Antibacterial and Antibiofilm Activity and Mode of Action of Magainin 2 against Drug-Resistant Acinetobacter baumannii.

Antimicrobial peptides (AMPs) are promising therapeutic agents for treating antibiotic-resistant bacterial infections. Previous studies showed that magainin 2 (isolated from African clawed fogs Xenopus laevis) has antimicrobial activity against gram-positive and gram-negative bacteria. The present study was conducted to investigate the antibacterial activity of magainin 2 against Acinetobacter baumannii. Magainin 2 showed excellent antibacterial activity against A. baumannii strains and high stability at physiological salt concentrations. This peptide was not cytotoxic towards HaCaT cells and showed no hemolytic activity. Biofilm inhibition and elimination were significantly induced in all A. baumannii strains exposed to magainin 2. We confirmed the mechanism of magainin 2 on the bacterial outer and inner membranes. Collectively, these results suggest that magainin 2 is an effective antimicrobial and antibiofilm agent against A. baumannii strains.

Inhibitory effect of snake venom toxin on NF-κB activity prevents human cervical cancer cell growth via increase of death receptor 3 and 5 expression.

We previously found that snake venom toxin inhibits nuclear factor kappa B (NF-κB) activity in several cancer cells. NF-κB is implicated in cancer cell growth and chemoresistance. In our present study, we investigated whether snake venom toxin (SVT) inhibits NF-κB, thereby preventing human cervical cancer cell growth (Ca Ski and C33A). SVT (0-12 µg/ml) inhibited the growth of cervical cancer cells by the induction of apoptotic cell death. These inhibitory effects were associated with the inhibition of NF-κB activity. However, SVT dose dependently increased the expression of death receptors (DRs): DR3, DR5 and DR downstream pro-apoptotic proteins. Exploration of NF-κB inhibitor (Phenylarsine oxide, 0.1 µM) synergistically further increased SVT-induced DR3 and DR5 expressions accompanied with further inhibition of cancer cells growth. Moreover, deletion of DR3 and DR5 by small interfering RNA significantly abolished SVT-induced cell growth inhibitory effects, as well as NF-κB inactivation. Using TNF-related apoptosis-inducing ligand resistance cancer cells (A549 and MCF-7), we also found that SVT enhanced the susceptibility of chemoresistance of these cancer cells through down-regulation of NF-κB, but up-regulation of DR3 and DR5. In vivo study also showed that SVT (0.5 and 1 mg/kg) inhibited tumor growth accompanied with inactivation of NF-κB. Thus, our present study indicates that SVT could be applicable as an anticancer agent for cervical cancer, or as an adjuvant agent for chemoresistant cancer cells.

Diagnostic accuracy of plasma free metanephrines in a seated position compared with 24-hour urinary metanephrines in the investigation of pheochromocytoma.

The aim of this study was to determine the diagnostic efficacy of free metanephrines in plasma samples drawn in the seated position compared with 24-h urinary metanephrines in detecting pheochromocytomas in Asian patients. This prospective study was conducted at Samsung Medical Center between May 2010 and July 2011. The study contained 245 subjects, including 28 patients with histologically-proven pheochromocytoma, 44 with histologically-proven non-pheochromocytoma, 112 controls suspected of having tumors but with negative investigations during two or more years of follow-up, and 45 healthy normotensive volunteers. Plasma-free metanephrines were measured by LC-MS/MS. The cut-off values with optimal sensitivity and specificity for plasma metanephrine and plasma normetanephrine were 0.33 nmol/L and 0.61 nmol/L, respectively. Both the plasma metanephrines measurement and urinary metanephrines measurement had a sensitivity of 96.4% (p = 1.00). However, the urinary metanephrines measurement was significantly more specific than the plasma metanephrines measurement (94.2% vs. 75.6%; p < 0.001). When we applied cut-off values based on BMI, specificity improved from 75.6% to 87.2%, with a comparable gain in sensitivity. From a diagnostic perspective, measurement of free metanephrines in plasma drawn in the seated position is highly sensitive but insufficiently specific when compared with measurement of 24-h urinary fractionated metanephrines. The specificity may be improved by applying cut-off values based on BMI. We suggest that free metanephrines in plasma drawn from seated position can also be used as an initial screening test to ensure that pheochromocytomas are not missed in Asian patients.

Germline mutation of Glu70Lys is highly frequent in Korean patients with von Hippel-Lindau (VHL) disease.

Von Hippel-Lindau (VHL) disease is an inherited tumor syndrome caused by germline mutations in the VHL tumor suppressor gene. It is characterized by hemangioblastoma in the central nervous system and retina, renal cell carcinoma, pancreatic tumor and cysts, and pheochromocytoma. In this study, we detected 26 germline mutations in the VHL gene of Korean patients, of which 1 was a novel mutation, c.417_418insT. We also integrated our data from this study with the published literature to identify 55 VHL germline mutations in Koreans, and identified a unique hotspot at codon 70. Nine unrelated patients (9/55, 16.4%) had the same amino-acid substitution at codon 70 (Glu70Lys) and showed VHL type 1 phenotypes. Although this mutation was shown to have a mild effect on VHL function, four of the nine patients (44.4%) subsequently developed multiple central nervous system hemangioblastomas or retinal hemangioblastoma. However, this hotspot has not been identified in Chinese or Japanese patients. This study provides information on the spectrum of VHL mutations in Korean VHL disease and contributes to a better understanding of VHL disease in terms of improvements in the clinical management of VHL families.

Prognostic implications of radioiodine avidity and serum thyroglobulin in differentiated thyroid carcinoma with distant metastasis.

BACKGROUND: Although differentiated thyroid carcinoma (DTC) rarely develops distant metastases, the present study was performed to evaluate factors that affect the survival of patients with DTC who present with distant metastasis. METHODS: Among 4,989 patients who underwent thyroid surgery for DTC, 82 presenting with distant metastasis were analyzed. Based on radioiodine ((131)I) avidity and the thyroid-stimulating hormone-stimulated serum thyroglobulin (sTg) level at the time of metastasis, patients were divided into three groups: group 1 ((131)I uptake + sTg ≤ 215 ng/mL, n = 46), group 2 ((131)I uptake + sTg > 215 ng/mL, n = 24), group 3 (no (131)I uptake, n = 12). Disease-specific survival (DSS) was estimated using the Kaplan-Meier method. Factors predicting the outcome were evaluated using Cox proportional hazard regression analysis. RESULTS: The age of patients (p = 0.04), frequency of follicular thyroid carcinoma (p = 0.002), tumor size (p < 0.001), and number of multiple metastatic sites (p = 0.004) differed significantly among the groups. With a median follow-up after surgery of 72 months, the 5- and 10-year DSSs for all patients were 84 and 69 %, respectively. The predictors of survival were age (p = 0.004), symptoms at the time of presentation (p = 0.045), histology (p = 0.01), sites of metastasis (p = 0.03), and (131)I avidity and sTg level at the time of metastasis (p = 0.002). In the multivariate analysis, age, histology, and (131)I avidity and sTg level at the time of metastasis remained significant factors for survival. CONCLUSIONS: Certain DTC patients with distant metastasis demonstrate favorable outcomes dependent on age, histology, and (131)I avidity and sTg level at the time of metastasis.

ERK phosphorylation is not increased in papillary thyroid carcinomas with BRAF(V600E) mutation compared to that of corresponding normal thyroid tissues.

BACKGROUND: An association between a BRAF(V600E) mutation and upregulation of mitogen-activated protein kinase (MAPK) pathways in human papillary thyroid carcinoma (PTC) tissues has not been demonstrated well outside of in vitro studies. The aims of this study were to evaluate the activation status of extracellular signal-regulated kinase 1/2 (ERK1/2) in human PTCs with BRAF(V600E) mutations compared to that of corresponding normal thyroid tissue and to determine the expressions of Raf kinase inhibitor protein (RKIP) and MAPK phosphatase 3 (MKP-3), possible regulators of ERK1/2 activation. METHODS: We analyzed the presence of BRAF(V600E) mutation and the expressions of BRAF, total ERK, p-ERK, RKIP, and MKP-3 in 33 PTCs and corresponding normal thyroid gland tissues using western blot analysis. RESULTS: BRAF(V600E) mutation was found in 28 (84.8%) of 33 PTCs, 96.4% (27/28) of which showed decreased p-ERK activity, while 75% (21/28) showed increased MKP-3 expression. There were significant differences in p-ERK and MKP-3 expressions between BRAF(V600E) (+) PTCs and normal thyroid glands (p < 0.001). There were no differences in expressions of BRAF, total ERK, and RKIP between PTCs and normal thyroid tissue, irrespective of the presence of BRAF(V600E) mutation. CONCLUSIONS: In human BRAF(V600E) (+) PTCs, ERK phosphorylation is decreased compared to normal thyroid glands and the observed decrease in ERK1/2 MAPK phosphorylation in BRAF(V600E) (+) PTCs may be associated with increased MKP-3 activity.

Effect of atorvastatin on lipoxygenase pathway-related gene expression in an in vitro model of lipid accumulation in hepatocytes.

Lipid accumulation in hepatocytes can result from an imbalance between lipid acquisition and lipid catabolism. In recent years, it has been discovered that eicosanoids derived from arachidonic acid (AA) have the potential to create specialized pro-resolving lipid mediators to actively resolve inflammation, but it is not clear whether AA and lipoxygenases exert effects on hepatic inflammation. Here, the effects of atorvastatin on the expression of cytoplasmic phospholipase A2 (cPLA2) and lipoxygenase pathway genes (ALOX5, ALOX12, ALOX15, and ALOX15B) were evaluated in an in vitro model of palmitic acid (PA)-induced hepatocyte lipid accumulation in McA-RH7777 (McA) cells. Palmitic acid increased cPLA2 expression, intracellular AA levels, and ALOX12 expression (P < 0.05). Atorvastatin at various concentrations had no significant effects on AA levels or on cPLA2, ALOX15, and ALOX15B expressions. ALOX5 was not detected, despite multiple measurements. Pro-inflammatory IL-1ß expression levels were upregulated by PA (P < 0.01) and attenuated by atorvastatin (P < 0.001). TNFα did not differ among groups. The expression levels of anti-inflammatory IL-10 decreased in response to PA (P < 0.05), but were not affected by atorvastatin. In conclusion, in an in vitro model of lipid accumulation in McA cells, atorvastatin reduced IL-1ß; however, its effect was not mediated by AA and the lipoxygenase pathway at the established doses and treatment duration. Further research is required to investigate time-response data, as well as other drugs and integrated cell systems that could influence the lipoxygenase pathway and modulate inflammation in liver diseases.

Association of Blood Pressure With Cardio-Renal Events and Mortality in Type 2 DM: A National Health Insurance Database.

CONTEXT: The relationship of blood pressure (BP) with cardio-renal events and all-cause mortality in type 2 diabetes mellitus (T2DM) is still controversial. OBJECTIVE: To investigate the optimal BP target in Korean individuals with T2DM. METHODS: Using the Korean National Health Insurance System database, data of individuals with T2DM who underwent regular health checks from January 1, 2007, to December 31, 2007, were extracted (N = 1 800 073). Among them, a total of 326 593 individuals were included in the final study. The study population was divided into 7 groups according to their observed systolic blood pressure (SBP) (<110, 110-119, 120-129, 130-139, 140-149, 150-159, 160-169, and ≥170 mmHg) and diastolic blood pressure (DBP) (<65, 65-69, 70-74, 75-79, 80-84, 85-89, and ≥90 mmHg). Hazard ratios (HRs) of cardio-renal events and all-cause mortality according to BP categories were analyzed. RESULTS: Compared with SBP of 120-129 mmHg and DBP of 75-79 mmHg, SBP of ≥130 mmHg and DBP of ≥ 80 mmHg were associated with an increase in HR of major cardiovascular adverse events (MACEs). SBP of 120-129 mmHg and DBP 75-79 mmHg were associated with the lowest HR of all-cause mortality. Both lower BP (SBP/DBP <120/70 mm) and higher BP (SBP/DBP ≥130/80 mmHg) were associated with an increased HR of all-cause mortality. Contrary to MACE, the lower the SBP, the lower the HR of renal events. CONCLUSION: In patients with T2DM, the optimal cutoff value of BP associated with a lower incidence of MACE and mortality may be 120-129 mmHg for SBP and 75-79 mmHg for DBP. However, lower SBP may be helpful for T2DM patients with a high risk of renal disease.

Complementary effects of dapagliflozin and lobeglitazone on metabolism in a diet-induced obese mouse model.

Thiazolidinedione, an insulin sensitizer, has beneficial effects on glucose metabolism; however, there are concerns regarding weight gain and heart failure. Sodium-glucose co-transporter 2 (SGLT2) inhibitors can reduce body weight, increase diuresis, and play a protective role in heart failure. We examined the complementary effects of dapagliflozin, an SGLT2 inhibitor, and lobeglitazone, a thiazolidinedione, in high-fat diet (HFD)-induced obese mice. We treated HFD-induced obese mice with vehicle, dapagliflozin, lobeglitazone, and their combination for 12 weeks. Oral glucose tolerance and insulin tolerance tests were performed after 12-week treatment, and body composition was measured by dual-energy X-ray absorptiometry before and after treatment. We analyzed oxygen consumption rate (OCR) using 3T3-L1 cells after treatment of ß-hydroxybutyrate and/or lobeglitazone. Treatment with a combination of dapagliflozin and lobeglitazone resulted in a significant decrease in postprandial hyperglycemia compared with dapagliflozin monotherapy, but not compared with lobeglitazone monotherapy. The addition of dapagliflozin to lobeglitazone treatment did not attenuate weight gain compared with lobeglitazone monotherapy in this study. However, this combination prevented the increase of organ weight of liver and heart, and OCR in 3T3-L1 cells was increased after treatment with a combination of ß-hydroxybutyrate and lobeglitazone compared to lobeglitazone monotherapy. We confirmed the beneficial effect of lobeglitazone on glucose metabolism; however, we did not find any beneficial effect of dapagliflozin on body weight in HFD-induced obese mice. However, the protective effects of dapagliflozin and lobeglitazone combined therapy on the liver, heart, energy consumption, and ß-cell senescence are worth investigating in clinical trials.

The ability of ß-cells to compensate for insulin resistance is restored with a reduction in excess growth hormone in Korean acromegalic patients.

The aim of this study was to assess the prevalence of diabetes and to study the effects of excess growth hormone (GH) on insulin sensitivity and ß-cell function in Korean acromegalic patients. One hundred and eighty-four acromegalic patients were analyzed to assess the prevalence of diabetes, and 52 naïve acromegalic patients were enrolled in order to analyze insulin sensitivity and insulin secretion. Patients underwent a 75 g oral glucose tolerance test with measurements of GH, glucose, insulin, and C-peptide levels. The insulin sensitivity index and ß-cell function index were calculated and compared according to glucose status. Changes in the insulin sensitivity index and ß-cell function index were evaluated one to two months after surgery. Of the 184 patients, 17.4% were in the normal glucose tolerance (NGT) group, 45.1% were in the pre-diabetic group and 37.5% were in the diabetic group. The insulin sensitivity index (ISI(0,120)) was significantly higher and the HOMA-IR was lower in the NGT compared to the diabetic group (P = 0.001 and P = 0.037, respectively). The ISI(0,120) and disposition index were significantly improved after tumor resection. Our findings suggest that both insulin sensitivity and ß-cell function are improved by tumor resection in acromegalic patients.

Association between the Diabetes Drug Cost and Cardiovascular Events and Death in Korea: A National Health Insurance Service Database Analysis.

BACKGRUOUND: This study aimed to investigate the long-term effects of diabetes drug costs on cardiovascular (CV) events and death. METHODS: This retrospective observational study used data from 2009 to 2018 from the National Health Insurance in Korea. Among the patients with type 2 diabetes, those taking antidiabetic drugs and who did not have CV events until 2009 were included. Patients were divided into quartiles (Q1 [lowest]-4 [highest]) according to the 2009 diabetes drug cost. In addition, the 10-year incidences of CV events (non-fatal myocardial infarction, stroke, hospitalization for heart failure, and coronary revascularization) and CV death (death due to CV events) were analyzed. RESULTS: A total of 441,914 participants were enrolled (median age, 60 years; men, 57%). CV events and death occurred in 28.1% and 8.36% of the patients, respectively. The 10-year incidences of CV events and deaths increased from Q1 to 4. After adjusting for sex, age, income, type of diabetes drugs, comorbidities, and smoking and drinking status, the risk of CV events significantly increased according to the sequential order of the cost quartiles. In contrast, the risk of CV death showed a U-shaped pattern, which was the lowest in Q3 (hazard ratio [HR], 0.953; 95% confidence interval [CI], 0.913 to 0.995) and the highest in Q4 (HR, 1.266; 95% CI, 1.213 to 1.321). CONCLUSION: Diabetes drug expenditure affects 10-year CV events and mortality. Therefore, affording an appropriate diabetes drug cost at a similar risk of CV is an independent protective factor against CV death.

Daily urine iodine excretion while consuming a low-iodine diet in preparation for radioactive iodine therapy in a high iodine intake area.

OBJECTIVE: Recommended durations of low-iodine diet (LID) in preparation for radioactive iodine therapy (RAIT) vary among major guidelines and are important for patients in areas where iodine intake is high. The aim of this study was to investigate daily changes in urine iodine excretion after starting a LID. DESIGN: The daily iodine/creatinine (I/Cr) ratios and simple iodine concentration (simple I) of morning spot urine from 19 patients with differentiated thyroid carcinoma were measured for 2 weeks from the start of LID for RAIT preparation. We set the cut-off of I/Cr and simple I for poor LID preparation at >66·2 µg/gCr and >150 µg/l, respectively. The day when daily I/Cr or simple I became equal to or below the cut-off both by 95% CI and 90th percentile was defined as the end-point for the appropriate duration of LID for RAIT. RESULTS: On day 6 of LID, the I/Cr ratio decreased below the cut-off (≤66·2 µg/gCr) both by 95% CI (0-60·8) and by 90th percentile (51·9). Simple I reached the cut-off (≤150 µg/l) on day 3 by both parameters (95%CI: 2·3-90·5; 90th percentile: 126·5). The morning spot-urine I/Cr and simple I on day 7 and day 14 were significantly lower than on day 0 (P < 0·05). CONCLUSIONS: One week of a strict LID is enough to decrease the level of urine iodine excretion in preparation for RAIT even in high iodine intake areas. These results provide essential data for future outcome studies regarding LID preparation for RAIT.

Identification of HLA-DRB1 alleles associated with Graves' disease in Koreans by sequence-based typing.

The human leukocyte antigen (HLA) region, particularly class II genes, plays a primary role in the susceptibility to development of GD. We investigated the allelic polymorphism of HLA class II DRB1 genes to examine its association with GD in Koreans. We performed the high resolution polymerase chain reaction-sequence based typing (PCR-SBT) of HLA-DRB1 in 133 patients with GD and 200 healthy controls. Compared to healthy controls, the patients with GD had increased frequencies of DRB1*030101 (4.9% vs.1.8%, p = 0.034), DRB1*080201 (5.3% vs. 2.3%, p = 0.050) and DRB1*140301 (3.4% vs. 1.0%, p = 0.043). In contrast, the frequencies of DRB1*070101 (3.0% vs. 7.3%, p = 0.024) and DRB1*130201 (4.1% vs. 9.0%, p = 0.010) were decreased in the patients with GD. However, the corrected p values were not significant in above all alleles. Patients with DRB1*040301 were significantly older than controls (45 years vs. 35 years, p = 0.017). DRB1*040301, DRB1*150201, DRB1*120101 and DRB1*120201 were associated with male predominance, strong familial associations, thyroid ophthalmopathy and radioactive iodine therapy, respectively. In conclusion, there were no significant HLA-DRB1 alleles associated with GD in Koreans, although some alleles were correlated with the clinical characteristics.

Anti-proliferative effect and action mechanism of dexamethasone in human medullary thyroid cancer cell line.

INTRODUCTION: Dexamethasone is known to inhibit the cell proliferation of certain transformed cell lines. In this study, the effect and action mechanism of dexamethasone were examined in the human medullary thyroid cancer cell line, TT cells. METHODS: TT cells were treated with or without dexamethasone. 5-Bromo-2'-deoxyuridine uptake assay was used to evaluate cell proliferation. Cell cycle and its regulatory proteins were assessed by flow cytometry and western blot analysis, respectively. Apoptosis was analyzed by Hoechst staining and Annexin V assay. RESULTS: Dexamethasone significantly reduced TT cell proliferation by 60% (p < 0.01). A substantial portion of cells was arrested at the G1 phase. The expression levels of cyclin D1, cyclin-dependent kinase (CDK)4, and CDK2 were decreased. In addition, the phosphorylation of retinoblastoma protein, which is a critical checkpoint protein in the transition of G1 to S phase, was decreased. On the other hand, the expression level of p27(Kip1), which is a cyclin/CDK inhibitor, was enhanced. Hoechst staining showed many fragmented nuclei in the dexamethasone-treated cells. The proportion of early apoptotic cells was also increased in the Annexin V assay. CONCLUSION: Dexamethasone inhibited the proliferation of TT cells through cell cycle arrest at the G1 phase and increased apoptosis.

Usefulness of iodine/creatinine ratio from spot-urine samples to evaluate the effectiveness of low-iodine diet preparation for radioiodine therapy.

OBJECTIVE: The success of a low-iodine diet (LID) is best determined by measurement of 24-h urine iodine (U-I) excretion. The aim of this study was to determine reliable estimates for 24-h U-I based on spot-urine samples and to provide cut-offs to determine the effectiveness of LID preparation. DESIGN: We prospectively measured iodine levels in 193 patients based on 24-h- and spot-urine samples before radioactive iodine therapy. The iodine was expressed as the 24-h U-I excretion (microg/day) and as two different indices from spot urine, simple iodine concentration (simple I) and the iodine/creatinine (I/Cr) ratio. Poor LID preparation was defined as I excretion of >150 microg/day according to the 24-h U-I measurement. RESULTS: The measured 24-h U-I was significantly higher than the two indices from spot urine (P < 0.001). However, there were statistically significant correlations between the 24-h U-I values and the two spot-urine-based indices; the correlation coefficient was 0.539 for simple I and 0.773 for I/Cr ratio (P < 0.001). The cut-off of I/Cr ratio for poor LID preparation was >66.2 microg/g Cr (sensitivity 96.4%, specificity 83.6%, positive predictive value 50.0% and negative predictive value 99.3%). CONCLUSIONS: We demonstrated that the I/Cr ratio from spot urine could serve as a useful and reliable alternative to 24-h urine collection as it has acceptable diagnostic values for detecting poor LID preparation.

Decreased health-related quality of life in disease-free survivors of differentiated thyroid cancer in Korea.

BACKGROUND: Concern regarding the health-related quality of life (HRQOL) of long-term survivors of thyroid cancer has risen due to the rapid increase in the incidence of thyroid cancer, which generally has an excellent prognosis. The aim of this study was to evaluate the status of HRQOL in disease-free survivors of differentiated thyroid carcinoma (DTC) and to evaluate the important determinants of HRQOL. METHODS: This was a cross-sectional study in which we interviewed consecutive disease-free survivors of DTC. Three different validated questionnaires ("EORTC QLQ-C30" for various functional domains, the "brief fatigue inventory (BFI)" and the "hospital anxiety and depression scale" (HADS)) were used. Data from a large, population based survey of 1,000 people were used as a control. RESULTS: The response rate for the questionnaires was 78.9% (316/401). Disease-free survivors of DTC showed a decreased HRQOL in all five functional domains (physical, role, cognitive, emotional, and social) on the EORTC QLQ-C30 compared with controls (P < 0.01). BFI and HADS-anxiety scores also showed greater distress in disease-free survivors of DTC than in controls (P < 0.05). A multiple regression analysis for the determinants of HRQOL showed that the HADS-anxiety, HADS-depression, and BFI scores were the most significant components of decreased HRQOL. CONCLUSIONS: Although disease-free survivors of DTC are expected to have disease-specific survival comparable to the general population, they experience a significantly decreased HRQOL. Anxiety, depression, and fatigue were the major determinants of the decreased HRQOL. Supportive psychological care should be integrated into the management of long-term survivors of DTC.

Localization of medullary thyroid carcinoma after surgery using (11)C-methionine PET/CT: comparison with (18)F-FDG PET/CT.

Tumor localization is difficult in patients with medullary thyroid carcinoma (MTC) that have persistent hypercalcitoninemia after thyroidectomy. In this study, the (11)C-methionine positron emission tomography/computed tomography (PET/CT) was compared with the (18)F-FDG PET/CT for diagnostic sensitivity in detecting residual or metastatic disease. (11)C-methionine PET/CT and (18)F-FDG PET/CT were performed on 16 consecutive patients with MTC that had persistent hypercalcitoninemia after surgery in this prospective, single-center study. Patient- and lesion-based analyses were performed using a composite reference standard which was the sum of the lesions confirmed by all combined modalities, including neck ultrasonography (US) with or without fine needle aspiration cytology, CT, bone scan, magnetic resonance imaging (MRI), and surgery. By patient-based analysis, the sensitivities of (11)C-methionine PET/CT and (18)F-FDG PET/CT were both 63%. By lesion-based analysis, the sensitivity of (11)C-methionine PET/CT was similar to (18)F-FDG PET/CT (73% vs. 80%). Excluding hepatic lesions, which could not be detected because of physiological uptake of methionine by the liver, the sensitivity of (11)C-methionine PET/CT was better than (18)F-FDG PET/CT especially for detecting cervical lymph node lesions; however, it was not superior to US. All patients with serum calcitonin levels ≥370 pg/mL showed uptake by (11)C-methionine PET/CT and (18)F-FDG PET/CT. This preliminary data showed that despite its similar sensitivity to (18)F-FDG PET/CT for detecting residual or metastatic MTC, (11)C-methionine PET/CT provided minimal additional information compared to combined (18)F-FDG PET/CT and neck US.

A case of resistance to thyroid hormone with thyroid cancer.

Resistance to thyroid hormone (RTH) is an autosomal dominant hereditary disorder that is difficult to diagnose because of its rarity and variable clinical features. The magnitude of RTH is caused by mutations in the thyroid hormone receptor beta (TR beta) gene. We recently treated a 38-yr-old woman with RTH who had incidental papillary thyroid carcinoma. She presented with goiter and displayed elevated thyroid hormone levels with an unsuppressed TSH. She was determined to harbor a missense mutation of M310T in exon 9 of the TR beta gene, and diagnosed with generalized RTH. This mutation has not yet been reported in Korea. RTH is very rare and easily overlooked, but should be considered in patients who present with goiter and elevated thyroid hormone levels with an unsuppressed TSH. The association between thyroid cancer and RTH needs further study.

Autosomal dominant hypocalcemia caused by an activating mutation of the calcium-sensing receptor gene: the first case report in Korea.

Hypoparathyroidism is an abnormality of calcium metabolism characterized by low serum levels of parathyroid hormone in spite of hypocalcemia. The causes of hypoparathyroidism are numerous. Activating mutations in the calcium-sensing receptor (CaSR) gene are well-known causes of familial isolated hypoparathyroidism, also known as autosomal dominant hypocalcemia (ADH). Here we describe members of a Korean family with a heterozygous Pro221Leu mutation causing ADH. This case is the first report in Korea.

The advantage of a decreasing right-hand superiority: the influence of laterality on a selected musical skill (sight reading achievement).

In this study, the unrehearsed performance of music, known as 'sight reading', is used as a model to examine the influence of motoric laterality on highly challenging musical performance skills. As expertise research has shown, differences in this skill can be partially explained by factors such as accumulated practise and an early start to training. However, up until now, neurobiological factors that may influence highly demanding instrumental performance have been widely neglected. In an experiment with 52 piano students at a German university music department, we could show that the most challenging musical skill, sight reading (which is characterized by extreme demands on the performer's real time information processing), is positively correlated with decreasing right-hand superiority of performers. Laterality was measured by the differences between left and right-hand performance in a speed tapping task. SR achievement was measured using an accompanying task paradigm. An overall superiority of 22% for non-right-handed pianists was found. This effect is gender-related and stronger in non-right-handed males (r(24) = -0.49, p<0.05) than in non-right-handed females (r(28) = -0.16, p>0.05). We conclude that non-right-handed motoric laterality is associated with neurobiological advantages required for sight reading, an extremely demanding musical subskill.