日本先天異常学会会報
Online ISSN : 2433-1503
Print ISSN : 0037-2285
43 巻 , 2 号
Congenital Anomalies
選択された号の論文の6件中1~6を表示しています
  • 2003 年 43 巻 2 号 p. 97-104
    発行日: 2003年
    公開日: 2021/08/04
    ジャーナル オープンアクセス
    ABSTRACT Fukuyama-type congenital muscular dystrophy (FCMD), Walker-Warburg syndrome (WWS), and muscle-eye-brain (MEB) disease are clinically similar autosomal recessive disorders characterized by congenital muscular dystrophy, lissencephaly, and eye anomalies. Through positional cloning, we identified the gene for FCMD and MEB, which encodes the fukutin protein and the protein O-linked mannose β1, 2-N-acetylgIucosaminy ltransferase (POMGnT1), respectively. Recent studies have revealed that posttranslational modification of α-dystro-glycan is associated with these congenital muscular dystrophies with brain malformations. In this review Fukuyama-type congenital muscular dystrophy (FCMD), other CMDs with brain malformations, and their relation with α-dystroglycan are discussed.
  • 2003 年 43 巻 2 号 p. 105-113
    発行日: 2003年
    公開日: 2021/08/04
    ジャーナル オープンアクセス
    ABSTRACT Cytomegalovirus (CMV) is the most significant infectious cause of congenital abnormalities of the central nervous system (CNS) with variation from the fatal cytomegalic inclusion disease to functional brain disorder. The phenotype and degree of the brain disorder depends on infection time during the developing stage, virulence, route of infection and the viral susceptibility of the cells. The pathogenesis of the CMV infection to the CNS seems to be strongly related to neural migration, neural death, cellular compositions and the immune system of the brain. To understand the complex mechanism of this disorder, we used organotypic brain slice cultures. In the brain slice culture system, migration of CMV-in-fected neuronal cells was observed, which reflects infectious dynamics in vivo. Neural progenitor cells or glial immature cells in the subventricular zone and marginal area are most susceptible to murine cytomegalovirus (MCMV) infection in this system. The susceptibility declined as the number of immature glial cells decreased with age. The immature glial cells proliferated in brain slice cultures during prolonged incubation, and the susceptibility to MCMV infection also increased in association with the proliferation of these cells. The brain slice from an immunocompromised mouse (Beige-SCID mouse) unexpectedly showed lower susceptibility than that of an immunocompetent mouse during any prolonged incubation. These results suggest that the number of immature glial cells might determine the susceptibility of CMV infection to the brain, independent of the immune system. We reviewed recent findings of CMV infection to the brain from the perspective of brain slice cultures and the possibility that this system could be a useful method to investigate mechanisms of congenital anomaly of the brain.
  • 2003 年 43 巻 2 号 p. 114-122
    発行日: 2003年
    公開日: 2021/08/04
    ジャーナル オープンアクセス
    ABSTRACT Numerous studies have shown the importance of the mesocorticolimbic dopamine system in the pathophysiology of attention deficit/hyperactivity disorder. However, there has been inconsistency in the findings of those studies. Varied and sometimes contradictory interpretation has been made on the basis of similar results. It is, therefore, still unclear whether the dopaminergic system is hypo- or hyperfunctioning in attention deficit/hyperactivity disorder. The majority of the functional brain imaging studies in both clinical and experimental settings support hypofunction of the basal ganglia which receive abundant dopaminergic afferent. The experimental studies, using dopamine-depleted animals, also support the hypodopaminergic hypothesis, whereas recent studies with the dopamine transporter knockout/knockdown mouse suggest hyperdopaminergic function as the underlying abnormality. In this review we attempt to clarify the issues raised by previous neuroimaging and functional neuroimaging studies. Research involving animal models with genetic traits, genetic manipulation or with brain lesions is analysed, concentrating on the significance of the dopaminergic system in the abnormal behavior of attention deficit/hyperactivity disorder. In addition, the functional state of the dopaminergic system is considered through the speculated mechanism of psychostimulant therapy of the disorder. No final conclusions have been reached regarding the pathological, biochemical and physiological mechanisms responsible for various symptoms. Inconsistency in the findings and their interpretations may indicate the heterogeneity of the pathogenesis of this syndrome.
  • 2003 年 43 巻 2 号 p. 123-132
    発行日: 2003年
    公開日: 2021/08/04
    ジャーナル オープンアクセス
    ABSTRACT It is widely believed that embryos and infants during development are highly sensitive to chemicals that cause serious damage to growth. However, knowledge on the mechanisms of developmental toxicity is scarce. One reason for this is limited convenient model system other than organ cultures using rodents to study the various aspects of developmental toxicology. Cultured cells are not always adequate for this purpose, since events in morphogenesis are processed through interactions with other tissues. We focused on zebrafish embryo (Danio rerio), one of the most important organisms in developmental biology. Saturation mutagenesis, applied to droso-phila and nematode to define the functions of genes, has been carried out in zebrafish but almost no other vertebrate, and several thousand lines are available due to the rapid growth and transparent body of this embryo. Enhanced databases for the genome and ESTs are available at websites with abundant genetic and biological background. By targeted gene knock-down with morpholino-modified antisense oligonucleotieds (morpholinos), the translation of a specific protein can be transiently blocked for several days. Many reporter systems in vivo have been established mainly as GFP-transgenic fish for environmental chemicals. Although several excellent studies have been performed with zebrafish embryos on the effects of chemicals, the developmental toxicology of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been most extensively studied to date. We have found that TCDD induces apoptosis in dorsal midbrain with a concomitant decrease in local blood flow, using developing zebrafish. TCDD seems to produce oxidative stress through CYP1A induction in vascular endothelium, resulting in local circulation failure and apoptosis in the dorsal midbrain. In addition to applications in toxicology, an experimental system with zebrafish embryos could help to clarify the mechanism of congenital anomaly, which arises from genetic mutation.
  • 2003 年 43 巻 2 号 p. 133-139
    発行日: 2003年
    公開日: 2021/08/04
    ジャーナル オープンアクセス
    ABSTRACT A genetic mouse model with a disrupted XPG allele was generated by insertion of neo cassette sequences into exon 3 of the XPG gene by using embryonic stem (ES) cell techniques. The xpg-deficient mice showed distinct developmental characteristics. Their body was marked smaller than that in wild-type littermates since the postnatal day 6, and this postnatal growth failure became more severe with developmental proceeding. Their life span was very short, all of the mutants died by postnatal day 23 after showing great weakness and emaciation. In addition, the mutant homozygous mice also showed some progressive neurological signs, like the lower level of activity and a progressive ataxia. Further examination indicated there was developmental retardation of the brain in the mutant mice. Their brain weight, and thickness of cerebral cortex and cerebellar cortex were significant different from the controls. These characteristics, like small size brain, brain developmental retardation and progressive neurological dysfunctions in the homozygotes were similar to the typical clinical phenotype of the XPG patients and Cockayne syndrome, we believe that the xpg-deficient mice will be an animal model for studying the function of the XP-G protein in nucleotide-excision repair and mechanisms related to the clinic symptoms of XP-G and Cockayne syndrome in humans.
  • 2003 年 43 巻 2 号 p. 140-141
    発行日: 2003年
    公開日: 2021/08/04
    ジャーナル オープンアクセス
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