White matter abnormalities in Parkinson's disease patients with glucocerebrosidase gene mutations

Glucocerebrosidase gene mutations represent a genetic risk factor for the development of Parkinson's disease. This study investigated brain alterations in Parkinson's disease patients carrying heterozygous glucocerebrosidase gene mutations using structural and diffusion tensor magnetic resonance imaging. Among 360 Parkinson's disease patients screened for glucocerebrosidase gene mutations, 19 heterozygous mutation carriers (5.3%) were identified. Of these, 15 patients underwent a neuropsychological evaluation and a magnetic resonance imaging scan. Sixteen age‐ and sex‐matched healthy controls and 14 idiopathic Parkinson's disease patients without glucocerebrosidase gene mutations were also studied. Tract‐based spatial statistics was used to perform a white matter voxel‐wise analysis of diffusion tensor magnetic resonance imaging metrics. Mean fractional anisotropy values were obtained from white matter tracts of interest. Voxel‐based morphometry was used to assess gray‐matter atrophy. Cognitive deficits were found in 9 mutation carrier patients (60%). Compared with controls, Parkinson's disease patients carrying glucocerebrosidase gene mutations showed decreased fractional anisotropy in the olfactory tracts, corpus callosum, and anterior limb of the internal capsule bilaterally, as well as in the right anterior external capsule, and left cingulum, parahippocampal tract, parietal portion of the superior longitudinal fasciculus, and occipital white matter. Mutation carrier patients also had decreased fractional anisotropy of the majority of white matter tracts compared with Parkinson's disease patients with no mutations. No white matter abnormalities were found in Parkinson's disease patients without glucocerebrosidase gene mutations. No gray matter difference was found between patients and controls. In Parkinson's disease patients, verbal fluency scores correlated with white matter abnormalities. Parkinson's disease patients carrying glucocerebrosidase gene mutations experience a distributed pattern of white matter abnormalities involving the interhemispheric, frontal corticocortical, and parahippocampal tracts. White matter pathology in these patients may have an impact on the clinical manifestations of the disease, including cognitive impairment. © 2013 Movement Disorder Society     

Alterations in the expression of signal-transducing CD3ζ chain in T cells from patients with chronic inflammatory/autoimmune diseases

The CD3ζ chain, a component of the T cell receptor (TCR)/CD3 complex, is considered to be a limiting factor in the assembly and transport of the TCR/CD3 complex to the cell surface and is crucial to receptor signaling function. Recent studies have demonstrated altered expression and function of this signal transduction molecule in T and natural killer cells in patients with chronic inflammatory/autoimmune diseases. In this review, current knowledge concerning the expression of CD3ζ chain as well as the mechanisms responsible for abnormal expression of this molecule in systemic lupus erythematosus, rheumatoid arthritis, and childhood idiopathic nephrotic syndrome are summarized.     

Synthesis,bioconjugation and stability studies of [18F]ethenesulfonyl fluoride

Fluorine‐18 labelled prosthetic groups (PGs) are often necessary for radiolabelling sensitive biological molecules such as peptides and proteins. Several shortcomings, however, often diminish the final yield of radiotracer. In an attempt to provide higher yielding and operationally efficient tools for radiolabelling biological molecules, we describe herein the first radiochemical synthesis of [¹⁸F]ethenesulfonyl fluoride ([¹⁸F]ESF) and its Michael conjugation with amino acids and proteins. The synthesis of [¹⁸F]ESF was optimised using a microfluidic reactor under both carrier‐added (c.a.) and no‐carrier‐added (n.c.a.) conditions, affording, in a straightforward procedure, 30‐50% radiochemical yield (RCY) for c.a. [¹⁸F]ESF and 60‐70% RCY for n.c.a. [¹⁸F]ESF. The conjugation reactions were performed at room temperature using 10 mg/mL precursor in aqueous/organic solvent mixtures for 15 min. The radiochemical stability of the final conjugates was evaluated in injectable formulation and rat serum, and resulted strongly substrate dependent and generally poor in rat serum. Therefore, in this work we have optimised a straightforward synthesis of [¹⁸F]ESF and its Michael conjugation with model compounds, without requiring chromatographic purification. However, given the general low stability of the final products, further studies will be required for improving conjugate stability, before assessing the use of this PG for PET imaging.