Doo Kwun Kim

A Case of Infantile Alexander Disease Accompanied by Infantile Spasms Diagnosed by DNA Analysis

Alexander disease (AD) is a rare leukodystrophy of the central nervous system of unknown etiology. AD is characterized by progressive failure of central myelination and the accumulation of Rosenthal fibers in astrocytes, and is inevitably lethal in nature. Symptomatically, AD is associated with leukoencephalopathy with macrocephaly, seizures, and psychomotor retardation in infants, and usually leads to death within the first decade. Its characteristic magnetic resonance imaging (MRI) findings have been described as demyelination predominantly in the frontal lobe. Moreover, dominant mutations in the GFAP gene, coding for glial fibrillary acidic protein (GFAP), a principal astrocytic intermediate filament protein, have been shown to lead to AD. The disease can now be detected by genetic diagnosis. We report the Korean case of an 8-month-old male patient with AD. He was clinically characterized due to the presence of psychomotor retardation, megalencephaly, spasticity, and recurrent seizures including infantile spasms which is a remarkable presentation. Demyelination in the frontal lobe and in a portion of the temporal lobe was demonstrated by brain MRI. Moreover, DNA analysis of peripheral blood showed the presence of a R239L mutation in the GFAP gene, involving the replacement of guanine with thymine.

Inducible nitric oxide synthase expression of tumor and stromal cells is associated with the progression of 7,12-dimethylbenz(a)anthracene-induced rat mammary tumors

The purpose of this study was to investigate the alteration of inducible nitric oxide synthase (iNOS) expression in rodent mammary tumors. We examined iNOS expression by immunohistochemistry and Western blot analysis in 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary tumors. In Western blot analysis, invasive carcinomas showed strong expression of iNOS; however, carcinomas in situ, atypical tumors and normal mammary tissue revealed insignificant expression. In immunohistochemistry, tumors revealed positive immunoreactivity in either tumor epithelial, stromal or endothelial cells. In particular, invasive carcinomas showed strong expression at the tumor cells bordering on glandular lumen containing necrotic or apoptotic nuclear debris. Invasive carcinomas showed higher positive immunoreactivity of iNOS compared with normal mammary tissue, atypical tumors, and carcinomas in situ. Stromal iNOS expression was correlated with apoptotic count. These results suggest that iNOS expression of tumor and stromal cells is associated with the progression of DMBA-induced rat mammary tumors.