Juvenile Dermatomyositis Diagnosed by (99m)Tc-HDP Three-phase Bone Scintigraphy / 핵의학분자영상

Juvenile dermatomyositis is a common inflammatory muscle disease of childhood, characterized by weakness in proximal muscles and specific skin rash. In case of juvenile dermatomyositis without characteristic clinical features, non-invasive imaging tools such as (99m)Tc-HDP three-phase bone scan are very helpful in diagnostic workup of myopathies. We report a case of 13-year old female with juvenile dermatomyositis, in which (99m)Tc-HDP three-phase bone scan was useful in diagnosis and assessing therapy response.

Clinical and Genetic Characteristics in Patients of Charcot-Marie-Tooth type 2A with Mitofusin 2 (MFN2) Mutations

BACKGROUND: Mitofusin 2 (MFN2) is a membrane protein and is an essential component of mitochondrial fusion machinery. Mitochondrial fusion is essential for various biological functions in mammalian cells. Thus mutations in MFN2 are the underlying cause of Charcot-Marie-Tooth neuropathy type 2A (CMT2A). However, there has been no reports investigating the MFN2 genes in Korean CMT patients. Therefore, we investigated to find the clinical and genetic characteristics in Korean patients with the MFN2 gene mutation. METHODS: We examined the mutations of the MFN2 gene in 137 Korean CMT families. According to criteria from the European CMT consortium, CMT2 was 45 families. Mutations were confirmed by both strands sequencing. Nerve conduction studies were carried out in CMT patients having each mutation. RESULTS: Eight pathogenic mutations were found in 10 families. Six mutations (Leu92Pro, Gly127Asp, His165Arg, Ser263Pro, Arg364Trp, Met376Thr) were determined to be novel, and those were not detected in the 100 healthy controls. A de novo missense mutation was found in three CMT families (30%). The frequency of the MFN2 mutation was 22.2%, which was higher than those found in the Cx32 mutation. In CMT2A, the frequencies with early age at onset (<10 years) and flat feet were 46.2%. CONCLUSIONS: We found MFN2 mutations in patients with sporadic or dominantly inherited CMT. In the majority of cases with CMT type 2, the axonal neuropathy, may be due to MFN2 mutations.

The Temporospatial Distribution of Glutamate Receptors and the Effect of MK-801 on Glutamate Receptors Activation in Kainate-induced Seizure Model: Quantitative Receptor Autoradiography of Ionotropic Glutamate Receptors

BACKGROUND: Excitotoxicity and epileptogenesis have often been associated with glutamate receptor activation. Some evidence indicates that selective down regulation of AMPA receptor may be the mechanism of delayed neuronal cell death in the hippocampus. METHODS: We used in situ hybridization to examine the hybridization density (HD) of NMDA and AMPA receptors on excitotoxicity and epileptogenesis in the hippocampus of the kainic acid (KA)-induced rat seizure model. Some Sprague-Dawley rats were injected with KA, and others with MK-801 prior to KA injection. The rats were killed at 8 hours or 4 weeks after KA or MK-801/KA injection. HD of [3H]MK-801 and [3H]AMPA bind-ing in subfields of the hippocampus was measured by an image analyzer. RESULTS: After 8 hours of KA injection, [3H]MK-801 binding was increased in CA1 and CA3, and decreased in dentate gyrus, and [3H]AMPA binding was decreased in all of CA1, CA3 and fascia dentata, and pretreatment of MK-801 did not affect [3H]AMPA binding in all of CA1, CA3 and dentate gyrus. After 4 weeks, both [3H]MK-801 and [3H]AMPA binding were prominently increased in inner molecular layer of dentate gyrus. CONCLUSIONS: Glutamate receptors, especially NMDA receptor, were associ-ated with excitotoxicity in the hippocampus but the selective down regulation of GluR2 subunit of AMPA receptor without NMDA receptor activation may not be sufficient to cause excitotoxic neuronal cell death in CA1 and CA3. In addition, the synaptic reorganization in inner molecular layer of dentate gyrus was proved to be chronically hyperex-citable in function and may contribute epileptogenesis.

Expression of E-cadherin in Benign, Borderline, and Malignant Ovarian Epithelial Tumors / 대한산부인과학회잡지

OBJECTIVE: To investigate the expression of E-cadherin in benign, borderline, and malignant ovarian tumors. METHODS: An immunohistochemical technique was applied to formalin-fixed paraffin-embedded samples of 20 benign cystic ovarian tumors, 14 borderline ovarian tumors and 13 ovarian carcinomas. Expressions of E-cadherin immunostaining in three histological types were compared, and the survival rate in malignant ovarian cancer according to E-cadherin expression was also assessed. RESULTS: E-cadherin was positively or heterogeneously expressed in both benign and borderline ovarian tumors. But it was negatively, heterogeneously, or positively expressed in malignant ovarian tumors. The difference of expression of E-cadherin between borderline and malignant ovarian tumors was statisticaIly significant (p<0.05). In ovarian carcinoma, there was difference between negative and positive group in survival (p<0.05). CONCLUSION: Our results suggest that alterations in E-cadherin seem to occur at a later stage of the ovarian carcinogenesis, and may have some prognostic value in malignant ovarian tumor.

Glutamate Receptor Subunits Gene Expression in Kainate-induced Temporal Lobe Epilpsy Model

BACKGROUND: There is considerable controversy about the exact molecular mechanisms of excitatory amino acid receptors in epileptogenesis. METHODS: We used in situ hybridization to examine the hybridization density (HD) of n-methyl- D-aspartic acid receptor type 1 (NMDAR-1) and alpha-amino-3-hydroxy -5-methyl-4-isoxazole-propionate (AMPA) receptor type 2 (GluR-2) mRNA, in the hippocampus obtained from the kainic acid (KA)-induced status epilep-ticus (SE) model. Some Sprague-Dawley rats were injected with KA (10 mg/Kg; I.p.), and others with MK-801 (4 mg/kg) 20 minutes prior to KA. The rats were allowed to have 4-hour SE and were killed at 8 hours or 4 weeks after KA or MK-801/KA injection. HD of NMDAR-1 and GluR-2 mRNA in subfields of the hippocampus was measured by an image analysis system. RESULTS: A typical neuropathological finding of hippocampal sclerosis and spontaneous repetitive seizures (SRS) were observed in the KA injected rats, but not in the MK-801 pretreated rats, killed at 4 weeks. Compared with controls, the rats killed at 8 hours after KA showed increased CA1, CA2, and CA3 NMDAR-1 HD, and stratum granulosum (SG) GluR-2 HD. The increase of NMDAR-1, not GluR-2, HD was blocked effectively by MK-801. The increase of SG GluR-2 HD remained until 4 weeks after the KA injection. CONCLUSIONS: Not only the NMDAR-1activa-tionbut also the GluR-2 activation is an important factor in delaying hippocampal neuronal loss and epileptogenesis. (J Korean Neurol Assoc 19(1):36~44, 2001

Skull or Brain Metastasis from Thyroid Carcinoma: Analysis of 7 Cases

Skull or brain metastasis from thyroid carcinoma is rare. Between Jan. 1993. and Jan. 2000. the authors experienced 7 cases of skull(4 cases) or brain(3 cases) metastasis from thyroid carcinoma. Clinical characteristics, radiologic findings and pathologic features were analyzed retrospectively. Among 4 cases of skull metastasis, 3 cases were follicular carcinoma and one was papillary carcinoma with follicular variant. All cases of brain metastasis were papillary carcinoma. We treated the patients by combination with surgical resection, radioactive iodine therapy and radiation therapy. Characteristics of skull or brain metastasis from thyroid carcinoma is reviewed with a pertinent literature.

Expression of E-cadherin according to the Presence of High Risk Prognostic Factors, Clinical Stages and Pathologic Types in Cervical Cancer Patients Treated by Radical Hysterectomy / 대한산부인과학회잡지

OBJECTIVE: To analyze the relationship between the degree of expression of E-cadherin and presence of high risk prognostic factors (lymph node metastasis or parametrium involvement), clinical stages and pathologic types in invasive cervical cancer. METHODS: An immunohistochemical technique has been applied to formalin-fixed, paraffin- embedded samples from 20 radical hysterectomy without risk factors and 16 radical hysterectomy with risk factors. The degree of expressions of E-cadherin immunostaining was compared with the International Federation of Gynecology and Obstetrics (FIGO) stage, presence of high risk prognostic factors, and pathologic types. RESULTS: The difference of the degree of expression of E-cadherin was not statistically significant between high-risk group (lymph node metastasis or parametrium invasion) and non-risk group. The difference of the degree of expression of E-cadherin was not statistically significant according to clinical stages and variable pathologic types either. CONCLUSIONS: These results suggest that the degree of the expression of E-cadherin has no relationship with known high risk prognostic factors, clinical stages and pathologic types in invasive cervical cancer.

Non-Salivary Type Adenocarcinoma of the Sinonasal Tract A case report with low and high grade histologies

Non-salivary type adenocarcinoma of the sinonasal tract is a rare entity and includes low grade and high grade adenocarcinomas, which show somewhat different clinical and histological features. We report a case of non-salivary type adenocarcinoma occurring in a 55-year-old man. Computed tomography showed a soft tissue mass in right nasal cavity and ethmoid sinus, which extended to the nasopharynx. Removed mass showed both high grade and low grade adenocarcinomatous areas, which have different histology from usual salivary type tumor. The high grade area mimicked intestinal adenocarcinoma and low grade area was similer to adenoma because of very well differentiated tumor glands.

Detecting p53 gene mutation of breast cancer and defining differences between silver staining PCR-SSCP and immunohistochemical staining

This study detects and defines the patterns of p53 gene mutations in breast cancers. We analyse p53 gene mutations through comparing the results of single-strand-conformation-polymorphism (SSCP) and immunohistochemistry (IHC), and we try to define the differences between the results of SSCP and IHC. Twenty-seven fresh primary breast cancer tissues and eight normal breast tissues were studied. The IHC was done with the usual streptavidin-biotin peroxidase complement method by using monoclonal antibody DO-7. The results of staining was scored. The SSCP method was done by using Cold SSCP Electrophoresis System. Overexpressions of p53 protein were seven (25.9%) among 27 cancer cases on IHC. Four (57.1%) of seven cases were positive in SSCP. In SSCP, the mutations were detected in 10 (37%) among 27 cancer cases. The mutations were two in exon 5, one in exon 8, and seven cases in exon 7. All of 10 mutations were proved by sequencing analysis. Of them, only four (40%) were positive in IHC. We consider the IHC as a screening method for p53 gene mutations.

Correlation of bcl-2 and p53 Expressions in Urinary Bladder Tumor / 대한비뇨기과학회지

PURPOSE: Alteration of p53 tumor suppressor genes is most frequently identified in human neoplasms, including urinary bladder tumor. The overexpression of the bcl-2 gene has been correlated with poor prognosis and chemotherapy resistance in other systems. We evaluated the significance of these gene expressions and correlation with prognostic factors in the urinary bladdder cancer. MATERIALS AND METHODS: The expression of bcl-2 and p53 oncoprotein were investigated serially in formalin-fixed and paraffin-embedded tissue specimens from 43 patients with primary transitioanl cell carcinoma in the urinary bladder. Thirty four were superficial bladder tumors and nine were invasive tumors. In histology grade according to WHO grading there were 9 grade I, 21 grade II and 13 grade III. RESULTS: Positive immunoreaction for bcl-2 was found in 3 out of 9 invasive bladder tumors, while 15 of 34 superficial tumors showed positive staining. Positive p53 immunostaining was found in 7 of 9 invasive tumors, while 18 of 34 superficial tumors showed positive staining. There was no significant correlation between bcl-2 or p53 expression and tumor stage(p=0.56, p=0.179). A higher incidence of bcl-2 staining was found in the grade I group than in the grade III group(p=0.041). There was no significant correlation between p53 expression and tumor grade (p=0.23). A significant inverse relationship was found between bcl-2 and p53 topographic expression(p=0.001). CONCLUSIONS: The results of this study indicated an inverse relationship between bcl-2 and p53 expression. These findings suggest bcl-2 expression may be associated with favorable prognosis in bladder tumor.

Mesothelial/Monocytic Incidental Cardiac Excrescences, So-called "Cardiac MICE": A case report

A rare case of mesothelial/monocytic incidental cardiac excrescences (cardiac MICE) is described in the aspect of pathological interest. This cardiac lesion is pathologically characterized by exuberant proliferation of mixed mesothelia and monocytes and might be misdiagnosed as metastatic carcinoma, rhabdomyosarcoma, and histiocytoid hemangioma, if the disease is not in the minds of pathologists. The reactive nodular hyperplasia due to irritation to mesothelia by various causes is a most prevailing pathogenetic mechanism. About 20 cases have been reported in the worldwide literature. A 67-year-old female patient presented with cough and dyspnea for 2 months, without any history of previous cardiac operation. 2D echocardiography of the heart revealed moderate amount of pericardial effusion with posterior wall thickening. Under the impression of metastatic malignancy, pericardiostomy was performed. Grossly, the tissue was dark hemorrhagic and friable and the histologic sections revealed the solid tumor-like proliferation of round to polygonal histiocytic cells admixed with small cuboidal mesothelial cells which formed strips and tubular arrays. They were found within the fibrinous network and there were scattered empty vacuolar spaces. Immunohistochemical staining confirmed their biphasic nature with the CD68 positivity of the histiocytes and the cytokeratin positivity of the cuboidal cells. Factor VIII positivity was not detected in any cell components. The lesion was considered the monocytic and mesothelial proliferation of reactive nature, so-called cardiac MICE in the pericardial cavity. We report a typical case of so-called MICE first in the Korean literature.

Expression of bel-2 Oncoprotein in Bladder Tumor / 대한비뇨기과학회지

PURPOSE: Expression of bel-2 is associated with inhibition of apoptosis and extension of cell survival. We investigated the expression of bel-2 oncoprotein in human bladder tumor. MATERIALS AND METHODS: The expression of bel-2 oncoprotein was investigated immunohistochemically in formalin-fixed and paraffin-embedded tissue specimens from 43 patients with primary transitional cell carcinoma in urinary bladder. Thirty four were superficial bladder tumors and nine were invasive bladder tumors. In histology grade according WHO grading there were 9 grade 1,21 grade II and 13 grade III. RESULTS: Strong positive staining was 5(11.62%), positive staining 13(30%) and negative staining 25(58%). Random distribution through the cancerous epithelium presented in 3 tumors but the other 15 tumors demonstrated cystoplasmic staining restricted to basal epithelial cells. Positive immunoreaction for bel-2 was found in 3 out of 9 invasive bladder tumors, while 15 of 34 superficial tumors showed positive staining. There was no significant correlation between bel-2 expression and tumor stage(p=0.56). 6 of grade I, 9 of grade II and 3 of grade III bladder tumors showed positive staining. There was no significant correlation between bcl-2 expression and tumor grade(p=0.12). CONCLUSIONS: The findings suggest that no clear relationship was found between tumor grade, stage and bel-2 expression.

In vitro and In vivo Characterization of EL4 Cell Transfected with TGF-B1 cDNA / 대한면역학회지

Transforming growth factor-B1 (TGF-B1) is well known to be one of the most potent Immunosuppressive cytokines. To determine whether TGF-B1 secreted in the latent form can be immunoregulatory, TGF-B1 cDNA driven by the human -actin promotor was transfected into a murine thymoma cell line, EL4 cells. The transfectants (ELJ4) secreted a latent torm of TGF-B1 at a concentration of 5 ng/ml under the influence of TPA. Transfected TGF-b1 transcripts was readily detected by RT-PCR in ELJ4 cells regardless of the presence of TPA, but not in EL4 cells. In addition, we found the degree of Thy-B1 expression, IL-2 secretion and the proliferation rate are not altered by the transfection. Finally, EL4 and ELJ4 cells were injected into C57BU6 mice (syngenic strain), subcutaneously. Tumor cell masses derived from both cell populations survived longer than 1 wk, and the size of tumor derived from ELJ4 was three times larger (2.5 cm of diameter) than that from EL4. Virtually, there was no histopathological difference between two tumors. Taken together, the results from the present study indicates that EL4 thymomas transfected with TGF-1 secretes a latent form of TGF-B1 which may suppress host immune defence system.

Cortical Dysplasia: MRI Findings According to the Pathological Grading

PURPOSE: To describe the MRI findings of cortical dysplasia (CD) according to pathological grading. MATERIALS AND METHODS: MRI findings in 24 patients with pathologically proven CD were retrospectively reviewed and weredescribed according to their histologic grading. The group consisted of 11 men and 13 women, and their median agewas 21.4(range, 5 to 41) years. Histologic findings were assigned one of three grades : Grade I (dyslamination ofcortical layers only); Grade II (additional dysplastic neurons); or Grade III(additional balloon cells). T1 and T2Wspin-echo MR images were obtained and were evaluated with specific reference to detection rate, location of theanomaly, the presence or absence of prolonged T2 relaxation in the underlying white matter, and configuration ofthe dysplastic cortex. RESULTS: Nine patients were found to be suffering from grade I CD, seven from grade II,and eight from grade III. MRI findings were abnormal in 58% of cases(14/24);three of these were grade I, four weregrade II, and seven were grade III. Among these 14 patients, four had the lesion in the frontal lobe;five, in thetemporal lobe;one, in the parietal lobe; two, in the sylvian fissure area, and two with tuberous sclerosis hadmultiple lesions. Of twelve patients with cortical dysplasia other than tuberous sclerosis, as seen on MRI, sixshowed poor gray-white matter differentiation, and six showed cortical thickening ; this ranged from 7-10mm inthickness with irregular, bumpy cortical surfaces. Areas of prolonged T2 relaxation in the underlying white matterwere present in six patients. CONCLUSION: MRI findings were abnormal in 58% of CD patients. The higher thepathological grading, the higher the detection rate of CD on MRI. To increase the detectability of slight corticaldysplasia, technical development, including new MR pulse sequences or imaging methods, is needed.

Study of the Relation between Rreduced E-cadherin Expression and Known Prognostic Factors in Breast Cancer

Breast Cancer in women poses a problem, and it can be difficult at times to evaluate the possibility of the cancer's recurrence in node negative early cancer. Reliable prognostic markers are needed in breast-cancer management to help clinicians identify patient with high risk of recurrence and arrive at more rational decisions for proper treatment. E-cadherin is a glycoprotein that mediates Ca2 -dependent cell-cell adhesion and maintenance of the epithelial cell phenotype. It has been implicated as an invasion-suppressing protein in experimental systems and in human tumors, and alterations in the cadherin function have been implicated in tumor progression in a number of adenocarcinomas. In this study, the expression of E-cadherin was reduced in 35.3% of the case reviewed(12/34), and we could find no clinical relation between the known prognostic factors except tumor stage(p<0.05), and the degree of E-cadherin expression.

Cyclin D1 Expression in 101 Cases of Breast Carcinoma

Cyclin D1, a cell cycle regulator essential for G1 phase progression, is a candidate proto-oncogene implicated in pathogenesis of several human carcinomas including breast carcinoma. We studied the cyclin D1 expression in 101 cases of primary breast carcinoma tissues. The overexpression of cyclin D1 was immunohistochemically demonstrated in 34 (37.8%) of 90 cases of invasive breast carcinoma. Positive cyclin D1 staining was seen in 32 of 79 invasive ductal carcinomas, and 2 of 3 mucinous carcinomas. All 5 medullary carcinomas, 2 invasive lobular carcinomas, and 1 metaplastic carcinoma were negative. Cyclin D1 overexpression was observed in 9 of 11 ductal carcinoma in situ (DCIS). Normal epithelial components, either ductal or lobular, were not immunoreactive for cyclin D1. No significant correlations were observed between cyclin D1 immunoreactivity and other parameters including tumor size, clinical stage, nuclear or histologic grades, lymphatic or angioinvasion, lymph node metastasis, and immunohistochemical status of progesterone receptor, p53 and c-erbB-2. The overexpression of cyclin D1 was positively correlated with estrogen receptor status (p=0.025). Based on our results, the cyclin D1 protein aberration may play a role in tumorigenesis of breast carcinoma, but does not seem to have prognostic value in invasive breast carcinoma without hormonal treatment.

A Case of Ovarian Low-Grade Stromal Sarcoma with Thecomatous Features: So-Called "Malignant Thecoma" / 대한산부인과학회잡지

Theca cell tumors of the ovary have been generally regarded as almost invariably benign neoplasms. Even though several case reports of the malignant variant of this tumor have appeared in the world literature, but the term "malignant thecoma" is controversial and doubtful. If a thecoma ever becomes malignant, the tumor cells dedifferentiate so that they can not be recognized any longer as theca cells: instead, they proliferate as a stromal sarcoma or fibrosarcoma. We have experienced a rare case of ovarian low-grade stromal sarcoma with thecomat ous features in a 66-year-old postmenopausal woman. The clinicopathologic finding and a review of literature on ovarian stromal sarcoma and malignant thecoma were described brie fly.

A Case of Malignant Mesothelioma of the Uterus / 대한암학회지

Malignant mesothelioma of the serosal surface of the uterus body is very rare and almost invariably malignant. Their diagnosis is made postoperatively in most instances.Various treatments have been described for malignant mesothelioma but effective method is still not known. A case of malignant mesothelioma of the uterus body with post-surgical pelvic persistence is presented. The diagnosis of carcinomatous mesothelioma was made postoperatively by pathologic examination and immunohistochemical reaction of the tumor cells.

Application of Cell Culture with Immunocytochemistry and Electron Microscopy to the Diagnosis of Central Neurocytoma

The purpose of this study was to determine the value of primary cell culture in combination with histololgical techniques as a method for the diagnosis of central neurocytoma ; it involved three patients who underwent resection at our hospital and three seen during consultation. Sterile fresh tumor tissues were mechanically and enzymatically dissociated into individual cells and seeded onto poly-L-lysine precoated Aclar coverslips. The cells attached to the surface of the coverslips within 12 to 24 hours, and a delicate cytoplasmic process developed within two to three days of preparation. Immunocytochemical stains for synaptophysin and MAP2 were strongly positive in the cultured tumor cells, and electron microscopic examination also supported their neuronal origin. Cell culture can thus be used as a rapid, reliable and reproducible method for the diagnosis of central neurocytoma, and may be valuable for the diagnosis of small round cell tumors localized in the intra- or periventricular region of the brain.

Expression of E-cadherin and a-catenin in Thyroid Carcinomas / 대한내분비학회지

BACKGROUND: Cell-cell adhesion in tissue is mainly regulated by hornotypic interaction of cadherin molecules, which are anchored to the cytoskeleton via cytoplasmic proteins, including a-and / 3-catenin. Loss of E-cadherin and catenin have been attributed a pathogenetic role in tumor invasion. METHODS: We examined the expression of E-cadherin and a-catenin in human thyroid carcinoma by immunohistochemistry. RESULTS: Normal tissue strongly expressed E-cadherin and a-catenin. However, E-cadherin and a-catenin expression were frequently reduced in thyroid carcinoma (E-cadherin: 62.5%, a-catenin: 81.3%). But the expression of E-cadherin and a-catenin in tumors with metastatic spreading were not different with tumors without metastasis. CONCLUSION: These results suggest that reduced E-eadherin and a-catenin expression may be a sensitive marker for disturbance in the adhesive function of the junctional complex, but further evaluation with more cases is needed for confirmation of the result of the same degree of expression in tumors with metastasis.