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Chan-Il Choi, Ki Hyun Yoo, Syed Mohammed Qasim Hussaini, Byeong Tak Jeon, John Welby, Haiyun Gan, Isobel Scarisbrick, Zhiguo Zhang, Darren J Baker, Jan M van Deursen, Moses Rodriguez, Mi-Hyeon Jang
Myelination, the process by which oligodendrocytes form the myelin sheath around axons, is key to axonal signal transduction and related motor function in the central nervous system (CNS). Aging is characterized by degenerative changes in the myelin sheath, although the molecular underpinnings of normal and aberrant myelination remain incompletely understood. Here we report that axon myelination and related motor function are dependent on BubR1, a mitotic checkpoint protein that has been linked to progeroid phenotypes when expressed at low levels and healthy lifespan when overabundant...
September 12, 2016: Aging
Hyesook Yoon, Isobel A Scarisbrick
Kallikrein-related peptidase 6 (Klk6) is elevated in the serum of multiple sclerosis patients and is hypothesized to participate in inflammatory and neuropathogenic aspects of the disease. To test this hypothesis, we investigated the impact of systemic administration of recombinant Klk6 on the development and progression of MOG35-55-induced experimental autoimmune encephalomyelitis (EAE). First, we determined that Klk6 expression is elevated in the spinal cord of mice with EAE at the peak of clinical disease and in immune cells upon priming with the disease initiating peptide in vitro...
August 17, 2016: Biological Chemistry
J J Scarisbrick
No abstract text is available yet for this article.
July 2016: British Journal of Dermatology
Julia J Scarisbrick
PURPOSE OF REVIEW: Currently, there are no curative therapies for cutaneous T-cell lymphoma (CTCL), and consecutive treatments tend to be given until loss of response. There is an urgent need for new and improved therapies in CTCL to treat symptoms such as pruritus and painful skin lesions and prolong survival. This article reviews new drugs available for CTCL. RECENT FINDINGS: CTCL encompasses a group of T-cell neoplasms presenting in the skin without systemic involvement...
September 2016: Current Opinion in Oncology
Maja Radulovic, Hyesook Yoon, Jianmin Wu, Karim Mustafa, Isobel A Scarisbrick
The deregulation of serine protease activity is a common feature of neurological injury, but little is known regarding their mechanisms of action or whether they can be targeted to facilitate repair. In this study we demonstrate that the thrombin receptor (Protease Activated Receptor 1, (PAR1)) serves as a critical translator of the spinal cord injury (SCI) proteolytic microenvironment into a cascade of pro-inflammatory events that contribute to astrogliosis and functional decline. PAR1 knockout mice displayed improved locomotor recovery after SCI and reduced signatures of inflammation and astrogliosis, including expression of glial fibrillary acidic protein (GFAP), vimentin, and STAT3 signaling...
September 2016: Neurobiology of Disease
Alexa Rose Shipman, Julia Scarisbrick
The article discusses imiquimod treatment for refractory early stage mycosis fungoides, with a review of the literature and three case studies.
January 2016: Indian Journal of Dermatology
Erin Logue, David M Scarisbrick, Nicholas S Thaler, James J Mahoney, Cady K Block, Russell Adams, James Scott
OBJECTIVE: The current study sought to validate the Cognitive Proficiency Index (CPI) against similar, well-established measures of attention and processing speed. Additionally, the sensitivity of the CPI and Attention Index of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and their ability to differentiate among clinical groups were compared. METHOD: The first objective was accomplished by calculating correlation coefficients between the CPI and similar attention and processing speed measures...
2015: Clinical Neuropsychologist
Julia J Scarisbrick, H Miles Prince, Maarten H Vermeer, Pietro Quaglino, Steven Horwitz, Pierluigi Porcu, Rudolf Stadler, Gary S Wood, Marie Beylot-Barry, Anne Pham-Ledard, Francine Foss, Michael Girardi, Martine Bagot, Laurence Michel, Maxime Battistella, Joan Guitart, Timothy M Kuzel, Maria Estela Martinez-Escala, Teresa Estrach, Evangelia Papadavid, Christina Antoniou, Dimitis Rigopoulos, Vassilki Nikolaou, Makoto Sugaya, Tomomitsu Miyagaki, Robert Gniadecki, José Antonio Sanches, Jade Cury-Martins, Denis Miyashiro, Octavio Servitje, Cristina Muniesa, Emilio Berti, Francesco Onida, Laura Corti, Emilia Hodak, Iris Amitay-Laish, Pablo L Ortiz-Romero, Jose L Rodríguez-Peralto, Robert Knobler, Stefanie Porkert, Wolfgang Bauer, Nicola Pimpinelli, Vieri Grandi, Richard Cowan, Alain Rook, Ellen Kim, Alessandro Pileri, Annalisa Patrizi, Ramon M Pujol, Henry Wong, Kelly Tyler, Rene Stranzenbach, Christiane Querfeld, Paolo Fava, Milena Maule, Rein Willemze, Felicity Evison, Stephen Morris, Robert Twigger, Rakhshandra Talpur, Jinah Kim, Grant Ognibene, Shufeng Li, Mahkam Tavallaee, Richard T Hoppe, Madeleine Duvic, Sean J Whittaker, Youn H Kim
PURPOSE: Advanced-stage mycosis fungoides (MF; stage IIB to IV) and Sézary syndrome (SS) are aggressive lymphomas with a median survival of 1 to 5 years. Clinical management is stage based; however, there is wide range of outcome within stages. Published prognostic studies in MF/SS have been single-center trials. Because of the rarity of MF/SS, only a large collaboration would power a study to identify independent prognostic markers. PATIENTS AND METHODS: Literature review identified the following 10 candidate markers: stage, age, sex, cutaneous histologic features of folliculotropism, CD30 positivity, proliferation index, large-cell transformation, WBC/lymphocyte count, serum lactate dehydrogenase, and identical T-cell clone in blood and skin...
November 10, 2015: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Maja Radulovic, Hyesook Yoon, Jianmin Wu, Karim Mustafa, Michael G Fehlings, Isobel A Scarisbrick
Inflammatory-astrogliosis exacerbates damage in the injured spinal cord and limits repair. Here we identify Protease Activated Receptor 2 (PAR2) as an essential regulator of these events with mice lacking the PAR2 gene showing greater improvements in motor coordination and strength after compression-spinal cord injury (SCI) compared to wild type littermates. Molecular profiling of the injury epicenter, and spinal segments above and below, demonstrated that mice lacking PAR2 had significantly attenuated elevations in key hallmarks of astrogliosis (glial fibrillary acidic protein (GFAP), vimentin and neurocan) and in expression of pro-inflammatory cytokines (interleukin-6 (IL-6), tumor necrosis factor (TNF) and interleukin-1 beta (IL-1β))...
November 2015: Neurobiology of Disease
Kristen L Drucker, Caterina Gianinni, Paul A Decker, Eleftherios P Diamandis, Isobel A Scarisbrick
BACKGROUND: Kallikreins have clinical value as prognostic markers in a subset of malignancies examined to date, including kallikrein 3 (prostate specific antigen) in prostate cancer. We previously demonstrated that kallikrein 6 is expressed at higher levels in grade IV compared to grade III astrocytoma and is associated with reduced survival of GBM patients. METHODS: In this study we determined KLK1, KLK6, KLK7, KLK8, KLK9 and KLK10 protein expression in two independent tissue microarrays containing 60 grade IV and 8 grade III astrocytoma samples...
2015: BMC Cancer
Manisha R Panchal, Julia J Scarisbrick
Cutaneous T-cell lymphoma (CTCL) is an umbrella term that encompasses a group of neoplasms that have atypical T-lymphocytes in the skin. Mycosis fungoides (MF) is the most common type of CTCL and Sézary syndrome (SS) is the leukemic form. Treatment for CTCL is dependent on the stage of disease and response to previous therapy. Therapy is divided into skin-directed treatment, which tends to be first line for early-stage disease, and systemic therapy, which is reserved for refractory CTCL. Bexarotene is a rexinoid and was licensed in Europe in 2002 for use in patients with advanced disease that have been refractory to a previous systemic treatment...
2015: OncoTargets and Therapy
Hyesook Yoon, Maja Radulovic, Kristen L Drucker, Jianmin Wu, Isobel A Scarisbrick
Hemorrhagic white matter injuries in the perinatal period are a growing cause of cerebral palsy yet no neuroprotective strategies exist to prevent the devastating motor and cognitive deficits that ensue. We demonstrate that the thrombin receptor (protease-activated receptor 1, PAR1) exhibits peak expression levels in the spinal cord at term and is a critical regulator of the myelination continuum from initiation to the final levels achieved. Specifically, PAR1 gene deletion resulted in earlier onset of spinal cord myelination, including substantially more Olig2-positive oligodendrocytes, more myelinated axons, and higher proteolipid protein (PLP) levels at birth...
May 2015: Glia
Cady K Block, Erin Logue, Nicholas S Thaler, David M Scarisbrick, James J Mahoney, James Scott, Kevin Duff
Poorer neuropsychological function is associated with increased medical burden (MB) and the use of more anticholinergic medications. However, the interaction between MB and anticholinergic cognitive burden (AB) on neuropsychological performance is unknown. In a sample of 290 elderly primary care patients, those with a greater level of AB demonstrated poorer Total Index performance on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Further, an interaction effect was noted such that there was a greater anticholinergic effect on RBANS Total, Attention, and Delayed Memory Index scores for participants with fewer MB...
March 2015: Archives of Clinical Neuropsychology: the Official Journal of the National Academy of Neuropsychologists
J J Scarisbrick, F L Dignan, S Tulpule, E D Gupta, S Kolade, B Shaw, F Evison, G Shah, E Tholouli, G Mufti, A Pagliuca, R Malladi, K Raj
DLIs are frequently used following haematopoietic SCT (HSCT) in patients with risk of relapse but data on GVHD following DLI are scarce. We report on 68 patients who received DLI following HSCT. Most patients developed GVHD following DLI (71%), which was acute in 22 patients (32%) almost half of whom had grade III-IV acute GVHD (aGVHD). Thirty patients (44%) developed cGVHD which followed aGVHD in four patients and was graded severe in nine patients. Corticosteroids were the most common first-line therapy for both acute and chronic GVHD...
January 2015: Bone Marrow Transplantation
Michael Panos, George P Christophi, Moses Rodriguez, Isobel A Scarisbrick
Recent studies provide a functional link between kallikrein 6 (Klk6) and the development and progression of disease in patients with multiple sclerosis (MS) and in its murine models. To evaluate the involvement of additional kallikrein family members, we compared Klk6 expression with four other kallikreins (Klk1, Klk7, Klk8, and Klk10) in the brain and spinal cord of mice infected with Theiler's murine encephalomyelitis virus, an experimental model of progressive MS. The robust upregulation of Klk6 and Klk8 in the brain during the acute phase of viral encephalitis and in the spinal cord during disease development and progression points to their participation in inflammation, demyelination, and progressive axon degeneration...
September 2014: Biological Chemistry
Daniel J Heyanka, Charles J Golden, Robert B McCue, David M Scarisbrick, John F Linck, Nancy I Zlatkin
The study of olfaction in neurodegeneration has primarily focused on Alzheimer's disease. Research of olfaction in frontotemporal dementia (FTD) has generally not been empirically studied. The current study compared olfaction in FTD to major depressive disorder (MDD) using the Alberta Smell Test (AST). Independent-samples t test results suggested olfaction in FTD was impaired when compared with participants diagnosed with MDD. The AST Total score (out of 20 trials) significantly predicted the diagnostic group and accounted for 40% of the variance in diagnostic group status with an odds ratio of 20...
2014: Applied Neuropsychology. Adult
R Dummer, M Duvic, J Scarisbrick, E A Olsen, S Rozati, N Eggmann, S M Goldinger, K Hutchinson, L Geskin, T M Illidge, E Giuliano, J Elder, Y H Kim
BACKGROUND: Forodesine is a potent inhibitor of purine nucleoside phosphorylase (PNP) that leads to intracellular accumulation of deoxyguanosine triphosphate (dGTP) in T and B cells, resulting in apoptosis. Forodesine has demonstrated impressive antitumor activity in early phase clinical trials in cutaneous T-cell lymphoma (CTCL). PATIENTS AND METHODS: In this phase II study, patients with CTCL who had already failed three or more systemic therapies were recruited...
September 2014: Annals of Oncology: Official Journal of the European Society for Medical Oncology
E Das-Gupta, F Dignan, B Shaw, K Raj, R Malladi, A Gennery, D Bonney, P Taylor, J Scarisbrick
Extracorporeal photopheresis (ECP) has been used for over 20 years to treat acute GVHD (aGVHD) and chronic GVHD. Evidence on the efficacy of response in aGVHD has continued to accrue and data suggest that there is a good response and prolonged survival in both children and adults with grade II-IV aGVHD. Unlike chronic GVHD where treatment schedules are typically one or two times monthly for 12-18 months, patients with aGVHD respond rapidly to an intense weekly treatment schedule for 8 weeks, typically allowing steroids to be discontinued without flare-ups of aGVHD...
October 2014: Bone Marrow Transplantation
Alya Abdul-Wahab, Soo-Yong Tang, Alistair Robson, Stephen Morris, Nita Agar, E Mary Wain, Fiona Child, Julia Scarisbrick, Michael Neat, Sean Whittaker
BACKGROUND: The t(14;18)(q32;q21) chromosomal translocation is found in the majority of nodal follicular lymphomas but only rarely in primary cutaneous follicle center cell lymphomas (PCFCL). Recent studies have postulated that the translocation is more prevalent in PCFCL than previously described and that it might be a molecular prognostic marker. OBJECTIVES: The purpose of our study was to analyze cases of PCFCL for the presence of a t(14;18) translocation using fluorescence in situ hybridization to detect balanced translocations involving either the BCL2 or MALT1 loci and to correlate the results with growth pattern, immunophenotype, and clinical outcome...
June 2014: Journal of the American Academy of Dermatology
J J Scarisbrick, Y H Kim, S J Whittaker, G S Wood, M H Vermeer, H M Prince, P Quaglino
Mycosis fungoides is the most prevalent form of primary cutaneous T-cell lymphoma. Patients frequently present with early-stage disease typically associated with a favourable prognosis and survival of 10-35 years, but over 25% may progress to advanced disease with a median survival < 4 years, and just 13 months in those with nodal involvement. Sézary syndrome presents in advanced disease with erythroderma, blood involvement and lymphadenopathy. The Bunn and Lamberg staging system (1979) includes stages IA-IIA (early-stage disease) and IIB-IVB (advanced-stage disease) and provides prognostic information, but some patients with tumour-stage disease (IIB) have a worse prognosis than those with erythrodermic-stage (III)...
June 2014: British Journal of Dermatology
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