The Apoptosis and Expression of Bcl-2, Bcl-xS, Bax Proteins in Fetal Brain after Treating Pregnant Mice with Endotoxin

PURPOSE: Apoptosis is active cell death which plays an important role in developing normal tissues. Various conditions such as genetic defects, drugs, ischemia or infections are known to induce apoptosis. We studied the effect of maternal infection on fetal brain development during pregnancy. METHODS: We treated 46 C3H pregnant mice with lipopolysaccharide (LPS) or phosphat-buffered saline and observed the changes in apoptosis and expression of bcl-2, bcl-xS, bax. The fetal brain tissues were removed 1-48 hours after LPS treatment. The number of apoptosis per 100 neurons and glial cells was counted in H&E stained tissue and was analyzed statistically. Immunohistochemical staining with primary antibodies of bcl-2, bcl-xS, bax was done and their expression was classified by the degree of staining. RESULTS: The number of apoptosis was increased significantly in both neurons and glial cells of LPS-treated group and its degree of staining was more remarkable in glial cells. Immunohisto chemistry for bcl-2, bcl-xS, bax oncoprotein revealed mildly decreased expression of bcl-2 and markedly increased expression of bax in both neurons and glial cells, but it was more remarkable in glial cells. Immunochemistry for bcl-xS revealed no expression in neurons and minimal expression of bcl-xS in glial cells in both study groups. CONCLUSOIN: We observed an increase in the number of apoptosis, mildly decreased expression of bcl-2 and markedly increased expression of bax in both neurons and glial cells of fetal brain after treating pregnant mice with LPS. Maternal infection during pregnancy may have profound effects on developing fetal brain.

Leptin Levels in Children with Type 1 Diabetes Mellitus / 대한소아내분비학회지

PURPOSE: Leptin is a product of ob gene in adipose tissue. This is a important factor for regulation of body weight, especially body fat mass. So it is interested in correlation of leptin with obesity or various diseases related with obesity, particularly diabetes mellitus. It was demonstrated that leptin level was increased in type 2 diabetes and insulin was associated with increased leptin level. This study is to measure leptin levels in type 1 diabetes without insulin resistance, to validate whether insulin increases leptin level and to investigate correlation of leptin with degree of diabetic control and pubertal progression. METHODS: This study included 114 children(boys; 57, girls; 57) with type 1 diabetes, whose blood samples were taken to measure leptin level using RIA(radioimmunoassay). We observed the correlation of leptin with body mass index, HbA1c, insulin dose, duration of disease, and pubertal degree. RESULTS: Mean values of age, BMI, insulin dose, and HbA1c at the measurement of leptin were 13.0+/-5.04 years-old, 18.9+/-3.5kg/m2, 36U/day, and 8.9+/-2.1%, respectively. Thirty seven children were prepubertal and fifty seven children had pubertal characteristics and the rests were not confirmed. With increment of BMI, serum leptin levels were significantly increased in the all subjects, with the same correlation in pubertal female group, but not in pubertal male. There was a relatively weak correlation(r=0.29) of leptin levels with insulin doses. In prepubertal male, there was a significant positive correlation(r=0.55) of leptin with insulin dose, whereas in pubertal male there was shown negative correlation(r=-0.41). Female patients had a significantly higher leptin levels than male, irrespective of pubertal changes or BMI. There was not a significant correlation of leptin levels with duration of diabetes and HbA1c level. CONCLUSION: It is suggested that blood levels of insulin and sex hormones play an important roles in determining the levels of leptin.

Factros Related to the Outcome of Neonatal Seizures

PURPOSE: Seizures during the neonatal period may be an important indicator of serious neurologic abnormalities and can cause permanent neurologic sequelae. We attempted to find and analyze the factors related to the outcome of neonatal seizures. METHODS: Seventy-six newborns with seizure were reviewed. The outcomes were analyzed according to etiologic diseases, gestational ages, characteristics of seizure, and neuroimaging and electroencephalographic study findings. RESULTS: Of the 76 patients, 29 showed normal outcome, 27 had neurologic sequelae(NS), 7 expired, 7 hopelessly discharged, and 6 were lost during follow-up. Of the 40 with perinatal problems, the outcomes were normal in 19 and NS was found in 16. Of the 36 without perinatal problem, 10 showed normal outcome and 11 had NS. Ten out of 25 with hypoxia showed NS, whereas only 1 out of 11 with late hypocalcemia had NS. Of the 19 whose seizure began within the first 24 hours, 8 had NS, 3 expired and 2 discharged hopelessly. Of the 27 with generalized tonic seizures, 11 were normal and 13 showed NS. Of the 49 with brief but repetitive seizures, 16 showed NS, 6 expired and 5 discharged hopelessly. Twenty-five out of 39 with abnormal neuroimaging findings had abnormal outcomes, whereas 5 out of 20 with normal findings showed NS. Sixteen out of 27 with EEG background abnormalities and 24 out of 46 with epileptiform discharges had NS. CONCLUSION: Neuroimaging and electroencephalographic findings rather than etiologic factors were more important in predicting neurologic outcomes in newborns with seizure.

Intractable Temporal Lobe Epilepsy in Children : Presurgical Evaluation and Surgical Treatment / 대한소아신경학회지

BACKGROUD: The purpose of our study was to evaluate the usefulness of the ictal semiology, interictal and ictal electro-encephalography(EEG), brain magnetic resonance imaging(MRI), interictal and ictal single photon emission computed tomography(SPECT), positron emission tomography(PET) and neuropsychometry for localization or lateralization of the ictal onset zone, and analyze the result of surgical treatment. METHODS: We evaluated 13 children with intractable temporal lobe epilepsy, who are diagnosed at children's hospital of Seoul National University, from January 1995 to August 1996. The ictal onset zone was determined by ictal semiology, electrophysiologic study, structural and functional neuroimaging, and neuropsychometry. RESULTS: 1) Ictal semiology : Sixty-nine% of the studied children had change of consciousness, 62% had automatism, 31% had aura, 23% had contralateral versive movement, and 23% had contralateral dystonic posturing. Secondarily generalized seizure occured in 38% of them. 2) Interictal EEG showed localized or lateralized value in 8 cases(62%). In interictal EEG, 12 cases(92%) showed epileptiform discharges on the ipsilateral temporal lobe. 3) Magnetic resonance imaging revealed ipsilateral temporal lobe lesion in 8 cases(62%). Interictal SPECT was performed in 6 cases, only one of them had decreased cerebral blood flow on the ipsilateral temporal lobe. Ictal SECT was done in all, 8 cases(67%) had localized or lateralized value. PET was performed in 11 cases, 8 cases(73%) of them had localized or lateralized value. 4) Neuropsychometry was performed in 7 cases, 6 cases(86%) of them had localized or lateralized value. 5) Nine patients underwent epileptic surgery, 6 of them had class I outcome and each one of the rest had class II, class III and class IV. CONCLUSIONS: Electroencephalography, neuropsychometry, MRI, ictal SPECT, and PET are valuable for localization and lateralization of the ictal onset zone, but interictal SPECT is valuless. The outcome after surgery is relatively good, but more extensive study including patient's social, cognitive and emotional status will be necessary.

A Pediatric Case of MELAS Syndrome Associated with Insulin-dependent Diabetes Mellitus

MELAS(mitochondrial myopathy, encephalopathy, lactic acidosis, and sroke like episodes) is a major subgroup of heterogeneous mitochondrial encephalopathy. Recent advances in molecular genetics revealed specific mutations in the mitochondrial DNA causing MELAS. We described clinical and molecular genetic findings of a 13-year-old boy with MELAS syndrome associated IDDM(insulin dependent diabetes mellitus). For molecular genetic studies, DNAs from peripheral blood nucleated cells were used. And the A-->G substitution at the nt position 3,243 in the mitochodrial tRNAleu(UUR) gene in a heteroplasmic fashion was confirmed in the patient and his mother, which supporting maternal transmission. The mother had no neuromuscular syndromes but was diabetic. The islet cell antibody was abscent in both the patient and his mother, proving an indirect evidence of beta cell destruction was caused by the definite mitochondrial DNA itself. The association of MELAS syndrome and IDDM has been reported very rarely, and this is the first case report in Korea.