Takashi Mimaki

Aicardi syndrome associated with an embryonal carcinoma

A Japanese girl is reported who had the typical clinical features of Aicardi syndrome associated with embryonal carcinoma. She developed infantile spasms at approximately 4 weeks of age; her seizures were intractable in spite of treatment with numerous antiepileptic drugs and ACTH. At 22 months of age, her left cheek gradually became swollen. Laboratory findings were normal except for a marked increase in serum alpha-fetoprotein. A transoral biopsy of the tumor revealed an embryonal carcinoma. This patient is the first reported with Aicardi syndrome and embryonal carcinoma. The relationship between congenital malformations and neoplasms is discussed.

Allelic heterogeneity in Group A xeroderma pigmentosum

The molecular basis of Group A xeroderma pigmentosum was investigated by restriction fragment length polymorphism analysis of PCR‐amplified DNA sequences using the two restriction enzymes, endonucleases AlwN I and Hph I. The clones of a patient with Group A xeroderma pigmentosum who had typical symptoms showed a G‐C substitution at the 3’ splice acceptor site of intron 3. However, of the two atypical Group A xeroderma pigmentosum patients with mild skin lesions and minimal neurological abnormalities, the milder one showed homozygosity for the nonsense mutation of exon 6, while the other patient with slightly greater central nervous involvement was shown to be a compound heterozygote for the splicing mutation of intron 3 and the nonsense mutation of exon 6, thus indicating an allelic heterogeneity in group A xeroderma pigmentosum.

Regional distribution of 14C-zonisamide in rat brain

Zonisamide (1,2-benzisoxazole-3-methane sulfonamide) is a new antiepileptic drug developed in Japan. This compound was proven to possess a strong inhibitory effect on convulsions of cortical origin, whether induced by electric or chemical stimuli. Regional distribution of 14C-zonisamide was investigated in rat brain using autoradiography. A high uptake of 14C activity was observed in the cerebral cortex and the midbrain. A pair-match analysis of primary motor cortex versus primary sensory cortex revealed a slightly higher uptake in primary motor cortex. In the cerebellum, a higher uptake was observed in the cortex than medulla. Sagittal section analyses revealed that a high uptake of 14C activity was observed in the cerebral cortex and colliculus, and a moderate uptake was seen in the cerebellum, thalamus, hypothalamus, and striatal body, thus suggesting the distribution of 14C-zonisamide is similar to that of flunitrazepam and phenytoin.

A case of tetrasomy 9p.

A case of mosaic 9p tetrasomy (46,XX/47,XX, + dic[9] [q21]) is reported. Clinical manifestations of the patient were generalized hypotonia, severe mental retardation and characteristic dysmorphic features of 9p tetrasomy. A brief review of the literature is also included.

Mature teratoma arising from intra-abdominal contralateral undescended testis in an infant: a case report

A 4-month-old male infant was seen because of an asymptomatic undescended left testis and a right sided abdominal mass. CT revealed a calcified retroperitoneal tumour. Histological examination of surgical specimens showed a mature primary teratoma of the contralateral undescended testis. While this is very rare, infants with undescended testis should be carefully examined to rule out intra-abdominal malignant tumours.

Outcome of Patients with West Syndrome: A Multicenter Cooperative Study.

years (range, 4.4-23.1 years). Patients were classified as generalized epilepsies (two) and localizationrelated epilepsies (1 1: LRE; multilobar, five; temporal, four; Rasmussens syndrome, two). Preoperative neuroimaging examinations revealed porencephaly in one patient, localized atrophy in three, microgyrus in one, tumor or cyst in three, dysgenesis in two, no abnormal findings in two, and nonspecific abnormalities in one. Seizures were frequent and resistant to multiple antiepileptic drugs (AEDs) in all 13 patients. Status epilepticusand epilepsia partialis continua were each experienced in two patients. All patients had been disabled in daily life because of frequent debilitating seizures. Epilepsy surgery was performed at ages ranging from 4.4 to 22 years with a mean of 13.6 years. Surgical procedures used for these patients were as follows; multiple subpial transections (six), focal resection (six), lobectomy (five), corpus callosotomy (five), and functional hemispherectomy (two). Duration of postoperative follow-up was 0.3-4.8 years with a mean of 1.84 years. All patients benefited from the surgery, although to various degrees. Postoperative outocomes, by using Engels criteria, were as follows: class 1A in five, class 1B in one, class 2A in four, class 2B in one, and class 3A in two. Corpus callosotomy was effective for three patients with tonic drop attacks. Those patients in whom neuroimaging studies had revealed structural abnormalities, such as hippocampal atrophy in temporal lobe epilepsy and hemiatrophy in hemispheric multilobar epilepsy, showed a significant improvement, whereas those without neuroimaging abnormalities did not. Epilepsy surgery should be seriously considered in children who have disabling seizures, resistant to various AEDs, and in whom the underlying structural abnormality can be assessed by neuroimaging examinations.

Effect of ACTH on resynthesis of GABA transaminase and GABAa receptor complex in rat brain

Abstract Adrenocorticotrophic hormone (ACTH) has clinical efficacy for some neurologic disorders, especially seizure disorders of childhood such as infantile spasms. In order to investigate the anticonvulsant mechanism of ACTH, the effect of ACTH1-24 injection on resynthesis of GABA transaminase (GABA-T) was investigated by enzyme histochemical techniques after systemic administration of gabaculine, an irreversible inhibitor of GABA-T. The effects of ACTH1-24 were also investigated on GAB-stimulated 36 Cl − uptake, [ 35 S] t -butylbicyclophosphorothionate (TBPS) binding and on [ 3 H]GABA binding in rat cerebrocortical membranes in vitro. Daily injection of ACTH1-24 accelerates resynthesis of GABA-T activity, suggesting the anticonvulsant potency of this compound. On the other hand, ACTH1-24 showed a dose-related inhibition of net uptake of 36 Cl − , and at higher concentrations, showed a statistically significant inhibitory effect on [ 3 H]GABA binding. ACTH1-24 also showed a significant dose-related enhanced effect on [ 35 S]TBPS binding in the presence of 1 μM exogenous GABA. These results demonstrate rather an antagonistic effect on GABAa receptor, which may correlate with the potential proconvulsant activity.

Clinical symptoms and molecular basis of group a xeroderman pigmentosum

Abstract The molecular basis of group A xeroderman pigmentosum (XP) was investigated by Southern blot analysis of genomic DNA for allelic heterogeneity in group A XP and comparison of clinical symptoms and severity of neurological complications. As previously reported, tow group A XP patients (XP-YK and XP-HH) with mild skin lesions and minimal neurological abnormalities had different mutations, one was a homozygote for the nonsense mutation of exon 6 (XP-YK), while the other was a compound heterozygote for the splicing mutation of intron 3 and the nonsense mutation of exon 6 (XP-HH). The present study revealed that one typical group A XP patient with severe skin lesions and severe neurological complications also was a compound heterozygote for the splicing mutation of intron 3 and the nonsense mutation of exon 6, thus suggesting the nonsense mutation of exon 6 is not always associated with mild skin lesions nor mild neurological manifestations. Further investigation of the sensitivity to UV radiation of fibroblasts from two atypical group A XP patients (XP-YK and XP-HH) with mild skin lesions and minimal neurological abnormalities showed intermediate post-UV colony-forming ability between that of typical group A and group C XP patients. These results suggest that DNA abnormalities are not always consistent with the severity of clinical symptoms, and that mild clinical symptoms may be explained by the residual ability of the cells to repair UV-damaged DNA.

Simultaneous measurement of hair and bone mineral content in severely handicapped children

Abstract Major and trace minerals were analyzed in the scalp hair of 73 severely handicapped children using the iductively coupled plasma (ICP) luminescent method, and compared with those in age-matched healthy children. Patients of either sex aged 6 years or younger showed significantly higher Ca and Mg and significantly lower Fe and Mn. In females but not males aged 6 years or younger, Zn and Co content was also decreased. However, in patients over 7 years of age, Ca, Mg and Zn content was not different from control, but in males over the age of 7 years, Fe and Mn content was decreased. Neither their physical activity nor treatment with anti-epileptic drugs had any effect on hair mineral content. In 12 patients with low levels of either Ca, Mg, Mn, Zn, or Cu, there was a significant decrease in bone mineralization measured by the DIP method; in eight of these patients, plasma 25-OH-D 3 was decreased and 1,25-(OH) 2 D 3 was normal, while 24,25-(OH) 2 D 3 was decreased in five of the eight patients. A convenient screening test of the mineral content of the hair appears very useful to predict and prevent fractures in handicapped children.