ABSTRACT
PURPOSE: Coronary arterial lesion assessment in children can be difficult, depending on the coronary dominance pattern. Although it is easier to determine coronary dominance with echocardiography in children than in adults, it is still difficult. This study aimed to examine the coronary dominance pattern according to the objective coronary artery (CA) indices. METHODS: The CA diameter, aortic valve annulus, and abdominal aorta of 69 children without any cardiovascular disease were measured with cross-sectional echocardiography at Chungnam National University Hospital. To evaluate the coronary dominance pattern, echocardiography was primarily used; additionally, coronary computed tomographic angiography or coronary angiography (CAG). Coronary dominance was determined according to the status of the CA that gives rise to the posterior descending artery. RESULTS: The mean age was 4.02±2.78 years, and the mean body surface area (BSA) was 0.70±0.22 m². Right dominance was present in 78% and left in 22% of the subjects. In those with left dominance, the CA to aortic valve annulus diameter ratio was 0.125±0.021 in the right coronary artery (RCA) and 0.255±0.032 in the left coronary artery (LCA). In those with right dominance, the corresponding ratio was 0.168±0.028 in the RCA and 0.216±0.030 in the LCA (P<0.05). Significant differences were also found in the diametric ratios of the CA to BSA and abdominal aorta (P<0.05). CONCLUSION: The CA indices showed significant difference according to the coronary dominance pattern in early childhood. It is possible to indirectly determine the coronary dominance pattern with the CA indices in children using echocardiography. The accuracy of coronary artery lesion diagnosis can be improved by taking coronary dominance into account.
Subject(s)
Adult , Child , Humans , Angiography , Aorta, Abdominal , Aortic Valve , Arteries , Body Surface Area , Cardiovascular Diseases , Coronary Angiography , Coronary Vessels , Diagnosis , Echocardiography , Mucocutaneous Lymph Node SyndromeABSTRACT
PURPOSE: To assess changes in ganglion cell-inner plexiform layer (GCIPL) thickness after cataract surgery using spectral-domain optical coherence tomography (OCT). METHODS: Forty-three eyes of 33 patients, who underwent cataract surgery were imaged with spectral-domain OCT before and after surgery to measure peripapillary retinal nerve fiber layer (RNFL) and GCIPL thickness, signal strength (SS), quadrant, 12 clock-hour RNFL thickness and sectoral GCIPL thickness. RESULTS: The postoperative SS, RNFL and GCIPL thickness were higher than before surgery (p < 0.05). Multivariate analysis showed that endothelial cell count and preoperative SS were significantly correlated with SS changes in RNFL parameters and preoperative SS was significantly correlated with SS changes in GCIPL parameters. Univariate analysis indicated that age was significantly correlated with RNFL thickness changes in RNFL parameters and no factor was correlated with GCIPL thickness in GCIPL parameters (p < 0.05). CONCLUSIONS: Cataracts may decrease peripapillary RNFL and GCIPL thickness measurements and SS on OCT scans. Peripapillary RNFL and GCIPL thickness measurements should be interpreted with caution in eyes with significant cataracts.
Subject(s)
Humans , Cataract , Endothelial Cells , Ganglion Cysts , Multivariate Analysis , Nerve Fibers , Retinaldehyde , Tomography, Optical CoherenceABSTRACT
PURPOSE: The cytotoxicities and anti-fibrotic effects of mitomycin C and pirfenidone on human dermal fibroblast were evaluated. METHODS: Initially, 24-hour cell cultures were exposed to transforming growth factor (TGF)-beta1, different concentrations of mitomycin C, and pirfenidone solutions in order to evaluate cytotoxicity. Expressions of fibronectin, collagen type 1, alpha smooth muscle, and beta-actin were evaluated by real-time reverse transcription-polymerase chain reaction (RT-PCR) and western blot in mitomycin C solutions at concentrations of 4 microg/mL and 20 microg/mL, and in pirfenidone solutions at 250 microg/mL and 500 microg/mL. RESULTS: In comparison to cell cultures exposed to TGF-beta1 solutions, cytotoxicities were increased in solutions of mitomycin C at 4 microg/mL, 20 microg/mL, 40 microg/mL and pirfenidone at 500 microg/mL, 750 microg/mL, 1,000 microg/mL (p < 0.05, Mann Whitney U-test). The results of real-time RT-PCR show that expressions of fibronectin, collagen type 1, and alpha smooth muscle were significantly more decreased in all concentrations of mitomycin C and pirfenidone compared to those in TGF-beta1 solution. In western blot analysis, expressions of fibronectin and alpha smooth muscle were decreased in all concentrations of mitomycin C and pirfenidone compared to TGF-beta1 solution. CONCLUSIONS: Both drugs have cytotoxicities and anti-fibrotic effects, but pirfenidone was found to have less cytotoxicity and mitomycin C was found to have more anti-fibrotic effects when compared to each other.
Subject(s)
Humans , Actins , Blotting, Western , Cell Culture Techniques , Collagen , Fibroblasts , Fibronectins , Mitomycin , Muscle, Smooth , Transforming Growth Factor beta1 , Transforming Growth FactorsABSTRACT
PURPOSE: To assess the reproducibility of circumpapillary retinal nerve fiber layer (cpRNFL) thickness measurement (measurement agreement) and its color-coded classification (classification agreement) by Cirrus spectral domain optical coherence tomography (OCT) in pseudophakic eyes. METHODS: Two-hundred five participants having glaucoma or glaucoma suspected eyes underwent two repeated Cirrus OCT scans to measure cpRNFL thickness (optic disc cube 200 x 200). After classifying participants into three different groups according to their lens status (clear media, cataract, and pseudophakic), values of intra-class coefficient (ICC), coefficient of variance, and test-retest variability were compared between groups for average retinal nerve fiber layer (RNFL) thicknesses and that corresponding to four quadrant maps. Linear weighted kappa coefficients were calculated as indicators of agreement of color code classification in each group. RESULTS: ICC values were all excellent (generally defined as 0.75 to 1.00) for the average and quadrant RNFL thicknesses in all three groups. ICC values of the clear media group tended to be higher than those in the cataract and pseudophakic groups for all quadrants and average thickness. Especially in the superior and nasal quadrants, the ICC value of the cataract group was significantly lower than that of the clear media and pseudophakic groups. For average RNFL thickness, classification agreement (kappa) in three groups did not show a statistically significant difference. For quadrant maps, classification agreement (kappa) in the clear media group was higher than those in the other two groups. CONCLUSIONS: Agreement of cpRNFL measurement and its color code classification between two repeated Cirrus OCT scans in pseudophakic eyes was as good as that in eyes with clear crystalline lens. More studies are required to ascertain the effect of lens status on the reproducibility of Cirrus OCT according to different stages of glaucoma patients.
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Cataract/complications , Cataract Extraction , Glaucoma/complications , Lens, Crystalline/cytology , Nerve Fibers/pathology , Optic Disk/pathology , Pseudophakia/complications , Reproducibility of Results , Retinal Ganglion Cells/pathology , Tomography, Optical Coherence/methodsABSTRACT
PURPOSE: To assess changes in peripapillary retinal nerve fiber layer (RNFL) thickness and optic nerve head parameters after cataract surgery by using spectral-domain optical coherence tomography (OCT). METHODS: Twenty-nine eyes of 26 patients, who underwent cataract surgery, were imaged with spectral-domain OCT before and after surgery to measure peripapillary RNFL thickness and optic nerve head parameters, signal strength (SS), quadrant, 12 clock-hour RNFL thickness, rim area, disc area, cup/disc area ratio, vertical cup/disc ratio, and cup volume. RESULTS: The postoperative RNFL thickness and SS were higher than before surgery (p < 0.05). Regarding optic nerve head parameters, rim area was 0.07 +/- 0.10 mm2 higher than before surgery and disc area, cup/disc area ratio, vertical cup/disc ratio, cup volume were 0.07 +/- 0.15 mm2, 0.04 +/- 0.04, 0.03 +/- 0.05, 0.04 +/- 0.06 mm3, respectively, lower than before surgery (p < 0.05). CONCLUSIONS: Cataracts may decrease peripapillary RNFL thickness measurement and SS on OCT scans and change other optic nerve head parameters. Peripapillary RNFL thickness and optic nerve head parameter measurements should be interpreted with caution in eyes with significant cataracts.
Subject(s)
Humans , Cataract , Eye , Nerve Fibers , Optic Disk , Optic Nerve , Retinaldehyde , Tomography, Optical CoherenceABSTRACT
Protein S is a vitamin K-dependent coagulation factor that acts as an anticoagulant. Deficiency of protein S increases the risk of thromboembolic events. We report a case of isolated protein S deficiency in a 39-year-old woman suffering arterial occlusion in both lower legs. She underwent a surgical procedure using thrombectomy and balloon angioplasty of her left lower extremity. Later, she had right trans-tibial amputation because of the reperfusion injury. Throughout the evaluation of thromboembolic events, we diagnosed a large thrombus in the right atrium and an asymptomatic pulmonary thromboembolism. The patient was successfully treated with right atrial thrombectomy and systemic anticoagulation. Careful evaluation for protein S levels may be necessary in patients with arterial thromboembolic events, especially young adults.
Subject(s)
Adult , Female , Humans , Young Adult , Amputation, Surgical , Angioplasty, Balloon , Blood Coagulation Factors , Heart Atria , Leg , Lower Extremity , Protein S , Protein S Deficiency , Pulmonary Embolism , Reperfusion Injury , Stress, Psychological , Thrombectomy , Thromboembolism , Thrombosis , VitaminsABSTRACT
Protein S is a vitamin K-dependent coagulation factor that acts as an anticoagulant. Deficiency of protein S increases the risk of thromboembolic events. We report a case of isolated protein S deficiency in a 39-year-old woman suffering arterial occlusion in both lower legs. She underwent a surgical procedure using thrombectomy and balloon angioplasty of her left lower extremity. Later, she had right trans-tibial amputation because of the reperfusion injury. Throughout the evaluation of thromboembolic events, we diagnosed a large thrombus in the right atrium and an asymptomatic pulmonary thromboembolism. The patient was successfully treated with right atrial thrombectomy and systemic anticoagulation. Careful evaluation for protein S levels may be necessary in patients with arterial thromboembolic events, especially young adults.
Subject(s)
Adult , Female , Humans , Young Adult , Amputation, Surgical , Angioplasty, Balloon , Blood Coagulation Factors , Heart Atria , Leg , Lower Extremity , Protein S , Protein S Deficiency , Pulmonary Embolism , Reperfusion Injury , Stress, Psychological , Thrombectomy , Thromboembolism , Thrombosis , VitaminsABSTRACT
BACKGROUND: In approach to an adrenal incidentaloma, early exclusion of pheochromocytoma is clinically important, due to the risk of catecholamine crisis. The aims of this study are to investigate the characteristics of incidentally detected pheochromocytomas, compared with that of the other adrenal incidentalomas, and to compare these characteristics with those of symptomatic pheochromocytomas. METHODS: In this retrospective study, we reviewed the medical records of 198 patients with adrenal incidentaloma from 2001 to 2010. We analyzed the clinical, laboratory and radiological data of pheochromocytomas, in comparison with those of the other adrenal incidentalomas. We also compared the characteristics of these incidentally detected pheochromocytomas with the medical records of 28 pathologically proven pheochromocytomas, diagnosed based on typical symptoms. RESULTS: Among the 198 patients with adrenal incidentaloma, nineteen patients were diagnosed with pheochromocytoma. Pheochromocytomas showed larger size and higher Hounsfield unit at precontrast computed tomography (CT) than did non-pheochromocytomas. All pheochromocytomas were larger than 2.0 cm, and the Hounsfield units were 19 or higher in precontrast CT. When both criteria of size > 2.0 cm and Hounsfield unit > 19 were met, the sensitivity and specificity for the diagnosis of pheochromocytoma were 100% and 79.3%, respectively. Compared with patients with pheochromocytoma, diagnosed based on typical symptoms, patients with incidentally detected pheochromocytoma were older, presented less often with hypertension, and showed lower levels of 24-hour urine metanephrine. CONCLUSION: Adrenal incidentaloma with < 2.0 cm in size or < or = 19 Hounsfield units in precontrast CT imaging was less likely to be a pheochromocytoma. Patients with incidentally discovered pheochromocytoma showed lower catecholamine metabolites, compared with those patients with symptomatic pheochromocytoma.
Subject(s)
Humans , Adrenal Gland Neoplasms , Adrenocortical Adenoma , Hypertension , Medical Records , Pheochromocytoma , Retrospective Studies , Sensitivity and SpecificityABSTRACT
PURPOSE: To evaluate the outcome of the part-time occlusion therapy with near activities in monocular amblyopic patients according to gender, age, severity of amblyopia, and the cause of amblyopia. METHODS: Fifty eight patients who were prescribed part-time occlusion therapy with near activity from July 1998 to October 2004, were included in this retrospective study. All patients were divided into groups by gender, age, severity of amblyopia, and the cause of amblyopia. Main outcome measures were best corrected visual acuity, line improvement, and success rate. RESULTS: At the end of patch therapy, visual acuity improved from baseline by an average of 3.2+/-2.5 lines (0.33+/-0.26 log MAR), and follow-up period was 19.71+/-14.61 months (1.62+/-1.20 years). At the last follow-up, visual acuity improved from baseline by an average of 3.7+/-2.4 lines (0.38+/-0.26 log MAR), and follow-up period was 37.41+/-25.83 months (3.08+/-2.12 years). The success rate was 86% (50 patients) at the end of patch therapy. In 44 patients out of 50 patients (88%), the visual acuity was maintained. While 43 patients out of 47 patients who were less than 7 years old (91%) achieved success, 7 patients out of 11 patients 7 years or older (64%) achieved success (p=0.035). CONCLUSIONS: Six-hour part-time occlusion treatment combined with near activities appears to be favorable in treating 58 children during follow-up of mean 3.08 years. The significant factor was the age at initial treatment.
Subject(s)
Child, Preschool , Female , Humans , Male , Activities of Daily Living , Amblyopia/physiopathology , Follow-Up Studies , Retrospective Studies , Sensory Deprivation , Time Factors , Treatment Outcome , Visual Acuity/physiologyABSTRACT
PURPOSE: To evaluate the outcome of the part-time occlusion therapy with near activities in monocular amblyopic patients according to gender, age, severity of amblyopia, and the cause of amblyopia. METHODS: Fifty eight patients who were prescribed part-time occlusion therapy with near activity from July 1998 to October 2004, were included in this retrospective study. All patients were divided into groups by gender, age, severity of amblyopia, and the cause of amblyopia. Main outcome measures were best corrected visual acuity, line improvement, and success rate. RESULTS: At the end of patch therapy, visual acuity improved from baseline by an average of 3.2+/-2.5 lines (0.33+/-0.26 log MAR), and follow-up period was 19.71+/-14.61 months (1.62+/-1.20 years). At the last follow-up, visual acuity improved from baseline by an average of 3.7+/-2.4 lines (0.38+/-0.26 log MAR), and follow-up period was 37.41+/-25.83 months (3.08+/-2.12 years). The success rate was 86% (50 patients) at the end of patch therapy. In 44 patients out of 50 patients (88%), the visual acuity was maintained. While 43 patients out of 47 patients who were less than 7 years old (91%) achieved success, 7 patients out of 11 patients 7 years or older (64%) achieved success (p=0.035). CONCLUSIONS: Six-hour part-time occlusion treatment combined with near activities appears to be favorable in treating 58 children during follow-up of mean 3.08 years. The significant factor was the age at initial treatment.
Subject(s)
Child, Preschool , Female , Humans , Male , Activities of Daily Living , Amblyopia/physiopathology , Follow-Up Studies , Retrospective Studies , Sensory Deprivation , Time Factors , Treatment Outcome , Visual Acuity/physiologyABSTRACT
PURPOSE: To assess the relationship between the retinal thickness analyzer (RTA) parameters, and those of the GDx VCC scanning laser polarimeter (GDx VCC), Stratus OCT optical coherence tomography (Stratus OCT), and Heidelberg retinal tomograph II confocal scanning laser ophthalmoscopy (HRT II). METHODS: Twenty-nine primary open-angle glaucoma patients were retrospectively included in this study. Measurements were obtained using the RTA, GDx VCC, Stratus OCT, and HRT II. We calculated the correlation coefficients between the parameters of RTA and those of the other studies. RESULTS: Among the optic disc parameters of RTA, the cup volume was best correlated with Stratus OCT (R=0.780, p<0.001) and HRT II (R=0.896, p<0.001). Among the posterior pole retinal thickness parameters, the posterior pole abnormally thin area (PPAT) of the RTA and the inferior average of the GDx VCC were best correlated (R=-0.596, p=0.001). The PPAT of the RTA and the inferior maximum of the Stratus OCT were best correlated (R=-0.489, p=0.006). The perifoveal minimum thickness (PFMT) of the RTA and the cup shape measurement of the HRT II were best correlated (R=-0.565, p=0.004). CONCLUSIONS: Many RTA optic disc parameters were significantly correlated with those of the Stratus OCT and HRT II. The RTA posterior pole retinal thickness parameters were significantly correlated with those of the GDx VCC, Stratus OCT and HRT II. The RTA optic disc and posterior pole retinal thickness parameters may be valuable in the diagnosis of glaucoma.
Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Diagnostic Techniques, Ophthalmological , Glaucoma, Open-Angle/diagnosis , Lasers , Ophthalmoscopy , Optic Disk/pathology , Optic Nerve Diseases/diagnosis , Retina/pathology , Retrospective Studies , Tomography, Optical CoherenceABSTRACT
PURPOSE: To compare satisfaction after laser in situ keratomileusis (LASIK) with satisfaction after wavefront guided customized LASIK. METHODS: One hundred fifty-nine patients were included in this randomized, comparative, clinical trial. A myopia-specific Quality of Life Questionnaire was used to evaluate postoperative satisfaction. RESULTS: Overall questionnaire scores improved after both procedures. Wavefront LASIK showed higher satisfaction scores with respect to "Difficulty in visiting others", "Need a lot of help from others", and "Improvement of quality of life". But, most of the questionnaires did not show differences in actual visual satisfaction of daily living. CONCLUSIONS: Conventional and wavefront LASIK improved the visual satisfaction of patients. However, for the most part there was no difference in improvement of daily living between the two procedures.
Subject(s)
Humans , Keratomileusis, Laser In Situ , Patient Satisfaction , Quality of Life , Surveys and QuestionnairesABSTRACT
PURPOSE: The purpose of this study is to find out the diagnostic significance of serum bile acid on total parenteral nutrition induced cholestasis in premature infants. METHODS: Infants without cholestasis were classified into postnatal days and each change of serum bile acid was measured and analyzed. Also, the serum direct bilirubin, serum bile acid, gamma-glutamic acid transferase, and alkaline phosphatase of premature infants with total parenteral nutrition induced cholestasis were measured for comparison and analysis of their correlation. RESULTS: Changes of serum bile acid analysis after birth showed no significant difference between boys and girls, between premature infants and term infants without cholestasis. Serum bile acid levels are constant after two weeks after birth in neonates without cholestasis. In premature infants with total parenteral nutrition induced cholestasis, the increase of serum direct bilirubin over 2 mg/ dL was 34.9+/-18.3 days after birth, and the increase of serum bile acid was 28.1+/-18.3 days. Its increase was about 1 week faster than serum direct bilirubin, however, there was no statistical significance(P=0.114). Comparing analysis of serum bile acid, gamma-glutamic acid transferase, and alkaline phosphatase, serum bile acid showed the highest correlation to serum direct bilirubin(r=0.487, P= 0.000). CONCLUSION: Serum bile acid is an important parameter of total parenteral nutrition induced cholestasis in premature infants and will be useful for early diagnosis and treatment.
Subject(s)
Female , Humans , Infant , Infant, Newborn , Alkaline Phosphatase , Bile , Bilirubin , Cholestasis , Early Diagnosis , Infant, Premature , Parenteral Nutrition, Total , Parturition , TransferasesABSTRACT
Infectious mononucleosis caused by primary infection of Epstein-Barr virus (EBV) is a self-limiting lymphoproliferative disease, and shows concomitant clinical features such as pyrexia, anorexia, sore throat, cervical lymphadenopathy, liver dysfunction and hepatosplenomegaly. In rare cases, EBV establishes a latent infection in B lymphocytes and runs a chronic course and shows infectious mononucleosis-like symptoms repeatedly. This syndrome, named chronic active EBV infection, may trigger an autoimmune disease that mainly affectes the liver and red blood cells, and carries a very poor prognosis. The cardiovascular complications of chronic active EBV infection are very rare and may be associated with coronary arterial disease. This case describes a 5-year-old boy, who developed chronic active EBV infection and was diagnosed as having autoimmune hepatitis with a coronary aneurysm.
Subject(s)
Child, Preschool , Humans , Male , Anorexia , Autoimmune Diseases , B-Lymphocytes , Coronary Aneurysm , Epstein-Barr Virus Infections , Erythrocytes , Fever , Hepatitis , Hepatitis, Autoimmune , Herpesvirus 4, Human , Infectious Mononucleosis , Liver , Liver Diseases , Lymphatic Diseases , Pharyngitis , PrognosisABSTRACT
Torsion of the spleen is a rare cause of abdominal pain in children and it may occur in conjunction with wandering spleen. Wandering spleen is the presence of the spleen in a location other than the left upper quadrant, and it is secondary to the congenital or functional absence of splenic ligaments. The occurrence of wandering spleen is rare in adults and it's even less common in children. The most common presentation is acute abdominal pain, although the signs and symptoms vary widely. Due to the risk of splenic infarction, making a rapid and accurate diagnosis is essential. When a wandering spleen is diagnosed, the treatment of choice is splenopexy, even if the patient is asymptomatic. If splenic necrosis is present, then splenectomy is usually required. We describe here a 4-year-old girl with torsion of a wandering spleen that was managed by splenopexy.
Subject(s)
Adult , Child , Child, Preschool , Female , Humans , Abdominal Pain , Diagnosis , Ligaments , Necrosis , Spleen , Splenectomy , Splenic Infarction , Wandering SpleenABSTRACT
BACKGROUND: To understand the mechanism of aging-related changes of the thyroid, the differentiated functions and growth of thyroid cells in response to TSH were investigated using aged or young thyrocytes. METHODS: FRTL-5 cells, with less than 10 or more than 45 passages, were used. After treatment with 1 U/L TSH or 1-100 mM NaI, the cAMP generation, iodide uptake, cellular proliferation or the expression of NIS mRNA or protein were measured. Sprague-Dawley rats were sacrificed at 5 and 16 weeks and 23 months, and their thyroids used for Northern blot analysis or immunohistochemistry of NIS. RESULTS: There were no differences in cAMP generation, iodide uptake, the proportions of G1/M or S phase, or intracellular DNA contents between the young and aged cells at basel levels. After TSH stimulation, these were increased in dose-dependent manners, with larger increments in the young cells. The changes in the NIS mRNA expression were similar in both the young and aged cells, but to a greater extent in the young cells. A similar phenomenon was observed in rat. However, the amount or intracellular distribution of NIS protein was not different. There was also no difference in the function or expression of NIS after treatment with a high dose of iodide. CONCLUSION: The aging-related decrease in the generation of cAMP might be thought of as one of the mechanisms of the decrement of iodide uptake or cellular proliferation with aging. The decreased expression of NIS mRNA seems to be the most important mechanism for the decreased iodide uptake capacity
Subject(s)
Animals , Rats , Aging , Blotting, Northern , Cell Proliferation , DNA , Immunohistochemistry , Rats, Sprague-Dawley , RNA, Messenger , S Phase , Thyroid GlandABSTRACT
BACKGROUND: Thyroid goiters are very common, however, the mechanism of development is not fully understood. A TSH receptor has been known to activate two different signaling pathways the cAMP/protein kinase A(PKA) and phospholipase C(PLC)/protein kinase C(PKC) systems. However, both systems are limited in the degree to which they explain the discrepancy between a goiter and TSH receptor activation. It has recently been reported that the expression of p66 Shc was increased by TSH stimulation in thyrocytes, suggesting that the p66 Shc molecule may play a critical role in the transition of the TSH-induced growth signals. METHODS AND RESULTS: In this study, we examined the expression of p66 Shc by stimulation of TSH, and the regulatory mechanisms of the TSH-induced expression of the p66 Shc in FRTL-5 cells. In FRTL-5 cells, TSH could increase the expression of the p66 Shc, and the this expression was decreased to basal levels after the removal of TSH. The TSH-induced p66 Shc expression was competitively inhibited by TSH receptor blocking antibodies. The increments of the expression of the p66 Shc protein caused by TSH were both time and concentration dependent, and it was same in the mRNA levels. Cholera toxin increased the expression of the p66 Shc, while pertussis toxin did not. The activators of the cAMP/PKA pathway (8-bromo-cAMP and forskolin) also stimulated the expression of p66 Shc, and the PKA inhibitor H89 decreased the expression, while the inhibition of the PKC pathway by GF109203X, or PMA, affected the expression of p66 Shc very little. CONCLUSION: Our data suggests that p66 Shc may play an important role in regulating the growth of thyrocytes. The TSH receptor - Gs protein - adenylate cyclase - cAMP - PKA pathway mainly mediates the TSH effects on the expression of p66 Shc molecules.
Subject(s)
Adenylyl Cyclases , Antibodies, Blocking , Cholera Toxin , Goiter , Pertussis Toxin , Phospholipases , Phosphotransferases , Receptors, Thyrotropin , RNA, Messenger , Thyroid GlandABSTRACT
BACKGROUND: Iodide has been known to control the function and the growth of the thyroid gland, and to be used as a substrate of thyroid hormone. Moreover, it has been suggested that excessive iodide stimulates the thyroid autoimmune responses. To evaluate the effects of iodide on thyrocytes, we investigated cell function and proliferation, or thyroid autoantigen expression after administering iodide to rats or FRTL-5 cells. MEHTODS AND RESULTS: Ten-weeks-old Sprague-Dawley rats were sacrificed after 7 days of NaI treatment. The expressions of thyroid autoantigens were examined by northern blot analysis. Chronic administration of iodide resulted in no effect on TSH receptor (TSHR) and thyroperoxidase (TPO) mRNA expression, while it increased thyroglobulin (TG) and diminished sodium-iodide symporter (NIS) mRNA expression. FRTL-5 cells were also treated with various concentrations of NaI. The generation of cAMP or iodide uptake was decreased, and the cellular growth was also inhibited by iodide. However, the expressions of all thyroid autoantigens (TSHR, TG, TPO, MHC class I and class II) except NIS were unchanged for 72 hours after iodide administration. The expression of NIS was mildly increased after 24 hours. CONCLUSION: Iodide resulted in decreased cell proliferation and cellular function of cAMP generation and iodide uptake. Chronic administration of iodide increased TG and diminished NIS mRNA expression in vivo but not in vitro
Subject(s)
Animals , Rats , Autoantigens , Autoimmunity , Blotting, Northern , Cell Proliferation , Ion Transport , Rats, Sprague-Dawley , Receptors, Thyrotropin , RNA, Messenger , Thyroglobulin , Thyroid GlandABSTRACT
BACKGROUND: With the prevalence of serum antithyroglobulin(anti-TG) and antithyroperoxidase(anti-TPO) autoantibodies increasing with age, it has been suggested that changes of thyroid autoimmunity with aging are associated with endemic iodine intake. To understand the mechanism of aging-related increases of thyroid autoimmune response, we investigated the expression of thyroid specific autoantigens of aged phenotype, and compared them with those of young phenotype both in vivo and in vitro. METHODS: Sprague-Dawley rats were sacrificed at 5, 10 and 16 weeks(young), and at 23 months(aged). Their FRTL-5 thyroid cells were harvested at cell passages less than 10(fresh) or more than 30 (aged). The expression of thyroid autoantigens, sodium-iodide symporter(NIS), TSH receptor (TSHR), TG and TPO, were examined by northern blot analysis. To evaluate the effects of iodide, 1mM of NaI was added to the medium for 24 hours, and following incubation the expressions of MHC class I and class II were also examined. RESULTS: The expressions of TPO were markedly increased in the aged rats, and those of TG were moderately. However, NIS and TSHR showed no differences in their expression levels between aged rats and young rats. In vitro, there were no differences in the expressions of TG or TPO, nor of NIS or TSHR, between aged cells and fresh cells. Neither did Iodide exhibit any influence on the expression of MHC molecules in aged cells or fresh cells. CONCLUSION: The expression levels of TPO and TG were increased in aged rats, which may partially explain the mechanism of increasing thyroid autoimmunity with age.
Subject(s)
Animals , Rats , Aging , Autoantibodies , Autoantigens , Autoimmunity , Blotting, Northern , Iodine , Phenotype , Prevalence , Rats, Sprague-Dawley , Receptors, Thyrotropin , Thyroglobulin , Thyroid GlandABSTRACT
BACKGROUND: Conventional biochemical screening for family members with hereditary medullary thyroid cancer (MTC) is associated with problems of sensitivity and, specificity and it frequently detects gene carriers only after disease progression. Molecular genetic screening tests that detect germ-line point mutations of the RET proto-oncogene has changed our approach to hereditary MTC. In this study we screened members of a large Korean family that had a history of hereditary MTC by a molecular genetic method and propose a therapeutic approach in managing the disorder. METHODS: Using DNA acquired from peripheral blood leukocytes of the index patient, we performed PCR and direct sequencing of exon 10 of the RET proto-oncogene. PCR-RFLP using an Mbo II restriction enzyme was performed on family members who were at risk of MTC according to the family pedigree. Basal serum calcitonin level was determined in family members who had a point mutation of the RET proto-oncogene and a pentagastrin stimulation test was performed in 3 members. RESULTS: Genetic analysis in the index case revealed a mutation in exon 10, codon 618 of the RET proto-oncogene (TGC to AGC). Out of 28 members who were at risk of MTC, 24 members participated in the screening test. 9 members tested positive for a mutation in the same chromosomal location as the index patient by PCR-RFLP. Basal serum calcitonins were above 100 pg/mL in 2 members. 3 members who had a RET point muatation but a normal basal serum calcitonin level participated in the pentagastrin stimulation test and the results were negative in all members. We found a small medullary thyroid carcinoma that had a diameter of 0.2 cm in a 16 years old boy according to a negative pentagastrin stimulation test and who had received a prophylactic total thyroidectomy. He had no evidence of a lymph node metastasis. CONCLUSION: We detected a germ-line mutation of the RET proto-oncogene in codon 618 of Exon 10 by a molecular genetic method in a family with a hereditary MTC and found 9 members that had a negative history of MTC but had a RET point mutation. There was a very small MTC found in a 16 years old boy who had a normal pentagastrin stimulation test result. Therefore, It is recommended that a prophylactic total thyroidectomy be performed as well as in members that have a mutation of the RET proto-oncogene because MTC can metastasize early in its disease course.'