Vitamin D maintains E-cadherin intercellular junctions by downregulating MMP-9 production in human gingival keratinocytes treated by TNF-α

PURPOSE: Despite the well-known anti-inflammatory effects of vitamin D in periodontal health, its mechanism has not been fully elucidated. In the present study, the effect of vitamin D on strengthening E-cadherin junctions (ECJs) was explored in human gingival keratinocytes (HGKs). ECJs are the major type of intercellular junction within the junctional epithelium, where loose intercellular junctions develop and microbial invasion primarily occurs. METHODS: HOK-16B cells, an immortalized normal human gingival cell line, were used for the study. To mimic the inflammatory environment, cells were treated with tumor necrosis factor-alpha (TNF-α). Matrix metalloproteinases (MMPs) in the culture medium were assessed by an MMP antibody microarray and gelatin zymography. The expression of various molecules was investigated using western blotting. The extent of ECJ development was evaluated by comparing the average relative extent of the ECJs around the periphery of each cell after immunocytochemical E-cadherin staining. Vitamin D receptor (VDR) expression was examined via immunohistochemical analysis. RESULTS: TNF-α downregulated the development of the ECJs of the HGKs. Dissociation of the ECJs by TNF-α was accompanied by the upregulation of MMP-9 production and suppressed by a specific MMP-9 inhibitor, Bay 11-7082. Exogenous MMP-9 decreased the development of ECJs. Vitamin D reduced the production of MMP-9 and attenuated the breakdown of ECJs in the HGKs treated with TNF-α. In addition, vitamin D downregulated TNF-α-induced nuclear factor kappa B (NF-κB) signaling in the HGKs. VDR was expressed in the gingival epithelium, including the junctional epithelium. CONCLUSIONS: These results suggest that vitamin D may avert TNF-α-induced downregulation of the development of ECJs in HGKs by decreasing the production of MMP-9, which was upregulated by TNF-α. Vitamin D may reinforce ECJs by downregulating NF-κB signaling, which is upregulated by TNF-α. Strengthening the epithelial barrier may be a way for vitamin D to protect the periodontium from bacterial invasion.

Substrate roughness induces the development of defective E-cadherin junctions in human gingival keratinocytes

PURPOSE: The entry of bacteria or harmful substances through the epithelial seal of human gingival keratinocytes (HGKs) in the junctional epithelium (JE) is blocked by specialized intercellular junctions such as E-cadherin junctions (ECJs). However, the influence of roughened substrates, which may occur due to apical migration of the JE, root planing, or peri-implantitis, on the development of the ECJs of HGKs remains largely unknown. METHODS: HGKs were cultured on substrates with varying levels of roughness, which were prepared by rubbing hydrophobic polystyrene dishes with silicon carbide papers. The activity of c-Jun N-terminal kinase (JNK) was inhibited with SP600125 or by transfection with JNK short hairpin RNA. The development of intercellular junctions was analyzed using scanning electron microscopy or confocal laser scanning microscopy after immunohistochemical staining of the cells for E-cadherin. The expression level of phospho-JNK was assessed by immunoblotting. RESULTS: HGKs developed tight intercellular junctions devoid of wide intercellular gaps on smooth substrates and on rough substrates with low-nanometer dimensions (average roughness [Ra]=121.3±13.4 nm), although the ECJs of HGKs on rough substrates with low-nanometer dimensions developed later than those of HGKs on smooth substrates. In contrast, HGKs developed short intercellular junctions with wide intercellular gaps on rough substrates with mid- or high-nanometer dimensions (Ra=505.3±115.3 nm, 867.0±168.6 nm). Notably, the stability of the ECJs was low on the rough substrates, as demonstrated by the rapid destruction of the cell junction following calcium depletion. Inhibition of JNK activity promoted ECJ development in HGKs. JNK was closely associated with cortical actin in the regulation of ECJs in HGKs. CONCLUSIONS: These results indicate that on rough substrates with nanometer dimensions, the ECJs of HGKs develop slowly or defectively, and that this effect can be reversed by inhibiting JNK.

Sciatic nerve regeneration using calcium phosphate coated conduit and brain-derived neurotrophic factor gene-transfected schwann cell in rat

PURPOSE OF STUDY: Peripheral nerve regeneration depends on neurotrophism of distal nerve stump, recovery potential of neuron, supporting cell like Schwann cell and neurotrophic factors such as BDNF. Peripheral nerve regeneration can be enhanced by the conduit which connects the both sides of transected nerve. The conduit maintains the effects of neurotrophism and BDNF produced by Schwann cells which can be made by gene therapy. In this study, we tried to enhance the peripheral nerve regeneration by using calcium phosphate coated porous conduit and BDNF-Adenovirus infected Schwann cells in sciatic nerve of rats. MATERIALS AND METHODS: Microporous filter which permits the tissue fluid essential for nerve regeneration and does not permit infiltration of fibroblasts, was made into 2mm diameter and 17mm length conduit. Then it was coated with calcium phosphate to improve the Schwann cell adhesion and survival. The coated filter was evaluated by SEM examination and MTT assay. For effective allogenic Schwann cell culture, dorsal root ganglia of 1-day old rat were extracted and treated with enzyme and antimitotic Ara-C. Human BDNF cDNA was obtained from cDNA library and amplified using PCR. BDNF gene was inserted into adenovirus shuttle vector pAACCMVpARS in which E1 was deleted. We infected the BDNF-Ad into 293 human mammary kidney cell-line and obtained the virus plaque 2 days later. RT-PCR was performed to evaluate the secretion of BDNF in infected Schwann cells. To determine the most optimal m.o.i of BDNF-Ad, we infected the Schwann cells with LacZ adenovirus in 1, 20, 50, 75, 100, 250 m.o.i for 2 hours and stained with beta-galactosidase. Rats(n=24) weighing around 300g were used. Total 14mm sciatic nerve defect was made and connected with calcium phosphate coated conduits. Schwann cells(1x10(6)) or BDNF-Ad infected Schwann cells(1x10(6)) were injected in conduit and only media(MEM) was injected in control group. Twelve weeks after surgery, degree of nerve regeneration was evaluated with gait analysis, electrophysiologic measurements and histomorphometric analysis. RESULTS: 1. Microporous Millipore filter was effective conduit which permitted the adhesion of Schwann cells and inhibited the adhesion of fibroblast. We could enhance the Schwann cell adhesion and survival by coating Millipore filter with calcium phosphate. 2. Schwann cell culture technique using repeated treatment of Ara-C and GDNF was established. The mean number of Schwann cells obtained 1 and 2 weeks after the culture were 1.54+/-4.0*10(6) and 9.66+/-9.6*10(6). 3. The mRNA of BDNF in BDNF-Ad infected Schwann cells was detected using RT-PCR. In Schwann cell 0.69 microgram/microliter of DNA was detected and in BDNF-Adenovirus transfected Schwann cell 0.795 microgram/microliter of DNA was detected. The most effective infection concentration was determined by LacZ Adenovirus and 75 m.o.i was found the most optimal. CONCLUSION: BDNF-Ad transfected Schwann cells successfully regenerated the 14mm nerve gap which was connected with calcium phosphate coated Millipore filter. The BDNF-Ad group showed better results compared with Schwann cells only group and control group in aspect to sciatic function index, electrophysiologic measurements and histomorphometric analysis.

The effect of periodontal flap surgery on Matrix metalloproteinases (MMPs) and Tissue inhibitors of matrix metalloproteinase-1 (TIMP-1) levels in gingival crevicular fluids of periodontitis patients / 대한치주과학회지

No abstract available.

Matrix metalloproteinases and Tissue inhibitors of matrix metalloproteinases in gingival crevicular fluids of periodontitis patients / 대한치주과학회지

No abstract available.

Histomorphometric study on the influence of steroid topical irrigation and implant surface on bone healing in the irradiated rabbit tibia

The purpose of this study was to evaluate and compare the influence of Steroid topical irrigation and implant surface on bone healing in the irradiated rabbit tibia. Implant to bone contact surface ratio and the pattern of bone healing around hydroxyapatite(HA) coated implant and pure titanium (Ti) implant which were inserted into the irradiated rabbit tibia were compared. 16 Korean house mature male rabbits were used as experimental animal. Each rabbit received 15 Gy of irradiation. 4 weeks after the irradiation, two holes were prepared in the irradiated tibia of each rabbits, where two surface type of implants were inserted :1) HA coated type and 2) pure Ti type. Right before placing implants, one group of rabbit received steroid irrigation and the other group did saline. After the irrigation, two implants of HA coated type and pure Ti type were inserted into the tibia of each rabbits. Each rabbit were sacrificed at 2nd, 4th, and 8th week after the implantation and the specimens were observed by the light microscope. The pattern of bone healing and histomorphometric analysis of the implant-bone interface were done. The results were as follows. 1. All implants inserted into the irradiated tibia of rabbit did not show any sign of clinical mobility and the bone around implants inserted into the irradiated tibia of rabbit did not show any resorption. 2. The bone to implant contact surface ratio around HA coated implants that received steroid irrigation got more bone to implant contact surface ratio than that of the saline irrigation. This result showed statistically significant(p<0.05). There was no statistically significant difference in 8th week group. 3. Though there was no statistically significant difference HA coated implants had more bone to implant contact surface ratio than pure Ti implant in 2nd and 4th groups, and there was no difference in 8th week group. 4. All implants inserted into the irradiated tibia of rabbit had exhibited successful osseointegraion.

Development of microporous calcium phosphate coated nerve conduit for peripheral nerve repair

This study was performed to develop a useful nerve conduit which provides favorable environment for Schwann cell viability and proliferation. Milipore membrane of 0.45um pore size was selected because it permits nutritional inflow from the outside of the conduit and prevents from invading the fibrotic tissue into the conduit. The membrane was rolled and sealed to form a conduit of 2mm diameter and 20mm length. To improve the axonal regeneration and to render better environment for endogenous and exogenous Schwann cell behaviour, the microgeometry and surface of conduit was modified by coating with thin film of calcium phosphate. Cellular viability within the conduit and attachment to its wall were assessed with MTT assay and SEM study. Milipore filter conduit showed significantly higher rate of Schwann cell attachment and viability than the culture dish. However, the reverse was true in case of fibroblast. Coating with thin film of low crystalline calcium phosphate made more favorable environment for both cells with minimal change of pore size. These findings means the porous calcium phosphate coated milipore nerve conduit can provide much favorable environment for endogenous Schwann cell proliferation and exogenous ones, which are filled within the conduit for the more advanced strategy of peripheral nerve regeneration, with potential of reducing fibrotic tissue production.

Vascular Endothelial Growth Factor in Cystic Fluid of Degenerative Cysts of Thyroid and Its Significance of Reaccumulation of Cystic Fluid Following Aspiration / 대한내분비외과학회지

PURPOSE: VEGF, a potent angiogenic factor, increases vascular permeability and induces the fluid accumulation in the peritoneal and pleural cavities. This study is designed to know whether the VEGF concentration are associated with the formation of cystic fluid of thyroid nodules and the results of treatment. METHODS: To know whether thyroid follicular cells produce VEGF, we measured the VEGF concentration in the conditioned medium after primary culture of the normal thyroid follicular cells (NT 1.0). Thirty seven patients, who had visited Ajou University Medical Center, were divided into two groups; group A (n=19) is patients whose cystic nodules disappeared completely with 1 or 2 times fine needle aspirations. In Group B (n=18), the cystic nodules recurred rapidly and required aspiration more than 3 times. Clinical records of patients were analyzed and compared with TSH and VEGF levels in cystic fluids. RESULTS: The VEGF concentration in basal conditioned medium were 8.2±1.2 ng/ml in NT 1.0 and 8.2±0.6 ng/ml in thyroid cancer cell line (FTC-133). NT 1.0 was not affected by TSH stimulation. Mean concentration of TSH of all cystic fluids was 4.36µIU/ml (0.13~21.7) and there was no difference between 2 groups. Mean concentration of VEGF of all cystic fluids was 140.7 ng/ml (11.1~688.8). The VEGF concentration (287.9±289.6 ng/ml) in group B was significantly higher than that (104.2±97.1 ng/ml) in group A (P<0.05). CONCLUSION: This study suggests that thyroid follicular cells produce and secrete VEGF, and VEGF is related with the accumulation of cystic fluid in degenerative cysts of thyroid. Cysts with high VEGF concentration promote rapid reaccumulation of the cystic fluid and possibly necessitate operation in selected patients.

Macrophage colony-stimulating factor promotes the survival of osteoclast precursors by up-regulating Bcl-XL

Macrophage colony-stimulating factor (M-CSF) is known as one of the factors essential for osteoclast development. In the present study, we examined effects of M-CSF on the apoptotic pathway of osteoclast precursors and their underlying molecular mechanisms. Osteoclast precursors underwent apoptosis in the absence of M-CSF, even in the presence of receptor activator of NF-kB ligand (RANKL). Active caspase-3 and -9 were detected in the osteoclast precursors and treatments of precursors with their specific inhibitors (Z- DEVD-FMK and Z-LEHD-FMK) decreased the apoptosis. M-CSF decreased apoptosis in a dose-dependent manner with decreasing in active caspases-3 and -9 levels and up-regulating Bcl-XL. Those effects of M-CSF on inhibiting apoptosis of osteoclasts precursor by regulating anti-apoptotic signals was more effective when combined with RANKL. These results demonstrate that M-CSF acts as a survival factor for the osteoclast precursors. Furthermore, it is believed that the apoptosis of osteoclast precursors may be involved in the activation of caspase-9 and that M-CSF may promote their survival through Bcl-XL-induced inhibition of caspase-9 activation.

Effects of TSH on the Production of VEGF, Angiogenesis, Growth, Invasion and Metastasis in Thyroid Cancer Cells / 대한내분비외과학회지

PURPOSE: Vascular endothelial growth factor (VEGF) is a vascular endothelial cell specific mitogen and a major regulator of angiogenesis. VEGF secretion is activated in some thyroid cancers and that VEGF secretion is stimulated by TSH. So we postulated that TSH may promote growth and invasion in some thyroid cancers by stimulating VEGF secretion and angiogenesis. METHODS AND RESULTS: We investigated the TSH effect for the VEGF secretion, endothelial cell proliferation and invasion in vitro with the primary cultured normal thyroid cell (NT-1) and thyroid cancer cell line (TPC-1). And to evaluate the relationship between TSH and VEGF, angiogenesis and tumor growth in vivo, we xenografted human dermal matrix inoculated with thyroid cells into nude mice or directly injected subcutaneously. For the study, mice were made hypothyroid (Group 1) by antithyroid hormone p.o, hyperthyroid (Group 2) by L-thyroxine injection and euthyroid (Group 3). One week after the treatment, significant difference were noted in T3, T4 and TSH level between each group, but the VEGF level showed significant difference in group 1 only compared with group 2 and 3. NT-1 or TPC-1 were seeded in the upper chamber of Transwell and HUVEC were cultured in lower chamber, and added different concentration of TSH. NT-1 and TPC-1 secreted VEGF under basal condition, but the level were similar. TPC-1 cells secreted significantly more VEGF than NT-1 after TSH (1, 10, 100 mIU/dl) stimulation, which were also parallel with the concentration of TSH. In low concentration of TSH (0, 1 mIU/dl), there were no difference of HUVEC proliferation between NT-1 and TPC 1. In high concentration of TSH (10, 100 mIU/dl), however, TPC-1 enhanced HUVEC proliferation than NT-1 significantly (p0.05). The number of blood vessels in tumor were also more increased in Group 1 and were commonly located in the peripheral portion of tumor. CONCLUSION: We conclude that thyroid cancer cell line secrete the VEGF and TSH secretion is more enhanced by the stimulation of TSH. And increased VEGF promote the vascular endothelial cell proliferation, invasion and angiogenesis in thyroid cancer.

Effects of fluoride on osteoclastic bone resorption during experimentally moved rat molars / 대한치과교정학회지

Orthodontic tooth movement requires remodelling of periodontal tissues, especially alveolar bone. Fluoride is known to be a potent inhibitor of osteoclastic bone resorption. The purpose of this study was to examine the effects of a consumption of fluoride on osteoclast numbers appearing on the pressure side of alveolar bones at experimental tooth movement. 40 male rats were exposed to 0, 10, 25 mg/kg/day of sodium fluoride(NaF) in their drinking water for up to 60 days. Orthodontic appliance were activated to mesially tip maxillary first molar with 50-70g. The rats were sacrificed at 1, 2, 4 days after initial activation. The number of osteoclast was counted in a 450 x 700 micrometer2 area interradicular septum on the pressure side of the maxillary first molar. The results were as follows, 1. There was significantly different osteoclast number between control group and 25 mg/kg/day group at all measured time. (p<0.05) 2. There was significantly different active bone-resorption area between control group and 25 mg/kg/day group except at 96 hours post activation. (p<0.05) 3. There was slight reduction of active bone-resorption area in control group from 48 hours to 96 hours but in both 10 mg/kg/day group and 25 mg/kg/day group a slight increase was observed from 48 hours to 96 hours.

Total radical TRapping antioxidant parameter, calculated / 대한내분비학회지

BACKGROUND: It has been suggested that diabetic patients are under high oxidative stress and plasma MDA concentration is a reliable marker for oxidative stress. However, some studies showed that plasma MDA is not a good marker for oxidative stress. Reeently, the total radical-trapping antioxidant parameter (TRAPc) has been proposed as a marker for the overall antioxidant property of plasma samples. Therefore, in this study, we tried to evaluate whether MDA and TRAPc are reliable markers of the oxidative stress-antioxidant system or not. METHODS: The plasma samples from 67 type 2 diabetic patients and 31 normal subjects were collected. The plasma MDA, protein-bound SH groups, uric acid and vitamin C were determined by fluorophotometry or spectrophotometry. Plasma vitamin E concentration was analyzed by HPLC. Calculated TRAP (TRAPc) were determined by the proposed calculation methods. RESULTS: 1. Diabetic patients had significantly lower TRAPc, compared with normal subjects. 2. SH groups, uric acid, vitamin C and vitamin E were not different between the two groups. 3. MDA and MDA/TG were significantly higher in diabetic subjects. CONCLUSION: From the results of this study, TRAPc seems to be a reliable parameter of overall plasma antioxidant system and the plasma MDA may be used as a marker of oxidative stress, but further long-term logitudinal studies are needed.

One Family of Familial Combined hyperlipidemia Associated with Various Metabolic Abnormalities / 대한내분비학회지

Familial combined hyperlipidemia is one af the manogenic disorders frequently found in humans and is seen in 0.5~2% of the general populatian, accounting for at least 10% of persons with pemature atlmmcletusis. The distinguishing feature of familial combined hyperlipidemia, in camparison with other single-gene abnarmalities of lipoprotein metabolism, is that not all affected members have the same plasma lipid phenotype; some individuals have an elevation of cholesterol concentration alane(type IIa lipoprotein pattern), while some athers have an elevation of triglyceride concentration alone(type IV pattem), and still others have elevations of both values(type IIb pattem). In any one persan, the lipid phenotype can change as a result of dietary or drug treatment. Familial combined hyperlipidemia should be suspected in those subjects with moderate hypertriglyceridemia and/or moderate hypercholestaolemia (lipoprotein types IIa, Ilb, IV), especially when premature coronary heart disease is evident in the family histary. Low plasma HDL-cholesterol, obesity, insulin resistance and hyperuricemia are often . Family members affected by familial combined hyperlipidemia should be identified and be treated, since tbe condition is associated with premature caronary heart diasease. We have found one family of familial combined hyperlipidemia with one member(case 1) associated with insulin resistance, hyperuricemia and gout, and another member(case 2) associated with diabetes mellitus and infertiTity.

A Case of Surgically Treated Insulinoma in Pregnancy / 대한내분비학회지

Insuliin secreting tumor is 70% prevalent disease in female and predoadnant in forth and sixth deeade. The incidence of insulinoma is one case per 250,000 patient-years. Insulinoma in pregnancy was extremely rare, and the prevalence was not reported. The diagnosis of an insulinoma is depend on demonstration of hypoglycemia with high insulin and C-peptide levels. Immunoreactive insulin/plasma glucose ratio0.3 in particular support the diagnosis of an insulinoma. Fetal complication would be developed because of hypoglycemia. In approximately half of the cases reported, surgical exploration was done during pregrancy, the remainder were treated after delivery. Insulinoma poses serious diagnostic and therapeutic problems when she is pregnant. We experienced a case of insulinoma in pregnancy that represented Whipples triad and was treated by surgical intervention.

Two Cases with Squamous Cell Carcinoma of the Thyroid Gland / 대한내분비학회지

Primary squamous cell carcinoma of the thyroid is rare, presenting much less than one percent of all primary thyroid malignancies. Most cases have been reported in elderly patients with a history of goiter. It is necessary to differentiate between primary squamous cell carcinoma and secondary involvement from other sites. Secondary involvement of the thyroid may be more amenable to palliation or cure. The treatment of choice in primary squamous cell carcinoma is radical surgery in resectable cases, but the squamous cell carcinoma behaves aggressively and carries a uniformly poor prognosis regardless of the treatment. We had an experience of a primary squamous cell carcinoma of the thyroid in two elderly patients. These patients presented a typical feature of a primary squamous cell carcinoma of the thyroid, which has been rarely reported in Korea.

Three Cases of Primary Hypothyroidism with Down Syndrome in Adult / 대한내분비학회지

Down syndrome is perhaps the most common genetic condition associated with mental retardation. In cytogenetic examination, trisomy 21 is in 95% of Down syndrome, and the others are mosaicism, translocation or deletion. There are many associated diseases with Down syndrome such as, thyroid function abnormality, congenital heart disease, intestinal blockage, and so on. Hypothyroidism appeared in 15% before adolescent in Down syndrome patients. In Korea, there were several reports of Down syndrome with hypothyroidism in childhood but not in adulthood. And we had three cases of hypothyroidism with Down syndrome in adulthood. Cytogenetic examination revealed trisomy 21 in the 2 cases and 1 case of mosaicism. Antithyroid antibody was positive in one case. None of these cases was admitted due to symptoms of hypothyroidism. It is very difficult to make the diagnosis of hypothyroidism in Down syndrome because of similarity in symptoms between Down syndrome and hypothyroidism. Thus, periodic thyroid function test should be made in Down syndrome, and this could be a part of improving quality of life in Down syndrome.

A Case with Multifocal Langerhans Cell Granulomatosis Involving the Thyroid Gland / 대한내분비학회지

Langerhans cell granulomatosis(LCG), previously termed 'Histiocytosis-X', is one of the rare disease. LCG is characterized by proliferation of Langerhans cells in a unifocal or multifocal pattern. And LCG may be manifested in a variety of way, ranging from a spontaneously regressing solitary lesion to a multisystem life-threatening disorder. This disease usually involves the bone, lung, skin and lymph node. The most common endocrinologic abnormalities in LCG are diabetes insipidus and growth hormone deficiency. LCG involving the thyroid gland is extremely rare and only a small numbers of cases have been reported worldwide. A 41-year-old diabetic female visited the hospital due to the neck swelling for 3 months and she also complained of polyuria, polydipsia and easy fatigue. LCG involving multiple organs included thyroid gland was diagnosed by high-resolution CT of lung, by characteristic histological findings of the thyroid lesion and by the immunohistochemical staining for S-100 protein and OKT 6(CD la). She is followed at OPD without any medication.

Impaired Glucose Tolerance Associated with Klinefalter Syndrome / 대한내분비학회지

Klinefelter syndrome is one of the most common forms of primary hypogonadism and infertility in males. It is a clinical syndrome consisting of gynecomastia, azoospermia, and increased urinary excretion of follicle-stimulating hormone. Fequency of diabetes mellitus, emphysema, asthma, breast cancer increase in Klinefelter syndrome. We report a 16-year-old male patient with impaired glucose tolerance in association with Klinefelter syndrome, which was confirmed by chromosome analysis. The mechanism of impaired glucose tolerance in this patient was peripheral insulin resistance which clarified by euglycemic hyperinsulinemic clamp test.

Antibody-dependent Cell-mediated Cytotoxitity as a Prognostic Indicator in the Medical Treatment of Graves' Disease / 대한내분비학회지

BACKGROUND: The several forms of treatment of Graves disease-thyroidectomy, antithyroid drugs and radioiodide therapy-are in wide use now. But which therapy is best is a matter of debate. Some authors reported that in patients who underwent thyroidectomy, higher titers of serum antimicrosomal antibody were associated with 1) higher formation rates of germinal centers, 2) more lymphocyte infiltration in the thyroid tissue, 3) higher incidence of hypothyroidism, and 4) lower incidence of recurrence. We were interested in the relationship of thyroid autoantibody titers, ADCC(antibody-dependent cell-mediated cytotoxicity) activity and the clinical response to antithyroid medication. METHODS: We measured ADCC activities from patients in Graves disease(n-48), Hashimoto thyroiditis(n=17) and normal control(n=9). The patients of Graves disease were followed up for more than 1 year, and they were grouped into A(n=17, well responsed group to antithyroid medication) and B(n=31, poorly responsed group). We examined ADCC activities of patients' sera by chromium release assay. RESULTS: 1) Mean age of patients with Graves disease was 34.4210.4 years and 15 patients were male(31%). 2) Results of thyroid function tests of the Graves' patients were T 585.9 +/- 255.3 ng/dL, T4 21.3 +/- 12.2 mg/dL, TSH 0.11 +/- 0.06mIU/mL. Concentrations of antimicrosomal antibody, antithyroglobulin antibody and thyrotropin binding inhibitory immunoglobulin were 1279.1 +/- 1486.7 IU/mL, 488.1 +/- 751.1 IU/mL, and 38.5 +/- 33.4U/L respectively. 3) There was no significant difference between levels of thyroid hormones or concentrations of thyroid autoantibodies and ADCC activities in graves patients. 4) The ADCC activity of the Graves patient group(24.49%) was significantly higher than that of the normal control group(3.76%), and significantly lower than that of the Hashimotos thyroiditis group(36.34%). 5) There was no significant difference in ADCC activity between group A(18.24 +/- 13.44%) and B(27.91 +20.02%). CONCLUSION: From this results, we suggested that ADCC activity seems to be no value as a prognostic factor in predicting the response to antithyroid drugs in Graves disease patients. But, further studies, larger number of patients and long-term follow up, are needed.

A Case of Methimazole Induced Agranulocytosis Complicated with Deep Neck Abscess / 대한내분비학회지

The thiourea derivatives, propylthiouracil and methimazole are in widespread use for the treatment of hyperthyroidism. The untoward side effects of these drugs are not infrequent and agranulocytosis is the most serious side effect them. We observed one case of methimazole induced agranulocytosis complicated by deep neck abscess. A 54-year-old woman was admitted because of fever, chilling and sore throat for 1 week. The symptom was developed after receiving methimazole 30mg daily day due to hyperthyroidism during last 3 months. Physical examination revealed hyperemic, enlarged tonsils and tender swelling of the right lower neck The peripheral blood total leukoeyte count was 1,500/mm' (absolute neutrophil count, ANC 9) and a peripheral blood smear revealed few neutrophil. The patient was administered G-CSF 2 mg/kg daily, and on the fifth day of hospitalization, fever subsided and ANC increased to 3,431. On the 11th day, fever developed again and the tenderness and swelling in both lower neck area were aggrevated. Computed tomography of the neck was performed, and revealed a large deep neck abscess. After pus aspiration and antibiotics therapy, the neck abscess was disappeared.