for effective management.

    Science.gov (United States)

    Kurtin, Sandra E; Demakos, Erin P; Hayden, Janet; Boglione, Claudia

    2012-06-01

    Myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid malignancies with variability in clinical presentation, disease trajectory, treatment goals, and expected outcomes. The treatment of patients with MDS, therefore, often differs from patient to patient. Tools are needed to aid effective communication with patients, their caregivers, and their dedicated team of healthcare professionals. The use of methods often employed in clinical trials can help healthcare providers diagnose and classify risk status, track trends within patient responses, manage adverse events, set treatment expectations, and provide ongoing supportive care. This article discusses several tools and strategies available for the management of patients with MDS throughout the continuum of their disease.

  19. Optic Neuritis Associated with Myelodysplastic Syndrome Accompanied by Eosinophilic Crisis.

    Science.gov (United States)

    Nagasaki, Joji; Nishimoto, Mitsutaka; Nakamae, Hirohisa; Nakane, Takahiko; Koh, Hideo; Yoshimoto, Kumiko; Shiraki, Kunihiko; Hino, Masayuki

    2015-01-01

    Myelodysplastic syndrome (MDS) was diagnosed in a 64-year-old man. Three months later, he presented with right-sided visual loss. A diagnosis of optic neuritis caused by both ischemic and non-ischemic changes was established. Concurrently, prominent eosinophilia was seen in both the peripheral blood and bone marrow. A partial improvement of visual loss was obtained concomitant with a rapid decrease of the eosinophils after treatment with corticosteroids. Optic neuritis related to MDS is a rare condition and its etiology has not yet been identified. We herein report a case of optic neuritis associated with MDS and accompanied by an eosinophilic crisis.

  20. SNP array karyotyping allows for the detection of uniparental disomy and cryptic chromosomal abnormalities in MDS/MPD-U and MPD.

    Directory of Open Access Journals (Sweden)

    Lukasz P Gondek

    Full Text Available We applied single nucleotide polymorphism arrays (SNP-A to study karyotypic abnormalities in patients with atypical myeloproliferative syndromes (MPD, including myeloproliferative/myelodysplastic syndrome overlap both positive and negative for the JAK2 V617F mutation and secondary acute myeloid leukemia (AML. In typical MPD cases (N = 8, which served as a control group, those with a homozygous V617F mutation showed clear uniparental disomy (UPD of 9p using SNP-A. Consistent with possible genomic instability, in 19/30 MDS/MPD-U patients, we found additional lesions not identified by metaphase cytogenetics. In addition to UPD9p, we also have detected UPD affecting other chromosomes, including 1 (2/30, 11 (4/30, 12 (1/30 and 22 (1/30. Transformation to AML was observed in 8/30 patients. In 5 V617F+ patients who progressed to AML, we show that SNP-A can allow for the detection of two modes of transformation: leukemic blasts evolving from either a wild-type jak2 precursor carrying other acquired chromosomal defects, or from a V617F+ mutant progenitor characterized by UPD9p. SNP-A-based detection of cryptic lesions in MDS/MPD-U may help explain the clinical heterogeneity of this disorder.

  1. Independent Validation of the SEND-PD and Correlation with the MDS-UPDRS Part IA.

    Science.gov (United States)

    Rodríguez-Violante, Mayela; Cervantes-Arriaga, Amin; Velázquez-Osuna, Salvador; Llorens-Arenas, Rodrigo; Calderón-Fajardo, Humberto; Piña-Fuentes, Dan; Martinez-Martin, Pablo

    2014-01-01

    Introduction. Neuropsychiatric symptoms in Parkinson's disease can be assessed by the MDS-UPDRS part IA. The Scale for Evaluation of Neuropsychiatric Disorders in Parkinson's disease (SEND-PD) has been recently developed to assess the severity of some neuropsychiatric symptoms. The objective of this study is to compare the performance of the SEND-PD with the corresponding items of the MDS-UPDRS part IA. Methods. Patients with Parkinson's disease were evaluated using the MDS-UPDRS and the SEND-PD by independent raters. Partial SEND-PD and neuropsychiatric MDS-UPDRS part IA were constructed with equivalent items for comparison. Results. A total of 260 consecutive patients were included. Overall, 61.2% of the patients did not report any psychotic symptom and 83.5% did not report any ICD symptom. On the other hand, 78.5% of the patients did report at least one symptom related to apathy, depression, or anxiety. The partial SEND-PD score was 2.9 ± 3.1 (range from 0 to 16). The neuropsychiatric MDS-UPDRS part IA score was 2.9 ± 3 (range from 0 to 14). The correlation coefficient between corresponding items ranged from 0.67 to 0.98 and between both summary indexes was r s = 0.93 (all, P UPDRS was found.

  2. [TOPICS-MDS: a versatile resource for generating scientific and social knowledge for elderly care].

    Science.gov (United States)

    van den Brink, Danielle; Lutomski, Jennifer E; Qin, Li; den Elzen, Wendy P J; Kempen, Gertrudis I J M; Krabbe, Paul F M; Steyerberg, Ewout W; Muntinga, Maaike; Moll van Charante, Eric P; Bleijenberg, Nienke; Olde Rikkert, Marcel G M; Melis, René J F

    2015-04-01

    Developed as part of the National Care for the Elderly Programme (NPO), TOPICS-MDS is a uniform, national database on the health and wellbeing of the older persons and caregivers who participated in NPO-funded projects. TOPICS-MDS Consortium has gained extensive experience in constructing a standardized questionnaire to collect relevant health care data on quality of life, health services utilization, and informal care use. A proactive approach has been undertaken not only to ensure the standardization and validation of instruments but also the infrastructure for external data requests. Efforts have been made to promote scientifically and socially responsible use of TOPICS-MDS; data has been available for secondary use since early 2014. Through this data sharing initiative, researchers can explore health issues in a broader framework which may have not been possible within individual NPO projects; this broader framework is highly relevant for influencing health policy. In this article, we provide an overview of the development and on-going progress of TOPICS-MDS. We further describe how information derived from TOPICS-MDS can be applied to facilitate future scientific innovations and public health initiatives to improve care for frail older persons and their caregivers.

  3. Monosomal karyotype predicts poor survival after allogeneic stem cell transplantation in chromosome 7 abnormal myelodysplastic syndrome and secondary acute myeloid leukemia

    NARCIS (Netherlands)

    Gelder, M. van; Wreede, L.C. de; Schetelig, J.; Biezen, A. van; Volin, L.; Maertens, J.; Robin, M.; Petersen, E.; Witte, T.J.M. de; Kroger, N.

    2013-01-01

    Treatment algorithms for poor cytogenetic-risk myelodysplastic syndrome (MDS), defined by chromosome 7 abnormalities or complex karyotype (CK), include allogeneic stem cell transplantation (alloSCT). We studied outcome of alloSCT in chromosome 7 abnormal MDS patients as this data are scarce in liter

  4. Pathohistological characteristics of myelodysplastic syndromes: Diagnostic and prognostic significance

    Directory of Open Access Journals (Sweden)

    Marisavljević Dragomir

    2005-01-01

    Full Text Available INTRODUCTION Pathohistological (PH analysis is recommended as basic diagnostic procedure during the investigation of myelodysplastic syndromes (MDS. AIM The aim of this paper was to investigate diagnostic and prognostic significance of bone marrow PH features in patients with MDS, and its relation to cytoiogical characteristics of bone marrow aspirate. METHODS Cellularity, disorder of marrow histotopography, quantity of hematopoiesis lineages, cellular atypia, the amount of myeloblasts, and stromal changes were particularly analyzed in trephines of 236 patients with primary MDS. RESULTS In most cases (78.4% hypercellular bone marrow was observed, although in 10.2% patients hypocellular subtype of MDS was diagnosed. Erythropoiesis dislocation was present in 64.7% patients, dislocation of MK-poiesis in 50.9% patients, while 61.3% had dislocation of granulopoesis (so-called ALIP phenomenon. In most cases three lineage hyperplasia was present, while relative hypoplasia of E- and MK-lineage was found in1/4 cases, each, particularly in advanced MDS. Morphological features of dyseritropoiesis and dysmegakaryocytopoiesis were present in 42.5% and 75.7% cases, respectively. Different stages of reticulin and collagen fibrosis were observed in 55.5% patients, while 7.6% had hyperfibrotic subtype of MDS. Comparative analysis of cytoiogical and histological features of MDS bone marrow showed positive correlation between two methods only in respect of estimation of eritropoiesis quantity, presence of dismegakaryocytopoiesis and „reactive" cells. The univariate analysis showed that MK- and G-lineage dislocation, quantity of E- and G-lineage, and presence of dysmegakaryocytopoiesis, were prognostic indicators for short survival and evolution of the disease in MDS patients. However, multivariate analysis showed that only G-lineage dislocation was independent prognostic variable for survival in MDS cases. CONCLUSION PH analysis is irreplaceable diagnostic

  5. Intrinsic Depletion or Not

    DEFF Research Database (Denmark)

    Klösgen, Beate; Bruun, Sara; Hansen, Søren;

      The presence of a depletion layer of water along extended hydrophobic interfaces, and a possibly related formation of nanobubbles, is an ongoing discussion. The phenomenon was initially reported when we, years ago, chose thick films (~300-400Å) of polystyrene as cushions between a crystalline...... giving rise to depletion layers, and the mechanisms and border conditions that control their presence and extension require still clarification. Recently, careful systematic reflectivity experiments were re-done on the same system. No depletion layers were found, and it was conjectured that the whole...

  6. On the Existence of Optimal Exact-Repair MDS Codes for Distributed Storage

    CERN Document Server

    Suh, Changho

    2010-01-01

    The high repair cost of (n,k) Maximum Distance Separable (MDS) erasure codes has recently motivated a new class of codes, called Regenerating Codes, that optimally trade off storage cost for repair bandwidth. In this paper, we address bandwidth-optimal (n,k,d) Exact-Repair MDS codes, which allow for any failed node to be repaired exactly with access to arbitrary d survivor nodes, where k<=d<=n-1. We show the existence of Exact-Repair MDS codes that achieve minimum repair bandwidth (matching the cutset lower bound) for arbitrary admissible (n,k,d), i.e., k

  7. The Mice Drawer System (MDS experiment and the space endurance record-breaking mice.

    Directory of Open Access Journals (Sweden)

    Ranieri Cancedda

    Full Text Available The Italian Space Agency, in line with its scientific strategies and the National Utilization Plan for the International Space Station (ISS, contracted Thales Alenia Space Italia to design and build a spaceflight payload for rodent research on ISS: the Mice Drawer System (MDS. The payload, to be integrated inside the Space Shuttle middeck during transportation and inside the Express Rack in the ISS during experiment execution, was designed to function autonomously for more than 3 months and to involve crew only for maintenance activities. In its first mission, three wild type (Wt and three transgenic male mice over-expressing pleiotrophin under the control of a bone-specific promoter (PTN-Tg were housed in the MDS. At the time of launch, animals were 2-months old. MDS reached the ISS on board of Shuttle Discovery Flight 17A/STS-128 on August 28(th, 2009. MDS returned to Earth on November 27(th, 2009 with Shuttle Atlantis Flight ULF3/STS-129 after 91 days, performing the longest permanence of mice in space. Unfortunately, during the MDS mission, one PTN-Tg and two Wt mice died due to health status or payload-related reasons. The remaining mice showed a normal behavior throughout the experiment and appeared in excellent health conditions at landing. During the experiment, the mice health conditions and their water and food consumption were daily checked. Upon landing mice were sacrificed, blood parameters measured and tissues dissected for subsequent analysis. To obtain as much information as possible on microgravity-induced tissue modifications, we organized a Tissue Sharing Program: 20 research groups from 6 countries participated. In order to distinguish between possible effects of the MDS housing conditions and effects due to the near-zero gravity environment, a ground replica of the flight experiment was performed at the University of Genova. Control tissues were collected also from mice maintained on Earth in standard vivarium cages.

  8. Addressing Ozone Layer Depletion

    Science.gov (United States)

    Access information on EPA's efforts to address ozone layer depletion through regulations, collaborations with stakeholders, international treaties, partnerships with the private sector, and enforcement actions under Title VI of the Clean Air Act.

  9. A phase II study of amifostine in children with myelodysplastic syndrome: a report from the Children's Oncology Group study (AAML0121).

    Science.gov (United States)

    Mathew, Prasad; Gerbing, Robert; Alonzo, Todd A; Wallas, Tanya; Gong, Jerald Z; Jasty, Rama; Jorstad, Dean T; Raimondi, Susana C; Chavez, Cathy M; Eisenberg, Nancy L; Hirsch, Betsy; Gamis, Alan; Smith, Franklin O; Arceci, Robert J

    2011-12-15

    Based on its potential role in adult myelodysplastic syndrome (MDS), the Children's Oncology Group (COG) embarked on a phase II study using amifostine in pediatric MDS (WHO 2001 criteria) patients. Responses were evaluated after two cycles. Ten patients were enrolled; five were deemed ineligible, and four withdrew after the first course. Only one patient completed two courses, and was found to be in complete remission. The study was closed after being open for 2 years due to slow accrual. Studying a rare disease like MDS may pose insurmountable obstacles even in a large clinical trials group such as COG, in part because of the changing definitions of MDS and the rarity of adult type MDS in children. The role of amifostine in pediatric MDS was not known at the time of study.

  10. NS-018, a selective JAK2 inhibitor, preferentially inhibits CFU-GM colony formation by bone marrow mononuclear cells from high-risk myelodysplastic syndrome patients.

    Science.gov (United States)

    Kuroda, Junya; Kodama, Ayumi; Chinen, Yoshiaki; Shimura, Yuji; Mizutani, Shinsuke; Nagoshi, Hisao; Kobayashi, Tsutomu; Matsumoto, Yosuke; Nakaya, Yohei; Tamura, Ayako; Kobayashi, Yutaka; Naito, Haruna; Taniwaki, Masafumi

    2014-05-01

    JAK2/STAT signaling promotes survival and expansion of myelodysplastic syndrome (MDS) clones, but little is known about the potential of JAK2/STAT as a therapeutic target in MDS. We investigated the effect of NS-018, a novel antagonist for JAK2, on the colony-forming ability of bone marrow mononuclear cells (BMMNCs) from high-risk MDS patients. NS-018 decreased colony-forming unit-granulocyte/macrophage (CFU-GM) colony numbers from MDS-derived BMMNCs in a dose-dependent manner, and this effect was significantly more potent than against normal BMMNCs. In addition, NS-018 suppressed the phosphorylation of STAT3 in colony-forming cells from MDS patients. Collectively, NS-018 could be a new therapeutic option for high-risk MDS.

  11. Megakaryocytic dysfunction in myelodysplastic syndromes and idiopathic thrombocytopenic purpura is in part due to different forms of cell death

    NARCIS (Netherlands)

    Houwerzijl, E. J.; Blom, N. R.; van der Want, J. J. L.; Vellenga, E.; de Wolf, J. T. M.

    2006-01-01

    Platelet production requires compartmentalized caspase activation within megakaryocytes. This eventually results in platelet release in conjunction with apoptosis of the remaining megakaryocyte. Recent studies have indicated that in low-risk myelodysplastic syndromes (MDS) and idiopathic thrombocyto

  12. Lenalidomide with or without erythropoietin in transfusion-dependent erythropoiesis-stimulating agent-refractory lower-risk MDS without 5q deletion.

    Science.gov (United States)

    Toma, A; Kosmider, O; Chevret, S; Delaunay, J; Stamatoullas, A; Rose, C; Beyne-Rauzy, O; Banos, A; Guerci-Bresler, A; Wickenhauser, S; Caillot, D; Laribi, K; De Renzis, B; Bordessoule, D; Gardin, C; Slama, B; Sanhes, L; Gruson, B; Cony-Makhoul, P; Chouffi, B; Salanoubat, C; Benramdane, R; Legros, L; Wattel, E; Tertian, G; Bouabdallah, K; Guilhot, F; Taksin, A L; Cheze, S; Maloum, K; Nimuboma, S; Soussain, C; Isnard, F; Gyan, E; Petit, R; Lejeune, J; Sardnal, V; Renneville, A; Preudhomme, C; Fontenay, M; Fenaux, P; Dreyfus, F

    2016-04-01

    After failure of erythropoiesis-stimulating agents (ESAs), lenalidomide (LEN) yields red blood cell (RBC) transfusion independence (TI) in 20-30% of lower-risk non-del5q myelodysplastic syndrome (MDS). Several observations suggest an additive effect of ESA and LEN in this situation. We performed a randomized phase III study in 131 RBC transfusion-dependent (TD, median transfusion requirement six RBC units per 8 weeks) lower-risk ESA-refractory non-del5q MDS. Patients received LEN alone, 10 mg per day, 21 days per 4 weeks (L arm) or LEN (same schedule) + erythropoietin (EPO) beta, 60,000 U per week (LE arm). In an intent-to-treat (ITT) analysis, erythroid response (HI-E, IWG 2006 criteria) after four treatment cycles (primary end point) was 23.1% (95% CI 13.5-35.2) in the L arm and 39.4% (95% CI 27.6-52.2) in the LE arm (P=0.044), while RBC-TI was reached in 13.8 and 24.2% of the patients in the L and LE arms, respectively (P=0.13). Median response duration was 18.1 and 15.1 months in the L and LE arms, respectively (P=0.47). Side effects were moderate and similar in the two arms. Low baseline serum EPO level and a G polymorphism of CRBN gene predicted HI-E. Combining LEN and EPO significantly improves erythroid response over LEN alone in lower-risk non-del5q MDS patients with anemia resistant to ESA.

  13. MR imaging findings of the femoral marrow in myelodysplastic syndrome

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    Tanaka, Osamu; Takagi, Shojiro; Matsuura, Katsuhiko; Ichikawa, Tamaki; Kobayashi, Yasuyuki; Nagai, Jun [Jichi Medical School, Minamikawachi, Tochigi (Japan)

    1995-10-01

    MR imaging of the femoral marrow was performed in 30 patients with myelodysplastic syndrome (MDS), 11 cases of which evolved to acute myeloid leukemia (AML). The MRI appearance was classified into five patterns: fatty marrow; faint signal; nodular pattern; heterogeneous infiltration; and diffuse infiltration. For each type of MDS, MRI patterns of the femoral marrow were evaluated and compared with those in normal subjects as well as in patients with aplastic anemia. Signal intensity alteration, a low signal on T1-weighted SE image and a high signal on STIR image, began in the proximal femoral marrow almost symmetrically in patients with MDS. The area of abnormal signal intensity tended to gradually extend towards the distal portion of the femur as the disease progressed. MRI patterns of the femoral marrow correlated with marrow cellularity, and diffuse marrow infiltration was noted in patients with a more advanced type of MDS or with severe anemia. There were limitations to making an accurate diagnosis of the MDS type on the basis of the MRI pattern. Progression of the MRI appearance in the course of MDS was thought to be a sign suggesting evolution to AML. It was difficult to differentiate hypoplastic MDS from aplastic anemia, although the nodular pattern was commonly seen in the latter disease. (author).

  14. Frequent chromatin rearrangements in myelodysplastic syndromes--what stands behind?

    Science.gov (United States)

    Pagáčová, E; Falk, M; Falková, I; Lukášová, E; Michalová, K; Oltová, A; Raška, I; Kozubek, S

    2014-01-01

    Myelodysplastic syndromes (MDS) represent a clinically and genetically heterogeneous group of clonal haematopoietic diseases characterized by a short survival and high rate of transformation to acute myeloid leukaemia (AML). In spite of this variability, MDS is associated with typical recurrent non-random cytogenetic defects. Chromosomal abnormalities are detected in the malignant bone-marrow cells of approximately 40-80 % of patients with primary or secondary MDS. The most frequent chromosomal rearrangements involve chromosomes 5, 7 and 8. MDS often shows presence of unbalanced chromosomal changes, especially large deletions [del(5), del(7q), del(12p), del(18q), del(20q)] or losses of whole chromosomes (7 and Y). The most typical cytogenetic abnormality is a partial or complete deletion of 5q- that occurs in roughly 30 % of all MDS cases either as the sole abnormality or in combination with other aberrations as a part of frequently complex karyotypes. The mechanisms responsible for the formation of MDS-associated recurrent translocations and complex karyotypes are unknown. Since some of the mentioned aberrations are characteristic for several haematological malignancies, more general cellular conditions could be expected to play a role. In this article, we introduce the most common rearrangements linked to MDS and discuss the potential role of the non-random higher-order chromatin structure in their formation. A contribution of the chromothripsis - a catastrophic event discovered only recently - is considered to explain how complex karyotypes may occur (during a single event).

  15. EFNS/MDS-ES/ENS recommendations for the diagnosis of Parkinson's disease

    NARCIS (Netherlands)

    Berardelli, A.; Wenning, G.K.; Antonini, A.; Berg, D. van den; Bloem, B.R.; Bonifati, V.; Brooks, D.; Burn, D.J.; Colosimo, C.; Fanciulli, A.; Ferreira, J.; Gasser, T.; Grandas, F.; Kanovsky, P.; Kostic, V.; Kulisevsky, J.; Oertel, W.; Poewe, W.; Reese, J.P.; Relja, M.; Ruzicka, E.; Schrag, A.; Seppi, K.; Taba, P.; Vidailhet, M.

    2013-01-01

    BACKGROUND: A Task Force was convened by the EFNS/MDS-ES Scientist Panel on Parkinson's disease (PD) and other movement disorders to systemically review relevant publications on the diagnosis of PD. METHODS: Following the EFNS instruction for the preparation of neurological diagnostic guidelines, re

  16. A generalization of the MDS method by mixed integer linear and nonlinear mathematical models

    Directory of Open Access Journals (Sweden)

    Sadegh Niroomand

    2014-09-01

    Full Text Available The Multi-Dimensional Scaling (MDS method is used in statistics to detect hidden interrelations among multi-dimensional data and it has a wide range of applications. The method’s input is a matrix that describes the similarity/dissimilarity among objects of unknown dimension. The objects are generally reconstructed as points of a lower dimensional space to reveal the geometric configuration of the objects. The original MDS method uses Euclidean distance, for measuring both the distance of the reconstructed points and the bias of the reconstructed distances from the original similarity values. In this paper, these distances are distinguished, and distances other than Euclidean are also used, generalizing the MDS method. Two different distances may be used for the two different purposes. Therefore the instances of the generalized MDS model are denoted as  model, where the first distance is the type of distance of the reconstructed points and the second one measures the bias of the reconstructed distances and the similarity values. In the case of   and   distances mixed-integer programming models are provided. The computational experiences show that the generalized model can catch the key properties of the original configuration, if any exist. Keywords: Multivariate Analysis; Multi-Dimensional Scaling; Optimization; Mixed Integer Linear Programming; Statistics.

  17. Validation of the MDS-UPDRS Part I for nonmotor symptoms in Parkinson's disease.

    Science.gov (United States)

    Gallagher, David A; Goetz, Christopher G; Stebbins, Glenn; Lees, Andrew J; Schrag, Anette

    2012-01-01

    The UPDRS has been the main outcome measure in studies of PD. Modifications have been made to improve scale properties and represent the breadth of manifestations of PD, particularly nonmotor symptoms (NMS), resulting in the Movement Disorder Society's revision of the UPDRS (MDS-UPDRS). This study was undertaken to determine the validity of MDS-UPDRS Part I (nonmotor experiences of daily living). The MDS-UPDRS and a number of validated scales for the NMS in PD were used in 94 patients with PD from Hoehn and Yahr stage I to V. We assessed reliability, floor and ceiling effects, and correlations with validated scales for the nonmotor symptoms of PD. MDS-UPDRS Part I showed high internal consistency (Cronbach's alpha: 0.85), small floor and ceiling effects (2% floor and 0% ceiling effect), and good concurrent validity (correlation with the original UPDRS Part I: r = 0.81, P UPDRS Part I score demonstrated high convergent validity with the composite z-score of nonmotor scales (r = 0.89, P UPDRS Part I total score has a strong relationship with a composite score of validated scales for the nonmotor aspects of PD.

  18. Chromosomal karyotype analysis of 33 cases of myelodysplastic syndrome%33例骨髓增生异常综合征的染色体核型分析

    Institute of Scientific and Technical Information of China (English)

    何涛

    2012-01-01

    目的 分析染色体核型异常在骨髓增生异常综合征(MDS)诊断、预后评估中的价值.方法 对33例MDS患者按常规行骨髓穿刺,进行形态学检查,同时对患者骨髓细胞进行染色体培养,采用直接法、短期培养法和RHG显带技术制备染色体,进行核型分析.结果 33例MDS患者中,染色体核型异常者15例,异常核型检出率45.4%,其中MDS - RA 1例占3%,MDS-RARS 1例占3%,MDS - RCMD 4例占12.1%,MDS - RAEB1 6例占18.2%,MDS - RAEB2 3例占9.1%.MDS - RAEB1、2较RA、RARS、RCMD检测到更高的异常核型比例.结论 MDS的染色体核型异常,各型之间差异较大,染色体核型分析对MDS的诊断、分型及预后评估有重要价值.%Objective To analyze the value of chromosome abnormal karyotype in diagnosis and prognosis of myelodysplastic syndrome (MDS). Methods 33 cases of MDS patients were carried out routine bone marrow aspiration and to be morphologically checked, while the bone marrow cells of the patients were chromosomally cultured, using direct method ,brief culture of cells and R - banding techniques, then karyotype analysis was performed. Results Among 33 cases of MDS patients, 15 cases were found with chromosomal abnormal karyotype, the abnormal karyotype detection rate was 45.4% , in which there were 1 case (3% ) of MDS - RA, 1 case (3% ) of MDS -RARS, 4 cases (12. 1% ) of MDS - RCMD, 6 cases (18. 2% ) of MDS - RAEB1, and 3 cases (9. 1% ) of MDS - RAEB2. The abnormal karyotype detection rate in MDS - RAEB1 and MDS - RAEB2 was much higher than that in RA, RARS, RCMD. Conclusion Karyotype abnormalities are the larger differences between various types of karyotype analysis of MDS, so karyotype analysis is very useful for diagnosis, typing and prognosis evaluation in MDS.

  19. Myeloid cell differentiation arrest by miR-125b-1 in myelodysplasic syndrome and acute myeloid leukemia with the t(2;11)(p21;q23) translocation

    NARCIS (Netherlands)

    M. Bousquet (Marina); C. Quelen (Cathy); R. Rosati (Roberto); V.M.D. Mas; R.L. Starza (Roberta); C. Bastard (Christian); E. Lippert (Eric); P. Talmant (Pascaline); M. Lafage-Pochitaloff (Marina); D. Leroux (Dominique); C. Gervais (Carine); F. Viguié (Franck); J.L. Lai; C. Terre (Christine); H.B. Beverloo (Berna); C. Sambani (Costantina); A. Hagemeijer (Anne); P. Marynen (Peter); G. Delsol (Georges); N. Dastugue (Nicole); C. Mecucci (Cristina); P. Brousset (Pierre)

    2008-01-01

    textabstractMost chromosomal translocations in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) involve oncogenes that are either up-regulated or form part of new chimeric genes. The t(2;11)(p21;q23) translocation has been cloned in 19 cases of MDS and AML. In addition to this, we ha

  20. Intrinsic Depletion or Not

    DEFF Research Database (Denmark)

    Klösgen, Beate; Bruun, Sara; Hansen, Søren;

    with an AFM (2).    The intuitive explanation for the depletion based on "hydrophobic mismatch" between the obviously hydrophilic bulk phase of water next to the hydrophobic polymer. It would thus be an intrinsic property of all interfaces between non-matching materials. The detailed physical interaction path......  The presence of a depletion layer of water along extended hydrophobic interfaces, and a possibly related formation of nanobubbles, is an ongoing discussion. The phenomenon was initially reported when we, years ago, chose thick films (~300-400Å) of polystyrene as cushions between a crystalline...

  1. Development of a Minimum Data Set (MDS) for C-Section Anesthesia Information Management System (AIMS).

    Science.gov (United States)

    Sheykhotayefeh, Mostafa; Safdari, Reza; Ghazisaeedi, Marjan; Khademi, Seyed Hossein; Seyed Farajolah, Seyedeh Sedigheh; Maserat, Elham; Jebraeily, Mohamad; Torabi, Vahid

    2017-04-01

    Caesarean section, also known as C-section, is a very common procedure in the world. Minimum data set (MDS) is defined as a set of data elements holding information regarding a series of target entities to provide a basis for planning, management, and performance evaluation. MDS has found a great use in health care information systems. Also, it can be considered as a basis for medical information management and has shown a great potential for contributing to the provision of high quality care and disease control measures. The principal aim of this research was to determine MDS and required capabilities for Anesthesia information management system (AIMS) in C-section in Iran. Data items collected from several selected AIMS were studied to establish an initial set of data. The population of this study composed of 115 anesthesiologists was asked to review the proposed data elements and score them in order of importance by using a five-point Likert scale. The items scored as important or highly important by at least 75% of the experts were included in the final list of minimum data set. Overall 8 classes of data (consisted of 81 key data elements) were determined as final set. Also, the most important required capabilities were related to airway management and hypertension and hypotension management. In the development of information system (IS) based on MDS and identification, because of the broad involvement of users, IS capabilities must focus on the users' needs to form a successful system. Therefore, it is essential to assess MDS watchfully by considering the planned uses of data. Also, IS should have essential capabilities to meet the needs of its users.

  2. Shear-affected depletion interaction

    NARCIS (Netherlands)

    July, C.; Kleshchanok, D.; Lang, P.R.

    2012-01-01

    We investigate the influence of flow fields on the strength of the depletion interaction caused by disc-shaped depletants. At low mass concentration of discs, it is possible to continuously decrease the depth of the depletion potential by increasing the applied shear rate until the depletion force i

  3. Negative effect of DNA hypermethylation on the outcome of intensive chemotherapy in older patients with high-risk myelodysplastic syndromes and acute myeloid leukemia following myelodysplastic syndrome

    DEFF Research Database (Denmark)

    Grövdal, Michael; Khan, Rasheed; Aggerholm, Anni

    2007-01-01

    PURPOSE: Promoter hypermethylation of, for example, tumor-suppressor genes, is considered to be an important step in cancerogenesis and a negative risk factor for survival in patients with myelodysplastic syndromes (MDS); however, its role for response to therapy has not been determined. This study...... was designed to assess the effect of methylation status on the outcome of conventional induction chemotherapy. EXPERIMENTAL DESIGN: Sixty patients with high-risk MDS or acute myeloid leukemia following MDS were treated with standard doses of daunorubicin and 1-beta-d-arabinofuranosylcytosine. Standard...

  4. Spotlight on decitabine for myelodysplastic syndromes in Chinese patients

    Directory of Open Access Journals (Sweden)

    Jing Y

    2015-10-01

    Full Text Available Yu Jing,1,* Xue Shen,2,* Qian Mei,3 Weidong Han3 1Department of Hematology, PLA General Hospital, 2Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, 3Department of Molecular Biology, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, People’s Republic of China *These authors contributed equally to this work Abstract: Myelodysplastic syndromes (MDSs are a group of heterogeneous clonal hematopoietic stem cell malignancies with advanced median age. The silencing of tumor suppressor genes caused by DNA hypermethylation plays a crucial role in the pathogenesis of MDS. Decitabine, the available hypomethylating agent, is successfully used for the treatment and improves the outcome of MDS, and has become one of the most frequently administered disease-modifying therapies. With an aging population and a growing number of people exposed to benzene, the incidence of MDS has been increasing rapidly. The blinded regimen choice and the lack of a unified strategy create challenges for the treatment of MDS. Here, we present a review of clinical progress and prospects of decitabine treatment of MDS in the People’s Republic of China. We also discuss the optimization of therapy issues to improve the cure rate and prolong survival in patients with MDS. Keywords: myelodysplastic syndromes (MDSs, decitabine, hypomethylating agents, People’s Republic of China, traditional Chinese medicine

  5. RECENT ADVANCES IN THE 5Q- SYNDROME

    Directory of Open Access Journals (Sweden)

    Andrea Pellagatti

    2015-05-01

    Full Text Available The 5q- syndrome is the most distinct of the myelodysplastic syndromes (MDS and patients with this disorder have a deletion of chromosome 5q [del(5q] as the sole karyotypic abnormality. Several genes mapping to the commonly deleted region of the 5q- syndrome have been implicated in disease pathogenesis in recent years. Haploinsufficiency of the ribosomal gene RPS14 has been shown to cause the erythroid defect in the 5q- syndrome. Loss of the microRNA genes miR-145 and miR-146a has been associated with the thrombocytosis observed in 5q- syndrome patients. Haploinsufficiency of CSNK1A1 leads to hematopoietic stem cell expansion in mice and may play a role in the initial clonal expansion in patients with 5q- syndrome. Moreover, a subset of patients harbor mutation of the remaining CSNK1A1 allele. Mouse models of the 5q- syndrome, which recapitulate the key features of the human disease, indicate that a p53-dependent mechanism underlies the pathophysiology of this disorder. Importantly, activation of p53 has been demonstrated in the human 5q- syndrome. Recurrent TP53 mutations have been associated with an increased risk of disease evolution and with decreased response to the drug lenalidomide in del(5q MDS patients. Potential new therapeutic agents for del(5q MDS include the translation enhancer L-leucine.

  6. The significance of colony culture and cell factor in the differential diagnosis of AA and MDS-RA%集落培养及细胞因子检测在AA与MDS-RA鉴别诊断中的意义

    Institute of Scientific and Technical Information of China (English)

    梁建英; 张宏; 孙兰云; 傅晋翔

    2002-01-01

    目的提高对再生障碍性贫血(AA)及骨髓增生异常综合征难治性贫血(MDS-RA)的鉴别诊断.方法对28例AA及16例MDS-RA患者进行骨髓单个核细胞(MNC)体外集落培养(CFU-GM及CFU-C)及血浆中多种细胞因子(IL-3、IL-6、IL-2、IL-8、γ-IFN及TNF-α)的检测.结果 AA及MDS-RA患者CFU-GM及CFU-C集落数均低于正常对照组,AA患者CFU-C集簇数低于正常对照组,MDS-RA患者CFU-GM及CFU-C集簇数与正常对照组无显著差异.AA与MDS-RA相比较,CFU-GM及CFU-C集落和集簇数均较低.AA及MDS-RA患者血浆中IL-3及IL-6与正常组无显著差异,AA患者IL-2、IL-8、γ-IFN、TNF-α及MDS-RA患者TNF-α均高于正常对照组,MDS-RA患者IL-2及IL-8低于AA组.结论 AA及MDS-RA患者骨髓MNC的CFU-GM及CFU-C集落及集簇数量以及血浆中某些细胞因子含量存在差异,有助于两者的鉴别.

  7. Myeloablative radioimmunotherapies in the conditioning of patients with AML, MDS and multiple myeloma prior to stem cell transplantation; Myeloablative Radioimmuntherapien zur Konditionierung bei Patienten mit AML, MDS und multiplem Myelom vor Stammzelltransplantation

    Energy Technology Data Exchange (ETDEWEB)

    Buchmann, I. [Abt. fuer Nuklearmedizin, Universitaetsklinik Heidelberg (Germany)

    2008-06-15

    Aggressive consolidation chemotherapy and hematopoietic stem cell transplantation have improved the prognosis of patients with acute myeloid leukemia (AML), myelodyplastic syndrome (MDS) and multiple myeloma. Nevertheless, only a minor fraction of patients achieve long-term disease-free survival after stem cell transplantation with disease recurrence being the most common cause of treatment failure. In addition, therapy-related effects such as toxicity of chemotherapy and complications of stem cell transplantation increase mortality rates significantly. Myeloablative radioimmunotherapy uses radiolabeled monoclonal antibodies (mAb) with affinity for the hematopoietic marrow. It applies high radiation doses in the bone marrow but spares normal organs. Adding myeloablative radioimmunotherapy to the conditioning schemes of AML, MDS and multiple myeloma before stem cell transplantation allows for the achievement of a pronounced antileukemic/antimyeloma effect for the reduction of relapse rates without significant increase of acute organ toxicity and therapy-related mortality. In order to optimise therapy, a rational design of the nuclide-antibody combination is necessary. {sup 90}Y, {sup 188}Re and {sup 131}I are the most frequently used {beta}{sup -}-particles. Of these, {sup 90}Y is the most qualified nuclide for myeloablation. Backbone stabilised DTPA are ideal chelators to stably conjugate {sup 90}Y to antibodies so far. For myeloablative conditioning, anti-CD66-, -45- and -33-mAb are used. The anti-CD66-antibody BW250/183 binds to normal hematopoietic cells but not to leukemic blasts and myeloma cells. The {sup 90}Y-2B3M-DTPA-BW250/183 is the most suited radioimmunoconjugate for patients with an infiltration grade of leukemic blasts in the bone marrow < 25%. The specific doses (Gy/GBq) are 10.2 {+-} 1.8 (bone marrow), 2.7 {+-} 2 (liver) and < 1 (kidneys). In contrast, radiolabeled anti-CD33- and anti-CD45-antibodies bind to both, most of white blood cells and

  8. Innate Immunity Dysregulation in Myelodysplastic Syndromes

    Science.gov (United States)

    2013-10-01

    IL, interleukin; ITAM, immunoreceptor tyrosine-based activating motif; MDS, myelodysplastic syndromes; NADPH, nicotinamide adenine dinucleotide...differentiation, including macrophage, skin cells and neurons.19,2on In this study, we have shown that knock down of JMJ03 in BM C034 + cells of lower

  9. Lenalidomid til behandling af transfusionskraevende myelodysplastisk syndrom

    DEFF Research Database (Denmark)

    Risum, Malene; Dufva, I.H.

    2010-01-01

    Lenalidomide is the first drug to induce transfusion independence and cytogenetic remission in patients with myelodysplastic syndrome (MDS) with deletion 5q and low or intermediate risk score. Transfusion independence can be obtained within five weeks. Three out of four patients also obtain...

  10. Standardization of flow cytometry in myelodysplastic syndromes: a report from an international consortium and the European LeukemiaNet Working Group.

    NARCIS (Netherlands)

    Westers, T.M.; Ireland, R.; Kern, W.; Alhan, C.; Balleisen, J.S.; Bettelheim, P.; Burbury, K.; Cullen, M.; Cutler, J.A.; Porta, M.G. Della; Drager, A.M.; Feuillard, J.; Font, P.; Germing, U.; Haase, D.; Johansson, U.; Kordasti, S.; Loken, M.R.; Malcovati, L.; Marvelde, J.G. Te; Matarraz, S.; Milne, T.; Moshaver, B.; Mufti, G.J.; Ogata, K.; Orfao, A.; Porwit, A.; Psarra, K.; Richards, S.J.; Subira, D.; Tindell, V.; Vallespi, T.; Valent, P.; Velden, V.H. van der; Witte, T.J.M. de; Wells, D.A.; Zettl, F.; Bene, M.C.; Loosdrecht, A.A. van de

    2012-01-01

    Flow cytometry (FC) is increasingly recognized as an important tool in the diagnosis and prognosis of myelodysplastic syndromes (MDS). However, validation of current assays and agreement upon the techniques are prerequisites for its widespread acceptance and application in clinical practice.

  11. Microcephaly, microtia, preauricular tags, choanal atresia and developmental delay in three unrelated patients: a mandibulofacial dysostosis distinct from Treacher Collins syndrome.

    NARCIS (Netherlands)

    Wieczorek, D.; Gener, B.; Gonzalez, M.J.; Seland, S.; Fischer, S.; Hehr, U.; Kuechler, A.; Hoefsloot, L.H.; Leeuw, N. de; Gillessen-Kaesbach, G.; Lohmann, D.R.

    2009-01-01

    Treacher Collins syndrome (TCS, OMIM 154500) is a well-defined mandibulofacial dysostosis characterized by symmetric facial anomalies consisting of malar hypoplasia, coloboma of the lower eyelid, dysplastic ears, micrognathia, cleft palate and deafness. Other mandibulofacial dysostoses (MDs) such as

  12. Is the MDS-UPDRS a Good Screening Tool for Detecting Sleep Problems and Daytime Sleepiness in Parkinson's Disease?

    Science.gov (United States)

    Horváth, Krisztina; Aschermann, Zsuzsanna; Acs, Péter; Bosnyák, Edit; Deli, Gabriella; Pál, Endre; Janszky, József; Faludi, Béla; Késmárki, Ildikó; Komoly, Sámuel; Bokor, Magdolna; Rigó, Eszter; Lajtos, Júlia; Klivényi, Péter; Dibó, György; Vécsei, László; Takáts, Annamária; Tóth, Adrián; Imre, Piroska; Nagy, Ferenc; Herceg, Mihály; Kamondi, Anita; Hidasi, Eszter; Kovács, Norbert

    2014-01-01

    Movement Disorder Society-sponsored Unified Parkinson's Disease Rating Scale (MDS-UPDRS) has separate items for measuring sleep problems (item 1.7) and daytime sleepiness (1.8). The aim of our study was to evaluate the screening sensitivity and specificity of these items to the PD Sleep Scale 2nd version (PDSS-2) and Epworth Sleepiness Scale (ESS). In this nationwide, cross-sectional study 460 PD patients were enrolled. Spearman's rank correlation coefficients were calculated between the individual items, domains, and the total score of PDSS-2 and item 1.7 of MDS-UPDRS. Similarly, the items and the total score of ESS were contrasted to item 1.8 of MDS-UPDRS. After developing generalized ordinal logistic regression models, the transformed and observed scores were compared by Lin's Concordance Correlation Coefficient. Only item 3 difficulties staying asleep and the "disturbed sleep" domain of PDSS-2 showed high correlation with "sleep problems" item 1.7 of the MDS-UPDRS. Total score of PDSS-2 had moderate correlation with this MDS-UPRDS item. The total score of ESS showed the strongest, but still moderate, correlation with "daytime sleepiness" item 1.8 of MDS-UPDRS. As intended, the MDS-UPDRS serves as an effective screening tool for both sleep problems and daytime sleepiness and identifies subjects whose disabilities need further investigation.

  13. Historical perspectives on myelodysplastic syndromes.

    Science.gov (United States)

    Steensma, David P

    2012-12-01

    Although Georg Hegel quipped, "We learn from history that we do not learn from history", Aldous Huxley expressed a more nuanced view: "The charm of history and its enigmatic lesson consist in the fact that, from age to age, nothing changes and yet everything is completely different." In order to understand present-day positions and peculiarities in any field of human endeavor, familiarity with the past is essential. Those of us who study myelodysplastic syndromes (MDS) or care for patients diagnosed with these troublesome conditions may wonder also how the current state of affairs evolved with respect to our narrow area of focus, and how we know what we think we know now about these still-enigmatic bone marrow diseases. Here, I review a number of developments that collectively represent a brief "history of MDS." I first highlight a few landmark observations that preceded any concept of MDS by hundreds of years. Twentieth-century case descriptions and series with hypotheses about the etiology and nature of disorders described as "refractory anemia", "preleukemia", and with other terminology culminated in the efforts of the French-American-British (FAB) Co-operative Group of morphologists, whose landmark 1976 and 1982 papers provided the first widely-used classification of MDS. More recent developments in the MDS field include new mechanistic biological insights, regulatory approval of several somewhat-effective treatments, and improved organizational support and advocacy. The history of a disease concept like MDS, as for history in general, provides both inspiration and cautionary tales that can inform present and future work.

  14. Pulmonary Complications of Azanucleoside Therapy in Patients with Myelodysplastic Syndrome and Acute Myelogenous Leukemia

    Directory of Open Access Journals (Sweden)

    Manuel Molina

    2015-01-01

    Full Text Available Our primary aim was to identify potential risk factors and clinical outcome of azanucleoside induced pulmonary complications in patients with myelodysplastic syndrome (MDS and Acute Myelogenous Leukemia (AML. We present an 89-year-old female with MDS derived AML who developed fatigability, hypoxemia, and bilateral lung infiltrates indicating interstitial lung disease after 11 cycles of azanucleoside. In addition, we describe a cohort of six MDS patients with fever, cough, dyspnea, and pulmonary infiltrates at early time point during azanucleoside treatment. Early and late onset of pulmonary manifestations suggest different pathogenic mechanisms. Brief azanucleoside discontinuation and steroids led to rapid improvement in symptoms.

  15. Clinical features and prognosis of patients with myelodysplastic syndromes who were exposed to atomic bomb radiation in Nagasaki.

    Science.gov (United States)

    Matsuo, Masatoshi; Iwanaga, Masako; Kondo, Hisayoshi; Soda, Midori; Jo, Tatsuro; Horio, Kensuke; Takasaki, Yumi; Kawaguchi, Yasuhisa; Tsushima, Hideki; Imaizumi, Yoshitaka; Imanishi, Daisuke; Taguchi, Jun; Sawayama, Yasushi; Hata, Tomoko; Miyazaki, Yasushi

    2016-10-01

    There is evidence that radiation exposure is a causative factor of myelodysplastic syndromes (MDS). However, little is known about whether radiation exposure is also a prognostic factor of MDS. We investigated the impact of radiation exposure on the prognosis of MDS in Nagasaki atomic bomb survivors using the International Prognostic Scoring System (IPSS) and the revised version (IPSS-R). Subjects were 140 patients with primary MDS diagnosed between 1985 and 2011 and evaluable for IPSS, IPSS-R, and exposure distance. Of those, 31 were exposed at atomic bomb survivors, but exposure distance was not associated with any poor outcomes. These suggest that exposure to the greater dose of atomic bomb radiation is associated with developing poor cytogenetic abnormalities in MDS, which might consequently lead to overt leukemia among atomic bomb survivors. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  16. Depletion of intense fields

    CERN Document Server

    Seipt, D; Marklund, M; Bulanov, S S

    2016-01-01

    The interaction of charged particles and photons with intense electromagnetic fields gives rise to multi-photon Compton and Breit-Wheeler processes. These are usually described in the framework of the external field approximation, where the electromagnetic field is assumed to have infinite energy. However, the multi-photon nature of these processes implies the absorption of a significant number of photons, which scales as the external field amplitude cubed. As a result, the interaction of a highly charged electron bunch with an intense laser pulse can lead to significant depletion of the laser pulse energy, thus rendering the external field approximation invalid. We provide relevant estimates for this depletion and find it to become important in the interaction between fields of amplitude $a_0 \\sim 10^3$ and electron bunches with charges of the order of nC.

  17. Learning about ozone depletion

    Energy Technology Data Exchange (ETDEWEB)

    Crutzen, J. P. [Department of Atmospheric Chemistry, Max Planck Institute for Chemistry, Mainz, Germany; Oppenheimer M. [Woodrow Wilson School of Public and International Affairs, Department of Geosciences, Princeton University, Princeton, NJ (United States)

    2008-07-15

    Stratospheric ozone depletion has been much studied as a case history in the interaction between environmental science and environmental policy. The positive influence of science on policy is often underscored, but here we review the photochemistry of ozone in order to illustrate how scientific learning has the potential to mislead policy makers. The latter may occur particularly in circumstances where limited observations are combined with simplified models of a complex system, such as may generally occur in the global change arena. Even for the well-studied case of ozone depletion, further research is needed on the dynamics of scientific learning, particularly the scientific assessment process, and how assessments influence the development of public policy.

  18. Depletion of Intense Fields

    Science.gov (United States)

    Seipt, D.; Heinzl, T.; Marklund, M.; Bulanov, S. S.

    2017-04-01

    The interaction of charged particles and photons with intense electromagnetic fields gives rise to multiphoton Compton and Breit-Wheeler processes. These are usually described in the framework of the external field approximation, where the electromagnetic field is assumed to have infinite energy. However, the multiphoton nature of these processes implies the absorption of a significant number of photons, which scales as the external field amplitude cubed. As a result, the interaction of a highly charged electron bunch with an intense laser pulse can lead to significant depletion of the laser pulse energy, thus rendering the external field approximation invalid. We provide relevant estimates for this depletion and find it to become important in the interaction between fields of amplitude a0˜1 03 and electron bunches with charges of the order of 10 nC.

  19. Increased expression of HERG K(+) channels contributes to myelodysplastic syndrome progression and displays correlation with prognosis stratification.

    Science.gov (United States)

    Lu, Li; Du, Wen; Liu, Wei; Guo, Dongmei; He, Xiaoqi; Li, Huiyu

    2016-12-01

    Human ether-a-go-go-related gene (HERG) K(+) channels are shown to be aberrantly expressed in a variety of cancer cells where they play roles in contributing to cancer progression. Myelodysplastic syndromes (MDS) are a group of clinical heterogeneous disorders characterized by bone marrow failure and dysplasia of blood cells. However, the involvement of HERG K(+) channels in MDS development is poorly understood. The expression of HERG K(+) channels in untreated MDS, acute myeloid leukemia (AML) patients and the control group was detected by flow cytometry. The roles of HERG K(+) channels in regulation of SKM-1 cell proliferation, apoptosis, and cell cycle were determined by CCK-8 assay and flow cytometry, respectively. We found that expression of HERG K(+) channels in MDS patients was significantly higher than controls and was lower than AML. Percentage of HERG K(+) channels on CD34+CD38- cells gradually increased from controls to high-grade MDS subtypes. And HERG K(+) channel levels showed an ascending tendency from low-risk to high-risk MDS group. In addition, the CCK-8 assay, apoptosis and cell cycle analysis were performed and showed that blockage of HERG K(+) channels decreased the proliferation of MDS cells but rarely had effects on cell apoptosis and cell cycle distribution. Our study demonstrated that HERG K(+) channels might be a potential tumor marker of MDS. These channels were likely to contribute to MDS progression and were helpful for predicting prognosis of MDS. Inhibition of HERG K(+) channels might be a novel therapeutic measure for MDS.

  20. Improving diffusion power of AES Rijndael with 8x8 MDS matrix

    Directory of Open Access Journals (Sweden)

    R.Elumalai,

    2011-01-01

    Full Text Available AES Rijndael is a block cipher developed by NIST as the Advanced Encryption Standard (AES replacing DES and published as FIPS 197 in November 2001 [5] to address the threatened key size of Data Encryption Standard (DES. AES-Rijndael was developed by Joan Daemen and Vincent Rijmen, Rijndael [4, 5] and was selected from five finalists. Advancement in computation speed every day puts lotsof pressure on AES and AES may not with stand attack for longer time. This work focuses on improving security of an encryption algorithm, beyond AES. Though there are various techniques available to enhance the security, an attempt is made to improve the diffusion strength of an algorithm. For enhancing the diffusion power AES Rijndael in MixColumn operation the branch number of MDS matrix is raised from 5 to 9 using a new 8X8 MDS matrix with trade off of speed [8, 9] and implemented on R8C microcontroller.

  1. BURDEN OF ABNORMAL HEMATOPOIETIC CLONE IN PATIENTS WITH MYELODYSPLASTIC SYNDROMES

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective To investigate the role of the burden of abnormal hematopoietic clone in the development of myelodys plastic syndromes (MDS).Methods The ratio of the bone marrow cells with abnormal chromosomes to the total counted bone marrow cells was regarded as the index of MDS clone burden. The disease severity related parameters including white blood cell count, hemoglobin, platelet count, lactate dehydrogenase level, bone marrow blast, myeloid differentiation index, micromegakaryocyte, transfusion, interleukin-2, tumor necrosis factor ( TNF), CD4 + and CD8 + T cells of MDS patients were assayed, and the correlations between those parameters and MDS clone burden were also analyzed.Results The clone burden of MDS patients was 67.4% ± 36. 2%. MDS clone burden positively correlated with bone marrow blasts (r=0.483, P<0.05), negatively with hemoglobin level (r=-0.445, P<0.05). The number of blasts, hemoglobin, and erythrocytes in high clone burden (>50%) and low clone burden (≤50%) groups were 7.78%±5.51% and 3.45%±3.34%, 56.06±14. 28 g/L and 76.40±24.44 g/L, (1.82±0.48)×1012/L and (2. 32±0.66)×1012/L, respectively (all P <0.05). CD4 + T lymphocytes of MDS patients and normal controls were (0. 274±0.719)×109/L and (0.455±0.206)×109/L, respectively (P<0.05). CD8 ± T lymphocytes of MDS patients and normal controls were (0.240±0.150)×109/L and (0.305 ±0.145)×109/L, respectively. The serum level of interleukin-2 of MDS patients (6.29±3.58 ng/mL) was significantly higher than normal control (3.11±1.40ng/mL, P<0.05). The serum level of TNF of MDS patients and normal control group were 2.42±1.79 ng/mL and 1.68 ±0.69 ng/mL, respectively. The ratio of CD4 to CD8 was higher in high clone burden MDS patients (1.90 ±0.52) than that in low clone burden patients (0.97±0.44, P<0.05).Conclusion The quantitive clonal karyotype abnormalities and deficient T cell immunity are important parameters for evaluating MDS severity and predicting its

  2. Serum iron metabolism and erythropoiesis in patients with myelodysplastic syndrome not receiving RBC transfusions

    OpenAIRE

    Cui, Rui; Gale, Robert Peter; Zhu, Guoqing; Xu, Zefeng; Qin, Tiejun; Zhang, Yue; Huang, Gang; Li, Bing; Fang, Liwei; Zhang, Hongli; Pan, Lijuan; Hu, Naibo; Qu, Shiqiang; Xiao, Zhijian

    2014-01-01

    Dysregulation of hepcidin, a key iron regulating hormone, is important in the pathogenesis of iron overload in patients with myelodysplatic syndrome (MDS). However, most studies of hepcidin levels are complicated by concomitant RBC transfusions. To evaluate the relationship between iron metabolism and erythropoiesis, we measured serum levels of hepcidin, growth-differentiation factor-15 (GDF15) and other markers of erythropoiesis in 107 subjects with MDS not receiving RBC transfusions. Patien...

  3. Measurement of the Mass Difference m(D_s^+) - m(D^+) at CDF II

    CERN Document Server

    Acosta, D; Ahn, M H; Akimoto, T; Albrow, M G; Alcorn, B; Alexander, C; Allen, D; Allspach, D H; Amaral, P; Ambrose, D; Amendolia, S R; Amidei, D; Amundson, J F; Anastassov, A; Anderson, J; Anikeev, K; Annovi, A; Antos, J; Aoki, M; Apollinari, G; Arguin, J F; Arisawa, T; Artikov, A; Asakawa, T; Ashmanskas, W; Attal, A; Avanzini, C; Azfar, F; Azzi-Bacchetta, P; Babik, M; Bacchetta, N; Bachacou, H; Badgett, W F; Bailey, S; Bakken, J; Barbaro-Galtieri, A; Bardi, A; Bari, M; Barker, G; Barnes, V E; Barnett, B A; Baroiant, S; Barone, M; Barsotti, E; Basti, A; Bauer, G; Beckner, D; Bedeschi, F; Behari, S; Belforte, S; Bell, W H; Bellendir, G; Bellettini, Giorgio; Bellinger, J; Benjamin, D; Beretvas, A; Berg, B; Bhatti, A A; Binkley, M; Bisello, D; Bishai, M; Blair, R E; Blocker, C; Bloom, K; Blumenfeld, B; Bocci, A; Bodek, A; Bogdan, M; Bölla, G; Bolshov, A; Booth, P S L; Bortoletto, Daniela; Boudreau, J; Bourov, S; Bowden, M; Box, D; Bromberg, C; Brown, W; Brozovic, M; Brubaker, E; Buckley-Geer, L; Budagov, Yu A; Budd, H S; Burkett, K; Busetto, G; Bussey, P; Byon-Wagner, A; Byrum, K L; Cabrera, S; Calafiura, P; Campanelli, M; Campbell, M; Canal, P; Canepa, A; Carithers, W C; Carlsmith, D; Carosi, R; Carrell, K; Carter, H; Caskey, W; Castro, A; Cauz, D; Cerri, A; Cerri, C; Cerrito, L; Chandler, J T; Chapman, J; Chappa, S; Chen, C; Chen, Y C; Cheng, M T; Chertok, M; Chiarelli, G; Chirikov-Zorin, I E; Chlachidze, G; Chlebana, F; Cho, I; Cho, K; Chokheli, D; Chu, M L; Chung, J Y; Chung, W H; Chung, Y S; Ciobanu, C I; Ciocci, M A; Cisko, S; Clark, A G; Coca, M; Coiley, K; Colijn, A P; Colombo, R M; Connolly, A; Convery, M; Conway, J; Cooper, G; Cordelli, M; Cortiana, G; Cranshaw, J; Cudzewicz, R; Culbertson, R; Currat, C; Cyr, D; Dagenhart, D; Dal Monte, L; Da Ronco, S; D'Auria, S; Davila, R; Dawson, J; Dawson, T; De Barbaro, P; De Baun, C; De Cecco, S; Dell'Agnello, S; Dell'Orso, Mauro; De Maat, R; Demar, P; Demers, S; Demortier, L; Deninno, M; De Pedis, D; Derwent, P F; Derylo, G; Devlin, T; Dionisi, C; Dittmann, J R; Doksus, P; Dominguez, A; Donati, S; Donno, F; D'Onofrio, M; Dorigo, T; Downing, R; Drake, G; Drennan, C; Drollinger, V; Dunietz, Isard; Dyer, A; Ebina, K; Eddy, N; Ely, R; Engels, E; Erbacher, R D; Erdmann, M; Errede, D; Errede, S; Eusebi, R; Fang, H C; Farrington, S; Feild, R G; Feindt, M; Fernández, J P; Ferretti, C; Field, R D; Fiori, I; Fischler, M; Flanagan, G; Flaugher, B; Flores-Castillo, L R; Foland, A D; Forrester, S; Foster, G W; Franklin, M; Frisch, H; Fromm, J; Fujii, Y; Furic, I; Galeotti, S; Galet, G; Gallas, A; Gallinaro, M; Ganel, O; García, C; García-Sciveres, M; Garfinkel, A F; Garwacki, M; Garzoglio, G; Gay, C; Gerberich, H; Gerdes, D W; Gerchtein, E; Gerstenslager, J; Giacchetti, L; Giagu, S; Giannetti, P; Gibson, A; Gillespie, G; Gingu, C; Ginsburg, C; Giolo, K; Giordani, M; Glagolev, V; Glenzinski, D A; Glossen, R; Gold, M; Goldschmidt, N; Goldstein, D B; Goldstein, J; Gómez, G; Goncharov, M; González, H; Gordon, S; Gorelov, I; Goshaw, A T; Gotra, Yu; Goulianos, K; Grado, J; Gregori, M; Gresele, A; Griffin, T; Grim, G; Grimm, C; Gromoll, S; Grosso-Pilcher, C; Gu, C; Guarino, V; Günther, M; Guimarães da Costa, J; Haber, C; Hahn, A; Hahn, K; Hahn, S R; Halkiadakis, E; Hall, C; Handler, R; Haney, M; Hao, W; Happacher, F; Hara, K; Hare, M; Harr, R F; Harrington, J; Harris, R M; Hartmann, F; Hatakeyama, K; Hauser, J; Hawke, T; Hays, C; Heider, E; Heinemann, B; Heinrich, J; Heiss, A; Hennecke, M; Herber, R; Herndon, M; Herren, M; Hicks, D; Hill, C; Hirschbuehl, D; Höcker, A; Hoff, J; Hoffman, K D; Hoftiezer, J H; Holloway, A; Holloway, L E; Holm, S; Holmgren, D; Hou, S; Houlden, M A; Howell, J; Hrycyk, M; Hubbard, P; Hughes, R E; Huffman, B T; Humbert, J; Huston, J; Ikado, K; Incandela, J R; Introzzi, G; Iori, M; Ishizawa, I; Issever, C; Ivanov, A; Iwata, Y; Iyutin, B; James, E; Jang, D; Jarrell, J; Jeans, D; Jensen, H; Jetton, R; Johnson, M; Jones, M; Jones, T; Jun, S Y; Junk, T R; Kallenbach, Jeff; Kamon, T; Kang, J; Karagoz-Unel, M; Karchin, P E; Kartal, S; Kasha, H; Kasten, M; Kato, Y; Kemp, Y; Kennedy, R D; Kephart, K; Kephart, R D; Khazins, D; Khotilovich, V; Kilminster, B; Kim, B J; Kim, D H; Kim, H S; Kim, J; Kim, M J; Kim, M S; Kim, S B; Kim, S H; Kim, T H; Kim, Y K; King, B T; Kirby, M; Kirk, M; Kirsch, L; Klein, R; Klimenko, S; Knapp, M; Knoblauch, D; Knuteson, B; Kobayashi, H; Koehn, P; Kondo, K; Kong, D J; Konigsberg, J; Kononenko, W; Kordas, K; Korn, A J; Korytov, A; Kotelnikov, K A; Kotwal, A; Kovalev, A; Kowalkowski, J B; Kraus, J; Kravchenko, I V; Kreymer, A; Kroll, J; Kruse, M; Krutelyov, V; Kuhlmann, S E; Kumar, A; Kuznetsova, N; Laasanen, A T; Lai, S; Lami, S; Lammel, S; Lamore, D; Lancaster, J; Lancaster, M; Lander, R; Lanfranco, G; Lannon, K; Lath, A; Latino, G; Lauhakangas, R; Lazzizzera, I; Le, Y; LeCompte, T J; Lee, J; Lee, K; Lee, S W; Lei, C M; Leininger, M; Leonardi, G L; Leonardo, N; Leone, S; Levshina, T; Lewis, F; Lewis, J D; Li, K; Lin, C S; Lindgren, M; Liss, T M; Litvintsev, D O; Liu, T; Liu, Y; Lobban, O; Lockyer, N S; Loginov, A; Loken, J; Loreti, M; Loskot, J; Loverre, P F; Lucchesi, D; Lukens, P; Lutz, P; Lyons, L; Lys, J; MacNerland, J; MacQueen, D; Madorsky, A; Madrak, R; Maeshima, K; Maksimovic, P; Malferrari, L; Mammini, P; Manca, G; Mandrichenko, I V; Manea, C; Marginean, R; Marrafino, J; Martin, A; Martin, M; Martin, V; Martínez, M; Maruyama, T; Matsunaga, H; Mayer, J; Mayers, G M; Mazzanti, P; McFarland, K S; McGivern, D; McIntyre, P M; McNamara, P; McNulty, R; Menzemer, S; Menzione, A; Merkel, P; Mesropian, C; Messina, A; Meyer, A; Miao, T; Michael, N; Miller, J S; Miller, L; Miller, R; Miquel, R; Miscetti, S; Mitselmakher, G; Miyamoto, A; Miyazaki, Y; Mizicko, D; Moccia, S; Moggi, A; Moggi, N; Montero, S; Moore, R; Moore, T; Morris, L; Morsani, F; Moulik, T; Mukherjee, A; Mulhearn, M; Müller, T; Mumford, R; Munar, A; Murat, P; Murgia, S; Nachtman, J; Nagaslaev, V; Nahn, S; Nakamura, I; Nakano, I; Napier, A; Napora, R; Necula, V; Nelson, C; Nelson, T; Neu, C; Neubauer, M S; Neuberger, D; Newby, W; Newcomer, F M; Newman-Holmes, C; Niell, F; Nielsen, J; Nicollerat, A S; Nigmanov, T; Niu, H; Nodulman, L; Noe, W; Österberg, K; Ogawa, T; Oh, S; Oh, Y D; Ohl, K; Ohsugi, T; Oishi, R; Okusawa, T; Oldeman, R G C; Orava, Risto; Orejudos, W; Orr, S; Pagani, G; Pagliarone, C; Palmonari, F; Ramos, I; Panacek, S; Pantano, D; Paoletti, R; Papadimitriou, V; Pasetes, R; Pashapour, S; Passuello, D; Paterno, M; Patrick, J; Pauletta, G; Paulini, M; Pauly, T; Paus, C; Pavlicek, V; Pavlon, S; Pellett, D; Penzo, Aldo L; Perington, B; Petragnani, G; Petravick, D; Phillips, T J; Photos, F; Piacentino, G; Picciolo, C; Piccoli, L; Piedra, J; Pitts, K T; Plunkett, R; Pompos, A; Pondrom, L; Pope, G; Poukhov, O; Prakoshyn, F; Pratt, T; Profeti, A; Pronko, A G; Proudfoot, J; Punzi, G; Rademacker, J; Rafaelli, F; Rakitine, A; Rappoccio, S; Ratnikov, F; Rauch, J; Ray, H; Rechenmacher, R; Reia, S; Reichold, A; Rekovic, V; Renton, P B; Rescigno, M; Rimondi, F; Rinnert, K; Ristori, L; Riveline, M; Rivetta, C; Robertson, W J; Robson, A; Rodrigo, T; Rolli, S; Román, M; Rosenberg, S I; Rosenson, L; Roser, R; Rossin, R; Rott, C; Ruiz, A; Russ, J; Ryan, D; Saarikko, H; Sabik, S; Sadler, L; Safonov, A; Saint-Denis, R; Sakumoto, W K; Saltzberg, D; Sánchez, C; Sanders, H; Sanders, R; Sandrew, M; Sansoni, A; Santi, L; Sarkar, S; Sarraj, H; Sarraj, J; Sato, H; Savard, P; Schemitz, P; Schlabach, P; Schmidt, E E; Schmidt, J; Schmidt, M P; Schmitt, M; Schmitt, R; Schmitz, M; Schofield, G L; Schuh, K; Schultz, K; Scodellaro, L; Scott, L; Scribano, A; Scuri, F; Sedov, A; Segler, S; Seidel, S; Seiya, Y; Semenov, A; Semeria, F; Sexton-Kennedy, L; Sfiligoi, I; Shallenberger, J; Shapiro, M D; Shaw, T; Shears, T G; Shenai, A; Shepard, P F; Shimojima, M; Shochet, M J; Shon, Y; Shoun, M; Sidoti, A; Siegrist, J L; Sieh, C; Siket, M; Sill, A; Silva, R; Simaitis, V; Sinervo, P; Sirotenko, V I; Sissakian, A N; Skiba, A; Slaughter, A J; Sliwa, K; Smith, J; Snider, F D; Snihur, R; Somalwar, S V; Spalding, J; Spezziga, M; Spiegel, L; Spinella, F; Spiropulu, M; Stadie, H; Stanek, R; Stanfield, N; Stelzer, B; Stelzer-Chilton, O; Strologas, J; Stuart, D; Stuermer, W; Sukhanov, A; Sumorok, K; Sun, H; Suzuki, T; Syu, J; Szymulanski, A; Taffard, A C; Takach, S F; Takano, H; Takashima, R; Takeuchi, Y; Takikawa, K; Tamburello, P; Tanaka, M; Tanaka, R; Tang, D; Tanimoto, N; Tannenbaum, B; Tapprogge, Stefan; Taylor, R D; Teafoe, G; Tecchio, M; Teng, P K; Terashi, K; Terentieva, T; Tesarek, R J; Tether, S; Thom, J; Thomas, A; Thompson, A S; Thomson, E; Thurman-Keup, R M; Timm, S; Tipton, P; Tkaczyk, S M; Toback, D; Tollefson, K; Tonelli, D; Tonnesmann, M; Torretta, D; Trimby, C; Trischuk, W; Trumbo, J; Tseng, J; Tsuchiya, R; Tsuno, S; Tsybychev, D; Turini, N; Turner, M; Ukegawa, F; Unverhau, T; Uozumi, S; Usynin, D; Vacavant, L; Vaiciulis, T; Van Berg, R; Varganov, A V; Vataga, E; Vejcik, S; Velev, G V; Veramendi, G; Vickey, T; Vidal, R; Vila, I; Vilar, R; Vittone, M; Voirin, J; Vollmer, B; Vollrath, I; Volobuev, I P; Von der Mey, M; Votava, M; Wagner, R G; Wagner, R L; Wagner, W; Wallace, N; Walter, T; Walters, A; Wan, Z; Wandersee, A; Wang, M J; Wang, S M; Ward, B; Waschke, S; Waters, D; Watts, T; Weber, M; Weems, L; Wenzel, H; Wester, W; Whitehouse, B; Wickenberg, W; Wicklund, A B; Wicklund, E; Wigmans, R; Wike, C; Wilkes, T; Williams, H H; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolter, M; Wong, M; Worcester, M; Worland, R; Worm, S; Wright, T; Wu, J; Wu, X; Würthwein, F; Wyatt, A; Yagil, A; Yamamoto, K; Yamashita, T; Yang, U K; Yao, W; Yarema, R J; Yeh, G P; Yi, K; Yocum, D R; Yoh, J K; Yoon, P; Yorita, K; Yoshida, T; Yu, I; Yu, S; Yu, Z; Yun, J C; Zalokar, M; Zanello, L; Zanetti, A; Zaw, I; Zetti, F; Zhou, J; Zimmerman, T; Zsenei, A; Zucchelli, S

    2003-01-01

    We present a measurement of the mass difference m(D+_s) - m(D+), where both the D+_s and D+ are reconstructed in the phi pi+ decay channel. This measurement uses 11.6 pb-1 of data collected by CDF II using the new displaced-track trigger. The mass difference is found to be: 99.41 +- 0.38 (stat) +- 0.21 (syst) MeV/c^2.

  4. Partial-MDS Codes and their Application to RAID Type of Architectures

    CERN Document Server

    Blaum, Mario; Hetzler, Steven

    2012-01-01

    A family of codes with a natural two-dimensional structure is presented, inspired by an application of RAID type of architectures whose units are solid state drives (SSDs). Arrays of SSDs behave differently to arrays of hard disk drives (HDDs), since hard errors in sectors are common and traditional RAID approaches (like RAID 5 or RAID 6) may be either insufficient or excessive. An efficient solution to this problem is given by the new codes presented, called partial-MDS (PMDS) codes.

  5. GPA-MDS: A Visualization Approach to Investigate Genetic Architecture among Phenotypes Using GWAS Results.

    Science.gov (United States)

    Wei, Wei; Ramos, Paula S; Hunt, Kelly J; Wolf, Bethany J; Hardiman, Gary; Chung, Dongjun

    2016-01-01

    Genome-wide association studies (GWAS) have identified tens of thousands of genetic variants associated with hundreds of phenotypes and diseases, which have provided clinical and medical benefits to patients with novel biomarkers and therapeutic targets. Recently, there has been accumulating evidence suggesting that different complex traits share a common risk basis, namely, pleiotropy. Previously, a statistical method, namely, GPA (Genetic analysis incorporating Pleiotropy and Annotation), was developed to improve identification of risk variants and to investigate pleiotropic structure through a joint analysis of multiple GWAS datasets. While GPA provides a statistically rigorous framework to evaluate pleiotropy between phenotypes, it is still not trivial to investigate genetic relationships among a large number of phenotypes using the GPA framework. In order to address this challenge, in this paper, we propose a novel approach, GPA-MDS, to visualize genetic relationships among phenotypes using the GPA algorithm and multidimensional scaling (MDS). This tool will help researchers to investigate common etiology among diseases, which can potentially lead to development of common treatments across diseases. We evaluate the proposed GPA-MDS framework using a simulation study and apply it to jointly analyze GWAS datasets examining 18 unique phenotypes, which helps reveal the shared genetic architecture of these phenotypes.

  6. Optimal Repair of MDS Codes in Distributed Storage via Subspace Interference Alignment

    CERN Document Server

    Cadambe, Viveck R; Jafar, Syed A; Li, Jin

    2011-01-01

    It is well known that an (n,k) code can be used to store 'k' units of information in 'n' unit-capacity disks of a distributed data storage system. If the code used is maximum distance separable (MDS), then the system can tolerate any (n-k) disk failures, since the original information can be recovered from any k surviving disks. The focus of this paper is the design of a systematic MDS code with the additional property that a single disk failure can be repaired with minimum repair bandwidth, i.e., with the minimum possible amount of data to be downloaded for recovery of the failed disk. Previously, a lower bound of (n-1)/(n-k) units has been established by Dimakis et. al, on the repair bandwidth for a single disk failure in an (n,k) MDS code . Recently, the existence of asymptotic codes achieving this lower bound for arbitrary (n,k) has been established by drawing connections to interference alignment. While the existence of asymptotic constructions achieving this lower bound have been shown, finite code cons...

  7. Myelodysplastic syndrome complicated by central diabetes insipidus and cerebral salt wasting syndrome with peculiar change in magnetic resonance images.

    Science.gov (United States)

    Sano, Soichi; Yamagami, Keiko; Morikawa, Takashi; Yoshioka, Katsunobu

    2010-01-01

    Central diabetes insipidus (CDI) could occurs in patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML), because of infiltration of leukemic cells into the neurohypophysis or some other reason and it is closely associated with abnormalities of chromosome 7. We report a case of MDS with abnormalities of chromosome 7, presenting as CDI followed by deterioration of polyuria and hyponatremia with a decreased extracellular fluid volume. Magnetic resonance imaging (MRI) revealed symmetrically enhanced lesions in the hypothalamus. Fludrocortisone treatment normalized his serum sodium level and cerebral salt wasting syndrome (CSWS) was suspected.

  8. Ozone-depleting Substances (ODS)

    Data.gov (United States)

    U.S. Environmental Protection Agency — This site includes all of the ozone-depleting substances (ODS) recognized by the Montreal Protocol. The data include ozone depletion potentials (ODP), global warming...

  9. Sonic Hedgehog Produced by Bone Marrow-Derived Mesenchymal Stromal Cells Supports Cell Survival in Myelodysplastic Syndrome

    Directory of Open Access Journals (Sweden)

    Jixue Zou

    2015-01-01

    Full Text Available The role of marrow microenvironment in the pathogenesis of myelodysplastic syndrome (MDS remains controversial. Therefore, we studied the influence of bone marrow-derived mesenchymal stromal cells (BMSCs from patients with different risk types of MDS on the survival of the MDS cell lines SKM-1 and MUTZ-1. We first demonstrated that the expression of Sonic hedgehog (Shh, smoothened (Smo, and glioma-associated oncogene homolog 1 (Gli1 was increased in MDS patients n=23; the increase in expression was positively correlated with the presence of high-risk factors. The Shh signaling inhibitor, cyclopamine, inhibited high-risk MDS BMSC-induced survival of SKM-1 and MUTZ-1 cells, suggesting a role for Shh signaling in MDS cell survival. Furthermore, cyclopamine-mediated inhibition of Shh signaling in SKM-1 and MUTZ-1 cells resulted in decreased DNMT1 expression and cell survival; however, exogenous Shh peptide had the opposite effect, suggesting that Shh signaling could regulate the expression of DNMT1, thereby modulating cell survival in MDS. In addition, the apoptosis of SKM-1 and MUTZ-1 cell increased significantly when cultured with cyclopamine and a demethylation agent, 5-Aza-2′-deoxycytidine. These findings suggest that Shh signaling from BMSCs is important in the pathogenesis of MDS and could play a role in disease progression by modulating methylation.

  10. Risk of myelodysplastic syndromes in people exposed to ionizing radiation: a retrospective cohort study of Nagasaki atomic bomb survivors.

    Science.gov (United States)

    Iwanaga, Masako; Hsu, Wan-Ling; Soda, Midori; Takasaki, Yumi; Tawara, Masayuki; Joh, Tatsuro; Amenomori, Tatsuhiko; Yamamura, Masaomi; Yoshida, Yoshiharu; Koba, Takashi; Miyazaki, Yasushi; Matsuo, Tatsuki; Preston, Dale L; Suyama, Akihiko; Kodama, Kazunori; Tomonaga, Masao

    2011-02-01

    The risk of myelodysplastic syndromes (MDS) has not been fully investigated among people exposed to ionizing radiation. We investigate MDS risk and radiation dose-response in Japanese atomic bomb survivors. We conducted a retrospective cohort study by using two databases of Nagasaki atomic bomb survivors: 64,026 people with known exposure distance in the database of Nagasaki University Atomic-Bomb Disease Institute (ABDI) and 22,245 people with estimated radiation dose in the Radiation Effects Research Foundation Life Span Study (LSS). Patients with MDS diagnosed from 1985 to 2004 were identified by record linkage between the cohorts and the Nagasaki Prefecture Cancer Registry. Cox and Poisson regression models were used to estimate relationships between exposure distance or dose and MDS risk. There were 151 patients with MDS in the ABDI cohort and 47 patients with MDS in the LSS cohort. MDS rate increased inversely with exposure distance, with an excess relative risk (ERR) decay per km of 1.2 (95% CI, 0.4 to 3.0; P atomic bomb survivors 40 to 60 years after radiation exposure. Clinicians should perform careful long-term follow-up of irradiated people to detect MDS as early as possible.

  11. Myelodysplastic syndromes: therapeutic problems and decisions (review

    Directory of Open Access Journals (Sweden)

    S. V. Semochkin

    2012-01-01

    Full Text Available Myelodysplastic syndromes (MDS are a group of heterogeneous clonal disorders of myeloid hematopoietic stem cells characterized by an ineffective hematopoiesis associated with cytopenias, morphologic dysplasia and a progression to acute myeloid leukemia. The only potentially curative MDS treatment is hematopoietic stem cell transplantation, which is usually not even discussed because most patients with advanced age at diagnosis. Currently only three drugs are approved by US Food and Drug Administration (FDA and European Medicines Agency for therapy of MDS. For low and intermediate-1 risk MDS del(5q the novel immunomodulatory drug lenalidomide is asserted, and for intermediate-2 and high risk the two hypomethylating agents (azacitidine, decitabine are approved. The results of completed clinical trials demonstrating the efficacy and safety of these agents are presented. The new data indicating that the successful future of MDS treatment rests in the combination of multiple treatments modalities to achieve improved clinical outcomes are discussed in this review.

  12. Myelodysplastic syndromes: therapeutic problems and decisions (review

    Directory of Open Access Journals (Sweden)

    S. V. Semochkin

    2014-07-01

    Full Text Available Myelodysplastic syndromes (MDS are a group of heterogeneous clonal disorders of myeloid hematopoietic stem cells characterized by an ineffective hematopoiesis associated with cytopenias, morphologic dysplasia and a progression to acute myeloid leukemia. The only potentially curative MDS treatment is hematopoietic stem cell transplantation, which is usually not even discussed because most patients with advanced age at diagnosis. Currently only three drugs are approved by US Food and Drug Administration (FDA and European Medicines Agency for therapy of MDS. For low and intermediate-1 risk MDS del(5q the novel immunomodulatory drug lenalidomide is asserted, and for intermediate-2 and high risk the two hypomethylating agents (azacitidine, decitabine are approved. The results of completed clinical trials demonstrating the efficacy and safety of these agents are presented. The new data indicating that the successful future of MDS treatment rests in the combination of multiple treatments modalities to achieve improved clinical outcomes are discussed in this review.

  13. Nuclear Nox4-Derived Reactive Oxygen Species in Myelodysplastic Syndromes

    Directory of Open Access Journals (Sweden)

    Marianna Guida

    2014-01-01

    Full Text Available A role for intracellular ROS production has been recently implicated in the pathogenesis and progression of a wide variety of neoplasias. ROS sources, such as NAD(PH oxidase (Nox complexes, are frequently activated in AML (acute myeloid leukemia blasts and strongly contribute to their proliferation, survival, and drug resistance. Myelodysplastic syndromes (MDS comprise a heterogeneous group of disorders characterized by ineffective hematopoiesis, with an increased propensity to develop AML. The molecular basis for MDS progression is unknown, but a key element in MDS disease progression is the genomic instability. NADPH oxidases are now recognized to have specific subcellular localizations, this targeting to specific compartments for localized ROS production. Local Nox-dependent ROS production in the nucleus may contribute to the regulation of redox-dependent cell growth, differentiation, senescence, DNA damage, and apoptosis. We observed that Nox1, 2, and 4 isoforms and p22phox and Rac1 subunits are expressed in MDS/AML cell lines and MDS samples, also in the nuclear fractions. Interestingly, Nox4 interacts with ERK and Akt1 within nuclear speckle domain, suggesting that Nox4 could be involved in regulating gene expression and splicing factor activity. These data contribute to the elucidation of the molecular mechanisms used by nuclear ROS to drive MDS evolution to AML.

  14. Anemia as the Main Manifestation of Myelodysplastic Syndromes.

    Science.gov (United States)

    Santini, Valeria

    2015-10-01

    Myelodysplastic syndromes (MDS) are a constellation of different diseases sharing anemia in the great majority of cases, and this cytopenia defines these pathologies and their most dramatic clinical manifestations. Anemia in MDS is due to ineffective erythropoiesis, with a high degree of apoptosis of marrow erythroid progenitors. These progenitors show distinctive dysplastic features that consent diagnosis, and are recognizable and differentiated, although not easily, from other morphologic alterations present in other types of anemia. Reaching the diagnosis of MDS in a macrocytic anemia and alleviating the symptoms of anemia are therefore an essential objective of the treating physician. In this work, the signs and symptoms of anemia in MDS, as well as its peculiar pathophysiology, are discussed. Erythopoietic stimulating agents (ESAs) are providing the best treatment for anemic MDS patients, but their use is still not approved by health agencies. While still waiting for this waiver, their clinical use is widespread and their effectivness is well known, as well as the dismal prognosis of patients who do not respond to ESAs and require transfusions. MDS with del5q constitute a unique model of anemia whose complex pathophysiology has been clarified at least partially, defining its link to ribosomal alterations likewise what observed in hereditary anemias like Blackfan Diamond anemia. Lenalidomide is the agent that has shown striking and specific erythropoietic activity in del5q MDS, and the basis of this response is starting to be understood. Several new agents are under evaluation for ESA refractory/relapsed MDS patients, targeting different putative mechanisms of ineffective erythropoiesis, and are here reviewed.

  15. Analyzing transformation of myelodysplastic syndrome to secondary acute myeloid leukemia using a large patient database.

    Science.gov (United States)

    Shukron, Ofir; Vainstein, Vladimir; Kündgen, Andrea; Germing, Ulrich; Agur, Zvia

    2012-09-01

    One-third of patients with myelodysplastic syndrome (MDS) progress to secondary acute myeloid leukemia (sAML), with its concomitant poor prognosis. Recently, multiple mutations have been identified in association with MDS-to-sAMLtransition, but it is still unclear whether all these mutations are necessary for transformation. If multiple independent mutations are required for the transformation, sAML risk should increase with time from MDS diagnosis. In contrast, if a single critical biological event determines sAML transformation; its risk should be constant in time elapsing from MDS diagnosis. To elucidate this question, we studied a database of 1079 patients with MDS. We classified patients according to the International Prognostic Scoring System (IPSS), using either the French-American-British (FAB) or the World Health Organization (WHO) criteria, and statistically analyzed the resulting transformation risk curves of each group. The risk of transformation after MDS diagnosis remained constant in time within three out of four risk groups, and in all four risk groups, when patients were classified according to FAB or to the WHO-determined criteria, respectively. Further subdivision by blast percentage or cytogenetics had no influence on this result. Our analysis suggests that a single random biological event leads to transformation to sAML, thus calling for the exclusion of time since MDS diagnosis from the clinical decision-making process.

  16. Variants of the Mitochondrial Displacement Loop in Patients with Myelodysplastic Syndromes

    Institute of Scientific and Technical Information of China (English)

    Xiaojing Hu; Yaqin Cong; Conggao Xu; Jinbo Feng; Yujie Jiang; Hong Jin

    2008-01-01

    OBJECTIVE Some mtDNA mutations have been detected in patients with myelodysplastic syndromes (MDSs).As the noncoding region of mitochondria,the displacement loop (D-loop)region of mtDNA contains important elements for mtDNA replication and transcription.Variants of the D-loop region were found to be related to the cause of many diseases.The aim of our study was to investigate mutations and single nucleotide polymorphisms in the D-loop region of MDS patients.METHODS The mutations and SNPs in the hypervariable regions of the D-loop were detected by direct sequencing in MDS patients and normal controls.RESULTS Sixty-four SNPs were found in the D-loop region in MDS cases and control group.Among the SNPs,the 16,189 variant (T > C transition) was found to have an increased frequency in the MDS group (P = 0.044).However,no mutations were detected in neither group.CONCLUSION Our data provide evidence for a highly polymorphic D-loop region in patients with MDS,but do not support the presence of mutations in the mitochondrial D-loop region in MDS cases.The mtDNA T16,189C variant,which may be a functional variant,is associated with increased susceptibility to a MDS.

  17. Outcomes for Patients with Chronic Lymphocytic Leukemia (CLL) and Acute Leukemia or Myelodysplastic Syndrome

    Science.gov (United States)

    Tambaro, Francesco Paolo; Garcia-Manero, Guillermo; O’Brien, Susan M.; Faderl, Stefan H.; Ferrajoli, Alessandra; Burger, Jan A.; Pierce, Sherry; Wang, Xuemei; Do, Kim-Anh; Kantarjian, Hagop M.; Keating, Michael J.; Wierda, William G.

    2016-01-01

    Acute leukemia (AL) and myelodysplastic syndrome (MDS) are uncommon in CLL. We retrospectively identified 95 patients with CLL also diagnosed with AL (n=38) or MDS (n=57), either concurrently (n=5) or subsequent (n=90) to CLL diagnosis and report their outcomes. Median number of CLL treatments prior to AL and MDS was 2(0–9) and 1(0–8), respectively; the most common regimen was purine analogue combined with alkylating agent±CD20 mAb. Twelve had no prior CLL treatment. Among 38 with AL, 33 had AML, 3 had ALL (1Ph+), 1 had biphenotypic, and 1 had extramedullary (bladder) AML. Unfavorable AML karyotype was noted in 26, intermediate-risk in 7. There was no association between survival from AL and number of prior CLL regimens or karyotype. Expression of CD7 on blasts was associated with shorter survival. Among MDS cases, all IPSS were represented; karyotype was unfavorable in 36, intermediate in 6, and favorable in 12 patients; 10 experienced transformation to AML. Shorter survival from MDS correlated with higher-risk IPSS, poor-risk karyotype, and increased number of prior CLL treatments. Overall, outcomes for patients with CLL subsequently diagnosed with AL or MDS were poor; AL/MDS occurred without prior CLL treatment. Effective therapies for these patients are desperately needed. PMID:26290497

  18. Use of azacitidine for myelodysplastic syndromes: controversial issues and practical recommendations

    Science.gov (United States)

    Kim, Yoo-Jin; Jang, Jun Ho; Kwak, Jae-Yong; Lee, Je-Hwan

    2013-01-01

    Azacitidine is recommended for patients with higher-risk myelodysplastic syndromes (MDS) who are not eligible for intensive therapy or for patients with lower-risk MDS who have thrombocytopenia or neutropenia or have anemia that is unresponsive to other therapies. However, standard treatment with azacitidine has not been optimized and many issues about the use of azacitidine remain unresolved. The use of azacitidine is expanding rapidly, but limited comparative clinical trial data are available to (i) define the optimal use of azacitidine in patients with higher-risk MDS or around the time of allogeneic hematopoietic stem cell transplantation, (ii) identify those patients with lower-risk MDS who may benefit from treatment, and (iii) guide physicians on alternative therapies after treatment failure. Increasing evidence suggests that the clinical features, prognostic factors, and cytogenetic profiles of patients with MDS in Asia differ significantly from those of patients in Western countries, so the aim of this review is to summarize the evidence and provide practical recommendations on the use of azacitidine in patients with MDS in the Republic of Korea. Evidence considered in this review is based on published clinical data and on the clinical experience of an expert panel from the acute myeloid leukemia/MDS Working Party of the Korean Society of Hematology. PMID:23826577

  19. [Hematologic response predictor factors in adults with myelodysplastic syndromes (SMD) treated with cyclosporin A (CSA)].

    Science.gov (United States)

    Zamora-Pérez, Elia; López-Karpovitch, Xavier

    2015-01-01

    Myelodysplastic syndromes (MDS) are clonal diseases of hematopoietic cells. The International Prognostic Scoring System (IPSS) is the risk scale most employed in MDS. Cyclosporin A (CsA) has been used in the treatment of cytopenias in MDS. To evaluate hematologic response and identify response predictive factors in adults with MDS treated with CsA. Patients with MDS diagnosed according World Health Organization (WHO) classification were recruited from January 1997 to June 2012. All patients were classified with IPSS, IPSS revised (IPSS-R),WHO Prognostic Scoring System (WPSS), and WPSS revised (WPSS-R) risk scales. Cyclosporin A was administered orally at a dose of 5 mg/kg/day. Hematologic response was evaluated following the International Working Group for MDS (2006 version) criteria. Inclusion criteria were met by 32 patients. Median age was 56.5 years, with a median follow-up of 3.1 years. Hematologic response was 56.2% and erythrocyte independence transfusion was found in 42.9% of patients. Age,hemoglobin level, and WPSS at diagnosis were independent predictive factors for CsA response. Survival was longer in responder than in nonresponder CsA patients (p=0.06). Cyclosporin A induced hematologic response in >50% of patients with MDS aged <57 years, with Hb<8 g/dl and low WPSS at diagnosis.

  20. Childhood MDS

    Science.gov (United States)

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  1. New treatment strategies in myelodysplastic syndromes and acute myeloid leukemia : Hypomethylating agents and proteasome inhibitors

    NARCIS (Netherlands)

    van der Helm, Lidia Henrieke

    2016-01-01

    New treatment strategies in leukemia and myelodysplastic syndromes Treatment of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) is challenging, especially in the large group of patients older than 60 years. In these patients, results of standard chemotherapy are often disappointing

  2. Ozone Depletion by Hydrofluorocarbons

    Science.gov (United States)

    Hurwitz, M.; Fleming, E. L.; Newman, P. A.; Li, F.; Mlawer, E. J.; Cady-Pereira, K. E.; Bailey, R.

    2015-12-01

    Hydrofluorocarbons (HFCs) are second-generation replacements for the chlorofluorocarbons (CFCs), halons and other substances that caused the 'ozone hole'. Atmospheric concentrations of HFCs are projected to increase dramatically in the coming decades. Coupled chemistry-climate simulations forced by these projections show that HFCs will impact the global atmosphere in 2050. As strong radiative forcers, HFCs modulate atmospheric temperature, thereby changing ozone-destroying catalytic cycles and enhancing the stratospheric circulation. These changes lead to a weak depletion of stratospheric ozone. Sensitivity simulations with the NASA Goddard Space Flight Center (GSFC) 2D model show that HFC-125 is the most important contributor to atmospheric change in 2050, as compared with HFC-23, HFC-32, HFC-134a and HFC-143a. Incorporating the interactions between chemistry, radiation and dynamics, for a likely 2050 climate, ozone depletion potentials (ODPs) for HFCs range from 4.3x10-4 to 3.5x10-2; previously HFCs were assumed to have negligible ODPs since these species lack chlorine or bromine atoms. The ozone impacts of HFCs are further investigated with the Goddard Earth Observing System Chemistry-Climate Model (GEOSCCM). The GEOSCCM is a three-dimensional, fully coupled ocean-atmosphere model with interactive stratospheric chemistry. Sensitivity simulations in which CO2, CFC-11 and HCFC-22 are enhanced individually are used as proxies for the atmospheric response to the HFC concentrations expected by the mid-21st century. Sensitivity simulations provide quantitative estimates of the impacts of these greenhouse gases on global total ozone, and can be used to assess their effects on the recovery of Antarctic ozone.

  3. Transformation of myelodysplastic syndromes into acute myeloid leukemias

    Institute of Scientific and Technical Information of China (English)

    施均; 邵宗鸿; 刘鸿; 白洁; 曹燕然; 何广胜; 凃梅峰; 王秀丽; 郝玉书; 杨天楹; 杨崇礼

    2004-01-01

    Background Myelodysplastic syndromes (MDSs), also called preleukemias, are a group of myeloid hematopoietic malignant disorders. We studied the transformation of MDS into acute myeloid leukemia (AML).Methods Leukemic transformation in 151 patients with MDS was dynamically followed up. The clinical manifestation, peripheral blood and bone marrow condition, karyotypes, immunophenotypes, response to treatment, and prognosis of AML evolution from MDS (MDS-AML) were also observed.Results During the course of this study, over the past eight years and seven months, 21 (13.91%) of 151 MDS patients progressed to overt leukemia, with a median interval of 5 (1-23) months. There were no significant differences between rates of leukemic transformation in comparison with the refractory anemia (RA), RA with excess of blasts (RAEB), and RAEB in transformation (RAEB-t) patient groups. Transformation occurred either gradually or rapidly. There were five parameters positively correlated to leukemic transformation: under 40 years of age, pancytopenia of 3 lineages, more than 15% blasts in the bone marrow, at least two abnormal karyotypes, and treatment with combined chemotherapy. All of the 21 patients with leukemia suffered from MDS-AML, and most of them were M2, M4, or M5. Two (9.52%) MDS-AML patients developed extramedullary infiltration. Leukopenia was found in 47.62% of these patients. Two thirds of these patients, whose bone marrows were generally hypercellular, suffered from neutropenia. After developing AML, 8 (47.06%) patients developed abnormal karyotypes. High expression of immature myeloid antigens, including CD33 [(49.83±24.50)%], CD13 [(36.38±33.84)%], monocytic antigen CD14 [(38.50±24.60)%], and stem cell marker CD34 [(34.67±30.59)%], were found on bone marrow mononuclear cells from MDS-AML patients after leukemic transformation. In some cases, lymphoid antigens, such as CD5, CD7, CD9, and CD19, coexisted with myeloid antigens. A low complete remission rate (31

  4. A phase 1b/2b multicenter study of oral panobinostat plus azacitidine in adults with MDS, CMML or AML with ⩽30% blasts.

    Science.gov (United States)

    Garcia-Manero, G; Sekeres, M A; Egyed, M; Breccia, M; Graux, C; Cavenagh, J D; Salman, H; Illes, A; Fenaux, P; DeAngelo, D J; Stauder, R; Yee, K; Zhu, N; Lee, J-H; Valcarcel, D; MacWhannell, A; Borbenyi, Z; Gazi, L; Acharyya, S; Ide, S; Marker, M; Ottmann, O G

    2017-05-26

    Treatment with azacitidine (AZA), a demethylating agent, prolonged overall survival (OS) vs conventional care in patients with higher-risk myelodysplastic syndromes (MDS). As median survival with monotherapy is <2 years, novel agents are needed to improve outcomes. This phase 1b/2b trial (n=113) was designed to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of panobinostat (PAN)+AZA (phase 1b) and evaluate the early efficacy and safety of PAN+AZA vs AZA monotherapy (phase 2b) in patients with higher-risk MDS, chronic myelomonocytic leukemia or oligoblastic acute myeloid leukemia with <30% blasts. The MTD was not reached; the RP2D was PAN 30 mg plus AZA 75 mg/m(2). More patients receiving PAN+AZA achieved a composite complete response ([CR)+morphologic CR with incomplete blood count+bone marrow CR (27.5% (95% CI, 14.6-43.9%)) vs AZA (14.3% (5.4-28.5%)). However, no significant difference was observed in the 1-year OS rate (PAN+AZA, 60% (50-80%); AZA, 70% (50-80%)) or time to progression (PAN+AZA, 70% (40-90%); AZA, 70% (40-80%)). More grade 3/4 adverse events (97.4 vs 81.0%) and on-treatment deaths (13.2 vs 4.8%) occurred with PAN+AZA. Further dose or schedule optimization may improve the risk/benefit profile of this regimen.Leukemia advance online publication, 14 July 2017; doi:10.1038/leu.2017.159.

  5. Functional Improvement Among Short-Stay Nursing Home Residents in the MDS 3.0

    Science.gov (United States)

    Wysocki, Andrea; Thomas, Kali S.; Mor, Vincent

    2015-01-01

    Objectives To examine the completeness of the activities of daily living (ADL) items on admission and discharge assessments and the improvement in ADL performance among short-stay residents in the newly adopted Minimum Data Set (MDS) 3.0. Design Retrospective analysis of MDS admission and discharge assessments. Setting Nursing homes from July 1, 2011, to June 30, 2012. Participants New nursing home residents admitted from acute hospitals with corresponding admission and discharge assessments between July 1, 2011, and June 30, 2012, who had a length of stay of 100 days or less. Measurements ADL self-performance items, including bed mobility, transfer, walking in room, walking in corridor, locomotion on unit, locomotion off unit, dressing, eating, toilet use, and personal hygiene, at admission and discharge. Results The ADL self-performance items are complete at both admission and discharge, with less than 1% missing for any item. More than 60% of residents improved over the course of their post-acute stay. New short-stay nursing home residents with conditions such as cognitive impairment, delirium, dementia, heart failure, and stroke showed less improvement in ADL performance during their stay. Conclusion The discharge assessment data in the MDS 3.0 provide new information to researchers and providers to examine and track ADL performance. Nursing homes can identify and track patients who require more intensive therapies or targeted interventions to achieve functional improvement during their stay. Future research can examine facility-level measures to better understand how ADL improvement varies across facilities. PMID:25659622

  6. Cytokine expression patterns and mesenchymal stem cell karyotypes from the bone marrow microenvironment of patients with myelodysplastic syndromes

    Energy Technology Data Exchange (ETDEWEB)

    Xiong, H.; Yang, X.Y.; Han, J.; Wang, Q.; Zou, Z.L. [Department of Hematology, Shanghai Clinical Research Center, Chinese Academy of Sciences, Shanghai Xuhui District Central Hospital, Shanghai (China)

    2015-01-20

    The purpose of this study was to explore cytokine expression patterns and cytogenetic abnormalities of mesenchymal stem cells (MSCs) from the bone marrow microenvironment of Chinese patients with myelodysplastic syndromes (MDS). Bone marrow samples were obtained from 30 cases of MDS (MDS group) and 30 healthy donors (control group). The expression pattern of cytokines was detected by customized protein array. The karyotypes of MSCs were analyzed using fluorescence in situ hybridization. Compared with the control group, leukemia inhibitory factor, stem cell factor (SCF), stromal cell-derived factor (SDF-1), bone morphogenetic protein 4, hematopoietic stem cell (HSC) stimulating factor, and transforming growth factor-β in the MDS group were significantly downregulated (P<0.05), while interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and programmed death ligand (B7-H1) were significantly upregulated (P<0.05). For chromosome abnormality analysis, the detection rate of abnormal karyotypes (+8, -8, -20, 20q-, -Y, -7, 5q-) was 30% in the MDS group and 0% in the control group. In conclusion, the up- and downregulated expression of these cytokines might play a key role in the pathogenesis of MDS. Among them, SCF and SDF-1 may play roles in the apoptosis of HSCs in MDS; and IFN-γ, TNF-α, and B7-H1 may be associated with apoptosis of bone marrow cells in MDS. In addition, the abnormal karyotypes might be actively involved in the pathogenesis of MDS. Further studies are required to determine the role of abnormal karyotypes in the occurrence and development of MDS.

  7. The DVB Channel Coding Application Using the DSP Development Board MDS TM-13 IREF

    Directory of Open Access Journals (Sweden)

    M. Slanina

    2004-12-01

    Full Text Available The paper deals with the implementation of the channel codingaccording to DVB standard on DSP development board MDS TM-13 IREF andPC. The board is based on Philips Nexperia media processor andintegrates hardware video ADC and DAC. The program libraries featuresused for MPEG based video compression are outlined and then thealgorithms of channel decoding (FEC protection against errors arepresented including the flowchart diagrams. The paper presents thepartial hardware implementation of the simulation system that coversselected phenomena of DVB baseband processing and it is used for realtime interactive demonstration of error protection influence ontransmitted digital video in laboratory and education.

  8. Cryptic splicing events in the iron transporter ABCB7 and other key target genes in SF3B1-mutant myelodysplastic syndromes.

    Science.gov (United States)

    Dolatshad, H; Pellagatti, A; Liberante, F G; Llorian, M; Repapi, E; Steeples, V; Roy, S; Scifo, L; Armstrong, R N; Shaw, J; Yip, B H; Killick, S; Kušec, R; Taylor, S; Mills, K I; Savage, K I; Smith, C W J; Boultwood, J

    2016-12-01

    The splicing factor SF3B1 is the most frequently mutated gene in myelodysplastic syndromes (MDS), and is strongly associated with the presence of ring sideroblasts (RS). We have performed a systematic analysis of cryptic splicing abnormalities from RNA sequencing data on hematopoietic stem cells (HSCs) of SF3B1-mutant MDS cases with RS. Aberrant splicing events in many downstream target genes were identified and cryptic 3' splice site usage was a frequent event in SF3B1-mutant MDS. The iron transporter ABCB7 is a well-recognized candidate gene showing marked downregulation in MDS with RS. Our analysis unveiled aberrant ABCB7 splicing, due to usage of an alternative 3' splice site in MDS patient samples, giving rise to a premature termination codon in the ABCB7 mRNA. Treatment of cultured SF3B1-mutant MDS erythroblasts and a CRISPR/Cas9-generated SF3B1-mutant cell line with the nonsense-mediated decay (NMD) inhibitor cycloheximide showed that the aberrantly spliced ABCB7 transcript is targeted by NMD. We describe cryptic splicing events in the HSCs of SF3B1-mutant MDS, and our data support a model in which NMD-induced downregulation of the iron exporter ABCB7 mRNA transcript resulting from aberrant splicing caused by mutant SF3B1 underlies the increased mitochondrial iron accumulation found in MDS patients with RS.

  9. Genome-wide profiling of methylation identifies novel targets with aberrant hypermethylation and reduced expression in low-risk myelodysplastic syndromes.

    Science.gov (United States)

    del Rey, M; O'Hagan, K; Dellett, M; Aibar, S; Colyer, H A A; Alonso, M E; Díez-Campelo, M; Armstrong, R N; Sharpe, D J; Gutiérrez, N C; García, J L; De Las Rivas, J; Mills, K I; Hernández-Rivas, J M

    2013-03-01

    Gene expression profiling signatures may be used to classify the subtypes of Myelodysplastic syndrome (MDS) patients. However, there are few reports on the global methylation status in MDS. The integration of genome-wide epigenetic regulatory marks with gene expression levels would provide additional information regarding the biological differences between MDS and healthy controls. Gene expression and methylation status were measured using high-density microarrays. A total of 552 differentially methylated CpG loci were identified as being present in low-risk MDS; hypermethylated genes were more frequent than hypomethylated genes. In addition, mRNA expression profiling identified 1005 genes that significantly differed between low-risk MDS and the control group. Integrative analysis of the epigenetic and expression profiles revealed that 66.7% of the hypermethylated genes were underexpressed in low-risk MDS cases. Gene network analysis revealed molecular mechanisms associated with the low-risk MDS group, including altered apoptosis pathways. The two key apoptotic genes BCL2 and ETS1 were identified as silenced genes. In addition, the immune response and micro RNA biogenesis were affected by the hypermethylation and underexpression of IL27RA and DICER1. Our integrative analysis revealed that aberrant epigenetic regulation is a hallmark of low-risk MDS patients and could have a central role in these diseases.

  10. Depleted zinc: Properties, application, production.

    Science.gov (United States)

    Borisevich, V D; Pavlov, A V; Okhotina, I A

    2009-01-01

    The addition of ZnO, depleted in the Zn-64 isotope, to the water of boiling water nuclear reactors lessens the accumulation of Co-60 on the reactor interior surfaces, reduces radioactive wastes and increases the reactor service-life because of the inhibitory action of zinc on inter-granular stress corrosion cracking. To the same effect depleted zinc in the form of acetate dihydrate is used in pressurized water reactors. Gas centrifuge isotope separation method is applied for production of depleted zinc on the industrial scale. More than 20 years of depleted zinc application history demonstrates its benefits for reduction of NPP personnel radiation exposure and combating construction materials corrosion.

  11. Myelodysplastic Syndromes and Iron Chelation Therapy

    Science.gov (United States)

    Angelucci, Emanuele; Urru, Silvana Anna Maria; Pilo, Federica; Piperno, Alberto

    2017-01-01

    Over recent decades we have been fortunate to witness the advent of new technologies and of an expanded knowledge and application of chelation therapies to the benefit of patients with iron overload. However, extrapolation of learnings from thalassemia to the myelodysplastic syndromes (MDS) has resulted in a fragmented and uncoordinated clinical evidence base. We’re therefore forced to change our understanding of MDS, looking with other eyes to observational studies that inform us about the relationship between iron and tissue damage in these subjects. The available evidence suggests that iron accumulation is prognostically significant in MDS, but levels of accumulation historically associated with organ damage (based on data generated in the thalassemias) are infrequent. Emerging experimental data have provided some insight into this paradox, as our understanding of iron-induced tissue damage has evolved from a process of progressive bulking of organs through high-volumes iron deposition, to one of ‘toxic’ damage inflicted through multiple cellular pathways. Damage from iron may, therefore, occur prior to reaching reference thresholds, and similarly, chelation may be of benefit before overt iron overload is seen. In this review, we revisit the scientific and clinical evidence for iron overload in MDS to better characterize the iron overload phenotype in these patients, which differs from the classical transfusional and non-transfusional iron overload syndrome. We hope this will provide a conceptual framework to better understand the complex associations between anemia, iron and clinical outcomes, to accelerate progress in this area. PMID:28293409

  12. Classification of Multiple Chinese Liquors by Means of a QCM-based E-Nose and MDS-SVM Classifier.

    Science.gov (United States)

    Li, Qiang; Gu, Yu; Jia, Jing

    2017-01-30

    Chinese liquors are internationally well-known fermentative alcoholic beverages. They have unique flavors attributable to the use of various bacteria and fungi, raw materials, and production processes. Developing a novel, rapid, and reliable method to identify multiple Chinese liquors is of positive significance. This paper presents a pattern recognition system for classifying ten brands of Chinese liquors based on multidimensional scaling (MDS) and support vector machine (SVM) algorithms in a quartz crystal microbalance (QCM)-based electronic nose (e-nose) we designed. We evaluated the comprehensive performance of the MDS-SVM classifier that predicted all ten brands of Chinese liquors individually. The prediction accuracy (98.3%) showed superior performance of the MDS-SVM classifier over the back-propagation artificial neural network (BP-ANN) classifier (93.3%) and moving average-linear discriminant analysis (MA-LDA) classifier (87.6%). The MDS-SVM classifier has reasonable reliability, good fitting and prediction (generalization) performance in classification of the Chinese liquors. Taking both application of the e-nose and validation of the MDS-SVM classifier into account, we have thus created a useful method for the classification of multiple Chinese liquors.

  13. Classification of Multiple Chinese Liquors by Means of a QCM-based E-Nose and MDS-SVM Classifier

    Directory of Open Access Journals (Sweden)

    Qiang Li

    2017-01-01

    Full Text Available Chinese liquors are internationally well-known fermentative alcoholic beverages. They have unique flavors attributable to the use of various bacteria and fungi, raw materials, and production processes. Developing a novel, rapid, and reliable method to identify multiple Chinese liquors is of positive significance. This paper presents a pattern recognition system for classifying ten brands of Chinese liquors based on multidimensional scaling (MDS and support vector machine (SVM algorithms in a quartz crystal microbalance (QCM-based electronic nose (e-nose we designed. We evaluated the comprehensive performance of the MDS-SVM classifier that predicted all ten brands of Chinese liquors individually. The prediction accuracy (98.3% showed superior performance of the MDS-SVM classifier over the back-propagation artificial neural network (BP-ANN classifier (93.3% and moving average-linear discriminant analysis (MA-LDA classifier (87.6%. The MDS-SVM classifier has reasonable reliability, good fitting and prediction (generalization performance in classification of the Chinese liquors. Taking both application of the e-nose and validation of the MDS-SVM classifier into account, we have thus created a useful method for the classification of multiple Chinese liquors.

  14. Survival benefits with transplantation in secondary AML evolving from myelodysplastic syndrome with hypomethylating treatment failure.

    Science.gov (United States)

    Shin, S-H; Yahng, S-A; Yoon, J-H; Lee, S-E; Cho, B-S; Eom, K-S; Lee, S; Min, C-K; Kim, H-J; Cho, S-G; Kim, D-W; Lee, J-W; Min, W-S; Park, C-W; Kim, Y-J

    2013-05-01

    The prognosis for patients with myelodysplastic syndrome with hypomethylating treatment failure (MDS-HTF) has been known to be poor. However, the clinical outcomes and optimal treatment options for secondary AML evolving from MDS-HTF (sAML/MDS-HTF) are not well known. This retrospective analysis was conducted to evaluate the clinical outcomes and influences of treatment options on survival in 46 consecutive patients with sAML/MDS-HTF. The median OS rates were 1.4 months in the best supportive care group (n=15) and 9.4 months in the active treatment group (n=31). One-year OS rates were 13.3% and 36.8%, respectively (P=0.001). Active treatment (PHTF if the patient is medically fit.

  15. Impact of Nagasaki atomic bomb exposure on myelodysplastic syndrome patients who are treated with azacitidine.

    Science.gov (United States)

    Jo, Tatsuro; Horio, Kensuke; Shigematsu, Kazuto

    2015-05-01

    High-dose radiation exposure greatly increases the risk of myelodysplastic syndromes (MDS), however the clinical characteristics of MDS among atomic bomb survivors have not been thoroughly investigated to date. We designed this study to identify these characteristics. We retrospectively evaluated data from 13 atomic bomb survivors with MDS and 15 elderly patients with de novo MDS who were diagnosed between April 2011 and April 2013 at the Nagasaki Genbaku Hospital. All patients were treated with azacitidine (AZA; a hypomethylating agent) and overall survival rates were estimated. No clear difference was observed in the clinical response to AZA between the two groups. However, atomic bomb survivors had a survival disadvantage, independent of their karyotype. Minute genetic alterations caused by exposure to atomic radiation can adversely affect the response to AZA, even 66 years after the exposure. Further studies are required to clarify the mechanisms underlying this phenomenon. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  16. Splicing factor gene mutations in the myelodysplastic syndromes: impact on disease phenotype and therapeutic applications.

    Science.gov (United States)

    Pellagatti, Andrea; Boultwood, Jacqueline

    2017-01-01

    Splicing factor gene mutations are the most frequent mutations found in patients with the myeloid malignancy myelodysplastic syndrome (MDS), suggesting that spliceosomal dysfunction plays a major role in disease pathogenesis. The aberrantly spliced target genes and deregulated cellular pathways associated with the commonly mutated splicing factor genes in MDS (SF3B1, SRSF2 and U2AF1) are being identified, illuminating the molecular mechanisms underlying MDS. Emerging data from mouse modeling studies indicate that the presence of splicing factor gene mutations can lead to bone marrow hematopoietic stem/myeloid progenitor cell expansion, impaired hematopoiesis and dysplastic differentiation that are hallmarks of MDS. Importantly, recent evidence suggests that spliceosome inhibitors and splicing modulators may have therapeutic value in the treatment of splicing factor mutant myeloid malignancies.

  17. 骨髓小粒在再生障碍性贫血和低增生骨髓增生异常综合征诊断和鉴别诊断中的意义%The significance of examination of marrow parvule in diagnosis and differential diagnosis in aregenerative anemia and hypomyeloplastic MDS

    Institute of Scientific and Technical Information of China (English)

    周格琛

    2013-01-01

    目的 探讨骨髓小粒在再生障碍性贫血(AA)和低增生骨髓增生异常综合征(MDS)的诊断和鉴别诊断中的意义.方法 对已明确诊断的30例AA和6例低增生MDS的骨髓小粒进行回顾性分析.结果 AA组的骨髓小粒中非造血细胞比率显著高于低增生MDS组(P<0.01),后者的原粒+早幼粒细胞比率高于前者(P<0.05),并有病态造血.结论 骨髓小粒分析对AA和低增生MDS的诊断与鉴别诊断有重要的参考价值.%Objective To explore the significance of examination of marrow parvules in diagnosis and differential diagnosis between are-generative anemia ( AA ) and myelodysplastic syndrome ( MDS ) with hypoplasia. Methods The data of examination of marrow parvules in 30 cases of AA and 6 cases of MDS with hypoplasia were retrospectively analyzed. Results The proportion of non - hematopoietic cells in marrow parvules of AA group was obviously higher than that of hypomyeloplastic MDS group ( P <0.01 ). The proportion of myeloblasts and promyelocytes in the latter was obviously higher than that of the former ( P < 0.05 ), moreover, dyshematopoiesis was appeared in the latter. Conclusion The analysis of marrow parvules has important reference value in diagnosis and differential diagnosis between AA and hypomyeloplastic MDS.

  18. Diagnosing PD-MCI by MDS Task Force criteria: how many and which neuropsychological tests?

    Science.gov (United States)

    Goldman, Jennifer G; Holden, Samantha; Ouyang, Bichun; Bernard, Bryan; Goetz, Christopher G; Stebbins, Glenn T

    2015-03-01

    The optimal properties of a comprehensive (level II) neuropsychological battery for determining Parkinson's disease mild cognitive impairment (PD-MCI) by Movement Disorder Society (MDS) Task Force criteria remain unresolved. Seventy-six nondemented PD patients underwent PD-MCI classification using a consensus diagnosis and level II criteria. We examined the optimal number of tests in each of the five designated cognitive domains, identified the best tests within each domain, and determined the best overall battery for PD-MCI level II diagnosis. A battery with two tests per domain provided a highly practical, robust diagnostic assessment. Level II testing with the two best tests and impairment defined as 2 standard deviations below norms was highly sensitive and specific for PD-MCI diagnosis. Our findings strongly support the MDS Task Force Level II testing recommendations, provide a framework for creating an optimal, efficient neuropsychological test battery for PD-MCI diagnosis, and offer specific test recommendations. © 2014 International Parkinson and Movement Disorder Society.

  19. Recovery of subsampled dimensions and configurations derived from napping data by MFA and MDS.

    Science.gov (United States)

    Nestrud, Michael A; Lawless, Harry T

    2011-05-01

    Napping is a multivariate sensory method in which participants physically place stimuli on a large sheet of paper and orient them so that the distance between pairs represents a measure of dissimilarity. The two-dimensional nature of the task may be a limitation to the ability of this and similar methodologies to recover information about complex stimuli. In the first investigation, eight simulated three-dimensional stimuli were created with two different levels for each attribute. Simulated napping experiments had groups of participants attend to two of the dimensions with different probabilities. Multiple factor analysis (an analytical multivariate statistical procedure that can be thought of as a principle components analysis on the individuals) and MDS-INDSCAL (a variation on multidimensional scaling that finds a common configuration through reducing a stress measure associated with lack of fit) recovered full dimensionality from these data, although MFA had trouble when attention was the most unbalanced. In the second experiment, a human napping experiment was designed using custom three-dimensional stimuli: shapes with two levels each of size, color, and shape attributes. This experiment confirmed the results of Experiment 1, as both MDS-INDSCAL and MFA analyses again recovered the full dimensionality of the stimuli.

  20. On Orbit Osteobiology Experiments: from "STROMA" to "MDS" -from in vitro to in vivo

    Science.gov (United States)

    Liu, Yi; Cancedda, Ranieri

    Spaceflight causes profound changes in the skeleton, in particular, in the weight-loading bones. Uncoupling of bone remodeling equilibrium between bone formation and resorption is con-sidered responsible for the microgravity-induced bone loss. These changes result in weak-ened and brittle bones prone to fracture on re-entry and in accelerated osteoporosis, making bone deterioration a major problem obstructing the prospects of long-duration manned space flight. Osteoblasts (bone forming cells) and osteocytes (bone resorption cells) are known to be mechano-sensors. Short-exposure of osteoblasts to simulated microgravity ensnarled cell adhe-sion and cytoskeleton. Also osteoblast precursors such as bone marrow stroma cells (BMSC) were shown to be sensitive to mechanical loading. We performed a series of STROMA space-flight experiments by culturing BMSC or co-culturing osteoblasts and osteoclast precursors in automated bioreactors on orbit. Genechip analysis revealed an inhibition of cell proliferation and an unexpected activation of nervous system development genes by spaceflight. To unravel effects of microgravity on genes governing bone mass, transgenic mice with a higher bone mass were flown to orbit inside the Mice Drawer System (MDS) payload. The MDS experiment was launched inside Shuttle Discovery in STS-128 on August 28 2009 at 23:58 EST, and returned to earth by Shuttle Atlantis in STS129 on November 27 2009 at 9:47 EST, marking it as the first long duration animal experiment on the International Space Station (ISS).

  1. Wormhole Detection Based on Ordinal MDS Using RTT in Wireless Sensor Network

    Directory of Open Access Journals (Sweden)

    Saswati Mukherjee

    2016-01-01

    Full Text Available In wireless communication, wormhole attack is a crucial threat that deteriorates the normal functionality of the network. Invasion of wormholes destroys the network topology completely. However, most of the existing solutions require special hardware or synchronized clock or long processing time to defend against long path wormhole attacks. In this work, we propose a wormhole detection method using range-based topology comparison that exploits the local neighbourhood subgraph. The Round Trip Time (RTT for each node pair is gathered to generate neighbour information. Then, the network is reconstructed by ordinal Multidimensional Scaling (MDS followed by a suspicion phase that enlists the suspected wormholes based on the spatial reconstruction. Iterative computation of MDS helps to visualize the topology changes and can localize the potential wormholes. Finally, a verification phase is used to remove falsely accused nodes and identify real adversaries. The novelty of our algorithm is that it can detect both short path and long path wormhole links. Extensive simulations are executed to demonstrate the efficacy of our approach compared to existing ones.

  2. Ego depletion impairs implicit learning.

    Science.gov (United States)

    Thompson, Kelsey R; Sanchez, Daniel J; Wesley, Abigail H; Reber, Paul J

    2014-01-01

    Implicit skill learning occurs incidentally and without conscious awareness of what is learned. However, the rate and effectiveness of learning may still be affected by decreased availability of central processing resources. Dual-task experiments have generally found impairments in implicit learning, however, these studies have also shown that certain characteristics of the secondary task (e.g., timing) can complicate the interpretation of these results. To avoid this problem, the current experiments used a novel method to impose resource constraints prior to engaging in skill learning. Ego depletion theory states that humans possess a limited store of cognitive resources that, when depleted, results in deficits in self-regulation and cognitive control. In a first experiment, we used a standard ego depletion manipulation prior to performance of the Serial Interception Sequence Learning (SISL) task. Depleted participants exhibited poorer test performance than did non-depleted controls, indicating that reducing available executive resources may adversely affect implicit sequence learning, expression of sequence knowledge, or both. In a second experiment, depletion was administered either prior to or after training. Participants who reported higher levels of depletion before or after training again showed less sequence-specific knowledge on the post-training assessment. However, the results did not allow for clear separation of ego depletion effects on learning versus subsequent sequence-specific performance. These results indicate that performance on an implicitly learned sequence can be impaired by a reduction in executive resources, in spite of learning taking place outside of awareness and without conscious intent.

  3. Depletable resources and the economy.

    NARCIS (Netherlands)

    Heijman, W.J.M.

    1991-01-01

    The subject of this thesis is the depletion of scarce resources. The main question to be answered is how to avoid future resource crises. After dealing with the complex relation between nature and economics, three important concepts in relation with resource depletion are discussed: steady state, ti

  4. Teaching program for the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale: (MDS-UPDRS).

    Science.gov (United States)

    Goetz, Christopher G; Stebbins, Glenn T; Chmura, Teresa A; Fahn, Stanley; Poewe, Werner; Tanner, Caroline M

    2010-07-15

    To accompany the newly developed Movement Disorder Society revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS), we developed a teaching program. The DVD-based program covers the four parts of the scale with visual and verbal instructions for uniform application. For the motor section (Part III), all items except rigidity are shown with an example of each rating option (0-4) as agreed upon by a panel of experts. The rate of agreement for the selected samples was always significant, with Kendall's coefficient of concordance W ranging between 0.99 and 0.72. The teaching program also provides a full patient examination with rating answers provided and four full MDS-UPDRS cases for a Certificate Program exercise of Part III. This training program is in English, but as non-English official translations of the MDS-UPDRS are developed, the program can be potentially modified into different languages.

  5. Expanded and independent validation of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS).

    Science.gov (United States)

    Martinez-Martin, Pablo; Rodriguez-Blazquez, Carmen; Alvarez-Sanchez, Mario; Arakaki, Tomoko; Bergareche-Yarza, Alberto; Chade, Anabel; Garretto, Nelida; Gershanik, Oscar; Kurtis, Monica M; Martinez-Castrillo, Juan Carlos; Mendoza-Rodriguez, Amelia; Moore, Henry P; Rodriguez-Violante, Mayela; Singer, Carlos; Tilley, Barbara C; Huang, Jing; Stebbins, Glenn T; Goetz, Christopher G

    2013-01-01

    The Movement Disorder Society-UPDRS (MDS-UPDRS) was published in 2008, showing satisfactory clinimetric results and has been proposed as the official benchmark scale for Parkinson's disease. The present study, based on the official MDS-UPDRS Spanish version, performed the first independent testing of the scale and adds information on its clinimetric properties. The cross-culturally adapted MDS-UPDRS Spanish version showed a comparative fit index ≥ 0.90 for each part (I-IV) relative to the English-language version and was accepted as the Official MDS-UPDRS Spanish version. Data from this scale, applied with other assessments to Spanish-speaking Parkinson's disease patients in five countries, were analyzed for an independent and complementary clinimetric evaluation. In total, 435 patients were included. Missing data were negligible and moderate floor effect (30 %) was found for Part IV. Cronbach's α index ranged between 0.79 and 0.93 and only five items did not reach the 0.30 threshold value of item-total correlation. Test-retest reliability was adequate with only two sub-scores of the item 3.17, Rest tremor amplitude, reaching κ values lower than 0.60. The intraclass correlation coefficient was higher than 0.85 for the total score of each part. Correlation of the MDS-UPDRS parts with other measures for related constructs was high (≥ 0.60) and the standard error of measurement lower than one-third baseline standard deviation for all subscales. Results confirm those of the original study and add information on scale reliability, construct validity, and precision. The MDS-UPDRS Spanish version shows satisfactory clinimetric characteristics.

  6. Research progress of myelodysplastic syndrome%骨髓增生异常综合征研究进展

    Institute of Scientific and Technical Information of China (English)

    何广胜

    2014-01-01

    骨髓增生异常综合征(myelodysplastic syndromes,MDS)亚克隆在低危组就达到很高比例,驱动基因导致疾病进展.RNA剪接子复合物基因突变与MDS有较高相对特异性,并与疾病临床表现和顸后相关.MDS的难治性血胞减少伴单系病态造血(refractory cytopenia with unilineage dysplasia,RCUD)中各亚型,MDS-U(MDS-unclassified,MDS-U)和MDS-RCMD(MDS-refractory cytopenia with multilineage dysplasia,MDS-RCMD)之间,病态造血、生存率和转白率无显著差异.IPSS的修订版和合并症指数更好地对MDS患者的预后和机体状态做出评价.规则去铁治疗可能改善MDS患者生活质量、生存期.促红细胞生成素早期失败者转白率和生存率均差.去甲化药物中阿扎胞苷可能疗效更佳.

  7. Higher Risk Myelodysplastic Syndromes in Patients with Well-Controlled HIV Infection: Clinical Features, Treatment, and Outcome

    Directory of Open Access Journals (Sweden)

    Bradley T. Williamson

    2016-01-01

    Full Text Available Introduction. In advanced HIV prior to combination antiretroviral therapy (ART, dysplastic marrow changes occurred and resolved with ART. Few reports of myelodysplastic syndromes (MDS in well-controlled HIV exist and management is undefined. Methods. Patients with well-controlled HIV and higher risk MDS were identified; characteristics, treatment, and outcomes were reviewed. Results. Of 292 MDS patients since 1996, 1 (0.3% was HIV-positive. A 56-year-old woman presented with cytopenias. CD4 was 1310 cells/mL and HIV viral load <40 copies/mL. Bone marrow biopsy showed RCMD and karyotype included del(5q and del(7q; IPSS was intermediate-2 risk. She received azacitidine at 75% dose. Cycle 2, at full dose, was complicated by marrow aplasia and possible AML; she elected palliation. Three additional HIV patients with higher risk MDS, aged 56–64, were identified from the literature. All had deletions involving chromosomes 5 and 7. MDS treatment of 2 was not reported and one received palliation; all died of AML. Conclusion. Four higher risk MDS in well-controlled HIV were below the median age of diagnosis for HIV-negative patients; all had adverse karyotype. This is the first report of an HIV patient receiving MDS treatment with azacitidine. Cytopenias were profound and dosing in HIV patients should be considered with caution.

  8. Clonal evolution in myelodysplastic syndromes

    Science.gov (United States)

    da Silva-Coelho, Pedro; Kroeze, Leonie I.; Yoshida, Kenichi; Koorenhof-Scheele, Theresia N.; Knops, Ruth; van de Locht, Louis T.; de Graaf, Aniek O.; Massop, Marion; Sandmann, Sarah; Dugas, Martin; Stevens-Kroef, Marian J.; Cermak, Jaroslav; Shiraishi, Yuichi; Chiba, Kenichi; Tanaka, Hiroko; Miyano, Satoru; de Witte, Theo; Blijlevens, Nicole M. A.; Muus, Petra; Huls, Gerwin; van der Reijden, Bert A.; Ogawa, Seishi; Jansen, Joop H.

    2017-01-01

    Cancer development is a dynamic process during which the successive accumulation of mutations results in cells with increasingly malignant characteristics. Here, we show the clonal evolution pattern in myelodysplastic syndrome (MDS) patients receiving supportive care, with or without lenalidomide (follow-up 2.5–11 years). Whole-exome and targeted deep sequencing at multiple time points during the disease course reveals that both linear and branched evolutionary patterns occur with and without disease-modifying treatment. The application of disease-modifying therapy may create an evolutionary bottleneck after which more complex MDS, but also unrelated clones of haematopoietic cells, may emerge. In addition, subclones that acquired an additional mutation associated with treatment resistance (TP53) or disease progression (NRAS, KRAS) may be detected months before clinical changes become apparent. Monitoring the genetic landscape during the disease may help to guide treatment decisions. PMID:28429724

  9. Testing fully depleted CCD

    Science.gov (United States)

    Casas, Ricard; Cardiel-Sas, Laia; Castander, Francisco J.; Jiménez, Jorge; de Vicente, Juan

    2014-08-01

    The focal plane of the PAU camera is composed of eighteen 2K x 4K CCDs. These devices, plus four spares, were provided by the Japanese company Hamamatsu Photonics K.K. with type no. S10892-04(X). These detectors are 200 μm thick fully depleted and back illuminated with an n-type silicon base. They have been built with a specific coating to be sensitive in the range from 300 to 1,100 nm. Their square pixel size is 15 μm. The read-out system consists of a Monsoon controller (NOAO) and the panVIEW software package. The deafualt CCD read-out speed is 133 kpixel/s. This is the value used in the calibration process. Before installing these devices in the camera focal plane, they were characterized using the facilities of the ICE (CSIC- IEEC) and IFAE in the UAB Campus in Bellaterra (Barcelona, Catalonia, Spain). The basic tests performed for all CCDs were to obtain the photon transfer curve (PTC), the charge transfer efficiency (CTE) using X-rays and the EPER method, linearity, read-out noise, dark current, persistence, cosmetics and quantum efficiency. The X-rays images were also used for the analysis of the charge diffusion for different substrate voltages (VSUB). Regarding the cosmetics, and in addition to white and dark pixels, some patterns were also found. The first one, which appears in all devices, is the presence of half circles in the external edges. The origin of this pattern can be related to the assembly process. A second one appears in the dark images, and shows bright arcs connecting corners along the vertical axis of the CCD. This feature appears in all CCDs exactly in the same position so our guess is that the pattern is due to electrical fields. Finally, and just in two devices, there is a spot with wavelength dependence whose origin could be the result of a defectous coating process.

  10. Real-world analysis of the Celgene Global Drug Safety database: early discontinuation of lenalidomide in patients with myelodysplastic syndromes due to non-serious rash

    OpenAIRE

    Weiss L; Gary D; Swern AS; Freeman J.; Sugrue MM

    2015-01-01

    Lilia Weiss,1 Dianna Gary,1 Arlene S Swern,2 John Freeman,1 Mary M Sugrue3 1Global Drug Safety, Celgene Corporation, Summit, 2Biometrics, Celgene Corporation, Berkeley Heights, 3Medical Affairs, Celgene Corporation, Summit, NJ, USA Background: Lenalidomide is approved for treating transfusion-dependent anemia due to lower-risk del(5q) myelodysplastic syndromes (MDS). In clinical trials, rash was common, although severe rash was infrequent. To examine rash in patients with MDS treated with l...

  11. Differential diagnosis of myelodysplastic syndrome and aplastic anemia using MRI

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Seung Eun; Park, Jung Mi; Lee, Jae Mun; Kim, Ki Tae; Kim, Dong Wook; Kim, Chun Choo; Kim, Chun Yul; Shinn, Kyung Sub [Catholic University Medical College, Seoul (Korea, Republic of)

    1995-04-15

    To assess the patterns of myelodysplastic syndrome (MDS) and aplastic anemia (AA) on MRI of the spinal bone marrow and to find the differential points between the two groups. Fourteen patients with MDS (n=7) and AA (n=7) were studied using magnetic resonance imaging. Sagittal images from the lower thoracic and lumbar vertebral marrow were evaluated on T1-weighted and STIR images. Five distinct patterns of signal intensity of the T1-weighted and STIR images were classified. T1 and T2 relaxation times and T1 marrow/fat signal intensity ratio were measured and analyzed (t-test). The cellularity of bone marrow was evaluated on histologic slides. MDS showed homogeneously low signal intensity on T1WI and high signal intensity on STIR image, indicating hypercellular marrow, whereas AA showed relative high signal intensity on T1WI and low signal intensity on STIR image, representing fatty marrow. T1 and T2 relaxation time (T1 for MDS=750.26 msec {+-} 177.50, T1 for AA=413.21 msec {+-} 167.39 ({rho} < 0.000), T2 for MDS=91.86 msec {+-} 14.16, T2 for AA=81.44 msec {+-} 15.31 ({rho} < 0.001) and T1 marrow/fat signal intensity ratio (0.22 {+-} 0.048 in MDS, 0.30 {+-} 0.083 in AA ({rho} < 0.000) revealed statistically significant difference between the two groups. Although the marrow aspiration and needle biopsy are mandatory in hematologic disease for diagnosis, there are limited in assessing the change of total marrow mass. Therefore MRI of bone marrow might be useful in distinguishing MDS from AA because of its ability of representation of total marrow mass.

  12. Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results.

    Science.gov (United States)

    Goetz, Christopher G; Tilley, Barbara C; Shaftman, Stephanie R; Stebbins, Glenn T; Fahn, Stanley; Martinez-Martin, Pablo; Poewe, Werner; Sampaio, Cristina; Stern, Matthew B; Dodel, Richard; Dubois, Bruno; Holloway, Robert; Jankovic, Joseph; Kulisevsky, Jaime; Lang, Anthony E; Lees, Andrew; Leurgans, Sue; LeWitt, Peter A; Nyenhuis, David; Olanow, C Warren; Rascol, Olivier; Schrag, Anette; Teresi, Jeanne A; van Hilten, Jacobus J; LaPelle, Nancy

    2008-11-15

    We present a clinimetric assessment of the Movement Disorder Society (MDS)-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS). The MDS-UDPRS Task Force revised and expanded the UPDRS using recommendations from a published critique. The MDS-UPDRS has four parts, namely, I: Non-motor Experiences of Daily Living; II: Motor Experiences of Daily Living; III: Motor Examination; IV: Motor Complications. Twenty questions are completed by the patient/caregiver. Item-specific instructions and an appendix of complementary additional scales are provided. Movement disorder specialists and study coordinators administered the UPDRS (55 items) and MDS-UPDRS (65 items) to 877 English speaking (78% non-Latino Caucasian) patients with Parkinson's disease from 39 sites. We compared the two scales using correlative techniques and factor analysis. The MDS-UPDRS showed high internal consistency (Cronbach's alpha = 0.79-0.93 across parts) and correlated with the original UPDRS (rho = 0.96). MDS-UPDRS across-part correlations ranged from 0.22 to 0.66. Reliable factor structures for each part were obtained (comparative fit index > 0.90 for each part), which support the use of sum scores for each part in preference to a total score of all parts. The combined clinimetric results of this study support the validity of the MDS-UPDRS for rating PD.

  13. Increased relative risk of myelodysplastic syndrome in atomic bomb survivors

    Energy Technology Data Exchange (ETDEWEB)

    Oda, Kenji [Hiroshima City Hospital (Japan); Kimura, Akiro; Matsuo, Tatsuki; Tomonaga, Masao; Kodama, Kazunori; Mabuchi, Kiyohiko

    1998-12-01

    It was investigated what blood disorders except leukemia increased the relative risk with dose dependency in atomic bomb survivors. Subjects were 217 patients of atomic bomb survivors in Hiroshima and Nagasaki, who had blood disorders except leukemia and died between 1950 and 1990. Their medical records were analyzed and their diagnoses were reevaluated. Sixteen cases were diagnosed as the aplastic anemia and 12 as the myelodysplastic syndrome (MDS). In the aplastic anemia, there was no correlation between the exposure dose and the mortality. In MDS, the excess relative risk (ERR)/bone marrow exposure dose of 1 Sv was very high (13.0). These results supports the hypothesis that MDS would be broken out by the clonal abnormality of the hematopoietic stem cell and radiation exposure could cause the appearance of the abnormal stem cell clone. (K.H.)

  14. Estimating view parameters from random projections for Tomography using spherical MDS

    Directory of Open Access Journals (Sweden)

    Murugappan Sundar

    2010-06-01

    Full Text Available Abstract Background During the past decade, the computed tomography has been successfully applied to various fields especially in medicine. The estimation of view angles for projections is necessary in some special applications of tomography, for example, the structuring of viruses using electron microscopy and the compensation of the patient's motion over long scanning period. Methods This work introduces a novel approach, based on the spherical multidimensional scaling (sMDS, which transforms the problem of the angle estimation to a sphere constrained embedding problem. The proposed approach views each projection as a high dimensional vector with dimensionality equal to the number of sampling points on the projection. By using SMDS, then each projection vector is embedded onto a 1D sphere which parameterizes the projection with respect to view angles in a globally consistent manner. The parameterized projections are used for the final reconstruction of the image through the inverse radon transform. The entire reconstruction process is non-iterative and computationally efficient. Results The effectiveness of the sMDS is verified with various experiments, including the evaluation of the reconstruction quality from different number of projections and resistance to different noise levels. The experimental results demonstrate the efficiency of the proposed method. Conclusion Our study provides an effective technique for the solution of 2D tomography with unknown acquisition view angles. The proposed method will be extended to three dimensional reconstructions in our future work. All materials, including source code and demos, are available on https://engineering.purdue.edu/PRECISE/SMDS.

  15. Analysis of local ionospheric variability based on SVD and MDS at low-latitude GNSS stations

    Science.gov (United States)

    Dabbakuti, J. R. K. Kumar; Devanaboyina, Venkata Ratnam; Kanchumarthi, S. Ramesh

    2016-06-01

    Investigation of ionospheric anomalies during equatorial and low latitude is of major concern for modeling and global navigation satellite system (GNSS) applications. Total electron content (TEC) varies with the ionospheric conditions, which will lead to the errors in the global positioning system (GPS) measurements. It is therefore a method that is necessary to characterize the ionospheric anomalies for satellite-based navigation systems. In this study, characterization of ionospheric variations based on the singular value decomposition (SVD) and classical multidimensional scaling (MDS) methods was studied. The yearly and daily variations are decomposed from the GPS-TEC, international reference ionosphere (IRI) 2007 and IRI 2012 models TEC over the three low-latitude GNSS stations located at Koneru Lakshmaiah University (KLU-Guntur), Hyderabad and Bangalore, respectively. From the results, it is found that there is a strong correlation between GPS-TEC and IRI models. The correlation coefficient for the first three singular values is more than 0.86. From this, it is possible to reconstruct more than 85 % of the variability contained in global GPS-derived VTEC data (for year 2013) by using only the first three modes. The semiannual variation has maximum value during March-April and September-October and has minimum value during June-July. It is observed that the annual variations have maximum value in summer and minimum value in winter, and the amplitudes decrease with increasing latitude. Further, opposite latitudinal asymmetry among annual and semiannual variations for three GNSS stations is noticed. SVD and MDS methods clearly show time-varying characteristics and the absence of the winter anomaly at low-latitude GNSS stations.

  16. Finding Gertrude: The Resident’s Voice in MDS 3.0

    Science.gov (United States)

    Wysocki, Andrea; Intrator, Orna; Mor, Vincent

    2014-01-01

    Purpose of the Study The new MDS 3.0 was designed to improve the assessment process by requiring nursing home (NH) staff to attempt to interview residents with scripted questions to assess subjective states such as pain, mood, and cognitive functioning. While the case has been made that resident self-report is important, it is unknown whether facilities are doing so in practice. We examined the frequency of attempts to interview residents in order to elucidate the types of residents able to be interviewed about their clinical conditions and facility characteristics related to the likelihood of attempt. Design and Methods Data come from MDS 3.0 annual assessments for 757,044 residents in 15,030 NHs during 2011–2012 and the 2011 Online Survey, Certification, and Reporting database. Hierarchical generalized linear models were conducted to test the association between resident and facility characteristics and the attempt rate of resident interview for three clinical domains (cognition, mood, and pain). Results Over 83% of long-stay residents attempted all three self-report clinical items. The rates of attempt for mood, cognition, and pain were 88%, 89%, 92%, respectively. Results from hierarchical generalized linear models suggest that certain resident characteristics are related to the likelihood of participating in interviews, in particular neither having a diagnosis of dementia nor cognitive impairment, exhibiting signs of delirium, nor a documented prognosis of six months or less to live. Residents in smaller, chain-affiliated nursing homes with fewer Medicare residents and fewer assessments per administrative nurse and registered nurse were more likely to attempt the resident interview items. Implications This paper documents the high rate of NH residents’ participation in interviews about their clinical states. Furthermore, we identify types of residents for whom additional investigation into ways to achieve higher rates of participation is required and

  17. Meeting report: Vienna 2008 Workshop of the German-Austrian Working Group for Studying Prognostic Factors in Myelodysplastic Syndromes.

    Science.gov (United States)

    Valent, Peter; Hofmann, Wolf-Karsten; Büsche, Guntram; Sotlar, Karl; Horny, Hans-Peter; Haase, Detlef; Haferlach, Torsten; Kern, Wolfgang; Bettelheim, Peter; Baumgartner, Christian; Sperr, Wolfgang R; Nösslinger, Thomas; Wimazal, Friedrich; Giagounidis, Aristoteles A; Lübbert, Michael; Krieger, Otto; Kolb, Hans-Jochem; Stauder, Reinhard; Pfeilstöcker, Michael; Gattermann, Norbert; Fonatsch, Christa; Aul, Carlo; Germing, Ulrich

    2009-07-01

    Criteria, scoring systems, and treatment algorithms for myelodysplastic syndromes (MDS) have been updated repeatedly in recent years. This apparently results from increased awareness and early recognition of the disease, an increasing number of new diagnostic and prognostic markers and tools, and new therapeutic options that may change the course and thus prognosis in MDS. To address these challenges and to create useful new diagnostic and prognostic parameters and scores, the German-Austrian Working Group for Studying Prognostic Factors in MDS was established in 2003 and later was extended to centers in Switzerland (D-A-CH group). In addition, the group cooperates with the European LeukemiaNet, the MDS Foundation, and other national and international working groups in order to improve diagnosis and prognostication. The current article represents a meeting report from the latest workshop organized by the group in Vienna in October 2008.

  18. Subsequent primary malignancies and acute myelogenous leukemia transformation among myelodysplastic syndrome patients treated with or without lenalidomide.

    Science.gov (United States)

    Rollison, Dana E; Shain, Kenneth H; Lee, Ji-Hyun; Hampras, Shalaka S; Fulp, William; Fisher, Kate; Al Ali, Najla H; Padron, Eric; Lancet, Jeffrey; Xu, Qiang; Olesnyckyj, Martha; Kenvin, Laurie; Knight, Robert; Dalton, William; List, Alan; Komrokji, Rami S

    2016-07-01

    The few studies that have examined rates of acute myeloid leukemia (AML) transformation in lenalidomide-treated myelodysplastic syndrome (MDS) patients have been limited to deletion 5q MDS. The association between lenalidomide and subsequent primary malignancies (SPMs) in MDS patients has not been evaluated previously. We conducted a retrospective cohort study to evaluate the risk of both SPM and AML in association with lenalidomide. A cohort of MDS patients (n = 1248) treated between 2004 and 2012 at Moffitt Cancer Center were identified, and incident cases of SPM and AML transformation were ascertained. Using a nested case-control design, MDS controls were 1:1 matched to SPM (n = 41) and AML (n = 150) cases, on age and date of MDS diagnosis, gender, follow-up time, IPSS, and del (5q). Associations between lenalidomide and (1) SPM incidence and (2) AML transformation were estimated with hazards ratios (HR) and 95% confidence intervals (CIs) in the cohort and odds ratios (OR) in the case-control analysis. SPM incidence did not differ significantly between cohort MDS patients treated with (0.7 per 100 person-years) or without lenalidomide (1.4 per 100 person-years) (HR = 1.04, 95% CI = 0.40-2.74), whereas a significantly reduced SPM risk was observed in the case-control sample (OR = 0.03, 95% CI = Lenalidomide was not associated with AML transformation in the cohort analysis (HR = 0.75, 95% CI = 0.44-1.27) or in the case-control analyses (OR = 1.16, 95% CI = 0.52-2.56), after adjustment for potential confounders. Lenalidomide was not associated with increased risk of SPM or AML transformation in a large cohort of MDS patients mostly including nondeletion 5q MDS.

  19. Diagnostic Utility of Flow Cytometry in Myelodysplastic Syndromes

    Science.gov (United States)

    Della Porta, Matteo G.; Picone, Cristina

    2017-01-01

    The pathological hallmark of myelodysplastic syndromes (MDS) is marrow dysplasia, which represents the basis of the WHO classification of these disorders. This classification provides clinicians with a useful tool for defining the different subtypes of MDS and individual prognosis. The WHO proposal has raised some concern regarding minimal diagnostic criteria particularly in patients with normal karyotype without robust morphological markers of dysplasia (such as ring sideroblasts or excess of blasts). Therefore, there is clearly need to refine the accuracy to detect marrow dysplasia. Flow cytometry (FCM) immunophenotyping has been proposed as a tool to improve the evaluation of marrow dysplasia. The rationale for the application of FCM in the diagnostic work up of MDS is that immunophenotyping is an accurate method for quantitative and qualitative evaluation of hematopoietic cells and that MDS have been found to have abnormal expression of several cellular antigens. To become applicable in clinical practice, FCM analysis should be based on parameters with sufficient specificity and sensitivity, data should be reproducible between different operators, and the results should be easily understood by clinicians. In this review, we discuss the most relevant progresses in detection of marrow dysplasia by FCM in MDS

  20. Hematological Changes Mimicking Myelodysplastic Syndrome Following Treatment for Osteosarcoma.

    Science.gov (United States)

    Løhmann, Ditte J A; Hasle, Henrik

    2015-04-01

    Therapy-related myelodysplastic syndrome/acute myeloid leukemia (t-MDS/AML) is a feared long-term complication of pediatric cancer. Few osteosarcoma patients develop t-MDS/AML, but the frequency of hematological abnormalities after therapy is unknown. We reviewed biochemistry from osteosarcoma patients up to 3 years posttreatment. All children diagnosed with osteosarcoma at our department from 2006 to 2012 without relapse 1 month posttherapy were included (n=14). Serial blood counts posttherapy were analyzed. The median increase of mean corpuscular volume (MCV) from baseline was 8 fL 6 months posttherapy and remained >5 throughout follow-up. All posttreatment levels of MCV were above 90 fL in 5 patients. Six months posttherapy, the median difference for platelets, white blood count, and absolute neutrophil count had decreased from baseline. They remained under baseline throughout follow-up. Hemoglobin remained stable. Ferritin level was associated with increased MCV. MDS with monosomy 7 was diagnosed in 1 patient. Hypoplastic refractory cytopenia was found in another patient showing spontaneous normalization of hematologic values. More than a third of patients treated for osteosarcoma developed hematological abnormalities mimicking early MDS, but only 1 developed t-MDS/AML. Close hematological monitoring of patients recovering from osteosarcoma is essential and it is worth noting that hematological abnormalities are frequent and may be transitory.

  1. EARLY DIAGNOSIS OF MYELODYSPLASTIC SYNDROMES USING CLONAL ANALYSES

    Institute of Scientific and Technical Information of China (English)

    钱军; 薛永权; 虞斐; 吴亚芳; 潘金兰; 陆定伟

    2002-01-01

    Objective: To study the value of clonal analysis to the early diagnosis of myelodysplastic syndrome (MDS). Methods: Four types of clonal analyses were performed on the bone marrow samples from 50 patients suspected of MDS: (1) Conventional Cytogenetics (CC) for clonal chromosomal abnormalities; (2) BrdU-Sister Chromatid Differentiation (BrdU-SCD) for cell cycle kinetics; (3) Fluorescence in Situ Hybridization (FISH) for trisomy 8; (4) Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) for N-ras mutation. Results: The diagnosis of forty-three patients was compatible with the FAB criteria for MDS. The other seven cases didn't meet the FAB criteria, with only one lineage of dyspoiesis or with no obvious dysplastic changes. Among these seven cases, two were morphologically diagnosed with suspicious refractory anemia, one with sideroblastic anemia, one with leukemoid reaction, one with hypercellular anemia and two with chronic aplastic anemia. Clonal analyses of the 7 patients showed that six cases had clonal karyotype abnormalities, four had prolonged cell cycle patterns, four had trisomy 8 of different proportions and one had mutation of the exon 1 of N-RAS. Thus, they were revaluated as MDS patients. Conclusion: The untypical MDS patients with one lineage dyspoiesis or without obvious dysplastic changes can be diagnosed early by combining multiple clonal analysis techniques such as CC, SCD, FISH and PCR-SSCR.

  2. "When the going gets tough, who keeps going?" Depletion sensitivity moderates the ego-depletion effect.

    Science.gov (United States)

    Salmon, Stefanie J; Adriaanse, Marieke A; De Vet, Emely; Fennis, Bob M; De Ridder, Denise T D

    2014-01-01

    Self-control relies on a limited resource that can get depleted, a phenomenon that has been labeled ego-depletion. We argue that individuals may differ in their sensitivity to depleting tasks, and that consequently some people deplete their self-control resource at a faster rate than others. In three studies, we assessed individual differences in depletion sensitivity, and demonstrate that depletion sensitivity moderates ego-depletion effects. The Depletion Sensitivity Scale (DSS) was employed to assess depletion sensitivity. Study 1 employs the DSS to demonstrate that individual differences in sensitivity to ego-depletion exist. Study 2 shows moderate correlations of depletion sensitivity with related self-control concepts, indicating that these scales measure conceptually distinct constructs. Study 3 demonstrates that depletion sensitivity moderates the ego-depletion effect. Specifically, participants who are sensitive to depletion performed worse on a second self-control task, indicating a stronger ego-depletion effect, compared to participants less sensitive to depletion.

  3. Significant association between polymorphism of the erythropoietin gene promoter and myelodysplastic syndrome

    Directory of Open Access Journals (Sweden)

    O'Brien Susan

    2010-11-01

    Full Text Available Abstract Background Myelodysplastic syndrome (MDS may be induced by certain mutagenic environmental or chemotherapeutic toxins; however, the role of susceptibility genes remains unclear. The G/G genotype of the single-nucleotide polymorphism (SNP rs1617640 in the erythropoietin (EPO promoter has been shown to be associated with decreased EPO expression. We examined the association of rs1617640 genotype with MDS. Methods We genotyped the EPO rS1617640 SNP in 189 patients with MDS, 257 with acute myeloid leukemia (AML, 106 with acute lymphoblastic leukemia, 97 with chronic lymphocytic leukemia, 353 with chronic myeloid leukemia, and 95 healthy controls. Results The G/G genotype was significantly more common in MDS patients (47/187; 25.1% than in controls (6/95; 6.3% or in patients with other leukemias (101/813; 12.4% (all P P = 0.03. Time to neutrophils recovery after therapy was significantly longer in MDS patients with the G/G genotype (P = 0.02. Conclusions These findings suggest a strong association between the rs1617640 G/G genotype and MDS. Further studies are warranted to investigate the utility of screening for this marker in individuals exposed to environmental toxins or chemotherapy.

  4. Hypocellular myelodysplastic syndrome with myelofibrosis in acute myeloid leukemia transformation: A case report.

    Science.gov (United States)

    Song, Kui; Xu, Xiaojun; Li, Min

    2015-07-01

    Primary myelodysplastic syndrome (MDS) with myelofibrosis is a rare hematological disorder that should be classified as a distinct subgroup of MDS. Treatment of MDS with myelofibrosis remains problematic and the prognosis is poor in these patients, particularly following transformation into acute myeloid leukemia (AML). The current study presents the case of a 28-year-old male diagnosed with MDS associated with myelofibrosis, together with hypocellular bone marrow features. Following induction chemotherapy consisting of mitoxantrone and cytarabine, the patient achieved complete remission, but developed severe myelofibrosis. The patient relapsed and the disease transformed into AML 12 months later. However, the extent of the myelofibrosis was markedly alleviated upon administration of a FLAG regimen that consisted of fludarabine, cytarabine and granulocyte colony-stimulating factor during the AML transformation. After one course of the FLAG regimen, the patient achieved a second complete remission. As there was no suitable donor for hematopoietic stem cell transplantation (HSCT), the patient relapsed and succumbed shortly after. In conclusion, MDS with fibrosis is an aggressive disease, but the degree of myelofibrosis may not be associated with the progression of hypocellular MDS, and allogeneic HSCT remains a potentially curative option for affected patients.

  5. Trisomy 8, a Cytogenetic Abnormality in Myelodysplastic Syndromes, Is Constitutional or Not?

    Directory of Open Access Journals (Sweden)

    Sílvia Saumell

    Full Text Available Isolated trisomy 8 is not considered presumptive evidence of myelodysplastic syndrome (MDS in cases without minimal morphological criteria. One reason given is that trisomy 8 (+8 can be found as a constitutional mosaicism (cT8M. We tried to clarify the incidence of cT8M in myeloid neoplasms, specifically in MDS, and the diagnostic value of isolated +8 in MDS. Twenty-two MDS and 10 other myeloid neoplasms carrying +8 were studied. Trisomy 8 was determined in peripheral blood by conventional cytogenetics (CC and on granulocytes, CD3+ lymphocytes and oral mucosa cells by fluorescence in situ hybridization (FISH. In peripheral blood CC, +8 was seen in 4/32 patients. By FISH, only one patient with chronic myelomonocytic leukemia showed +8 in all cell samples and was interpreted as a cT8M. In our series +8 was acquired in all MDS. Probably, once discarded cT8M by FISH from CD3+ lymphocytes and non-hematological cells, +8 should be considered with enough evidence to MDS.

  6. Chromothripsis Is a Recurrent Genomic Abnormality in High-Risk Myelodysplastic Syndromes

    Science.gov (United States)

    Abáigar, María; Robledo, Cristina; Benito, Rocío; Ramos, Fernando; Díez-Campelo, María; Hermosín, Lourdes; Sánchez-del-Real, Javier; Alonso, Jose M.; Cuello, Rebeca; Megido, Marta; Rodríguez, Juan N.; Martín-Núñez, Guillermo; Aguilar, Carlos; Vargas, Manuel; Martín, Ana A.; García, Juan L.; Kohlmann, Alexander; del Cañizo, M. Consuelo; Hernández-Rivas, Jesús M.

    2016-01-01

    To explore novel genetic abnormalities occurring in myelodysplastic syndromes (MDS) through an integrative study combining array-based comparative genomic hybridization (aCGH) and next-generation sequencing (NGS) in a series of MDS and MDS/myeloproliferative neoplasms (MPN) patients. 301 patients diagnosed with MDS (n = 240) or MDS/MPN (n = 61) were studied at the time of diagnosis. A genome-wide analysis of DNA copy number abnormalities was performed. In addition, a mutational analysis of DNMT3A, TET2, RUNX1, TP53 and BCOR genes was performed by NGS in selected cases. 285 abnormalities were identified in 71 patients (23.6%). Three high-risk MDS cases (1.2%) displayed chromothripsis involving exclusively chromosome 13 and affecting some cancer genes: FLT3, BRCA2 and RB1. All three cases carried TP53 mutations as revealed by NGS. Moreover, in the whole series, the integrative analysis of aCGH and NGS enabled the identification of cryptic recurrent deletions in 2p23.3 (DNMT3A; n = 2.8%), 4q24 (TET2; n = 10%) 17p13 (TP53; n = 8.5%), 21q22 (RUNX1; n = 7%), and Xp11.4 (BCOR; n = 2.8%), while mutations in the non-deleted allele where found only in DNMT3A (n = 1), TET2 (n = 3), and TP53 (n = 4). These cryptic abnormalities were detected mainly in patients with normal (45%) or non-informative (15%) karyotype by conventional cytogenetics, except for those with TP53 deletion and mutation (15%), which had a complex karyotype. In addition to well-known copy number defects, the presence of chromothripsis involving chromosome 13 was a novel recurrent change in high-risk MDS patients. Array CGH analysis revealed the presence of cryptic abnormalities in genomic regions where MDS-related genes, such as TET2, DNMT3A, RUNX1 and BCOR, are located. PMID:27741277

  7. Depleting depletion: Polymer swelling in poor solvent mixtures

    Science.gov (United States)

    Mukherji, Debashish; Marques, Carlos; Stuehn, Torsten; Kremer, Kurt

    A polymer collapses in a solvent when the solvent particles dislike monomers more than the repulsion between monomers. This leads to an effective attraction between monomers, also referred to as depletion induced attraction. This attraction is the key factor behind standard polymer collapse in poor solvents. Strikingly, even if a polymer exhibits poor solvent condition in two different solvents, it can also swell in mixtures of these two poor solvents. This collapse-swelling-collapse scenario is displayed by poly(methyl methacrylate) (PMMA) in aqueous alcohol. Using molecular dynamics simulations of a thermodynamically consistent generic model and theoretical arguments, we unveil the microscopic origin of this phenomenon. Our analysis suggests that a subtle interplay of the bulk solution properties and the local depletion forces reduces depletion effects, thus dictating polymer swelling in poor solvent mixtures.

  8. Significance of CD34-and CD34+ Cell Apoptosis and Proliferation in Bone Marrow of Patients with MDS and Their Impact on Survival%骨髓增生异常综合征患者骨髓CD34-和CD34+细胞凋亡与增殖的意义及对生存的影响

    Institute of Scientific and Technical Information of China (English)

    夏冰; 郭青; 赵丹丹; 赵海丰; 韩晓蘋; 王卉; 吴晓雄; 张翼鷟

    2012-01-01

    Alteration in the balance between cell apoptosis and proliferation is one of the pathophysiological mechanisms of the myelodysplastic syndromes (MDS). The question of whether the excessive apoptosis and/ or proliferation predominantly involve the subset of progenitor cells (CD34+ cells) or mature cells (CD34- cells) remains a controversial issue. This study was purposed to analyze the apoptosis and proliferation status of CD34+ and CD34" cells in bone marrow(BM) of patients with MDS, to investigate the pathogenesis of MDS and to determine the relation of apoptosis and proliferation status of CD34+ and CD34" cells with prognosis of MDS. The proprotion of CD34+ cells, the apoptosis and proliferation ratio(A/P) of CD34+ and CD34" cells in BM of 40 patients with MDS, including 20 cases of high-risk MDS and 20 cases of low-risk MDS, and 10 normal persons as control were detected by flow cytometry; the influence of CD34+ and CD34" cell apoptosis and proliferation levels on prognosis of MDS was evaluated by unvariate and multivariate analysis of survival. The results showed that the proportion of CD34+ cells in BM of high-risk MDS patients was significantly higher than that in BM of low-risk MDS patients and in normal BM [(1.92±0.10)% , (1.09±0.04)% , (1.03±0.05)% respectively]. The apoptotic rates (AR) ofbothCD34+ and CD34+ cells were significantly higher in low-risk MDS [(54.75 ±2.18)% ,(80.36 ±1.68)% ] than in high-risk MDS [(24.87 ±2.69)%, (23. 12 ±1.23)%] and in normal BM [(18.51 ±2.74)%, (20.98 ±2.21)%]. When compared between CD34+ cells and CD34- cells in low-risk MDS, a greater AR of CD34- cells was found. However, the higher proliferative rate of CD34+ cells was observed in high-risk MDS. In low-risk MDS, a higher A/P ratio was found in CD34- cells than in CD34+ cells; whereas this ratio was equalized or inverted in high-risk MDS. In addition, the survival and prognosis correlated significantly with AR of CD34+ cells. It is concluded that the early MDS

  9. [Iron chelation therapy and its influence on the alleviation of EPO resistance in MDS patients].

    Science.gov (United States)

    Zhang, Yao; Xiao, Chao; Gu, Shu-Cheng; Chang, Chun-Kang

    2014-08-01

    This study was aimed to investigate the changes of erythropoietin (EPO), hemoglobin(Hb) and recombinant EPO (rEPO) levels in MDS patients receiving iron chelation therapy, and to explore the relationship between EPO and serum ferritin(SF). A total of 172 MDS patients and 30 healthy controls were studied. The levels of SF, EPO, serum iron (SI), total iron binding capacity (TIBC), C-reaction protein (CRP) and Hb were measured respectively, the level of SF was adjusted according to the changes of CRP. Among them, there were 34 cases of low-risk (SF>1 000 mg/L) receiving deferoxamine therapy, whose changes of SF, EPO, SI, TIBC, Hb levels were detected and compared before and after treatment. Besides, the difference in the incidence of EPO resistance in iron overload group and non-iron overload group was assessed before and after therapy, and 58 cases of low-risk and EPOEPO in non-iron overload group was higher than that in the normal control group (997.44 ± 473.48 vs 467.27 ± 238.49, P EPO in iron overload group was higher than that in non-iron overload group and control group (3257.59 ± 697.19 vs 997.44 ± 473.48, P = 0.012, 3257.59 ± 697.19 vs 467.27 ± 238.49, P = 0.002). Otherwise, the incidence of EPO resistance in iron overload group was higher than that in non-iron overload group (18/35 vs 2/23, P = 0.001), and the level of EPO and SF was positively related to each other in iron overload group (r = 0.310,P = 0.036). After receiving iron chelation therapy, the levels of SF, SI, TIBC and EPO in iron overload group were significantly lower than that before therapy (3942.38 ± 641.82 vs 2266.35 ± 367.31, P = 0.028;48.61 ± 10.65 vs 28.52 ± 12.61, P = 0.034;59.84 ± 12.62 vs 33.76 ± 15.43, P = 0.045;3808.01 ± 750.22 vs 1954.78 ± 473.18, P = 0.042). Moreover, the level of Hb increased (35 ± 18 vs 57 ± 21, P = 0.046) and the EPO resistance in some patients was decreased. It is concluded that iron chelation therapy can improve the efficacy of EPO to alleviate

  10. Rotational Mixing and Lithium Depletion

    CERN Document Server

    Pinsonneault, M H

    2010-01-01

    I review basic observational features in Population I stars which strongly implicate rotation as a mixing agent; these include dispersion at fixed temperature in coeval populations and main sequence lithium depletion for a range of masses at a rate which decays with time. New developments related to the possible suppression of mixing at late ages, close binary mergers and their lithium signature, and an alternate origin for dispersion in young cool stars tied to radius anomalies observed in active young stars are discussed. I highlight uncertainties in models of Population II lithium depletion and dispersion related to the treatment of angular momentum loss. Finally, the origins of rotation are tied to conditions in the pre-main sequence, and there is thus some evidence that enviroment and planet formation could impact stellar rotational properties. This may be related to recent observational evidence for cluster to cluster variations in lithium depletion and a connection between the presence of planets and s...

  11. Charge depletion in organic heterojunction

    Science.gov (United States)

    Ng, T. W.; Lo, M. F.; Lee, S. T.; Lee, C. S.

    2012-03-01

    Until now two types of organic-organic heterojunction (OHJ) have been observed in P-N junctions formed between undoped-organic semiconductors. Charge-transfers across OHJs are either negligible or showing electron transfer from P-type to N-type materials, leading to charges accumulation near the interface. Here, we observed that junction of 4,4',4''-tris(2-methylphenyl-phenylamino)triphenylamine (m-MTDATA)/bathocuproine (BCP) show the third-behavior. Electrons in BCP (N-type) transfer to m-MTDATA (P-type), leading to depletion of mobile majority carriers near the junction. While "depletion junctions" are typical in inorganic semiconductors, there are no reports in undoped-OHJ. Formation mechanism of depletion OHJs and fundamental differences between inorganic and organic HJs are discussed.

  12. Therapeutic approaches in myelofibrosis and myelodysplastic/myeloproliferative overlap syndromes

    Directory of Open Access Journals (Sweden)

    Sochacki AL

    2016-04-01

    Full Text Available Andrew L Sochacki,1 Melissa A Fischer,1 Michael R Savona1,2 1Department of Internal Medicine, Vanderbilt University Medical Center, 2Vanderbilt-Ingram Cancer Center, Nashville, TN, USA Abstract: The discovery of JAK2V617F a decade ago led to optimism for a rapidly developing treatment revolution in Ph- myeloproliferative neoplasms. Unlike BCR–ABL, however, JAK2 was found to have a more heterogeneous role in carcinogenesis. Therefore, for years, development of new therapies was slow, despite standard treatment options that did not address the overwhelming symptom burden in patients with primary myelofibrosis (MF, post-essential thrombocythemia MF, post-polycythemia vera MF, and myelodysplastic syndrome (MDS/myeloproliferative neoplasm (MPN syndromes. JAK–STAT inhibitors have changed this, drastically ameliorating symptoms and ultimately beginning to show evidence of impact on survival. Now, the genetic foundations of myelofibrosis and MDS/MPN are rapidly being elucidated and contributing to targeted therapy development. This has been empowered through updated response criteria for MDS/MPN and refined prognostic scoring systems in these diseases. The aim of this article is to summarize concisely the current and rationally designed investigational therapeutics directed at JAK–STAT, hedgehog, PI3K–Akt, bone marrow fibrosis, telomerase, and rogue epigenetic signaling. The revolution in immunotherapy and novel treatments aimed at previously untargeted signaling pathways provides hope for considerable advancement in therapy options for those with chronic myeloid disease. Keywords: MDS/MPN neoplasms, emerging therapy

  13. Prognostic analysis of refractory anaemia in adult myelodysplastic syndromes

    Institute of Scientific and Technical Information of China (English)

    WANG Xiao-qin; CHEN Zi-xing; CHEN Shu-chang; LIN Guo-wei; JI Mei-rong; LIANG Jian-ying; LIU Dun-dan; LI De-gao; MA Yan

    2008-01-01

    Background Patients with myelodysplastic syndrome (MDS) display a very diverse pattem. In this study, we investigated prognostic factors and survival rate in adult patients with MDS refractory anaemia (MDS-RA) diagnosed according to French-American-British classification and evaluated the International Prognostic Scoring System (IPSS) for Chinese patients.Methods A multi-center study on diagnosis of MDS-RA was conducted to charactedze the clinical features of Chinese MDS patients. The morphological criteria for the diagnosis of MDS-RA were first standardized. Clinical data of 307 MDS-RA patients collected from Shanghai, Suzhou and Beijing from 1995 to 2006 were analyzed using Kaplan-Meier curve, log rank and Cox regression model.Results The median age of 307 MDS-RA cases was 52 years. The frequency of 2 or 3 lineage cytopenias was 85.6%. Abnormal karyotype occurred in 35.7% of 235 patients. There were 165 cases (70.2%) in the good IPSS cytogenetic subgroup, 44 cases (18.7%) intermediate and 26 cases (11.1%) poor. IPSS showed 20 (8.5%) categodzed as low dsk,195 cases (83.0%) as intermediate-I risk and 20 cases (8.5%) as intermediate-ll dsk. The 1-, 2-, 3-, 4- and 5-year survival rates were 90.8%, 85.7%, 82.9%, 74.9% and 71.2% respectively. Fifteen cases (4.9%) transformed to acute myeloid leukaemia (median time 15.9 months, range 3-102 months). Lower white blood ceil count (<1.5x109/L), platelet count (<30x109/L) and cytogenetic abnormalities were independent prognostic factors by multivariate analysis, but age (≥65 years), IPSS cytogenetic subgroup and IPSS risk subgroup were not independent prognostic factors associated with survival time.Conclusions Chinese patients were younger, and had lower incidence of cytogenetic abnormalities, more severe cytopenias but a more favourable prognosis than Western patients. The major prognostic factors were lower white blood cell count, lower platelet count and fewer abnormal karyotypes. The intemational prognostic scodng

  14. Myelodysplastic Syndrome with Myelofibrosis Transformed to a Precursor B-Cell Acute Lymphoblastic Leukemia: A Case Report with Review of the Literature

    Directory of Open Access Journals (Sweden)

    Ayed A. Algarni

    2012-01-01

    Full Text Available Myelodysplastic syndromes (MDS comprise a group of heterogeneous clonal hematopoietic cell disorders characterized by cytopenias, bone marrow hypercellularity, and increased risk of transformation to acute leukemias. MDS usually transformed to acute myeloid leukemia, and transformation to acute lymphoblastic leukemia (ALL is rare. Herein, we report a unique patient who presented with MDS with myelofibrosis. Two months after the initial diagnosis, she progressed to a precursor B-cell acute lymphoblastic leukemia. She was treated with induction therapy followed by allogenic stem cell transplantation. She was alive and doing well upon last followup. We have also reviewed the literature and discussed the clinicopathologic features of 36 MDS patients who progressed to ALL reported in the literature.

  15. A phase II study of AZD2171 (cediranib) in the treatment of patients with acute myeloid leukemia or high-risk myelodysplastic syndrome.

    Science.gov (United States)

    Mattison, Ryan; Jumonville, Alcee; Flynn, Patrick James; Moreno-Aspitia, Alvaro; Erlichman, Charles; LaPlant, Betsy; Juckett, Mark B

    2015-07-01

    Patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) not fit for intensive treatment need novel therapy options. Vascular endothelial growth factor (VEGF) receptor inhibition is one potential mechanism by which AML and MDS could be treated. The receptor tyrosine kinase inhibitor AZD2171 (cediranib) has activity against VEGF receptors KDR and FLT-1. This multicenter phase II study was designed to test cediranib's activity in patients with AML or high-risk MDS. The primary endpoint was confirmed disease response defined as a composite of complete remission, partial remission or hematologic improvement. The study enrolled 23 subjects in the AML cohort and 16 subjects in the MDS cohort. There were no confirmed responses in either group. Since the study met the stopping rule after the first stage of enrollment, the trial was closed to further accrual. Common adverse events in both cohorts included thrombocytopenia, neutropenia, anemia, fatigue, dyspnea, diarrhea, nausea and dehydration.

  16. 2014 NCCN指南骨髓增生异常综合征新进展%2014 NCCN interpretation of myelodysplastic syndromes

    Institute of Scientific and Technical Information of China (English)

    吴雪; 陈宝安

    2014-01-01

    Progress toward improving management of myelodysplastic syndromes (MDS) occurred every year.This review focused on the new developments of classification,diagnoses,prognostic stratification and therapy on MDS in recent five years.In addiction,a brief introduction of pediatric MDS was presented here.All this were for a better exploration in the future.%骨髓增生异常综合征(MDS)的研究每年均会取得很大的进展.现对近5年来MDS分类、诊断、预后、治疗等4个方面的最新研究成果进行总结,并简要介绍儿童MDS的特点,为将来更好地探索MDS打下基础.

  17. Early lenalidomide treatment for low and intermediate-1 International Prognostic Scoring System risk myelodysplastic syndromes with del(5q) before transfusion dependence.

    Science.gov (United States)

    Oliva, Esther N; Lauseker, Michael; Aloe Spiriti, Maria Antonietta; Poloni, Antonella; Cortelezzi, Agostino; Palumbo, Giuseppe A; Balleari, Enrico; Sanpaolo, Grazia; Volpe, Antonio; Ricco, Alessandra; Ronco, Francesca; Alati, Caterina; D'Errigo, Maria Grazia; Santacaterina, Irene; Kündgen, Andrea; Germing, Ulrich; Latagliata, Roberto

    2015-12-01

    Lenalidomide is approved for the treatment of transfusion-dependent (TD) del(5q) myelodysplastic syndromes (MDS). However, few data are available in patients with transfusion-independent (TI) del(5q) MDS. In the first, observational, part of this 2-part study, we assessed the impact of transfusion dependence on overall survival (OS) and non-leukemic death in untreated del(5q) MDS patients who were TD (n = 136), TI with hemoglobin (Hb) ≥10 mg/dL (n = 88), or TI with Hb lenalidomide (10 mg/day) in 12 patients with TI del(5q) MDS and Hb lenalidomide (+12.5; P = 0.020). Evaluable TI patients experienced early increases in Hb levels, and all attained an erythroid response. Our findings suggest that TI patients with moderate anemia may benefit from early treatment with lenalidomide.

  18. The biology of myelodysplastic syndromes: unity despite heterogeneity

    Directory of Open Access Journals (Sweden)

    Azra Raza

    2010-06-01

    Full Text Available Myelodysplastic syndromes (MDS traditionally have been grouped together as a disease entity based on clinical phenomena seen in association. Despite the similarities, there is great heterogeneity among the syndromes. Recent insights have shown, however, that there exists a biologically cohesive theme that unifies and thereby validates the conceptual interconnectedness. The first suggestion that such a relationship existed where biology could directly explain the observed cytopenias was the finding of excessive premature apoptosis of hematopoietic cells in MDS marrows. This apoptosis was mediated by paracrine as well as autocrine factors implicating both the seed and the soil in the pathology of the disease. Pro-inflammatory cytokines in the marrow microenvironment were mainly the paracrine mediators of apoptosis, but how the clonal cells committed suicide because of autocrine stimulation had remained a mystery for more than a decade. It has been shown now that deregulation of ribosome biogenesis can initiate a stress response in the cell through the p53 signaling pathway. Congenital anemias had been associated with mutations in ribosomal protein genes. The surprise came with the investigation of 5q- syndrome patients where haplo-insufficiency of the ribosomal protein gene RPS14 was found to be the cause of this MDS subtype. Similar ribosomal deregulation was shown to be present in all varieties of MDS patients, serving as another unifying characteristic. In addition to these findings, there are other DNA-related abnormalities such as uniparental disomy, mutations in the TET2 gene, and epigenetic phenomena that are associated with and occur across all types of MDS. This paper summarizes the themes unifying this heterogeneous group of diseases.

  19. Impact of mineral resource depletion

    CSIR Research Space (South Africa)

    Brent, AC

    2006-09-01

    Full Text Available In a letter to the editor, the authors comment on BA Steen's article on "Abiotic Resource Depletion: different perceptions of the problem with mineral deposits" published in the special issue of the International Journal of Life Cycle Assessment...

  20. Global depletion of groundwater resources

    NARCIS (Netherlands)

    Wada, Y.; Beek, L.P.H. van; van Kempen, C.M.; Reckman, J.W.T.M.; Vasak, S.; Bierkens, M.F.P.

    2010-01-01

    In regions with frequent water stress and large aquifer systems groundwater is often used as an additional water source. If groundwater abstraction exceeds the natural groundwater recharge for extensive areas and long times, overexploitation or persistent groundwater depletion occurs. Here we provid

  1. Therapy-related patterns of cytogenetic abnormalities in acute myeloid leukemia and myelodysplastic syndrome post polycythemia vera: single center experience and review of literature.

    Science.gov (United States)

    Swolin, Birgitta; Rödjer, Stig; Westin, Jan

    2008-06-01

    A minor fraction of patients with polycythemia vera (PV) develop a terminal acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Analysis of the cytogenetic abnormalities during AML or MDS may help in understanding if this development is part of the natural course of the disease or induced by myelosuppressive therapy. Thirty-six cases with AML or MDS post PV, collected in a single Swedish institution during a 33-year period, are described with special regard to time to development of AML or MDS, therapy given during active PV, and cytogenetic findings during AML or MDS. A further 118 cases of AML or MDS post PV, in whom type of therapy during active PV and cytogenetic findings during AML or MDS were reported, were collected from the literature. AML or MDS developed in our own series after 1-30 years with a fairly constant rate (two cases per year). The most frequent cytogenetic abnormalities were +1q, -5, 5q-, -7, 7q-, +8, +9, 11q-, 13q-, and 20q-. When patients in the total material (n = 154) were divided with regard to treatment during active PV, marked differences were observed. The highest frequency of abnormalities was found in patients given multiple lines of therapy (n = 61), dominating features being -5/5q- in 28 patients (46%), -7/7q- in 19 patients (31%), numerous translocations in 24 patients (39%), and unidentified markers in 22 patients (36%). Half of the patients treated with hydroxyurea alone showed a -5 or 5q- abnormality. In patients treated with phlebotomy alone, +8 and +9 were the most frequent findings. The type of therapy given during active PV influences the type of chromosome abnormalities present during terminal AML or MDS and can also be instrumental in the development of leukemia.

  2. C-Codes: Cyclic Lowest-Density MDS Array Codes Constructed Using Starters for RAID 6

    CERN Document Server

    Li, Mingqiang

    2011-01-01

    The distance-3 cyclic lowest-density MDS array code (called the C-Code) is a good choice for RAID 6 because of its optimal storage efficiency, optimal update complexity, optimal length, and cyclic symmetry. In this paper, the underlying connections between C-Codes (or quasi-C-Codes) and starters in group theory are revealed. It is shown that each C-Code (or quasi-C-Code) of length $2n$ can be constructed using an even starter (or even multi-starter) in $(Z_{2n},+)$. It is also shown that each C-Code (or quasi-C-Code) has a twin C-Code (or quasi-C-Code). Then, four infinite families (three of which are new) of C-Codes of length $p-1$ are constructed, where $p$ is a prime. Besides the family of length $p-1$, C-Codes for some sporadic even lengths are also presented. Even so, there are still some even lengths (such as 8) for which C-Codes do not exist. To cover this limitation, two infinite families (one of which is new) of quasi-C-Codes of length $2(p-1)$ are constructed for these even lengths.

  3. Secondary Myelodysplastic Syndrome May Happen Same as Paraneoplastic Syndrome in a Period of Time and Prior to The Appearance of Malignancy: A case Study of 6 Patients

    OpenAIRE

    Aznab, Mozaffar; Kavianymoghadam, Kaveh

    2013-01-01

    Myelodysplastic syndrome is a bone marrow failure in which differentiation and maturity do not happen naturally and dysplasia exists in each of 3 cell categories in Bone marrow. Refractory anemia is one of the major complaints with which the patients come to hematology clinics, which in diagnostic considerations lead to MDS as diagnosis. Often there is no recognized reason for this, so it is called “primary MDS”. In practice, we meet some patients who have MDS criteria however we can also fin...

  4. Autologous stem cell transplantation for therapy-related acute myeloid leukemia and myelodysplastic syndrome.

    NARCIS (Netherlands)

    Kroger, N.; Brand, R.; Biezen, A. van; Cahn, J.; Slavin, S.; Blaise, D.; Sierra, J.; Zander, A.; Niederwieser, D.; Witte, T.J.M. de

    2006-01-01

    We report the results of 65 patients with treatment-related myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML) who were transplanted from an autograft and reported to the EBMT. The median age was 39 years (range, 3-69), and stem cell source was bone marrow (n = 31), or peripheral blood

  5. Tumor suppressor microRNAs are downregulated in myelodysplastic syndrome with spliceosome mutations

    DEFF Research Database (Denmark)

    Aslan, Derya; Garde, Christian; Nygaard, Mette Katrine;

    2016-01-01

    Spliceosome mutations are frequently observed in patients with myelodysplastic syndromes (MDS). However, it is largely unknown how these mutations contribute to the disease. MicroRNAs (miRNAs) are small noncoding RNAs, which have been implicated in most human cancers due to their role in post...

  6. Darbepoetin alpha for the treatment of anaemia in low-intermediate risk myelodysplastic syndromes

    DEFF Research Database (Denmark)

    Musto, Pellegrino; Lanza, Francesco; Balleari, Enrico;

    2005-01-01

    Thirty-seven anaemic subjects with low-to-intermediate risk myelodysplastic syndrome (MDS) received the highly glycosylated, long-acting erythropoiesis-stimulating molecule darbepoetin-alpha (DPO) at the single, weekly dose of 150 microg s.c. for at least 12 weeks. Fifteen patients (40.5%) achiev...

  7. Reduced expression of FLIPSHORT in bone marrow of low risk myelodysplastic syndrome

    NARCIS (Netherlands)

    Campos, Paula de Melo; Traina, Fabiola; Santos Duarte, Adriana da Silva; Lorand-Metze, Irene; Costa, Fernando F.; Saad, Sara T. O.

    2007-01-01

    Apoptosis is dysregulated in patients with myelodysplastic syndrome (MDS) and acute myelogenous leukaemia (AML). FLIP (FLICE (FAS-associated death-domain-like IL-1 beta-converting enzyme)-inhibitory protein) has been described as an anti-apoptotic protein. Here, we characterize the expression level

  8. Fatal bacteremia by neisseria cinerea in a woman with myelodysplastic syndrome: a case report.

    Science.gov (United States)

    Zhu, Xiaofei; Li, Min; Cao, Huiling; Yang, Xuewen

    2015-01-01

    Neisseria cinerea has been rarely found in blood cultures. In this study, we are reporting a case of a Myelodysplastic Syndrome (MDS) patient in whose blood Neisseria cinerea was found and led a fatal consequence. This case will call our attentions to the uncommon pathogens in the pathogenicity of end-stage patients.

  9. Fatal bacteremia by neisseria cinerea in a woman with myelodysplastic syndrome: a case report

    OpenAIRE

    Zhu, Xiaofei; Li, Min; Cao, Huiling; Yang, Xuewen

    2015-01-01

    Neisseria cinerea has been rarely found in blood cultures. In this study, we are reporting a case of a Myelodysplastic Syndrome (MDS) patient in whose blood Neisseria cinerea was found and led a fatal consequence. This case will call our attentions to the uncommon pathogens in the pathogenicity of end-stage patients.

  10. Study of nucleophosmin (NPM) gene mutation in patients with acute myeloid leukemia and myelodysplastic syndromes

    Institute of Scientific and Technical Information of China (English)

    张悦

    2006-01-01

    Objective To investigate nucleophosmin (NPM) gene mutations in patients with de novo acute myeloid leukemia (AML) with normal cytogenetics and primary myelodysplastic syndromes (MDS). Methods Genomic DNA corresponding to exon 12 of NPM gene was amplified by polymerase chain reaction (PCR) in 40 AML patients (28 case untreated and 12 in first remission) and

  11. Practical recommendations on the use of lenalidomide in the management of myelodysplastic syndromes.

    NARCIS (Netherlands)

    Giagounidis, A.; Fenaux, P.; Mufti, G.J.; Muus, P.; Platzbecker, U.; Sanz, G.; Cripe, L.; Lilienfeld-Toal, M. von; Wells, R.A.

    2008-01-01

    Lenalidomide, an oral immunomodulatory agent, has received approval in the USA from the Food and Drug Administration (FDA) for the management of myelodysplastic syndromes (MDS) classified by the International Prognostic Scoring System (IPSS) as low risk or intermediate-1 risk and with a deletion 5q

  12. Longitudinal Analysis of DNA Methylation in CD34+ Hematopoietic Progenitors in Myelodysplastic Syndrome

    DEFF Research Database (Denmark)

    Wong, Yan Fung; Micklem, Chris N; Taguchi, Masataka

    2014-01-01

    Myelodysplastic syndrome (MDS) is a disorder of hematopoietic stem cells (HSCs) that is often treated with DNA methyltransferase 1 (DNMT1) inhibitors (5-azacytidine [AZA], 5-aza-2'-deoxycytidine), suggesting a role for DNA methylation in disease progression. How DNMT inhibition retards disease pr...

  13. Role of chromosome 1 pericentric heterochromatin (1q) in pathogenesis of myelodysplastic syndromes: report of 2 new cases.

    Science.gov (United States)

    Millington, Karmaine; Hudnall, S David; Northup, Jill; Panova, Neli; Velagaleti, Gopalrao

    2008-04-01

    Chromosome 1 pericentromeric heterochromatin (1q) has been shown to play an important role in the pathogenesis of non-Hodgkin lymphoma and multiple myeloma. Myelodysplastic syndrome (MDS) results from marrow failure in two or more cell lineages. Although trisomy 1q has been reported in MDS, it is usually present with additional common abnormalities such as trisomy 8, monosomy 5 or monosomy 7, leading to speculation that 1q abnormalities are mostly secondary events representing clonal evolution. We report two cases of MDS in which consistent involvement of 1q heterochromatin is seen as the primary clonal abnormality. Both patients presented with fatigue and pancytopenia. Based on the published reports and our cases, we propose that the 1q heterochromatin plays a vital role in the pathophysiology of MDS. Abnormalities involving 1q result in aberrant heterochromatin/euchromatin junctions, leading to gene dosage abnormalities. Further studies of 1q abnormalities in MDS might provide specific insights as to the exact role of the excess 1q heterochromatin in the etiology of MDS.

  14. [Methylation of FHIT gene promoter region in DNA from plasma of patients with myelodysplastic syndromes and demethylating effect of decitabine].

    Science.gov (United States)

    Deng, Yin-Fen; Zhang, Lei; Zhang, Xiu-Qun; Hu, Ming-Qiu; Dai, Dan; Zhang, Xue-Zhong; Xu, Yan-Li

    2012-10-01

    This study was aimed to detect the methylation status of FHIT gene promoter region in the DNA from plasma of patients with myelodysplastic syndrome (MDS), and to investigate the demethylating effect of decitabine. Methylation-specific PCR method was used to detect the methylation status of FHIT gene promoter region in the DNA from plasma of 4 patients with MDS before and after treatment with decitabine plus semis CAG therapy (among them, 1 case of newly diagnosed MDS, 3 cases progressed into acute leukemia). The results indicated that 3 cases were found to have an increased methylation in the promoter region. After treatment with decitabine plus semis CAG, increased methylation was reversed in 2 cases. In 4 cases, 2 cases displayed clinical response. It is concluded that FHIT gene hypermethylation is associated with MDS pathogenesis. Decitabine has demethylating effect on the FHIT gene hypermethylation of plasma from MDS patients. Detecting the methylation status of FHIT gene in DNA from plasma may play a role in MDS auxiliary diagnosis or prognosis.

  15. Correlation between the Movement Disorders Society Unified Parkinson's Disease rating scale (MDS-UPDRS) and the Unified Parkinson's Disease rating scale (UPDRS) during L-dopa acute challenge.

    Science.gov (United States)

    Merello, Marcelo; Gerschcovich, Eliana Roldan; Ballesteros, Diego; Cerquetti, Daniel

    2011-11-01

    While Movement Disorders Society Unified Parkinson's Disease rating scale (MDS-UPDRS) validation has been exhaustive; performance evaluation to detect acute changes arising after administration of a single dose of L-dopa has yet to be explored. To determine the correlation between UPDRS and MDS-UPDRS during the acute challenge with Ldopa and the MDS-UPDRS equivalent to 30% cutoff score of UPDRS for defining responsiveness, 64 patients were assessed. Consecutive assessments were performed immediately before and after administration of a single dose of L-dopa/carbidopa 250/25 mg using the motor section of the UPDRS and the MDS-UPDRS. Good diagnostic accuracy, consistent with published findings of high correlation between scales was observed. Area under the curve (AUC) was 0.99 (CI = 0.97-1.00, P UPDRS and MDS-UPDRS and that the 30% of variation in UPDRS score used for predicting sustained long term L-dopa response was equivalent to 24% in MDS-UPDRS.

  16. The Mice Drawer System Tissue Sharing Program (MDS-TSP): osteobiology in microgravity

    Science.gov (United States)

    Ruggiu, Alessandra; Cancedda, Ranieri; Biticchi, Roberta; Cilli, Michele; Cotronei, Vittorio; Costa, Delfina; Liu, Yi; Piccardi, Federica; Pignataro, Salvatore; Tasso, Roberta; Tavella, Sara

    The capacity of bone tissue to alter its mass and architecture in response to mechanical request has long been known. Bone not only develops as a structure designed specifically for mechanical demands, but it can adapt during life toward more efficient mechanical performance. In partic-ular, the skeletal effects of microgravity result in the development of an osteoporotic phenotype with several bone defects including a bone mass decrease resembling the bone modifications occurring in elder people and in bed rest conditions. This is particularly true for weight bearing bones such as spine, femur and tibiae. In contrast non-weight bearing bones like calvaria etc didn't show bone mineral density decrease in weightlessness. Given the interest of our labora-tory in the microgravity induced skeleton alterations, we focused our attention on a transgenic mouse overexpressing pleiotrophin (PTN) under the control of the bone specific human os-teocalcin promoter. This protein is a heparin-binding cytokine with different functions. In particular PTN-transgenic mice (PTN-Tg) show an increase in the bone mass and mineral-ization, with a calcium content/mg bone of 10We used this mouse model in the MDS flight experiment to study the PTN potential role in counteracting bone loss in microgravity. Three PTN-transgenic mice (Tg) and three wild type (Wt) mice were housed in the MDS (Mouse Drawer System) at the ISS for three months. During these three months two wt and one tg mice died and therefore could be only frozen for subsequent skeletal analysis. The other three mice, daily checked for their health status, were viable and in good condition throughout the all three months at the ISS. At the end of November 2009 the three mice came back to Earth and after blood collection were immediately sacrificed and the different bones isolated. From blood cell analysis no major hematological alterations were noticed in the blood cell count except a slight increase in the number of erythrocytes

  17. Ozone Depletion from Nearby Supernovae

    CERN Document Server

    Gehrels, N; Jackman, C H; Cannizzo, J K; Mattson, B J; Chen, W; Gehrels, Neil; Laird, Claude M.; Jackman, Charles H.; Cannizzo, John K.; Mattson, Barbara J.; Chen, Wan

    2003-01-01

    Estimates made in the 1970's indicated that a supernova occurring within tens of parsecs of Earth could have significant effects on the ozone layer. Since that time, improved tools for detailed modeling of atmospheric chemistry have been developed to calculate ozone depletion, and advances have been made in theoretical modeling of supernovae and of the resultant gamma-ray spectra. In addition, one now has better knowledge of the occurrence rate of supernovae in the galaxy, and of the spatial distribution of progenitors to core-collapse supernovae. We report here the results of two-dimensional atmospheric model calculations that take as input the spectral energy distribution of a supernova, adopting various distances from Earth and various latitude impact angles. In separate simulations we calculate the ozone depletion due to both gamma-rays and cosmic rays. We find that for the combined ozone depletion roughly to double the ``biologically active'' UV flux received at the surface of the Earth, the supernova mu...

  18. Ozone Depletion from Nearby Supernovae

    Science.gov (United States)

    Gehrels, Neil; Laird, Claude M.; Jackman, Charles H.; Cannizzo, John K.; Mattson, Barbara J.; Chen, Wan; Bhartia, P. K. (Technical Monitor)

    2002-01-01

    Estimates made in the 1970's indicated that a supernova occurring within tens of parsecs of Earth could have significant effects on the ozone layer. Since that time improved tools for detailed modeling of atmospheric chemistry have been developed to calculate ozone depletion, and advances have been made also in theoretical modeling of supernovae and of the resultant gamma ray spectra. In addition, one now has better knowledge of the occurrence rate of supernovae in the galaxy, and of the spatial distribution of progenitors to core-collapse supernovae. We report here the results of two-dimensional atmospheric model calculations that take as input the spectral energy distribution of a supernova, adopting various distances from Earth and various latitude impact angles. In separate simulations we calculate the ozone depletion due to both gamma rays and cosmic rays. We find that for the combined ozone depletion from these effects roughly to double the 'biologically active' UV flux received at the surface of the Earth, the supernova must occur at approximately or less than 8 parsecs.

  19. Ozone depletion, paradigms, and politics

    Energy Technology Data Exchange (ETDEWEB)

    Iman, R.L.

    1993-10-01

    The destruction of the Earth`s protective ozone layer is a prime environmental concern. Industry has responded to this environmental problem by: implementing conservation techniques to reduce the emission of ozone-depleting chemicals (ODCs); using alternative cleaning solvents that have lower ozone depletion potentials (ODPs); developing new, non-ozone-depleting solvents, such as terpenes; and developing low-residue soldering processes. This paper presents an overview of a joint testing program at Sandia and Motorola to evaluate a low-residue (no-clean) soldering process for printed wiring boards (PWBs). Such processes are in widespread use in commercial applications because they eliminate the cleaning operation. The goal of this testing program was to develop a data base that could be used to support changes in the mil-specs. In addition, a joint task force involving industry and the military has been formed to conduct a follow-up evaluation of low-residue processes that encompass the concerns of the tri-services. The goal of the task force is to gain final approval of the low-residue technology for use in military applications.

  20. Multiple tests for wind turbine fault detection and score fusion using two- level multidimensional scaling (MDS)

    Science.gov (United States)

    Ye, Xiang; Gao, Weihua; Yan, Yanjun; Osadciw, Lisa A.

    2010-04-01

    Wind is an important renewable energy source. The energy and economic return from building wind farms justify the expensive investments in doing so. However, without an effective monitoring system, underperforming or faulty turbines will cause a huge loss in revenue. Early detection of such failures help prevent these undesired working conditions. We develop three tests on power curve, rotor speed curve, pitch angle curve of individual turbine. In each test, multiple states are defined to distinguish different working conditions, including complete shut-downs, under-performing states, abnormally frequent default states, as well as normal working states. These three tests are combined to reach a final conclusion, which is more effective than any single test. Through extensive data mining of historical data and verification from farm operators, some state combinations are discovered to be strong indicators of spindle failures, lightning strikes, anemometer faults, etc, for fault detection. In each individual test, and in the score fusion of these tests, we apply multidimensional scaling (MDS) to reduce the high dimensional feature space into a 3-dimensional visualization, from which it is easier to discover turbine working information. This approach gains a qualitative understanding of turbine performance status to detect faults, and also provides explanations on what has happened for detailed diagnostics. The state-of-the-art SCADA (Supervisory Control And Data Acquisition) system in industry can only answer the question whether there are abnormal working states, and our evaluation of multiple states in multiple tests is also promising for diagnostics. In the future, these tests can be readily incorporated in a Bayesian network for intelligent analysis and decision support.

  1. Adaptation of mouse skeletal muscle to long-term microgravity in the MDS mission.

    Directory of Open Access Journals (Sweden)

    Dorianna Sandonà

    Full Text Available The effect of microgravity on skeletal muscles has so far been examined in rat and mice only after short-term (5-20 day spaceflights. The mice drawer system (MDS program, sponsored by Italian Space Agency, for the first time aimed to investigate the consequences of long-term (91 days exposure to microgravity in mice within the International Space Station. Muscle atrophy was present indistinctly in all fiber types of the slow-twitch soleus muscle, but was only slightly greater than that observed after 20 days of spaceflight. Myosin heavy chain analysis indicated a concomitant slow-to-fast transition of soleus. In addition, spaceflight induced translocation of sarcolemmal nitric oxide synthase-1 (NOS1 into the cytosol in soleus but not in the fast-twitch extensor digitorum longus (EDL muscle. Most of the sarcolemmal ion channel subunits were up-regulated, more in soleus than EDL, whereas Ca(2+-activated K(+ channels were down-regulated, consistent with the phenotype transition. Gene expression of the atrophy-related ubiquitin-ligases was up-regulated in both spaceflown soleus and EDL muscles, whereas autophagy genes were in the control range. Muscle-specific IGF-1 and interleukin-6 were down-regulated in soleus but up-regulated in EDL. Also, various stress-related genes were up-regulated in spaceflown EDL, not in soleus. Altogether, these results suggest that EDL muscle may resist to microgravity-induced atrophy by activating compensatory and protective pathways. Our study shows the extended sensitivity of antigravity soleus muscle after prolonged exposition to microgravity, suggests possible mechanisms accounting for the resistance of EDL, and individuates some molecular targets for the development of countermeasures.

  2. Transient myelodysplastic syndrome in X-linked agammaglobulinemia with a novel Btk mutation.

    Science.gov (United States)

    Narula, Gaurav; Currimbhoy, Zinet

    2008-12-01

    X-linked agammaglobulinemia (XLA) is a rare disorder in which recurrent infections occur due to low serum globulins and circulating B lymphocytes caused by a mutation in the Bruton tyrosine kinase (Btk) gene. While myelodysplastic syndrome (MDS) associated with low B lymphocyte counts has been described, clonal cytogenetic abnormalities in confirmed cases of XLA have never been reported. We describe a case of XLA with a novel Btk mutation who also had a persistent clonal population in the bone marrow with abnormal cytogenetics in multiple chromosomes that resolved 1(1/2) years after treatment with IVIG, mimicking a picture of transient MDS.

  3. Suppression of the DNA damage response in acute myeloid leukemia versus myelodysplastic syndrome.

    Science.gov (United States)

    Boehrer, S; Adès, L; Tajeddine, N; Hofmann, W K; Kriener, S; Bug, G; Ottmann, O G; Ruthardt, M; Galluzzi, L; Fouassier, C; Tailler, M; Olaussen, K A; Gardin, C; Eclache, V; de Botton, S; Thepot, S; Fenaux, P; Kroemer, G

    2009-06-04

    The molecular mechanisms responsible for the evolution from the preleukemic entities of low-risk myelodysplastic syndrome (MDS) to the less favorable forms of high-risk MDS, as well as those enabling transformation to acute myeloid leukemia (AML), are still incompletely understood. Abundant evidence from solid tumors demonstrates that preneoplastic lesions activate signaling pathways of a DNA damage response (DDR), which functions as an 'anticancer barrier' hindering tumorigenesis. Testing the hypothesis that subgroups of MDS and AML differ with respect to DDR, we first assessed markers of DDR (phosphorylation of ATM, Chk-1, Chk-2 and H2AX) in cell lines representing different entities of MDS (P39, MOLM-13) and AML (MV4-11, KG-1) before and after gamma-irradiation. Although gamma-irradiation induced apoptosis and G(2)/M arrest and a concomitant increase in the phosphorylation of ATM, Chk-1 and H2AX in MDS-derived cell lines, this radiation response was attenuated in the AML-derived cell lines. It is noteworthy that KG-1, but not P39 cells exhibit signs of an endogenous activation of the DDR. Similarly, we found that the frequency of P-ATM(+) cells detectable in bone marrow (BM) biopsies increased in samples from patients with AML as compared with high-risk MDS samples and significantly correlated with the percentage of BM blasts. In contrast, the frequency of gamma-H2AX(+) cells was heterogeneous in all subgroups of AML and MDS. Whereas intermediate-1 MDS samples contained as little P-Chk-1 and P-Chk-2 as healthy controls, staining for both checkpoint kinases increased in intermediate-2 and high-risk MDS, yet declined to near-to-background levels in AML samples. Thus the activation of Chk-1 and Chk-2 behaves in accord with the paradigm established for solid tumors, whereas ATM is activated during and beyond transformation. In conclusion, we demonstrate the heterogeneity of the DDR response in MDS and AML and provide evidence for its selective suppression in AML

  4. Myelodysplastic Syndromes and Acute Myeloid Leukemia After Radiotherapy for Prostate Cancer: A Population-Based Study.

    Science.gov (United States)

    Wang, Rong; Zeidan, Amer M; Yu, James B; Soulos, Pamela R; Davidoff, Amy J; Gore, Steven D; Huntington, Scott F; Gross, Cary P; Ma, Xiaomei

    2017-04-01

    To understand the impact of radiotherapy on the development of myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) among elderly prostate cancer patients. We performed a retrospective cohort study of elderly prostate cancer patients diagnosed during 1999-2011 by using the National Cancer Institute's Surveillance, Epidemiology and End Results-Medicare linked database. Competing risk analyses adjusting for patient characteristics were conducted to assess the impact of radiotherapy on the development of subsequent MDS/AML, compared with surgery. Of 32,112 prostate cancer patients, 14,672 underwent radiotherapy, and 17,440 received surgery only. The median follow-up was 4.68 years. A total of 157 (0.47%) prostate cancer patients developed subsequent MDS or AML, and the median time to develop MDS/AML was 3.30 (range: 0.16-9.48) years. Compared with prostate cancer patients who received surgery only, patients who underwent radiotherapy had a significantly increased risk of developing MDS/AML (hazard ratio [HR] =1.51, 95% confidence interval [CI]: 1.07-2.13). When radiotherapy was further categorized by modalities (brachytherapy, conventional conformal radiotherapy, and intensity-modulated radiotherapy [IMRT]), increased risk of second MDS/AML was only observed in the IMRT group (HR = 1.66, 95% CI: 1.09-2.54). Our findings suggest that radiotherapy for prostate cancer increases the risk of MDS/AML, and the impact may differ by modality. Additional studies with longer follow-up are needed to further clarify the role of radiotherapy in the development of subsequent myeloid malignancies. A better understanding may help patients, physicians, and other stakeholders make more informed treatment decisions. Prostate 77:437-445, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  5. [Recent advances of studies on abnormal HOX gene in myelodysplastic syndromes and its molecular mechanisms].

    Science.gov (United States)

    Xie, Xin-Yan; Shao, Zong-Hong

    2015-02-01

    HOX gene encodes a group of homeodomain transcription factors which are highly conserved. The caudal-type homeobox (CDX) , ten-eleven translocation (TET) genes and polycomb group (PcG) , trithorax group (TrxG) proteins act as upstream regulators of HOX genes that manipulate the targeted gene expression through genetic and epigenetic mechanisms. The abnormal expression of HOX genes and their fusions contribute to myelodysplastic syndromes (MDS) pathogenesis. Aberrant DNA methylation and NUP98-HOX translocation serve as molecular mediators of dysfunction in MDS which can be used for the evaluation of biology and therapy. This article provides an overview of recent advances of studies on HOX gene and its abnormal molecular mechanisms, as well as potential correlation with MDS.

  6. The Case of Ozone Depletion

    Science.gov (United States)

    Lambright, W. Henry

    2005-01-01

    While the National Aeronautics and Space Administration (NASA) is widely perceived as a space agency, since its inception NASA has had a mission dedicated to the home planet. Initially, this mission involved using space to better observe and predict weather and to enable worldwide communication. Meteorological and communication satellites showed the value of space for earthly endeavors in the 1960s. In 1972, NASA launched Landsat, and the era of earth-resource monitoring began. At the same time, in the late 1960s and early 1970s, the environmental movement swept throughout the United States and most industrialized countries. The first Earth Day event took place in 1970, and the government generally began to pay much more attention to issues of environmental quality. Mitigating pollution became an overriding objective for many agencies. NASA's existing mission to observe planet Earth was augmented in these years and directed more toward environmental quality. In the 1980s, NASA sought to plan and establish a new environmental effort that eventuated in the 1990s with the Earth Observing System (EOS). The Agency was able to make its initial mark via atmospheric monitoring, specifically ozone depletion. An important policy stimulus in many respects, ozone depletion spawned the Montreal Protocol of 1987 (the most significant international environmental treaty then in existence). It also was an issue critical to NASA's history that served as a bridge linking NASA's weather and land-resource satellites to NASA s concern for the global changes affecting the home planet. Significantly, as a global environmental problem, ozone depletion underscored the importance of NASA's ability to observe Earth from space. Moreover, the NASA management team's ability to apply large-scale research efforts and mobilize the talents of other agencies and the private sector illuminated its role as a lead agency capable of crossing organizational boundaries as well as the science-policy divide.

  7. The development of the Older Persons and Informal Caregivers Survey Minimum DataSet (TOPICS-MDS: a large-scale data sharing initiative.

    Directory of Open Access Journals (Sweden)

    Jennifer E Lutomski

    Full Text Available INTRODUCTION: In 2008, the Ministry of Health, Welfare and Sport commissioned the National Care for the Elderly Programme. While numerous research projects in older persons' health care were to be conducted under this national agenda, the Programme further advocated the development of The Older Persons and Informal Caregivers Survey Minimum DataSet (TOPICS-MDS which would be integrated into all funded research protocols. In this context, we describe TOPICS data sharing initiative (www.topics-mds.eu. MATERIALS AND METHODS: A working group drafted TOPICS-MDS prototype, which was subsequently approved by a multidisciplinary panel. Using instruments validated for older populations, information was collected on demographics, morbidity, quality of life, functional limitations, mental health, social functioning and health service utilisation. For informal caregivers, information was collected on demographics, hours of informal care and quality of life (including subjective care-related burden. RESULTS: Between 2010 and 2013, a total of 41 research projects contributed data to TOPICS-MDS, resulting in preliminary data available for 32,310 older persons and 3,940 informal caregivers. The majority of studies sampled were from primary care settings and inclusion criteria differed across studies. DISCUSSION: TOPICS-MDS is a public data repository which contains essential data to better understand health challenges experienced by older persons and informal caregivers. Such findings are relevant for countries where increasing health-related expenditure has necessitated the evaluation of contemporary health care delivery. Although open sharing of data can be difficult to achieve in practice, proactively addressing issues of data protection, conflicting data analysis requests and funding limitations during TOPICS-MDS developmental phase has fostered a data sharing culture. To date, TOPICS-MDS has been successfully incorporated into 41 research projects, thus

  8. Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Process, format, and clinimetric testing plan.

    Science.gov (United States)

    Goetz, Christopher G; Fahn, Stanley; Martinez-Martin, Pablo; Poewe, Werner; Sampaio, Cristina; Stebbins, Glenn T; Stern, Matthew B; Tilley, Barbara C; Dodel, Richard; Dubois, Bruno; Holloway, Robert; Jankovic, Joseph; Kulisevsky, Jaime; Lang, Anthony E; Lees, Andrew; Leurgans, Sue; LeWitt, Peter A; Nyenhuis, David; Olanow, C Warren; Rascol, Olivier; Schrag, Anette; Teresi, Jeanne A; Van Hilten, Jacobus J; LaPelle, Nancy

    2007-01-01

    This article presents the revision process, major innovations, and clinimetric testing program for the Movement Disorder Society (MDS)-sponsored revision of the Unified Parkinson's Disease Rating Scale (UPDRS), known as the MDS-UPDRS. The UPDRS is the most widely used scale for the clinical study of Parkinson's disease (PD). The MDS previously organized a critique of the UPDRS, which cited many strengths, but recommended revision of the scale to accommodate new advances and to resolve problematic areas. An MDS-UPDRS committee prepared the revision using the recommendations of the published critique of the scale. Subcommittees developed new material that was reviewed by the entire committee. A 1-day face-to-face committee meeting was organized to resolve areas of debate and to arrive at a working draft ready for clinimetric testing. The MDS-UPDRS retains the UPDRS structure of four parts with a total summed score, but the parts have been modified to provide a section that integrates nonmotor elements of PD: I, Nonmotor Experiences of Daily Living; II, Motor Experiences of Daily Living; III, Motor Examination; and IV, Motor Complications. All items have five response options with uniform anchors of 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. Several questions in Part I and all of Part II are written as a patient/caregiver questionnaire, so that the total rater time should remain approximately 30 minutes. Detailed instructions for testing and data acquisition accompany the MDS-UPDRS in order to increase uniform usage. Multiple language editions are planned. A three-part clinimetric program will provide testing of reliability, validity, and responsiveness to interventions. Although the MDS-UPDRS will not be published until it has successfully passed clinimetric testing, explanation of the process, key changes, and clinimetric programs allow clinicians and researchers to understand and participate in the revision process.

  9. Current State of the Art: Management of Higher Risk Myelodysplastic Syndromes.

    Science.gov (United States)

    Komrokji, Rami S

    2016-08-01

    The higher risk myelodysplastic syndrome (MDS) patients, defined by the International Prognostic Scoring System (IPSS) as intermediate-2 or high-risk groups, compromise a third of MDS patients who have an expected survival of less than 1.5 years. Our ability to better define higher risk MDS improved with the proposal of new clinical risk models such as the revised IPSS and by integration of molecular data, including somatic gene mutations. Allogeneic hematopoietic stem-cell transplantation (AHSCT) remains the only curative option. In higher risk MDS patients, proceeding early with AHSCT is associated with maximum survival gain. The decision to pursue AHSCT is individualized according to disease risk, comorbidities, and functional status. The role of therapy before AHSCT remains controversial, and the role of post-AHSCT maintenance is evolving. Hypomethylating agents are the only medications that alter the natural history of the disease. Azacitidine is the only drug reported to improve overall survival in higher risk MDS patients. Appropriate use and assessment of response is key for assuring patients benefit of such limited options. Treatment after failure of hypomethylating agents is an unmet need. The role of detectable somatic gene mutations in prognosis and tailoring therapy continue to emerge.

  10. Automated screening for myelodysplastic syndromes through analysis of complete blood count and cell population data parameters.

    Science.gov (United States)

    Raess, Philipp W; van de Geijn, Gert-Jan M; Njo, Tjin L; Klop, Boudewijn; Sukhachev, Dmitry; Wertheim, Gerald; McAleer, Tom; Master, Stephen R; Bagg, Adam

    2014-04-01

    The diagnosis of myelodysplastic syndromes (MDS) requires a high clinical index of suspicion to prompt bone marrow studies as well as subjective assessment of dysplastic morphology. We sought to determine if data collected by automated hematology analyzers during complete blood count (CBC) analysis might help to identify MDS in a routine clinical setting. We collected CBC parameters (including those for research use only and cell population data) and demographic information in a large (>5,000), unselected sequential cohort of outpatients. The cohort was divided into independent training and test groups to develop and validate a random forest classifier that identifies MDS. The classifier effectively identified MDS and had a receiver operating characteristic area under the curve (AUC) of 0.942. Platelet distribution width and the standard deviation of red blood cell distribution width were the most discriminating variables within the classifier. Additionally, a similar classifier was validated with an additional, independent set of >200 patients from a second institution with an AUC of 0.93. This retrospective study demonstrates the feasibility of identifying MDS in an unselected outpatient population using data routinely collected during CBC analysis with a classifier that has been validated using two independent data sets from different institutions.

  11. Therapy related myelodysplastic syndrome: A case report and review of literature

    Directory of Open Access Journals (Sweden)

    Smita Sonawane

    2011-01-01

    Full Text Available Therapy related myeloid neoplasm is directly related to previous cytotoxic chemotherapy or radiation therapy. We present a 47-year-old lady who developed therapy related myelodysplastic syndrome (MDS 2.5 years after she received four cycles of chemotherapy and local radiation therapy for carcinoma breast. She presented with bicytopenia with trilineage dyspoiesis in the peripheral blood, bone marrow aspirate and biopsy. Fluorescent in-situ hybridization studies did not reveal any of the common abnormalities associated with MDS. A diagnosis of therapy related MDS was rendered. Different studies have shown that patients treated with alkylating agents and ionizing radiation present as MDS with a latent period of 3-10 years. Our patient developed MDS within 2.5 years of starting chemotherapy and radiotherapy and did not reveal any of the conventional cytogenetic abnormalities. It highlights the importance of simple tests like a complete blood count and peripheral blood smear examination in follow-up of the patients treated with chemotherapy.

  12. [Point mutations of genes encoding proteins involvedin RNA splicing in patients with myelodysplastic syndromes].

    Science.gov (United States)

    Barańska, Marta; Czerwińska-Rybak, Joanna; Gil, Lidia; Komarnicki, Mieczysław

    2015-01-01

    The myelodysplastic syndromes (MDS) constitute heterogeneous group of clonal disorders, characterized by ineffective hematopoiesis, peripheral cytopenia and increased risk of acute myeloid leukemia development. Molecular mechanisms behind MDS have not been fully explained, however recent studies based on new technologies confirmed that epigenetic abnormalities and somatic mutation in the spliceasome machinery are crucial in pathogenesis of these diseases. Abnormal mRNA splicing (excision of intronic sequences from mRNA) has been found in over half of all MDS patients and resulted in accumulation of cytogenetical and molecular changes. The biological impact of splicing factor genes mutations has been evaluated only in a limited extend and current studies concentrate on analysis of MDS transcriptome. Molecular characteristic of classical and alternative splicing is presented in the paper, according to current knowledge. We review the most prominent findings from recent years concerning mutation in the spliceasome machinery with respect to MDS phenotype and disease prognosis. Perspectives in applying of novel diagnostic and therapeutic possibilities for myelodysplasia, based on spliceosome mutations identification are also presented.

  13. [Cold autoimmune hemolytic anemia complicated with relapsed myelodysplastic syndrome after allogeneic hematopoietic cell transplantation].

    Science.gov (United States)

    Okamura, Hiroshi; Nakane, Takahiko; Fujino, Keizo; Koh, Shiro; Yoshimura, Takuro; Nishimoto, Mitsutaka; Hayashi, Yoshiki; Koh, Hideo; Nakao, Yoshitaka; Nakamae, Hirohisa; Hino, Masayuki

    2015-04-01

    Myelodysplastic syndrome (MDS) is known to often be complicated by a range of autoimmune diseases. We herein present a case with MDS complicated by cold autoimmune hemolytic anemia (cold AIHA). The patient was a 51-year-old woman. She was diagnosed with MDS (refractory cytopenia with multilineage dysplasia) in May 2009. In January 2010, she underwent unrelated allogeneic bone marrow transplantation but was re-admitted in October 2010 for treatment of relapsed MDS. Despite daily transfusions of red blood cells, her anemia failed to improve. Her laboratory examinations showed a low haptoglobin level and elevation of indirect bilirubin and LDH. The direct Coombs test was positive at a low and at room temperature and cold agglutinin was negative. After confirming the diagnosis of cold AIHA, all transfusion fluids were warmed but her anemia still failed to improve. In addition to the warmed transfusion fluids, we administered corticosteroids, immunosuppressive agents and high-dose intravenous immunoglobulin infusions. This management strategy ameliorated the patient's hemolytic anemia. To our knowledge, MDS cases complicated by cold AIHA are rare. Our patient thus provides a valuable contribution to medical knowledge.

  14. Label-free imaging and identification of typical cells of acute myeloid leukaemia and myelodysplastic syndrome by Raman microspectroscopy

    NARCIS (Netherlands)

    Vanna, R.; Ronchi, P.; Lenferink, A.T.M.; Terstappen, L.W.M.M.; Tresoldi, C.; Morasso, C.; Mehn, D.; Bedoni, M.; Ciceri, F.; Otto, C.; Gramatica, F.

    2015-01-01

    In clinical practice, the diagnosis and classification of acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) start from the manual examination of stained smears of bone marrow (BM) and peripheral blood (PB) by using an optical microscope. This step is subjective and scarcely reproducib

  15. Thyroid function appears to be significantly reduced in Space-borne MDS mice

    Science.gov (United States)

    Saverio Ambesi-Impiombato, Francesco; Curcio, Francesco; Fontanini, Elisabetta; Perrella, Giuseppina; Spelat, Renza; Zambito, Anna Maria; Damaskopoulou, Eleni; Peverini, Manola; Albi, Elisabetta

    It is known that prolonged space flights induced changes in human cardiovascular, muscu-loskeletal and nervous systems whose function is regulated by the thyroid gland but, until now, no data were reported about thyroid damage during space missions. We have demonstrated in vitro that, during space missions (Italian Soyuz Mission "ENEIDE" in 2005, Shuttle STS-120 "ESPERIA" in 2007), thyroid in vitro cultured cells did not respond to thyroid stimulating hor-mone (TSH) treatment; they appeared healthy and alive, despite their being in a pro-apopotic state characterised by a variation of sphingomyelin metabolism and consequent increase in ce-ramide content. The insensitivity to TSH was largely due to a rearrangement of specific cell membrane microdomains, acting as platforms for TSH-receptor (TEXUS-44 mission in 2008). To study if these effects were present also in vivo, as part of the Mouse Drawer System (MDS) Tissue Sharing Program, we performed experiments in mice maintained onboard the Interna-tional Space Station during the long-duration (90 days) exploration mission STS-129. After return to earth, the thyroids isolated from the 3 animals were in part immediately frozen to study the morphological modification in space and in part immediately used to study the effect of TSH treatment. For this purpose small fragments of tissue were treated with 10-7 or 10-8 M TSH for 1 hour by using untreated fragments as controls. Then the fragments were fixed with absolute ethanol for 10 min at room temperature and centrifuged for 20 min. at 3000 x g. The supernatants were used for cAMP analysis whereas the pellet were used for protein amount determination and for immunoblotting analysis of TSH-receptor, sphingomyelinase and sphingomyelin-synthase. The results showed a modification of the thyroid structure and also the values of cAMP production after treatment with 10-7 M TSH for 1 hour were significantly lower than those obtained in Earth's gravity. The treatment with TSH

  16. Dicentric chromosomes and 20q11.2 amplification in MDS/AML with apparent monosomy 20.

    Science.gov (United States)

    Mackinnon, R N; Campbell, L J

    2007-01-01

    FISH analysis of 41 previously karyotyped cases of MDS and AML with apparent monosomy of chromosome 20 revealed a variety of dicentric abnormalities involving chromosome 20. These usually, but not always, involved a breakpoint in the long arm of chromosome 20 and loss of the common deleted region at 20q12. Not one case of true monosomy 20 was confirmed. We found evidence for dicentric chromosome formation in 21 of 24 unbalanced translocations containing chromosome 20 and that were studied in more detail. Subsequent loss of one of the centromeres had occurred in eight of these 24 cases, and was more frequent than centromere inactivation as a means of resolving the inherent instability of a dicentric chromosome. In the three cases with dicentric chromosomes from which proximal 20q had been excised along with the 20 centromere, the excised segment was retained, and in two of these it was amplified. Proximal 20q was clearly retained in all but three cases, and present in three or more copies in 17 of 41 cases. The retention and amplification of proximal 20q provides support for the hypothesis that there is an oncogene located in this region of 20q that is activated in cases of MDS/AML with del(20q). Apparent monosomy 20 in MDS/AML should be treated as evidence of unidentified chromosome 20 abnormalities, and familiarity with the typical G-banded morphology of these derivatives can help with their identification. The reported incidence of dicentric chromosomes is clearly an under-estimate but is increasing in myeloid disorders as more cases are studied with methods allowing their detection.

  17. Action orientation overcomes the ego depletion effect.

    Science.gov (United States)

    Dang, Junhua; Xiao, Shanshan; Shi, Yucai; Mao, Lihua

    2015-04-01

    It has been consistently demonstrated that initial exertion of self-control had negative influence on people's performance on subsequent self-control tasks. This phenomenon is referred to as the ego depletion effect. Based on action control theory, the current research investigated whether the ego depletion effect could be moderated by individuals' action versus state orientation. Our results showed that only state-oriented individuals exhibited ego depletion. For individuals with action orientation, however, their performance was not influenced by initial exertion of self-control. The beneficial effect of action orientation against ego depletion in our experiment results from its facilitation for adapting to the depleting task.

  18. Cardiac iron overload in chronically transfused patients with thalassemia, sickle cell anemia, or myelodysplastic syndrome.

    Science.gov (United States)

    de Montalembert, Mariane; Ribeil, Jean-Antoine; Brousse, Valentine; Guerci-Bresler, Agnes; Stamatoullas, Aspasia; Vannier, Jean-Pierre; Dumesnil, Cécile; Lahary, Agnès; Touati, Mohamed; Bouabdallah, Krimo; Cavazzana, Marina; Chauzit, Emmanuelle; Baptiste, Amandine; Lefebvre, Thibaud; Puy, Hervé; Elie, Caroline; Karim, Zoubida; Ernst, Olivier; Rose, Christian

    2017-01-01

    The risk and clinical significance of cardiac iron overload due to chronic transfusion varies with the underlying disease. Cardiac iron overload shortens the life expectancy of patients with thalassemia, whereas its effect is unclear in those with myelodysplastic syndromes (MDS). In patients with sickle cell anemia (SCA), iron does not seem to deposit quickly in the heart. Our primary objective was to assess through a multicentric study the prevalence of cardiac iron overload, defined as a cardiovascular magnetic resonance T2*8 ECs in the past year, and age older than 6 years. We included from 9 centers 20 patients with thalassemia, 41 with SCA, and 25 with MDS in 2012-2014. Erythrocytapharesis did not consistently prevent iron overload in patients with SCA. Cardiac iron overload was found in 3 (15%) patients with thalassemia, none with SCA, and 4 (16%) with MDS. The liver iron content (LIC) ranged from 10.4 to 15.2 mg/g dry weight, with no significant differences across groups (P = 0.29). Abnormal T2* was not significantly associated with any of the measures of transfusion or chelation. Ferritin levels showed a strong association with LIC. Non-transferrin-bound iron was high in the thalassemia and MDS groups but low in the SCA group (P<0.001). Hepcidin was low in thalassemia, normal in SCA, and markedly elevated in MDS (P<0.001). Two mechanisms may explain that iron deposition largely spares the heart in SCA: the high level of erythropoiesis recycles the iron and the chronic inflammation retains iron within the macrophages. Thalassemia, in contrast, is characterized by inefficient erythropoiesis, unable to handle free iron. Iron accumulation varies widely in MDS syndromes due to the competing influences of abnormal erythropoiesis, excess iron supply, and inflammation.

  19. Cardiac iron overload in chronically transfused patients with thalassemia, sickle cell anemia, or myelodysplastic syndrome

    Science.gov (United States)

    de Montalembert, Mariane; Ribeil, Jean-Antoine; Brousse, Valentine; Guerci-Bresler, Agnes; Stamatoullas, Aspasia; Vannier, Jean-Pierre; Dumesnil, Cécile; Lahary, Agnès; Touati, Mohamed; Bouabdallah, Krimo; Cavazzana, Marina; Chauzit, Emmanuelle; Baptiste, Amandine; Lefebvre, Thibaud; Puy, Hervé; Elie, Caroline

    2017-01-01

    The risk and clinical significance of cardiac iron overload due to chronic transfusion varies with the underlying disease. Cardiac iron overload shortens the life expectancy of patients with thalassemia, whereas its effect is unclear in those with myelodysplastic syndromes (MDS). In patients with sickle cell anemia (SCA), iron does not seem to deposit quickly in the heart. Our primary objective was to assess through a multicentric study the prevalence of cardiac iron overload, defined as a cardiovascular magnetic resonance T2*8 ECs in the past year, and age older than 6 years. We included from 9 centers 20 patients with thalassemia, 41 with SCA, and 25 with MDS in 2012-2014. Erythrocytapharesis did not consistently prevent iron overload in patients with SCA. Cardiac iron overload was found in 3 (15%) patients with thalassemia, none with SCA, and 4 (16%) with MDS. The liver iron content (LIC) ranged from 10.4 to 15.2 mg/g dry weight, with no significant differences across groups (P = 0.29). Abnormal T2* was not significantly associated with any of the measures of transfusion or chelation. Ferritin levels showed a strong association with LIC. Non-transferrin-bound iron was high in the thalassemia and MDS groups but low in the SCA group (P<0.001). Hepcidin was low in thalassemia, normal in SCA, and markedly elevated in MDS (P<0.001). Two mechanisms may explain that iron deposition largely spares the heart in SCA: the high level of erythropoiesis recycles the iron and the chronic inflammation retains iron within the macrophages. Thalassemia, in contrast, is characterized by inefficient erythropoiesis, unable to handle free iron. Iron accumulation varies widely in MDS syndromes due to the competing influences of abnormal erythropoiesis, excess iron supply, and inflammation. PMID:28257476

  20. Monosomal karyotype predicts poor survival after allogeneic stem cell transplantation in chromosome 7 abnormal myelodysplastic syndrome and secondary acute myeloid leukemia.

    Science.gov (United States)

    van Gelder, M; de Wreede, L C; Schetelig, J; van Biezen, A; Volin, L; Maertens, J; Robin, M; Petersen, E; de Witte, T; Kröger, N

    2013-04-01

    Treatment algorithms for poor cytogenetic-risk myelodysplastic syndrome (MDS), defined by chromosome 7 abnormalities or complex karyotype (CK), include allogeneic stem cell transplantation (alloSCT). We studied outcome of alloSCT in chromosome 7 abnormal MDS patients as this data are scarce in literature. We specifically focused on the impact of the extra presence of CK and monosomal karyotype (MK). The European Group for Blood and Marrow Transplantation database contained data on 277 adult MDS patients with a chromosome 7 abnormality treated with alloSCT. Median age at alloSCT was 45 years. Median follow-up of patients alive was 5 years. Five-year progression-free survival (PFS) and overall survival (OS) were 22% and 28%, respectively. In multivariate analysis, statistically significant predictors for worse PFS were higher MDS stages treated, but not in complete remission (CR) (hazards ratio (HR) 1.7), and the presence of CK (HR 1.5) or MK (HR 1.8). Negative predictive factors for OS were higher MDS stages treated, but not in CR (HR 1.8), and the presence of CK (HR 1.6) or MK (HR 1.7). By means of the cross-validated log partial likelihood, MK showed to have a better predictive value than CK. The results are relevant when considering alloSCT for higher-stage MDS patients having MK including a chromosome 7 abnormality.

  1. The translocation t(2;11)(p21;q23) without MLL gene rearrangement--a possible marker of good prognosis in myelodysplastic syndrome patients.

    Science.gov (United States)

    Dvorak, Pavel; Lysak, Daniel; Vokurka, Samuel; Michalova, Kyra; Sarova, Iveta; Jonasova, Anna; Hruba, Martina; Rykovska, Anna; Subrt, Ivan

    2014-06-01

    The translocation t(2;11)(p21;q23) is associated with de novo myelodysplastic syndromes (MDS) and has an overall frequency of approximately 1%. The outcome of MDS patients with this translocation is not clear until now, because most of the clinical data addressing the t(2;11)(p21;q23) has been collected without investigating the status of the mixed lineage leukemia (MLL) gene. In this report, we present seven new patients with MDS diagnosis and the t(2;11)(p21;q23) in bone marrow cells; all of them without MLL gene rearrangement. They were found in two databases consisting of 1185 patients of two Czech institutions. These patients tended to be younger and showed a strong male predominance. A cytological and histological assessment of bone marrow at diagnosis revealed only mild MDS with marked dysplasia in megakaryopoiesis. Similar to other primary abnormalities in MDS (e.g. deletion of 11q), the t(2;11)(p21;q23) was frequently associated with deletion of 5q. Our results stress the common clinicopathological features of this entity and indicate that the t(2;11)(p21;q23) may be associated with a good prognosis for MDS patients (median survival 72 months).

  2. Pesticide exposure as a risk factor for myelodysplastic syndromes: a meta-analysis based on 1,942 cases and 5,359 controls.

    Directory of Open Access Journals (Sweden)

    Jie Jin

    Full Text Available Pesticide exposure has been linked to increased risk of cancer at several sites, but its association with risk of myelodysplastic syndromes (MDS is still unclear. A meta-analysis of studies published through April, 2014 was performed to investigate the association of pesticide exposure with the risk of MDS.Studies were identified by searching the Web of Science, Cochrane Library and PubMed databases. Summary odds ratios (ORs with corresponding 95% confidence intervals (CIs were calculated using random- or fixed-effect models.This meta-analysis included 11 case-control studies, all of which demonstrated a correlation between pesticide exposure and a statistically significant increased risk of MDS (OR=1.95, 95% CI 1.23-3.09. In subgroup analyses, patients with pesticide exposure had increased risk of developing MDS if they were living in the Europe or Asia and had refractory anemia (RA or RA with ringed sideroblasts (RARS. Moreover, in the analysis by specific pesticides, increased risk was associated with exposure to insecticides (OR=1.71, 95% CI 1.22-2.40 but not exposure to herbicides or fungicides.This meta-analysis supports the hypothesis that exposure to pesticides increases the risk of developing MDS. Further prospective cohort studies are warranted to verify the association and guide clinical practice in MDS prevention.

  3. Cyclosporine Combined with Levamisole for Lower-Risk Myelodysplastic Syndromes.

    Science.gov (United States)

    Li, Xingxin; Shi, Jun; Wang, Min; Nie, Neng; Shao, Yingqi; Ge, Meili; Huang, Jinbo; Huang, Zhendong; Zhang, Jing; Zheng, Yizhou

    2015-01-01

    Clinical and experimental evidence suggests an immune-mediated pathophysiology in subjects with lower-risk myelodysplastic syndromes (MDS) in whom immunosuppressive therapy may be effective. The novel immunosuppressive strategy of cyclosporine A (CsA) alternately combined with levamisole (LMS; CsA + LMS regimen) can dramatically improve the response rate and survival in aplastic anemia from those of our previous study. Herein, we retrospectively analyzed the data of 89 lower-risk MDS patients who received the CsA + LMS regimen. A total of 63 patients (70.8%) achieved either complete remission or hematological improvement at 4 months. Overall, 51, 41 and 19 patients had erythroid, platelet and neutrophil responses, respectively. Following the CsA + LMS regimen, 6 patients progressed to more advanced MDS at a median interval of 5 months (range, 3-42 months). The estimated 24-month progression-free survival was 82.2% (95% CI, 72.84-91.56) for all patients. Within the median follow-up of 18.5 months (range, 7.0-61.0), 6 patients died. In conclusion, the CsA + LMS regimen alleviated cytopenias and improved survival and freedom from evolution, suggesting that it could be reserved as an alternative choice for lower-risk MDS.

  4. Myelodysplastic Syndromes in the Elderly: Treatment Options and Personalized Management.

    Science.gov (United States)

    Burgstaller, Sonja; Wiesinger, Petra; Stauder, Reinhard

    2015-11-01

    Myelodysplastic syndromes (MDS) are typical diseases of the elderly, with a median age of 68-75 years at initial diagnosis. Demographic changes producing an increased proportion of elderly in our societies mean the incidence of MDS will rise dramatically. Considering the increasing number of treatment options, ranging from best supportive care to hematopoietic stem cell transplantation (HSCT), decision making is rather complex in this cohort of patients. Moreover, aspects of the aging process also have to be considered in therapy planning. Treatment of elderly MDS patients is dependent on the patient's individual risk and prognosis. Comorbidities play an essential role as predictors of survival and therapy tolerance. Age-adjusted models and the use of geriatric assessment scores are described as a basis for individualized treatment algorithms. Specific treatment recommendations for the different groups of patients are given. Currently available therapeutic agents, including supportive care, erythropoiesis-stimulating agents (ESAs), immune-modulating agents, hypomethylating agents, and HSCT are described in detail and discussed with a special focus on elderly MDS patients. The inclusion of elderly patients in clinical trials is of utmost importance to obtain data on efficacy and safety in this particular group of patients. Endpoints relevant for the elderly should be integrated, including maintenance of quality of life and functional activities as well as evaluation of use of healthcare resources.

  5. Diagnostic Utility of Flow Cytometry in Myelodysplastic Syndromes

    Science.gov (United States)

    Aanei, Carmen Mariana; Picot, Tiphanie; Tavernier, Emmanuelle; Guyotat, Denis; Campos Catafal, Lydia

    2016-01-01

    Myelodysplastic syndromes (MDSs) are clonal disorders of hematopoiesis that exhibit heterogeneous clinical presentation and morphological findings, which complicates diagnosis, especially in early stages. Recently, refined definitions and standards in the diagnosis and treatment of MDS were proposed, but numerous questions remain. Multiparameter flow cytometry (MFC) is a helpful tool for the diagnostic workup of patients with suspected MDS, and various scores using MFC data have been developed. However, none of these methods have achieved the sensitivity that is required for a reassuring diagnosis in the absence of morphological abnormalities. One reason may be that each score evaluates one or two lineages without offering a broad view of the dysplastic process. The combination of two scores (e.g., Ogata and Red Score) improved the sensitivity from 50–60 to 88%, but the positive (PPV) and negative predictive values (NPV) must be improved. There are prominent differences between study groups when these scores are tested. Further research is needed to maximize the sensitivity of flow cytometric analysis in MDS. This review focuses on the application of flow cytometry for MDS diagnosis and discusses the advantages and limitations of different approaches. PMID:27446807

  6. Superoxide anion production by neutrophils in myelodysplastic syndromes (preleukemia.

    Directory of Open Access Journals (Sweden)

    Takahashi,Isao

    1988-02-01

    Full Text Available Superoxide anion (O2- production by neutrophils from 14 untreated patients with acute nonlymphocytic leukemia (ANLL was significantly less than that of healthy controls (4.93 +/- 1.99 vx 6.20 +/- 1.53 nmol/min/10(6 neutrophils, p less than 0.05. In 10 patients with myelodysplastic syndrome (MDS, however, it was not significantly different from the control level although 6 of the 10 patients had low levels, when individual patients were compared with the lower limit of the control range. An inverse correlation between the O2- production of neutrophils and the percentage of leukemic cells in the marrow existed in ANLL (r = -0.55, p less than 0.01, but not in MDS. Three of 4 MDS patients who died of pneumonia prior to leukemic conversion showed a low level of O2- production. The impaired O2- production by neutrophils from some MDS patients, probably due to the faulty differentiation from leukemic clones, may be one of the causes of enhanced susceptibility to infection.

  7. "When the going gets tough, who keeps going?" Depletion sensitivity moderates the ego-depletion effect

    NARCIS (Netherlands)

    Salmon, Stefanie J.; Adriaanse, Marieke A.; De Vet, Emely; Fennis, Bob M.; De Ridder, Denise T D

    2014-01-01

    Self-control relies on a limited resource that can get depleted, a phenomenon that has been labeled ego-depletion. We argue that individuals may differ in their sensitivity to depleting tasks, and that consequently some people deplete their self-control resource at a faster rate than others. In thre

  8. "When the going gets tough, who keeps going?" : Depletion sensitivity moderates the ego-depletion effect

    NARCIS (Netherlands)

    Salmon, Stefanie J.; Adriaanse, Marieke A.; De Vet, Emely; Fennis, Bob M.; De Ridder, Denise T. D.

    2014-01-01

    Self-control relies on a limited resource that can get depleted, a phenomenon that has been labeled ego-depletion. We argue that individuals may differ in their sensitivity to depleting tasks, and that consequently some people deplete their self-control resource at a faster rate than others. In thre

  9. "When the going gets tough, who keeps going?" : Depletion sensitivity moderates the ego-depletion effect

    NARCIS (Netherlands)

    Salmon, Stefanie J.; Adriaanse, Marieke A.; De Vet, Emely; Fennis, Bob M.; De Ridder, Denise T. D.

    2014-01-01

    Self-control relies on a limited resource that can get depleted, a phenomenon that has been labeled ego-depletion. We argue that individuals may differ in their sensitivity to depleting tasks, and that consequently some people deplete their self-control resource at a faster rate than others. In thre

  10. Physics of Fully Depleted CCDs

    CERN Document Server

    Holland, S E; Kolbe, W F; Lee, J S

    2014-01-01

    In this work we present simple, physics-based models for two effects that have been noted in the fully depleted CCDs that are presently used in the Dark Energy Survey Camera. The first effect is the observation that the point-spread function increases slightly with the signal level. This is explained by considering the effect on charge-carrier diffusion due to the reduction in the magnitude of the channel potential as collected signal charge acts to partially neutralize the fixed charge in the depleted channel. The resulting reduced voltage drop across the carrier drift region decreases the vertical electric field and increases the carrier transit time. The second effect is the observation of low-level, concentric ring patterns seen in uniformly illuminated images. This effect is shown to be most likely due to lateral deflection of charge during the transit of the photogenerated carriers to the potential wells as a result of lateral electric fields. The lateral fields are a result of space charge in the fully...

  11. The 1988 Antarctic ozone depletion - Comparison with previous year depletions

    Science.gov (United States)

    Schoeberl, Mark R.; Stolarski, Richard S.; Krueger, Arlin J.

    1989-01-01

    The 1988 spring Antarctic ozone depletion was observed by TOMS to be substantially smaller than in recent years. The minimum polar total ozone values declined only 15 percent during September 1988, compared to nearly 50 percent during September 1987. At southern midlatitudes, exceptionally high total ozone values were recorded beginning in July 1988. The total integrated southern hemispheric ozone increased rapidly during the Austral spring, approaching 1980 levels during October. The high midlatitude total ozone values were associated with a substantial increase in eddy activity as indicated by the standard deviation in total ozone in the zonal band 30-60 deg S. Mechanisms through which the increased midlatitude eddy activity could disrupt the formation of the Antarctic ozone hole are briefly discussed.

  12. Establishment and validation of an updated diagnostic FCM scoring system based on pooled immunophenotyping in CD34+ blasts and its clinical significance for myelodysplastic syndromes.

    Directory of Open Access Journals (Sweden)

    Feng Xu

    Full Text Available Abnormal immunophenotypes of hematopoietic cells can be detected by flow cytometry (FCM to assist the diagnosis of myelodysplastic syndromes (MDS. We previously established a FCM scoring system for the diagnosis of low-grade MDS. In this study, additional valuable antigens were involved in an updated FCM scoring system (u-FCMSS for all MDS subtypes. The u-FCMSS showed better sensitivity and specificity (89.4% and 96.5% in distinguishing MDS from non-clonal cytopenia diseases. Validation analysis of u-FCMSS exhibited comparable sensitivity and specificity (86.7% and 93.3% and high agreement rate (88.9% of FCM diagnosis with morphological diagnosis at optimal cut-off (score 3. The distribution of FCM scores in different disease stages was also analyzed. The results suggested that early scoring from abnormal expression of mature myeloid/lymphoid antigens and advanced scoring from abnormal expression of stem/progenitor antigens expression constituted the majority of FCM scores of low-grade and high-grade MDS, respectively. High early scoring was generally accompanied by low IPSS-R score and superior survival, whereas high advanced scoring was accompanied by high IPSS-R score and inferior survival. In addition, the low-risk MDS patients with high early scoring and low advanced scoring were revealed as candidates for immunosuppressive therapy, whereas those with high advanced scoring and low early scoring may be more suitable for decitabine treatment. In conclusion, the u-FCMSS is a useful tool for diagnosis, prognosis and treatment selection in MDS. Differences in classes of antigens expressed and in distribution of FCM scores may reflect distinctive stage characteristics of MDS during disease progression.

  13. MECP2 Duplication Syndrome: Evidence of Enhanced Oxidative Stress. A Comparison with Rett Syndrome.

    Science.gov (United States)

    Signorini, Cinzia; De Felice, Claudio; Leoncini, Silvia; Møller, Rikke S; Zollo, Gloria; Buoni, Sabrina; Cortelazzo, Alessio; Guerranti, Roberto; Durand, Thierry; Ciccoli, Lucia; D'Esposito, Maurizio; Ravn, Kirstine; Hayek, Joussef

    2016-01-01

    Rett syndrome (RTT) and MECP2 duplication syndrome (MDS) are neurodevelopmental disorders caused by alterations in the methyl-CpG binding protein 2 (MECP2) gene expression. A relationship between MECP2 loss-of-function mutations and oxidative stress has been previously documented in RTT patients and murine models. To date, no data on oxidative stress have been reported for the MECP2 gain-of-function mutations in patients with MDS. In the present work, the pro-oxidant status and oxidative fatty acid damage in MDS was investigated (subjects n = 6) and compared to RTT (subjects n = 24) and healthy condition (subjects n = 12). Patients with MECP2 gain-of-function mutations showed increased oxidative stress marker levels (plasma non-protein bound iron, intraerythrocyte non-protein bound iron, F2-isoprostanes, and F4-neuroprostanes), as compared to healthy controls (P ≤ 0.05). Such increases were similar to those observed in RTT patients except for higher plasma F2-isoprostanes levels (P < 0.0196). Moreover, plasma levels of F2-isoprostanes were significantly correlated (P = 0.0098) with the size of the amplified region. The present work shows unique data in patients affected by MDS. For the first time MECP2 gain-of-function mutations are indicated to be linked to an oxidative damage and related clinical symptoms overlapping with those of MECP2 loss-of-function mutations. A finely tuned balance of MECP2 expression appears to be critical to oxidative stress homeostasis, thus shedding light on the relevance of the redox balance in the central nervous system integrity.

  14. MECP2 Duplication Syndrome: Evidence of Enhanced Oxidative Stress. A Comparison with Rett Syndrome.

    Directory of Open Access Journals (Sweden)

    Cinzia Signorini

    Full Text Available Rett syndrome (RTT and MECP2 duplication syndrome (MDS are neurodevelopmental disorders caused by alterations in the methyl-CpG binding protein 2 (MECP2 gene expression. A relationship between MECP2 loss-of-function mutations and oxidative stress has been previously documented in RTT patients and murine models. To date, no data on oxidative stress have been reported for the MECP2 gain-of-function mutations in patients with MDS. In the present work, the pro-oxidant status and oxidative fatty acid damage in MDS was investigated (subjects n = 6 and compared to RTT (subjects n = 24 and healthy condition (subjects n = 12. Patients with MECP2 gain-of-function mutations showed increased oxidative stress marker levels (plasma non-protein bound iron, intraerythrocyte non-protein bound iron, F2-isoprostanes, and F4-neuroprostanes, as compared to healthy controls (P ≤ 0.05. Such increases were similar to those observed in RTT patients except for higher plasma F2-isoprostanes levels (P < 0.0196. Moreover, plasma levels of F2-isoprostanes were significantly correlated (P = 0.0098 with the size of the amplified region. The present work shows unique data in patients affected by MDS. For the first time MECP2 gain-of-function mutations are indicated to be linked to an oxidative damage and related clinical symptoms overlapping with those of MECP2 loss-of-function mutations. A finely tuned balance of MECP2 expression appears to be critical to oxidative stress homeostasis, thus shedding light on the relevance of the redox balance in the central nervous system integrity.

  15. IPMDS-Sponsored Scale Translation Program: Process, Format, and Clinimetric Testing Plan for the MDS-UPDRS and UDysRS.

    Science.gov (United States)

    Goetz, Christopher G; Stebbins, Glenn T; Wang, Lu; LaPelle, Nancy R; Luo, Sheng; Tilley, Barbara C

    2014-06-01

    We present the methodology and results of the clinimetric testing program for non-English translations of International Parkinson and Movement Disorder Society (MDS)-sponsored scales. The programs focus on the MDS revision of the UPDRS (MDS-UPDRS) and the Unified Dyskinesia Rating Scale (UDysRS). The original development teams of both the MDS-UPDRS and UDysRS envisioned official non-English translations and instituted a rigorous translation methodology. The formal process includes five core steps: (1) registration and start-up; (2) translation and independent back-translation; (3) cognitive pretesting to establish that the translation is clear and that it is comfortably administered to and completed by native-speaker raters and patients; (4) field testing in the native language using a large sample of Parkinson's disease patients; and (5) full clinimetric testing. To date, the MDS-UPDRS has 21 active language programs. Nine official translations are available, having completed all phases successfully, and the others are in different stages of development. For the UDysRS, 19 programs are active, with three official translations now available and the rest in development at different stages. Very few scales in neurology and none in movement disorders have fully validated translations, and this model may be adopted or modified by other scale programs to allow careful validation of translations. Having validated translations allows for maximal homogeneity of tools utilized in multicenter research or clinical trial programs.

  16. Study on the FANCF Protein Expression and Methylation in Myelodysplastic Syndrome%骨髓增生异常综合征中FANCF蛋白及甲基化研究

    Institute of Scientific and Technical Information of China (English)

    娄晔; 于艺冰; 詹立辉; 邓娜; 李巍巍; 樊华

    2013-01-01

    目的研究骨髓增生异常综合征(MDS)中FANCF基因甲基化状态及其蛋白表达,探讨FANCF基因甲基化及蛋白表达与MDS发病的相关性.方法 以MDS患者骨髓提取的单个核细胞为研究对象,采用免疫组织化学染色法、Western blot检测FANCF蛋白表达、甲基化特异聚合酶链反应(MSP)检测FANCF基因的甲基化状态.结果 FANCF蛋白在MDS-RA组低表达,MDS-RAEB/T组更低表达,对照组正常表达;MDS组与对照组比较表达明显减低,差异有统计学意义(P<0.05).MDS组有明显甲基化,与对照组比较差异有统计学意义(P<0.05).结论 FANCF蛋白在MDS组中表达下调,FA通路不能形成,可能与MDS发病有相关性.FANCF基因在MDS患者中呈现高甲基化状态,提示FANCF基因的高甲基化状态可能在MDS的疾病发生过程中起到一定的作用;MDS-RAEB/T组甲基化状态高于MDS-RA组,提示FANCF基因的甲基化可能与MDS的预后相关.%Objective To investigate the methylation status of FANCF gene and the expression of FANCF protein in myelodysplastic syndrome (MDS).Methods Mono-nucleus cells were isolated from bone marrow of MDS.Expression of FANCF protein was detected by immunohistochemistry method and Western blot.Methylation special PCR was used to detect the methylation status of FANCF' CpG island.Results The FANCF protein is low expressed in MDS-RA group and MDS-RAEB/T group (significantly lower),but normal in negative controls.The expressions of MDS are lower than negative controls with a statistical significance (P < 0.05).Methylation status of FANCF gene were significantly higher in MDS group than in negative controls (P < 0.05).Conclusion The FANCF protein is lower expressed in both high-danger and low-danger MDS,which subsequent disrupt the FA pathway.That may be correlated with the prognosis of MDS.Methylation of FANCF is obviously higher in MDS group than negative control,suggesting it may play a role in the pathogenesis of MDS

  17. Depleted uranium disposal options evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Hertzler, T.J.; Nishimoto, D.D.; Otis, M.D. [Science Applications International Corp., Idaho Falls, ID (United States). Waste Management Technology Div.

    1994-05-01

    The Department of Energy (DOE), Office of Environmental Restoration and Waste Management, has chartered a study to evaluate alternative management strategies for depleted uranium (DU) currently stored throughout the DOE complex. Historically, DU has been maintained as a strategic resource because of uses for DU metal and potential uses for further enrichment or for uranium oxide as breeder reactor blanket fuel. This study has focused on evaluating the disposal options for DU if it were considered a waste. This report is in no way declaring these DU reserves a ``waste,`` but is intended to provide baseline data for comparison with other management options for use of DU. To PICS considered in this report include: Retrievable disposal; permanent disposal; health hazards; radiation toxicity and chemical toxicity.

  18. Recurrent DNMT3A R882 Mutations in Chinese Patients with Acute Myeloid Leukemia and Myelodysplastic Syndrome

    OpenAIRE

    2011-01-01

    Somatic mutations of DNMT3A gene have recently been reported in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We examined the entire coding sequences of DNMT3A gene by high-resolution melting analysis and sequencing in Chinese patients with myeloid malignancies. R882 mutations were found in 12/182 AML and in 4/51 MDS, but not in either 79 chronic myeloid leukemia (CML), or 57 myeloproliferative neoplasms (MPNs), or 4 chronic monomyelocytic leukemia. No other DNMT3A mutation...

  19. Reduced evolvability of Escherichia coli MDS42, an IS-less cellular chassis for molecular and synthetic biology applications

    Directory of Open Access Journals (Sweden)

    Blattner Frederick R

    2010-05-01

    Full Text Available Abstract Background Evolvability is an intrinsic feature of all living cells. However, newly emerging, evolved features can be undesirable when genetic circuits, designed and fabricated by rational, synthetic biological approaches, are installed in the cell. Streamlined-genome E. coli MDS42 is free of mutation-generating IS elements, and can serve as a host with reduced evolutionary potential. Results We analyze an extreme case of toxic plasmid clone instability, and show that random host IS element hopping, causing inactivation of the toxic cloned sequences, followed by automatic selection of the fast-growing mutants, can prevent the maintenance of a clone developed for vaccine production. Analyzing the molecular details, we identify a hydrophobic protein as the toxic byproduct of the clone, and show that IS elements spontaneously landing in the cloned fragment relieve the cell from the stress by blocking transcription of the toxic gene. Bioinformatics analysis of sequence reads from early shotgun genome sequencing projects, where clone libraries were constructed and maintained in E. coli, suggests that such IS-mediated inactivation of ectopic genes inhibiting the growth of the E. coli cloning host might happen more frequently than generally anticipated, leading to genomic instability and selection of altered clones. Conclusions Delayed genetic adaptation of clean-genome, IS-free MDS42 host improves maintenance of unstable genetic constructs, and is suggested to be beneficial in both laboratory and industrial settings.

  20. PR-domain-containing Mds1-Evi1 is critical for long-term hematopoietic stem cell function.

    Science.gov (United States)

    Zhang, Yi; Stehling-Sun, Sandra; Lezon-Geyda, Kimberly; Juneja, Subhash C; Coillard, Lucie; Chatterjee, Gouri; Wuertzer, Charles A; Camargo, Fernando; Perkins, Archibald S

    2011-10-06

    The Mds1 and Evi1 complex locus (Mecom) gives rise to several alternative transcripts implicated in leukemogenesis. However, the contribution that Mecom-derived gene products make to normal hematopoiesis remains largely unexplored. To investigate the role of the upstream transcription start site of Mecom in adult hematopoiesis, we created a mouse model with a lacZ knock-in at this site, termed ME(m1), which eliminates Mds1-Evi1 (ME), the longer, PR-domain-containing isoform produced by the gene (also known as PRDM3). β-galactosidase-marking studies revealed that, within hematopoietic cells, ME is exclusively expressed in the stem cell compartment. ME deficiency leads to a reduction in the number of HSCs and a complete loss of long-term repopulation capacity, whereas the stem cell compartment is shifted from quiescence to active cycling. Genetic exploration of the relative roles of endogenous ME and EVI1 isoforms revealed that ME preferentially rescues long-term HSC defects. RNA-seq analysis in Lin(-)Sca-1(+)c-Kit(+) cells (LSKs) of ME(m1) documents near complete silencing of Cdkn1c, encoding negative cell-cycle regulator p57-Kip2. Reintroduction of ME into ME(m1) LSKs leads to normalization of both p57-Kip2 expression and growth control. Our results clearly demonstrate a critical role of PR-domain-containing ME in linking p57-kip2 regulation to long-term HSC function.

  1. Prognostic value of isocitrate dehydrogenase mutations in myelodysplastic syndromes: a retrospective cohort study and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Jie Jin

    Full Text Available Recent genomic sequencing efforts have identified a number of recurrent mutations in myelodysplastic syndromes (MDS that may contribute to disease progression and overall survival, including mutations in isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2.Pretreatment bone marrow (BM samples were acquired from mononuclear cells in 146 adult patients with de novo MDS from January 2006 to June 2013. Polymerase chain reaction (PCR and direct sequencing were performed on exon 4 of IDH1/2 genes and mutation status was correlated with overall survival (OS and leukemia-free survival (LFS. We then performed a meta-analysis combining previously published and current studies to explore the effect of IDH mutations on OS and LFS in MDS.In our study, somatic mutations of either IDH gene were discovered in 11 MDS patients (7.53% and were significantly correlated with poorer OS (P = 0.007. IDH mutations were specifically associated with a poorer OS in the intermediate-1 risk group by the International Prognostic Scoring System (IPSS (P = 0.039. In addition, we discovered decitabine achieved a better therapeutic effect compared to other treatments in IDH mutation-positive patients (P = 0.023. We identified six previous studies of IDH mutations in MDS. A meta-analysis of these studies included 111 MDS patients IDH mutations and 1671 MDS patients with wild-type IDH1/2. The hazard ratios (HRs of OS and LFS for patients with IDH mutations were 1.62 (95% CI, 1.27-2.09 and 2.21 (95% CI, 1.48-3.30, respectively.The results from our study and the meta-analysis provide firm evidence that IDH mutations are significantly associated with poorer clinical outcomes in MDS. Identification of IDH mutations may be pivotal for better risk stratification in MDS patients and improving IPSS score. Additionally, hypomethylating agents may be an effective treatment option for MDS patients with IDH mutations.

  2. Inflammatory arthritis in patients with myelodysplastic syndromes: a multicenter retrospective study and literature review of 68 cases.

    Science.gov (United States)

    Mekinian, Arsène; Braun, Thorsten; Decaux, Olivier; Falgarone, Géraldine; Toussirot, Eric; Raffray, Loic; Omouri, Mohamed; Gombert, Bruno; De Wazieres, Benoit; Buchdaul, Anne-Laure; Ziza, Jean-Marc; Launay, David; Denis, Guillaume; Madaule, Serge; Rose, Christian; Grignano, Eric; Fenaux, Pierre; Fain, Olivier

    2014-01-01

    We describe the characteristics and outcome of inflammatory arthritis in patients with myelodysplastic syndrome (MDS) in a French multicenter retrospective study. Twenty-two patients with MDS (median age, 77.5 yr [interquartile range, 69-81]; 10 women) were included. Inflammatory arthritis presented as polyarthritis in 17 cases (77%) and with symmetric involvement in 15 cases (68%). At diagnosis, the median disease activity score 28 based on C-reactive protein (DAS28-CRP) was 4.5 [2-6.5]. Two patients had anti-citrullinated protein antibodies (ACPAs), and 1 had radiologic erosions. The median time between the diagnoses of arthritis and MDS was 10 months [6-42], with a median articular symptom duration of 3 months [2-8]. The diagnosis of both diseases was concomitant in 6 cases (27%); arthritis preceded MDS in 12 cases (55%), and occurred after MDS in 4 (18%). While the number of swollen and tender joints significantly decreased during follow-up, as did the median DAS28-CRP (from 4.3 [3.8-4.6] at baseline to 2.9 [1.75-3.3]; p 20 mg/L) in 8 patients (42%). Nevertheless, radiographic progression and new ACPA positivity were not observed during a median follow-up of 29 months [9-76]. While most of the patients were treated with steroids (n = 16) for arthritis, additional treatment was administered in only 4 patients (hydroxychloroquine, n = 2; sulfasalazine [Salazopyrin] and etanercept, n = 1, respectively). Eleven patients died during follow-up from acute myeloid leukemia (n = 5); infections (n = 3); or cerebral bleeding, cardiorespiratory failure, or undetermined cause (n = 1, respectively). Inflammatory arthritis associated with MDS can have various presentations and is often seronegative and nonerosive. Steroids alone are the most common treatment in MDS-associated arthritis, but that treatment is insufficient to control arthritis. Steroid-sparing strategies need to be identified.

  3. Scheie syndrome

    Science.gov (United States)

    ... Hurler syndrome) MPS II (Hunter syndrome) MPS IV (Morquio syndrome) MPS III (Sanfilippo syndrome) Causes Scheie syndrome ... Autosomal recessive Cloudy cornea Hearing loss Hurler syndrome Morquio syndrome Review Date 4/20/2015 Updated by: ...

  4. Ego depletion increases risk-taking.

    Science.gov (United States)

    Fischer, Peter; Kastenmüller, Andreas; Asal, Kathrin

    2012-01-01

    We investigated how the availability of self-control resources affects risk-taking inclinations and behaviors. We proposed that risk-taking often occurs from suboptimal decision processes and heuristic information processing (e.g., when a smoker suppresses or neglects information about the health risks of smoking). Research revealed that depleted self-regulation resources are associated with reduced intellectual performance and reduced abilities to regulate spontaneous and automatic responses (e.g., control aggressive responses in the face of frustration). The present studies transferred these ideas to the area of risk-taking. We propose that risk-taking is increased when individuals find themselves in a state of reduced cognitive self-control resources (ego-depletion). Four studies supported these ideas. In Study 1, ego-depleted participants reported higher levels of sensation seeking than non-depleted participants. In Study 2, ego-depleted participants showed higher levels of risk-tolerance in critical road traffic situations than non-depleted participants. In Study 3, we ruled out two alternative explanations for these results: neither cognitive load nor feelings of anger mediated the effect of ego-depletion on risk-taking. Finally, Study 4 clarified the underlying psychological process: ego-depleted participants feel more cognitively exhausted than non-depleted participants and thus are more willing to take risks. Discussion focuses on the theoretical and practical implications of these findings.

  5. An update on the safety and efficacy of decitabine in the treatment of myelodysplastic syndromes

    Directory of Open Access Journals (Sweden)

    Jacqueline S Garcia

    2010-02-01

    Full Text Available Jacqueline S Garcia1, Nitin Jain1, Lucy A Godley1,21Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL, USA; 2Cancer Research Center, The University of Chicago, Chicago, IL, USAAbstract: Myelodysplastic syndromes (MDS are clonal bone marrow malignancies characterized by peripheral cytopenias and dysplastic changes in the bone marrow with various clinical features. Patients with MDS, in particular those with intermediate-2 (Int-2 and high-risk disease, have a poor prognosis. The mainstay of treatment includes cytoxic chemotherapy and supportive care. Over the last decade, promising results from studies focusing on hypomethylating agents, such as decitabine (5-aza-deoxycytidine and 5-azacitidine, have led to the expansion of the therapeutic arsenal for MDS. This review presents the current data available on the clinical efficacy and safety profile for decitabine as a treatment for MDS. Although not fully understood, decitabine’s antitumor activity may involve its ability to induce hypomethylation and reactivation of genes responsible for cellular differentiation, stimulate an immune response, induce DNA damage/apoptotic response pathways, and/or augment stem cell renewal. Future studies that use epigenetic therapies that combine hypomethylating agents with histone deacetylase inhibitors (HDACi and head-to-head comparison studies of decitabine and 5-azacitidine will provide valuable pre-clinical and clinical data, enhancing our understanding of these drugs.Keywords: decitabine, 5-aza-deoxycytidine, 5-azacitidine, myelodysplastic syndromes

  6. Potential environmental benefits of improving recycling of polyolefines – LCA of Magnetic density separation (MDS) developed in the EU FP7 funded project W2Plastic

    DEFF Research Database (Denmark)

    Olsen, Stig Irving; Bonou, Alexandra

    2012-01-01

    The core of the EU FP7 funded project W2Plastic is development of a magnetic density separation (MDS) of polyolefines in order to improve the sorting efficiency of these polymer types in different waste fractions. As part of the project a life cycle assessment is performed in order to firstly...... identify eco-design criteria for the development and secondly to document the potential environmental improvement of polyolefin recycling using the MDS technology. A preliminary study focusing solely on the carbon footprint benefits of recycling plastic waste compared to virgin production of polymers...

  7. Pleural effusions in patients with acute leukemia and myelodysplastic syndrome.

    Science.gov (United States)

    Faiz, Saadia A; Bashoura, Lara; Lei, Xiudong; Sampat, Keeran R; Brown, Tiffany C; Eapen, George A; Morice, Rodolfo C; Ferrajoli, Alessandra; Jimenez, Carlos A

    2013-02-01

    Pleural effusions are rarely observed in patients with acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL) and myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN). Therefore the underlying etiology of pleural effusions and the efficacy and safety of pleural procedures in this population has not been well studied. In a retrospective review of cases from 1997 to 2007, we identified 111 patients with acute leukemia or MDS/MPN who underwent pleural procedures. Clinical characteristics were reviewed, and survival outcomes were estimated by Kaplan-Meier methods. A total of 270 pleural procedures were performed in 111 patients (69 AML, 27 ALL, 15 MDS/MPN). The main indications for pleural procedures were possible infection (49%) and respiratory symptoms (48%), and concomitant clinical symptoms included fever (34%), dyspnea (74%), chest pain (24%) and cough (37%). Most patients had active disease (61%). The most frequent etiology of pleural effusions was infection (47%), followed by malignancy (36%). Severe thrombocytopenia (platelet count < 20 × 10(3)/µL) was present in 43% of the procedures, yet the procedural complication rate was only 1.9%. Multivariate analysis revealed that older age, AML, MDS/MPN and active disease status were associated with a shorter median overall survival. Infection and malignant involvement are the most common causes of pleural effusion in patients with acute leukemia or MDS. After optimizing platelet count and coagulopathy, thoracentesis may be performed safely and with high diagnostic yield in this population. Survival in these patients is determined by the response to treatment of the hematologic malignancy.

  8. Investigation of intranodal depletion effects

    Energy Technology Data Exchange (ETDEWEB)

    Forslund, P. E-mail: petri.forslund@se.abb.com; Mueller, E.; Lindahl, S

    2001-02-01

    The modeling of depletion induced intranodal effects on important neutron physical parameters in nodal diffusion theory is addressed. Consideration is given to two situations where these aspects are of particular interest, namely, in mixed oxide cores where strong interaction between uranium and plutonium mixed oxide assemblies occur, and in boiling water reactor cores where significant control rod history effects are encountered. A model based on a low order polynomial representation of intranodal cross-section spatial behaviour is considered. Two approaches for determining the constraints for the polynomial fitting procedure are applied. The first one is a conventional method employing intranodal exposure values, whereas the second model combines intranodal exposure and isotopic inventory information. Numerical studies are performed in order to evaluate the relative merits of the different models. It is demonstrated that pin power predictions are significantly influenced by intranodal effects. It is also found that the combined use of intranodal isotopic inventory and exposure distributions for estimating intranodal cross-section behaviour significantly improves the accuracy in pin powers over the more traditional approach of utilizing exposure distributions only.

  9. Depleted argon from underground sources

    Energy Technology Data Exchange (ETDEWEB)

    Back, H.O.; /Princeton U.; Alton, A.; /Augustana U. Coll.; Calaprice, F.; Galbiati, C.; Goretti, A.; /Princeton U.; Kendziora, C.; /Fermilab; Loer, B.; /Princeton U.; Montanari, D.; /Fermilab; Mosteiro, P.; /Princeton U.; Pordes, S.; /Fermilab

    2011-09-01

    Argon is a powerful scintillator and an excellent medium for detection of ionization. Its high discrimination power against minimum ionization tracks, in favor of selection of nuclear recoils, makes it an attractive medium for direct detection of WIMP dark matter. However, cosmogenic {sup 39}Ar contamination in atmospheric argon limits the size of liquid argon dark matter detectors due to pile-up. The cosmic ray shielding by the earth means that Argon from deep underground is depleted in {sup 39}Ar. In Cortez Colorado a CO{sub 2} well has been discovered to contain approximately 500ppm of argon as a contamination in the CO{sub 2}. In order to produce argon for dark matter detectors we first concentrate the argon locally to 3-5% in an Ar, N{sub 2}, and He mixture, from the CO{sub 2} through chromatographic gas separation. The N{sub 2} and He will be removed by continuous cryogenic distillation in the Cryogenic Distillation Column recently built at Fermilab. In this talk we will discuss the entire extraction and purification process; with emphasis on the recent commissioning and initial performance of the cryogenic distillation column purification.

  10. Durable Hematological and Major Cytogenetic Response in a Patient with Isolated 20q Deletion Myelodysplastic Syndrome Treated with Lenalidomide

    Directory of Open Access Journals (Sweden)

    Bagi Jana

    2014-01-01

    Full Text Available Myelodysplastic syndrome (MDS is a clonal bone marrow disorder characterized by ineffective hematopoiesis. It is characterized by peripheral blood cytopenia and significant risk of progression to acute myeloid leukemia result. Deletion of the long arm of chromosome 20 (20q deletion is present in 3–7% of patients with MDS. Lenalidomide is an immunomodulatory agent with antiangiogenic activity. It is FDA approved for the treatment of anemia in patients with low or int-1 risk MDS with chromosome 5q deletion with or without additional cytogenetic abnormalities. Study of lenalidomide in patients with MDS without 5q deletion but other karyotypic abnormalities demonstrated meaningful activity in transfusion dependent patients; however, response of patients with isolated 20q deletion to lenalidomide is not known. We are reporting a patient with 20q deletion MDS treated with lenalidomide after he failed to respond to azacytidine; to our knowledge this is the first report of a patient with isolated 20q deletion treated with lenalidomide.

  11. A phase I/II trial of Erlotinib in higher risk myelodysplastic syndromes and acute myeloid leukemia after azacitidine failure.

    Science.gov (United States)

    Thepot, Sylvain; Boehrer, Simone; Seegers, Valérie; Prebet, Thomas; Beyne-Rauzy, Odile; Wattel, Eric; Delaunay, Jacques; Raffoux, Emmanuel; Hunault, Mathilde; Jourdan, Eric; Chermat, Fatiha; Sebert, Marie; Kroemer, Guido; Fenaux, Pierre; Adès, Lionel

    2014-12-01

    Survival after azacitidine (AZA) failure in higher-risk myelodysplastic syndromes (MDS) is poor and new treatment options are needed. Erlotinib, an oral inhibitor of the epidermal-growth-factor-receptor (EGFR), has shown in preclinical models some efficacy in higher risk MDS and acute myeloid leukemia (AML). In this phase I/II trial, 30 patients received 100mg/day (n=5) or 150mg/day (n=25) of Erlotinib orally after primary or secondary resistance to AZA treatment. Eighteen MDS and 12 AML patients were treated. This outpatient treatment was well tolerated with limited grade III-IV extra hematological toxicities (skin (n=1), and diarrhea (n=3). Response was observed in 6 patients (20%) including 1 complete remission (CR), 1 marrow CR and 4 hematological improvement (2 erythroid and 2 on platelets). Median duration of response was 5 months. Erlotinib appears to induce a significant number of responses in higher risk MDS/AML having failed AZA treatment. Given the good safety profile of Erlotinib, its combination with other drugs could be tested in the future in MDS and AML.

  12. Recurrent DNMT3A R882 mutations in Chinese patients with acute myeloid leukemia and myelodysplastic syndrome.

    Directory of Open Access Journals (Sweden)

    Jiang Lin

    Full Text Available Somatic mutations of DNMT3A gene have recently been reported in acute myeloid leukemia (AML and myelodysplastic syndrome (MDS. We examined the entire coding sequences of DNMT3A gene by high-resolution melting analysis and sequencing in Chinese patients with myeloid malignancies. R882 mutations were found in 12/182 AML and in 4/51 MDS, but not in either 79 chronic myeloid leukemia (CML, or 57 myeloproliferative neoplasms (MPNs, or 4 chronic monomyelocytic leukemia. No other DNMT3A mutations were detected in all patients. R882 mutations were associated with old age and more frequently present in monoblastic leukemia (M4 and M5, 7/52 compared to other subtypes (5/130. Furthermore, 14/16 (86.6% R882 mutations were observed in patients with normal karyotypes. The overall survival of mutated MDS patients was shorter than those without mutation (median 9 and 25 months, respectively. We conclude that DNMT3A R882 mutations are recurrent molecular aberrations in AML and MDS, and may be an adverse prognostic event in MDS.

  13. Prognostic value of trisomy 8 as a single anomaly and the influence of additional cytogenetic aberrations in primary myelodysplastic syndromes.

    Science.gov (United States)

    Saumell, Sílvia; Florensa, Lourdes; Luño, Elisa; Sanzo, Carmen; Cañizo, Consuelo; Hernández, Jesus M; Cervera, José; Gallart, Miguel A; Carbonell, Félix; Collado, Rosa; Arenillas, Leonor; Pedro, Carme; Bargay, Joan; Nomdedeu, Benet; Xicoy, Blanca; Vallespí, Teresa; Raya, José M; Belloch, Luis; Sanz, Guillermo F; Solé, Francesc

    2012-11-01

    Trisomy 8 is the most common chromosomal gain in myelodysplastic syndromes (MDS), however, little is known about the features of MDS with isolated trisomy 8 and the influence of additional cytogenetic aberrations. We determined the characteristics and prognostic factors of 72 patients with trisomy 8 as a single anomaly and analysed also the impact of other aberrations added to trisomy 8 in another 62 patients. According to our study, MDS with isolated trisomy 8 was more frequent in men, with more than one cytopenia in most patients (62%) and having about 4% bone marrow blasts. The multivariate analysis demonstrated that platelet count and percentage bone marrow blasts had the strongest impact on overall survival (OS). The median OS for isolated trisomy 8, trisomy 8 plus one aberration (tr8 + 1), plus two (tr8 + 2) and plus three or more aberrations (tr8 + ≥3) was 34·3, 40, 23·4 and 5·8 months, respectively (P < 0·001). Trisomy 8 confers a poorer prognosis than a normal karyotype in MDS patients with ≥5% bone marrow blasts. This study supports the view that MDS with isolated trisomy 8 should be included in the intermediate cytogenetic risk group. © 2012 Blackwell Publishing Ltd.

  14. Prognostic significance of SETBP1 mutations in myelodysplastic syndromes, chronic myelomonocytic leukemia, and chronic neutrophilic leukemia: A meta-analysis

    Science.gov (United States)

    Shou, Li-Hong; Cao, Dan; Dong, Xiao-Hui; Fang, Qiu; Wu, Ying; Zhang, Yan; Fei, Ju-Ping; Xu, Bao-Lian

    2017-01-01

    Objectives This meta-analysis investigates the prognostic effect of SET binding protein 1 (SETBP1) mutations in patients with myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), or chronic neutrophilic leukemia (CNL). Methods Eligible studies from Pubmed, Embase, and Web of Science were searched from database inception through April 2016. Hazard ratios (HRs) and 95% confidence interval (CI) of overall survival (OS) were pooled to calculate the prognostic significance of SETBP1 mutation in patients. Results A total of 12 studies with 2321 patients were included in this meta-analysis; 4 studies for MDS, 5 studies for CMML, and 3 studies for CNL. Pooled results suggested that MDS and CMML patients with SETBP1 mutations had a significantly poorer prognosis when compared with patients with wild-type SETBP1 (MDS: HR = 1.808, 95% CI (1.218–2.685), P = 0.001; CMML: HR = 2.223, 95% CI (1.493–3.308), P<0.001). SETBP1 mutations in CNL patients however, showed no significant effect on the overall survival (HR = 1.773, 95% CI (0.877–3.582), P = 0.111). The Begg’s and Egger’s tests did not show significant publication bias in any groups. Conclusions Current evidence shows that SETBP1 mutation is associated with a poor prognosis in patients with MDS and CMML, but not in patients with CNL. PMID:28158286

  15. Construction of a yeast artificial chromosome contig encompassing the human acidic fibroblast growth factor (FGF1) gene: Toward the cloning of the ANLL/MDS tumor-suppressor gene

    Energy Technology Data Exchange (ETDEWEB)

    Chiu, Ing-Ming; Gilmore, E.C.; Liu, Yang; Payson, R.A. (Ohio State Univ., Columbus, OH (United States))

    1994-02-01

    The region surrounding the human acidic fibroblast growth factor (FGF1) locus on chromosome 5q31 is of particular interest since it represents a critical region consistently lost in acute nonlymphocytic leukemia (ANLL) or myelodysplastic syndrome (MDS) patients who have a demonstrable deletion of the distal portion of the long arm of chromosome 5. It is proposed that an ANLL/MDS leukemia suppressor gene resides on 5q31. The authors have previously shown that the gene is most likely localized between FGF1 and PDGFRB/CSF1R loci. The region has also been linked to at least four other genetic diseases, Treacher Collins syndrome, diastrophic dysplasia, limb-girdle muscular dystrophy, and an autosomal dominant deafness, by linkage analysis. Here, they describe yeast artificial chromosomes (YAC) spanning 450 kb around the FGF1 gene. Six YAC clones were isolated from a human YAC library and their restriction enzyme maps were determined. The overlap of the clones with each other and with FGF1 cosmid and phage clones was characterized. Three of the YAC clones were found to contain the entire FGF1 gene, which spans more than 100 kb. Proximal and distal ends of several of these YAC clones were isolated for further overlap cloning. The proximal ends of both Y2 and Y4 were localized to previously isolated FGF1 DNA by sequence analysis. The distal ends of these two clones also hybridized to a human-hamster hybrid containing chromosome 5 as the only human genetic material. These results suggest that these YAC clones represent colinear DNA around the FGF1 locus. None of the YAC clones were found to contain the CD 14 and GRL genes, the closest known proximal and distal markers (relative to the centromere) to the FGF1 gene, respectively. This contig is useful for the overlap cloning of the 5q31 region and for reverse genetic strategies for the isolation of disease genes in the region. 46 refs., 7 figs., 5 tabs.

  16. A randomized study of granulocyte colony-stimulating factor applied during and after chemotherapy in patients with poor risk myelodysplastic syndromes : a report from the HOVON Cooperative Group

    NARCIS (Netherlands)

    Ossenkoppele, GJ; van der Holt, B; Verhoef, GEG; Daenen, SMGJ; Verdonck, LF; Sonneveld, P; Wijermans, PW; van der Lelie, J; van Putten, WLJ; Lowenberg, B

    1999-01-01

    The purpose of this study was to determine the safety and efficacy of filgrastim as an adjunct to induction and consolidation chemotherapy in poor risk patients with myelodysplastic syndrome (MDS). Filgrastim was given both during and after chemotherapy with the objective to accelerate hematopoietic

  17. Allogeneic stem cell transplantation for patients with acute myeloid leukemia or myelodysplastic syndrome who have chromosome 5 and/or 7 abnormalities.

    NARCIS (Netherlands)

    Straaten, H.M. van der; Biezen, A. van; Brand, R.; Schattenberg, A.V.M.B.; Egeler, R.M.; Barge, R.M.; Cornelissen, J.J.L.M.; Schouten, H.C.; Ossenkoppele, G.J.; Verdonck, L.F.

    2005-01-01

    BACKGROUND AND OBJECTIVES: Chromosome 5 and/or 7 abnormalities are cytogenetic findings indicative of a poor prognosis in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). The only potential cure for such patients is allogeneic stem cell transplantation (SCT). As data on

  18. Standardization of flow cytometry in myelodysplastic syndromes: a report from an international consortium and the European LeukemiaNet Working Group.

    NARCIS (Netherlands)

    Westers, T.M.; Ireland, R.; Kern, W.; Alhan, C.; Balleisen, J.S.; Bettelheim, P.; Burbury, K.; Cullen, M.; Cutler, J.A.; Porta, M.G. Della; Drager, A.M.; Feuillard, J.; Font, P.; Germing, U.; Haase, D.; Johansson, U.; Kordasti, S.; Loken, M.R.; Malcovati, L.; Marvelde, J.G. Te; Matarraz, S.; Milne, T.; Moshaver, B.; Mufti, G.J.; Ogata, K.; Orfao, A.; Porwit, A.; Psarra, K.; Richards, S.J.; Subira, D.; Tindell, V.; Vallespi, T.; Valent, P.; Velden, V.H. van der; Witte, T.J.M. de; Wells, D.A.; Zettl, F.; Bene, M.C.; Loosdrecht, A.A. van de

    2012-01-01

    Flow cytometry (FC) is increasingly recognized as an important tool in the diagnosis and prognosis of myelodysplastic syndromes (MDS). However, validation of current assays and agreement upon the techniques are prerequisites for its widespread acceptance and application in clinical practice. Therefo

  19. In vivo measurements of the T1 relaxation processes in the bone marrow in patients with myelodysplastic syndrome. A magnetic resonance imaging study

    DEFF Research Database (Denmark)

    Jensen, K E; Nielsen, H; Thomsen, C

    1989-01-01

    Nine patients with myelodysplastic syndrome (MDS) were examined with magnetic resonance imaging and in vivo T1 relaxation time measurements of the vertebral bone marrow in a 1.5 tesla whole body scanner. Two patients underwent transformation to acute myeloid leukemia and were evaluated at follow...

  20. Lenalidomide for the Treatment of Low- or Intermediate-1-Risk Myelodysplastic Syndromes Associated with Deletion 5q Cytogenetic Abnormality: An Evidence Review of the NICE Submission from Celgene

    NARCIS (Netherlands)

    H.M. Sluimer-Blommestein (Hedwig); N. Armstrong (Nigel); S. Ryder; S. Deshpande (Sohan); G. Worthy (Gill); C. Noake; R. Riemsma; J. Kleijnen (Jos); J.L. Severens (Hans); M.J. Al (Maiwenn)

    2016-01-01

    textabstractThe National Institute for Health and Care Excellence (NICE) invited the manufacturer of lenalidomide (Celgene) to submit evidence of the clinical and cost effectiveness of the drug for treating adults with myelodysplastic syndromes (MDS) associated with deletion 5q cytogenetic abnormali

  1. Refractory primary immune thrombocytopenia with subsequent del(5q) MDS: complete remission of both after lenalidomide.

    Science.gov (United States)

    Mortensen, Thomas Bech; Frederiksen, Henrik; Marcher, Claus Werenberg; Preiss, Birgitte

    2017-01-04

    A patient with refractory primary immune thrombocytopenia (ITP) characterised by severe skin and mucosal bleedings was treated with several ITP-directed therapies including cyclophosphamide. He later developed therapy-related del(5q) myelodysplastic syndrome with no dysplastic morphological features in bone marrow. He remained severely thrombocytopenic, which suggests ongoing immune mediated platelet destruction. After two 3 week cycles of low-dose lenalidomide, complete cytogenetic remission and complete normalisation of platelet count were observed. This suggests that lenalidomide may be a viable treatment option for ITP in the presence of del(5q) not responding to standard treatments.

  2. The proliferation index of specific bone marrow cell compartments from myelodysplastic syndromes is associated with the diagnostic and patient outcome.

    Directory of Open Access Journals (Sweden)

    Sergio Matarraz

    Full Text Available Myelodysplastic syndromes (MDS are clonal stem cell disorders which frequently show a hypercellular dysplastic bone marrow (BM associated with inefficient hematopoiesis and peripheral cytopenias due to increased apoptosis and maturation blockades. Currently, little is known about the role of cell proliferation in compensating for the BM failure syndrome and in determining patient outcome. Here, we analyzed the proliferation index (PI of different compartments of BM hematopoietic cells in 106 MDS patients compared to both normal/reactive BM (n = 94 and acute myeloid leukemia (AML; n = 30 cases using multiparameter flow cytometry. Our results show abnormally increased overall BM proliferation profiles in MDS which significantly differ between early/low-risk and advanced/high-risk cases. Early/low-risk patients showed increased proliferation of non-lymphoid CD34(+ precursors, maturing neutrophils and nucleated red blood cells (NRBC, while the PI of these compartments of BM precursors progressively fell below normal values towards AML levels in advanced/high-risk MDS. Decreased proliferation of non-lymphoid CD34(+ and NRBC precursors was significantly associated with adverse disease features, shorter overall survival (OS and transformation to AML, both in the whole series and when low- and high-risk MDS patients were separately considered, the PI of NRBC emerging as the most powerful independent predictor for OS and progression to AML. In conclusion, assessment of the PI of NRBC, and potentially also of other compartments of BM precursors (e.g.: myeloid CD34(+ HPC, could significantly contribute to a better management of MDS.

  3. The Proliferation Index of Specific Bone Marrow Cell Compartments from Myelodysplastic Syndromes Is Associated with the Diagnostic and Patient Outcome

    Science.gov (United States)

    Matarraz, Sergio; Teodosio, Cristina; Fernandez, Carlos; Albors, Manuel; Jara-Acevedo, María; López, Antonio; Gonzalez-Gonzalez, María; Gutierrez, María Laura; Flores-Montero, Juan; Cerveró, Carlos; Pizarro-Perea, Marlies; Garrastazul, María Paz; Caballero, Gonzalo; Gutierrez, Oliver; Mendez, Guy Daniel; González-Silva, Manuel; Laranjeira, Paula; Orfao, Alberto

    2012-01-01

    Myelodysplastic syndromes (MDS) are clonal stem cell disorders which frequently show a hypercellular dysplastic bone marrow (BM) associated with inefficient hematopoiesis and peripheral cytopenias due to increased apoptosis and maturation blockades. Currently, little is known about the role of cell proliferation in compensating for the BM failure syndrome and in determining patient outcome. Here, we analyzed the proliferation index (PI) of different compartments of BM hematopoietic cells in 106 MDS patients compared to both normal/reactive BM (n = 94) and acute myeloid leukemia (AML; n = 30 cases) using multiparameter flow cytometry. Our results show abnormally increased overall BM proliferation profiles in MDS which significantly differ between early/low-risk and advanced/high-risk cases. Early/low-risk patients showed increased proliferation of non-lymphoid CD34+ precursors, maturing neutrophils and nucleated red blood cells (NRBC), while the PI of these compartments of BM precursors progressively fell below normal values towards AML levels in advanced/high-risk MDS. Decreased proliferation of non-lymphoid CD34+ and NRBC precursors was significantly associated with adverse disease features, shorter overall survival (OS) and transformation to AML, both in the whole series and when low- and high-risk MDS patients were separately considered, the PI of NRBC emerging as the most powerful independent predictor for OS and progression to AML. In conclusion, assessment of the PI of NRBC, and potentially also of other compartments of BM precursors (e.g.: myeloid CD34+ HPC), could significantly contribute to a better management of MDS. PMID:22952954

  4. A phase 2, randomized, double-blind, multicenter study comparing siltuximab plus best supportive care (BSC) with placebo plus BSC in anemic patients with International Prognostic Scoring System low- or intermediate-1-risk myelodysplastic syndrome.

    Science.gov (United States)

    Garcia-Manero, Guillermo; Gartenberg, Gary; Steensma, David P; Schipperus, Martin R; Breems, Dimitri A; de Paz, Raquel; Valcárcel, David; Kranenburg, Britte; Reddy, Manjula; Komrokji, Rami S

    2014-09-01

    Interleukin-6 (IL-6) may play an important role in the pathophysiology of anemia of inflammation associated with myelodysplastic syndrome (MDS). This double-blind, placebo-controlled, phase 2 study assessed the efficacy and safety of siltuximab, a chimeric anti-IL-6 monoclonal antibody, in patients with low- and intermediate-1-risk MDS who require transfusions for MDS anemia. Patients were randomized in a 2:1 ratio to siltuximab 15 mg kg(-1) every 4 weeks + best supportive care (BSC) or placebo + BSC for 12 weeks. The primary endpoint was reduction in red blood cell (RBC) transfusions to treat MDS anemia, defined as ≥50% relative decrease and ≥2-unit absolute decrease in RBC transfusions. Fifty and 26 patients were randomized to the siltuximab and placebo groups, respectively. The study did not meet its prespecified hypothesis, with six (12%) patients in the siltuximab group and one (3.8%) in the placebo group having reductions in RBC transfusions (P = 0.271). At the time of the planned futility analysis, the prespecified cutoff criteria were not met, and the study was terminated early due to lack of efficacy. No unexpected safety findings were observed. In conclusion, compared to placebo, treatment with siltuximab did not reduce RBC transfusions in transfusion-dependent patients with low- and intermediate-1-risk MDS. Future studies might explore siltuximab in patients with less iron overload and with elevated IL-6 levels and/or using higher doses for MDS.

  5. Depletion sensitivity predicts unhealthy snack purchases

    NARCIS (Netherlands)

    Salmon, Stefanie J.; Adriaanse, Marieke A.; Fennis, Bob M.; Vet, De Emely; Ridder, De Denise T.D.

    2016-01-01

    The aim of the present research is to examine the relation between depletion sensitivity - a novel construct referring to the speed or ease by which one's self-control resources are drained - and snack purchase behavior. In addition, interactions between depletion sensitivity and the goal to lose

  6. Depletion sensitivity predicts unhealthy snack purchases

    NARCIS (Netherlands)

    Salmon, Stefanie J.; Adriaanse, Marieke A.|info:eu-repo/dai/nl/304823023; Fennis, Bob M.; De Vet, Emely; De Ridder, Denise T D

    2016-01-01

    The aim of the present research is to examine the relation between depletion sensitivity - a novel construct referring to the speed or ease by which one's self-control resources are drained - and snack purchase behavior. In addition, interactions between depletion sensitivity and the goal to lose

  7. The Chemistry and Toxicology of Depleted Uranium

    Directory of Open Access Journals (Sweden)

    Sidney A. Katz

    2014-03-01

    Full Text Available Natural uranium is comprised of three radioactive isotopes: 238U, 235U, and 234U. Depleted uranium (DU is a byproduct of the processes for the enrichment of the naturally occurring 235U isotope. The world wide stock pile contains some 1½ million tons of depleted uranium. Some of it has been used to dilute weapons grade uranium (~90% 235U down to reactor grade uranium (~5% 235U, and some of it has been used for heavy tank armor and for the fabrication of armor-piercing bullets and missiles. Such weapons were used by the military in the Persian Gulf, the Balkans and elsewhere. The testing of depleted uranium weapons and their use in combat has resulted in environmental contamination and human exposure. Although the chemical and the toxicological behaviors of depleted uranium are essentially the same as those of natural uranium, the respective chemical forms and isotopic compositions in which they usually occur are different. The chemical and radiological toxicity of depleted uranium can injure biological systems. Normal functioning of the kidney, liver, lung, and heart can be adversely affected by depleted uranium intoxication. The focus of this review is on the chemical and toxicological properties of depleted and natural uranium and some of the possible consequences from long term, low dose exposure to depleted uranium in the environment.

  8. TP53 overexpression is an independent adverse prognostic factor in de novo myelodysplastic syndromes with fibrosis.

    Science.gov (United States)

    Loghavi, Sanam; Al-Ibraheemi, Alyaa; Zuo, Zhuang; Garcia-Manero, Guillermo; Yabe, Mariko; Wang, Sa A; Kantarjian, Hagop M; Yin, Cameron C; Miranda, Roberto N; Luthra, Raja; Medeiros, L Jeffrey; Bueso-Ramos, Carlos E; Khoury, Joseph D

    2015-10-01

    Bone marrow (BM) fibrosis is associated with poor prognosis in patients with de novo myelodysplastic syndromes (MDS). TP53 mutations and TP53 (p53) overexpression in MDS are also associated with poor patient outcomes. The prevalence and significance of TP53 mutations and TP53 overexpression in MDS with fibrosis are unknown. We studied 67 patients with de novo MDS demonstrating moderate to severe reticulin fibrosis (MDS-F). Expression of TP53 was evaluated in BM core biopsy specimens using dual-colour CD34/TP53 immunohistochemistry with computer-assisted image analysis. Mutation analysis was performed using next-generation sequencing, or Sanger sequencing methods. TP53 mutations were present in 47·1% of cases. TP53 mutation was significantly associated with TP53 expression (P = 0·0294). High levels of TP53 expression (3 +  in ≥10% cells) were associated with higher BM blast counts (P = 0·0149); alterations of chromosomes 5 (P = 0·0009) or 7 (P = 0·0141); complex karyotype (P = 0·0002); high- and very-high risk IPSS-R groups (P = 0·009); and TP53 mutations (P = 0·0003). High TP53 expression independently predicted shorter overall survival (OS) by multivariate analysis (P = TP53 by CD34-positive cells was associated with shorter OS and leukaemia-free survival (P = 0·0428). TP53 overexpression is a predictor of poor outcome in patients with MDS-F.

  9. High homocysteine induces betaine depletion.

    Science.gov (United States)

    Imbard, Apolline; Benoist, Jean-François; Esse, Ruben; Gupta, Sapna; Lebon, Sophie; de Vriese, An S; de Baulny, Helene Ogier; Kruger, Warren; Schiff, Manuel; Blom, Henk J

    2015-04-28

    Betaine is the substrate of the liver- and kidney-specific betaine-homocysteine (Hcy) methyltransferase (BHMT), an alternate pathway for Hcy remethylation. We hypothesized that BHMT is a major pathway for homocysteine removal in cases of hyperhomocysteinaemia (HHcy). Therefore, we measured betaine in plasma and tissues from patients and animal models of HHcy of genetic and acquired cause. Plasma was collected from patients presenting HHcy without any Hcy interfering treatment. Plasma and tissues were collected from rat models of HHcy induced by diet and from a mouse model of cystathionine β-synthase (CBS) deficiency. S-adenosyl-methionine (AdoMet), S-adenosyl-homocysteine (AdoHcy), methionine, betaine and dimethylglycine (DMG) were quantified by ESI-LC-MS/MS. mRNA expression was quantified using quantitative real-time (QRT)-PCR. For all patients with diverse causes of HHcy, plasma betaine concentrations were below the normal values of our laboratory. In the diet-induced HHcy rat model, betaine was decreased in all tissues analysed (liver, brain, heart). In the mouse CBS deficiency model, betaine was decreased in plasma, liver, heart and brain, but was conserved in kidney. Surprisingly, BHMT expression and activity was decreased in liver. However, in kidney, BHMT and SLC6A12 expression was increased in CBS-deficient mice. Chronic HHcy, irrespective of its cause, induces betaine depletion in plasma and tissues (liver, brain and heart), indicating a global decrease in the body betaine pool. In kidney, betaine concentrations were not affected, possibly due to overexpression of the betaine transporter SLC6A12 where betaine may be conserved because of its crucial role as an osmolyte.

  10. Specification for the VERA Depletion Benchmark Suite

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kang Seog [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2015-12-17

    CASL-X-2015-1014-000 iii Consortium for Advanced Simulation of LWRs EXECUTIVE SUMMARY The CASL neutronics simulator MPACT is under development for the neutronics and T-H coupled simulation for the pressurized water reactor. MPACT includes the ORIGEN-API and internal depletion module to perform depletion calculations based upon neutron-material reaction and radioactive decay. It is a challenge to validate the depletion capability because of the insufficient measured data. One of the detoured methods to validate it is to perform a code-to-code comparison for benchmark problems. In this study a depletion benchmark suite has been developed and a detailed guideline has been provided to obtain meaningful computational outcomes which can be used in the validation of the MPACT depletion capability.

  11. Time to redefine PD? Introductory statement of the MDS Task Force on the definition of Parkinson's disease.

    Science.gov (United States)

    Berg, Daniela; Postuma, Ronald B; Bloem, Bastiaan; Chan, Piu; Dubois, Bruno; Gasser, Thomas; Goetz, Christopher G; Halliday, Glenda M; Hardy, John; Lang, Anthony E; Litvan, Irene; Marek, Kenneth; Obeso, José; Oertel, Wolfgang; Olanow, C Warren; Poewe, Werner; Stern, Matthew; Deuschl, Günther

    2014-04-01

    With advances in knowledge disease, boundaries may change. Occasionally, these changes are of such a magnitude that they require redefinition of the disease. In recognition of the profound changes in our understanding of Parkinson's disease (PD), the International Parkinson and Movement Disorders Society (MDS) commissioned a task force to consider a redefinition of PD. This review is a discussion article, intended as the introductory statement of the task force. Several critical issues were identified that challenge current PD definitions. First, new findings challenge the central role of the classical pathologic criteria as the arbiter of diagnosis, notably genetic cases without synuclein deposition, the high prevalence of incidental Lewy body (LB) deposition, and the nonmotor prodrome of PD. It remains unclear, however, whether these challenges merit a change in the pathologic gold standard, especially considering the limitations of alternate gold standards. Second, the increasing recognition of dementia in PD challenges the distinction between diffuse LB disease and PD. Consideration might be given to removing dementia as an exclusion criterion for PD diagnosis. Third, there is increasing recognition of disease heterogeneity, suggesting that PD subtypes should be formally identified; however, current subtype classifications may not be sufficiently robust to warrant formal delineation. Fourth, the recognition of a nonmotor prodrome of PD requires that new diagnostic criteria for early-stage and prodromal PD should be created; here, essential features of these criteria are proposed. Finally, there is a need to create new MDS diagnostic criteria that take these changes in disease definition into consideration. © 2014 International Parkinson and Movement Disorder Society.

  12. Measurement properties of the EQ-5D across four major geriatric conditions: Findings from TOPICS-MDS.

    Science.gov (United States)

    Lutomski, Jennifer E; Krabbe, Paul F M; Bleijenberg, Nienke; Blom, Jeanett; Kempen, Gertrudis I J M; MacNeil-Vroomen, Janet; Muntinga, Maaike E; Steyerburg, Ewout; Olde-Rikkert, Marcel G M; Melis, René J F

    2017-03-03

    As populations age, chronic geriatric conditions linked to progressive organ failure jeopardize health-related quality of life (HRQoL). Thus, this research assessed the validity and applicability of the EQ-5D (a common HRQoL instrument) across four major chronic geriatric conditions: hearing issues, joint damage, urinary incontinence, or dizziness with falls. The study sample comprised 25,637 community-dwelling persons aged 65 years and older residing in the Netherlands (Data source: TOPICS-MDS, www.topics-mds.eu ). Floor and ceiling effects were examined. To assess convergent validity, random effects meta-correlations (Spearman's rho) were derived between individual EQ-5D domains and related survey items. To further examine construct validity, the association between sociodemographic characteristics and EQ-5D summary scores were assessed using linear mixed models. Outcomes were compared to the overall study population as well as a 'healthy' subgroup reporting no major chronic conditions. Whereas ceiling effects were observed in the overall study population and the 'healthy' subgroup, such was not the case in the geriatric condition subgroups. The majority of hypotheses regarding correlations between survey items and sociodemographic associations were supported. EQ-5D summary scores were lower in respondents who were older, female, widowed/single, lower educated, and living alone. Increasing co-morbidity had a clear negative effect on EQ-5D scores. This study supported the construct validity of the EQ-5D across four major geriatric conditions. For older persons who are generally healthy, i.e. reporting few to no chronic conditions, the EQ-5D confers poor discriminative ability due to ceiling effects. Although the overall dataset initially suggested poor discriminative ability for the EQ-5D, such was not the case within subgroups presenting with major geriatric conditions.

  13. Relationship between the non-motor items of the MDS-UPDRS and Quality of Life in patients with Parkinson's disease

    NARCIS (Netherlands)

    Skorvanek, Matej; Rosenberger, Jaroslav; Minar, Michal; Grofik, Milan; Han, Vladimir; Groothoff, Johan W.; Valkovic, Peter; Gdovinova, Zuzana; van Dijk, Jitse P.

    2015-01-01

    The Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is a newly developed comprehensive tool to assess Parkinson's disease (PD), which covers a wider range of non-motor PD manifestations than the original UPDRS scale. The aim of this study was to assess the relationship

  14. Non-intensive treatment with low-dose 5-aza-2'-deoxycytidine (DAC) prior to allogeneic blood SCT of older MDS/AML patients.

    Science.gov (United States)

    Lübbert, M; Bertz, H; Rüter, B; Marks, R; Claus, R; Wäsch, R; Finke, J

    2009-11-01

    Novel, non-intensive treatment options in older MDS/AML patients planned for allografting, with the goal of down-staging the underlying disease and bridging time to transplantation, are presently being developed. 5-azacytidine and decitabine (DAC) are of particular interest, as they can be given repetitively, with very limited non-hematologic toxicity and result in responses both in MDS and AML even at low doses. We describe 15 consecutive patients (median age 69 years, range 60-75 years) with MDS (n=10) or AML (n=5) who all received first-line treatment with DAC and subsequent allografting (from sibling donor in four patients, unrelated donor in 11) after reduced-intensity conditioning with the FBM regimen. Successful engraftment was attained in 14/15 patients, all of whom achieved a CR, with a median duration of 5 months (range 1+ to 51+). Six of these 14 patients are alive (4 with complete donor chimerism), 8 have died either from relapse (n=4) or treatment-related complications while in CR (n=4). We conclude that allografting after low-dose DAC and subsequent conditioning with FBM is feasible, with no unexpected toxicities and appears as a valid alternative to standard chemotherapy ('InDACtion instead of induction') in elderly patients with MDS/AML.

  15. Potential environmental benefits of improving recycling of polyolefines – LCA of Magnetic density separation (MDS) developed in the EU FP7 funded project W2Plastic

    DEFF Research Database (Denmark)

    Olsen, Stig Irving; Bonou, Alexandra

    2012-01-01

    The core of the EU FP7 funded project W2Plastic is development of a magnetic density separation (MDS) of polyolefines in order to improve the sorting efficiency of these polymer types in different waste fractions. As part of the project a life cycle assessment is performed in order to firstly...

  16. Prognostic value of circulating CD34+ cells in myelodysplastic syndromes.

    Science.gov (United States)

    Cesana, Clara; Klersy, Catherine; Brando, Bruno; Nosari, Annamaria; Scarpati, Barbara; Scampini, Linda; Molteni, Alfredo; Nador, Guido; Santoleri, Luca; Formenti, Marta; Valentini, Marina; Mazzone, Antonino; Morra, Enrica; Cairoli, Roberto

    2008-11-01

    We studied circulating (C)CD34(+) cells by flow cytometry in 96 patients with myelodysplastic syndromes (MDS) at diagnosis, and in a subset of 35 cases during follow-up. CCD34(+) counts were stratified within both International Prognostic Scoring System (IPSS) and World Health Organization (WHO) categories. Counts >10/microl were associated with poorer leukemia-free survival, a prognostic value for evolution independent from that of WHO, and a higher progression probability within intermediate-risk IPSS and WHO classes. When serial measurements were performed, counts >10/microl more frequently correlated to evolution. Separating newly diagnosed patients on the basis of 10/microl cut-off of circulating CD34(+) cells retains prognostic utility, especially in intermediate-risk MDS.

  17. [Molecular biology in myelodysplastic syndromes and acute myeloid leukemias "smoldering"].

    Science.gov (United States)

    Martinelli, Giovanni; Sartor, Chiara; Papayannidis, Cristina; Iacobucci, Ilaria; Paolini, Stefania; Clissa, Cristina; Ottaviani, Emanuela; Finelli, Carlo

    2014-03-01

    Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic disorders of the myeloid lineage characterized by peripheral cytopenias and frequent leukemic evolution. MDS differ for clinical presentation, disease behavior and progression and this is the reflection of remarkable variability at molecular level. To this moment disease diagnosis is still dependent on bone marrow morphology that, although high concordance rates among experts are reported, remains subjective. Karyotype analysis is mandatory but diagnosis may be difficult in presence of normal karyotype or non-informative cytogenetics. Standardized molecular markers are needed to better define diagnosis, prediction of disease progression and prognosis. Furthermore, a molecular biology analysis could provide an important therapeutic tool towards tailored therapy and new insights in the disease's biology.

  18. The perception of the clinical relevance of the MDS-Home Care(C) tool by trainers in general practice in Belgium.

    Science.gov (United States)

    Duyver, Corentin; Van Houdt, Sabine; De Lepeleire, Jan; Dory, Valerie; Degryse, Jean-Marie

    2010-12-01

    comprehensive geriatric assessment has been advocated as an effective way to first identify multidimensional needs and second to establish priorities for organizing an individual health care plan for community-dwelling elderly. This paper reports on the perception of an internationally evaluated assessment system for use in community care programmes, the Minimal Data Set-Home Care (MDS-HC), by a group of experienced GP trainers. the primary study aim was to determine the perception of a standardized home care assessment system (MDS-HC) by GP trainers in terms of acceptability, perceived clinical relevance, care planning empowerment and valorization of the GP. sixty-five first-year GP trainees were educated about the MDS-HC and the use of a first version of an electronic interface. Each trainee included two elderly patients, based on strict inclusion criteria. Prior to the assessment, GP trainers and trainees were invited to complete together a basic medical record on the basis of their knowledge of the included patients. Next, the collected data, covering the multiple domains by MDS-HC, were introduced in the electronic interface by the trainee. Based on the collected data for each patient, a series of clinical assessment protocols (CAP's) were generated. Afterwards, these CAP's were critically discussed with the trainer. To investigate how the application of the MDS-HC was perceived, a 21 Likert-type item scale was drawn up based on four dimensions regarding the tool. the perception questionnaire had a good internal consistency (Cronbach's alpha 0.93). The first version of the electronic interface was considered not 'user-friendly' enough and the introduction of data time-consuming. The perception of the GP's about the overall clinical relevance of the MDS-HC was found to have little added value for the GP in the establishment of a personal management plan. many developments in health care result in an increasing demand for a standardized home care assessment

  19. Possible ozone depletions following nuclear explosions

    Science.gov (United States)

    Whitten, R. C.; Borucki, W. J.; Turco, R. P.

    1975-01-01

    The degree of depletion of the ozone layer ensuing after delivery of strategic nuclear warheads (5000 and 10,000 Mton) due to production of nitrogen oxides is theoretically assessed. Strong depletions are calculated for 16-km and 26-km altitudes, peaking 1-2 months after detonation and lasting for three years, while a significant depletion at 36 km would peak after one year. Assuming the explosions occur between 30 and 70 deg N, these effects should be much more pronounced in this region than over the Northern Hemisphere as a whole. It is concluded that Hampson's concern on this matter (1974) is well-founded.-

  20. 骨髓增生异常综合征细胞周期相关分子表达的初步研究%Expressions of cell cycle related molecules in myelodysplastic syndrome

    Institute of Scientific and Technical Information of China (English)

    赵佑山; 郭娟; 顾树程; 费成明; 张曦; 李晓; 常春康

    2013-01-01

    Objective To investigate the expression of cyclin-dependent kinase inhibitors (p21cipl, p27kipl, p57kip2) and change of cell cycle in patients with myelodysplastic syndrome (MDS). Methods Flow cytometric analysis of cell cycle of bone marrow mononuclear cells (BMNCs) was performed. Expressions of p21cipl, p27kipl and p57kip2 mRNA were detected by real-time fluorescence quantitative PCR. Results Expression of p21cipl was reduced in high risk MDS and MDS-AML groups when compared with healthy controls (P=0.008, 0.029, respectively). However, there was no significant difference between low risk MDS group and healthy control. The expression of p27kipl was not different significantly among the four groups. p57kip2 expression was reduced significantly in low risk MDS, high risk MDS and MDS-AML groups when compared with healthy controls (P<0.001). The ratio of S phase cells in high risk MDS and MDS-AML groups was statistically higher than that in healthy controls. No significant differences were found in ratio of G0/G1 and G2/M phase cells. Conclusions The BMNCs from patients with MDS have abnormality in expression of cyclin-dependent kinase inhibitors, which is correlated with the change in cell cycle.%目的:研究骨髓增生异常综合征(myelodysplastic syndrome,MDS)患者细胞周期负性调控因子(p21cip1、p27kip1、p57kip2)的表达水平及细胞周期改变.方法:采用流式细胞仪检测MDS患者骨髓单个核细胞(bone marrow mononuclear cell,BMNCs)细胞周期情况,应用实时荧光定量PCR检测其p21cip1、p27kip1、p57kip2 mRNA表达水平.结果:高危MDS组及MDS-AML组(包括10例MDS转白血病患者及8例AML患者)的p21cip1表达水平显著低于正常对照组(P值分别为0.008、0.029),而低危MDS组与正常对照组差异无统计学意义;p27kip1表达水平在各组间差异无统计学意义;低危MDS组、高危MDS组及MDS-AML组p57kip2表达均显著低于正常对照组(P<0.001);高危MDS组及MDS-AML组的S期细

  1. [Clinical observation of decitabine-treating patients with myelodysplastic syndrome and acute myeloid leukemia].

    Science.gov (United States)

    Yang, Hua; Zhu, Hai-Yan; Jiang, Meng-Meng; Wang, Quan-Shun; Han, Xiao-Ping; Huang, Wen-Rong; Jing, Yu; Wang, Shu-Hong; Zhang, Song-Song; Mei, Jun-Hui; Yu, Li

    2013-02-01

    This study was purposed to investigate the clinical efficiencies and adverse reactions of treating the myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) by using decitabine. The clinical data of 12 MDS and AML patients treated with decitabine were analyzed retrospectively. Among 12 patients there were 1 case of MDS-RA, 2 cases of MDS-RAEB-I, 3 cases of MDS-RAEB-II, 2 cases of AML-M4, 2 cases of AML-M5, 1 case of AML-M6 and 1 case of AML-M0. In decitabine chemotherapy program for 5 days (n = 8), decitabine 20 mg/(m(2)·d) × 5 days was applied, 4 weeks for 1 cycle; in program for 3 days (n = 2), decitabine 15 mg/m(2), once 8 h for 3 days, 6 weeks for 1 cycle; another program (n = 2), decitabine 20 mg/(m(2)·d) every other day for 5 times. For 1 patient achieved complete remission (CR) after treatment with decitabine, ID4 gene methylated level was detected by MS-PCR and ML-PCR before and after treatment. The results showed that 2 cases achieved CR, 1 case partial remission, 5 cases stable disease, 1 case progress of disease and 3 cases died. Disease control rate was 66.67% (8/12), the effective rate 25% (3/12). The average survival time was (11.5 ± 2.1) months. 1-year OS rate was 40%, 2-year OS rate was 16.7%. MS-PCR detection showed that the decitabine could significantly reduce the ID4 gene methylation level. It is concluded that decitabine can stabilize disease status of MDS patients, reduce blood transfusion dependence and improve the life quality of patients, and even some patients who transformed from MDS to leukemia achieved CR after treatment with decitabine. Decitabine can reduce the ID4 gene methylation level. The main adverse reaction of decitabine was myelosuppression, infection and so on. So the blood transfusions, antibiotics and other supportive treatments for these patients are needed. Most of patients well tolerate the adverse effects of decitabine after active symptomatic and supportive treatment. The efficacy and survival rate of

  2. Polar stratospheric clouds and ozone depletion

    Science.gov (United States)

    Toon, Owen B.; Turco, Richard P.

    1991-01-01

    A review is presented of investigations into the correlation between the depletion of ozone and the formation of polar stratospheric clouds (PSCs). Satellite measurements from Nimbus 7 showed that over the years the depletion from austral spring to austral spring has generally worsened. Approximately 70 percent of the ozone above Antarctica, which equals about 3 percent of the earth's ozone, is lost during September and October. Various hypotheses for ozone depletion are discussed including the theory suggesting that chlorine compounds might be responsible for the ozone hole, whereby chlorine enters the atmosphere as a component of chlorofluorocarbons produced by humans. The three types of PSCs, nitric acid trihydrate, slowly cooling water-ice, and rapidly cooling water-ice clouds act as important components of the Antarctic ozone depletion. It is indicated that destruction of the ozone will be more severe each year for the next few decades, leading to a doubling in area of the Antarctic ozone hole.

  3. [Hepatomioneuropathy secondary to mitochondrial DNA depletion].

    Science.gov (United States)

    Blanco-Barca, M O; Gómez-Lado, C; Campos-González, Y; Castro-Gago, M

    2007-04-01

    Mitochondrial DNA depletion (mtDNA) is an highly heterogeneous condition characterized by a decreased number of mtDNA copies. The patient is a 22-month-old girl with generalized hypotonia, marked weakness, respiratory failure, arterial hypertension, hyperlactacidemia, hepatosplenomegaly and mild hypertransaminasemia without hepatic failure neither hypoketotic hypoglycemia. Electromyographic findings were consistent with neuromyopathy and muscle biopsy suggested a neurogenic atrophy. Electron microscopy revealed lipid droplets, subsarcolemmal accumulation of mitochondrias and glycogen granules. Respiratory chain enzime activities were normal. Genetic study in muscle showed mtDNA depletion, and the diagnosis of spinal muscular atrophy caused by survival motoneuron gene deletion was excluded. This case might be a novel phenotype of mtDNA depletion which could be named hepatomioneuropatyc form. A normal result of respiratory chain enzimes in muscle doesn't excluded mtDNA depletion.

  4. Evidence- and consensus-based practice guidelines for the therapy of primary myelodysplastic syndromes. A statement from the Italian Society of Hematology

    DEFF Research Database (Denmark)

    Alessandrino, Emilio Paolo; Amadori, Sergio; Barosi, Giovanni

    2002-01-01

    BACKGROUND AND OBJECTIVES: Novel therapeutic agents and strategies have been introduced into the management of myelodysplastic syndromes (MDS) in the last years. This has led to more treatment options and a better chance of long-term survival for MDS patients, but also to uncertainty regarding...... the optimal use and possible side effects of these treatments. The Italian Society of Hematology commissioned a project to develop guidelines for the therapy of MDS using evidence-based knowledge and consensus-formation techniques. DESIGN AND METHODS: An Advisory Council (AC) shaped the project around...... a series of key clinical questions, performed a systematic search for evidence and graded the available evidence according to the Scottish Intercollegiate Guidelines Network (SIGN). A list of clinical questions was mailed to each of 10 senior hematologists composing the Expert Panel (EP): the panelists...

  5. Progressive transfusion and growth factor independence with adjuvant sertraline in low risk myelodysplastic syndrome treated with an erythropoiesis stimulating agent and granulocyte-colony stimulating factor

    Directory of Open Access Journals (Sweden)

    Kirtan Nautiyal

    2015-01-01

    Full Text Available Refractoriness to growth factor therapy is commonly associated with inferior outcome in patients with low-risk myelodysplastic syndrome (LR-MDS who require treatment for cytopenias. However, the mechanisms leading to refractoriness are unknown. Here we describe a clinically depressed 74-year-old male with refractory cytopenia with multilineage dysplasia (RCMD and documented growth factor refractory anemia after erythropoeisis stimulating agent (ESA therapy, who attained transfusion and growth factor independence after the addition of sertraline to his medication regimen. Our case demonstrates hematological improvement-erythroid (HI-E in growth factor refractory, low risk MDS and highlights a potential mechanistic link between common inflammatory diseases and LR-MDS.

  6. A study of high-dose lenalidomide induction and low-dose lenalidomide maintenance therapy for patients with hypomethylating agent refractory myelodysplastic syndrome.

    Science.gov (United States)

    Cherian, Mathew A; Tibes, Raoul; Gao, Feng; Fletcher, Theresa; Fiala, Mark; Uy, Geoffrey L; Westervelt, Peter; Jacoby, Meagan A; Cashen, Amanda F; Stockerl-Goldstein, Keith; DiPersio, John F; Vij, Ravi

    2016-11-01

    Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders characterized by bone marrow failure which frequently progress to acute myeloid leukemia. Patients who fail to respond to, or progress on first-line DNA hypomethylating agents (HMA) have a poor prognosis. Conventionally dosed lenalidomide has activity in 5q-MDS. In other subtypes, it may reduce RBC transfusion requirements but does not result in cytogenetic responses. We previously reported that high-dose lenalidomide induction (50 mg/day) results in complete remissions in a high fraction of patients. We, therefore, conducted a Phase 2 trial of the same regimen in MDS refractory to HMA. Marrow complete remissions were seen in 33% of patients and hematological improvement in 8% of patients. Significant infections complicated more than 50% of cases. Future trials to explore alternative dosing schedules of high-dose lenalidomide to increase efficacy while decreasing toxicity are warranted.

  7. Depleted bulk heterojunction colloidal quantum dot photovoltaics

    Energy Technology Data Exchange (ETDEWEB)

    Barkhouse, D.A.R. [Department of Electrical and Computer Engineering, University of Toronto, 10 King' s College Road, Toronto, Ontario M5S 3G4 (Canada); IBM Thomas J. Watson Research Center, Kitchawan Road, Yorktown Heights, NY, 10598 (United States); Debnath, Ratan; Kramer, Illan J.; Zhitomirsky, David; Levina, Larissa; Sargent, Edward H. [Department of Electrical and Computer Engineering, University of Toronto, 10 King' s College Road, Toronto, Ontario M5S 3G4 (Canada); Pattantyus-Abraham, Andras G. [Department of Electrical and Computer Engineering, University of Toronto, 10 King' s College Road, Toronto, Ontario M5S 3G4 (Canada); Quantum Solar Power Corporation, 1055 W. Hastings, Ste. 300, Vancouver, BC, V6E 2E9 (Canada); Etgar, Lioz; Graetzel, Michael [Laboratory for Photonics and Interfaces, Institute of Chemical Sciences and Engineering, School of Basic Sciences, Swiss Federal Institute of Technology, CH-1015 Lausanne (Switzerland)

    2011-07-26

    The first solution-processed depleted bulk heterojunction colloidal quantum dot solar cells are presented. The architecture allows for high absorption with full depletion, thereby breaking the photon absorption/carrier extraction compromise inherent in planar devices. A record power conversion of 5.5% under simulated AM 1.5 illumination conditions is reported. (Copyright copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  8. Depleted Bulk Heterojunction Colloidal Quantum Dot Photovoltaics

    KAUST Repository

    Barkhouse, D. Aaron R.

    2011-05-26

    The first solution-processed depleted bulk heterojunction colloidal quantum dot solar cells are presented. The architecture allows for high absorption with full depletion, thereby breaking the photon absorption/carrier extraction compromise inherent in planar devices. A record power conversion of 5.5% under simulated AM 1.5 illumination conditions is reported. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Effects of Riverbed Conductance on Stream Depletion

    Science.gov (United States)

    Lackey, G.; Neupauer, R. M.; Pitlick, J.

    2012-12-01

    In the western United States and other regions of the world where growing population and changing climates are threatening water supplies, accurate modeling of potential human impacts on water resources is becoming more important. Stream depletion, the reduction of surface water flow due to the extraction of groundwater from a hydraulically connected aquifer, is one of the more direct ways that development can alter water availability, degrade water quality and endanger aquatic habitats. These factors have made the accurate modeling of stream depletion an important step in the process of installing groundwater wells in regions that are susceptible to this phenomenon. Proper estimation of stream depletion requires appropriate parameterization of aquifer and streambed hydraulic properties. Although many studies have conducted numerical investigations to determine stream depletion at specific sites, they typically do not measure streambed hydraulic conductivity (Kr), but rather assume a representative value. In this work, we establish a hypothetical model aquifer that is 2000 m by 1600 m and has a meandering stream running through its center. The Kr of the model stream is varied from 1.0x10-9 m s-1 to 1.0x10-2 m s-1 in order to determine the sensitivity of the stream depletion calculations to this parameter. It was found that when Kr is in the lower part of this range, slight changes in K¬r lead to significant impacts on the calculated stream depletion values. We vary Kr along the stream channel according to naturally occurring patterns and demonstrate that alterations of the parameter over a few orders of magnitude can affect the estimated stream depletion caused by a well at a specified location. The numerical simulations show that the mean value of Kr and its spatial variability along the channel should be realistic to develop an accurate model of stream depletion.

  10. A theoretical model of atmospheric ozone depletion

    Science.gov (United States)

    Midya, S. K.; Jana, P. K.; Lahiri, T.

    1994-01-01

    A critical study on different ozone depletion and formation processes has been made and following important results are obtained: (i) From analysis it is shown that O3 concentration will decrease very minutely with time for normal atmosphere when [O], [O2] and UV-radiation remain constant. (ii) An empirical equation is established theoretically between the variation of ozone concentration and time. (iii) Special ozone depletion processes are responsible for the dramatic decrease of O3-concentration at Antarctica.

  11. Anatomy of Depleted Interplanetary Coronal Mass Ejections

    Science.gov (United States)

    Kocher, M.; Lepri, S. T.; Landi, E.; Zhao, L.; Manchester, W. B., IV

    2017-01-01

    We report a subset of interplanetary coronal mass ejections (ICMEs) containing distinct periods of anomalous heavy-ion charge state composition and peculiar ion thermal properties measured by ACE/SWICS from 1998 to 2011. We label them “depleted ICMEs,” identified by the presence of intervals where C6+/C5+ and O7+/O6+ depart from the direct correlation expected after their freeze-in heights. These anomalous intervals within the depleted ICMEs are referred to as “Depletion Regions.” We find that a depleted ICME would be indistinguishable from all other ICMEs in the absence of the Depletion Region, which has the defining property of significantly low abundances of fully charged species of helium, carbon, oxygen, and nitrogen. Similar anomalies in the slow solar wind were discussed by Zhao et al. We explore two possibilities for the source of the Depletion Region associated with magnetic reconnection in the tail of a CME, using CME simulations of the evolution of two Earth-bound CMEs described by Manchester et al.

  12. Therapy-related myelodysplastic syndrome and acute myeloid leukemia following chemotherapy (paclitaxel and carboplatin) and radiation therapy in ovarian cancer: a case report.

    Science.gov (United States)

    Ishikawa, M; Nakayama, K; Rahman, M T; Rahman, M; Katagiri, H; Katagiri, A; Ishibashi, T; Iida, K; Nakayama, N; Miyazaki, K

    2014-01-01

    In recent years, the incidence of therapy-related myelodysplastic syndrome (t-MDS) and therapy-related acute myeloid leukemia (t-AML) that occur during chemotherapy for ovarian cancer has increased. While alkylating agents and topoisomerase II inhibitors are particularly mutagenic and have strong leukemogenic potential, paclitaxel and combination chemotherapy/radiation therapy also appear to induce t-MDS. The present authors report a case of t-MDS that developed during chemotherapy and radiation therapy for ovarian cancer. The patient was a 75-year-old woman who received six courses of cyclophosphamide/doxorubicin/cisplatin (CAP) therapy after initial surgery for Stage IIIc grade ovarian cancer in 1995. Beginning in February 2005, the patient experienced multiple recurrences due to sternal metastasis. Chemotherapy, including paclitaxel and carboplatin (TC), was administered intermittently and was combined with radiation therapy to a sternal metastatic lesion. Pancytopenia was observed in December 2008, and she was diagnosed with t-MDS (WHO subtype, refractory cytopenias with multilineage dysplasia [RCMD]): the time from first chemotherapy to t-MDS onset was 106 months. Without evidence of blast crisis, the recurrent lesions continued to grow and caused multiple cerebral infarctions, from which she eventually died. The cumulative doses of paclitaxel and carboplatin administered to this patient were 1,968 mg and 6,480 mg, respectively.

  13. Analysis of WHO-Based Prognostic Scoring System (WPSS) of Myelodysplastic Syndrome and Its Comparison with International Prognostic Scoring System (IPSS) in 100 Chinese Patients

    Institute of Scientific and Technical Information of China (English)

    Jia Wei; Xiao-fen Zhou; Jian-feng Zhou; Yan Chen

    2009-01-01

    Objective: The aims of this study were to assess the prognostic significance of WHO-based Prognostic Scoring System (WPSS) in myelodysplastic syndrome (MDS) from a single center institute and to compare WPSS with the international prognostic scoring system (IPSS).Methods: A total of 100 cases with de novo MDS were reviewed and their karyotypes were detected. All of them were followed up and classified according to IPSS and WPSS risk groups. SPSS 13.0 software was applied to deal with all the data. The statistical methods included Kaplan - Meier, Log-rank test and cox regression.Results: Multivariate cox regression analysis indicated that WHO Classification (P=0.0190), karyotype abnormalities categorized according to IPSS (P=0.0159) and red blood cell (RBC) transfusion (P=0.0009) were the three most important independent factors for predicting overall survival (OS) of MDS. WPSS and IPSS both had great capacity in predicting the OS of MDS at the time of diagnosis (P<0.0001). In time-dependent analysis, WPSS can predict the OS accurately in the following three years after diagnosis (P<0.0001), while IPSS failed to predict the OS 24 months after diagnosis (P=0.1094).Conclusion: Our single center results proved that WPSS is a dynamic prognostic system which can predict the OS of MDS patients at any time during the course of their disease. This time-dependent prognostic scoring system may replace the IPSS in the near future.

  14. MLL gene amplification in acute myeloid leukemia and myelodysplastic syndromes is associated with characteristic clinicopathological findings and TP53 gene mutation.

    Science.gov (United States)

    Tang, Guilin; DiNardo, Courtney; Zhang, Liping; Ravandi, Farhad; Khoury, Joseph D; Huh, Yang O; Muzzafar, Tariq; Medeiros, L Jeffrey; Wang, Sa A; Bueso-Ramos, Carlos E

    2015-01-01

    MLL gene rearrangements are well-recognized aberrations in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). In contrast, MLL gene amplification in AML/MDS remains poorly characterized. Here, we report a series of 21 patients with myeloid neoplasms associated with MLL gene amplification from 1 institution. This series included 13 men and 8 women, with a median age of 64 years. Eleven patients presented as AML with myelodysplasia-related changes, 6 as therapy-related AML, and 4 as therapy-related MDS. All patients had a highly complex karyotype, including frequent -5/del(5q), -18, and -17/del(17p) abnormalities; 16 patients were hypodiploid. TP53 mutations were detected in all 12 patients tested, and 3 patients showed TP53 mutation before MLL amplification. Morphologically, the leukemic cells frequently showed cytoplasmic vacuoles, bilobed nuclei, and were associated with background dyspoiesis. Immunophenotypically, 15 patients had a myeloid and 4 had myelomonocytic immunophenotype. Laboratory coagulopathies were common; 7 patients developed disseminated intravascular coagulopathy, and 3 died of intracranial bleeding. All patients were refractory to therapy; the median overall survival was 1 month, after MLL gene amplification was detected. We concluded that AML/MDS with MLL gene amplification is likely a subset of therapy-related AML/MDS or AML with myelodysplasia-related changes, associated with distinct clinicopathological features, frequent disseminated intravascular coagulopathy, a highly complex karyotype, TP53 deletion/mutation, and an aggressive clinical course.

  15. Lenalidomide as a disease-modifying agent in patients with del(5q) myelodysplastic syndromes: linking mechanism of action to clinical outcomes.

    Science.gov (United States)

    Giagounidis, Aristoteles; Mufti, Ghulam J; Fenaux, Pierre; Germing, Ulrich; List, Alan; MacBeth, Kyle J

    2014-01-01

    Deletion of the long arm of chromosome 5, del(5q), is the most prevalent cytogenetic abnormality in patients with myelodysplastic syndromes (MDS). In isolation, it is traditionally associated with favorable prognosis compared with other subtypes of MDS. However, owing to the inherent heterogeneity of the disease, prognosis for patients with del(5q) MDS is highly variable depending on the presence of factors such as additional chromosomal abnormalities, >5 % blasts in the bone marrow (BM), or transfusion dependence. Over recent years, the immunomodulatory drug lenalidomide has demonstrated remarkable efficacy in patients with del(5q) MDS. Advances in the understanding of the pathogenesis of the disease have suggested that lenalidomide targets aberrant signaling pathways caused by haplosufficiency of specific genes in a commonly deleted region on chromosome 5 (e.g., SPARC, RPS14, Cdc25C, and PP2A). As a result, the agent specifically targets del(5q) clones while also promoting erythropoiesis and repopulation of the bone marrow in normal cells. This review discusses recent developments in the understanding of the mechanism of action of lenalidomide, and how this underlies favorable outcomes in patients with del(5q) MDS. In addition, we discuss how improved understanding of the mechanism of disease will facilitate clinicians' ability to predict/monitor response and identify patients at risk of relapse.

  16. Acute Fibrinous and Organizing Pneumonia with Myelodysplastic Syndrome: Corticosteroid Monotherapy Led to Successful Ventilator Weaning

    OpenAIRE

    Yamamoto, Mari; Murata, Kengo; Kiriu, Takahiro; Kouzai, Yasuji; Takamori, Mikio

    2016-01-01

    A 62-year-old man with myelodysplastic syndrome (MDS) presented to our hospital with a high fever. Although treatment with broad-spectrum antibiotics was initiated, his respiratory status worsened to the point that he required mechanical ventilation. However, he was successfully treated with a corticosteroid without immunosuppression. Sequential transbronchial lung biopsies revealed abundant fibrin exudate in the alveolar spaces, which was subsequently replaced by fibroblasts, showing that ac...

  17. PERSISTANT MULLERIAN DUCT SYNDROME IN AN ADULT MALE DIAGNOSED DURING HERNIORAPHY

    OpenAIRE

    Vidyadhar Kinhal; Mahesh Desai; Syeda Siddiqua Banu; Varun Kumar

    2015-01-01

    Persistent Mullerian duct syndrome (PMDS) is a rare form of internal male pseudohermaphroditism in which Mullerian duct derivatives are seen in a genotypically as well as phenotypically normal male patient. Very few cases have been repo rted in the literature. P MDS is likely to be encountered during surgery for undescended testis and inguinal hernia. Thus awareness of this disorder and the options of surgical management are necessary. We report a case of PMDS in a 35 yea...

  18. Aloimmunity against HLA class I antigens in patients with myelodysplastic syndrome and aplastic anemia

    OpenAIRE

    2005-01-01

    Myelodysplastic syndrome (MDS) and aplastic anemia (AA) are two of the hematological disorders which present peripheral cytopenias, with extensive clinical manifestations that vary from slight anemia to severe pancytopenia; the latter requiring continuous transfusional reposition of red cell (RC) and platelet concentrates (PC), which can induce aloimunization in patients. Such patients can develop a post-transfusional refractory state, rendering further transfusions unviable. The objective of...

  19. The value of fludarabine in addition to ARA-C and G-CSF in the treatment of patients with high-risk myelodysplastic syndromes and AML in elderly patients.

    NARCIS (Netherlands)

    Ossenkoppele, G.J.; Graveland, W.J.; Sonneveld, P.; Daenen, S.M.G.J.; Biesma, D.H.; Verdonck, L.F.; Schaafsma, M.R.; Westveer, P.H.; Peters, G.J.; Noordhuis, P.; Muus, P.; Selleslag, D.; Holt, B. van der; Delforge, M.; Lowenberg, B.; Verhoef, G.E.

    2004-01-01

    Fludarabine in addition to cytosine-arabinoside (ARA-C) increases the accumulation of ARA-C-5'-triphosphate (ARA-CTP), which is responsible for the cytotoxic effect in leukemic blasts. In a randomized phase 3 trial, patients with high-risk myelodysplastic syndrome (MDS) (n = 91) or elderly patients

  20. The value of fludarabine in addition to ARA-C and G-CSF in the treatment of patients with high-risk myelodysplastic syndromes and AML in elderly patients

    NARCIS (Netherlands)

    Ossenkoppele, GJ; Graveland, WJ; Sonneveld, P; Daenen, SMGJ; Biesma, DH; Verdonck, LF; Schaafsma, R; Westveer, PHM; Peters, F; Noordhuis, P; Muus, P; van der Holt, R; Delforge, M; Lowenberg, B; Verhoef, GEG

    2004-01-01

    Fludarabine in addition to cytosine-arabinoside (ARA-C) increases the accumulation of ARA-C-5'-triphosphate (ARA-CTP), which is responsible for the cytotoxic effect in leukemic blasts. In a randomized phase 3 trial, patients with high-risk myelodysplastic syndrome (MDS) (n = 91) or elderly patient's

  1. Therapy-related acute myeloid leukemia and myelodysplastic syndrome after hematopoietic cell transplantation for lymphoma.

    Science.gov (United States)

    Yamasaki, S; Suzuki, R; Hatano, K; Fukushima, K; Iida, H; Morishima, S; Suehiro, Y; Fukuda, T; Uchida, N; Uchiyama, H; Ikeda, H; Yokota, A; Tsukasaki, K; Yamaguchi, H; Kuroda, J; Nakamae, H; Adachi, Y; Matsuoka, K-I; Nakamura, Y; Atsuta, Y; Suzumiya, J

    2017-04-03

    Therapy-related acute myeloid leukemia and myelodysplastic syndrome (t-AML/MDS) represent severe late effects in patients receiving hematopoietic cell transplantation (HCT) for lymphoma. The choice between high-dose therapy with autologous HCT and allogeneic HCT with reduced-intensity conditioning remains controversial in patients with relapsed lymphoma. We retrospectively analyzed incidence and risk factors for the development of t-AML/MDS in lymphoma patients treated with autologous or allogeneic HCT. A total of 13 810 lymphoma patients who received autologous (n=9963) or allogeneic (n=3847) HCT between 1985 and 2012 were considered. At a median overall survival (OS) of 52 and 46 months in autologous and allogeneic HCT groups, respectively, lymphoma patients receiving autologous HCT (1.38% at 3 years after autologous HCT) had a significant risk for developing t-AML/MDS compared to allogeneic HCT (0.37% at 3 years after allogeneic HCT, Pafter autologous and allogeneic HCT were high-stage risk at HCT (P=0.04) or secondary malignancies (P<0.001) and receiving cord blood stem cell (P=0.03) or involved field radiotherapy (P=0.002), respectively. Strategies that carefully select lymphoma patients for autologous HCT, by excluding lymphoma patients with high-stage risk at HCT, may allow the identification of individual lymphoma patients at particular high risk for t-AML/MDS.Bone Marrow Transplantation advance online publication, 3 April 2017; doi:10.1038/bmt.2017.52.

  2. Up-front allogeneic hematopoietic cell transplantation in acute myeloid leukemia arising from the myelodysplastic syndrome.

    Science.gov (United States)

    Choi, Yunsuk; Kim, Sung-Doo; Park, Young-Hoon; Lee, Jae Seok; Kim, Dae-Young; Lee, Jung-Hee; Lee, Kyoo-Hyung; Seol, Miee; Lee, Young-Shin; Kang, Young-Ah; Jeon, Mijin; Jung, Ah Rang; Lee, Je-Hwan

    2015-01-01

    In patients with secondary acute myeloid leukemia (s-AML) arising from the myelodysplastic syndrome (MDS), treatment outcome is unsatisfactory. We compared up-front allogeneic hematopoietic cell transplantation (HCT) to induction chemotherapy (IC) as an initial treatment in patients with s-AML arising from MDS. This retrospective study included 85 patients who were diagnosed with s-AML arising from MDS; 11 patients proceeded to up-front HCT without IC (HCT group) and 74 received IC (IC group) as an initial treatment for s-AML, 28 of whom subsequently underwent HCT. In the IC group, 41.9% achieved complete remission (CR) compared to 81.8% in the HCT group (p = 0.013). The HCT group showed a significantly longer event-free survival (EFS) than the IC group (median 29.2 vs. 5.2 months, p = 0.042). Overall survival of the HCT group was higher than that of the IC group, but the difference was not statistically significant (median 34.6 vs. 7.6 months, p = 0.149). After adjustment for other clinical factors, outcome in the HCT group was significantly better than in the IC group in terms of CR rate (hazard ratio, HR, 11.195; p = 0.007) and EFS (HR, 0.384; p = 0.029). Up-front HCT is a viable option in s-AML arising from MDS if an appropriate donor is available.

  3. U2AF1 mutations in Chinese patients with acute myeloid leukemia and myelodysplastic syndrome.

    Directory of Open Access Journals (Sweden)

    Jun Qian

    Full Text Available Somatic mutations of U2AF1 gene have recently been identified in myelodysplastic syndrome (MDS and acute myeloid leukemia (AML. In this study, we analyzed the frequency and clinical impact of U2AF1 mutations in a cohort of 452 Chinese patients with myeloid neoplasms. Mutations in U2AF1 were found in 2.5% (7/275 of AML and 6.3% (6/96 of MDS patients, but in none of 81 CML. All mutations were heterozygous missense mutations affecting codon S34 or Q157. There was no significant association of U2AF1 mutation with blood parameters, FAB subtypes, karyotypes and other gene mutations in AML. The overall survival (OS of AML patients with U2AF1 mutation (median 3 months was shorter than those without mutation (median 7 months (P = 0.035. No difference in the OS was observed between MDS patients with and without U2AF1 mutations. Our data show that U2AF1 mutation is a recurrent event at a low frequency in AML and MDS.

  4. Spectrum of complex chromosomal aberrations in a myelodysplastic syndrome and a brief review

    Directory of Open Access Journals (Sweden)

    Bani Bandana Ganguly

    2016-01-01

    Full Text Available Myelodysplastic syndrome (MDS is a heterogeneous premalignant condition characterized by cytopenia, ineffective hematopoiesis, dysplastic marrow, and risk of progression to acute myeloid leukemia. Cytogenetic abnormalities, including del(3q/5q/7q/11q/12p/20q, monosomy 5/7, trisomy 8/19, i(17q, and -Y, are the indicators of diagnosis and risk stratification. The present case with bicytopenia detected with highly complex chromosome rearrangements with variability in numerical and structural combinations. Chromosome analysis was carried out following unstimulated marrow culture and G-banding. In addition to known MDS-aberrations, der(9p, der(12 dic(12;?19, +15, −18, and ring and marker chromosomes were recorded having, at least, nine abnormal chromosomes/cell. To our knowledge, this is the first case with all MDS-aberrations in one single individual. The case has been discussed in relevance to current MDS research. In the present case, i(17q/-17, der(12p, del(5q26, del(7q36, and del(20q11 indicate possible alterations in TP53, ETV6, IDH2, EZH2, and SRSF2 genes, which are responsible for pathomechanism, genetic instability, clonal evolution, and advancement of disease condition.

  5. Decitabine of reduced dosage in Chinese patients with myelodysplastic syndrome: a retrospective analysis.

    Directory of Open Access Journals (Sweden)

    Xiao Li

    Full Text Available Decitabine has been approved for the treatment of all subtypes of myelodysplastic syndrome (MDS. However, the optimal regimen for decitabine treatment is not well established. In this study, an observational, retrospective and multi-center analysis was performed to explore the decitabine schedule for the treatment of MDS. A total of 79 patients received reduced dosage decitabine treatment (15 mg/M2/day intravenously for five consecutive days every four weeks. Fifty-three out of the 79 patients were defined as intermediate-2/high risk by international prognostic scoring system (IPSS risk category. 67.1% of MDS patients achieved treatment response including complete response (CR (n = 23, Partial response (n = 1, marrow CR (mCR with hematological improvement (HI (n = 11, mCR without HI (n = 11 and HI alone (n = 7 with a median of 4 courses (range 1-11. The median overall survival (OS was 18.0 months. The median OS was 22.0, 17.0 and 12.0 months in the patients with CR, those with other response, and those without response, respectively. In addition, this regimen contributed to zero therapy-related death and punctual course delivery, although III or IV grade of cytopenia was frequently observed. In conclusion, the 15 mg/M2/d×5 day decitabine regimen was effective and safe for Chinese MDS patients with IPSS score of 0.5 or higher.

  6. Myelodysplastic syndromes.

    Science.gov (United States)

    Koeffler, H P

    1996-04-01

    These two issues of the Seminars in Hematology will provide the physician the necessary knowledge to help make sense of this somewhat confusing array of diseases. The subdivisions of MDS reflect the precision of our techniques of dissection, with morphological and histochemical analyses forming the foundation to identify and subdivide MDS. Although steady refinement has occurred over the last half-century, the basic morphologic technique is unchanged. Cytogenetic analysis, which has been possible since the 1960s and 1970s, should be done at least at initial presentation in all patients to provide refinement of diagnosis and prognosis. FISH is not, at this time, useful as a screening technique. Although the 1990s is an era of rapidly growing knowledge and technical abilities in molecular biology, the use of these techniques in MDS is in its infancy. Very few genes have been identified which are altered in MDS, although many must exist. The molecular assays continue to be cumbersome and impractical to use in the clinical laboratory and remain the domain of the research scientist. Nevertheless, in the future, molecular biology will enable the internist to give each individual a clearer diagnosis and prognosis and may even provide targetted therapies of patients with MDS. At this time the center of management is good supportive care. Some patients, however, will benefit from special interventions, which include the use of growth factors, BMT, and in selected patients, aggressive chemotherapy. Induction of differentiation of the abnormal hematopoietic clone remains only a dream, although some of the differentiation agents may have applicability for their ability to induce apoptosis and prevent growth of the MDS clone of cells. Many of the major advances in our knowledge of cancer developed through the study of hematopoietic malignancy. A lot of these advances are due to the ease of obtaining the abnormal cells. MDS provides an excellent model for studying the

  7. The interplay between SUCLA2, SUCLG2, and mitochondrial DNA depletion

    DEFF Research Database (Denmark)

    Miller, Chaya; Wang, Liya; Ostergaard, Elsebet;

    2011-01-01

    SUCLA2-related mitochondrial DNA (mtDNA) depletion syndrome is a result of mutations in the β subunit of the ADP-dependent isoform of the Krebs cycle succinyl-CoA synthase (SCS). The mechanism of tissue specificity and mtDNA depletion is elusive but complementation by the GDP-dependent isoform...... encoded by SUCLG2, and the association with mitochondrial nucleoside diphosphate kinase (NDPK), is a plausible link. We have investigated this relationship by studying SUCLA2 deficient fibroblasts derived from patients and detected normal mtDNA content and normal NDPK activity. However, knockdown of SUCLG...... and that mitochondrial NDPK is involved. Although results pertain to a cell culture system, the findings might explain the pathomechanism and tissue specificity in mtDNA depletion caused by defective SUCLA2....

  8. Prognostic relevance of morphological classification models for myelodysplastic syndromes in an era of the revised International Prognostic Scoring System.

    Science.gov (United States)

    van Spronsen, Margot F; Ossenkoppele, Gert J; Westers, Theresia M; van de Loosdrecht, Arjan A

    2016-03-01

    Numerous morphological classification models have been developed to organise the heterogeneous spectrum of myelodysplastic syndromes (MDS). While the 2008 update of the World Health Organisation (WHO) is the current standard, the publication of the revised International Prognostic Scoring System (IPSS-R) has illustrated the need for supplemental prognostic information. The aim of this study was to investigate whether morphological classification models for MDS - of both the French-American-British (FAB) group and WHO - provide reliable criteria for their classification into homogeneous and clinically relevant categories with prognostic relevance beyond the IPSS-R. We reclassified 238 MDS patients using each of the FAB, WHO 2001 and WHO 2008 criteria and studied classification categories in terms of clinical, haematological and cytogenetic features. Subsequently, we calculated prognostic scores using the IPSS-R and investigated whether the morphological classification models had significantly prognostic value in patients stratified by the IPSS-R and vice versa. By adopting the FAB, WHO 2001 and WHO 2008 classifications, MDS patients were organised into homogeneous categories with intrinsic prognostic information. However, whereas the morphological classification models showed no prognostic value beyond the IPSS-R, the IPSS-R had significant prognostic value beyond the FAB, WHO 2001 and WHO 2008 classifications. Even though morphological classification models for MDS might be clinically relevant from a prognostic point of view, their relevance in terms of risk stratification is evidently limited in light of the IPSS-R. Therefore, we suggest to stop the use of morphological classification models for MDS for risk stratification in routine clinical practice.

  9. Identification of gene expression-based prognostic markers in the hematopoietic stem cells of patients with myelodysplastic syndromes.

    Science.gov (United States)

    Pellagatti, Andrea; Benner, Axel; Mills, Ken I; Cazzola, Mario; Giagounidis, Aristoteles; Perry, Janet; Malcovati, Luca; Della Porta, Matteo G; Jädersten, Martin; Verma, Amit; McDonald, Emma-Jane; Killick, Sally; Hellström-Lindberg, Eva; Bullinger, Lars; Wainscoat, James S; Boultwood, Jacqueline

    2013-10-01

    The diagnosis of patients with myelodysplastic syndromes (MDS) is largely dependent on morphologic examination of bone marrow aspirates. Several criteria that form the basis of the classifications and scoring systems most commonly used in clinical practice are affected by operator-dependent variation. To identify standardized molecular markers that would allow prediction of prognosis, we have used gene expression profiling (GEP) data on CD34+ cells from patients with MDS to determine the relationship between gene expression levels and prognosis. GEP data on CD34+ cells from 125 patients with MDS with a minimum 12-month follow-up since date of bone marrow sample collection were included in this study. Supervised principal components and lasso penalized Cox proportional hazards regression (Coxnet) were used for the analysis. We identified several genes, the expression of which was significantly associated with survival of patients with MDS, including LEF1, CDH1, WT1, and MN1. The Coxnet predictor, based on expression data on 20 genes, outperformed other predictors, including one that additionally used clinical information. Our Coxnet gene signature based on CD34+ cells significantly identified a separation of patients with good or bad prognosis in an independent GEP data set based on unsorted bone marrow mononuclear cells, demonstrating that our signature is robust and may be applicable to bone marrow cells without the need to isolate CD34+ cells. We present a new, valuable GEP-based signature for assessing prognosis in MDS. GEP-based signatures correlating with clinical outcome may significantly contribute to a refined risk classification of MDS.

  10. New Approach For Prediction Groundwater Depletion

    Science.gov (United States)

    Moustafa, Mahmoud

    2017-01-01

    Current approaches to quantify groundwater depletion involve water balance and satellite gravity. However, the water balance technique includes uncertain estimation of parameters such as evapotranspiration and runoff. The satellite method consumes time and effort. The work reported in this paper proposes using failure theory in a novel way to predict groundwater saturated thickness depletion. An important issue in the failure theory proposed is to determine the failure point (depletion case). The proposed technique uses depth of water as the net result of recharge/discharge processes in the aquifer to calculate remaining saturated thickness resulting from the applied pumping rates in an area to evaluate the groundwater depletion. Two parameters, the Weibull function and Bayes analysis were used to model and analyze collected data from 1962 to 2009. The proposed methodology was tested in a nonrenewable aquifer, with no recharge. Consequently, the continuous decline in water depth has been the main criterion used to estimate the depletion. The value of the proposed approach is to predict the probable effect of the current applied pumping rates on the saturated thickness based on the remaining saturated thickness data. The limitation of the suggested approach is that it assumes the applied management practices are constant during the prediction period. The study predicted that after 300 years there would be an 80% probability of the saturated aquifer which would be expected to be depleted. Lifetime or failure theory can give a simple alternative way to predict the remaining saturated thickness depletion with no time-consuming processes such as the sophisticated software required.

  11. Risks of iron overload for patients with myelodysplastic syndrome and the efficacy of deferasirox%铁过载对骨髓增生异常综合征患者的危害及地拉罗司祛铁疗效探讨

    Institute of Scientific and Technical Information of China (English)

    刘容容

    2012-01-01

    长期规律输血是骨髓增生异常综合征(M DS)最为重要的支持疗法,然而长期输血带来的铁过载会导致器官损害,严重影响患者的生存预后.祛铁治疗对于改善MDS患者造血机能、减少心脏事件、延长生存起着重要作用.地拉罗司是一种新型的口服铁螯合剂,能有效改善MDS患者的造血机能、促进血液学缓解并改善脏器功能,是MDS患者祛铁治疗的一线药物.本文就铁过载对MDS患者的危害、MDS祛铁治疗指南及地拉罗司在MDS铁过载治疗中的应用做一综述.%Long-term regular transfusion is the most important supportive treatment for patients with myelodysplastic syndrome (MDS). However, iron overload caused by long-term transfusion could lead to organ dysfunction, and remarkably shorten patients' survival. Iron chelation treatment (ICT) plays a significant role in improving hematopoiesis of MDS patients, decreasing cardiac events and increasing their survival. Deferasirox is a new type of oral iron chelators, which effectively improves hematopoietic response and organ functions of MDS patients. Also, deferasirox is recommended as the first-line chelator for MDS patients in most of MDS treatment guidelines. This review summarized the risks of iron overload for MDS patients, ICT guideline for MDS patients and efficacy of deferasirox in MDS patients.

  12. Characterization of defective megakaryocytic development in patients with myelodysplastic syndromes.

    Science.gov (United States)

    Hofmann, W K; Kalina, U; Wagner, S; Seipelt, G; Ries, C; Hoelzer, D; Ottmann, O G

    1999-03-01

    Megakaryocytic differentiation of progenitor cells was investigated in nine patients with low-risk myelodysplastic syndromes (MDS) (eight refractor anemia [RA] and one RA with ringed sideroblasts [RARS] and five patients with high-risk MDS (two RA with excess of blasts [RAEB] and three RAEB in transformation [RAEB-T]). Bone marrow-derived CD34+ cells were enriched to a purity of 87% +/- 2% (mean +/- SEM) and assayed in short-term suspension cultures in the presence of 10 ng/mL of PEGylated recombinant human megakaryocyte (MK) growth and development factor (PEG-rHuMGDF) and in addition to 50 ng/mL stem cell factor and 10 ng/mL interleukin-3. Cells of the megakaryocytic lineage were identified by flow cytometric analysis of CD42b (GP1b) and mature MKs by morphologic criteria. Transcription of c-mpl receptor-specific mRNA in the CD34+ cells of these patients was investigated by full-length reverse transcriptase polymerase chain reaction of the p form of c-mpl as well as of the alternative splice product c-mpl k. CD34+ cells from seven healthy bone marrow donors served as controls. Differentiation along the MK pathway was stimulated in five patients with RA. C-mpl mRNA was expressed in the CD34+ cells in all cases. In three low-risk patients the capacity for in vitro MK growth was absent or minimal even though mRNA for c-mpl receptor was detected in the CD34+ cells of this group as well. In patients with high-risk MDS, PEG-rHuMGDF stimulated in vitro MK growth from CD34+ cells in only one of five cases. As in the patients with low-risk MDS, c-mpl mRNA for both c-mpl p and c-mpl k splicing products was detected. These results indicate that the in vitro response to stimulation with c-mpl ligand discriminates between two groups of patients with low-risk MDS and that the observed defect in megakaryocytic development is unrelated to the level of c-mpl expression in both low-risk and high-risk MDS.

  13. [Exploration of academic thoughts on treating myelodysplastic syndrome with combination of disease and syndrome by Prof. Ma Rou].

    Science.gov (United States)

    Gao, Fei; Xu, Shu; Sun, Shu-zhen; Hu, Xiao-mei; Ma, Rou

    2013-03-01

    The diagnosis and treatment pattern using combination of disease and syndrome, fully developing the advantages of both traditional Chinese medicine (TCM) and Western medicine (WM) and being widely used clinically, has been constructed in the long history of TCM. Prof. MA Rou, as a hematology specialist of integrative medicine (IM), uses modern medical equipment to diagnose diseases and takes traditional Chinese medical methods to treat diseases. He is loyal to TCM sciences and refers to the advantages of WM. He holds the essence of MDS lies in toxic stasis according to its pathogenic features. He detoxifies and removes stasis using Qinghuang Powder. Meanwhile, according to patients' clinical manifestations, he summarized two common syndrome types, Pi-Shen yang deficiency syndrome and Gan-Shen yin deficiency syndrome. Better efficacy could be achieved by combining Chinese herbs for tonifying Pi-Shen. In recent years the application of Qinghuang Powder won some achievements in clinical study and experimental study, thus providing scientific reliance for Prof. MA Rou's academic thought on treating MDS.

  14. VizieR Online Data Catalog: Candidate rotating M dwarfs from PS1-MDS (Kado-Fong+, 2016)

    Science.gov (United States)

    Kado-Fong, E.; Williams, P. K. G.; Mann, A. W.; Berger, E.; Burgett, W. S.; Chambers, K. C.; Huber, M. E.; Kaiser, N.; Kudritzki, R.-P.; Magnier, E. A.; Rest, A.; Wainscoat, R. J.; Waters, C.

    2017-05-01

    The Pan-STARRS1 Medium-Deep Survey (PS1-MDS) was performed on the 1.8m Pan-STARRS1 telescope situated on Mount Haleakala, Hawai'i, equipped with five broadband filters, (grizy)P1. The PS1 filters are similar to those used in the Sloan Digital Sky Survey (SDSS), but include a yP1 filter (λeff~9600Å), a bluer cutoff in the z band (Δλ~1000Å rather than 1400Å), a 200Å redder cutoff in the g band, and no u band. We identified candidate cool dwarfs using color cuts as described in section 2.4. We searched for periodic variations in the light curves of our candidate cool stars using the multiband extension of the Lomb-Scargle periodogram introduced by VanderPlas & Ivezic (2015ApJ...812...18V); see section 3. We list the confirmed rotators in Table 3. (2 data files).

  15. Dumping Syndrome

    Science.gov (United States)

    ... System & How it Works Digestive Diseases A-Z Dumping Syndrome What is dumping syndrome? Dumping syndrome occurs when food, especially sugar, ... the colon and rectum—and anus. What causes dumping syndrome? Dumping syndrome is caused by problems with ...

  16. Groundwater depletion embedded in international food trade

    Science.gov (United States)

    Dalin, Carole; Wada, Yoshihide; Kastner, Thomas; Puma, Michael J.

    2017-03-01

    Recent hydrological modelling and Earth observations have located and quantified alarming rates of groundwater depletion worldwide. This depletion is primarily due to water withdrawals for irrigation, but its connection with the main driver of irrigation, global food consumption, has not yet been explored. Here we show that approximately eleven per cent of non-renewable groundwater use for irrigation is embedded in international food trade, of which two-thirds are exported by Pakistan, the USA and India alone. Our quantification of groundwater depletion embedded in the world’s food trade is based on a combination of global, crop-specific estimates of non-renewable groundwater abstraction and international food trade data. A vast majority of the world’s population lives in countries sourcing nearly all their staple crop imports from partners who deplete groundwater to produce these crops, highlighting risks for global food and water security. Some countries, such as the USA, Mexico, Iran and China, are particularly exposed to these risks because they both produce and import food irrigated from rapidly depleting aquifers. Our results could help to improve the sustainability of global food production and groundwater resource management by identifying priority regions and agricultural products at risk as well as the end consumers of these products.

  17. The New MCNP6 Depletion Capability

    Energy Technology Data Exchange (ETDEWEB)

    Fensin, Michael Lorne [Los Alamos National Laboratory; James, Michael R. [Los Alamos National Laboratory; Hendricks, John S. [Los Alamos National Laboratory; Goorley, John T. [Los Alamos National Laboratory

    2012-06-19

    The first MCNP based inline Monte Carlo depletion capability was officially released from the Radiation Safety Information and Computational Center as MCNPX 2.6.0. Both the MCNP5 and MCNPX codes have historically provided a successful combinatorial geometry based, continuous energy, Monte Carlo radiation transport solution for advanced reactor modeling and simulation. However, due to separate development pathways, useful simulation capabilities were dispersed between both codes and not unified in a single technology. MCNP6, the next evolution in the MCNP suite of codes, now combines the capability of both simulation tools, as well as providing new advanced technology, in a single radiation transport code. We describe here the new capabilities of the MCNP6 depletion code dating from the official RSICC release MCNPX 2.6.0, reported previously, to the now current state of MCNP6. NEA/OECD benchmark results are also reported. The MCNP6 depletion capability enhancements beyond MCNPX 2.6.0 reported here include: (1) new performance enhancing parallel architecture that implements both shared and distributed memory constructs; (2) enhanced memory management that maximizes calculation fidelity; and (3) improved burnup physics for better nuclide prediction. MCNP6 depletion enables complete, relatively easy-to-use depletion calculations in a single Monte Carlo code. The enhancements described here help provide a powerful capability as well as dictate a path forward for future development to improve the usefulness of the technology.

  18. The impact of TP53 mutations and TP53 deletions on survival varies between AML, ALL, MDS and CLL: an analysis of 3307 cases.

    Science.gov (United States)

    Stengel, A; Kern, W; Haferlach, T; Meggendorfer, M; Fasan, A; Haferlach, C

    2017-03-01

    Alterations in TP53 have been described in many cancer types including hematological neoplasms. We aimed at comparing TP53 mutations (mut) and deletions (del) in a large cohort of patients with hematological malignancies (n=3307), including AML (n=858), MDS (n=943), ALL (n=358), CLL (n=1148). Overall, alterations in TP53 were detected in 332/3307 cases (10%). The highest frequency was observed in ALL (total: 19%; mut+del: 6%; mut only: 8%; del only: 5%) and AML (total: 13%; mut+del: 5%; mut only: 7%; del only: 1%), whereas TP53 alterations occurred less frequently in CLL (total: 8%) and MDS (total: 7%). TP53 mutations were significantly more frequent in patients ⩾60 vs TP53 deletion and mutation status.

  19. 骨髓增生异常综合征患者骨髓间充质干细胞的免疫抑制作用%Immuno-suppressive effects mediated by mesenchymal stem cells of myelodysplastic syndrome patients

    Institute of Scientific and Technical Information of China (English)

    韩艳鑫; 丛雅琴; 王志敏

    2012-01-01

    Objective To investigate expression levels of transforming growth factor-β (TGF-β1) and hepatocyte growth factor (HGF) in mesenchymal stem cells (MSC) of myelodysplastic syndrome-refractory anemia (MDS-RA) and myelodysplastic syndrome-refractory anemia with excess blasts (MDS-RAEB), and to discuss the immuno-suppressive effects of MSC in the pathogenesis of MDS. Methods Bone marrow samples were collected from patients with MDS at diagnosis (n =23, 14 from MDS-RA, 9 from MDS-RAEB) and 12 controls. MSCs from bone marrow samples were isolated, cultured and expanded. The morphology of MSCs of the three groups was compared. The transforming growth factor-β1 and hepatocyte growth factor mRNA expression levels were detected by RT-PCR, the TGF-βl and HGF concentrations of MSCs were tested by enzyme-linked immunosorbent assay (ELISA). Results The cultured cells from the patients with MDS presented a typical fibroblast-like morphology, which had no significant change compared with that of the controls. TGF-β1 and HGF mRNA expression levels and the TGF-β1 and HGF concentration levels in the MSCs of MDS-RA and MDS-RAEB groups were significantly lower than those of the control group (P< 0. 05). TGF-βl and HGF mRNA expression levels and TGF-βl and HGF concentration levels in the MSCs had no significant difference between the MDS-RA and MDS-RAEB groups (P >0.05). Conclusions TGF-β1 and HGF mRNA expression levels and TGF-β1 and HGF concentration levels in the MSCs of MDS-RA and MDS-RAEB groups were significantly lower than those of the control group, resulting in the decreasing ability of MSC immune suppression. Its mechanism may be related to lower immune surveillance and abnormal monoclonal hematopoiesis.%目的 本研究通过检测骨髓增生异常综合征-难治性贫血(MDS-RA)及难治性贫血伴原始细胞增多(MDS-RAEB)患者骨髓间充质干细胞(MSC)转化生长因子(TGF-β1)、肝细胞生长因子(HGF)的表达,

  20. Omphalocele in Miller-Dieker syndrome: Expanding the phenotype

    Energy Technology Data Exchange (ETDEWEB)

    Chitayat, D. [Toronto Hospital-General Division, Ontario (Canada)]|[Univ. of Toronto, Ontario (Canada); Moola, S.; Yarkoni, D. [Toronto Hospital-General Division, Ontario (Canada)] [and others

    1997-03-31

    We report on a patient prenatally diagnosed with omphalocele, mild cerebral ventriculomegaly, nuchal fold thickening, and cystic changes in the umbilical cord who was found postnatally to have lissencephaly type I. Prenatal chromosome analysis showed a normal male karyotype; however, postnatal high resolution banding and FISH analysis, using a probe for locus D17S379 in chromosome region 17p13.3, demonstrated a deletion at 17p13.3 consistent with Miller-Dieker syndrome (MDS). A review documented four more cases with MDS/isolated lissencephaly/17p-, with omphalocele. Because MDS is a contiguous gene disorder, we speculate that a gene or genes in this region have a major role in the closure of the lateral folds or the return of the midgut from the body stalk to the abdomen at 5-11 weeks of gestation. Prenatal diagnosis of omphalocele with mild ventriculomegaly should prompt FISH analysis for a deletion in 17p13.3. 44 refs., 7 figs., 1 tab.

  1. Ego depletion in visual perception: Ego-depleted viewers experience less ambiguous figure reversal.

    Science.gov (United States)

    Wimmer, Marina C; Stirk, Steven; Hancock, Peter J B

    2017-02-22

    This study examined the effects of ego depletion on ambiguous figure perception. Adults (N = 315) received an ego depletion task and were subsequently tested on their inhibitory control abilities that were indexed by the Stroop task (Experiment 1) and their ability to perceive both interpretations of ambiguous figures that was indexed by reversal (Experiment 2). Ego depletion had a very small effect on reducing inhibitory control (Cohen's d = .15) (Experiment 1). Ego-depleted participants had a tendency to take longer to respond in Stroop trials. In Experiment 2, ego depletion had small to medium effects on the experience of reversal. Ego-depleted viewers tended to take longer to reverse ambiguous figures (duration to first reversal) when naïve of the ambiguity and experienced less reversal both when naïve and informed of the ambiguity. Together, findings suggest that ego depletion has small effects on inhibitory control and small to medium effects on bottom-up and top-down perceptual processes. The depletion of cognitive resources can reduce our visual perceptual experience.

  2. The modality effect of ego depletion: Auditory task modality reduces ego depletion.

    Science.gov (United States)

    Li, Qiong; Wang, Zhenhong

    2016-08-01

    An initial act of self-control that impairs subsequent acts of self-control is called ego depletion. The ego depletion phenomenon has been observed consistently. The modality effect refers to the effect of the presentation modality on the processing of stimuli. The modality effect was also robustly found in a large body of research. However, no study to date has examined the modality effects of ego depletion. This issue was addressed in the current study. In Experiment 1, after all participants completed a handgrip task, one group's participants completed a visual attention regulation task and the other group's participants completed an auditory attention regulation task, and then all participants again completed a handgrip task. The ego depletion phenomenon was observed in both the visual and the auditory attention regulation task. Moreover, participants who completed the visual task performed worse on the handgrip task than participants who completed the auditory task, which indicated that there was high ego depletion in the visual task condition. In Experiment 2, participants completed an initial task that either did or did not deplete self-control resources, and then they completed a second visual or auditory attention control task. The results indicated that depleted participants performed better on the auditory attention control task than the visual attention control task. These findings suggest that altering task modality may reduce ego depletion.

  3. Ozone depletion and chlorine loading potentials

    Science.gov (United States)

    Pyle, John A.; Wuebbles, Donald J.; Solomon, Susan; Zvenigorodsky, Sergei; Connell, Peter; Ko, Malcolm K. W.; Fisher, Donald A.; Stordal, Frode; Weisenstein, Debra

    1991-01-01

    The recognition of the roles of chlorine and bromine compounds in ozone depletion has led to the regulation or their source gases. Some source gases are expected to be more damaging to the ozone layer than others, so that scientific guidance regarding their relative impacts is needed for regulatory purposes. Parameters used for this purpose include the steady-state and time-dependent chlorine loading potential (CLP) and the ozone depletion potential (ODP). Chlorine loading potentials depend upon the estimated value and accuracy of atmospheric lifetimes and are subject to significant (approximately 20-50 percent) uncertainties for many gases. Ozone depletion potentials depend on the same factors, as well as the evaluation of the release of reactive chlorine and bromine from each source gas and corresponding ozone destruction within the stratosphere.

  4. Plasmonic nanoprobes for stimulated emission depletion microscopy

    CERN Document Server

    Cortes, Emiliano; Sinclair, Hugo G; Guldbrand, Stina; Peveler, William J; Davies, Timothy; Parrinello, Simona; Görlitz, Frederik; Dunsby, Chris; Neil, Mark A A; Sivan, Yonatan; Parkin, Ivan P; French, Paul M; Maier, Stefan A

    2016-01-01

    Plasmonic nanoparticles influence the absorption and emission processes of nearby emitters due to local enhancements of the illuminating radiation and the photonic density of states. Here, we use the plasmon resonance of metal nanoparticles in order to enhance the stimulated depletion of excited molecules for super-resolved microscopy. We demonstrate stimulated emission depletion (STED) microscopy with gold nanorods with a long axis of only 26 nm and a width of 8 nm that provide an enhancement of the resolution compared to fluorescent-only probes without plasmonic components irradiated with the same depletion power. These novel nanoparticle-assisted STED probes represent a ~2x10^3 reduction in probe volume compared to previously used nanoparticles and we demonstrate their application to the first plasmon-assisted STED cellular imaging. We also discuss their current limitations.

  5. Molten-Salt Depleted-Uranium Reactor

    CERN Document Server

    Dong, Bao-Guo; Gu, Ji-Yuan

    2015-01-01

    The supercritical, reactor core melting and nuclear fuel leaking accidents have troubled fission reactors for decades, and greatly limit their extensive applications. Now these troubles are still open. Here we first show a possible perfect reactor, Molten-Salt Depleted-Uranium Reactor which is no above accident trouble. We found this reactor could be realized in practical applications in terms of all of the scientific principle, principle of operation, technology, and engineering. Our results demonstrate how these reactors can possess and realize extraordinary excellent characteristics, no prompt critical, long-term safe and stable operation with negative feedback, closed uranium-plutonium cycle chain within the vessel, normal operation only with depleted-uranium, and depleted-uranium high burnup in reality, to realize with fission nuclear energy sufficiently satisfying humanity long-term energy resource needs, as well as thoroughly solve the challenges of nuclear criticality safety, uranium resource insuffic...

  6. Self-regulation, ego depletion, and inhibition.

    Science.gov (United States)

    Baumeister, Roy F

    2014-12-01

    Inhibition is a major form of self-regulation. As such, it depends on self-awareness and comparing oneself to standards and is also susceptible to fluctuations in willpower resources. Ego depletion is the state of reduced willpower caused by prior exertion of self-control. Ego depletion undermines inhibition both because restraints are weaker and because urges are felt more intensely than usual. Conscious inhibition of desires is a pervasive feature of everyday life and may be a requirement of life in civilized, cultural society, and in that sense it goes to the evolved core of human nature. Intentional inhibition not only restrains antisocial impulses but can also facilitate optimal performance, such as during test taking. Self-regulation and ego depletion- may also affect less intentional forms of inhibition, even chronic tendencies to inhibit. Broadly stated, inhibition is necessary for human social life and nearly all societies encourage and enforce it.

  7. Depletion of the nuclear Fermi sea

    CERN Document Server

    Rios, A; Dickhoff, W H

    2009-01-01

    The short-range and tensor components of the bare nucleon-nucleon interaction induce a sizeable depletion of low momenta in the ground state of a nuclear many-body system. The self-consistent Green's function method within the ladder approximation provides an \\textit{ab-initio} description of correlated nuclear systems that accounts properly for these effects. The momentum distribution predicted by this approach is analyzed in detail, with emphasis on the depletion of the lowest momentum state. The temperature, density, and nucleon asymmetry (isospin) dependence of the depletion of the Fermi sea is clarified. A connection is established between the momentum distribution and the time-ordered components of the self-energy, which allows for an improved interpretation of the results. The dependence on the underlying nucleon-nucleon interaction provides quantitative estimates of the importance of short-range and tensor correlations in nuclear systems.

  8. Sensitivity study of control rod depletion coefficients

    OpenAIRE

    Blomberg, Joel

    2015-01-01

    This report investigates the sensitivity of the control rod depletion coefficients, Sg, to different input parameters and how this affects the accumulated 10B depletion, β. Currently the coefficients are generated with PHOENIX4, but the geometries can be more accurately simulated in McScram. McScram is used to calculate Control Rod Worth, which in turn is used to calculate Nuclear End Of Life, and Sg cannot be generated in the current version of McScram. Therefore, it is also analyzed whether...

  9. Increased frequency of dicentric chromosomes in therapy-related MDS and AML compared to de novo disease is significantly related to previous treatment with alkylating agents and suggests a specific susceptibility to chromosome breakage at the centromere.

    Science.gov (United States)

    Andersen, M K; Pedersen-Bjergaard, J

    2000-01-01

    Dicentric chromosomes are observed in many malignant diseases including myelodysplasia (MDS) and acute myeloid leukemia (AML) and have often been observed in a subset of these diseases, namely therapy-related MDS (t-MDS) and AML (t-AML). Using fluorescence in situ hybridization (FISH) with centromere-specific probes, we investigated the frequency and type of dicentric chromosomes in 180 consecutive patients with t-MDS and t-AML and in 231 consecutive patients with de novo MDS and AML, whose karyotypes had been studied previously by conventional G-banding. Twenty-seven out of 180 patients with t-MDS or t-AML presented dicentric chromosomes compared to only seven out of 231 patients with de novo disease (P = 0.00003). A dic(1q;7p) was observed in 10 cases, a dic(5p;17q) was observed in six cases, whereas various isodicentric chromosomes were observed in six cases. Excluding these six cases with isodicentrics, all 25 patients with dicentric chromosomes had involvement of at least one of the chromosome arms 1q, 5p, or 7p resulting in monosomy for 5q or 7q, and/or trisomy for 1q. Patients with dicentric chromosomes presented significantly more often as t-MDS compared to patients without dicentrics (P = 0.046), and the presence of a dicentric chromosome was significantly related to previous therapy with alkylating agents (P = 0.026). Thus, only one out of 27 patients with a dicentric chromosome had not previously received an alkylating agent. A specific susceptibility to breakage at the centromere after exposure to alkylating agents is suggested and may explain the frequent loss of whole chromosomes, in particular chromosomes 5 and 7 in t-MDS and t-AML, if the breaks are not followed by rejoining. Leukemia (2000) 14, 105-111.

  10. 骨髓增生异常综合征患者外周血JAK2V617F 基因检测及临床意义%The detection and clinical significance of JAK2V617F mutations in myelodysplastic syndrome patients

    Institute of Scientific and Technical Information of China (English)

    王婷; 潘琳莉; 吴杰; 王艳军; 张磊; 李光耀

    2016-01-01

    目的:比较骨髓增生异常综合征(MDS)难治性贫血(MDS-RA)型与难治性贫血伴原始细胞增多(MDS-RAEB)型患者外周血 JAK2V617F基因表达水平,进而监测 MDS 的病情进展。方法建立 JAK2V617F基因表达的荧光定量 FQ-PCR 检测方法,回顾性分析确诊为 MDS 的患者共22例(其中 MDS-RAEB1型6例, MDS-RAEB2型4例,MDS-RA 型12例),抽取同期健康体检者20例,应用 FQ-PCR 方法监测健康人群、MDS-RA 型患者、MDS-RAEB 型患者外周血 JAK2V617F基因表达水平。结果健康人外周血 JAK2V617F基因不表达或低表达,拷贝数为(596.98±470.46),MDS-RA 患者为(4631.11±3851.96),MDS-RA 患者显著高于健康人(t =3.61,P <0.01);MDS-RAEB 患者为(22545.98±11084.17),显著高于 MDS-RA 患者(t =4.87,P <0.01)。结论JAK2V617F基因有可能参与了 MDS 的发病及其恶性转变,监测外周血 JAK2V617F基因表达有助于监测 MDS 的病情进展、判断预后和进行基因调控治疗。%Objective To explore the pathogenesis of myelodysplastic syndrome (MDS)transformation, JAK2V617F mRNA expression levels were compared in peripheral blood of MDS-RA(refractory anemia,RA)and MDS-RAEB(RA with excess blasts,RAEB)patients.Methods JAK2V617F mRNA expression level was detected by fuorescent quantitative polymerase chain reaction(FQ-PCR),and this research reviewed 22 patients diagnosed with MDS,including outpatient and hospitalized patients.20 cases of normal control group were healthy ones.FQ-PCR method was applied to monitor JAK2V617F mRNA expression level in peripheral blood of MDS-RA and MDS-RAEB patients.Results The JAK2V617F gene was not expressed or expressed in healthy subjects,and the copy number was (3 851.96 ±470.46).The patients with MDS-RA(4 631.11 ±3 851.96)was significantly higher than that in healthy subjects(t =3.61,P <0.01);MDS-RAEB patients was (22 545.98 ±11 084.17),and was

  11. Lenalidomide induces lipid raft assembly to enhance erythropoietin receptor signaling in myelodysplastic syndrome progenitors.

    Science.gov (United States)

    McGraw, Kathy L; Basiorka, Ashley A; Johnson, Joseph O; Clark, Justine; Caceres, Gisela; Padron, Eric; Heaton, Ruth; Ozawa, Yukiyasu; Wei, Sheng; Sokol, Lubomir; List, Alan F

    2014-01-01

    Anemia remains the principal management challenge for patients with lower risk Myelodysplastic Syndromes (MDS). Despite appropriate cytokine production and cellular receptor display, erythropoietin receptor (EpoR) signaling is impaired. We reported that EpoR signaling is dependent upon receptor localization within lipid raft microdomains, and that disruption of raft integrity abolishes signaling capacity. Here, we show that MDS erythroid progenitors display markedly diminished raft assembly and smaller raft aggregates compared to normal controls (p = 0.005, raft number; p = 0.023, raft size). Because lenalidomide triggers raft coalescence in T-lymphocytes promoting immune synapse formation, we assessed effects of lenalidomide on raft assembly in MDS erythroid precursors and UT7 cells. Lenalidomide treatment rapidly induced lipid raft formation accompanied by EpoR recruitment into raft fractions together with STAT5, JAK2, and Lyn kinase. The JAK2 phosphatase, CD45, a key negative regulator of EpoR signaling, was displaced from raft fractions. Lenalidomide treatment prior to Epo stimulation enhanced both JAK2 and STAT5 phosphorylation in UT7 and primary MDS erythroid progenitors, accompanied by increased STAT5 DNA binding in UT7 cells, and increased erythroid colony forming capacity in both UT7 and primary cells. Raft induction was associated with F-actin polymerization, which was blocked by Rho kinase inhibition. These data indicate that deficient raft integrity impairs EpoR signaling, and provides a novel strategy to enhance EpoR signal fidelity in non-del(5q) MDS.

  12. Lenalidomide induces lipid raft assembly to enhance erythropoietin receptor signaling in myelodysplastic syndrome progenitors.

    Directory of Open Access Journals (Sweden)

    Kathy L McGraw

    Full Text Available Anemia remains the principal management challenge for patients with lower risk Myelodysplastic Syndromes (MDS. Despite appropriate cytokine production and cellular receptor display, erythropoietin receptor (EpoR signaling is impaired. We reported that EpoR signaling is dependent upon receptor localization within lipid raft microdomains, and that disruption of raft integrity abolishes signaling capacity. Here, we show that MDS erythroid progenitors display markedly diminished raft assembly and smaller raft aggregates compared to normal controls (p = 0.005, raft number; p = 0.023, raft size. Because lenalidomide triggers raft coalescence in T-lymphocytes promoting immune synapse formation, we assessed effects of lenalidomide on raft assembly in MDS erythroid precursors and UT7 cells. Lenalidomide treatment rapidly induced lipid raft formation accompanied by EpoR recruitment into raft fractions together with STAT5, JAK2, and Lyn kinase. The JAK2 phosphatase, CD45, a key negative regulator of EpoR signaling, was displaced from raft fractions. Lenalidomide treatment prior to Epo stimulation enhanced both JAK2 and STAT5 phosphorylation in UT7 and primary MDS erythroid progenitors, accompanied by increased STAT5 DNA binding in UT7 cells, and increased erythroid colony forming capacity in both UT7 and primary cells. Raft induction was associated with F-actin polymerization, which was blocked by Rho kinase inhibition. These data indicate that deficient raft integrity impairs EpoR signaling, and provides a novel strategy to enhance EpoR signal fidelity in non-del(5q MDS.

  13. Contrasts between Antarctic and Arctic ozone depletion.

    Science.gov (United States)

    Solomon, Susan; Portmann, Robert W; Thompson, David W J

    2007-01-09

    This work surveys the depth and character of ozone depletion in the Antarctic and Arctic using available long balloon-borne and ground-based records that cover multiple decades from ground-based sites. Such data reveal changes in the range of ozone values including the extremes observed as polar air passes over the stations. Antarctic ozone observations reveal widespread and massive local depletion in the heart of the ozone "hole" region near 18 km, frequently exceeding 90%. Although some ozone losses are apparent in the Arctic during particular years, the depth of the ozone losses in the Arctic are considerably smaller, and their occurrence is far less frequent. Many Antarctic total integrated column ozone observations in spring since approximately the 1980s show values considerably below those ever observed in earlier decades. For the Arctic, there is evidence of some spring season depletion of total ozone at particular stations, but the changes are much less pronounced compared with the range of past data. Thus, the observations demonstrate that the widespread and deep ozone depletion that characterizes the Antarctic ozone hole is a unique feature on the planet.

  14. Global Warming: Lessons from Ozone Depletion

    Science.gov (United States)

    Hobson, Art

    2010-01-01

    My teaching and textbook have always covered many physics-related social issues, including stratospheric ozone depletion and global warming. The ozone saga is an inspiring good-news story that's instructive for solving the similar but bigger problem of global warming. Thus, as soon as students in my physics literacy course at the University of…

  15. Global Warming: Lessons from Ozone Depletion

    Science.gov (United States)

    Hobson, Art

    2010-01-01

    My teaching and textbook have always covered many physics-related social issues, including stratospheric ozone depletion and global warming. The ozone saga is an inspiring good-news story that's instructive for solving the similar but bigger problem of global warming. Thus, as soon as students in my physics literacy course at the University of…

  16. An analysis of the demographic profile, clinical manifestations, investigations and outcome of paediatric myelodysplastic syndrome: A single centre, cross-sectional study

    Directory of Open Access Journals (Sweden)

    Appaji Lingegowda

    2015-09-01

    Full Text Available Purpose: Pediatric myelodysplastic syndrome (MDS is a relatively rare entity, with distinct clinical features and more aggressive course than its adult counterpart. The aim of this study was to analyze the incidence of pediatric myelodysplastic syndrome at a tertiary cancer care center in southern India along with clinical manifestations, investigations and outcome.Methods: On retrospective analysis of 1094 cases of pediatric hematological malignancies over a five-year period from September 2009 to August 2014, a total of seven cases of pediatric myelodysplastic syndrome were identified. Presenting complaints, physical examination, investigations including haemogram, biochemistry, bone marrow examination and cytogenetics were reviewed. The diagnosis of MDS was made if there was dysplasia in at least 10% of cells in two or more cell lineages. All patients were risk stratified using the revised IPSS. Results: Out of 1094 cases of pediatric hematological malignancies presenting at our institute within the study period, there were only seven cases of pediatric MDS with an incidence of 0.65%. There were no genetic predispositions nor any cases of therapy related MDS. The most common presentation was with fever and all patients had significant splenomegaly. All patients had anemia (Median-6.2 gm / dL with elevated WBC counts (Median-30,900 / uL and thrombocytopenia (Median-50,000 / uL. The marrow cytogenetics was normal in five patients. Most patients fell into the high and very high-risk category of the revised IPSS, with only two patients of low risk. All seven patients were given only supportive care but one progressed to AML for which he was treated with remission induction. Only two patients were alive at the time of analysis and median survival was 9 months. Conclusion: Pediatric MDS is a rare disease with a short clinical history, aggressive course and generally poor outcomes as compared to the adult variant. A hematopoietic stem cell

  17. Cerebral salt wasting syndrome in a patient with tuberculous meningitis.

    Science.gov (United States)

    Ravishankar, B; Mangala; Prakash, G K; Shetty, K J; Ballal, H S

    2006-05-01

    We report a case of a 65 year male with meningitis who had polyuria, severe hyponatremia, volume depletion and very high urinary sodium excretion. He was diagnosed to have cerebral salt wasting syndrome based on clinical and laboratory parameters.

  18. Early lymphocyte recovery predicts superior overall survival after unmanipulated haploidentical blood and marrow transplant for myelodysplastic syndrome and acute myeloid leukemia evolving from myelodysplastic syndrome.

    Science.gov (United States)

    Chang, Ying-Jun; Zhao, Xiang-Yu; Xu, Lan-Ping; Liu, Dai-Hong; Liu, Kai-Yan; Chen, Yu-Hong; Wang, Yu; Zhang, Xiao-Hui; Zhao, Xiao-Su; Han, Wei; Chen, Huan; Wang, Feng-Rong; Lv, Meng; Huang, Xiao-Jun

    2013-12-01

    We investigated whether early lymphocyte recovery, after unmanipulated, haploidentical, blood and marrow transplant (HBMT), affected clinical outcomes in 78 patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia evolving from MDS. Lymphocyte recovery was based on the absolute lymphocyte count on day 30 (ALC-30). Patients with high ALC-30 (≥ 300 cells/μL) had lower relapse rates (13.8% vs. 35.5%, p = 0.049) and lower incidence of bacterial infections (3.4% vs. 25.8%, p = 0.015) than those with low ALC-30 values. Multivariate analysis showed that a high ALC-30 was associated with improved overall survival (OS, hazard ratio [HR]: 0.099, 95% confidence interval [CI]: 0.029-0.337; p leukemia-free survival (HR: 0.245, 95% CI: 0.112-0.539; p after unmanipulated HBMT.

  19. “When the going gets tough, who keeps going?” Depletion sensitivity moderates the ego-depletion effect

    Science.gov (United States)

    Salmon, Stefanie J.; Adriaanse, Marieke A.; De Vet, Emely; Fennis, Bob M.; De Ridder, Denise T. D.

    2014-01-01

    Self-control relies on a limited resource that can get depleted, a phenomenon that has been labeled ego-depletion. We argue that individuals may differ in their sensitivity to depleting tasks, and that consequently some people deplete their self-control resource at a faster rate than others. In three studies, we assessed individual differences in depletion sensitivity, and demonstrate that depletion sensitivity moderates ego-depletion effects. The Depletion Sensitivity Scale (DSS) was employed to assess depletion sensitivity. Study 1 employs the DSS to demonstrate that individual differences in sensitivity to ego-depletion exist. Study 2 shows moderate correlations of depletion sensitivity with related self-control concepts, indicating that these scales measure conceptually distinct constructs. Study 3 demonstrates that depletion sensitivity moderates the ego-depletion effect. Specifically, participants who are sensitive to depletion performed worse on a second self-control task, indicating a stronger ego-depletion effect, compared to participants less sensitive to depletion. PMID:25009523

  20. “When the going gets tough, who keeps going?” Depletion sensitivity moderates the ego-depletion effect

    NARCIS (Netherlands)

    Salmon, S.J.; Adriaanse, M.A.; Vet, de E.W.M.L.; Fennis, B.M.; Ridder, de D.T.D.

    2014-01-01

    Self-control relies on a limited resource that can get depleted, a phenomenon that has been labeled ego-depletion. We argue that individuals may differ in their sensitivity to depleting tasks, and that consequently some people deplete their self-control resource at a faster rate than others. In thre

  1. How Depleted is the MORB mantle?

    Science.gov (United States)

    Hofmann, A. W.; Hart, S. R.

    2015-12-01

    Knowledge of the degree of mantle depletion of highly incompatible elements is critically important for assessing Earth's internal heat production and Urey number. Current views of the degree of MORB source depletion are dominated by Salters and Stracke (2004), and Workman and Hart (2005). The first is based on an assessment of average MORB compositions, whereas the second considers trace element data of oceanic peridotites. Both require an independent determination of one absolute concentration, Lu (Salters & Stracke), or Nd (Workman & Hart). Both use parent-daughter ratios Lu/Hf, Sm/Nd, and Rb/Sr calculated from MORB isotopes combined with continental-crust extraction models, as well as "canonical" trace element ratios, to boot-strap the full range of trace element abundances. We show that the single most important factor in determining the ultimate degree of incompatible element depletion in the MORB source lies in the assumptions about the timing of continent extraction, exemplified by continuous extraction versus simple two-stage models. Continued crust extraction generates additional, recent mantle depletion, without affecting the isotopic composition of the residual mantle significantly. Previous emphasis on chemical compositions of MORB and/or peridotites has tended to obscure this. We will explore the effect of different continent extraction models on the degree of U, Th, and K depletion in the MORB source. Given the uncertainties of the two most popular models, the uncertainties of U and Th in DMM are at least ±50%, and this impacts the constraints on the terrestrial Urey ratio. Salters, F.J.M. and Stracke, A., 2004, Geochem. Geophys. Geosyst. 5, Q05004. Workman, R.K. and Hart, S.R., 2005, EPSL 231, 53-72.

  2. Cushing syndrome

    Science.gov (United States)

    Hypercortisolism; Cortisol excess; Glucocorticoid excess - Cushing syndrome ... The most common cause of Cushing syndrome is taking too much ... exogenous Cushing syndrome . Prednisone, dexamethasone, and ...

  3. Serotonin syndrome

    Science.gov (United States)

    Hyperserotonemia; Serotonergic syndrome; Serotonin toxicity; SSRI - serotonin syndrome; MAO - serotonin syndrome ... two medicines that affect the body's level of serotonin are taken together at the same time. The ...

  4. Clinical, hematological, and cytogenetic profile of adult myelodysplastic syndrome in a tertiary care center

    Directory of Open Access Journals (Sweden)

    Narayanan S

    2017-02-01

    Full Text Available Santhosh Narayanan Department of Medicine, Government Medical College, Kozhikode, Kerala, India Background: Myelodysplastic syndrome (MDS, a disorder of clonal hematopoiesis, is an important clinical entity, but most of the studies available are conducted among the Western population. Its etiological factors and clinicohematological profile in the Indian population are quite diverse. The information regarding its prognostic factors and cytogenetics is very scarce.Objectives: (1 To assess the clinicohematological profile, cytogenetics, prognostic factors, and outcome of MDS and (2 to study its progression to acute myeloid leukemia (AML in the selected patients over the study period.Methods: A prospective observational study was performed with patients from Department of Medicine and Hematology, Government Medical College, Kozhikode, who were diagnosed with MDS within the study period (from 1 January 2014 to 31 July 2015. Secondary causes of dysplasia were excluded. In possible cases, the international prognostic scoring system was followed. These patients were followed up for an additional 6 months to assess the progression of MDS to AML based on symptoms, signs, hemogram, or repeat peripheral smear/bone marrow studies.Results: Of the 60 patients, 73% were aged >60 years. Disease was common in males, with a male:female ratio of 7:3. Thirty-five percent of the patients were working in agricultural and allied fields and had pesticide exposure. Patients with prior radiation exposure had significant association with adverse outcome. Fatigue was the prominent symptom and was reported by 90% of the patients. Blasts were >5% in peripheral smear; bone marrow cytopenia and dysplasia at the time of diagnosis had significant association with risk of transforming to AML. Refractory anemia (RA, observed in 22 patients, was the most common type of MDS. Most of the patients with RA with excess blasts type-1 and RA with excess blasts type-2 transformed to AML

  5. Immunophenotypic, cytogenetic, and mutational characterization of cell lines derived from myelodysplastic syndrome patients after progression to acute myeloid leukemia.

    Science.gov (United States)

    Palau, Anna; Mallo, Mar; Palomo, Laura; Rodríguez-Hernández, Ines; Diesch, Jeannine; Campos, Diana; Granada, Isabel; Juncà, Jordi; Drexler, Hans G; Solé, Francesc; Buschbeck, Marcus

    2017-03-01

    Leukemia cell lines have been widely used in the hematology field to unravel mechanistic insights and to test new therapeutic strategies. Myelodysplastic syndromes (MDS) comprise a heterogeneous group of diseases that are characterized by ineffective hematopoiesis and frequent progress to acute myeloid leukemia (AML). A few cell lines have been established from MDS patients after progression to AML but their characterization is incomplete. Here we provide a detailed description of the immunophenotypic profile of the MDS-derived cell lines SKK-1, SKM-1, F-36P; and MOLM-13. Specifically, we analyzed a comprehensive panel of markers that are currently applied in the diagnostic routine for myeloid disorders. To provide high-resolution genetic data comprising copy number alterations and losses of heterozygosity we performed whole genome single nucleotide polymorphism-based arrays and included the cell line OHN-GM that harbors the frequent chromosome arm 5q deletion. Furthermore, we assessed the mutational status of 83 disease-relevant genes. Our results provide a resource to the MDS and AML field that allows researchers to choose the best-matching cell line for their functional studies. © 2016 Wiley Periodicals, Inc.

  6. The role of p53 in myelodysplastic syndromes and acute myeloid leukemia: molecular aspects and clinical implications.

    Science.gov (United States)

    Zhang, Ling; McGraw, Kathy L; Sallman, David A; List, Alan F

    2017-08-01

    TP53 gene mutations occurring in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) are associated with high-risk karyotypes including 17p abnormalities, monosomal and complex cytogenetics. TP53 mutations in these disorders portend rapid disease progression and resistance to conventional therapeutics. Notably, the size of the TP53 mutant clone as measured by mutation allele burden is directly linked to overall survival (OS) confirming the importance of p53 as a negative prognostic variable. In nucleolar stress-induced ribosomopathies, such as del(5q) MDS, disassociation of MDM2 and p53 results in p53 accumulation in erythroid precursors manifested as erythroid hypoplasia. P53 antagonism by lenalidomide or other therapeutics such as antisense oligonucleotides, repopulates erythroid precursors and enhances effective erythropoiesis. These findings demonstrate that p53 is an intriguing therapeutic target that is currently under investigation in MDS and AML. This study reviews molecular advances in understanding the role of p53 in MDS and AML, and explores potential therapeutic strategies in this era of personalized medicine.

  7. Significance of genome-wide analysis of copy number alterations and UPD in myelodysplastic syndromes using combined CGH - SNP arrays.

    Science.gov (United States)

    Ahmad, Ausaf; Iqbal, M Anwar

    2012-01-01

    Genetic information is an extremely valuable data source in characterizing the personal nature of cancer. Chromosome instability is a hallmark of most cancer cells. Chromosomal abnormalities are correlated with poor prognosis, disease classification, risk stratification, and treatment selection. Copy number alterations (CNAs) are an important molecular signature in cancer initiation, development, and progression. Recent application of whole-genome tools to characterize normal and cancer genomes provides the powerful molecular cytogenetic means to enumerate the multiple somatic, genetic and epigenetic alterations that occur in cancer. Combined array comparative genomic hybridization (aCGH) with single nucleotide polymorphism (SNP) array is a useful technique allowing detection of CNAs and loss of heterozygosity (LOH) or uni-parental disomy (UPD) together in a single experiment. It also provides allelic information on deletions, duplications, and amplifications. UPD can result in an abnormal phenotype when the chromosomes involved are imprinted. Myelodysplastic syndromes (MDS) are the most common clonal stem cell hematologic malignancy characterized by ineffective hematopoiesis, which leads to rapid progression into acute myeloid leukemia. UPD that occurs without concurrent changes in the gene copy number is a common chromosomal defect in hematologic malignancies, especially in MDS. Approximately 40-50% of MDS patients do not have karyotypic abnormalities that are detectable using classical metaphase cytogenetic techniques (MC) because of inherent limitations of MC, low resolution and the requirement of having dividing cells. In this review, we highlight advances in the clinical application of microarray technology in MDS and discuss the clinical potential of microarray.

  8. Beckwith-Wiedemann syndrome and pseudohypoparathyroidism type Ib in a patient with multilocus imprinting disturbance: a female-dominant phenomenon?

    Science.gov (United States)

    Sano, Shinichiro; Matsubara, Keiko; Nagasaki, Keisuke; Kikuchi, Toru; Nakabayashi, Kazuhiko; Hata, Kenichiro; Fukami, Maki; Kagami, Masayo; Ogata, Tsutomu

    2016-08-01

    Although recent studies have often revealed the presence of multilocus imprinting disturbance (MLID) at differentially methylated regions (DMRs) in patients with imprinting disorders (IDs), most patients exhibit clinical features of the original ID only. Here we report a Japanese female patient with Beckwith-Wiedemann syndrome and pseudohypoparathyroidism type Ib. Molecular studies revealed marked methylation defects (MDs) at the Kv-DMR and the GNAS-DMRs and variable MDs at four additional DMRs, in the absence of a mutation in ZFP57, NLRP2, NLRP7, KHDC3L and NLRP5. It is likely that the MDs at the Kv-DMR and the GNAS-DMRs were sufficient to cause clinically recognizable IDs, whereas the remaining MDs were insufficient to result in clinical consequences or took place at DMRs with no disease-causing imprinted gene(s). The development of MLID and the two IDs of this patient may be due to a mutation in a hitherto unknown gene for MLID, or to a reduced amount of DNA methyltransferase-1 (DNMT1) available for the methylation maintenance of DMRs because of the consumption of DNMT1 by the maintenance of X-inactivation. In support of the latter possibility, such co-existence of two IDs has primarily been identified in female patients, and MLID has predominantly been identified as loss of methylations.

  9. Pre-transplant weight loss predicts inferior outcome after allogeneic stem cell transplantation in patients with myelodysplastic syndrome.

    Science.gov (United States)

    Radujkovic, Aleksandar; Becker, Natalia; Benner, Axel; Penack, Olaf; Platzbecker, Uwe; Stölzel, Friedrich; Bornhäuser, Martin; Hegenbart, Ute; Ho, Anthony D; Dreger, Peter; Luft, Thomas

    2015-10-27

    Allogeneic stem cell transplantation (alloSCT) represents a curative therapeutic option for patients with myelodysplastic syndrome (MDS), but relapse and non-relapse mortality (NRM) limit treatment efficacy. Based on our previous observation in acute myeloid leukemia we investigated the impact of pre-transplant weight loss on post-transplant outcome in MDS patients. A total of 111 patients diagnosed with MDS according to WHO criteria transplanted between 2000 and 2012 in three different transplant centers were included into the analysis. Data on weight loss were collected from medical records prior to conditioning therapy and 3-6 months earlier. Patient, disease and transplant characteristics did not differ between patients with weight loss (2-5%, n = 17; > 5%, n = 17) and those without (n = 77). In a mixed effect model, weight loss was associated with higher risk MDS (p = 0.046). In multivariable analyses, pre-transplant weight loss exceeding 5% was associated with a higher incidence of relapse (p transplant weight loss of 2-5% and > 5% were independent predictors of worse disease-free (p = 0.023 and p transplantation. Prospective studies addressing pre-transplant nutritional interventions are highly warranted.

  10. Analysis of the efficacy of lenalidomide in patients with intermediate-1 risk myelodysplastic syndrome without 5q deletion.

    Science.gov (United States)

    Yang, Yan; Gao, Sujun; Fan, Hongqiong; Lin, Hai; Li, Wei; Wang, Juan

    2013-09-01

    The aim of this study was to evaluate the efficacy and adverse effects of lenalidomide in the treatment of intermediate-1 risk non-5q deletion [non-del (5q)] myelodysplastic syndrome (MDS). A total of 30 patients with MDS were classified through G-banding chromosome karyotype analysis and fluorescence in situ hybridization (FISH). According to the International Prognostic Scoring System scores, among the 30 patients, 23 and seven cases had scores of 0.5 and 1.0, respectively. Lenalidomide (Revlimid(®)), 10 mg/day) was administered for 21 days every 28 days. All 30 cases were treated with lenalidomide for at least three cycles, including 20 cases with four cycles. The patients did not require erythropoietin, cyclosporine or iron chelation treatments. Statistical analysis was performed using SPSS statistical software version 13.0, and comparisons among groups were conducted using a t-test. The efficacy of lenalidomide was demonstrated in patients with intermediate-1 risk non-del (5q) MDS. Peripheral blood cell counts were improved following treatment, and absolute neutrophil, haemoglobin and platelet counts increased following 2-4 cycles of treatment. All patients became stable having undergone three cycles of treatment; however, 17 patients with chromosomal abnormalities had no cytogenetic response to the treatment, as confirmed through the FISH test. Patients with intermediate-1 risk non-del (5q) MDS treated with lenalidomide did not achieve complete haematological remission, although they demonstrated haematological improvement.

  11. Treatment of Bone Marrow Failure Syndrome with Integrated Traditional and Western Medicine

    Institute of Scientific and Technical Information of China (English)

    MA Rou

    2007-01-01

    @@ Aplastic anemia (AA) and myelodysplastic syndrome (MDS) are both included in the bone marrow failure syndromes (BMFS). AA is a group of diseases characterized by hematopoietic stem/progenitor cell damage,peripheral blood cytopenia, and clinical manifestations including anemia, bleeding and infection, which eventually lead to bone marrow failure.The incidence rate of AA in China is 7.4/106, higher than that in Western countries, among which the morbidity of acute AA and chronic AA (CAA) is 1.4/106 and 6.0/106,respectively.

  12. A High Occurrence of Acquisition and/or Expansion of C-CBL Mutant Clones in the Progression of High-Risk Myelodysplastic Syndrome to Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Hsiao-Wen Kao

    2011-11-01

    Full Text Available The molecular pathogenesis of myelodysplastic syndrome (MDS and its progression to secondary acute myeloid leukemia (sAML remain to be explored. Somatic C-CBL mutations were recently described in MDS. Our study aimed to determine the role of C-CBL mutations in the progression of MDS to sAML and sought to correlate with clinicohematological features and outcome. Bone marrow samples from 51 patients with high-risk MDS (13 with refractory cytopenia with multilineage dysplasia, 19 with refractory anemia with excess blast 1, and 19 with refractory anemia with excess blast 2 were analyzed for C-CBL mutations at both diagnosis and sAML in the same individuals. Mutational analysis was performed for exons 7 to 9 of C-CBL gene. Of the 51 paired samples, C-CBL mutations were identified in 6 patients at the sAML phase. One patient retained the identical C-CBL mutation (G415S at sAML evolution and exhibited clonal expansion. The other five patients acquired C-CBL mutations (Y371S, F418S, L370_Y371 ins L, L399V, and C416W during sAML evolution. Three of the six patients harboring C-CBL mutations at sAML had additional gene mutations including JAK2V617F, PTPN11, or N-RAS. There was no significant difference in clinicohematological features and overall survival with respect to C-CBL mutation status. Our results show that C-CBL mutation is very rare (0.6% in MDS, but acquisition and/or expansion of C-CBL mutant clones occur in 11.8% of patients during sAML transformation. The findings suggest that C-CBL mutations play a role at least in part in a subset of MDS patients during sAML transformation.

  13. Higher fetuin-A, lower adiponectin and free leptin levels mediate effects of excess body weight on insulin resistance and risk for myelodysplastic syndrome.

    Science.gov (United States)

    Dalamaga, Maria; Karmaniolas, Konstantinos; Chamberland, John; Nikolaidou, Athina; Lekka, Antigoni; Dionyssiou-Asteriou, Amalia; Mantzoros, Christos S

    2013-12-01

    Excess body weight has been implicated in the pathogenesis of myelodysplastic syndrome (MDS). We thus explored the role of serum fetuin-A reflecting ectopic hepatic fat deposition when storage capacity of adipocytes has been exceeded, free leptin reflecting overall fat mass and adiponectin reflecting visceral fat mass, all potential mediators of the effects of obesity on insulin resistance and, consequently, to MDS risk. In a hospital-based case-control study, we studied 101 cases with incident, histologically confirmed primary MDS and 101 controls matched on gender, age and date of diagnosis, between 2004 and 2007. Serum fetuin-A, adiponectin, leptin, leptin receptor, free leptin and insulin were determined. Higher serum fetuin-A, lower adiponectin and lower free leptin were all individually and independently associated with higher risk of MDS before and after controlling for matching and risk factors, such as age, gender, date of diagnosis, body mass index (BMI), family history of lymphohematopoietic cancer, smoking history and serum insulin. Interestingly, we have shown that these associations were prominent among overweight/obese individuals and persisted after controlling for BMI and serum insulin indicating that their effects are above and beyond insulinemia only. Elevated serum fetuin-A but lower adiponectin and free leptin are associated with higher risk of MDS particularly among overweight/obese individuals. These findings suggest that the association between excessive weight gain and the risk of MDS could be mediated by fetuin-A, adiponectin and free leptin, which may have potential clinical and preventive implications. © 2013.

  14. Disruption of SF3B1 results in deregulated expression and splicing of key genes and pathways in myelodysplastic syndrome hematopoietic stem and progenitor cells.

    Science.gov (United States)

    Dolatshad, H; Pellagatti, A; Fernandez-Mercado, M; Yip, B H; Malcovati, L; Attwood, M; Przychodzen, B; Sahgal, N; Kanapin, A A; Lockstone, H; Scifo, L; Vandenberghe, P; Papaemmanuil, E; Smith, C W J; Campbell, P J; Ogawa, S; Maciejewski, J P; Cazzola, M; Savage, K I; Boultwood, J

    2015-05-01

    The splicing factor SF3B1 is the most commonly mutated gene in the myelodysplastic syndrome (MDS), particularly in patients with refractory anemia with ring sideroblasts (RARS). We investigated the functional effects of SF3B1 disruption in myeloid cell lines: SF3B1 knockdown resulted in growth inhibition, cell cycle arrest and impaired erythroid differentiation and deregulation of many genes and pathways, including cell cycle regulation and RNA processing. MDS is a disorder of the hematopoietic stem cell and we thus studied the transcriptome of CD34(+) cells from MDS patients with SF3B1 mutations using RNA sequencing. Genes significantly differentially expressed at the transcript and/or exon level in SF3B1 mutant compared with wild-type cases include genes that are involved in MDS pathogenesis (ASXL1 and CBL), iron homeostasis and mitochondrial metabolism (ALAS2, ABCB7 and SLC25A37) and RNA splicing/processing (PRPF8 and HNRNPD). Many genes regulated by a DNA damage-induced BRCA1-BCLAF1-SF3B1 protein complex showed differential expression/splicing in SF3B1 mutant cases. This is the first study to determine the target genes of SF3B1 mutation in MDS CD34(+) cells. Our data indicate that SF3B1 has a critical role in MDS by affecting the expression and splicing of genes involved in specific cellular processes/pathways, many of which are relevant to the known RARS pathophysiology, suggesting a causal link.

  15. Lenalidomide: a review of its use in patients with transfusion-dependent anaemia due to low- or intermediate-1-risk myelodysplastic syndrome associated with 5q chromosome deletion.

    Science.gov (United States)

    Syed, Yahiya Y; Scott, Lesley J

    2013-07-01

    Lenalidomide (Revlimid(®)), a thalidomide analogue, is an orally administered second generation immunomodulator with anti-angiogenic, antineoplastic, anti-inflammatory and pro-erythropoietic properties. It is approved for the treatment of patients with transfusion-dependent anaemia due to International Prognostic Scoring System low- or intermediate-1-risk myelodysplastic syndrome (MDS) associated with either chromosome 5q deletion [del(5q)] with or without additional cytogenetic abnormalities (US, Japan and Switzerland etc.), or with an isolated del(5q) cytogenetic abnormality when other therapeutic options are insufficient or inadequate (EU) [featured indication]. In a randomized, double-blind, multicentre, registrational trial (MDS-004; n = 205) in this patient population, a significantly higher proportion of lenalidomide recipients than placebo recipients achieved red blood cell transfusion independence for ≥26 consecutive weeks (primary endpoint for efficacy) and cytogenetic responses. The erythroid response to lenalidomide was accompanied by an increase in the haemoglobin levels. These efficacy outcomes are generally consistent with those seen in an earlier noncomparative registrational trial (MDS-003; n = 148). In MDS-004, lenalidomide also significantly improved health-related quality of life compared with placebo at 12 weeks. Retrospective analyses that compared outcomes between lenalidomide-treated patients with low- or intermediate-1-risk del(5q) MDS and multicentre registry cohorts showed that lenalidomide treatment did not appear to increase the risk of progression to acute myeloid leukaemia. Lenalidomide had a manageable safety profile in the registrational trials, with ≤20 % of patients discontinuing treatment because of adverse events. The most common adverse events (incidence ≥20 %) occurring in lenalidomide recipients were thrombocytopenia and neutropenia, which were generally managed by dosage reductions and/or interruptions, and

  16. High level of full-length cereblon mRNA in lower risk myelodysplastic syndrome with isolated 5q deletion is implicated in the efficacy of lenalidomide.

    Science.gov (United States)

    Jonasova, Anna; Bokorova, Radka; Polak, Jaroslav; Vostry, Martin; Kostecka, Arnost; Hajkova, Hana; Neuwirtova, Radana; Siskova, Magda; Sponerova, Dana; Cermak, Jaroslav; Mikulenkova, Dana; Cervinek, Libor; Brezinova, Jana; Michalova, Kyra; Fuchs, Ota

    2015-07-01

    Downregulation of cereblon (CRBN) gene expression is associated with resistance to the immunomodulatory drug lenalidomide and poor survival outcomes in multiple myeloma (MM) patients. However, the importance of CRBN gene expression in patients with myelodysplastic syndrome (MDS) and its impact on lenalidomide therapy are not clear. In this study, we evaluate cereblon expression in mononuclear cells isolated from bone marrow [23 lower risk MDS patients with isolated 5q deletion (5q-), 37 lower risk MDS patients with chromosome 5 without the deletion of long arms (non-5q-), and 24 healthy controls] and from peripheral blood (38 patients with 5q-, 52 non-5q- patients and 25 healthy controls) to gain insight into, firstly, the role of cereblon in lower risk MDS patients with or without 5q deletion and, secondly, into the mechanisms of lenalidomide action. Patients with 5q- lower risk MDS have the highest levels of CRBN mRNA in comparison with both lower risk MDS without the deletion of long arms of chromosome 5 and healthy controls. CRBN gene expression was measured using the quantitative TaqMan real-time PCR. High levels of CRBN mRNA were detected in all lenalidomide responders during the course of therapy. A significant decrease of the CRBN mRNA level during lenalidomide treatment is associated with loss of response to treatment and disease progression. These results suggest that, similar to the treatment of MM, high levels of full-length CRBN mRNA in lower risk 5q- patients are necessary for the efficacy of lenalidomide.

  17. Splicing factor SF3B1 mutations and ring sideroblasts in myelodysplastic syndromes: a Brazilian cohort screening study

    Directory of Open Access Journals (Sweden)

    Flávia Sacilotto Donaires

    Full Text Available ABSTRACT Background: Myelodysplastic syndromes (MDS comprise a group of malignant clonal hematologic disorders characterized by ineffective hematopoiesis and propensity for progression to acute myeloid leukemia. Acquired mutations in the gene encoding RNA splicing factor 3B subunit 1 (SF3B1 are highly associated with the MDS subtypes presenting ring sideroblasts, and represent a specific nosological entity. The effects of these mutations on clinical outcomes are diverse and contrasting. Methods: A cohort of 91 Brazilian MDS patients, including patients with ring sideroblasts in the bone marrow, were screened for mutations in the SF3B1 hotspots (exons 12-15 by direct Sanger sequencing. Results: SF3B1 heterozygous mutations were identified in six patients (7%, all of them with ring sideroblasts, thus confirming the association between SF3B1 mutations and myelodysplastic syndrome subtypes bearing this morphologic feature (frequency of 6/13, p-value < 0.0001. Conclusion: This is the first screening of SF3B1 mutations in a cohort of Brazilian myelodysplastic syndrome patients. Our findings confirm that mutations in this splicing gene correlate with bone marrow ringed sideroblasts.

  18. Haploinsufficiency of RPS14 in 5q− syndrome is associated with deregulation of ribosomal- and translation-related genes

    Science.gov (United States)

    Pellagatti, Andrea; Hellström-Lindberg, Eva; Giagounidis, Aristoteles; Perry, Janet; Malcovati, Luca; Della Porta, Matteo G; Jädersten, Martin; Killick, Sally; Fidler, Carrie; Cazzola, Mario; Wainscoat, James S; Boultwood, Jacqueline

    2008-01-01

    We have previously demonstrated haploinsufficiency of the ribosomal gene RPS14, which is required for the maturation of 40S ribosomal subunits and maps to the commonly deleted region, in the 5q− syndrome. Patients with Diamond-Blackfan anaemia (DBA) show haploinsufficiency of the closely related ribosomal protein RPS19, and show a consequent downregulation of multiple ribosomal- and translation-related genes. By analogy with DBA, we have investigated the expression profiles of a large group of ribosomal- and translation-related genes in the CD34+ cells of 15 myelodysplastic syndrome (MDS) patients with 5q− syndrome, 18 MDS patients with refractory anaemia (RA) and a normal karyotype, and 17 healthy controls. In this three-way comparison, 55 of 579 ribosomal- and translation-related probe sets were found to be significantly differentially expressed, with approximately 90% of these showing lower expression levels in the 5q− syndrome patient group. Using hierarchical clustering, patients with the 5q− syndrome could be separated both from other patients with RA and healthy controls solely on the basis of the deregulated expression of ribosomal- and translation-related genes. Patients with the 5q− syndrome have a defect in the expression of genes involved in ribosome biogenesis and in the control of translation, suggesting that the 5q− syndrome represents a disorder of aberrant ribosome biogenesis. PMID:18477045

  19. Outcomes and survival analysis of patients with AML and high risk MDS treated by CAG regimen%CAG方案治疗AML和高危MDS患者的疗效及生存分析

    Institute of Scientific and Technical Information of China (English)

    倪蓓文; 陈芳源; 韩洁英; 钟华; 钟璐; 黄洪晖; 沈莉菁; 肖菲

    2009-01-01

    目的 评价CAG方案对初治、难治、复发性急性髓系白血病(AML)和高危骨髓增生异常综合征(MDS)患者的临床疗效和不良反应,分析影响患者长期生存的相关因素.方法 对61例AML患者(其中初治27例,复发16例,难治18例)和9例高危MDS患者实施CAG方案诱导缓解治疗.治疗前后进行心电图,肝、肾功能和骨髓检查,观察CAG方案的不良反应.根据患者的临床表现、外周血和骨髓细胞学检查结果评价近期疗效;随访分析患者总体生存期(OS)和无病生存期(DFS),评判CAG方案的长期疗效.运用生存曲线的Log-rank检验分析影响患者长期生存的因素.结果 CAG方案治疗一个疗程的总有效率为71%,其中34例(49%)达到完全缓解.本组中位随访时间45个月,中位OS为28个月,中位DFS为23个月.年龄、初发时乳酸脱氢酶(LDH)水平、CAG方案治疗一个疗程是否达缓解或是否采用HD-Ara-C作为巩固治疗方案均是患者OS和DFS的影响因素.临床不良反应主要为骨髓抑制,其中粒细胞缺乏(中性粒细胞<0.5×10~9/L)的中位持续时间为13 d,血小板减少(血小板<20×10~9/L)中位持续时间9 d.结论 采用CAG方案治疗初治、难治、复发AML和高危MDS患者,不良反应轻,远期疗效较好.发病年龄、发病时LDH水平、是否一个疗程缓解及是否予以HD-Ara-C作为巩固治疗方案是影响患者生存期的主要因素.%Objective To evaluate the clinical efficacy and adverse effects of CAG regimen in treatment of primary, refractory and relapsed acute myeloid leukemia (AML) and high risk myelodysplastic syndrome (MDS), and analyse the factors influencing long-term survival. Methods Sixty-one patients with AML ( primary, n = 27; refractory, n = 18; relapsed, n = 16) and 9 patients with MDS were treated with CAG regimen. Examinations on liver and renal function, electrocardiogram and bone marrow cytology were performed before and after treatment, and adverse effects of

  20. Gardner Syndrome

    Science.gov (United States)

    ... Home > Types of Cancer > Gardner Syndrome Request Permissions Gardner Syndrome Approved by the Cancer.Net Editorial Board , 06/2014 What is Gardner syndrome? Gardner syndrome is a subtype of familial ...

  1. Neutron-activation revisited: the depletion and depletion-activation models.

    Science.gov (United States)

    Abdel-Rahman, Wamied; Podgorsak, Ervin B

    2005-02-01

    The growth of a radioactive daughter in neutron activation is commonly described with the saturation model that ignores the consumption of parent nuclei during the radio-activation process. This approach is not valid when radioactive sources with high specific activities are produced or when the particle fluence rates used are very high. Assuming a constant neutron fluence rate throughout the activation target, a neutron-activation model that accounts for the depletion in parent nuclei is introduced. This depletion model is governed by relationships similar to those describing the parent-daughter-granddaughter decay series, and, in contrast to the saturation model, correctly predicts the practical limit of the daughter specific activity, irrespective of the particle fluence rate. Also introduced is a neutron-activation model that in addition to parent depletion accounts for the neutron activation of daughter nuclei in situations where the cross section for this effect is high. The model is referred to as the depletion-activation model and it provides the most realistic description for the daughter specific activity in neutron activation. Three specific neutron activation examples of interest to medical physics are presented: activation of molybdenum-98 into molybdenum-99 described by the saturation model; activation of cobalt-59 into cobalt-60 described by the depletion model; and activation of iridium-191 into iridium-192 described by the depletion-activation model.

  2. Immune Mechanisms in Myelodysplastic Syndrome

    DEFF Research Database (Denmark)

    Glenthøj, Andreas; Ørskov, Andreas Due; Hansen, Jakob Werner

    2016-01-01

    diseases are common in patients with MDS, fueling hypotheses of common etiological mechanisms. Both innate and adaptive immune pathways are overly active in the hematopoietic niche of MDS. Although supportive care, growth factors, and hypomethylating agents are the mainstay of MDS treatment, some patients......-especially younger low-risk patients with HLA-DR15 tissue type-demonstrate impressive response rates after immunosuppressive therapy. This is in contrast to higher-risk MDS patients, where several immune activating treatments, such as immune checkpoint inhibitors, are in the pipeline. Thus, the dual role of immune...... mechanisms in MDS is challenging, and rigorous translational studies are needed to establish the value of immune manipulation as a treatment of MDS....

  3. MDS Quality Measures

    Data.gov (United States)

    U.S. Department of Health & Human Services — A list of the quality measures displayed on Nursing Home Compare, excluding Measures of Rehospitalization, Emergency Room Visit, and Community Discharge. Each row...

  4. Replacements For Ozone-Depleting Foaming Agents

    Science.gov (United States)

    Blevins, Elana; Sharpe, Jon B.

    1995-01-01

    Fluorinated ethers used in place of chlorofluorocarbons and hydrochlorofluorocarbons. Replacement necessary because CFC's and HCFC's found to contribute to depletion of ozone from upper atmosphere, and manufacture and use of them by law phased out in near future. Two fluorinated ethers do not have ozone-depletion potential and used in existing foam-producing equipment, designed to handle liquid blowing agents soluble in chemical ingredients that mixed to make foam. Any polyurethane-based foams and several cellular plastics blown with these fluorinated ethers used in processes as diverse as small batch pours, large sprays, or double-band lamination to make insulation for private homes, commercial buildings, shipping containers, and storage tanks. Fluorinated ethers proved useful as replacements for CFC refrigerants and solvents.

  5. Assessment of Preferred Depleted Uranium Disposal Forms

    Energy Technology Data Exchange (ETDEWEB)

    Croff, A.G.; Hightower, J.R.; Lee, D.W.; Michaels, G.E.; Ranek, N.L.; Trabalka, J.R.

    2000-06-01

    The Department of Energy (DOE) is in the process of converting about 700,000 metric tons (MT) of depleted uranium hexafluoride (DUF6) containing 475,000 MT of depleted uranium (DU) to a stable form more suitable for long-term storage or disposal. Potential conversion forms include the tetrafluoride (DUF4), oxide (DUO2 or DU3O8), or metal. If worthwhile beneficial uses cannot be found for the DU product form, it will be sent to an appropriate site for disposal. The DU products are considered to be low-level waste (LLW) under both DOE orders and Nuclear Regulatory Commission (NRC) regulations. The objective of this study was to assess the acceptability of the potential DU conversion products at potential LLW disposal sites to provide a basis for DOE decisions on the preferred DU product form and a path forward that will ensure reliable and efficient disposal.

  6. Screening features to improve the class prediction of acute myeloid leukemia and myelodysplastic syndrome.

    Science.gov (United States)

    Li, Kaishi; Yang, Meixue; Sablok, Gaurav; Fan, Jianping; Zhou, Fengfeng

    2013-01-10

    After more than three decades of intensive investigations, the underpinning mechanism of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) pathogenesis still remains largely uncharacterized, and their diagnosis relies heavily on the subjective factors. Recently gene expression profiling technique showed significant improvement in classifying some subtypes of AML, but the model's discriminating power of MDS from AML is still in its infancy. Feature selection plays an important role in the classification of the samples on the basis of the gene expression profiles. Our hypothesis explains that a better choice of features could improve the classification of the diseased and normal stage samples, and the potential application of feature screening to produce feature sets, with better accuracies and lowest number of embedded features. The observed results suggest that feature selection proves to be an essential and affirmative step in the biomedical data mining models based on gene expression profiles.

  7. Late effect of atomic bomb radiation on myeloid disorders: leukemia and myelodysplastic syndromes.

    Science.gov (United States)

    Tsushima, Hideki; Iwanaga, Masako; Miyazaki, Yasushi

    2012-03-01

    Leukemia was the first malignancy linked to radiation exposure in atomic bomb survivors. Clear evidence of the dose-dependent excess risk of three major types of leukemia (acute lymphocytic leukemia, acute myeloid leukemia [AML], and chronic myeloid leukemia) was found, especially in people exposed at young ages. Such leukemia risks were at their highest in the late 1950s, and declined gradually thereafter over the past 50 years. Findings from recent risk analyses, however, suggest the persistence of AML risk even after 1990, and evidence of increased risk of myelodysplastic syndromes (MDS) due to atomic bomb radiation has recently been shown. High-risk MDS and forms involving complex chromosomal aberrations were found to be much more frequent in people exposed to higher radiation doses. These lines of epidemiological evidence suggest that the risk of radiation-induced hematological malignancies has persisted for six decades since the initial exposure.

  8. Myelodysplastic Syndrome Clinically Presenting with the “Classic TTP Pentad”

    Science.gov (United States)

    Polanco Jácome, Evelyn Carolina; Guevara, Elizabeth; Mattoo, Vijay

    2017-01-01

    The clinical presentation of myelodysplastic syndrome (MDS) is not specific. Many patients can be asymptomatic and can be detected only due to an abnormal complete blood cell count (CBC) on routine exam or for other reasons while others can be symptomatic as a consequence of underlying cytopenias. Thrombotic thrombocytopenic purpura (TTP) usually is suspected under the evidence of microangiopathic hemolytic anemia (MAHA) and thrombocytopenia and because it is a life-threatening condition (medical emergency) immediate initiation of plasmapheresis could be life-saving. The following case illustrates an unusual presentation of MDS in a patient who came in to the emergency room with the classic TTP “pentad” of fever, renal involvement, MAHA, mental status changes, and thrombocytopenia. We will focus our discussion in the clinical presentation of this case. PMID:28255478

  9. Ecological and corrosion behavior of depleted uranium

    Directory of Open Access Journals (Sweden)

    Stojanović Mirjana D.

    2015-01-01

    Full Text Available Environmental pollution with radionuclides, particularly uranium and its decay products is a serious global problem. The current scientific studies estimated that the contamination originating from TENORM, caused by nuclear and non-nuclear technologies, has significantly increased natural level of radioactivity in the last thirty years. During the last decades all the more were talking about the "new pollutant" - depleted uranium (DU, which has been used in anti-tank penetrators because of its high density, penetration and pyrophoric properties. It is estimated that during the Gulf War, the war in Bosnia and Yugoslavia and during the invasion of Iraq, 1.4 million missiles with depleted uranium was fired. During the NATO aggression against the ex Yugoslavia in 1999., 112 locations in Kosovo and Metohija, 12 locations in southern Serbia and two locations in Montenegro were bombed. On this occasion, approximately 10 tons of depleted uranium were entered into the environment, mainly on land, where the degree of contamination ranged from 200 Bq / kg to 235 000 Bq/kg, which is up to 1000 times higher than the natural level. Fourteen years ago there was very little information about the behavior of ecological systems damaged by DU penetrators fired. Today, unfortunately, we are increasingly faced with the ―invisible threat" of depleted uranium, which has a strong radioactive and hemotoxic impact on human health. Present paper provides a detailed overview of the current understanding of corrosion and corrosion behavior of DU and environmental factors that control corrosion, together with indicators of environmental impact in order to highlight areas that need further attention in developing remediation programs.

  10. The ultimate disposition of depleted uranium

    Energy Technology Data Exchange (ETDEWEB)

    Lemons, T.R. [Uranium Enrichment Organization, Oak Ridge, TN (United States)

    1991-12-31

    Depleted uranium (DU) is produced as a by-product of the uranium enrichment process. Over 340,000 MTU of DU in the form of UF{sub 6} have been accumulated at the US government gaseous diffusion plants and the stockpile continues to grow. An overview of issues and objectives associated with the inventory management and the ultimate disposition of this material is presented.

  11. Effective Depletion Potential of Colloidal Spheres

    Institute of Scientific and Technical Information of China (English)

    LI Wei-Hua; MA Hong-Ru

    2004-01-01

    @@ A new semianalytical method, which is a combination of the density functional theory with Rosenfeld density functional and the Ornstein-Zernike equation, is proposed for the calculation of the effective depletion potentials between a pair of big spheres immersed in a small hard sphere fluid. The calculated results are almost identical to the integral equation method with the Percus-Yevick approximation, and are also in agreement well with the Monte Carlo simulation results.

  12. Barium depletion in hollow cathode emitters

    Energy Technology Data Exchange (ETDEWEB)

    Polk, James E., E-mail: james.e.polk@jpl.nasa.gov; Mikellides, Ioannis G.; Katz, Ira [Jet Propulsion Laboratory, California Institute of Technology, Pasadena, California 91109 (United States); Capece, Angela M. [Graduate Aerospace Laboratories, California Institute of Technology, Pasadena, California 91125 (United States)

    2016-01-14

    Dispenser hollow cathodes rely on a consumable supply of Ba released by BaO-CaO-Al{sub 2}O{sub 3} source material in the pores of a tungsten matrix to maintain a low work function surface. The examination of cathode emitters from long duration tests shows deposits of tungsten at the downstream end that appear to block the flow of Ba from the interior. In addition, a numerical model of Ba transport in the cathode plasma indicates that the Ba partial pressure in the insert may exceed the equilibrium vapor pressure of the dominant Ba-producing reaction, and it was postulated previously that this would suppress Ba loss in the upstream part of the emitter. New measurements of the Ba depletion depth from a cathode insert operated for 8200 h reveal that Ba loss is confined to a narrow region near the downstream end, confirming this hypothesis. The Ba transport model was modified to predict the depletion depth with time. A comparison of the calculated and measured depletion depths gives excellent qualitative agreement, and quantitative agreement was obtained assuming an insert temperature 70 °C lower than measured beginning-of-life values.

  13. Mitochondrial DNA depletion analysis by pseudogene ratioing.

    Science.gov (United States)

    Swerdlow, Russell H; Redpath, Gerard T; Binder, Daniel R; Davis, John N; VandenBerg, Scott R

    2006-01-30

    The mitochondrial DNA (mtDNA) depletion status of rho(0) cell lines is typically assessed by hybridization or polymerase chain reaction (PCR) experiments, in which the failure to hybridize mtDNA or amplify mtDNA using mtDNA-directed primers suggests thorough mitochondrial genome removal. Here, we report the use of an mtDNA pseudogene ratioing technique for the additional confirmation of rho0 status. Total genomic DNA from a U251 human glioma cell line treated with ethidium bromide was amplified using primers designed to anneal either mtDNA or a previously described nuclear DNA-embedded mtDNA pseudogene (mtDNApsi). The resultant PCR product was used to generate plasmid clones. Sixty-two plasmid clones were genotyped, and all arose from mtDNApsi template. These data allowed us to determine with 95% confidence that the resultant mtDNA-depleted cell line contains less than one copy of mtDNA per 10 cells. Unlike previous hybridization or PCR-based analyses of mtDNA depletion, this mtDNApsi ratioing technique does not rely on interpretation of a negative result, and may prove useful as an adjunct for the determination of rho0 status or mtDNA copy number.

  14. Decitabine versus best supportive care in older patients with refractory anemia with excess blasts in transformation (RAEBt) - results of a subgroup analysis of the randomized phase III study 06011 of the EORTC Leukemia Cooperative Group and German MDS Study Group (GMDSSG).

    Science.gov (United States)

    Becker, Heiko; Suciu, Stefan; Rüter, Björn Hans; Platzbecker, Uwe; Giagounidis, Aristoteles; Selleslag, Dominik; Labar, Boris; Germing, Ulrich; Salih, Helmut R; Muus, Petra; Pflüger, Karl-Heinz; Hagemeijer, Anne; Schaefer, Hans-Eckart; Fiaccadori, Valeria; Baron, Frédéric; Ganser, Arnold; Aul, Carlo; de Witte, Theo; Wijermans, Pierre W; Lübbert, Michael

    2015-12-01

    In the European Organisation for Research and Treatment of Cancer (EORTC)/GMDSSG phase III trial 06011, we compared decitabine (15 mg/m(2) every 8 h for 3 days) with best supportive care (BSC) in patients ≥60 years with myelodysplastic syndromes (MDS) by French-American-British (FAB) criteria. Here, we reinvestigate trial 06011 for the activity and efficacy specifically in patients with refractory anemia with excess blasts in transformation (RAEBt). Response rates in the decitabine arm (N = 40) were as follows: complete or partial remission, 15 %; hematologic improvement, 15 %; resistant disease, 30 %. RAEBt patients in the decitabine arm had longer progression-free survival (PFS; hazard ratio (HR) 0.30, 95 % confidence interval (CI) 0.18-0.51; median, 6.2 vs 2.8 months) and overall survival (OS; HR 0.68, 95 % CI 0.42-1.11; median, 8.0 vs 6.0 months) than in the BSC arm (N = 35). Censoring at allogeneic hematopoietic stem cell transplantation, the OS difference between the treatment groups increased, particularly among patients aged 60-74 years (HR 0.48, 95 % CI 0.26-0.89). After regrouping the study cohort according to World Health Organization (WHO) criteria, patients with acute myeloid leukemia (AML) (i.e., ≥20 % blasts) in the decitabine arm (N = 27) also had longer PFS than in the BSC arm (N = 23) (HR 0.46, 95 % CI 0.26-0.83; median, 6.2 vs 2.8 months). In conclusion, 3-day decitabine displays clinical activity and efficacy in MDS and/or AML with 5-30 % blood or 20-30 % marrow blasts.

  15. Using Cognitive Pretesting in Scale Development for Parkinson’s Disease: The Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Example

    Science.gov (United States)

    Tilley, Barbara C.; LaPelle, Nancy R.; Goetz, Christopher G.; Stebbins, Glenn T.

    2016-01-01

    Background Cognitive pretesting, a qualitative step in scale development, precedes field testing and assesses the difficulty of instrument completion for examiners and respondents. Cognitive pretesting assesses respondent interest, attention span, discomfort, and comprehension, and highlights problems with the logical structure of questions/response options that can affect understanding. In the past this approach was not consistently used in the development or revision of movement disorders scales. Methods We applied qualitative cognitive pretesting using testing guides in development of the Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). The guides were based on qualitative techniques, verbal probing and “think-aloud” interviewing, to identify problems with the scale from the patient and rater perspectives. English-speaking Parkinson’s disease patients and movement disorders specialists (raters) from multiple specialty clinics in the United States, Western Europe and Canada used the MDS-UPDRS and completed the testing guides. Results Two rounds of cognitive pretesting were necessary before proceeding to field testing of the revised scale to assess clinimetric properties. Scale revisions based on cognitive pretesting included changes in phrasing, simplification of some questions, and addition of a reassuring statement explaining that not all PD patients experience the symptoms described in the questions. Conclusions The strategy of incorporating cognitive pretesting into scale development and revision provides a model for other movement disorders scales. Cognitive pretesting is being used in translating the MDS-UPDRS into multiple languages to improve comprehension and acceptance and in the development of a new Unified Dyskinesia Rating Scale for Parkinson’s disease patients. PMID:24613868

  16. Using cognitive pretesting in scale development for Parkinson's disease: the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) example.

    Science.gov (United States)

    Tilley, Barbara C; LaPelle, Nancy R; Goetz, Christopher G; Stebbins, Glenn T

    2014-01-01

    Cognitive pretesting, a qualitative step in scale development, precedes field testing and assesses the difficulty of instrument completion for examiners and respondents. Cognitive pretesting assesses respondent interest, attention span, discomfort, and comprehension, and highlights problems with the logical structure of questions/response options that can affect understanding. In the past this approach was not consistently used in the development or revision of movement disorders scales. We applied qualitative cognitive pretesting using testing guides in development of the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS). The guides were based on qualitative techniques, verbal probing and "think-aloud" interviewing, to identify problems with the scale from the patient and rater perspectives. English-speaking Parkinson's disease patients and movement disorders specialists (raters) from multiple specialty clinics in the United States, Western Europe and Canada used the MDS-UPDRS and completed the testing guides. Two rounds of cognitive pretesting were necessary before proceeding to field testing of the revised scale to assess clinimetric properties. Scale revisions based on cognitive pretesting included changes in phrasing, simplification of some questions, and addition of a reassuring statement explaining that not all PD patients experience the symptoms described in the questions. The strategy of incorporating cognitive pretesting into scale development and revision provides a model for other movement disorders scales. Cognitive pretesting is being used in translating the MDS-UPDRS into multiple languages to improve comprehension and acceptance and in the development of a new Unified Dyskinesia Rating Scale for Parkinson's disease patients.

  17. Prognoses of MDS subtypes RARS, RCMD and RCMD-RS are comparable but cytogenetics separates a subgroup with inferior clinical course.

    Science.gov (United States)

    Bacher, Ulrike; Kern, Wolfgang; Alpermann, Tamara; Schnittger, Susanne; Haferlach, Claudia; Haferlach, Torsten

    2012-07-01

    In 2008, the WHO combined the former categories RCMD (refractory cytopenia with multilineage dysplasia) and RCMD-RS (ring sideroblasts ≥ 15%). We studied the clinical impact and genetic background of RARS, RCMD, and RCMD-RS in 1082 patients. Good karyotypes (IPSS) were similarly frequent in RARS, RCMD, and RCMD-RS. 2-year overall survival (OS) rates were similar in RARS, RCMD, and RCMD-RS (85.9%/89.0%/91.7%; n.s.). The 2-year OS rate was better in good than intermediate or poor karyotypes (pcytogenetic criteria for these MDS subtypes.

  18. Lithium Depletion in Fully Convective Pre-Main Sequence Stars

    CERN Document Server

    Bildsten, L; Matzner, C D; Ushomirsky, G; Bildsten, Lars; Brown, Edward F.; Matzner, Christopher D.; Ushomirsky, Greg

    1996-01-01

    We present an analytic calculation of the thermonuclear depletion of lithium in contracting, fully convective, pre-main sequence stars of mass M 0.08 M_sun) and for constraining the masses of lithium depleted stars.

  19. (JASR) Vol. 12, No. 2, 2012 DEPLETING FOREST RESOURCES OF ...

    African Journals Online (AJOL)

    HP

    undisturbed lands leading to depletion of the forest cover and increase on the sand dunes .... depletion of the ozone layer leading to a rise in global temperature. ... Nigeria has good correlation with greenhouse gas emission which can cause ...

  20. Depletions at Browns Park National Wildlife Refuge [Draft

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Estimated depletion associated with the operation of Spitzie Marsh in Browns Park National Wildlife Refuge. Attached are the methods used to estimate depletion....