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Epstein-Barr virus (EBV), or human herpesvirus 4 (HHV-4), infects the vast majority of adults worldwide, and establishes both nonproductive (latent) and productive (lytic) infections. Host immune responses directed against both the lytic and latent cycle-associated EBV antigens induce a diversity of clinical symptoms in patients with chronic active EBV infections who usually contain an oligoclonal pool of EBV-infected lymphocyte subsets in their blood. Episomal EBV genes in the latent infection utilize an array of evasion strategies from host immune responses: the minimized expression of EBV antigens targeted by host cytotoxic T lymphocytes (CTLs), the down-regulation of cell adhesion molecule expression, and the release of virokines to inhibit the host CTLs. The oncogenic role of latent EBV infection is not yet fully understood, but latent membrane proteins (LMPs) expressed during the latency cycle have essential biological properties leading to cellular gene expression and immortalization, and EBV-encoded gene products such as viral interleukin-10 (vIL-10) and bcl-2 homologue function to survive the EBV-infected cells. The subsequent oncogenic DNA damage may lead to the development of neoplasms. EBV-associated NK/T cell lymphoproliferative disorders are prevalent in Asia, but quite rare in Western countries. The genetic immunological background, therefore, is closely linked to the development of EBV-associated neoplasms.

A report is made of a 52-year-old male whose main complaint was a painless tumor at the right side of the palate resulting in speech disturbance. He was diagnosed as a case of what Stout called benign mesenchymoma. Some discussion is also made of the tumor pathology in terms of genetic factors, predirective sites, age range, sex differences and therapy.

Parkinson's disease (PD) is one of the main causes of neurological disability in the elderly. Levodopa is the gold standard for treating this disease, but chronic levodopa therapy is complicated by motor fluctuation and dyskinesia. The catechol-O-methyltransferase (COMT) inhibitors represent a new class of antiparkinsonian drugs. When coadministered with levodopa/decarboxylase inhibitor, 2 COMT inhibitors, tolcapone and entacapone have been shown to improve the clinical benefit of levodopa. COMT activity is genetically polymorphic, and individuals with the low activity (COMT(L/L)) genotype have a thermolabile COMT protein; studies suggest that this genotype is less common in Asians than in Caucasians. Differences in COMT activity may determine the individual response to levodopa and result in ethnic differences in PD susceptibility. Our recent study suggests that the COMTL allele can interact with the MAOB gene to increase the occurrence of PD in Taiwanese. In order to understand this new class of antiparkinsonian drugs, we review their basic properties, pharmacology, and clinical efficacy. The frequency distribution of COMT genetic polymorphisms among different populations and its implications in the etiology and drug response is also discussed.

Genetic and molecular biological methodologies are being applied to the study of patients with epilepsy at an ever-increasing pace. Accurate classification of epilepsy within large families has allowed identification of genes through linkage analysis and then isolation of gene products. Mutations causing ion channel abnormalities coupled with clinical patterns of focal epilepsy syndromes are beginning to change our thinking about the etiology of recurrent seizures in all patients. Molecular methodology is beginning to have impact on understanding of the mechanisms of actions of drugs used to treat epilepsy and will have an impact on how future treatments are designed.

<p>A cytogenetic study was performed on 74 children with at least three major or minor congenital malformations and mental retardation, and whose phenotypes did not fit any well-defined syndrome. The chromosomes were examined routinely using banding techniques. A total of 11 patients (14.9%) was found to have a major chromosome abnormality: one patient had a sex chromosome structural abnormality and 10 patients had an autosomal structural abnormality, including 4 patients with partial trisomies, 4 patients with partial monosomies, and 2 patients with tertiary trisomies. Two of them had probable intrachromosomal duplication which would not have been identified by conventional staining alone. Familial transmission was ascertained in 5 of 10 cases in which both parents were studied. In addition, 5 patients (6.8%) were noted to have the following chromosome heteromorphisms: partial inv 1qh, inv 9qh, 9qh+, and Yqh+. These results show that chromosome abnormalities contribute much to the etiology of unclassifiable multiple malformations associated with mental retardation. Furthermore, the demonstration of subtle chromosome rearrangements by means of banding techniques provides important implications in medical practice for the diagnosis of affected patients as well as for the genetic counseling of the families.</p>

We report the first case in Japan, i.e., the first case among oriental subject of Farber's disease. This is a rare disorder of lipid metabolism in infancy subsequent to a genetically-determined defect in ceramide degradation. Main features are characterized clinically by hoarseness, joint swelling, subcutaneous nodules and retarded psychomotor development. Lipid analysis and pathological investigation on the material obtained from a subcutaneous nodule confirmed clearly the presence of ceramide and intracytoplasmic inclusion bodies characteristic for Farber's disease. In this case, we experienced also corneal opacity and striking abnormalities in electroencephalogram, which have apparently not been noticed in the 17 cases hitherto reported.

We analyzed nucleotide changes in 3 genes, ARIX, PHOX2B, and KIF21A, in 6 patients of 3 families with congenital superior oblique muscle palsy. Three exons of ARIX, 3 exons of PHOX2B, and exons 8, 20, and 21 of KIF21A were amplified by polymerase chain reaction from genomic DNA isolated from the peripheral blood. The DNA fragments were directly sequenced in both directions. In 2 different families, a heterozygous nucleotide change, ARIX 153G>A, in the 5’-untranslated region was found in common between a father and daughter with muscle palsy and between a mother and daughter with muscle palsy (Family No. 1 and No. 3). In the other family (Family No. 2), a heterozygous 15-nucleotide deletion, PHOX2B 1124del15, resulting in loss of 5 alanine residues in the alanine repeat of the protein, was found in the daughter with muscle palsy and her father with normal traits, but was not found in the mother with muscle palsy. No KIF21A nucleotide change was found in any patients. The ARIX 153G>A polymorphism might be a genetic risk factor for the development of congenital superior oblique muscle palsy.

The molecular defects in the catalase gene, levels of m-RNA and properties of the residual catalase studied by scientists are reviewed in human (Japanese, Swiss and Hungarian) and non-human (mouse and beagle dog) acatalasemia with reference to the bioinformatics. Japanese acatalasemia-I, the G to A transition at the fifth position of intron 4 of the catalase gene, limited the correct splicing of the mRNA and synthesized trace catalase with normal properties. Hungarian acatalasemia type C showed a splicing mutation. In the Japanese acatalasemia II and the type A and B of Hungarian acatalasemia, the deletion or insertion of nucleotides was observed in the coding regions, and the frame shift altered downstream amino acid sequences and formed truncated proteins. In the Hungarian acatalasemia D, the substitution of a nucleotide in the exon was found. In mouse and beagle dog acatalasemia, the substitution of nucleotides in the coding regions was also observed. Studies of residual catalase in Swiss, mouse and beagle dog acatalasemia showed that aberrant catalase protein degrades more quickly than normal catalase in cells. The experimental research in genetic toxicology concerning the effect of oxidative stressors (nitrogen monoxide, nitrogen dioxide and so on) on Japanese acatalasemic blood and acatalasemic mice is described. The clinical features of Japanese and Hungarian acatalasemic subjects are also described.

Autoimmune hepatitis (AIH) is a chronic and progressive disease characterized by histological interface hepatitis, hypergammaglobulinemia, and circulating autoantibodies. Multiple factors, including molecular mimicry, a genetic background including major histocompatibility complex class II, and defective function of regulatory T-cells, are involved in the pathogenesis. The diagnosis is made based on the scoring system of the International Autoimmune Hepatitis Group, the sensitivity and specificity of which are90%, respectively. AIH is classified into 3 sub-types based on the profiles of circulating autoantibodies: anti-nuclear antibody and/or smooth muscle antibody-positive (type 1), anti-liver-kidney microsomal antibody-positive (type 2), and anti-soluble liver antigen/liver-pancreas antigen antibody- positive (type 3). Recently, however, the number of atypical cases lacking the usual features has increased-for example, patients with acute-onset or fulminant-type AIH, autoantibody-negative patients, male patients, and patients with bile duct injury-and thus the clinical features of AIH have been diversified. AIH is responsive to immunosuppressive treatment in most cases; however, relapse occurs in more than 80% of patients within 1 year after immunosuppressive treatment withdrawal. The 10-year survival rate and the 10-year hepatocellular carcinoma-free rate are90%, respectively, indicating that some patients reach liver failure or develop hepatocellular carcinoma. To improve the prognosis of these patients, persistent normalization of transaminase is required.