Endocrinology and Metabolism

Volume 15(2); June 2000

Review Articles

Selective Estrogen Receptor Modulators(SERMs).: Hyoung Moo Park; J Korean Endocr Soc. 2000;15(2):139-149. Published online January 1, 2001

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Biochemical and Molecular Changes in Response to Environmental Hormones.: Jeong Mi Kim, In Ho Jo; J Korean Endocr Soc. 2000;15(2):150-157. Published online January 1, 2001

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Editorial

Urine Free Cortisol and Secondary Adrenal Insufficiency.: Ho Young Son; J Korean Endocr Soc. 2000;15(2):158-161. Published online January 1, 2001

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Abstract PDF: No Abstract Available.

Original Articles

Usefullness of Urinary Free Cortisol Measurement in Diagnosis of Iatrogenic Cushing Syndrome.: Yong Hyun Kim, Sang Jin Kim, Dong Seop Choi; J Korean Endocr Soc. 2000;15(2):162-169. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Although insulin induced hypoglycemia test is a standard diagnostic method in assessment of hypothalamo-pituitary-adrenal axis, rapid ACTH stimulation test using 250microgram has been used as a first line diagnostic test especially in secondary adrenal insufficiency due to iatrogenic Cushing syndrome because it is easy and safe. However, it was suggested that a maximal cortisol response can be achieved with a much lower ACTH dose and 1microgram ACTH enhances the sensitivity without decreasing specificity of test. Also recently, there was a report that midnight to morning urine cortisol increment is more accurate, noninvasive method can be used for measurement of hypothalmo-pituitary-adrenal axis. In this study, we compared the 1microgram ACTH stimulation test with midnight to morning urinary free cortisol increment in secondary adrenal insufficiency due to iatrogenic Cushing syndrome to study the agreement of two test and accuracy of increment of urinary free cortisol in diagnosis of adrenal insufficiency. METHODS: Double voided urine sample were collected at midnight and 8 A.M. in 12 patients who have Cushing-like feature and history of taking glucocorticoids and in 12 normal controls. Urinary free cortisol was measured and cortisol increment was defined as the morning urine free cortisol minus the midnight urine free cortisol. The 1microgram ACTH stimulation test was performed in 12 iatrogenic Cushing syndrome patients at the same day and compard with the result of cortisol increment. RESULTS: Using the results of 12 controls, normal urine free cortisol increment was defined as greater than 165.5nmol/L(6.0microgram/dL). Subnormal cortisol response in 1microgram ACTH stimulation test was noted in 8 out of 12 patients group and urinary free cortisol increment was not observed in 7 out of 8 subnormal response group. Normal cortisol response in 1microgram ACTH stimulation test was noted in 4 out of 12 patients group and urinary free cortisol increment was observed in 3 out of 4 normal response group. So 83% of concordance rate between 1microgram ACTH stimulation test and urine free cortisol increment was recorded. CONCLUSION: Urinary free cortisol increment has high concordance rate with 1microgram ACTH stimulation test and simple, easy test in diagnosing secondary adrenal insufficiency due to iatrogenic Cushing syndrome. Further study including more patients will be helpful to know the adequacy and reliability of test in evaluation of hypothalamo-pituitary-adrenal axis.

Comparison of Clinical Features and MRI Findings between Adamantinous and Papillary Craniopharyngioma.: Tae Wook Kang, Jong Ryeal Hahm, Sung Uk Kwon, Gun Young Cho, Ji Min Lee, Mun Hee Bae, In Kyung Chung, Tae Young Yang, Jae Hoon Chung, Yong Ki Min, Myung Shik Lee, Moon Kyu Lee, Jong Hyun Kim, Yeun Lim Suh, Jae Wook Ryoo, Dong Kyu Na, Kwang Won Kim; J Korean Endocr Soc. 2000;15(2):170-178. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Craniopharyngioma is a suprasellar or intrasellar epithelial neoplasm that occurs in both children and adults. It accounts for 1.2 to 3 % of intracranial tumors with an incidence of 0.5 to 2 cases per one million populations each year. Recently, it has been postulated that it may have two pathogenetically separate subtypes, which are adamantinous and papillary craniopharyngioma, and that their clinical features may be different. However, there are some disagreements in this postulation. Therefore, we studied 22 consecutive patients with craniopharyngioma to evaluate the differences in clinical features and MRI findings between two subtypes. METHODS: We studied 22 patients with histologically proven craniopharyngioma after surgery at Samsung Medical center from 1995 to 1999. Thirteen patients were male, and nine patients were female. The average age was 30 years, with a range from 1 to 58 years. We divided 22 patients into two histopathologically separate subtypes; adamantinous and papillary subtypes. We compared the clinical features and MRI findings of two subtypes by reviewing medical records. RESULTS: Out of 22 patients with craniopharyngioma, 19 patients had an adamantinous subtype and 3 patients had a papillary subtype. The adamantinous subtype occurred frequently in the fifth decade and below twenty years, while the papillary subtype occurred predominantly in forth and fifth decades. The adamantinous subtype located in suprasellar or intrasellar portion as well as extrasellar portion, while the papillary subtype was restricted to the suprasellar location. The average tumor size of the adamantinous subtype was 3.7 cm, with a range from 1.4 to 6.0 cm, which was larger than that of the papillary subtype (average size 1.8 cm with a range from 1.5 to 2.3 cm, p< 0.05). The adamantinous subtype was predominantly cystic, while the papillary subtype was predominantly solid (p< 0.05). There were no significant differences in the preoperative clinical features and the postoperative complications between two subtypes. CONCLUSION: The adamantinous subtype had two peaks of occurrence in the fifth decade and below twenty years, while the papillary subtype occurred predominantly in forth and fifth decades. The adamantinous subtype was larger and had cystic portion, while the papillary subtype was smaller and had solid portion. The preoperative clinical features and the postoperative complications between two subtypes seemed not to be different.

Regulation of FSH Gene Expression and Release in Cultured Rat Anterior Pituitary Cells.: Min Seok Cheon, Deok Bae Park, Yong Bin Park, Kyung Yoon Kam, Kyung Za Ryu; J Korean Endocr Soc. 2000;15(2):179-189. Published online January 1, 2001

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Abstract PDF: BACKGROUND
FSH is a heterodimeric glycoprotein and is composed of alpha and beta subunits. alpha subunit is common to FSH and LH, while an unique beta subunit determines the biological specificity of each hormone. The synthesis of beta subunit is the primary rate-limiting step in the synthesis of each hormone. Although FSH plays a pivotal role in folliculogenesis and ovulation, very little studies have been performed on the regulation of FSH beta gene expression. Therefore, the present study attempted to examine the effect of GnRH or activin on the expression of FSH beta mRNA as well as FSH release and signaling pathway involved in their actions. METHODS: The primary cultures of rat anterior pituitary were used for this study. To determine FSH beta mRNA levels, northern blotting method was used. The concentration of FSH in the culture medium was evaluated by using a specific radioimmunoassay for rat FSH. RESULTS: PMA, an activator of PKC, increased FSH beta mRNA levels and FSH release, whereas forskolin, an activator of adenylate cyclase, showed no effect. The application of GnRH augmented FSH release, but not FSH beta mRNA levels. However, the administration of activin increased FSH beta mRNA levels as well as FSH release. Staurosporine, an inhibitor of PKC, suppressed activin-induced increment of FSH beta mRNA levels and FSH release. CONCLUSION: The present study demonstrated that activin rather than GnRH is a major regulator for FSH beta mRNA expression, and suggest that PKC-dependent pathway is also involved in the action of activin on the expression of FSH beta mRNA and FSH release.

Measurement of Anti-GAD65 Autoantibodies in Patients with Type 1 Diabetes Mellitus with / without Autoimmune Thyroid Diseases (Immunoblotting followed by Immunoprecipitation).: Yong Soo Park, Hye Won Park, Jin Bae Kim, Dong Sun Kim, Woong Hwan Choi, Tae Hwa Kim, Joon Yong Chung, Sei Won Yang, Won Bae Kim; J Korean Endocr Soc. 2000;15(2):190-203. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Type 1 diabetes mellitus is frequently associated with other autoimmune diseases. The broad concept of polyendocrinopathies takes into consideration that patients affected by at least one endocrine disease may have another autoimmune disorder or express specific autoantibodies. Anti-glutamic acid decarboxylase autoantibodies, now recognized as one of the major serological markers for type 1 diabetes has been reported to be higher in type 1 diabetes patients with autoimmune thyroid diseases (ATD) than in those without ATD. The objective of the present study was to evaluate the prevalences of GAD65 antibodies applying a newly developed assay(anti-GAD65) in type 1 diabetes patients with and without ATD. METHODS: We developed a new anti-GAD65 assay after mammalian expression of a recombinant GAD65 antigen. Since the detection of anti-GAD65 is rather complicated and insensitive due to inherent antigenic difference of antibody recognition in conventional assays, we applied this new approach in measuring anti-GAD autoantibodies and compared the result with ICA and anti-GAD measurement using the purified porcine GAD (anti-GAD) in 109 cases of type 1 diabetes, 29 of whom had concomitant ATD (mean age at diagnosis: 7.9 yr, mean duration of type 1 diabetes: 4.5 yrs). RESULTS: The overall prevalence of anti-GAD65 antibodies was 65% (71 of 109) in patients with Korean type 1 diabetes. Prevalences and titers of anti-GAD65 had not changed much after controlling for the duration and the status of concomitant ATD. In contrast, the prevalence of anti-GAD was 56%(61 of 109), while that of ICA(+) WAS 36% in type 1 diabetes patients. We found significant, but not strong association of anti-GAD65 either with anti-GAD(r=0.4, p<0.01) or with ICA(r=0.6, p< 0.001). CONCLUSION: From this, we could assess that autoantibodies are present at comparable sensitivity and specificity in Korean type 1 diabetes patients. This anti-GAD65 assay, another immunologic marker for type 1 diabetes might also confer disease susceptibility among Koreans, but no increase in the prevalence or in the titer in patients with ATD may suggest that this marker is unlikely to give much benefit, for the detection of the overlapping disease of type 1 diabetes and ATD.

The Regulation of OPG/OCIF mRNA Epression by IL-1beta in Peripheral Blood Mononuclear Cells.: In Gul Moon, Ho Yeon Chung, Chang Sun Hwang, Young Soon Kang, Mi Sun Chung, Han Jin Oh, Kyu Hong Choi, Sun Woo Kim, Eui Hyun Kim, Youn Yee Kim, Chang Hoon Yim, Ki VOk Han, Hak Chul Jang, Hyun Koo Yoon, In Kwon Han; J Korean Endocr Soc. 2000;15(2):204-213. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Osteoprotegerin(OPG) is a soluble member of the tumor necrosis factor(TNF) receptor family and inhibits osteoclastogenesis by interrupting the cell-to-cell interaction between osteoblastic/stromal cells and osteoclast progenitors. OPG is expressed in many tissues including osteoblasts and may act on bone tissues in a paracrine and/or autocrine fashion. Futhermore, many cytokines and growth factors are known to influence the regulation of OPG expression in osteoblastic/stromal cells. The aims of the present study were to examine whether or not OPG was expressed in human peripheral blood mononuclear cells(PBMCs) and to investigate the effects of IL-1beta, which were known as potent osteotropic agents, on the regulation of OPG mRNA in PBMCs. METHODS: PBMCs were isolated by centrifugation over Ficoll-Hypaque density gradients from postmenopausal women and cultured in 6-well plates containing alpha-MEM supplemented with 5% FBS. The expression of OPG mRNA in PBMCs was observed by RT-PCR in adherent and nonadherent cells on culture plates. To observe the effect of OPG expression by IL-1beta, we measured the concentration of OPG mRNA by altering the concentration and incubation time of IL-1beta. The measurement of OPG mRNA was done by semi-quantitative PCR and indicated as OPG/GAPDH. RESULTS: OPG was expressed both in cells attached to the surface of culture plates and in non-adherent cells for the incubation of peripheral blood mononuclear cells. The effect of OPG mRNA by IL-1beta tend to increase in accordance with the length of incubation time and maximizes at 12 hours of incubation time and shows 1.2-3.5 times higher than the standard level at the concentration of 0.5ng/ml. However, the increased quantity in concentration varies according to individuals.] CONCLUSION: OPG mRNA is expressed in peripheral blood mononuclear cells and known to be increased by IL-1beta.

The Nonthyroidal Illness Syndrome: Prognostic Value and Circulating Cytokines after Allogeneic Bone Marrow Transplantation.: Ki Won Oh, Moo Il Kang, Won Young Lee, Hyun Shik Son, Kun Ho Yoon, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang, Wan Sik Shin, Woo Sung Min, Choon Choo Kim, Byung Young Ahn, Hyung Sun Sohn; J Korean Endocr Soc. 2000;15(2):214-225. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Alteration of thyroid hormone parameters are frequently observed in sick patients and commonly known as nonthyroidal illness syndrome(NTIS) or euthyroid sick syndrome(ESS). NTIS is seen in starvation, surgery, severe illness, and also bone marrow transplantation(BMT). The degree of reduction in thyroid hormone parameters correlated with the severity of NTIS and might predict the prognosis of underlying illness. Recently, particular attention is focused on the role of cytokines in developing the NTIS. This prospective study was designed to assess the relationship of serum thyroid hormone parameters and serum cytokine levels before and in the short-term follow-up after allogeneic BMT in order to predict patients outcome. METHODS: Included 80 patients that were mainly leukemia and severe aplastic anemia. Serum thyroid hormone parameters and serum cytokine levels were measured before and 7, 14, 21, 28 days and 3, and 6 months after BMT. RESULTS: Near-all patients experienced significant decrease of thyroid hormone levels and also significant increase of cytokine levels after BMT. After post-BMT 3 weeks, the serum cytokine levels were negatively correlated with the serum T3 and T4 levels, but not with the serum TSH levels. The patients treated with high-dose steroid or total-body irradiation tended to show lower levels of TSH and more delayed recovery compared to non-treated patients. The patients died after BMT represented generally lower levels of all thyroid hormone parameters than survival patients during entire follow-up period. CONCLUSION: Development of NTIS is associated with higher probability of fatal outcome after BMT and has prognostic relationship in this group of patients. Increased levels of cytokines, especially IL-6 and TNF-alpha, are often found in post-BMT NTIS patients and correlated with the changes in the levels of thyroid hormone parameters.

Changes of Biochemical Bone Markers and Bone Mineral Density after Hormone Replacement Therapy in Korean Women.: Kyong Soo Park, Do Joon Park, Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee, Jae Hyeon Kim, Jeong Goo Kim; J Korean Endocr Soc. 2000;15(2):226-236. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Biochemical bone markers have been suggested to reflect postmenopausal high bone turnover. These markers could be useful in following response to hormone replacement therapy (HRT). But we have few studies about the sequential changes of biochemical bone markers and bone mass after HRT in Korean women, and it is unclear whether women with early menopause have different response to HRT from women with normal menopause. The aims of the present study were to see the sequential changes of biochemical bone markers and bone mass after HRT in Korean women, to examine whether a single baseline biochemical bone marker or a change in biochemical bone marker could predict subsequent bone mass, and to determine the difference of response to HRT between women with early menopause and women with normal menopause. METHODS: Postmenopausal women (n=21) were divided with into three groups according to their age at menopause (AAM): the first group with AAM < or = 43 years (early menopause group, n=7), the second group with 43 years < or = AAM < or = 50 years (n=4), and the third group with AAM > or = 50 years (normal menopause group, n=10). For the HRT, conjugated estrogen (0.625mg per day) and continuous or cyclic medroxyprogesterone (2.5-10mg per day) were administered. Bone mineral density (BMD) was measured at baseline and 12 months and biochemical bone markers were measured at baseline and 3, 6, and 12 months during HRT. RESULTS: Deoxypyridinoline, type 1 collagen N-telopeptide, bone alkaline phosphatase, and osteocalcin were significantly decreased at 3 months, and mean percent changes from baseline of bone resorption markers were larger than those of bone formation markers. At 12 months, BMD was significantly increased at lumbar spine and Ward's triangle. But BMD was not significantly increased at femur neck and femur trochanter. Two baseline bone markers (bone alkaline phosphatase and type 1 collagen N-telopeptide) correlated with changes of BMD but any changes of bone markers at 3, 6 months didn't correlate with changes of BMD. In early menopause group, changes of bone markers and BMD were larger than those in normal menopause group, but the difference between the two groups was not significant. CONCLUSION: All four bone markers showed significant reduction at 3 months, but bone resorption markers were decreased more markedly and rapidly, and some baseline bone markers can predict the change of BMD after HRT. The difference of response to HRT between early menopause group and normal menopause group was not significant.

A Study on the Relationship Between Genotype and Phenotype in Korean Patients with Congenital Adrenogenital Syndrome Caused by 21-hydroxylase Deficiency.: Dong Kyu Jin, Jung Sim Kim, Seung Mi Song, Sung Joon Park, He Zin Hwang, Hwa Young On, Phil Soo Oh, Si Whan Koh, Mee Ryung Uhm, Dong Hwan Lee, Jah Hoon Shin, Heon Seok Han, Hong Sik Kim, Cheol Woo Ko, Han Wook Yoo, Jin Sung Lee, Duk Hee Kim; J Korean Endocr Soc. 2000;15(2):237-247. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Congenital adrenal hyperplasia (CAH) results from an inherited defect in enzymatic steps required to synthesize cortisol from cholesterol. 21-hydroxylase deficiency accounts for 95% cases of CAH. It appears that the frequency and the type of the responsible mutations differ according to the ethnic background and the type of mutation can predict the clinical outcomes such as salt losing type (SL), simple virilizing type (SV) and non-classic type (NC). METHODS: We have analyzed CYP21 genes in 55 Korean cases (110 chromosomes) of CAH by Southern blotting, PCR-dot hybridization and PCR amplification-created restriction site method. The patients include 43 cases of SL and 12 of SV. None of the NC was found. RESULTS: We found the mutations in 94% (103/110) of the examined chromosomes. A total of 10 types of mutations were discovered. The mutations include aberrant splicing of intron 2 (i2, 35%), CYP21 gene deletion (32%) and I172N (11%) in order. When the relationship between the clinical types and genotypes were correlated, most of the SL patients have either i2 (42%) or CYP21 gene deletion (41%), while SV patients have I172N (33%) or P30L (21%). The parents' mutation was investigated in 20 cases. In 4 families, one of the parents was not the obligatory heterozygote carrier i.e. did not have a mutation. The results suggest the high incidence of de novo mutation. CONCLUSION: We have identified the frequency of mutations of the CYP21 in Korean AGS patients. Our results shows that the clinical type of AGS can be predicted from the genotypes of CYP21. Also the high incidence of de novo mutation of CYP21 confirmed the genetic instability of major histocompatibility III region where the CYP21 is located.

The Correlation of Plasma Homocysteine and Mitochondrial DNA Content in Peripheral Blood in Healthy Women.: Soo Lim, Won Shik Shin, Kyong Soo Park, Seong Yeon Kim, Jong Ho Lee, Mi Ja Yim, Ji Hyun Song, Hong Kyu Lee; J Korean Endocr Soc. 2000;15(2):248-261. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Hyperhomocysteinemia is an independent risk factor for cardiovascular diseases. Previous reports showed that homocysteine damages mitochondrial gene expression, function and structure. In recent years, homocysteine and mitochondrial DNA (mtDNA) content are reported to relate with insulin resistance. The aim of this study is to investigate the correlation of plasma homocysteine level and mitochondrial DNA content in peripheral blood. METHODS: The mtDNA content, homocysteine and insulin resistance parameters were measured in healthy women (n=60). Plasma homocysteine level was measured by ion-exchange chromatography method and the mtDNA content in peripheral blood was measured by real time PCR method using ABI Prism 7700 machine. RESULTS: Significant correlation was found between homocysteine and mtDNA content (r=-0.507, p<0.05). Homocysteine was correlated with age (r=0.397), cholesterol (r=0.327), LDL-cholesterol (r=0.318), apolipoprotein B (r=0.387), HbA1c (r=0.274) positively and folate (r=-0.262), apolipoprotein A1 (r=-0.293), VO2max (r=-0.332) negatively. Mitochondrial DNA content was correlated with age (r=-0.535), BMI (r=-0.397), cholesterol (r=-0.340), LDL-cholesterol (r=-0.319), apolipoprotein B (r=-0.367) negatively and apolipoprotein A1 (r=0.346), lactate (r=0.307), VO2max (r=0.308) positively. All correlations were statistically significant(p<0.05). CONCLUSION: In this study, plasma homocysteine level was related with mitochondrial DNA content negatively and these two factors are estimated to be concerned with insulin resistance.

IL-10 Plasmid DNA Delivery in NOD Mice for the Prevention of Autoimmune Pancreatic Beta Cell Destruction.: Jae Joon Koh, Kyung Soo Ko, Jong Sang Park, Won Bae Kim, Kyong Soo Park, Seong Yeon Kim, Hong Kyu Lee, San Goo Shin, Sung Wan Kim; J Korean Endocr Soc. 2000;15(2):262-271. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Recently, we have reported that biodegradable poly [-(4-aminobutyl)-L-glycolic acid] (PAGA) can condense and protect plasmid DNA from DNase I. In this study, we investigated whether the systemic administration of pCAGGS mouse IL-10 (mIL-10) expression plasmid complexed with PAGA can reduce the development of insulitis in non-obese diabetic (NOD) mice. METHODS: PAGA/mIL-10 plasmid complexes were stable for more than 60 minutes, but the naked DNA was destroyed within 10 minutes by DNase I. The PAGA/DNA complexes were injected into the tail vein of 3 week-old NOD mice. RESULTS: Serum mIL-10 level peaked at 5 days after injection, could be detected for more than 7 weeks. The prevalence of severe insulitis at 12 week-old NOD mice was markedly reduced by the intravenous injection of PAGA/DNA complex (15.7%) compared to that of naked DNA injection (34.5%) and non-treated controls (90.9%). In conclusion, systemic administration of pCAGGS mIL-10 plasmid/PAGA complexes can reduce the severity of insulitis in NOD mice. CONCLUSION: The study presents the PAGA/DNA complex has the potential for the application of the prevention of autoimmune diabetes mellitus.

The Effect of Sodium Butyrate (SB), Halofuginone Hydrobromide (HH) and High Glucose Concentration on Cell Growth and Gene Expression in Human Aortic Smooth Muscle Cell.: June Ho Park, Sang Jun Lee, Yeo Jun Ki, Young Jung Jeon, Ki Young Kwon, Hong Suk Song, Seung Beom Han, In Kyu Lee, Jung Chul Kim; J Korean Endocr Soc. 2000;15(2):272-285. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Vascular smooth muscle cell (VSMC) proliferation associated with arterial injury causes restenosis, which remains to be resolved in cardiovascular disease, especially after balloon angioplasty. Although numerous factors including hyperglycemia, hyperinsulinemia, angiotensin, basic fibroblast growth factor (BFGF), etc are suggested as potent mitogens for VSMCs, other mechanisms are still needed to take into new consideration. Advances in molecular biology have led to the development of powerful methods for the analysis of differential gene expression. There, we clarified the effect of glucose, sodium butyrate and halofuginon hydrobromide on gene expression which play a role in VSMC growth. METHODS: Therefore, we evaluate the changes of gene expression in response to high glucose concentration, sodium butyrate which is an inhibitor of platelet-derived growth factor (PDGF), and halofuginon hydrobromide which is an inhibitor of specific type 1 collagen, using differntial expressed sequence tag (EST) sequencing and cDNA microarray hybridization. Human mammary artery VSMC isolated from patients undergoing coronary bypass surgery. Cells from passage 3 to 5 were used in experiment with serum-free media with varying conditions. RESULTS: After 6 days of culture, the cells (VSMC) were resuspended with PBS and counted in a hemocytometer, and viable cells were counted using the trypan blue test. VSMC number reached 36?04 cell under high glucose concentration (H/G: 22mM) and 29?04 cell under low glucose concentration(L/G: 5.5 mM) at 6 day of culture (p<0.01). Sodium butyrate(SB) inhibited VSMC growth at varying butyrate concentrations (0.625, 1.25, 2.5, 5.0, 10.0mM) by 84%, 87%, 94%, 96%, 98%, respectively. Halofuginon hydrobromide(HH) also inhibited VSMC growth at varying halofuginon concentrations (10-11, 10-9, 10-7, 10-5mM) by 15%, 30%, 85%, 100%, respectively. Using a differential EST screening technique to assay the relative level of expression of each of large numbers of cloned cDNA sequences after treatment with high glucose concentration (22mM), sodium butyrate (5 mM), and halofuginon (1microM). Among the total 1,730 cDNA clones, 6 cDNA clones were down-regulated after treatment with sodium butyrate (5mM) and halofuginon (1microM). Those were revealed homology to genes encoding connective tissue growth factor (cTGF), Betaig-H3, nm23-H1 nm23-H2, enigma and copine 1. On the contrary, four clones were up-regulated after treatment with high glucose concentration (22mM). Those clones (BO94-5, K1316-5, K1764-5, B1835-5) didn't match any sequence in the public data base. CONCLUSION: These results indicate that this EST analysis is useful technique in targeting genes which are associated with atherosclerosis in VSMC. These identified clones may be used to assist in the positional cloning of genes which are related with atherosclerosis.

A Case of Osteomalacia with Long Term Carbamazepine Therapy.: Hee Soo Kim, Dong Sun Kim, Nak Won Choi, Sang Hyun Baik, Sung Hoon Kim, Chang Beom Lee, Yong Soo Park, Woong Hwan Choi, You Hern Ahn, Tae Hwa Kim; J Korean Endocr Soc. 2000;15(2):286-290. Published online January 1, 2001

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Abstract PDF: Anticonvusant therapy with any of several agents, especially phenytoin, phenobarbital, and primidone causes disturbances in bone mineral metabolism. Anticonvulsants stimulate the hepatic microsomal mixed-oxidase enzymes and hence increase the rate of clearance of vitamin D and its metabolism. The severity of clinical manifestations in any given individual appears to be a function of the combined effects of variety of factors including drug type and total drug dose, dietary vitamin D intake, sunlight exposure, and physical activity level. We report a case of osteomalacia associated with long term carbamazepine therapy in a 21-year-old male with less exposure to sunlight.

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