ABSTRACT
BACKGROUND: Gamma-interferon (gamma-IFN) is known to suppress thyroperoxidase (TPO), thyroglobulin (Tg), thyrotropin receptor (TSHR) mRNA expression via unclarified mechanism. Thyroid transcription factor-1 (TTF-1) is a nuclear protein involved in the maximal expression and tissue specific expression of thyroid-specific antigens (TPO, Tg, TSHR, NIS) in thyrocytes. Although It's plausible that gamam-IFN induced suppression of thyroid-specific antigen expression may be mediated by decrease of TTF-1 expression, such an effect has not been documented yet. In this study we investigated the effect of gamma-IFN on the expression of TTF-1 in the rat thyroid cell, FRTL-5, and determined whether such an effect is mediated by sclass 2 transactivator (CIITA). METHEODS: The mRNA expression of TTF-1 was quantitated by northern blot analysis after treatment of gamma-IFN, and after expression of CIITA in FRTL-5 cells. Four different promoter constructs were made by cloning into the pRSV-luciferase vector, each contained 5'flanking sequence of different lengths (-5.18 kb, -4.11 kb, -1.94 kb, -1.15 kb) of rat TTF-1 gene. Effects of gamma-IFN and CIITA on promoter activities were analyzed by luciferase assay in FRTL-5 cells into which each promoter construct had been transfected by DEAE-dextran method. RESULTS: Steady state TTF-1 mRNA level at 48 h after gamma-IFN treatment (100 U/mL) was significantly decreased from that of the pre-treatment level (1.65+/-0.16 vs. unit, p<0.05). In all 4 promoter constructs gamma-IFN significantly suppressed promoter activities compared to the vector only transfected cells. CIITA expression in FRTL-5 cells significantly decreased the steady state TTF-1 mRNA level when compared to that in mock-transfected cells (1.69+/-0.31 vs. 1.17+/-0.44 arbitrary unit, p<0.05). CIITA expression in FRTL-5 cells caused suppression of promoter activities in -5.18 kb and -4.11 kb constructs, but had no effects on those activities in -1.94 kb; and -1.15 kb constructs. CONCLUSION: gamma-IFN, directly and indirectly via CIITA expression, suppressed the transcription of TTF-1 gene in the FRTL-5 cells. It may be one of the mechanisms involved in the gamma-IFN-induced suppression of thyroid-specific protein expressions in thyrocytes 1.25+/-0.27 arbitrary
Subject(s)
Animals , Rats , Blotting, Northern , Clone Cells , Cloning, Organism , DEAE-Dextran , Interferon-gamma , Luciferases , Nuclear Proteins , Receptors, Thyrotropin , RNA, Messenger , Thyroglobulin , Thyroid Gland , Trans-ActivatorsABSTRACT
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.
Subject(s)
Animals , Mice , Deoxyribonuclease I , Diabetes Mellitus, Type 1 , DNA , Genetic Therapy , Injections, Intravenous , Insulin-Secreting Cells , Interleukin-10 , Mice, Inbred NOD , Plasmids , Prevalence , VeinsABSTRACT
OBJECTIVES: To compare the prevalence and metabolic profiles of glucose tolerance categories according to World Health Organization(WHO) and 1997 American Diabetes Association(ADA) fasting criteria for the diagnosis of diabetes mellitus and impaired glucose metabolism in the Korean population. METHODS: 2251 subjects without previous history of diabetes, who participated in the Yonchon diabetes epidemiology survey in 1993, were classified according to both criteria. The prevalence of glucose tolerance categories and the agreement across all categories of glucose tolerance were calculated. Metabolic characteristics of different glucose tolerance categories were compared. RESULTS: The prevalence of diabetes and impaired fasting glucose(IFG) according to ADA fasting criteria was similar to those of diabetes and impaired glucose tolerance(IGT) according to WHO criteria, respectively. However, 35.5+ACU- of the subjects who were diagnosed as diabetes by WHO criteria were reclassified as either IFG or normal fasting glucose (NFG), and 38.5+ACU- of diabetic patients according to ADA fasting criteria were IGT or normal glucose tolerance (NGT) by WHO criteria. Only 31.3+ACU- of IGT subjects remained as IFG and 62.1+ACU- were reclassified as NFG. Similarly, 69.4+ACU- of IFG subjects were NGT by WHO criteria. The agreement between the two criteria was poor (K +AD0- 0.31). Discordant diabetes groups had higher WHR, systolic and diastolic blood pressure, cholesterol and triglyceride levels than concordant non-diabetes group. Non-diabetes(WHO)/diabetes(ADA) group had higher WHR than diabetes (WHO)/non-diabetes(ADA) group. There were no differences in other metabolic characteristics between the two discordant diabetes groups. IGT/NFG and NGT/IFG group showed higher BMI, WHR, systolic and diastolic blood pressure, cholesterol and triglyceride levels than NGT/NFG group. Metabolic characteristics of IGT/NFG group were not different from those of NGT/IFG group except IGT/NFG subjects were older than NGT/IFG subjects. CONCLUSION: The agreement between WHO and ADA fasting criteria was poor. ADA fasting criteria can detect new diabetic patients and subjects with impaired glucose metabolism who are not classified as diabetes or IGT by WHO criteria. However, a substantial number of subjects, who may have increased cardiovascular risk and/or increased risk for the development of diabetes and its complication, will be missed when using ADA fasting criteria.
Subject(s)
Adult , Aged , Female , Humans , Male , Blood Glucose , Comparative Study , Diabetes Mellitus/metabolism , Diabetes Mellitus , Diabetes Mellitus , Glucose Tolerance Test , Korea/epidemiology , Middle Aged , Population Surveillance , Prevalence , Probability , Reproducibility of Results , Sensitivity and Specificity , United States , Voluntary Health Agencies , World Health OrganizationABSTRACT
BACKGROUND: Although serum thyroglobulin (Tg) has been proved to be a good tumor marker in the follow-up of the well differentiated thyroid cancer, some patients show low detectable Tg with negative 131I scan. In the present study, we tried to determine the lowest level of serum Tg which suggests requirement of aggressive work-up for the recurrent or metastatic thyroid cancer. METHODS: Serum Tg levels were measured in 102 patients with well differentiated thyroid cancer who had underwent thyroidectomy followed by 131I ablative therapy. Of 102 patients, 44 patients had no remnant thyroid tissue, while 58 patients had remnant thyroid. Serum Tg levels were measured while TSH-suppressive dose of T4 was administered (on T4 therapy) and then T4 was discontinued for 4 weeks to increase serum TSH level (off T4 therapy), then serum Tg levels were analyzed in relation to the presence or absence of recurrent or metastatic thyroid cancer, assessed by I scan and operation with reference to the physical examination, chest X-ray and thyroid ultrasonogram. RESULTS: Of 102 patients, 16 patients were found to have recurrent or matastatic thyroid cancer. Among them, 10 patients didnt have any remnant thyroid, while 6 patients had remnant thyroid. Serum Tg was undetectable on T4 therapy in 6 patients, but rose higher than 30 ng/mL off T4 therapy in 2 patients, while Tg remained undetectable in other 4 patients. In all 10 patients whoseTg levels were higher than 1 ng/mL. on T4 therapy, Tg rose higher than 30 ng/mL off T4 therapy. The best cut-off value of serum Tg which suggests recurrent or metastatic disease in patients without remnant thyroid was 3 ng/mL on T therapy (sensitivity 60%, specificity 91%, accuracy 84%) and 30 ng/mL off T4 therapy (sensitivity 80%, specificity 75%, accuracy 77%). In patients with remnant thyroid, cut-off value of serum Tg could not be determined because of the low sensitivity and specificity. CONCLUSION: In patients with well differentiated thyroid cancer who have no remnant thyroid, serum Tg level lower than 3 ng/mL on T4 therapy can warrant following-up of patients only with such clinical measures only such as physical examination and thyroid ultrasonogram. However, patients with Tg level of 3 ng/mL or more requires Tg measurements off T4 therapy and 131I scan to evaluate the possibility of recurrent or metastatic thyroid cancer.
Subject(s)
Humans , Follow-Up Studies , Physical Examination , Sensitivity and Specificity , Thorax , Thyroglobulin , Thyroid Gland , Thyroid Neoplasms , Thyroidectomy , UltrasonographyABSTRACT
No abstract available.