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51. To Re-Litigate, Or Not To Re-Litigate, That Is The Question

Author

Curtis, Claire

Subjects
Administrative agencies -- Laws, regulations and rules, Workers -- Laws, regulations and rules, Res judicata -- Laws, regulations and rules -- Reports, Government regulation, Business, international
Abstract

What is res judicata? Res judicata is the doctrine which prevents a party from re-litigating an issue or a defence which has already been determined (known as cause of action [...]

Published
2014

52. Abnormalities affecting tyrosine kinase signalling in atypical myeloproliferative disorders

Author

Hidalgo-Curtis, Claire. and Hidalgo-Curtis, Claire.

Abstract

The myeloproliferative disorders (MPDs) are a group of haematopoietic stem cell diseases, characterised by proliferation of one or more cells of the myeloid lineage. Several lines of evidence have highlighted the importance of aberrant tyrosine kinase signalling in the pathogenesis of these disorders. Cloning of rare chromosomal translocations and point mutation analysis in the MPDs has identified diverse deregulated tyrosine kinase genes, notably PDGFRA, PDGFRB, FGFR1 and JAK2. However the majority of atypical MPDs still remain to be characterised and identification of patients harbouring fusions, particularly those involving the PDGF receptors is of increasing importance, as they are likely to be responsive to targeted therapy with imatinib. I am investigating MPD patients for abnormalities affecting tyrosine kinase signalling, and have used three approaches, translocation cloning, expression analysis and SNP array analysis to detect regions of loss of heterozygosity (LOH). Thus far, by translocation cloning I have identified a previously undescribed partner gene fused to PDGFRB and two new PDGFRA fusion genes. I have also designed two reverse transcriptase PCR (RT-PCR) assays and a cDNA MLPA assay to detect over-expression of specific tyrosine kinases screening approximately 200 patients. Each assay identified all patients previously diagnosed with known fusions. Additionally, two patients identified with overexpression of PDGFRB have been found to have cryptic ETV6-PDGFRB fusions and overexpression of PDGFRA in one patient lead to the discovery of a previously undescribed fusion involving a novel partner gene (KIF5B). Recent evidence has indicated that acquired isodisomy is a novel mechanism by which mutations in cancer may be reduced to homozygosity. Typically, acquired isodisomy is associated with oncogenic changes rather than tumour suppressor genes, eg. the activating JAK2 V617F mutation and 9p aUPD. I have undertaken a screen using Affymetrix 50K SN

Published
2009

59. Inactivation of Polycomb Repressive Complex 2 Components in Myeloproliferative and Myelodysplastic/Myeloproliferative Neoplasms

Author

Cross, Nicholas C.P., primary, Score, Joannah, additional, Hidalgo-Curtis, Claire, additional, Jones, Amy V, additional, Winkelmann, Nils, additional, Skinner, Alison, additional, Ward, Daniel, additional, Zoi, Katerina, additional, Ernst, Thomas, additional, Stegelmann, Frank, additional, Dohner, Konstanze, additional, and Chase, Andrew J, additional

Published
2011
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60. Prognostic Impact of EZH2 and ASXL1 Mutation in Myelofibrosis

Author

Guglielmelli, Paola, primary, Biamonte, Flavia, additional, Score, Johannah, additional, Hidalgo-Curtis, Claire, additional, Cervantes, Francisco, additional, Maffioli, Margherita, additional, Fanelli, Tiziana, additional, Ernst, Thomas, additional, Winkelman, Nils, additional, Jones, Amy V, additional, Zoi, Katerina, additional, Reiter, Andreas, additional, Duncombe, Andrew, additional, Villani, Laura, additional, Paoli, Chiara, additional, Bosi, Alberto, additional, Barosi, Giovanni, additional, Cross, Nicholas C.P., additional, and Vannucchi, Alessandro M., additional

Published
2011
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61. EZH2 mutational status predicts poor survival in myelofibrosis

Author

Guglielmelli, Paola, primary, Biamonte, Flavia, additional, Score, Joannah, additional, Hidalgo-Curtis, Claire, additional, Cervantes, Francisco, additional, Maffioli, Margherita, additional, Fanelli, Tiziana, additional, Ernst, Thomas, additional, Winkelman, Nils, additional, Jones, Amy V., additional, Zoi, Katerina, additional, Reiter, Andreas, additional, Duncombe, Andrew, additional, Villani, Laura, additional, Bosi, Alberto, additional, Barosi, Giovanni, additional, Cross, Nicholas C. P., additional, and Vannucchi, Alessandro M., additional

Published
2011
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63. Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders

Author

Ernst, Thomas, primary, Chase, Andrew J, additional, Score, Joannah, additional, Hidalgo-Curtis, Claire E, additional, Bryant, Catherine, additional, Jones, Amy V, additional, Waghorn, Katherine, additional, Zoi, Katerina, additional, Ross, Fiona M, additional, Reiter, Andreas, additional, Hochhaus, Andreas, additional, Drexler, Hans G, additional, Duncombe, Andrew, additional, Cervantes, Francisco, additional, Oscier, David, additional, Boultwood, Jacqueline, additional, Grand, Francis H, additional, and Cross, Nicholas C P, additional

Published
2010
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65. Frequent Inactivating Mutations of TET2 and CBL Are Associated with Acquired Uniparental Disomy in Atypical Chronic Myeloid Leukemia and Related Disorders.

Author

Ernst, Thomas, primary, Chase, Andrew, additional, Hidalgo-Curtis, Claire, additional, Zoi, Katerina, additional, Zoi, Christine, additional, Hochhaus, Andreas, additional, Reiter, Andreas, additional, Vainchenker, William, additional, Grand, Francis, additional, and Cross, Nicholas C.P., additional

Published
2009
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67. E-Disclosure: The Cost Of Noncompliance Uncovered

Author

Curtis, Claire

Subjects
Disclosure of information -- Methods -- Analysis, Electronic records -- Safety and security measures -- Analysis, Business, international
Abstract

Electronic Disclosure ('e-disclosure') is the process by which the parties exchange relevant electronically stored documents (such as emails, text files and voicemails) during litigation. With the expanding integration of technology [...]

Published
2013

68. Tell The Truth Or Face The Consequences: False Statements Of Truth

Author

Curtis, Claire

Subjects
Business, international
Abstract

Statements of truth are a common feature in a range of legal documents including statements of case, disclosure reports, witness statements and expert reports. Signing a statement of truth to [...]

Published
2013

69. Frequent CBL Mutations Associated with 11q Acquired Uniparental Disomy in Myeloproliferative Neoplasms

Author

Grand, Francis, primary, Hidalgo-Curtis, Claire, primary, Ernst, Thomas, primary, Zoi, Katerina, primary, Zoi, Christine, primary, McGuire, Carolann, primary, Kreil, Sebastian, primary, Metzgeroth, Georgia, primary, Oscier, David, primary, Hall, Andrew, primary, Brandts, Christian, primary, Serve, Hubert, primary, Reiter, Andreas, primary, Chase, Andrew, primary, and Cross, Nicholas C.P., primary

Published
2008
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72. Durable responses to imatinib in patients with PDGFRB fusion gene–positive and BCR-ABL–negative chronic myeloproliferative disorders

Author

David, Marianna, primary, Cross, Nicholas C. P., additional, Burgstaller, Sonja, additional, Chase, Andrew, additional, Curtis, Claire, additional, Dang, Raymond, additional, Gardembas, Martine, additional, Goldman, John M., additional, Grand, Francis, additional, Hughes, George, additional, Huguet, Francoise, additional, Lavender, Louise, additional, McArthur, Grant A., additional, Mahon, Francois X., additional, Massimini, Giorgio, additional, Melo, Junia, additional, Rousselot, Philippe, additional, Russell-Jones, Robin J., additional, Seymour, John F., additional, Smith, Graeme, additional, Stark, Alastair, additional, Waghorn, Katherine, additional, Nikolova, Zariana, additional, and Apperley, Jane F., additional

Published
2006
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73. Transient response to imatinib in a chronic eosinophilic leukemia associated with ins(9;4)(q33;q12q25) and a CDK5RAP2‐PDGFRA fusion gene

Author

Walz, Christoph, primary, Curtis, Claire, additional, Schnittger, Susanne, additional, Schultheis, Beate, additional, Metzgeroth, Georgia, additional, Schoch, Claudia, additional, Lengfelder, Eva, additional, Erben, Philipp, additional, Müller, Martin C., additional, Haferlach, Torsten, additional, Hochhaus, Andreas, additional, Hehlmann, Rüdiger, additional, Cross, Nicholas C. P., additional, and Reiter, Andreas, additional

Published
2006
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74. Minimal molecular response in polycythemia vera patients treated with imatinib or interferon alpha

Author

Jones, Amy V., primary, Silver, Richard T., additional, Waghorn, Katherine, additional, Curtis, Claire, additional, Kreil, Sebastian, additional, Zoi, Katerina, additional, Hochhaus, Andreas, additional, Oscier, David, additional, Metzgeroth, Georgia, additional, Lengfelder, Eva, additional, Reiter, Andreas, additional, Chase, Andrew J., additional, and Cross, Nicholas C. P., additional

Published
2006
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77. Transient Response to Imatinib in an Atypical Chronic Myeloproliferative Disease Associated with ins(9;4)(q34;q21q31) and a CDK5RAP2-PDGFRA Fusion Gene.

Author

Walz, Christoph, primary, Schultheis, Beate, primary, Metzgeroth, Georgia, primary, Schoch, Claudia, primary, Curtis, Claire, primary, Lengfelder, Eva, primary, Haferlach, Torsten, primary, Berger, Ute, primary, Hochhaus, Andreas, primary, Hehlmann, Rüdiger, primary, Cross, Nicholas C.P., primary, and Reiter, Andreas, primary

Published
2005
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79. A Qualitative Study of Binge Eating and Obesity From an Addiction Perspective.

Author

Curtis, Claire and Davis, Caroline

Subjects
*BULIMIA diagnosis, *OBESITY & psychology, *ANTHROPOMETRY, *BULIMIA, *COMPARATIVE studies, *COMPULSIVE eating, *FOOD habits, *INTERVIEWING, *RESEARCH methodology, *CLASSIFICATION of mental disorders, *WOMEN'S health, *QUALITATIVE research, *STATISTICAL power analysis, *THEMATIC analysis, *BODY mass index, *DESCRIPTIVE statistics, *DIAGNOSIS
Abstract

The purpose of this study was to explore how obese women with and without binge eating disorder (BED) experience overeating in relation to theDSM-5symptoms of addiction. Findings from this study demonstrate that food addiction can occur in obese individuals with and without BED. It is important that health care professionals identify individuals who may require a specific treatment approach that incorporates techniques used in the treatment of addictions. [ABSTRACT FROM AUTHOR]

Published
2014
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82. An evaluation in UK schools of a classroom-based physical activity programme - TAKE 10! ®: A qualitative analysis of the teachers' perspective.

Author

Gately, Paul, Curtis, Claire, and Hardaker, Rachel

Subjects
CHILDREN, ELEMENTARY education, ELEMENTARY schools, INTERVIEWING, RESEARCH methodology, MEDICAL cooperation, RESEARCH, RESEARCH funding, TEACHERS, QUALITATIVE research, THEMATIC analysis, HUMAN services programs, PHYSICAL activity, EVALUATION of human services programs
Abstract

The article discusses primary school teachers in Great Britain's attitudes towards implementing the TAKE 10! physical activity programme into their curriculum. Topics include obstacles to implementing the TAKE 10! programme, the benefits of the physical activity programme, and positive improvements to students and the classroom environments from the programme. Details related to a study of eight Yorkshire, England teachers' views of the TAKE 10! programme is provided.

Published
2013

83. Frequent CBLmutations associated with 11q acquired uniparental disomy in myeloproliferative neoplasms

Author

Grand, Francis H., Hidalgo-Curtis, Claire E., Ernst, Thomas, Zoi, Katerina, Zoi, Christine, McGuire, Carolann, Kreil, Sebastian, Jones, Amy, Score, Joannah, Metzgeroth, Georgia, Oscier, David, Hall, Andrew, Brandts, Christian, Serve, Hubert, Reiter, Andreas, Chase, Andrew J., and Cross, Nicholas C.P.

Abstract

Recent evidence has demonstrated that acquired uniparental disomy (aUPD) is a novel mechanism by which pathogenetic mutations in cancer may be reduced to homozygosity. To help identify novel mutations in myeloproliferative neoplasms (MPNs), we performed a genome-wide single nucleotide polymorphism (SNP) screen to identify aUPD in 58 patients with atypical chronic myeloid leukemia (aCML; n = 30), JAK2mutation–negative myelofibrosis (MF; n = 18), or JAK2mutation–negative polycythemia vera (PV; n = 10). Stretches of homozygous, copy neutral SNP calls greater than 20Mb were seen in 10 (33%) aCML and 1 (6%) MF, but were absent in PV. In total, 7 different chromosomes were involved with 7q and 11q each affected in 10% of aCML cases. CBLmutations were identified in all 3 cases with 11q aUPD and analysis of 574 additional MPNs revealed a total of 27 CBLvariants in 26 patients with aCML, myelofibrosis or chronic myelomonocytic leukemia. Most variants were missense substitutions in the RING or linker domains that abrogated CBL ubiquitin ligase activity and conferred a proliferative advantage to 32D cells overexpressing FLT3. We conclude that acquired, transforming CBLmutations are a novel and widespread pathogenetic abnormality in morphologically related, clinically aggressive MPNs.

Published
2009
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84. Durable responses to imatinib in patients with PDGFRBfusion gene–positive and BCR-ABL–negative chronic myeloproliferative disorders

Author

David, Marianna, Cross, Nicholas C.P., Burgstaller, Sonja, Chase, Andrew, Curtis, Claire, Dang, Raymond, Gardembas, Martine, Goldman, John M., Grand, Francis, Hughes, George, Huguet, Francoise, Lavender, Louise, McArthur, Grant A., Mahon, Francois X., Massimini, Giorgio, Melo, Junia, Rousselot, Philippe, Russell-Jones, Robin J., Seymour, John F., Smith, Graeme, Stark, Alastair, Waghorn, Katherine, Nikolova, Zariana, and Apperley, Jane F.

Abstract

Fusion genes derived from the platelet-derived growth factor receptor beta (PDGFRB) or alpha (PDGFRA) play an important role in the pathogenesis of BCR-ABL–negative chronic myeloproliferative disorders (CMPDs). These fusion genes encode constitutively activated receptor tyrosine kinases that can be inhibited by imatinib. Twelve patients with BCR-ABL–negative CMPDs and reciprocal translocations involving PDGFRB received imatinib for a median of 47 months (range, 0.1-60 months). Eleven had prompt responses with normalization of peripheral-blood cell counts and disappearance of eosinophilia; 10 had complete resolution of cytogenetic abnormalities and decrease or disappearance of fusion transcripts as measured by reverse transcriptase–polymerase chain reaction (RT-PCR). Updates were sought from 8 further patients previously described in the literature; prompt responses were described in 7 and persist in 6. Our data show that durable hematologic and cytogenetic responses are achieved with imatinib in patients with PDGFRBfusion–positive, BCR-ABL–negative CMPDs.

Published
2007
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85. Widespread occurrence of the JAK2 V617F mutation in chronic myeloproliferative disorders

Author

Jones, Amy V., Kreil, Sebastian, Zoi, Katerina, Waghorn, Katherine, Curtis, Claire, Zhang, Lingyan, Score, Joannah, Seear, Rachel, Chase, Andrew J., Grand, Francis H., White, Helen, Zoi, Christine, Loukopoulos, Dimitris, Terpos, Evangelos, Vervessou, Elisavet-Christine, Schultheis, Beate, Emig, Michael, Ernst, Thomas, Lengfelder, Eva, Hehlmann, Rüdiger, Hochhaus, Andreas, Oscier, David, Silver, Richard T., Reiter, Andreas, and Cross, Nicholas C. P.

Abstract

The analysis of rare chromosomal translocations in myeloproliferative disorders has highlighted the importance of aberrant tyrosine kinase signaling in the pathogenesis of these diseases. Here we have investigated samples from 679 patients and controls for the nonreceptor tyrosine kinase JAK2 V617F mutation. Of the 480 myeloproliferative disorder (MPD) samples, the proportion of positive cases per disease subtype was 30 (20%) of 152 for atypical or unclassified MPD, 2 of 134 (2%) for idiopathic hypereosinophilic syndrome, 58 of 72 (81%) for polycythemia vera, 24 of 59 (41%) essential thrombocythemia (ET), and 15 of 35 (43%) for idiopathic myelofibrosis. V617F was not identified in patients with systemic mastocytosis (n = 28), chronic or acute myeloid leukemia (n = 35), secondary erythrocytosis (n = 4), or healthy controls (n = 160). Homozygosity for V617F was seen in 43% of mutant samples and was closely correlated with chromosome 9p uniparental disomy. Homozygosity was significantly less common in ET compared with other MPD subtypes. In 53 cases analyzed, the median level of PRV1 expression was significantly higher in V617F-positive cases compared with cases without the mutation. We conclude that V617F is widespread in MPDs. Detection of this acquired mutation is likely to have a major impact on the way patients with MPD are diagnosed, as well as serving as an obvious target for signal transduction therapy. (Blood. 2005;106:2162-2168)

Published
2005
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86. Widespread occurrence of the JAK2V617F mutation in chronic myeloproliferative disorders

Author

Jones, Amy V., Kreil, Sebastian, Zoi, Katerina, Waghorn, Katherine, Curtis, Claire, Zhang, Lingyan, Score, Joannah, Seear, Rachel, Chase, Andrew J., Grand, Francis H., White, Helen, Zoi, Christine, Loukopoulos, Dimitris, Terpos, Evangelos, Vervessou, Elisavet-Christine, Schultheis, Beate, Emig, Michael, Ernst, Thomas, Lengfelder, Eva, Hehlmann, Rüdiger, Hochhaus, Andreas, Oscier, David, Silver, Richard T., Reiter, Andreas, and Cross, Nicholas C.P.

Abstract

The analysis of rare chromosomal translocations in myeloproliferative disorders has highlighted the importance of aberrant tyrosine kinase signaling in the pathogenesis of these diseases. Here we have investigated samples from 679 patients and controls for the nonreceptor tyrosine kinase JAK2V617F mutation. Of the 480 myeloproliferative disorder (MPD) samples, the proportion of positive cases per disease subtype was 30 (20%) of 152 for atypical or unclassified MPD, 2 of 134 (2%) for idiopathic hypereosinophilic syndrome, 58 of 72 (81%) for polycythemia vera, 24 of 59 (41%) essential thrombocythemia (ET), and 15 of 35 (43%) for idiopathic myelofibrosis. V617F was not identified in patients with systemic mastocytosis (n = 28), chronic or acute myeloid leukemia (n = 35), secondary erythrocytosis (n = 4), or healthy controls (n = 160). Homozygosity for V617F was seen in 43% of mutant samples and was closely correlated with chromosome 9p uniparental disomy. Homozygosity was significantly less common in ET compared with other MPD subtypes. In 53 cases analyzed, the median level of PRV1expression was significantly higher in V617F-positive cases compared with cases without the mutation. We conclude that V617F is widespread in MPDs. Detection of this acquired mutation is likely to have a major impact on the way patients with MPD are diagnosed, as well as serving as an obvious target for signal transduction therapy. (Blood. 2005;106:2162-2168)

Published
2005
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88. Transient Response to Imatinib in an Atypical Chronic Myeloproliferative Disease Associated with ins(9;4)(q34;q21q31) and a CDK5RAP2-PDGFRAFusion Gene.

Author

Walz, Christoph, Schultheis, Beate, Metzgeroth, Georgia, Schoch, Claudia, Curtis, Claire, Lengfelder, Eva, Haferlach, Torsten, Berger, Ute, Hochhaus, Andreas, Hehlmann, Rüdiger, Cross, Nicholas C.P., and Reiter, Andreas

Abstract

Chronic myeloproliferative disorders (CMPD) associated with rearrangements of the ‘platelet-derived growth factor receptor A' (PDGFRA) at chromosome 4q12 are excellent candidates for targeted therapy with imatinib. To date, two fusion genes involving PDGFRAhave been described: FIP1L1-PDGFRAand BCR-PDGFRA. Here we report a female patient who presented in advanced phase of an atypical myeloproliferative disease. Routine cytogenetic analysis revealed an ins(9;4)(q34;q21q31). Although no break was visible at 4q12, FISH analysis with flanking BAC probes indicated that PDGFRAwas disrupted. To identify the partner gene we employed 5′-RACE PCR, exploiting the fact that all known PDGFRAfusions involve exon 12 of this gene. The resulting PCR-products consisted of 5′-sequences derived from CDK5RAP2(CDK5 regulatory subunit associated protein 2) located on 9q33 and 3′-sequences derived from PDGFRA. CDK5RAP2encodes a protein that is believed to be involved in centrosomal regulation. FISH analysis confirmed the co-localization of 5′ CDK5RAP2and 3′ PDGFRAsequences. RT-PCR confirmed the in-frame mRNA fusion between exon 13 of CDK5RAP2, a 40-bp insert which was partially derived from PDGFRAintron 11 and a truncated PDGFRAexon 12. No reciprocal fusion transcript could be amplified by RT-PCR. The predicted CDK5RAP2-PDGFRA protein consists of 1003 amino acids and retains both tyrosine kinase domains of PDGFRA and several potential dimerisation domains of CDK5RAP2 suggesting a mechanism of tyrosine kinase activation similar to BCR-ABL. Treatment with 400 mg imatinib was initiated and the patient achieved a complete cytogenetic and molecular remission. However, hematological response was only partial with residual blasts repeatedly detectable in the blood and marrow. The patient rapidly developed acute leukemia while still remaining in complete cytogenetic and molecular remission suggesting the outgrowth of a second imatinib-resistant leukemic clone. These findings and the fact that the ins(9;4) was only seen in 24% of metaphases at diagnosis suggests that CDK5RAP2-PDGFRAmay have been a secondary abnormality. In summary, we have identified a third fusion gene involving PDGFRA,underlining the fundamental role of activated tyrosine kinases in CMPD's and their possible response to targeted therapy with imatinib.

Published
2005
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89. Transcription factor mutations in myelodysplastic/myeloproliferative neoplasms.

Author

Ernst T, Chase A, Zoi K, Waghorn K, Hidalgo-Curtis C, Score J, Jones A, Grand F, Reiter A, Hochhaus A, and Cross NC

Subjects
CCAAT-Enhancer-Binding Proteins genetics, Comparative Genomic Hybridization, DNA Mutational Analysis, Gene Dosage, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Myelopoiesis genetics, Nuclear Proteins genetics, Nucleophosmin, Prognosis, WT1 Proteins genetics, Mutation, Myelodysplastic Syndromes genetics, Myeloproliferative Disorders genetics, Transcription Factors genetics
Abstract

Background: Aberrant activation of tyrosine kinases, caused by either mutation or gene fusion, is of major importance for the development of many hematologic malignancies, particularly myeloproliferative neoplasms. We hypothesized that hitherto unrecognized, cytogenetically cryptic tyrosine kinase fusions may be common in non-classical or atypical myeloproliferative neoplasms and related myelodysplastic/myeloproliferative neoplasms., Design and Methods: To detect genomic copy number changes associated with such fusions, we performed a systematic search in 68 patients using custom designed, targeted, high-resolution array comparative genomic hybridization. Arrays contained 44,000 oligonucleotide probes that targeted 500 genes including all 90 tyrosine kinases plus downstream tyrosine kinase signaling components, other translocation targets, transcription factors, and other factors known to be important for myelopoiesis., Results: No abnormalities involving tyrosine kinases were detected; however, nine cytogenetically cryptic copy number imbalances were detected in seven patients, including hemizygous deletions of RUNX1 or CEBPA in two cases with atypical chronic myeloid leukemia. Mutation analysis of the remaining alleles revealed non-mutated RUNX1 and a frameshift insertion within CEBPA. A further mutation screen of 187 patients with myelodysplastic/myeloproliferative neoplasms identified RUNX1 mutations in 27 (14%) and CEBPA mutations in seven (4%) patients. Analysis of other transcription factors known to be frequently mutated in acute myeloid leukemia revealed NPM1 mutations in six (3%) and WT1 mutations in two (1%) patients with myelodysplastic/myeloproliferative neoplasms. Univariate analysis indicated that patients with mutations had a shorter overall survival (28 versus 44 months, P=0.019) compared with patients without mutations, with the prognosis for cases with CEBPA, NPM1 or WT1 mutations being particularly poor., Conclusions: We conclude that mutations of transcription and other nuclear factors are frequent in myelodysplastic/myeloproliferative neoplasms and are generally mutually exclusive. CEBPA, NPM1 or WT1 mutations may be associated with a poor prognosis, an observation that will need to be confirmed by detailed prospective studies.

Published
2010
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90. Education level moderates learning on two versions of the Iowa Gambling Task.

Author

Davis C, Fox J, Patte K, Curtis C, Strimas R, Reid C, and McCool C

Subjects
Adult, Educational Status, Female, Humans, Male, Middle Aged, Models, Psychological, Decision Making physiology, Gambling psychology, Learning physiology, Neuropsychological Tests
Abstract

The Iowa Gambling Task (IGT) is the major plank of behavioral support for the Somatic Marker Hypothesis--a prominent theory of emotionally-based decision making. Despite its widespread use, some have questioned the ecological and discriminative validity of the IGT because a substantial proportion of neurologically-normal adults display a response pattern indistinguishable from those with ventromedial prefrontal cortical brain lesions. In a large sample of healthy adults, we examined the statistical influence of several demographic variables on two versions of the IGT, with the specific prediction that educational attainment would moderate learning across trials. Results confirmed a highly significant effect of education. On the commonly used original version of the IGT, performance tended to improve more rapidly, and reach a higher eventual positive score, as the level of education increased. Age and gender were nonsignificant effects in the model, and Caucasians had slightly better IGT performance than their non-Caucasian counterparts. Conclusions are that education level, among neurologically-normal adults, should be treated as a stratification or matching variable in case-control research using this task.

Published
2008
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91. Durable responses to imatinib in patients with PDGFRB fusion gene-positive and BCR-ABL-negative chronic myeloproliferative disorders.

Author

David M, Cross NC, Burgstaller S, Chase A, Curtis C, Dang R, Gardembas M, Goldman JM, Grand F, Hughes G, Huguet F, Lavender L, McArthur GA, Mahon FX, Massimini G, Melo J, Rousselot P, Russell-Jones RJ, Seymour JF, Smith G, Stark A, Waghorn K, Nikolova Z, and Apperley JF

Subjects
Adult, Aged, Aged, 80 and over, Benzamides, Biomarkers, Tumor blood, Child, Child, Preschool, Drug Evaluation, Eosinophilia etiology, Female, Follow-Up Studies, Humans, Imatinib Mesylate, Infant, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative blood, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative drug therapy, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative genetics, Male, Middle Aged, Myeloproliferative Disorders blood, Myeloproliferative Disorders genetics, Oncogene Proteins, Fusion genetics, RNA, Messenger blood, RNA, Neoplasm blood, Receptor, Platelet-Derived Growth Factor beta genetics, Retrospective Studies, Reverse Transcriptase Polymerase Chain Reaction, Translocation, Genetic, Treatment Outcome, Antineoplastic Agents therapeutic use, Fusion Proteins, bcr-abl blood, Myeloproliferative Disorders drug therapy, Oncogene Proteins, Fusion blood, Piperazines therapeutic use, Protein Kinase Inhibitors therapeutic use, Pyrimidines therapeutic use, Receptor, Platelet-Derived Growth Factor beta blood
Abstract

Fusion genes derived from the platelet-derived growth factor receptor beta (PDGFRB) or alpha (PDGFRA) play an important role in the pathogenesis of BCR-ABL-negative chronic myeloproliferative disorders (CMPDs). These fusion genes encode constitutively activated receptor tyrosine kinases that can be inhibited by imatinib. Twelve patients with BCR-ABL-negative CMPDs and reciprocal translocations involving PDGFRB received imatinib for a median of 47 months (range, 0.1-60 months). Eleven had prompt responses with normalization of peripheral-blood cell counts and disappearance of eosinophilia; 10 had complete resolution of cytogenetic abnormalities and decrease or disappearance of fusion transcripts as measured by reverse transcriptase-polymerase chain reaction (RT-PCR). Updates were sought from 8 further patients previously described in the literature; prompt responses were described in 7 and persist in 6. Our data show that durable hematologic and cytogenetic responses are achieved with imatinib in patients with PDGFRB fusion-positive, BCR-ABL-negative CMPDs.

Published
2007
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