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137 results on '"Doody, G. A."'

4. A System for In Vitro Generation of Mature Murine Plasma Cells Uncovers Differential Blimp-1/Prdm1 Promoter Usage

Author

Robinson, E, Care, M, Walker, K, Campbell, M, Tooze, R, and Doody, G

Abstract

Upon encounter with Ag, B cells undergo a sequential process of differentiation to become Ab-secreting plasma cells. Although the key drivers of differentiation have been identified, research has been limited by the lack of in vitro models recapitulating the full process for murine B cells. In this study, we describe methodology using BCR or TLR ligation to obtain plasma cells that are phenotypically mature, have exited cell cycle and express a gene signature concordant with long-lived plasma cells. Dependent on the initial stimuli, the transcriptomes also show variation including the enhanced expression of matrisome components after BCR stimulation, suggestive of unique functional properties for the resultant plasma cells. Moreover, using the new culture conditions we demonstrate that alternative promoter choice regulating the expression of the master transcription factor Blimp-1/Prdm1 can be observed; when the canonical B cell promoter for Prdm1 is deleted, differentiating B cells exhibit flexibility in the choice of promoter, dictated by the initiating stimulus, with preferential maintenance of expression following exposure to TLR ligation. Thus our system provides a readily tractable model for furthering our understanding of plasma cell biology.

Published
2022

11. B cell tetherin : a flow‐cytometric cell‐specific assay for response to Type‐I interferon predicts clinical features and flares in SLE

Author

El‐Sherbiny, YM, Yusof, MYM, Psarras, A, Hensor, EMA, Kabba, KZ, Dutton, K, Mohamed, AAA, Elewaut, D, McGonagle, D, Tooze, R, Doody, G, Wittmann, M, Emery, P, and Vital, EM

Subjects
BIOMARKER, DIFFERENTIATION, MONOCYTES, PATHOGENESIS, SIGNATURE, Medicine and Health Sciences, Biology and Life Sciences, PERIPHERAL-BLOOD, skin and connective tissue diseases, DISEASE-ACTIVITY, THERAPY, VALIDATION, GENE-EXPRESSION
Abstract

Objective:Type I interferon (IFN-I) responses are broadly associated with autoimmune disease including SLE. Given the cardinal role of autoantibodies in SLE, we investigated whether a B cell-specific IFN assay might correlate with SLE activity. METHODS: B cells and PBMCs were stimulated with IFN-I and IFN-II. Gene expression was scrutinized for pathway-related membrane protein expression. A flow-cytometric assay for tetherin (CD317), an IFN-induced protein ubiquitously expressed on leucocytes, was validated in vitro then clinically against SLE diagnosis, plasmablast expansion, and BILAG-2004 score in a discovery cohort (156 SLE; 30 RA; 22 healthy controls). A second longitudinal validation cohort of 80 patients was also evaluated for SLE flare prediction. RESULTS: In vitro, a close cell-specific and dose-responsive relationship between IFN-I responsive genes and cell surface tetherin in all immune subsets existed. Tetherin expression on multiple cell subsets was selectively responsive to stimulation with IFN-I compared to IFN-II and -III. In patient samples from the discovery cohort memory B-cell tetherin was best associated with diagnosis (SLE/HC: effect size=0.11, p=0.003; SLE/RA: effect size=0.17, p

Published
2020

28. Theory of mind and psychoses

Author

DOODY, G. A., GOTZ, M., JOHNSTONE, E. C., FRITH, C. D., and OWENS, D. G. CUNNINGHAM

Published
1998

30. Antipsychotic treatment resistance in first-episode psychosis: prevalence, subtypes and predictors

Author

Demjaha, Arsime, Lappin, J. M., Stahl, D., Patel, M. X., MacCabe, J. H., Howes, O. D., Heslin, M., Reininghaus, Ulrich A., Donoghue, K., Lomas, B., Charalambides, M., Onyejiaka, A., Fearon, P., Jones, P., Doody, G., Morgan, C., Dazzan, P., Murray, R. M., and Demjaha, A.

Subjects
Schizophrenia, First-Episode- Psychosis, Treatment-Response, Clozapine, Treatment-Resistant
Abstract

Background: We examined longitudinally the course and predictors of treatment resistance in a large cohort of first-episode psychosis (FEP) patients from initiation of antipsychotic treatment. We hypothesized that antipsychotic treatment resistance is: (a) present at illness onset; and (b) differentially associated with clinical and demographic factors.Method: The study sample comprised 323 FEP patients who were studied at first contact and at 10-year follow-up. We collated clinical information on severity of symptoms, antipsychotic medication and treatment adherence during the follow-up period to determine the presence, course and predictors of treatment resistance.Results: From the 23% of the patients, who were treatment resistant, 84% were treatment resistant from illness onset. Multivariable regression analysis revealed that diagnosis of schizophrenia, negative symptoms, younger age at onset, and longer duration of untreated psychosis predicted treatment resistance from illness onset.Conclusions: The striking majority of treatment-resistant patients do not respond to first-line antipsychotic treatment even at time of FEP. Clinicians must be alert to this subgroup of patients and consider clozapine treatment as early as possible during the first presentation of psychosis.

Published
2017

31. Antipsychotic treatment resistance in first-episode psychosis:prevalence, subtypes and predictors

Author

Demjaha, A, Lappin, JM, Stahl, D, Patel, MX, MacCabe, JH, Howes, OD, Heslin, M, Reininghaus, Ulrich, Donoghue, K, Lomas, B, Charalambides, M, Onyejiaka, A, Fearon, P, Jones, P, Doody, G, Morgan, C, Dazzan, P, and Murray, RM

Subjects
Treatment-Resistant, First-Episode- Psychosis, Schizophrenia, Clozapine, Treatment-Response
Abstract

BACKGROUND: We examined longitudinally the course and predictors of treatment resistance in a large cohort of first-episode psychosis (FEP) patients from initiation of antipsychotic treatment. We hypothesized that antipsychotic treatment resistance is: (a) present at illness onset; and (b) differentially associated with clinical and demographic factors.METHOD: The study sample comprised 323 FEP patients who were studied at first contact and at 10-year follow-up. We collated clinical information on severity of symptoms, antipsychotic medication and treatment adherence during the follow-up period to determine the presence, course and predictors of treatment resistance.RESULTS: From the 23% of the patients, who were treatment resistant, 84% were treatment resistant from illness onset. Multivariable regression analysis revealed that diagnosis of schizophrenia, negative symptoms, younger age at onset, and longer duration of untreated psychosis predicted treatment resistance from illness onset.CONCLUSIONS: The striking majority of treatment-resistant patients do not respond to first-line antipsychotic treatment even at time of FEP. Clinicians must be alert to this subgroup of patients and consider clozapine treatment as early as possible during the first presentation of psychosis.

Published
2017

33. Mapping the undergraduate dermatology curriculum: a useful tool towards implementation of national recommendations.

Author

Sharma, M., Scorer, M., Kent, D., Murphy, R., and Doody, G.

Subjects
CURRICULUM alignment, NATIONAL curriculum, DERMATOLOGY, CURRICULUM, MEDICAL schools, CURRICULUM evaluation
Abstract

Summary: Background: Despite the high prevalence of skin complaints in primary care and secondary care, dermatology undergraduate (UG) education remains inconsistent across medical schools. The British Association of Dermatologists (BAD) published a revised national UG curriculum in 2016 to guide UK medical schools on the minimum competencies required in dermatology. Aim: The aim of the study was to determine the alignment of the BAD UG curriculum with the dermatology curriculum of the University of Nottingham School of Medicine. Methods: A curriculum mapping study was undertaken with the development of an electronic searchable database tool to map key areas. Results: Of the 70 intended learning outcomes (ILOs) for dermatology in the medical school, 55 (79%) were mapped to the BAD curriculum, while 14 (20%) required modifications to align them with the BAD ILOs. Two BAD ILOs were unspecified in the current curriculum, and one was deemed redundant. Conclusion: Curriculum mapping is a useful tool to standardize local dermatology ILOs to national recommendations and provides transparency to stakeholders for implementation of the dermatology curriculum. [ABSTRACT FROM AUTHOR]

Published
2020
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35. Volumetric magnetic resonance imaging study of the brain in subjects with sex chromosome aneuploidies.

Author

Warwick, M M, Doody, G A, Lawrie, S M, Kestelman, J N, Best, J J, and Johnstone, E C

Subjects
BRAIN anatomy, ANALYSIS of variance, ANEUPLOIDY, COMPARATIVE studies, MAGNETIC resonance imaging, RESEARCH methodology, MEDICAL cooperation, RESEARCH, RESEARCH funding, SEX chromosomes, EVALUATION research
Abstract

Objectives: Cognitive impairment has been reported in people with sex chromosome aneuploides (SCAs) and it has been proposed that the presence of an extra sex chromosome may have an adverse effect on neurodevelopment. This study examines the hypothesis with structural MRI of the brain.Methods: Thirty two subjects with SCA (XXX (n=12), XYY (n=10), and XXY (n=10)) from a birth cohort study were matched groupwise for age, parental social class, and height with normal controls (13 female, 26 male). Brain MRI, measurements of IQ, and a structured psychiatric interview were performed.Results: The XXX females and XXY males had significantly smaller whole brain volumes than controls of the same phenotypic sex (p=0.003 and pConclusions: The main result of reduced brain volumes in XXX and XXY subjects, but not in XYY subjects, indicates that the presence of a supernumerary X chromosome has a demonstrable effect on brain development. [ABSTRACT FROM AUTHOR]

Published
1999

36. 'Pfropfschizophrenie' revisited.

Author

Doody, G. A., Johnstone, E. C., Sanderson, T. L., Owens, D. G. Cunningham, and Muir, W. J.

Subjects
SCHIZOPHRENIA, LEARNING disabilities, COGNITION disorders, DISABILITIES, PSYCHOSES, PATHOLOGICAL psychology, MENTAL illness, MENTAL health, PSYCHIATRY
Abstract

Background It is reported that people with mild learning disability have a higher point prevalence of schizophrenia than the normal population, the reasons for which are unclear. Method Thirty-nine subjects with mild learning disability and schizophrenia, 34 control subjects with schizophrenia and 28 control subjects with mild learning disability were seen. Interviews with relatives and carers were also conducted. Assessments were made of clinical variables, psychopathology, neurological ‘soft’ signs, IQ, memory and family history. Blood was taken for karyotypic analysis from comorbid subjects. Results The comorbid group had more negative symptoms, episodic memory deficits, soft neurological signs, epilepsy and receive more community supports than control subjects with schizophrenia. Comorbid subjects had a tendency to belong to multiply affected families and show high rates of chromosomal variants on routine karyotypic testing. Conclusions Future work on the generality of schizophrenia should include people with premorbid learning disability, as a discrete subtype from whom valuable genetic aetiological clues may be obtained. [ABSTRACT FROM AUTHOR]

Published
1998
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