Endocrinology and Metabolism

Volume 15(4-5); October 2000

Review Articles

What is the Uncoupling Protein?.: Woong Hwan Choi; J Korean Endocr Soc. 2000;15(4-5):453-462. Published online January 1, 2001

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DNA Chip.: Jong Hoon Park; J Korean Endocr Soc. 2000;15(4-5):463-467. Published online January 1, 2001

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Vascular Endocrinology-New Scope of Endocrinology.: Hyung Joon Yoo; J Korean Endocr Soc. 2000;15(4-5):468-478. Published online January 1, 2001

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Editorial

Treatment of Benign Nodular Thyroid disease.: Won Bae Kim; J Korean Endocr Soc. 2000;15(4-5):479-485. Published online January 1, 2001

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Original Articles

Effect of Acute Hyperglycemia - and Isoproterenol - induced Hypothalamic Somatostatin Release on the Thyroid Hormone Releasing Hormone - induced Thyroid Stimulating Hormone Secretion.: Cheol Young Park, In Myung Yang, Seung Joon Oh, Deog Yoon Kim, Jeong Taek Woo, Sung Woon Kim, Jin Woo Kim, Young Seol Kim, Young Kil Choi; J Korean Endocr Soc. 2000;15(4-5):486-492. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Acute hyperglycemia stimulates somatostatin (SRIH) release from the hypothalamus, and which in turn suppress growth hormone (GH) secretion and thyroid stimulating hormone (TSH) from the anterior pituitary gland. Beta-adrenergic pathway is known to stimulate the hypothalamus SRIH release. Recently, We demonstrated that isoproterenol, a beta-adrenergic agonist, had an additional suppressive effect on the suppression by glucose of GHRH-stimulated GH response. Therefore, the present study aimed to determine whether isoproterenol has an additional suppressive effect on the suppression by glucose of TRH-stimulated TSH response. METHODS: Seven healthy young men, aged 24 to 27 years, were studied. Four different TRH stimulation tests were carried out. (Test 1) TRH (Hoechst AG, Germany), 200 microgram bolus, was given intravenously at 0 minute. (Test 2) Glucose, 100 g, was given orally 30 min before TRH administration. (Test 3) Isoproterenol(Isuprel, Sanofi Winthrop, USA), 0.012 pg/kg, was infused continuously for 120 min after TRH administration. (Test 4) After pretreatment with glucose as Test 2, isoproterenol and TRH were administered as Test 3. RESULTS: Oral glucose ingestion significantly suppressed the TRH-stimulated TSH secretion. Isoproterenol infusion significantly suppressed the TRH-stimulated TSH secretion. Glucose-induced suppression of the TSH response was significantly greater than that by isoproterenol. 1soproterenol infusion after glucose pretreatment did not show any additional suppressive effect on the glucose-induced suppression of TSH response to TRH. CONCLUSION: The results suggest that isoproterenol infusion in addition to glucose pretreatment before the TRH stimulation test is not necessary for the development of stronger stimulation test for the hypothalamic somatostatin secretion.

Serum Leptin Levels during Growth Hormone Treatment in Children with Growth Hormone Deficiency.: Jin Hee Oh, Byung Churl Lee; J Korean Endocr Soc. 2000;15(4-5):493-501. Published online January 1, 2001

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Leptin the ob gene product is secreted by adipocytes and binds to specific receptors in the central nervous system regulating energe intake and expenditure. Correlation between fat mass and leptin level is well established. However, data on the hormonal regulation of the leptin in human are scarce. Growth hormone (GH) has lypolytic action and patients with growth hormone deficiency (GHD) have showed higher leptin levels than expected for the obesity We investigated the changes in serum leptin levels and body mass index in children with GHD during GH therapy. METHODS: Thirty children with GHD participated. All subjects were 5~13 years old and in prepubertal stage. The causes of GHD were idiopathic in 15 and organic in 15 children. Patients received GH 0.6.7 IU/kg/week subcutaneously, in 67 divided doses and investigated at baseline and after 6 and 12 months of GH treatment. Serum leptin levels were determined with a human leptin and IGF-1 radioimmunoassay (Linco Research and Nichols Institute, USA). RESULTS: The height velocity was increased significantly after 12 months of GH treatment. Serum leptin concentrations were significantly reduced after 6 and 12 months of treatment but revealed no significant differences in the sex and the causes of GHD. Body mass indices were significantly reduced after treatment. Serum leptin levels positively correlated with body mass index at baseline and after 6 and 12 months of GH treatment. The serum IGF-1 level were increased significantly after GH treatment and did not significantly correlated with leptin levels at baseline and after treatment. CONCLUSION: This study demonstrated that serum leptin and body mass index were decreased with significant positive correlation during GH treatment in children with GHD.

Retroviral - mediated Transduction of Leptin Gene in Genetically Obese Mice.: Young Jun Byun, In Cheol Jeong, Sang Hwan Oh, Moo Youn Cho; J Korean Endocr Soc. 2000;15(4-5):502-512. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Leptin gene is known to be related to obesity in human and animals and complete genetic defect of the gene in ob/ob mouse has been identified. Therefore, ob/ob mouse is widely used as an animal model for the study of etiology and therapy of obesity. The main biological function of leptin was thought to involve in the regulation of food intake and weight gain, however, the regulatory mechanisms by which leptin functions in the weight reduction and lowering the blood glucose level are uncertain. In the present study, retroviral-mediated leptin gene transduction into ob/ob mouse was attempted for the correction of biochemical parameters of obesity. METHODS: Leptin cDNA was inserted into pLXSN retroviral vector (pLXSN-lep) and recombinant leptin expressing retrovirus particles (3 X10 CFU/mL) were produced in psi2 ecotropic packaging cells and subsequent transfection into PA317 amphotropic packaging cells. The leptin expressing recombinant viruses (LER) were transduced into NIH3T3 mouse fibroblasts and insertion of leptin cDNA into chromosomal DNA of PA317 and MH3T3 mouse fibroblasts was confirmed by Southern blot hybridizations. Leptin mRNA and its protein expressed in the cells were identified by Northern blot hybridization and Western blot immunodetection method, respectively. LER were injected I. P. into ob/ob mice, and body weight, food intake, serum leptin level and blood glucose level were measured. RESULTS: Expression of leptin was identified in PA317 and NIH3T3 mouse fibroblasts transduced with LER. Leptin content in sera of mice transfused with LER was drastically increased after 1 week and decreased to the almost basal level at 3 weeks after the transfusion. The body weight as well as food intake of ob/ob mouse transduced by LER decreased for the first 3 weeks and slightly increased thereafter. The reduction of both body weight and food intake in ob/ob mice transduced with LER was observed with the concomitant increase of serum leptin level, indicating that retroviral-mediated transduction of leptin gene in ob/ob mouse in vivo produced a biologically active leptin protein and released it into blood circulation. CONCLUSION: A transient expression of leptin cDNA in ob/ob mice by a retroviral-mediated transduction was performed and further studies are required for long term expression of the gene in vivo.

The Clinical Utility of HBME - 1 Immunostaining in the Diagnosis of Follicular Carcinoma of Thyroid.: Young Goo Shin, Kyi Bum Lee, Yoon Sok Chung, Hyeon Man Kim; J Korean Endocr Soc. 2000;15(4-5):513-521. Published online January 1, 2001

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Currently, in follicular lesion of aspirates of thyroid, pathologic evaluation of surgical specimen is the only diagnostic method whether the patient had follicular thyroid malignancy or not. The aim of this study is the evaluation of the clinical utility of HBME-1 immunostaining in the diagnosis of follicular thyroid malignancy in surgical specimen, and to establish the diagnostic guideline of HBME-1 immunostaining. METHODS: From 1994 to Sep. 1999, the 72 paraffin embedded tissue, which was already diagnosed as thyroid follicular carcinoma or adenoma through the pathologic evaluation of surgical specimen, were studied. Among 72 specimens, the 29 follicular carcinoma were included, and the others were follicular adenoma. The specimens were stained with HBME-1 monoclonal antibody by standard avidin-biotin peroxidase complex methods. One limited pathologist had read the findings of the immunostaining with a basis such as percent of tumor area. These percentage were divided to 4 grade as follows: 1) Grade 0: negative stained, 2) Grade 1: stained area < 30%, 3) Grade 2: 30 < or = stained area < 60%, and 4) Grade 3: stained area > or = 60%. After we had set a basis of follicular carcinoma as more than Grade 2, defined the clinical utility of HBME-1 immunostaining. The clinical utility was based that the concordance rate between pathologic diagnosis and the findings of immunostaining was more than 80% in both groups. RESULTS: 1) There was significant difference between two groups in intensity of cellular staining (p=0.04, x2). But, there might not be helpful to rule out follicular carcinoma of thyroid from adenoma in fine-needle aspirates. 2) In both groups, the percent of stained area of tumor was very diverse from 0% to 100%, and was statistically significant different (p=0.007). 3) Because the only 5 cases of normal tissue in both groups were stained weakly, the HBME-1 immunostaining was like to specific reaction with tumor tissue in both groups. 4) When we had set a basis of follicular thyroid carcinoma as more than Grade 2 (> or = 30%), the concordance rate between pathologic diagnosis and the findings of immuno- staining was 69.7% in follicular adenoma, 65.5% in follicular carcinoma, respectively. CONCLUSION: The HBME-1 immunostaining may not be help to differentiate follicular carcinoma from adenoma.

Enhanced Effect of Iodide - Uptake in Thyroid Carcinoma Cells by Infecting Adenovirus - Human Sodium Iodide Symporter (Ad - hNIS).: Kun Koo Park, Jung Sun Jin, Seong Jin Lee, Jung Yoon Park, Heui Ran Lee, Dae Hyuk Moon, Il Min Ahn, Hye Sook Chang; J Korean Endocr Soc. 2000;15(4-5):522-531. Published online January 1, 2001

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The sodium-iodide-symporter (NIS) is a plasma membrane glycoprotein with 13 putative transmembrane domains, which is responsible for concentrating iodide into the thyroid by an active transport and provides the mechanism for radioactive-iodine (RAI) therapy for thyroid cancer. However, undifferentiated thyroid cancers and about 2050% of differentiated thyroid cancers do not take up the RAI at therapeutic dose. The NIS has been cloned from rat and human (hNIS) and characterized recently. In an attempt to develop a new therapeutic strategy using hNIS gene for improving the efficacy of RAI therapy in thyroid cancers, we have constructed a recombinant adenovirus encoding the hNIS (Ad-hNIS) and tested its function by an iodide uptake by infecting human thyroid cancer cells. METHODS: RT-PCR was performed to measure an intrinsic hNIS expression in thyroid cancer cell lines, such as NPA, FRO and ARO. To generate the hNIS adenovirus, hNIS cDNA was isolated and ligated into Swa I site of cosmid shuttle vector (pAxCAwt). We have produced recombinant adenovirus by co-transfecting the cosmid with DNA-TPC to 293 cell line. Adenovirus that express (beta-Galactosidase (LacZ) was also prepared by the similar strategy. Adenovirus infection efficiency was measured in three thyroid cancer cell lines. Finally, 24 hours after infection of ad-hNIS into the cells, I125-uptake was measured. RESULTS: Endogenous hNIS expression was detected only in FRO cells but not in NPA, ARO and Hela cells by RT-PCR. X-Gal staining after infection of Ad-LacZ to thyroid cancer cell (NPA, ARO, FRO) showed that an infection rate in ARO cells was 98.5+0.5%, 97.0+0.2% in FRO cells and 75.5+5.0% in NPA cells. We selected ARO cells for the infection of Ad-hNIS due to the highest infection efficiency and the absence of endogenous hNIS expression. When ARO cells were infected with the ad-hNIS, I125 uptake was increased 504+6.4%. CONCLUSION: Overexpression of hNIS gene in thyroid cancer cells elicited over 5 fold increase in I-uptake, suggesting that the Ad-hNIS infection to the thyroid cancer cells may improve the efficiency of radioactive iodine therapy.

The Efficacy of Thyroxine Suppression Therapy in Benign Thyroid Nodules.: Seog Ki Yun, Chul Hee Kim, Young Sun Kim, Dong Won Byun, Kyo Il Suh, Myung Hi Yoo; J Korean Endocr Soc. 2000;15(4-5):532-541. Published online January 1, 2001

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Benign pathologic findings are shown in 800% of thyroid nodules by fine needle aspiration cytology (FNAC) or needle biopsy. About half of these benign nodules are follicular lesions which are presented only as thyroid follicles or thyroid cell clumps. Differential diagnosis of follicular adenoma, follicular carcinoma and adenomatous goiter is impossible by FNAC or needle biopsy. Thyroxine suppression therapy has been performed traditionally in order to discriminate malignant nodules, but few studies are available which confirmed the efficacy of thyroxine suppression therapy in thyroid nodules of those the initial pathologic findings were follicular lesions. So we tried to evaluate the efficacy of thyroxine suppression therapy in benign thyroid nodules and also the incidence of thyroid cancer of the thyroid nosules which were not decreased on thyroxine suppression therapy after surgical resection. METHODS: Total 1027 patients with thyroid nodules were evaluated by FNAC or needle biopsy at Soonchunhyang university hospital from 1990 to 1996. Among 1027 patients, 507 patients showed follicular lesions in FNAC or needle biopsy and they received thyroxine suppression therapy. Thyroid nodule volume was measured before and after thyroxine suppression therapy using ultrasonography. We studied 184 patients who were followed up for more than 1 year. Serial changes of thyroid function tests, thyroid nodule volume, serum thyroglubulin (Tg) level before and after therapy were analyzed. RESULTS: l. In 80 (43.5%) of the 184 patients, nodule volumes decreased more than 50 percent after thyroxine suppression therapy. 2. There was no significant difference in serum T3, T4, TSH levels before and after thyroxine suppression therapy between group I (nodule volume decreased less than 50%) and group II (nodule volume decreased more than 50%). 3. In group II patients, thyroid nodule volumes were decreased continuously at 12 month, 18 month and 30 month after thyroxine suppression (p<0.05). 4. There was no significant difference between the group I and group II in the frequency of multiple thyroid nodules on ultrasonography. 5. Among 37 patients who underwent thyroidectomy, 19 cases (51.4%) were revealed as malignant thyroid nodules (papillary cancer 4 cases, follicular cancer 15 cases). Eighteen cases (48.6%) were revealed as benign thyroid nodules (follicular adenoma 10 cases, adenomatous goiter 8 cases). 6. There was no significant difference in the frequency of multiple nodules on ultrasonography between benign and malignant nodules. CONCLUSION: Our data suggested thyroxine suppression therapy was effective in discriminating malignant thyroid nodules from benign nodules, especially in selecting follicular carcinoma from follicular lesion by FNAC or biopsy.

The Role of Preoperative and Postoperative Thyroglobulin Measurements in The Detection of Well Differentiated Thyroid Carcinomas Recurrence.: Seong Jin Lee, Jong Chul Won, Ha Young Kim, Jung Hee Han, Eun Ju Lee, Sang Wook Kim, Jin Sook Ryu, Dae Hyuk Moon, Suk Joon Hong, Il Min Ahn; J Korean Endocr Soc. 2000;15(4-5):542-553. Published online January 1, 2001

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Thyroglobulin (Tg) measurement is primarily used to monitor patients with well differentiated thyroid carcinomas (WDTC) for tumor recurrence. We evaluated the correlations between fold responses of thyroglobulin levels and TNM stages (and MACIS scores) at recurrent group. Also correlations between preoperative Tg levels and Tg (on or off replacement) levels at the time of recurrence were evaluated. Postoperative Tg levels between recurrent and non-recurrent groups were analyzed for the use of assessing risk of recurrence. METHODS: One hundred twenty five cases of WDTC who had total thyroidectomy and (131)I remnant thyroid ablation were finally included in this study. After optimal TSH stimulations (>30 microIU/mL), (131)I whole body scan (WBS) was performed. We interpreted as a recurrence only when abnormal findings on the (131)I WBS were detected. Preoperative, immediate postoperative and follow-up Tg tlevels were regularly measured. RESULTS: Difference of preoperative Tg levels between recurrent and non-recurrent groups was not significant (27.5+/-4.2 ng/mL vs. 16.0+/-10.9 ng/mL). Also differences of immediate postoperative Tg (on or off replacement) levels between two groups was not significant (2.4+/-3.8 ng/mL vs. 3.6+/-3.l ng/mL, 33.4+/-4.8 ng/ml vs. 24.5+/-4.8 ng/mL, respectively). Tg levels on replacement at 24 months after surgery between recurrent and non-recurrent groups were significantly different (2.2+/-4.8 ng/mL, 15.9+/-6.5 ng/mL, p<0.001) and also Tg levels off replacement between recurrent and non-recurrent groups were significantly different (4.0+/-6.6ng/mL vs. 49.4+/-9.3 ng/mL, p<0.001). Fold responses between recurrent and non-recurrent groups were significantly different (2.0+/-3.1 ng/mL, 5.0+/-4.1 ng/mL, p=0.009). Fold responses between recurrent and non- recurrent groups were significantly different according to TNM stages (p=0.002) but not different according to MACIS scores. Preoperative Tg levels were correlated Tg (on or off replacement) levels at the time of recurrence (p=0.02, r=0.4: p<0.001, r=0.6, respectively). Sensitivity, specificity, accuracy of Tg levels over 2 ng/mL on replacement were 95%, 73%, 84% but those of Tg levels over 7 ng/mL off replacement were 83%, 70%, 77%. CONCLUSION: Fold responses may predict prognosis of WDTC. Small postoperative increase in serum Tg levels may indicate a large increase of tumor mass in cases of normal or low preoperative Tg levels. Tg levels over 2 ng/mL on replacement or 7 ng/mL off replacement during follow-up may suggest the recurrence of WDTC.

Hepatic Injury during Treatment with Antithyroid Drugs in Patients with Hyperthyroidism.: Ki Young Lee, Yun Jeong Lee, Soon Hong Hong, Sung Kwoen Jung, Hwa Eun Lee, Chan Jong Seo, Yon Sil Jung, Sung Kwang Lee, Hong Kyu Kim, Hye Young Park, Moon Ho Kang; J Korean Endocr Soc. 2000;15(4-5):554-560. Published online January 1, 2001

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Propylthiouracil (PIV) and methimazole (MMI) were widely used for the treatment of hyperthyroidism. Hepatic injury caused by these agents is a rare but serious complication. This study is to investigate the clinical features of hepatotoxicity from antithyroid drugs. METHODS: We reviewed 17 cases of hepatic injury during treatment with antithyroid drugs in patients with hyperthyroidism. Included were 6 cases we experienced and 11 cases reported in Korean literature from 1986 to 1999. We analyzed the clinical features of hepatic injury. RESULTS: Of 17 cases of hepatic injury, 12 were PTU cases and 5 MMI cases. The mean age of PTU cases was 40 years with 6/12 patients over 40 years old and 2/5 MMI cases were over 40 years old. The dose of PTU was 300 mg/d or more in 10/12 cases (83%) and the dose of MMI was 30 mg/d in 3/5 cases (60%). The hepatic injury occurred within 3 months in 8/12 PTU cases (67%) and within 2 months in 4/5 MMI cases (80%). The duration of hepatic injury tended to be longer in MMI cases than in PTV cases (median; 80 vs 41 days, p=0.102). In PTU cases, the duration of hepatic injury was correlated with the duration of drug use before hepatic injury (p<0.05). All of 8 biopsied cases who took PTU had predominantly hepatocellular necrosis. Two biopsied cases who took MMI had cholestatic jaundice and nonspecific abnormality, respectively. Biochemical findings of all MMI cases were compatible with cholestatic jaundice. As to the treatment of hyperthyroidism after hepatic injury, 4/12 PTU cases were treated with RAI therapy, 5 with MMI and one with surgery, and treatment was unknown in two. On the other hand 3/5 MMI cases interestingly entered into spontaneous remission after hepatic injury and 2/5 had RAI therapy. Hepatic dysfunction recurred in each one whom treatment by changing to MMI or PTU was tried on. CONCLUSION: Most of hepatic injury during treatment with antithyroid drugs developed within two to three months of drug use. The hepatic injury related to PTU was mainly cytotoxic whereas that related to MMI was cholestatic. Since there is a cross-reaction between PTU and MMI in hepatotoxicity, RAI therapy or operation shoud be considered as an alternative treatment of hyperthyroidism after hepatic injury.

The Effect of Bone Marrow Transplantation on Bone Mineral Metabolism: 2 - Year Prospective Study.: Won Young Lee, Moo Il Kang, Eun Sook Oh, Ki Won Oh, Je Ho Han, 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; J Korean Endocr Soc. 2000;15(4-5):561-570. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Loss of bone mass is usually detected after bone marrow transplantation (BMT), especially during the early post-transplant period. But little is known about the long-term effects of BMT on bone mineral metabolism. METHODS: We have investigated prospectively 12 patients undergoing BMT (4 autologous, 8 allogeneic) for hematologic diseases (8 leukemia, 3 SAA, 1 MDS). Serum concentrations of calcium, phosphorus, creatinine, gonadotropins, sex hormones and bone turnover markers (osteocalcin and ICTP) were measured. The samples were collected before BMT and 1, 2, 3, 4, and 12 weeks, 6 months and 1, 2 years thereafter. Bone mineral density (BMD) was measured with DEXA (Dual Energy X-ray Absorptiometry) before BMT, 1 year and 2 year after BMT. In patients with amenorrbea, hormone replacement therapy was started from around 1 year after BMT RESULTS: 1. The mean bone loss in the lumbar spine, calculated as the percent change from the baseline to the level at 1 year and 2 year was 7.3% and 1.9%, respectively. The mean bone loss in the total proximal femur from the baseline to the level at 1 year and 2 year was 8.0% and 8.3% respectively. 2. The serum ICTP increased progressively until four weeks after BMT. Thereafter, it decreased gradually to reach basal values after one year and thereafter no more change until 2 year. Serum osteocalcin decreased progressively until three weeks after BMT. After that, it increased and reached basal values after 3 months. Osteocalcin increased at 6 month transiently but thereafter, it decreased to the level of slightly above basal value at 2 year. 3. Patients who were treated with TBI or pateints with GVHD had a tendency of lower BMD at l year and 2 year after BMT than those of patients without TBI or GVHD. 4. Eight out of nine women went into a menopausal state immediately after BMT and remained amenorrhea, evidenced by high gonadotropins and low estradiol levels. In contrast to women, gonadotropins and testosterone levels were not changed significantly in men after BMT. CONCLUSION: The rapid impairment of bone formation and the increase in bone resorption, as shown by the biochemical markers in this study, might play a role in bone loss after BMT. The efficacy of HRT for the correction of hypogonadism and bone loss was evidenced by 2 year BMD which was much more increased compared to 1 year BMD, especially in vertebra.

The Effect of Hematopoietic Stem Cell Transplantation in the Origin and the Osteoblastic Differentiation of the Human Bone Marrow Stromal Cell.: Moo Il Kang, Seong Won Cho, Eun Sook Oh, Ki Hyun Baik, Won Young Lee, Ki Won Oh, Hye Soo Kim, Je Ho Han, Kun Ho Yoon, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang, Choon Choo Kim; J Korean Endocr Soc. 2000;15(4-5):571-581. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Bone marrow transplantation is the treatment of choice for patients with certain- hematological malignancies, many of whom will survive many years thereafter. Bone disease is a potential longterm complication. But, little is known about the effects of bone marrow transplantation on bone. METHODS: In this study, bone marrow was obtained from healthy donor and transplant recipients. Then mononuclear cells including marrow stromal cells were isolated and cultured. At near confluence, bone marrow stromal cells were subcultured. Thereafter alkaline phosphatase activities of each group were measured by time course of secondary culture. We also analysed the origin of marrow stromal cells by the polymerase chain reaction using YNZ 22 minisatellite probe. RESULTS: l. Cells cultured in our system showed the characteristics of marrow stromal cells differentiated to osteoblasts. They were in fibroblast-like spindle shape and positive to alkaline pbosphatase histochemistry and Von Kossa histochemistry in secondary cultures. 2. The time required for the near confluence in the primary culture was 15 days and 22.9 days on the average in healthy donors and transplant recipients, respectively (p=0.003). 3. In secondary cultures, healthy donors and transplant recipients showed peak alkaline phosphatase activity at 10 days and 17 days, respectively (p=0.031). Alkaline phosphatase activity was lower in BMT recipients than in healthy donors during the whole period of secondary cultures. 4. In polymerase chain reaction analysis using YNZ 22 minisatellite probe, bone marrow stromal cells were of recipient origin. CONCLUSION: Recipient-derived bone marrow stromal cells may be damaged secondary to the effect of chemotherapy, glucocorticoid & total body irradiation which have given before bone marrow transplantation. So it may affect the differentiation of bone marrow stromal cells into the osteoblasts.

The Effects of Type 1 diabetes on the Metabolism and Density of Bone in Children.: Sang Jun Lee, Dong Wook Lee, Hyun Dae Yoon, Kyu Chang Won, Hyoung Woo Lee, Yoon Jung Cho, Heung Sik Kim, Seung Beom Han, In Kyu Lee, Hee Ja Lee; J Korean Endocr Soc. 2000;15(4-5):582-590. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The effects of type 1 diabetes mellitus on the metabolism and density of bone in children are still controversial. The aim of this study was to evaluate the effects of type 1 diabetes on markers of bone metaboism and BMD in children by analyzing BMI, HbA1c, biochemical markers, sex hormones, bone metabolism and BMD related factors. MRTHODS: We compared 36 patients (15 males, 21 females) with type 1 diabetes mellitus to 167 healthy children (84 males, 83 females) who lived in Taegu. We measured FBS, serum calcium, phosphorus, HbA1c, osteocalcin, testosterone and estradiol for analyzing the factors which influence on bone metabolism and BMD. BMD was measured at lumbar spine, femur and total body by DEXA. RESULTS: The BMI and serum level of osteocalcin were not different in both groups. Serum calcium level was significantly lower in the diabetic group than that of control group. BMD had no difference in both groups. There was no correlation between BMD and glycemic control (HbA1c) or duration of diabetes. There was good correlation (r=0.78, p<0.01) between serum testosterone level and BMD in male patient group. There was negative correlation (r=-0.4) between serum osteocalcin level and BMD. There was significant correlation (male: r=0.76, female: r=0.66) between lean body mass and BMD in both group. CONCLUSION: The BMD was not decreased significantly and bone turn-over was normal in children with noncomplicated type 1 diabetes mellitus, and BMD was not influenced by the duration or degree of metabolic control of diabetes. But, we need further study including other risk factors that have influences on BMD and bone metabolism in type 1 diabetes mellitu.

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