3D Histology Using the Synchrotron Radiation Propagation Phase Contrast Cryo-microCT / 체질인류학회지

3D histology is a imaging system for the 3D structural information of cells or tissues. The synchrotron radiation propagation phase contrast micro-CT has been used in 3D imaging methods. However, the simple phase contrast micro-CT did not give sufficient micro-structural information when the specimen contains soft elements, as is the case with many biomedical tissue samples. The purpose of this study is to develop a new technique to enhance the phase contrast effect for soft tissue imaging. Experiments were performed at the imaging beam lines of Pohang Accelerator Laboratory (PAL). The biomedical tissue samples under frozen state was mounted on a computer-controlled precision stage and rotated in 0.18° increments through 180°. An X-ray shadow of a specimen was converted into a visual image on the surface of a CdWO4 scintillator that was magnified using a microscopic objective lens (X5 or X20) before being captured with a digital CCD camera. 3-dimensional volume images of the specimen were obtained by applying a filtered back-projection algorithm to the projection images using a software package OCTOPUS. Surface reconstruction and volume segmentation and rendering were performed were performed using Amira software. In this study, We found that synchrotron phase contrast imaging of frozen tissue samples has higher contrast power for soft tissue than that of non-frozen samples. In conclusion, synchrotron radiation propagation phase contrast cryo-microCT imaging offers a promising tool for non-destructive high resolution 3D histology.

A New Facial Composite Flap Model(Panorama Facial Flap) with Sensory and Motor Nerve from Cadaver Study for Facial Transplantation

PURPOSE: The purpose of this study was to investigate the possibility that a dynamic facial composite flap with sensory and motor nerves could be made available from donor facial composite tissue. METHODS: The faces of 3 human cadavers were dissected. The authors studied the donor faces to assess which facial composite model would be most practicable. A "panorama facial flap" was excised from each facial skeleton with circumferential incision of the oral mucosa, lower conjunctiva and endonasal mucosa. In addition, the authors measured the available length of the arterial and venous pedicles, and the sensory nerves. In the recipient, the authors evaluated the time required to anastomose the vessels and nerve coaptations, anchor stitches for donor flaps, and skin stitches for closure. RESULTS: In the panorama facial flap, the available anastomosing vessels were the facial artery and vein. The sensory nerves that required anastomoses were the infraorbital nerve and inferior alveolar nerve. The motor nerve requiring anstomoses was the facial nerve. The vascular pedicle of the panorama facial flap is the facial artery and vein. The longest length was 78mm and 48mm respectively. Sensation of the donor facial composite is supplied by the infraorbital nerve and inferior alveolar nerve. Motion of the facial composite is supplied by the facial nerve. Some branches of the facial nerve can be anastomosed, if necessary. CONCLUSION: The most practical facial composite flap would be a mid and lower face flap, and we proposed a panorama facial flap that is designed to incorporate the mid and lower facial skin with and the unique tissue of the lip. The panorama facial composite flap could be considered as one of the practicable basic models for facial allotransplantation.

Evaluation of Phase-Contrast Microscopic Imaging with Synchrotron Radiation in the Diagnosis of Breast Cancer and Differentiation of Various Breast Diseases: Preliminary Results / 한국유방암학회지

PURPOSE: A significant improvement of imaging using synchrotron radiation (SR) is obtained by introducing phase-contrast technique. This technique provides greatly enhanced contrast and good soft tissue discrimination with high spatial resolution. The aim of this study was to observe microstructures of pathologic breast specimens including invasive breast cancer using phase-contrast technique with SR and to evaluate the feasibility of phase-contrast imaging in clinical application. METHODS: Phase-contrast microscopic image of normal breast tissue and the images of various breast diseases such as fibrocystic change, ductal carcinoma in situ, invasive ductal carcinoma, Paget's disease were obtained using hard X-ray microscopy with an 11.1 keV monochromatic beam from SR source and CsI (TI) scintillation crystal. Zernike phase-shifter was adapted for phase-contrast hard X-ray microscopy. The visual image was magnified 20 times by microscopic objective lens and captured using a full frame charge-coupled device camera. Obtained images were compared with corresponding histopathologic findings in the optical microscopy. RESULTS: The SR images of various breast diseases were obtained with a good contrast and high visibility by phase-contrast technique. It was possible to observe the microstructures with high spatial resolution down to the micron region. The characteristic features of each disease were consistent with the histopathologic findings of corresponding sample and the images of breast cancer and the other diseases were distinct from each other. CONCLUSION: Using phase-contrast technique, SR images of various breast diseases including breast cancer were obtained. These images were comparable with standard histopathologic findings and showed different features for each disease. The results suggest that phase-contrast microscopic imaging with SR has potential as a diagnostic tool and also its clinical application is feasible, especially in breast imaging.

The Effects of Antidepressants on the Energy Metabolism in LETO Rat / 대한정신약물학회지

Objectives : A diverse range of adverse effects has been linked to the application of antidepressants for the treatment of depressive disorder. Recently, evidence has been emerging of the adverse metabolic effects of antidepressants. This study investigated the effects of antidepressants on plasma glucose and other factors in the fat and muscle tissue relating to metabolism. METHODS : Long-Evans-Tokushima-Ostuka (LETO) rats were used to evaluate the effects of different antidepressants. Amitriptyline, fluoxetine, and mirtazapine were administered to each of three subgroups for 4 weeks, between 11 and 15 weeks old, while a fourth subgroup was administered no antidepressant during the same period. Changes of weight and daily intake were monitored. Tissues and blood were collected at 15 weeks. RESULTS : The fluoxetine subgroup showed lower weight gain and lower food efficacy ratio than did the other subgroups. Blood glucose and other circulating factors showed no significant differences among groups, except for the leptin levels of the fluoxetine subgroup. However, the amitriptyline and mirtazapine subgroups showed similar patterns in the response of mRNA expression of peroxisome proliferator-activated receptors gamma cofactor-1 and uncoupling protein-1, 2, 3. CONCLUSION : These results could indicate possible differences in metabolic response based on the kind of antidepressant used.

Relation between HPV and cyclooxygenase 2 overexpression in cervical carcinoma in situ and carcinoma / 대한산부인과학회지

OBJECTIVE: The aim of this study was to identify the relation between HPV infection and cyclooxygenase 2 (COX-2) overexpression in cervical carcinoma in situ (CIS) and carcinoma. METHODS: Fourteen patients with CIS, 14 patients with invasive cervical carcinoma, and 14 patients with myoma as control were enrolled. Polymerase chain reaction was used to detect high risk types of HPV, and immunohistochemistry was used to detect COX-2 expression. RESULTS: The frequencies of high risk types of HPV infections in CIS or carcinoma were significantly higher than control [CIS: 11 (78.6%), carcinoma: 14 (100%), control: 1 (7.1%), P-value>0.001]. COX-2 expressions in CIS were higher than control (P=0.037), and those in carcinoma were higher than CIS (P=0.002). Three patients with CIS did not show HPV infection and showed lower COX-2 expression than the other patients with HPV infection in CIS group (P=0.013). There was strong correlation between COX-2 expression and HPV infection (P>0.001). However, in multivariate analysis, disease progression from normal to invasive carcinoma was the only independent factor to affect COX-2 overexpression. CONCLUSION: Disease progression from normal to invasive carcinoma might be more important factor to affect COX-2 overexpression than high risk types of HPV infection.

Synchrotron Radiation Imaging of Female Breast Tissues Using Phase Contrast Technique / 한국유방암학회지

PURPOSE: X-ray microscopy with synchrotron radiation might be a useful tool for novel x-ray imaging in the clinical and laboratory settings. This technique provides detailed images of internal structures non-invasively. It also has the potential to resolve some of the limitations of conventional breast imaging. We evaluated high resolution synchrotron imaging of breast tissues from normal breasts and breasts with fibroadenomas and cancer. METHODS: A new x-ray microscope was installed on the 1B2 beamline of a Pohang Light Source, at a third generation synchrotron radiation facility in Pohang, Korea. The phase contrast x-ray energy was set at 6.95 keV and the x-ray beam was monochromatized by a W/B4C monochromator. Formalinfixed or unfixed female breast tissue from normal breast as well as breasts with fibroadenomas and carcinoma were attached onto the Kapton film. The sample was positioned 25 m away from the beam source. The x-ray image of the sample was converted into a visual image on the CsI (TI) scintillation crystal, and magnified 20 times by the microscopic objective lens. After an additional 10 fold digital magnification, this visual image was captured by a full frame CCD camera. RESULTS: The monochromated x-ray microscopic images of female breast tissue from normal breast, fibroadenoma and carcinoma cases were evaluated. The total magnifying power of the microscope was x200. This synchrotron radiation imaging enabled us to observe detailed structures of breast tissue without sample preparation such as staining or fixation. CONCLUSION: Using monochromated synchrotron radiation, the x-ray microscopic images of the normal breast and breasts with fibroadenomas and cancer were obtained. From the images obtained, the x-ray microscopic imaging of breast tissue with synchrotron radiation appears to have great potential for clinical and research purposes such as oncology studies, early detection of cancer and as an aid to the pathological diagnosis in the future.

The Properties of Glycoconjugates in the Rat Nasal Mucosa following Inhalation of Formaldehyde / 대한해부학회지

The present study was carried out to investigate the glycoconjugate properties of the nasal mucosa in the rat after inhalation of formaldehyde. Sprague-Dawley male rats were inhalated 30 ppm formaldehyde for 3 times with 3 hours exposure. The olfactory and respiratory mucosa in the nasal mucosa were taken from the animals on 3, 6,9 days and 2, 3, 4, 5 weeks after inhalation of formaldehyde. The properties of glycoconjugate of the olfactory and respiratory mucosa were investigated using nine biotinylated lectins (PSA, UEA I, PHA-L, BSL I, PNA, MAL I, DBA, BSL II or sWGA). In experimental groups, the degenerative changes of the olfactory epithelium were observed until 3 weeks after inhalation of formaldehyde, but the respiratory epithelium was no change. In control group, the olfactory cells in the olfactory epithelium reacted with PSA, UEA I, PNA, DBA, BSL II, sWGA, and the supporting cells reacted with PSA, PHA-L, PNA, MAL I, DBA, BSL II, sWGA, and Bowman's glands reacted with all the lectins. In experimental groups, the olfactory cells reacted with UEA I, DBA, and the supporting cells reacted with PHA-L, MAL I, DBA, UEA I, and the positive reaction of Bowman's glands was increased. In control group, the goblet cells in the respiratory epithelium reacted with UEA I, MAL I, and the ciliated columnar cells reacted with PSA, UEA I, PHA-L, BSL I, DBA, BSL II, sWGA, and the septal nasal glands reacted with all the lectins except UEA I. In experimental groups, the goblet cells reacted with UEA I, MAL I and PNA. Conclusively, the olfactory mucosa was shown a lot of changes in the properties of glycoconjugates following inhalation of formaldehyde, but respiratory mucosa was shown feeble change. These results suggest that there were different sugar residues of glycoconjugate in the olfactory and respiratory mucosa following inhalation of formaldehyde, respectively.

A Case of McCune-Albright Syndrome with Associated Multiple Endocrinopathies

McCune-Albright syndrome (MAS) is a rare disorder that develops from an activating mutation in the Gs gene. It is characterized by an association with Polyostotic fibrous dysplasia, and precocious puberty, Caf-au-lait pigmentation, and other endocrinopathies that result from the hyperactivity of a variety of endocrine glands. Recently we encountered a patient with MAS with fibrous dysplasia, skin pigmentation, acromegaly, hyperprolactinemia and a thyroid nodule. A 23-year-old male presented for an evaluation of a change in his facial structures. Fibrous dysplasia was diagnosed by a bone biopsy and radiographic studies. The GH level increased paradoxically after an oral glucose load. The plasma prolactin, IGF-1 and alkaline phosphatase were high. Thyroid ultrasonography revealed multiple nodules. The brain MRI demonstrated a mass in the left pituitary gland. Genetic analysis identified a change from Arg (CGT) at codon 201 to Cys (TGT).

Morphological Study for Osteoinduction by Human Fibroblasts Transduced with rhBMP-7 Adenovirus / 대한해부학회지

To evaluate availability of the BMP-7 adenovirus (AdBMP-7) as a gene therapy for osteoinduction, we investigated in morphological aspect at 1, 2, 4, 6 weeks after cells injection. Primary cultured human dermal fibroblasts, transduced with AdBMP-7, were injected into gastrocnemius muscle of the nude mice. One week after fibroblasts transplantation new tissue was observed in the muscle. Majority of new tissue was evaluated as cartilage and calcification in the matrix was confirmed by Von Kossa stain as well as electron microscopy. Two weeks after transplantation, spongy bone was built up and adipocytes were observed in intertrabecular spaces. Osteoblasts and osteoclasts were observed in the bony tissue surface. In the result of Von Kossa-Van Gieson stain, osteolysis was dominant in bony trabeculae. Bone marrow was established in 4th weeks with intertrabecular space filled up by hematopoietic cells. At the 6th weeks, the number of trabeculae decreased and thickness of the cortical bone was increased. A great part of bone matrix has laminar structure which run paralleled to surface and which included osteocytes and canaliculi. These data demonstrate that cell mediated AdBMP-7 for gene therapy initiate development of cartilage and calcification of matrix within 1 week and complete bone and bone marrow formation within 4 weeks, so then, could be made practical application for promotion of osteoinduction.

Iatrogenic Spinal Infection after Injection Therapy in Spine / 대한척추외과학회지

STUDY DESIGNS: A retrospective study of clinical experience. OBJECTIVES: To investigate and report the iatrogenic form of spinal infections that occur after injection therapy in the spine. SUMMARY OF LITERATURE REVIEW: An iatrogenic infection after injection therapy in the spine is rarely reported to be a serious complication. However, an increase in the number of immunocompromised patients, the aging of the population, and particularly an increase in spinal procedureshave precipitated a rise in the incidence of spinal infections. MATERIALS AND METHOD: Iatrogenic spinal infections occurred in 8 patients after various injection therapy in the spine, which included an epidural steroid injection or trigger point injection for various spinal conditions. The medical records and images of these patients regarding the clinical findings, risk factors, and treatments were analyzed. RESULTS: The pathologic conditions of the spinal infection were discitis in four patients with a concomitant infection in the epidural space and paraspinal muscles, an epidural abscess, and solitary muscular abscess or myositis in the other 3 patients. The systemic risk factors contributing to the infections were diabetes mellitus, metastatic cancer, and chronic liver disease in four patients. For treatment, intensive antibiotic therapy was applied to all patients. Six of the 8 patients underwent surgical drainage for abscesses and/or fusion to stabilize the infected segments. The infections were eventually controlled in all patients. CONCLUSION: Iatrogenic pyogenic infections of the spine after injection therapy in the spine is a serious complication with regard morbidity and treatment. To avoid these serious complications, a specialist experienced in aseptic techniques should perform these spinal procedures, particularly in those patients with the risk factors.

Increased expression of dopamine receptors and transporter and hypomethylation of dopamine transporter gene in uterine leiomyoma / 대한산부인과학회지

OBJECTIVE: Dopamine plays a key role in the proliferation regulation of the smooth muscle cells. The purpose of this study was to observe the degree of expression of dopamine D1 and D2 receptors and dopamine transporter (DAT) and to evaluate the influence of methylation about control of expression of DAT in uterine leiomyoma and normal myometrial tissue. METHODS: In 20 patients who underwent hysterectomy due to uterine leiomyoma, normal myometrial and leiomyoma specimens were obtained. The expression of dopamine D1 and D2 receptors and DAT was demonstrated by using RT-PCR and immunohistochemistry in each normal myometrium and leiomyoma. Analysis of the DNA methylation status of DAT was conducted using HpaII digestion and the methylation-sensitive PCR. RESULTS: The mRNA level of dopamine D1 receptor was relatively higher in normal myometrium than D2 receptor and it was also unchanged in leiomyomas. However, the mRNA levels of dopamine D2 receptor and DAT in leiomyomas were much higher than normal myometrium. Consistent with elevated mRNA levels, high levels of dopamine receptors protein expression were detected by immunohistochemistry in leiomyomas. The degree of methylation at CpG sites of the area intron 1 of DAT (genomic position, +377 - +888) was decreased in leiomyomas. CONCLUSION: These results suggest that overexpressed dopamine D2 receptor and DAT would be associated with proliferation of human uterine leiomyomas and the methylation status of the CpG island of DAT determines its expression.

Management of Low Back Pain Patient and Prevention of Low Back Pain / 대한척추외과학회지

No abstract available.

Management of Low Back Pain Patient and Prevention of Low Back Pain / 대한척추외과학회지

No abstract available.

Cardioprotective Effects of Minocycline in Rat Myocardiac Cell Culture Induced by Hypoxia / 소아과

PURPOSE: Minocycline appears to reduce the mortality rate of patients with myocardial infarction. Therefore, the cardioprotective effects of minocycline through reduction of apoptosis were studied in a rat myocardiac cell culture induced by hypoxia. METHODS: Cultured cells from the hearts of Sprague-Dawley rats were divided into two sets of groups: normoxia groups treated with 5% O2 and hypoxia groups treated with 1% O2. After several days of incubation, the control groups were not treated with minocycline, while the sample groups were treated with 1 mug/mL of minocycline. The damaged cells were observed under a microscope, while apoptosis was detected using a Tdt-mediated dUTP nick and labeling(TUNEL) assay control-stained with 4'-6'-diamidino-2-phenylindole-2HCl(DAPI). RESULTS: In normoxia, the control group showed a statistically significant difference from the sample group treated with 1 mug/mL of minocycline. In addition, in hypoxia, there was also a statistically significant difference between the two groups. When comparing the normoxia and hypoxia groups to each other, there was a statistically significant difference between the control groups and sample groups. CONCLUSION: Minocycline was found to be protective for heart in normoxia and in hypoxia in the model of rat myocardiac cell culture.

An Association Study of the Impulsiveness and Aggressiveness in Adolescent Prisoners with Serotonin Transporter Gene Promoter Region Polymorphism / 신경정신의학

OBJECTIVES: This study was carried out to explore the relationship between the impulsiveness and aggressiveness in adolescent prisoners and a polymorphism of the promoter region of the 5-HTT gene (5HTTLPR). METHODS: 198 adolescent prisoner volunleers and 68 male medical students as a normal control group were included in this study. The characteristics of adolescent prisoners and control subjects were assessed by using Barratt Impulsiveness Scale and Achenbach's Child Behavior Checklist (CBCL). Genotypes of 5-HTTLPR were analysed with the primers flanking the regulatory region from genomic DNA. RESULTS: Adolescent prisoners were significantly more aggressive (t=4.780, df=248, p<0.001), impulsive (t=5.220, df=248, p<0.001), and delinquent (t=12.299, df=173.554, p<0.001) than control group. There were no statistically significant differences in genotype frequencies of 5-HTT between adolescent prisoners and control group (chi2=2.378, df=6, p=0.882). There were no statistically significant differences in allelic frequencies of 5-HTT between adolescent prisoners and control group (chi2=2.027, df=4, p=0.731). CONCLUSION: In view of the negative results in the association of the promoter region polymorphism of serotonin transporter and the characteristics of adolescent prisoner, the promoter region polymorphism dose not appear to be a candidate gene for the characteristics of adolescent prisoner group. Further systematic researches including varying variables of phenotype would be required.

Distribution Patterns of Involucrin in the Stratum Corneum of the Normal and Psoriatic Artificial Skins / 대한해부학회지

Cornified envelope is highly insoluble structure formed beneath the plasma membrane during terminal differentiation of keratinocytes and is stabilized by cross linking of various proteins, including involucrin, loricrin, and cornifin. Psoriasis is a chronic skin disease characterizing inflammatory reaction and hyperproliferation of keratinocyte. There are some differences in involucrin immunolabelling in stratum corneum between normal and psoriasis epidermis. Labelling was convergent to cornified envelope in psoriasis skin but throughout cytoplasm in normal skin. To compare terminal differentiation patterns of normal and psoriasis keratinocytes, we reconstructed normal and psoriatic artificial skin by using primary cultured keratinocytes from normal and psoriasis skin and then performed immunogold labelling for involucrin in stratum corneum. Psoriatic artificial skin had thin and poorly organized corneal layer. Immunogold labelling for involucrin revealed same pattern of that in vivo by showing throughout cytoplasm in lower layer but convergent cornified envelope in upper layer. Compared with psoriatic artificial skin, normal artificial skin had well organized and thick stratum corneum. Involucrin labelling was throughout cytoplasm in most of corneal layer but convergent to cornified envelope in some uppermost cells. Even though some cells show convergent pattern in normal artificial skin, absolute number of this pattern was no lesser than in artificial psoriatic skin because of normal artificial skin had thick stratum corneum. This result showed there was no difference in involucrin distribution in terminal differentiation of normal and psoriasis keratinocytes in organotypic culture model. It is concluded that although well organized multiple corneal layers are formed in normal artificial skin, they can not reach to full maturation of cornified envelope, and difference of involucrin localization in cornified envelope of psoriasis epidermis is related with not peculiarities of the cells but rapid growing in vivo.

Homozygous Exon 4 Deletion in Parkin Gene in a Korean Family with Autosomal Recessive Early Onset Parkinsonism

The gene responsible for autosomal recessive parkinsonism, parkin, has recently been identified on chromosome 6q. It has been shown to be mutated in Japanese and European families, most of whom had early-onset parkinsonism. Here, we present a family with young-onset parkinsonism of an autosomal recessive inheritance. A homozygous exon 4 deletion in the parkin gene was found in 3 family members. To the best of the authors' knowledge, this is the first report in Korea of familial parkinsonism with the parkin gene mutation.

Neuroprotective Effects of Minocycline in Rat Brain Cortical Cell Culture Induced by Hypoxia

PURPOSE: In vivo, minocycline appears to be neuroprotective. Thus, the neuroprotective effects of minocycline were studied in a rat brain cortical cell culture induced by hypoxia. METHODS: Cultured cells from the brains of Sprague-Dawley rats were divided into two sets of groups : normoxia groups treated with 5% CO2 and hypoxia groups treated with 1% CO2. After several days of incubation, the control groups were not treated with minocycline, while the sample groups were treated with either 1 or 10 g/mL of minocycline. The damaged cells were observed under a microscope, while apoptosis was detected using a TUNEL assay control-stained with DAPI. RESULTS: Among the normoxia groups, the control and sample groups treated with 1 and 10 g/mL of minocycline were all statistically significantly different from each other. Meanwhile, among the hypoxia groups, although the control was significantly different from the sample groups, there was no statistically significant difference between the sample groups. When comparing the normoxia and hypoxia groups, there was a statistically significant difference between the control groups and sample groups treated with 1 g/mL of minocycline, yet no significant difference between the sample groups treated with 10 g/mL of minocycline. CONCLUSION: Minocycline was found to be neuroprotective in normoxia and hypoxia induced rat brain cortical cell cultures.

Posterolateral Fusion for Unstable Thoracolumbar Junction / 대한척추외과학회지

STUDY DESIGN: A retrospective study of patients with a posterolateral spinal fusion for an unstable thoracolumbar junction. OBJECTIVES: To evaluate the efficacy of a posterolateral spinal fusion for an unstable thoracolumbar junction. SUMMARY OF LITERATURE REVIEW: Posterolateral spinal fusions are well documented for their efficacy in the lumbar and lumbosacral spine, and have also been applied to the thoracolumbar junction in the lumbar area. The thoracolumbar junction, however, is a little different from the lumbar spine, in its anatomical and biomechanical aspects, and posterolateral fusions have not been well evaluated in these respects. MATERIALS AND METHODS: Fourteen consecutive patients, who had posterolateral spinal fusions, with instrumentation for an unstable condition, including T12-L1 segment, and followed for more than one year, were included. In 11 patients, all the fractures had been decompressed posteriorly, for degenerative conditions in 2, and for a neoplastic pathology in the other one. The radiographs concerning the lateral fusion mass were reviewed according to Lenke's classification, the change in the segmental sagittal angle of the fused segment and the fixation failure of the instrumentation. The medical records relating to the neurological recovery were reviewed using the modified Frankel grading, and the overall clinical results of treatment by the Kirkaldy-Willis criteria. RESULTS: All patients disclosed big, bilateral and solid fusion masses, with the exception of one patient who revealed a big, solid fusion mass on one side, and small, thin fusion mass on the other. No patient revealed more than 3 degrees of mobility on flexion-extension lateral radiographs, any evidence of fixation failure of the instrumentation. The neurological recovery, by the modified Frankel grading system, showed an average 1.3 improvement. The clinical results were excellent in 6, good in 6 and fair in 2 patients, with no poor results. CONCLUSIONS: A posterolateral spinal fusion can be effectively applied in an unstable thoracolumbar junction, such as in the lumbar and lumbosacral spine, provided there is precise preparation of the graft beds, enough bone grafts and correction of the excessive kyphotic angle by the compression fixation of the posterior instrumentation.

Mutations of SCN1B in Generalized Epilepsy with Febrile Seizures Plus(GEFS+) / 대한소아신경학회지

PURPOSE: Febrile seizures affect 2-5% of all children younger than 6 years old. A small proportion of children with febrile seizures later develop epilepsy. Generalized epilepsy with febrile seizures plus(GEFS+) is an important childhood genetic epilepsy syndrome with heterogeneous phenotypes, including febrile seizures(FS) and generalized epilepsies of variable severity. It was reported that the gene locus for GEFS+ exists in the chromosome 19q13.1, and has relationship with a 387 C->G mutation in the voltage- gated sodium channel beta1 subunit(SCN1B) gene. This study is to determine whether there are mutations in children with GEFS+ and FS. METHODS: Eighteen GEFS+ and thirteen FS patients were screened for mutations in the sodium channel beta-subunits SCN1B. The primer pairs used to amplify the exons of SCN1B are given in the supplementary data on the Neurology web site. All exons were amplified by PCR and PCR products were subsequently sequenced. Single-stranded conformation polymorphism(SSCP) was carried out using 8% polyacrylamide gel. RESULTS: Twenty four patients(77%) were younger than 10 years old, three(10%) were between 10 and 14 years old, and four(13%) older than 14 years old. The ratio of female to male was 0.55:1.0. In phenotypes of GEFS+, fourteen patients(88%) had generalized tonic-clonic seizures, one patient(6%) myoclonic seizures and one patient(6%) atonic seizures. In EEG findings of GEFS+, eleven(78%) patients had normal findings, five(28%) patients generalized spike waves and two patients(11%) diffuse slowings. In sequencing and SSCP of PCR products, we could observe added C mutations between 224G and 225C of exon 3 in two unrelated patients with GEFS+. CONCLUSION: We proved the existence of a new mutation of SCN1B in two unrelated patients with GEFS+.