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Biomedical subjects

John J Hong

Publications and source records attributed to John J Hong.

10 recordsLinked to original sources

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↗

A simple modification of the water maze test to enhance daily detection of spatial memory in rats and mice.

The water maze is one of the most frequently used tools in behavioral neuroscience. Many variations of the water maze task have been used; however, established water maze protocols have several disadvantages. Notably, these protocols demand considerable time to perform reference and probe tests separately. Here, we suggest a modified protocol, which is rapidly performed, is sensitive to cognitive deficits, and can assay reference as well as strategy-switching ability. The platform is relocated randomly within the target quadrant with each training trial. Because the rodents must spend more time searching within the target quadrant, every trial effectively becomes a probe trial. The rodents are then run in the switching strategy test, where the platform is randomly placed along the wall of the pool. The best new strategy would thus be to search along the walls of the pool systematically. The percent distance traveled and time spent near the wall is evaluated across trials, as is the distance traveled and time spent in the previously correct quadrant. In this way one can assess whether the rodent is continuing to search in the older platform location (i.e., displaying a strategy-switching problem) or whether it has successfully adopted a new search strategy.

Animals↗

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↗

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↗

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↗

Increased prefrontal D2 protein in Tourette syndrome: a postmortem analysis of frontal cortex and striatum.

The precise neuropathological mechanism underlying Tourette syndrome (TS) is unknown. In order to evaluate a variety of proposed dopaminergic abnormalities, postmortem tissue samples were obtained from three individuals with TS (two typical males with childhood onset, ages 29 and 77, and a 62-year-old female with adult-onset) and three age- and sex-matched controls. Samples from caudate, putamen, ventral striatum, and prefrontal cortex (Brodmann's area 9, BA9) were analyzed by semiquantitative immunoblotting for relative densities of dopamine receptors (D1, D2), transporter (DAT), monoamine terminals (vesicular monoamine transporter type 2), vesicular docking and release proteins (VAMP-2, synaptotagmin, SNAP-25, syntaxin, synaptophysin), and receptors inhibiting dopamine release (alpha 2-adrenergic receptors, alpha-2A). Concentrations of monoamine neurotransmitters and their metabolites were assessed by high performance liquid chromatography. Data from each TS sample was calculated as a percent value of its control. Results showed that prefrontal cortex, rather than striatum, had the greatest number of changes in the two typical TS cases, including increases for D2, DAT, VAMP-2, and alpha-2A. All three TS subjects had increased densities of prefrontal D2 receptor protein, greater than 140% of their matched control. These results suggest the presence of a prefrontal-dopaminergic abnormality in TS and emphasize the need for a more specific focus on the frontal lobe.

3,4-Dihydroxyphenylacetic Acid↗

Oral vitamin a therapy for a patient with a severely symptomatic postradiation anal ulceration: report of a case.

Squamous-cell carcinoma of the anus is an uncommon but treatable gastrointestinal malignancy. Radiation, in addition to chemotherapy, is widely accepted as the standard of care for treatment in most patients. However, significant anal complications, such as stricture, fistula, and ulceration, may result from radiation therapy. Some medical therapies have been used for radiation proctopathy, but treatments for radiation-induced anal injury other than surgical diversion are unknown. Vitamin A has been shown in laboratory studies to facilitate wound healing and prevent radiation-induced gastrointestinal damage. However, it has not been used clinically in patients with radiation enteritis, proctopathy, or anal ulceration. We report a case of a patient with human immunodeficiency virus infection who developed a symptomatic anal ulcer after receiving high-dose radiotherapy for anal squamous-cell carcinoma. We prescribed 8,000 IU of oral vitamin A twice daily and within seven weeks his anorectal symptoms and anal ulcer completely resolved. Vitamin A seems to be very effective in the treatment of radiation-induced anorectal damage, with little toxicity and expense.

Administration, Oral↗

A prospective randomized study of clinical assessment versus computed tomography for the diagnosis of acute appendicitis.

BACKGROUND: The objective of this study was to determine if routine use of computed tomography (CT) for the diagnosis of appendicitis is warranted. METHODS: During a one-year study period, all patients who presented to the surgical service with possible appendicitis were studied. One hundred eighty-two patients with possible appendicitis were randomized to clinical assessment (CA) alone, or clinical evaluation and abdominal/pelvic CT. A true-positive case resulted in a laparotomy that revealed a lesion requiring operation. A true-negative case did not require operation at one-week follow-up evaluation. Hospital length of stay, hospital charges, perforation rates, and times to operation were recorded. RESULTS: The age and gender distributions were similar in both groups. Accuracy was 90% in the CA group and 92% for CT. Sensitivity was 100% for the CA group and 91% for the CT group. Specificity was 73% for CA and 93% for CT. There were no statistically significant differences in hospital length of stay (CA = 2.4 +/- 3.2 days vs. CT = 2.2 +/- 2.2 days, p = 0.55), hospital charges (CA = 10,728 US dollars +/- 10,608 vs. CT = 10,317 US dollars +/- 7,173, p = 0.73) or perforation rates (CA = 6% vs. CT = 9%, p = 0.4). Time to the operating room was shorter in the CA group, 10.6 +/- 8.4 h vs. CT, 19.0 +/- 19.0 h (p < 0.01). CONCLUSIONS: Clinical assessment unaided by CT reliably identifies patients who need operation for acute appendicitis, and they undergo surgery sooner. Routine use of abdominal/pelvic CT is not warranted. Further research is needed to identify sub-groups of patients who may benefit from CT. Computed tomography should not be considered the standard of care for the diagnosis of appendicitis.

Adult↗