Biomedical subjects

Dustin Y Yoon

Publications and source records attributed to Dustin Y Yoon.

7 recordsLinked to original sources

PubMed2007

Dopaminergic polymorphisms in Tourette syndrome: association with the DAT gene (SLC6A3).

Tourette syndrome (TS) is a chronic neuropsychiatric disorder characterized by involuntary motor and phonic tics. The pattern of inheritance and associated genetic abnormality has yet to be fully characterized. A dopaminergic abnormality in this disorder is supported by response to specific therapies, nuclear imaging, and postmortem studies. In this protocol, dopaminergic polymorphisms were examined for associations with TS and attention-deficit hyperactivity disorder (ADHD). Polymorphisms investigated included the dopamine transporter (DAT1 DdeI and DAT1 VNTR), dopamine receptor (D4 Upstream Repeat and D4 VNTR), dopamine converting enzyme (dopamine beta-hydroxylase), and the acid phosphatase locus 1 (ACP1) gene. DNA was obtained from 266 TS individuals +/- ADHD and 236 controls that were ethnicity-matched. A significant association, using a genotype-based association analysis, was identified for the TS-total and TS-only versus control groups for the DAT1 DdeI polymorphism (AG vs. AA, P = 0.004 and P = 0.01, respectively). Population structure, estimated by the genotyping of 27 informative SNP markers, identified 3 subgroups. A statistical re-evaluation of the DAT1 DdeI polymorphism following population stratification confirmed the association for the TS-total and TS-only groups, but the degree of significance was reduced (P = 0.017 and P = 0.016, respectively). This study has identified a significant association between the presence of TS and a DAT polymorphism. Since abnormalities of the dopamine transporter have been hypothesized in the pathophysiology of TS, it is possible that this could be a functional allele associated with clinical expression.

Adolescent↗

PubMed2006

Antibrain antibodies in children with autism and their unaffected siblings.

Serum autoantibodies to human brain, identified by ELISA and Western immunoblotting, were evaluated in 29 children with autism spectrum disorder (22 with autistic disorder), 9 non-autistic siblings and 13 controls. More autistic subjects than controls had bands at 100 kDa in caudate, putamen and prefrontal cortex (p<0.01) as well as larger peak heights of bands at 73 kDa in the cerebellum and cingulate gyrus. Both autistic disorder subjects and their matched non-autistic siblings had denser bands (peak height and/or area under the curve) at 73 kDa in the cerebellum and cingulate gyrus than did controls (p<0.01). Results suggest that children with autistic disorder and their siblings exhibit differences compared to controls in autoimmune reactivity to specific epitopes located in distinct brain regions.

Autistic Disorder↗

PubMed2006

Norepinephrine transporter polymorphisms in Tourette syndrome with and without attention deficit hyperactivity disorder: no evidence for significant association.

Noradrenergic abnormalities have been proposed in the pathophysiology of Tourette syndrome and attention-deficit hyperactivity disorder. Patients with Tourette syndrome with (n=115) and without (n=110) attention-deficit hyperactivity disorder were evaluated for association with two single nucleotide polymorphisms of the norepinephrine transporter gene (SLC6A2); a T-182C single nucleotide polymorphism located in the 5' flanking promoter region and a silent mutation (G1287A) occurring in exon 9. A polymerase chain reaction restriction enzyme assay was developed for the T-182C single nucleotide polymorphism based on a prior sequencing methodology. In this case-control study, no association was identified between either polymorphism and Tourette syndrome or attention-deficit hyperactivity disorder. In a small subset, these NET polymorphisms did not predict therapeutic response to the noradrenergic transporter inhibitor atomoxetine. Further research with additional NET polymorphisms and larger sample sizes are indicated in the pursuit of biomarkers for therapeutic responders.

Attention Deficit Disorder with Hyperactivity↗

PubMed2006

Review of three tests of motor proficiency in children.

The present purpose is to provide clinicians, occupational and physical therapists, and educators with a comparative analysis of three tests of motor proficiency. The Bruininks-Oseretsky Test of Motor Proficiency, Movement Assessment Battery for Children, and Tufts Assessment of Motor Performance were developed to assess the motor skills of children with developmental delays. The selection criteria, interrater reliability, reproducibility, and recommended use of each test are reported here. Recommendations for use of each test include standardization of the sample population to ensure its appropriateness.

Adolescent↗

PubMed2005

Serum autoantibodies do not differentiate PANDAS and Tourette syndrome from controls.

BACKGROUND: An autoimmune-mediated mechanism has been proposed for both pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS) and Tourette syndrome (TS). Confirmatory evidence has, in part, been based on controversial findings of autoantibodies in the sera of children with these disorders. OBJECTIVE: To compare antineuronal antibody profiles in subjects with TS and PANDAS to age-matched controls. METHODS: Sera were obtained from 48 children with PANDAS, 46 with TS, and 43 age-matched controls. Serum autoantibodies were measured by use of ELISA and Western immunoblotting against a variety of epitopes, including human postmortem caudate, putamen, and prefrontal cortex (Brodmann area 10). Immunoreactivity was also measured against commercially available alpha- and gamma-enolase, aldolase C, and pyruvate kinase M1. Several assays were repeated after preabsorption of sera with M6 strain streptococci. RESULTS: Median ELISA optical density readings were similar among the groups. Western blot analyses showed complex staining patterns with no differences in any tissue region based on the number of bands, reactivity peaks at molecular weights 98, 60, 45, and 40 kDa, or total area under ScanPack (Biometra, Gottingen, Germany)-derived peaks. Immunoreactivity against four putative pathologic antigens did not differentiate the clinical groups. Repeat immunoblotting after serum preabsorption with streptococci showed no loss of reactivity. ELISA values exceeding a specified cutoff did not predict changes in binding to either brain epitopes or commercial antigens. CONCLUSIONS: Results do not support the hypothesis that PANDAS and Tourette syndrome are secondary to antineuronal antibodies. Longitudinal studies are required to determine whether autoantibodies correlate with fluctuations in clinical activity.

Adolescent↗

PubMed2005

Methodologic factors affect the measurement of anti-basal ganglia antibodies.

An autoimmune etiology has been proposed for a variety of movement disorders, making the detection of autoantibodies a high investigative priority. Recognizing the existence of different methodologic approaches to identify these antibodies, we sought to investigate the effects of tissue preparation, antibody selection, and Western immunoblot detection methods on outcome. ELISA and immunoblotting studies were performed in healthy controls evaluating non-pathogenic autoantibodies. Our results indicate that enhanced data can be obtained by using fresh, rather than frozen, postmortem tissue homogenates for Western immunoblots and enzyme-linked immunosorbent assays and support the use of electrochemiluminescent detection for Western immunoblots. Molecular localization is significantly affected by the selected standard. Removal of lipids from homogenates does not affect anti-basal ganglia antibody (ABGA) results. Methodological variables should be taken into consideration when performing and interpreting neuroimmunological assays using sera or isolated IgG.

Adult↗

PubMed2004

Microarray analysis in Tourette syndrome postmortem putamen.

Gene expression patterns in the postmortem putamen of patients with Tourette syndrome (TS) were investigated using cDNA microarrays. A cDNA neuroarray comprising 1537 genes known to be related to neurological or neuropsychiatric disorders was used to compare patient samples (n=3) with those from control subjects (n=4). Z test and Z ratio were used to analyze results; seven genes were found to be upregulated according to our definition (P<0.1, two-tailed, for Z test; P<0.05 for Z ratio) and three were found to be downregulated. Validation experiments were performed using reverse transcription polymerase chain reaction (RT-PCR) and semiquantitative Western blot analyses. RT-PCR showed concordance with microarray in seven of nine selected genes. In contrast, Western blot analyses performed with five proteins showed that only two of five had similar trends between protein content and level of gene expression. The authors note the inherent difficulty in applying microarray technology to complex neurological disorders such as the TS and conclude that further investigations are required to understand how altered expression of these genes is related to the pathophysiology of the disorder.

Adult↗