A significant decrease in the incidence of cleft lip without change in embryonic mortality was observed in CL/Fr mice by administering 100 to 500 mg/kg of urethane to dams on day 9 of gestation. No significant change in cleft lip incidence was observed when treated on day 8 and 10.
Ultraviolet (UV) sensitivity of cultured skin fibroblasts derived from heterozygotes and patients with Cockayne syndrome (CS) was measured in terms of counting survival colonies. UV sensitivity of CS heterozygotes was ranged between normal control and CS patients significantly. Measurement of UV sensitivity is one of the useful methods for the detection of carrier or atypical CS patients in family with overt CS patient.
There are two opposing concepts about the time of appearance of glial cells in the central nervous system (CNS). According to His, cells belonging to neuroglial cell lineage coexist with cells forming neurons from beginning of its development. On the other hand, from the results of autoradiographical study Fujita proposed that development of CNS takes place stepwise, and noted that glial cells are produced first after the production of neurons ends. Recently, Rakic and others claimed that migration of neuroblasts from the matrix layer to the cortical plate took place along the cell body of a kind of glial cells ("radial glia"), which were thought to exist in the time of neuroblast formation, and they insisted that glial cells exist in earlier stages than suggested by autoradiographical study. Fujita and his co-workers pointed out, however, that there has been no convincing evidences indicating glial nature of the radial elements in the stage of neuroblast-formation. From the findings of SEM-fractography they concluded that the bundle of processes of the matrix cells may play the role of guidance for the migration of neuroblasts. Using EM-autoradiography we have investigated transition of morphology glial cells retrospectively from adult age to embryonic stage, and could identify their progenitor cells, immature glioblasts, in stage III. These facts suggest strongly that no glial cells exist at the time of neuroblast-formation and before it.
Histogenesis of the cerebral cortex takes place according to the following steps: proliferation of matrix cells in the ventricular zone; differentiation of matrix cells into young neurons after completion of final division; migration of young neurons to the outer zone of the brain mantle to form the cortical plate; and growth and maturation of cortical neurons. Each step can be affected by environmental factors directly or indirectly, and any disturbance in these steps can cause histogenetic abnormalities. Thus, the sensitive period for histogenetic abnormalities covers the entire fetal period. According to experimental studies, the sensitive period for microcephaly by environmental factors was found to be the stage in which the young neurons began to differentiate from the proliferating matrix cells. In order to analyze the high sensitivity of the developing brain in the above stage to external agents, the author examined the radiosensitivity of matrix cells in the different cell cycle phases in the telencephalon of day 13 mouse fetuses. High radiosensitivity of G_1 phase matrix cells or young neurons just after the final division may contribute to the high sensitivity in this stage.
The ultrastructure of changes in synapses after injury in newborn rats were studied. The ethanol-phosphotungstic acid method of staining proved to be most useful for this purpose. The two characteristic findings were obtained from the qualitative and quantitative investigations: (1) the formation of synaptic junctions may develop according to circumstances; (2) the possibility that ouabainsensitive and K+_dependent p-nitrophenylphosphatase of the Na^+-K^+-ATPase complex is closely related to plasticity of the synapse may be proposed.
One of the behavioral problems in present day pediatrics is a syndrome known as Minimal Brain Dysfunction (MBD). Despite many studies, little is known regarding the etiology, pathophysiology and neuropathology of this disorder. Hyperkinetic behavior is one of the most crucial disorders in MBD. With the experimental paradigms utilized to study hyperkinetic behavior, several animal models with similar symptomatology have been developed in recent years. In this review the author proposed two major methods inducing MBD-like syndrome: early electrical stimulation and neonatal hippocampal lesions. By these experimental treatments to the developing rat pups, several behavioral alterations which are strikingly similar to the MBD patients were obtained at different developmental stages. At the same time, our data could demonstrate the developmental retardation in synaptogenesis of the hippocampus in a group of rats which received electrical stimulation in early developmental stage as well as the functional compensation effects in a group of rats which received hippocampal damage in the neonatal stage. Thus, it was suggested that these morphological and/or functional changes might be related to the later physiological and/or behavioral disorders such as hyperkinetic behaviors and learning deficits in MBD.
Neuropathological findings of 373 cases with developmental impairments registered in the Museum of Human Neuropathology are reported. Among these, clinical symptoms and neuropathological findings in 75 cases with severe mental retardation from Fuchu Ryoiku Center (Metropolitan Medical Center for the Severely Handicapped) were chiefly investigated. The characteristic neuropathological changes in mental retardation were summarized according to the causes of the retardation. Mental retardation due to prenatal factors include holoprosencephaly, congenital hydrocephalus, pachygyria, micropolygyria (Fukuyama-type), and midline malformations. These cases often show many other anomalies in various parts of the brain. Factors occurring during the late foetal period may cause both destructive processes and malformations in the same case. Retardation caused by perinatal factors shows a cystic degeneration of the brain or an atrophic brain, and the latter includes fibrillary gliosis of the cerebral white matter, atrophy of the anterior half of the cerebrum, atrophy of Ammon's horn and atrophy of the thalamus and basal ganglia. The changes are thought to occur within one year after birth and are quite similar to lesions of perinatal origin. On the other hand, various neuropsychiatric diseases were seen on cases which had been previously diagnosed as having mental retardation. Severe mental retardation is classified into several subgroups according to the brain lesions ; speech behavioral idiocy, acerebrate state etc.
The defective development of the thymus and immune function in congenitally athymic nude mutant of the mouse (nu/mu) and rat (rnu/rnu) were described. The thymic anlage in nude mouse and rat is unable to differentiate into keratinizing epithelial cells that might result in defective induction of functional T cells. Athymic nude animals have little T cell function but enhanced natural killer activity which provides defense mechanism against malignancy. The T and NK cell-deprived model prepared by injecting rabbit anti-asialo GM1 antibody into nude mice demonstrates suppressive role of asialo GM1^+ NK cells against tumor growth and metastasis in vivo. In addition, asialo GM1^+ cells in nude spleen are shown to be precursor for Thy-1^+, Lyt-^2+ cytotoxic T cells induced by alloantigen in nude mice.
5'-Nucleotidase (5'-NT) has been reported to have an important role for the dephosphorylation of purine deoxynucleoside monophosphate. However, recent works have claimed that there is no evidence of a systemic reduction in the degradation of nucleotides in patients with 5'-NT deficiency. We re-evaluated a role of 5'-NT in normal human lymphocytes and obtained a possible result that acid phosphatase might be involved in the dephosphorylation of purine deoxyribonucleoside monophosphate rather than 5'-NT. Although adenine, which accumulates in adenine phosphoribosyl transferase (APRT) deficient patients, is cytotoxic to human lymphocytes in vitro, APRT deflations is not associated with immunodeficiency. Three possible solutions were tested for the normal immunity in APRT deficiency. One is that only the lymphocytes from APRT deficiency retain the APRT activity. The residual activity prevents lymphocytes from the accumulation of adenine. Another exists that adenine toxicity is dependent on the phosphorylation by APRT. The phosphorylated adenine disturbs the lymphocyte metabolism but not adenine itself. The last is that the oxidization of adenine to 2,8-dihydroxyadenine by xanthine oxidase is the protective mechanism by which the adverse effect of adenine is cancelled. However, none of these possibilities could account for the normal immunity in APRT deficiency. The precise mechanism remains to be elucidated.