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Biomedical subjects

Pei-Wen Wang

Publications and source records attributed to Pei-Wen Wang.

At least 19 recordsLinked to original sources

A common mitochondrial DNA variant and increased body mass index as associated factors for development of type 2 diabetes: Additive effects of genetic and environmental factors.

OBJECTIVE: The suggested correlation between a T-to-C transition at the nucleotide 16189 in mitochondrial DNA (mtDNA) with increasing insulin resistance and adult-onset diabetes mellitus (DM) is debatable. METHODS: Our study examined mtDNA from 462 subjects with type 2 diabetes (T2DM) and 592 normoglycemic controls (non-DM). Each participant's body mass index (BMI), fasting plasma glucose, fasting insulin concentration, insulin resistance index, and beta-cell function were measured. Sequencing for mtDNA, focusing on exploration of the hypervariable polycytosine tract within the control region, was also conducted in all subjects. RESULTS: Prevalence of the mtDNA 16189 variant was significantly different between DM and non-DM subjects (39.2% vs. 30.7% respectively; P = 0.004). Increased incidence of DM was noted in those harboring the 16189 variant compared with those lacking the variant (multivariate odds ratio, 1.38; 95% confidence interval, 1.07-1.80). Moreover, increased BMI was identified as an aggravating factor for development of DM in subjects harboring the variant. Odds ratio determinations yielded 2.14 in overweight and 4.63 in obese subjects harboring the variant in comparison with subjects without (1.83 in overweight and 2.16 in obese subjects). This is consistent with a progressively increased prevalence of the mtDNA 16189 variant in the non-DM groups with higher fasting insulin concentration, insulin resistance index, and beta-cell function (all P(trend) < 0.005). CONCLUSION: The mtDNA 16189 variant can influence development of T2DM. The demonstrated dynamic between the 16189 variant and increased BMI exemplify an additive effect of genetic and environmental factors on the pathogenesis of T2DM.

Adult↗

Proteomic analysis of Down's syndrome patients with gout.

BACKGROUND: In this study, the expression of hypoxanthine-guanine phosphoribosyl transferase (HPRT) in Down's syndrome patients with gout (DS/G) was determined, and possible underlying mechanisms of gout were characterized using proteomic tools. METHODS: Serum was obtained from DS/G, healthy controls and gout patients (without DS), recruited from the rheumatology clinic. Baseline enzyme assays were recorded and RT-PCR used to identify HPRT gene expression. 2-D electrophoresis and mass spectrometry were utilized to determine a plausible explanation concerning the mechanisms leading to increased uric acid levels in DS patients. RESULTS: Two DS patients were diagnosed with gouty arthritis. Their HPRT enzyme activity was slightly lower than that of normal controls. HPRT expression was also slightly decreased in DS/G patients compared with controls. Serum protein profiles of these two DS/G patients revealed that haptoglobin alpha chain and apolipoprotein A1 (ApoA1) were both significantly down-regulated. Protein expression was validated by immunoblot. CONCLUSION: Our results revealed that low levels of haptoglobin in the two DS/G patients were related to renal dysfunction may have affected uric acid excretion and caused gout. However, decreased ApoA1 revealed a positive correlation between defective lipid metabolism and gouty arthritis in DS/G patients.

Adult↗

Glucocorticoid pretreatment suppresses chemokine expression and inflammatory cell infiltration in cholestatic rats receiving biliary intervention.

AIM: Biliary intervention may augment chemokine expression and inflammatory cell infiltration and aggravates liver injury in cholestatic rats. We tested the efficacy of glucocorticoid pretreatment to prevent the complications. METHODS: A model of biliary intervention was established in rats without (sham) or with bile duct ligation (BDL). Before biliary intervention, rats were randomly assigned to receiving intravenous injection of dexamethasone (DX group) or normal saline (NS group). Plasma levels of monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-2 (MIP-2) were measured with enzyme-linked immunosorbent assay, and liver messenger RNA of these chemokines was quantified with real-time quantitative reverse transcriptase-polymerase chain reaction. Monocytes, Kupffer cells, and neutrophils in the rat liver were characterized with antibodies to ectodermal dysplasia 1 (ED1), ED2, and myeloperoxidase, respectively. RESULTS: By 3 hours after biliary intervention, plasma MCP-1 and MIP-2 proteins in BDL-NS rats were significantly higher than in BDL-DX. At 3 hours, liver MCP-1 and MIP-2 messenger RNA levels were significantly upregulated in BDL-NS than in BDL-DX. The amount of ED1-, ED2- and myeloperoxidase-staining cells were significantly greater in BDL-NS than in BDL-DX. Most of the changes returned to baseline levels by 24 hours. CONCLUSION: Glucocorticoid pretreatment suppresses chemokine expression and inflammatory cell infiltration, which may consequently alleviate liver injury in cholestatic rats receiving biliary intervention.

Animals↗

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↗

Thyroid dysfunction in patients with chronic hepatitis C receiving a combined therapy of interferon and ribavirin: incidence, associated factors and prognosis.

BACKGROUND AND AIMS: Interferon (IFN) plus ribavirin therapy for chronic hepatitis C (CHC) virus infection has been associated with thyroid dysfunction. The goal of our current study was to elucidate predictive factors of: (i) thyroid dysfunction associated with combination therapy; and (ii) long-term reversibility of thyroid dysfunction. METHODS: In total, 461 patients with CHC and normal baseline thyroid functions were enrolled. All patients received IFN-alpha-2b, 3 or 5 million units thrice weekly, or pegylated (PEG)-IFN-alpha-2b 80 or 100 microg weekly combined with ribavirin 1-1.2 g daily for 24-48 weeks. Assays for serum thyroid stimulating hormone (TSH) and free thyroxine were performed. RESULTS: By the end of the treatment, thyroid dysfunction (TSH <0.1 or >5 mU/L) had developed in 58 patients (12.6%). Female gender was significantly associated with thyroid dysfunction (P < 0.001 odds ratio (OR) = 2.85; 95% confidence interval (CI) = 1.6-5.1). The incidence of thyroid dysfunction was similar for standard IFN and PEG-IFN-treated patients (49/391 vs 9/70; P = 1.00). Under a nested case-control design, detailed laboratory assessment was carried out on frozen serum samples from patients and age- (+/- 5 years) and sex-matched controls (n = 58). Multivariate analysis revealed significant association between higher positive rates of pretreatment TMA and patients who developed thyroid dysfunction (OR = 5.8, 95% CI = 1.2-27.9). Ten patients ( approximately 2%) remained thyroid dysfunctional at the end of follow up (median, 26.5 months). For these patients, no risk factor can predict the reversibility of thyroid function. CONCLUSIONS: Female gender and pretreatment TMA positivity are associated with thyroid dysfunction. Long-term thyroid dysfunction may persist in a small group of patients ( approximately 2%).

Antiviral Agents↗

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↗

Malignant hypertension secondary to cortisol-secreting adrenal tumour.

Adrenal cortical tumour-induced malignant hypertension is rare, except for some documented aldosterone-producing adenomas. Hypertension is a common feature of Cushing's syndrome, whereas malignant hypertension is rarely seen. This case in Taiwan is only the second reported case with malignant hypertension secondary to a cortisol-secreting adrenal tumour. The immunohistochemical study of the excised tumour showed strong positive staining of interleukin (IL)-6. IL-6 can trigger inflammatory vascular damage, which is typical in the malignant phase of hypertension. We hypothesise that IL-6 may have played an important role in this case.

Adrenal Cortex Neoplasms↗

PCB126 induces differential changes in androgen, cortisol, and aldosterone biosynthesis in human adrenocortical H295R cells.

Dioxins and polychlorinated biphenyls (PCBs) have been shown to accumulate in the adrenal glands when incorporated into the body. However, the impacts of exposure on adrenal steroidogenesis have not been thoroughly investigated. In this study, we demonstrated that dioxin-like PCB126 altered androgen, cortisol, and aldosterone biosynthesis differentially in human adrenocortical H295R cells. PCB126 diminished basal and cAMP-induced androstenedione production as well as CYP17 mRNA expression in a dose-dependent and time-dependent manner. The CYP17 repression was accompanied with decreases in the encoded 17 alpha-hydroxylase and 17,20-lyase activities, particularly the latter. In contrast, high concentrations of PCB126 stimulated basal cortisol and aldosterone biosynthesis, including induction of CYP21B, CYP11B1, and CYP11B2 mRNA expression and elevation of the conversion of cortisol from 17-OH-progesterone and aldosterone from progesterone. cAMP abolished the positive effect of PCB126 on cortisol synthesis, while it synergistically enhanced PCB126 stimulation on CYP11B2 expression and aldosterone production. It seemed likely that the downregulation of CYP21B caused by the combination of PCB126 and cAMP counteracted the CYP11B1 induction stimulated by the co-treatment. In addition, high concentrations of PCB126 might sensitize the regulation of adrenocorticotropin (ACTH) on the adrenocortical cells by increasing ACTH receptor levels. Because adrenal steroids have profound influences on glucose tolerance, insulin sensitivity, lipid metabolism, obesity, vascular function, and cardiac remodeling, this article also discusses the potential association of the detected adrenocortical alterations with increased diabetic and cardiovascular risk found among highly exposed people.

Adrenal Cortex↗

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↗

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↗

Reactivation of Epstein-Barr virus can be triggered by an Rta protein mutated at the nuclear localization signal.

Rta, an immediate-early protein of Epstein-Barr virus (EBV), is a transcriptional activator that induces lytic gene expression and triggers virus reactivation. Being located predominantly in the nucleus, Rta can exert its transactivation function through either direct DNA binding or certain indirect mechanisms mediated by cellular signalling and other transcriptional factors. This study examined whether the subcellular localization of Rta was critical for the induction of target genes. First, 410KRKK413 was identified as a nuclear localization signal (NLS) of Rta. An Rta mutant with the NLS converted to 410AAAA413 showed cytoplasmic localization and failed to activate the promoter of BGLF5. Interestingly, ectopic expression of the Rta mutant still disrupted EBV latency in an epithelial cell line. Reporter gene assays revealed that the NLS-mutated Rta retained the ability to activate two lytic promoters, Zp and Rp, at a considerable level. Thus, the cytoplasmic Rta mutant could induce expression of endogenous Zta and Rta, triggering reactivation of EBV.

Cell Nucleus↗

Mild cutaneous manifestation in two young women with extraordinary hyperandrogenemia.

Hyperandrogenism with hyperandrogenemia should be considered in those with severe acne of sudden onset or conspicuous male-pattern baldness with hairline recession, although the majority of female patients with acne or androgenetic alopecia possess no endocrine disorder. Herein we describe on the contrary 2 young women with primary amenorrhea displaying prominent hyperandrogenemia but subtle cutaneous manifestation. The first one presenting vertical alopecia had an elevated level of serum dehydroepiandrosterone sulfate (>800 microg/dl) and was suspected to be a case of late-onset, non-classical adrenal hyperplasia. The second case with mild acne had a soaring serum level of total testosterone >9,000 ng/dl derived from an androgen-secreting adrenal adenoma overexpressing steroidogenic acute regulatory protein, P450 side-chain cleavage enzyme and aromatase. A careful patient history and a complete physical examination are mandatory in each individual female case with acne or alopecia. The possibility of adrenal tumor should be explored in patients with escalated circulating testosterone.

Acne Vulgaris↗

Increased oxidative damage with altered antioxidative status in type 2 diabetic patients harboring the 16189 T to C variant of mitochondrial DNA.

A transition of T to C at nucleotide position 16189 in mitochondrial DNA (mtDNA) has attracted biomedical researchers for its probable correlation with the development of diabetes mellitus in adult life. In diabetes, persistent hyperglycemia may cause high production of free radicals. Reactive oxygen species are thought to play a role in a variety of physiologic and pathophysiologic processes in which increased oxidative stress may play an important role in disease mechanisms. The aim of the present study was to clarify the degree of oxidative damage and plasma antioxidant status in diabetic patients and to see the potential influence of the 16189 variant of mtDNA on the oxidative status in these patients. An indicative parameter of lipid peroxidation, malondialdehyde (MDA), and total free thiols were measured from plasma samples of 165 type 2 diabetic patients with or without this variant and 168 normal subjects. Here we report an increase in the plasma levels of MDA and total thiols in type 2 diabetic patients compared with control subjects. The levels of plasma thiols in diabetic patients with the 16189 variant of mtDNA were not different from those in controls. These results suggest an increase in the oxidative damage and a compensatory higher antioxidative status in patients with type 2 diabetes. Harboring the 16189 mtDNA variant may impair the ability of a cell to respond properly to oxidative stress and oxidative damage.

Antioxidants↗

Recurrent Klebsiella pneumoniae liver abscess in a diabetic patient followed by Streptococcus bovis endocarditis--occult colon tumor plays an important role.

Klebsiella pneumoniae is the leading cause of liver abscess in diabetic patients in Taiwan. We report the case of a diabetic patient with a history of four episodes of K. pneumoniae liver abscess within 3 years. The patient later developed Streptococcus bovis bacteremia originating from a colon tumor with complications of endocarditis, osteomyelitis, and silent splenic abscess. Occult colon tumor may have played an important role in our case, with recurrent infection arising from colonizers of the gastrointestinal tract. As our case shows, the possible association between occult colon tumor and K. pneumoniae liver abscess in diabetic patients should be surveyed.

Adenoma, Villous↗

Polychlorinated biphenyl 126 stimulates basal and inducible aldosterone biosynthesis of human adrenocortical H295R cells.

To understand the effects of polychlorinated biphenyls (PCBs) on adrenal aldosterone biosynthesis, we have performed a systematical study to characterize the corresponding steroidogenic response of human adrenocortical cell line H295R to PCB126 exposure. We found that PCB126 at high concentrations stimulated basal and inducible aldosterone production. The aldosterone induction occurred concomitantly with activation of the CYP11B2 gene. Despite the fact that PCB126 acted in synergy with both potassium and angiotensin II (Ang II) in activation of aldosterone synthesis, PCB126 only modestly increased CYP11B2 mRNA expression in the presence of Ang II contrary to the synergistic transcriptional induction elicited by PCB126 and potassium. This implicated that PCB126 had differential interactions with the potassium and Ang II signaling systems in the regulation of aldosterone biosynthesis. In addition, high concentrations of PCB126 elevated transcriptional expression of the type I Ang II receptor (AT(1)) and might thus sensitize the cellular Ang II responsiveness in both basal and inducible aldosterone biosynthesis. SF-1 was not involved in the PCB126-induced transcriptional regulation despite its importance in steroidogenic gene activation.

Adrenal Cortex↗

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↗

Influence of 131I diagnostic dose on subsequent ablation in patients with differentiated thyroid carcinoma: discrepancy between the presence of visually apparent stunning and the impairment of successful ablation.

BACKGROUND: In the management of patients with differentiated thyroid carcinoma, direct comparison of the presence of scintigraphic stunning after a diagnostic dose of 131I with subsequent successful ablation has not been evaluated. METHODS: This study included 245 patients who received a dose of 2775-3700 MBq of 131I for thyroid remnant ablation. In all patients, the thyroid-stimulating hormone (TSH) level before ablation was more than 30 microlU x ml. One hundred and twenty-six patients (Group A) were given a 185 MBq diagnostic scan (Dscan) 4-11 days before 131I ablation, and 119 patients (Group B) received 131I ablation directly after thyroidectomy. Scintigraphic stunning was considered to be present on any post-ablation scan that revealed either fewer foci or obviously less prominent uptake compared with the earlier corresponding Dscan. Successful ablation was defined as no visible uptake in the neck region or anywhere else on a follow-up Dscan 6-12 months later. RESULTS: Our results revealed that only 13 of the 126 patients (10.3%) in Group A had visually apparent thyroid stunning. Successful ablation was obtained in 56 of 126 cases (44.4%) in Group A, compared with 86 of 119 cases (72.2%) in Group B (P<0.001). In Group A, the success rate of ablation in patients with stunning (5/13) was not statistically different from that in those without (51/113) (odds ratio, 0.76; 95% CI, 0.23-2.47). Multiple logistic regression analysis revealed that the independent determinants of successful ablation were the use of Dscan before ablation (odds ratio, 0.23; 95% CI, 0.10-0.56) and the ablation dose of 131I (odds ratio, 1.05; 95% CI, 1.00-1.10). CONCLUSIONS: Visually apparent stunning is infrequent and may not be sufficiently sensitive to detect the influence of a 185 MBq Dscan on subsequent ablation outcome. For patients with differentiated thyroid carcinoma, we recommend that ablation should be performed directly after thyroidectomy.

Adult↗

Expression, by functional proteomics, of spontaneous tolerance in rat orthotopic liver transplantation.

Orthotopic liver transplants (OLT) performed in certain combinations of donor and recipient rat strains, such as DA (RT1a) to PVG (RT1c), without immunosuppressive drugs could completely overcome major histocompatibility complex barriers. Although other organs transplanted in a similar fashion within the same combination have been promptly rejected, 60 day post-OLT serum (POD 60) has been proven competent in rapidly reversing the established rejection in animal models. In order to understand the functional role of tolerogenic serum proteins and their involvement with immune response regulation, a comprehensive analysis surveying global changes in complex OLT systems by proteomic techniques was applied. The results display the varying protein expressions in sera extracted from naïve and transplanted animals on POD 60 with regard to immunosuppression. Among these proteins, haptoglobin (Hp) which is related to inhibition of T-cell proliferation was found to be up-regulated following OLT. In addition, the transcriptional expression level and intracellular localization of Hp correlated with the immune events. Hp also exhibited a strong in vitro immunosuppressive effect on the mixed lymphocyte reaction. In conclusion, the presence of Hp may play an important role in modulating the spontaneous tolerance of liver transplantation. Furthermore, the serum proteome map could provide guidance with respect to discovering potential protein targets in OLT tolerance and eventually prolong hepatic allograft survival in the future.

Amino Acid Sequence↗