Biomedical subjects

Rue-Tsuan Liu

Publications and source records attributed to Rue-Tsuan Liu.

12 recordsLinked to original sources

PubMed2006

Sequential follow-up of serum thyroglobulin and whole body scan in thyroid cancer patients without initial metastasis.

OBJECTIVE: To investigate the usefulness of whole body scan (WBS) and serum thyroglobulin (Tg) measurement after thyroxine withdrawal during sequential follow-ups in patients with differentiated thyroid cancer (DTC). DESIGN: Two hundred and sixty-five consecutive DTC patients were enrolled. They were previously treated with near-total thyroidectomy and I-131 remnant ablation, without initial metastases or Tg antibodies. All had the first follow-up WBS and serum Tg measurement 6-12 months after initial treatment, and 165 patients received the second follow-up without further therapy. Positive/negative predictive values (PPV/NPV) were calculated by the outcome of patients being followed up for more than 8 years (mean+/-SD: 133+/-26 months). RESULTS: Serum Tg levels while the patients were off thyroxine therapy decreased spontaneously in 39.3% of the cases without further therapy. The NPV of the first follow-up serum Tg level was excellent: <2 microg/L and <0.5 microg/L were 95.1% and 98.2%, respectively. However, the PPV of the first follow-up serum Tg level was low: >10 microg/L and 2-10 microg/L were 40% and 9.6%, respectively. The trend of Tg levels was more informative; the PPV was 62.5% in cases with an increase of serum Tg of >10 microg/L and 16.6% with an increase of <5 microg/L. However, decreasing Tg levels may associate with rapid deterioration of disease, in which cases decrease of Tg indicated dedifferentiation of the tumor. The diagnostic WBS showed the same picture in 91.5% of the patients. Only one patient (0.6%) turned from negative study to positive during the follow-up. In the meanwhile his serum Tg levels increased from 0.56 to 13.6 microg/L. CONCLUSION: It is most informative when both the trend and the levels of Tg during sequential follow-up are considered. The diagnostic WBS may be performed for selected patients with indication based on Tg levels to localize the disease.

Adult↗

PubMed2005

Association of mitochondrial deoxyribonucleic acid 16189 variant (T->C transition) with metabolic syndrome in Chinese adults.

OBJECTIVE: A common variant in mitochondrial DNA (mtDNA) at bp 16189 (T-->C transition) has been associated with small birth size, adulthood hyperglycemia, and insulin resistance in Caucasians. In this study, we investigated whether mtDNA 16189 variant is associated with metabolic syndrome in Chinese subjects. METHODS: Six hundred fifteen Chinese adults, aged 40 yr or older, were recruited in this study. The 16189 variant of mtDNA was detected using PCR and restriction enzyme digestion. Metabolic syndrome was diagnosed on modified National Cholesterol Education Program Adult Treatment Panel III guidelines, using body mass index (BMI) instead of waist circumference. An association study was performed with chi2 test and logistic regression analysis. RESULTS: The prevalence of the 16189 variant was higher in patients with metabolic syndrome than in those without: 44% (125 of 284) vs. 33.2% (110 of 331) (P = 0.006). The association between this 16189 variant of mtDNA and metabolic syndrome (P = 0.021) remained significant even after correcting for age and BMI. As to the individual traits, the prevalence of fasting plasma glucose of at least 110 mg/dl (> or =6.1 mmol/liter) [(51.5% (121 of 235) vs. 42.1% (160 of 380); P = 0.023], type 2 diabetes mellitus [48.1% (113 of 235) vs. 39.2% (149 of 380); P = 0.031], and hypertriglyceridemia [44.3% (104 of 235) vs. 35.8% (136 of 380); P = 0.037] were significantly higher in subjects harboring the 16189 variant of mtDNA than those with the wild type. However, the prevalence of hypertension [53.2% (125 of 235) vs. 47.6% (181 of 380); P = 0.180], BMI greater than 25 kg/m2 [48.5% (114 of 235) vs. 43.9% (167 of 380); P = 0.270], and low high-density lipoprotein cholesterol [61.3% (144 of 235) vs. 54.7% (208 of 380); P = 0.111] did not reach a significant difference between the two groups. Furthermore, there was a trend of increasing frequency of occurrence of the 16189 variant in individuals having an increasing number of components of metabolic syndrome (Ptrend < 0.005). CONCLUSION: Our data strongly suggest that mtDNA 16189 variant underlies susceptibility to metabolic syndrome in the Chinese population.

Aged↗

PubMed2005

Orlistat for obesity: benefits beyond weight loss.

Orlistat lowers lipids and improves insulin sensitivity, but its effect on other metabolic syndrome related parameters is not known. To assess its influence on adiponectin, high sensitive C-reactive protein (hs-CRP) and other metabolic syndrome related parameters, this study enrolled 106 participants in a weight-reduction program and categorized them into a group of 51 who had been treated with orlistat 360 mg/day for one year and a group of 55 age and sex and body mass index (BMI) matched controls. The orlistat group had greater changes in BMI, % body fat (% BF), waist circumference, and insulin resistance, hs-CRP, leptin and adiponectin levels after one year on the program than the controls. After adjusting for % BF and waist circumference, change of serum leptin and adiponectin levels remained significantly different. It was found that orlistat could effectively manage obesity related co-morbidities, especially insulin resistance and atherosclerosis risk. It decreases leptin and increases adiponectin independent of % BF and waist circumference. Therefore, orlistat appears to have anti-diabetic and anti-atherogenic properties and may help prevent metabolic syndrome in the overweight people.

Adult↗

PubMed2005

Low prevalence of RET rearrangements (RET/PTC1, RET/PTC2, RET/PTC3, and ELKS-RET) in sporadic papillary thyroid carcinomas in Taiwan Chinese.

Somatic rearrangement of the tyrosine kinase receptor RET is restricted to papillary thyroid carcinoma (PTC). The prevalence of RET/PTC1, RET/PTC2, and RET/PTC3 has been found to vary between 0% and 20% in most series of sporadic (nonradiation-induced) PTCs analyzed by type-specific reverse transcription-polymerase chain reaction (RT-PCR) alone. However, high prevalence reported from Taiwan (6 out of 11, 55%) indicates RET rearrangement is an important genetic lesion underlying the development of PTC in Taiwan. Because the high prevalence of RET rearrangements in Chinese patients was particularly striking, we were prompted to reexamine chimeric transcripts of RET/PTC1, RET/PTC2, and RET/PTC3 using the same experimental designs in a larger number of cases in the same population. RT-PCR was performed to amplify fusion products of RET/PTC1, RET/PTC2, RET/PTC3, and ELKS-RET from frozen tissue of 105 sporadic PTCs. RT-PCR was also performed with two different primer sets for RET/PTC1, RET/PTC2, and RET/PTC3 followed by Southern hybridization in the first 62 tumors. In our study, RET/PTC1, RET/PTC2, and RET/PTC3 oncogenes were found in only 7 of 105 (7%) sporadic PTCs. Of these tumors, 3 involved RET/PTC1 and 4 involved RET/PTC3. No RET/PTC2 rearrangements were observed. In the first 62 tumor samples, another two different primer sets for each rearrangement also gave concordant results. Furthermore, application of Southern hybridization in these 62 PTCs did not identify additional tumor harboring RET chimeric transcripts. We identified one tumor as having an ELKS-RET rearrangement (1 of 105, 1%). In conclusion, we detected RET rearrangements in 8 of 105 (8%) sporadic PTCs in Taiwan, a much lower prevalence than previously reported for this population but comparable to those reported in other nations using similar methodology. RET chimeric oncogenes only account for a small fraction of PTCs in Taiwan.

Adaptor Proteins, Signal Transducing↗

PubMed2005

No correlation between BRAFV600E mutation and clinicopathological features of papillary thyroid carcinomas in Taiwan.

OBJECTIVE: Genetic alterations in four oncogenes, namely RAS point mutations, RET rearrangements (RET/PTC), NTRK1 rearrangements (TRK) and BRAF point mutations have been identified in human papillary thyroid carcinomas (PTCs). These oncogenes act along the RET/PTC(TRK)-RAS-BRAF-MEK-MAPK kinase pathway, mediating a number of cellular fates including growth, proliferation and survival in thyroid cells. In this study, we analysed mutations of BRAF in a cohort of PTCs. METHODS: To screen for BRAF mutations, the genomic DNA of 105 PTCs were amplified by polymerase chain reaction (PCR) with primers flanking exon 15 and PCR products were directly sequenced with an automatic sequencer. These results, together with data from our previous studies on RAS, RET rearrangements and NTRK1 rearrangements in the same tumours, were compared to determine their individual significance in the pathogenesis of PTCs in Taiwan. RESULTS: BRAF mutations were detected in 49 of 105 (47%) tumour samples. All mutations involved a thymine-to-adenine transversion at nucleotide 1799 and were heterozygous. There was no overlap between papillary carcinomas harbouring RET rearrangements, NTRK1 rearrangements and BRAF mutations. In this cohort, correlation between BRAF mutations and various clinicopathological parameters in 101 papillary carcinomas did not reveal any association with age at diagnosis, sex, tumour size, histological variants of PTC, multicentricity, cervical lymph node metastases, extrathyroidal invasion, distant metastases and clinical stage. CONCLUSIONS: BRAFV600E mutation is the most prevalent oncogene in PTCs in Taiwan. Our data did not suggest that BRAFV600E mutation could be a potentially useful marker of prognosis in patients with papillary carcinomas in the population studied.

Adult↗

PubMed2004

Selective occurrence of ras mutations in benign and malignant thyroid follicular neoplasms in Taiwan.

Previous studies have demonstrated that point mutations in all three ras genes (H-ras, K-ras, and N-ras) may occur in thyroid neoplasia. However, the overall incidence of ras mutations in thyroid tumors and their frequency in specific histologic types varies widely in different series. Many earlier studies have chosen allele-specific oligonucleotide hybridization approaches to examine ras mutations without further confirmation of the positive samples by DNA sequencing. In this study, mutational hot spots in exon 1 (codons 12/13) and exon 2 (codon 61) of the H-ras, K-ras, and N-ras were polymerase chain reaction (PCR) amplified and sequenced with an automatic sequencer. ras mutations were detected in 4 of 89 (4.5%) benign and malignant thyroid tumors. Three of 8 follicular carcinomas exhibited mutations in codon 61 of H-ras, K-ras, and N-ras, respectively, and mutation at codon 61 of N-ras was found in 1 of 12 follicular adenomas. No mutations were observed in the other tumors, which included 20 nodular goiters, 5 Hürthle cell adenomas, 42 papillary carcinomas, and 2 undifferentiated carcinomas. Our results, obtained by the direct sequencing technique, indicate a lower overall prevalence of ras oncogenes in thyroid tumors than reports in earlier series. However, the frequency of ras mutations in specific histotype of thyroid tumors and their exclusive involvement of codon 61 in our series are similar to those studies utilizing DNA sequencing to detect or to confirm ras gene alterations. The selective occurrence of ras mutations in benign and malignant follicular neoplasms indicates that ras gene alterations have a specific and early role in the development of follicular type of thyroid tumors in Taiwan.

Adenocarcinoma, Follicular↗

PubMed2004

Cytotoxic T lymphocyte-associated molecule-4 polymorphism and relapse of Graves' hyperthyroidism after antithyroid withdrawal.

We studied the A/G single nucleotide polymorphism (SNP) at position 49 in exon 1 of the cytotoxic T lymphocyte-associated molecule-4 gene in 148 Chinese Graves' disease (GD) patients and 171 controls. Our primary aim was to test for the association of this SNP with the relapse of the hyperthyroidism after antithyroid withdrawal. Our secondary aim was to investigate the relationship between GD patients and controls according to the SNP genotypes. All GD patients were divided into the following three groups according to the time of relapse after drug discontinuation: group 1, early relapse within 9 months; group 2, relapse between 10 and 36 months; and group 3, relapse 3 or more years after discontinuation of treatment. There was a significant difference of genotype frequencies (P < 0.001) and allele frequencies (P < 0.001) among the three groups of patients. The frequency of the G/G genotype decreased from 79% to 64% and 39% in groups 1, 2, and 3, respectively. Compared with controls, a strong association (P < 0.001) of G allele was found for group 1, and moderate significance (P = 0.04) was found for group 2, but no association (P = 0.33) was found for group 3. At the end of treatment, the percentage of patients with persistent TSH-receptor antibody was statistically different (A/A, 9.0%; A/G, 20.8%; G/G, 45.5%; P = 0.004). Using 3 yr as the cutoff point for multivariate logistic regression analysis, we found that the G/G genotype (adjusted odds ratio, 3.1 compared with A/G plus A/A; 95% confidence interval, 1.3-7.1), larger goiter size at the end of treatment, and positive TSH-receptor antibody at the end of treatment were independent risk factors of recurrence. We conclude that the A/G polymorphism of the cytotoxic T lymphocyte-associated molecule-4 gene affects the progress of GD. The G/G genotype is associated with poor outcome.

Adult↗

PubMed2004

Bone mineral density in women receiving thyroxine suppressive therapy for differentiated thyroid carcinoma.

BACKGROUND AND PURPOSE: Most patients with well-differentiated thyroid carcinoma have an excellent prognosis and are likely to live long enough to be subjected to osteoporosis. The purpose of this study was to investigate the consequences of treatment with a supraphysiological dose of levothyroxine (l-T4) on bone mineral density (BMD) in Taiwanese women with differentiated thyroid cancer. METHODS: A total of 69 (44 premenopausal, 25 postmenopausal) Taiwanese women with differentiated thyroid cancer were included in this retrospective study. These patients were free of disease recurrence after initial near-total thyroidectomy and I-131 radioablation, and had undergone regular l-T4 suppressive therapy for more than 3 years (mean, 7.3 +/- 3.0 years; range, 3 to 15 years). The degree of thyroid-stimulating hormone (TSH) suppression was determined based on the mean TSH score for each patient which was determined by analysis of all available follow-up TSH data, where 1 = undetectable TSH (< 0.2 mIU/mL); 2 = subnormal TSH (0.2 to 0.39 mIU/mL); 3 = normal TSH (0.4 to 4.0 mIU/mL); and 4 = elevated TSH (> 4.0 mIU/mL). The patients were divided into a full TSH suppression group with a mean TSH score in the range 1.0 to 1.99, and a partial TSH suppression group with a mean TSH score in the range 2.0 to 2.99. BMD was measured by dual-energy X-ray absorptiometry at the lumbar spine, femoral neck, Ward's triangle and total hip. Comparisons between subgroups of patients and controls were performed by unpaired t test. Correlation between BMD and other clinical variables was assessed by Pearson's correlation analysis. RESULTS: Postmenopausal patients (aged 57.7 +/- 6.9 years) had significantly higher serum calcium levels and decreased BMD at all sites of the spine and hip as compared with premenopausal patients (aged 38.6 +/- 6.7 years) with similar BMI and duration of TSH suppression. Comparison of BMD between postmenopausal patients and BMI- and age-matched controls revealed that the patient group had decreased BMD at all sites of measurement, although this difference was not significant. This phenomenon was not observed in the premenopausal patients. Furthermore, when BMD was compared between patients categorized as having full and partial suppression of TSH, only patients with full suppression in the postmenopausal group showed a tendency to lower BMD. There was a strong correlation of BMD with age, BMI and serum calcium level. However, no correlation was found between BMD and degree of TSH suppression or duration of l-T4 suppression therapy. CONCLUSION: Women with differentiated thyroid cancer who had long-term (mean, 7.3 +/- 3.0 years) l-T4 therapy and suppressed TSH levels had no evidence of lower BMD. However, patients with full suppression in the postmenopausal group showed a tendency towards lower BMD. Therefore, careful monitoring of BMD in postmenopausal women during suppression therapy is mandatory.

Absorptiometry, Photon↗

PubMed2002

Overexpression of tumor susceptibility gene TSG101 in human papillary thyroid carcinomas.

Functional inactivation of tumor susceptibility gene tsg101 leads to cellular transformation and tumorigenesis in mice. While human TSG101 is located in a region where frequent loss of heterozygosity can be detected in a variety of cancers, no genomic deletion in TSG101 gene has been reported, casting a doubt on the role of TSG101 as a classical tumor suppressor. Some studies have revealed that TSG101 is a frequent target of splicing defects, which correlate with cellular stress and p53 status. Furthermore, recent reports have identified TSG101 as a part of the MDM2/p53 regulatory circuitry, a well-recognized circuitry that upon deregulation results in tumorigenesis. Interestingly, overexpression of tsg101 from an adventitious promoter also leads to neoplastic transformation. On the basis of this information, we have analysed TSG101 gene expression in 20 human papillary thyroid carcinomas (PTCs) by immunohistochemistry and demonstrated that the overexpression of TSG101 protein is closely associated with human PTCs. Further sequence analysis reveals no mutation in cDNA region encoding steadiness box in these PTC specimens, indicating that the upregulation of TSG101 protein is not caused by the alteration of this region. In situ hybridization analysis confirms that overexpression of TSG101 also occurs at the transcriptional level. In addition, semi-quantitative RT-PCR and subsequent Southern hybridization verify that the amounts of TSG101 transcripts are indeed lower in three normal thyroid tissues than in PTC specimens. Here we report the upregulation of TSG101 expression in PTC cells, providing the first evidence of the association of TSG101 overexpression with human tumors and suggesting that upregulation of TSG101 steady-state level might play a role in mediating tumorigenesis of human PTC.

Antibody Specificity↗

PubMed2002

Serum leptin concentrations of patients with sequential thyroid function changes.

BACKGROUND: Leptin, a recently discovered protein produced in adipocytes, regulates body weight by suppressing food intake and/or increasing energy expenditure. Thyroid hormones, which increase the basal metabolic rate and thermogenesis, have been reported to be one of leptin's regulating factors because alternations in thyroid status might lead to compensatory changes in circulating leptin. OBJECTIVE: The aim of this study was to assess the influence of sequential changes in thyroid function on serum leptin levels. PATIENTS AND METHODS: The thyroid function status of 65 patients (55 women and 10 men, aged 40.6 +/- 15.2 years, mean +/- SD) with differentiated thyroid cancer who had received near-total thyroidectomy was studied before I-131 ablation therapy and after 2-4 and 6 months of levo-thyroxine suppressive therapy. Thirty-three (26 women, seven men; aged 41.0 +/- 10.4 years, mean +/- SD) of them were found to have become hypothyroid, then euthyroid and subsequently subclinically hyperthyroid. Their body mass index (BMI), body fat (%BF) by electrical bioimpedance, thyroid function and fasting serum leptin in these states were assessed and compared to those of 38 controls (30 women, eight men, aged 40.2 +/- 11.3 years, mean +/- SD). The controls had no past history or family history of thyroid diseases, and had the same range of BMI, between 20 and 30 kg/m2, as the patients. RESULTS: No difference in serum leptin levels was found between patients and controls with comparable age, sex, and BMI distribution in the euthyroid state. Using a repeated measures anova, tests of TSH, free T4 (FT4), BMI,%BF and leptin were performed on the 33 patients with sex as a grouping factor and thyroid state as a time factor. The sex difference for %BF and leptin proved to be statistically significant (P < 0.0001, and P = 0.0003, respectively). Serum leptin levels increased significantly from the hypothyroid to the subclinical hyperthyroid state (P < 0.0001) with a more pronounced increase found in females than in males (P = 0.03). Change of BMI during sequential thyroid function alterations was significant (P = 0.04) while change in %BF was not significant (P = 0.09). Pearson correlation analysis showed that serum leptin levels significantly correlated with BMI, %BF, FT4, and TSH (all P < 0.05). Using the generalized estimating equations, multivariate regression analysis revealed that FT4 was a statistically independent predictor for serum leptin (P < 0.0001). While other parameters were held constant, the mean serum leptin level increased by 1.47 units when serum FT4 was increased by one unit. CONCLUSION: In conclusion, our data indicate that circulating thyroid hormone plays a relevant role in regulating leptin metabolism independent of BMI and body fat.

Adult↗

PubMed2002

Relative impact of low-density lipoprotein-cholesterol concentration and insulin resistance on carotid wall thickening in nondiabetic, normotensive volunteers.

The relative effect of an increase in low-density lipoprotein-cholesterol (LDL-C) concentration, as compared with insulin resistance and its manifestations, on intimal medial thickening (IMT) of the common carotid artery was defined in 72 healthy men and women. Insulin-mediated glucose disposal was quantified by the insulin suppression tests, in which the height of the steady-state plasma glucose (SSPG) concentration during the last 30 minutes of a 180-minute infusion of octreotide, insulin, and glucose provides an estimate of insulin resistance. IMT was determined by high-resolution B-mode ultrasonography. Univariate analyses defined statistically significant correlation coefficients between IMT and LDL-C concentration (r =.25, P <.05), SSPG concentration (r =.32, P <.01), triglycerides (TG) (r =.25, P <.05), and high-density lipoprotein-cholesterol (HDL-C) (r = -.28, P <.05) concentrations (changes associated with insulin resistance) and ratio of waist-to-hip girth (r =.29, P <.05). When forward step-wise linear regression analysis was used, concentrations of SSPG, LDL-C and HDL-C all emerged as independent predictors of IMT (P <.05). Furthermore, the magnitude of their relationship to IMT values was comparable. These results provide evidence that insulin resistance is as significant a predictor of degree of atherogenesis (estimated by IMT) of the common carotid artery as a high LDL-C concentration.

Adult↗

PubMedDate not supplied

Screening for diabetic retinopathy by one-field, non-mydriatic, 45 degrees digital photography is inadequate.

PURPOSE: To evaluate the sensitivity and specificity of one-field, non-mydriatic, 45 degrees digital photography for screening for diabetic retinopathy compared to indirect ophthalmoscopy using a slit-lamp, the reference standard. METHODS: A total of 100 consecutive diabetic patients (200 eyes) who underwent digital fundus photography and ocular examinations from June 2002 to November 2002 were included in this retrospective study. The patients, recruited from a hospital-based, retina referral practice, underwent 45 degrees, non-mydriatic, digital fundus photography using a non-mydriatic fundus camera. One image was obtained focusing the mid fundus between the optic disc and the macula. The fundus images were printed and graded by endocrinologists and a retinal specialist separately. The patients also underwent complete standard ocular examinations as the reference method for determining diabetic retinopathy, including dilation of their pupils and slit-lamp biomicroscopy done by ophthalmologists. The sensitivity and specificity of the digital photographic method were calculated by comparison to the reference method. RESULTS: The sensitivity and specificity of the retinal specialist's diabetic retinopathy grades were 53.8 and 89.0%, respectively. The sensitivity and specificity of the endocrinologists' grades were 45 and 75.3%, respectively. The false negative rates were 22 and 21.5% for endocrinologists and the retinal specialist, respectively. CONCLUSIONS: Screening for diabetic retinopathy using one-field, non-mydriatic, 45 degrees digital photography is inadequate.

Adult↗