Biomedical subjects

Bong Soo Cha

Publications and source records attributed to Bong Soo Cha.

At least 37 records · Page 2Linked to original sources

PubMed2005

Normative values of carotid artery intima-media thickness in healthy Korean adults and estimation of macrovascular diseases relative risk using this data in type 2 diabetes patients.

The objectives of this study were to determine normative values of carotid intima-media thickness (IMT) in healthy Korean subjects and to use these values to estimate the relative risk of macrovascular diseases in patients with type 2 diabetes mellitus (T2DM). High-resolution B-mode ultrasonography was performed in 1,229 healthy subjects and 830 T2DM patients. Height, weight, blood pressure, fasting plasma glucose, total cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol, and fasting insulin level were measured. Subjects were classified as healthy subjects; T2DM patients without ischemic heart disease (IHD), stroke, and peripheral arterial occlusive diseases (PAOD); T2DM patients with IHD, stroke, or PAOD. IMT was significantly increased as age increased. Patients with T2DM had higher IMTs compared to healthy subjects. Independent risk factors of IMT were age, systolic blood pressure, BMI for healthy subjects, and age, duration of diabetes, LDL-cholesterol for T2DM subjects. According to presence of increased IMT, the relative risks of IHD, stroke, and PAOD in diabetic subjects, were 2.34 (CI; 1.32-4.14), 2.95 (CI; 1.46-5.54), and 3.64 (CI; 1.66-7.40), respectively. This study suggests normative values that can be used as an index for carotid artery IMT of healthy Korean subjects, and that IMT data reflects the risk of macrovascular diseases in T2DM.

Adult↗

PubMed2005

Duodenal somatostatinoma associated with diabetic ketoacidosis presumably caused by somatostatin-28 hypersecretion.

CONTEXT: Extrapancreatic somatostatinoma is very rare and clinically distinguished from its pancreatic counterpart because somatostatinoma syndrome with mild diabetes is rare in extrapancreatic somatostatinoma because of poor secretion of somatostatin. Moreover, because somatostatin inhibits the secretion of insulin and glucagon simultaneously, true diabetic ketoacidosis (DKA) seldom ensues. PATIENT: A 23-yr-old woman presented with DKA and an abdominal mass. A computed tomography scan showed a huge, encapsulated mass in a duodenal submucous portion. A high circulating level of somatostatin was detected (67.2 pmol/liter; reference range, 0.6-7.3 pmol/liter). INTERVENTION: The tumor mass was successfully removed with Whipple's procedure, and the patient gradually recovered both clinically and biochemically. RESULTS: Immunohistochemical staining of the tumor tissue exhibited diffusely positive for somatostatin and somatostatin-28 but negative for insulin, glucagon, calcitonin, serotonin, and S-100. CONCLUSION: As far as we know, this is the first case report of gastrointestinal somatostatinoma associated with DKA.

Adult↗

PubMed2005

The prevalence of the metabolic syndrome in Korean adults: comparison of WHO and NCEP criteria.

The aims of this study were to compare the prevalence of the metabolic syndrome according to the WHO and NCEP ATP III criteria in Korean adults, and to compare the prevalence of the metabolic syndrome with the results in previous Korean studies. The study comprised 1,230 subjects (627 men, 603 women) aged 30-79 years (mean 52.4 +/- 10.3 years) who underwent medical check-up from April to June, 2001 in the Korea Association of Health (KAH). The prevalence of the metabolic syndrome according to the modified WHO criteria was 21.8 % of men and 19.4 % of women. However, the prevalence was increased 1.6 times (34.2 % ) in men and 2.0 times (38.7 % ) in women using the modified NCEP criteria. The prevalence of the metabolic syndrome has varied widely according to differences in the criteria. Thus, further studies are necessary to define the appropriate criteria of the metabolic syndrome for Korean adults.

Adult↗

PubMed2005

Relationship of serum high sensitivity C-reactive protein to metabolic syndrome and microvascular complications in type 2 diabetes.

The high sensitivity C-reactive protein (hsCRP) is known to be a sensitive predictor of coronary heart disease and type 2 diabetes. This study evaluated the association between the serum hsCRP and the components of metabolic syndrome (MS) and microvascular complications in type 2 diabetes. Two hundred and sixty-nine patients with type 2 diabetes were enrolled. All the subjects underwent measurement of MS and carotid intima-media thickness (IMT). The serum hsCRP concentrations and the 24 h urine albumin excretion amounts were measured. Ophthalmoscope examinations and nerve conduction velocity tests were performed to evaluate microvascular complications. The hsCRP was significantly higher in the patients with MS than in those without (p=0.019). The serum hsCRP was significantly correlated with all the components of MS. There were no differences between the serum hsCRP levels of those with and without retinopathy and neuropathy. The serum hsCRP was correlated with the 24 h urine albumin excretion amount. Serum hsCRP level has a significant correlation with MS and might be used as the future criteria of MS. Among microvascular complications, only diabetic nephropathy is associated with the serum hsCRP level. It suggests that the inflammatory process plays a role in nephropathy in type 2 diabetes.

Biomarkers↗

PubMed2005

Safety and efficacy of adeno-associated viral vector-mediated insulin gene transfer via portal vein to the livers of streptozotocin-induced diabetic Sprague-Dawley rats.

BACKGROUND: Previous studies demonstrating the efficacy of insulin gene therapy have mostly involved use of adenoviral vectors or naked DNA to deliver the insulin gene. However, this procedure may not guarantee long-term insulin production. To improve the performance, we prepared recombinant adeno-associated viral vectors (rAAV) harboring the gene encoding a furin-modified human insulin under the cytomegalovirus (CMV) promoter [rAAV-hPPI(F12)]. METHODS: Streptozotocin (STZ)-induced diabetic Sprague-Dawley rats were used as a diabetic animal model. The levels of blood glucose, insulin, and HbA1c were measured to test the effect. An intraperitoneal glucose tolerance test was performed to test the capability of blood glucose disposal. Immunohistochemical staining and Northern blot analyses were performed to survey the expression pattern of the therapeutic insulin gene. RESULTS: STZ-induced diabetic Sprague-Dawley rats infused via the portal vein with rAAV-hPPI(F12) produced human insulin and after a 6-h fast were normoglycemic for over 90 days post-treatment, whereas diabetic rats treated with recombinant adenoviral vector harboring the hPPI(F12) gene [rAV-hPPI(F12)] were normoglycemic only for days 3 to 13 post-treatment. Insulin mRNA was detected mainly in the liver of the rAAV-hPPI(F12)-treated diabetic rats. The glucose tolerance capability of the rAAV-hPPI(F12)-treated diabetic rats was comparable to that of non-diabetic rats, even without injection of recombinant insulin. Furthermore, blood HbA1c concentrations in rAAV-hPPI(F12)-treated diabetic rats were reduced to almost the normal level. Importantly, studies of rAV or rAAV vector-dependent side effects on the targeted liver strongly suggested that only rAAV treatment caused no side effects. CONCLUSIONS: These results demonstrate that our rAAV-mediated in vivo insulin gene therapy provides safer maintenance of the insulin gene expression required for long-term and thus more effective blood glycemic control.

Animals↗

PubMed2005

Effects of Pro12Ala polymorphism of peroxisome proliferator-activated receptor gamma2 gene on rosiglitazone response in type 2 diabetes.

OBJECTIVE: The aim of this study was to examine the effects of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor (PPAR) gamma2 gene on the response to rosiglitazone in patients with type 2 diabetes mellitus. METHODS: A total of 198 patients with type 2 diabetes mellitus were treated with rosiglitazone (4 mg/d) for 12 weeks without a change in previous medications. All patients were genotyped for the PPARgamma2 Pro12Ala polymorphism. RESULTS: The Ala12 allele frequency was 0.04. Of the 198 patients, 183 had the Pro12Pro genotype and 15 had the Pro12Ala genotype. The Ala12Ala genotype was not observed. The decrease in fasting plasma glucose level was significantly greater in subjects with the Ala12 allele than in those without the allele (50.6 +/- 27.8 mg/dL versus 24.3 +/- 41.9 mg/dL, P = .026). In addition, the decrease in hemoglobin A(1c) level was significantly greater in subjects with the Ala12 allele than in those without the allele (1.41% +/- 1.47% versus 0.57% +/- 1.16%, P = .015). There was a significant difference in the response rate to rosiglitazone treatment between the Pro12Pro group and the Pro12Ala variant group (43.72% versus 86.67%, P = .002). CONCLUSION: Patients with the Pro12Ala genotype in the PPARgamma2 gene had a better therapeutic response to rosiglitazone than did patients with the Pro12Pro genotype. The genetic variations in the PPARgamma2 gene can affect the response to rosiglitazone treatment in patients with type 2 diabetes mellitus.

Adult↗

PubMed2005

Predictive clinical parameters for therapeutic efficacy of rosiglitazone in Korean type 2 diabetes mellitus.

This study evaluated the efficacy of rosiglitazone in non-obese and obese Korean type 2 diabetic patients of long duration. A total of 125 patients (M:F=44:81, mean age: 58.4+/-9.1 years, BMI: 24.2+/-2.7 kg/m2, duration of diabetes: 11.0+/-6.4 years) were randomly allocated to 12 weeks of rosiglitazone treatment (4 mg per day) or a control group. Responders were defined as patients who experienced fasting plasma glucose (FPG) reduction of >20% or HbA1c reduction of >1 (%). Rosiglitazone significantly improved glycemic control by reducing FPG and HbA1c (-3.4 mmol/l and -1.1%, P<0.001, respectively). It also significantly increased HOMA(beta-cell function) (+9.7, P<0.01) and QUICKI (+0.029, P<0.001), and decreased HOMA(IR) (-1.73, P<0.001). Females and those with higher waist-hip ratio made up a greater portion of rosiglitazone-responders. Responders (45 patients, 75%) also showed significantly higher FPG, HbA1c, systolic blood pressures, fasting insulin levels and HOMA(IR), and lower QUICKI than nonresponders. Among these parameters of responders, waist-hip ratio of non-obese subgroup, initial glycemic control of obese subgroup, and systolic blood pressure of both subgroups lost their significance after subdivision analysis. However, the baseline HOMA(IR) and QUICKI were significantly correlated with the response rate to rosiglitazone. Moreover, in multiple logistic regression analysis, HOMA(IR) and QUICKI retained their significance as the independent predictors. Even in Korean type 2 diabetic patients of long duration but with relatively preserved beta-cell function, rosiglitazone improved glycemic control, insulin sensitivity, and beta-cell function. In this ethnic group, female gender, central obesity, and especially severe insulin resistance were identified as predictive clinical parameters of rosiglitazone-responders.

Adult↗

PubMed2005

Limitation of the validity of the homeostasis model assessment as an index of insulin resistance in Korea.

Homeostasis model assessment of insulin resistance (HOMA-IR) is a less invasive, inexpensive, and less labor-intensive method to measure insulin resistance (IR) as compared with the glucose clamp test. The aim of this study was to evaluate the validity of HOMA-IR by comparing it with the euglycemic clamp test in determining IR. We assessed the validity of HOMA-IR by comparing it with the total glucose disposal rate measured by the 3-hour euglycemic-hyperinsulinemic clamp in subjects with type 2 diabetes (n = 47), impaired glucose tolerance (n = 21), and normal glucose tolerance (n = 22). There was a strong inverse correlation (r = -0.558; P < .001) between the log-transformed HOMA-IR and the total glucose disposal rate. There was moderate agreement between the 2 methods in the categorization according to the IR (weighted kappa = 0.294). The magnitude of the correlation coefficients was smaller in the subjects with a lower body mass index (BMI <25.0 kg/m2 , r = -0.441 vs BMI > or =25.0 kg/m2 , r = -0.615; P = .032), a lower HOMA-beta cell function (HOMA- beta <60.0, r = -0.527 vs HOMA- beta > or =60.0, r = -0.686; P = .016), and higher fasting glucose levels (fasting glucose < or =5.66 mmol/L, r = -0.556 vs fasting glucose >5.66 mmol/L, r = -0.520; P = .039). The limitation of the validity of the HOMA-IR should be carefully considered in subjects with a lower BMI, a lower beta cell function, and high fasting glucose levels such as lean type 2 diabetes mellitus with insulin secretory defects.

Adult↗

PubMed2005

High prevalence of c-RET expression in papillary thyroid carcinomas from the Korean population.

BACKGROUND: Activation of the RET proto-oncogene, located on the long arms of chromosome 10, contributes to the development of thyroid cancers in two different ways. First, somatic rearrangements of RET with variable activation genes are frequently found in papillary thyroid carcinomas. Second, germ-line point mutations are responsible for the development of medullary thyroid carcinomas and multiple endocrine neoplasia type 2 (MEN 2). There are several conflicting reports on the influences of RET expression and RET/PTC rearrangements on the clinical outcome of thyroid cancers. Therefore, the wild-type RET gene expression and RET/PTC-1, RET/PTC-2, RET/PTC-3 rearrangements were examined in thyroid carcinomas and other thyroid diseases. MATERIALS AND METHODS: Thirty-six papillary thyroid carcinomas (PTCs), 8 follicular thyroid carcinomas (FTCs), 4 anaplastic thyroid carcinomas (ATC), 7 follicular adenomas (FAs), 23 hyperplasias, 6 normal thyroid tissues, and 39 normal portions from each tumor were included in this study. Reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical analyses were used to identify the RET gene and RET/PTC rearrangements. RESULTS: From the RT-PCR analysis, 68.9% of the PTCs, a single case of FTC, and 22.2% of the hyperplasias expressed the RET gene. No RET gene expression was observed in ATCs, FAs, or normal thyroid tissues. One RET/PTC-1 and one RET/PTC-2 rearrangement were detected in the PTCs. No RET/PTC-3 rearrangement was detected in any specimen. The immunohistochemical results revealed that 66.7% of PTCs, 28.6% of FAs, and 18.2% of hyperplastic thyroid tissue specimens showed high levels of RET protein expression. Neither the normal thyroid tissues nor the FTCs and ATC, showed high levels of RET protein expression. The two methods are agreed in PTC and hyperplastic nodules, but not in FA and FTC. CONCLUSION: PTCs among Koreans rarely showed RET/PTC rearrangements, but commonly showed increased RET gene expression. Compared to earlier reports indicating that the expression of the RET gene was limited to PTCs, the RET gene was also expressed in hyperplasias in this study.

Adenocarcinoma, Papillary↗

PubMed2005

Is high-sensitivity C-reactive protein associated with carotid atherosclerosis in healthy Koreans?

BACKGROUND: There is a positive association between chronic inflammation and the risk of cardiovascular disease, but whether there is an association between C-reactive protein (CRP) and carotid atherosclerosis is controversial. We investigated the relationship between high-sensitivity CRP (hsCRP) levels and carotid intima-media thickness (IMT) in healthy Koreans. DESIGN: We measured hsCRP levels, the carotid IMT, and conventional cardiovascular risk factors including obesity parameters, blood pressure, lipid profiles, insulin resistance, and smoking habits in 820 volunteers (35-79 years old) in a cross-sectional study. RESULTS: Higher hsCRP quartile groups had higher mean IMTs, as compared with the lowest quartile (P < 0.001 for the trend across quartiles). However, after adjustment for age, the relationship between hsCRP level and IMT was substantially weaker (P = 0.018). After additional adjustments for conventional cardiovascular risk factors, no significant association was observed (P = 0.548). The unadjusted risk for a high carotid IMT value (> or = 1.0 mm) was also positively related to hsCRP quartile, but this relationship was not significant after adjustment for age and other cardiovascular risk factors. CONCLUSIONS: Both hsCRP levels and the carotid IMT were strongly correlated with conventional cardiovascular risk factors, but there was no independent association between hsCRP levels and carotid IMT in healthy Korean adults.

Adult↗

PubMed2005

Clinical features of bone metastases resulting from thyroid cancer: a review of 28 patients over a 20-year period.

Bone is the second most frequent site of metastasis resulting from thyroid cancer. Many studies have investigated clinical features and prognostic factors of distant metastases stemming from thyroid cancer in Western countries. The purpose of this study was to review clinical characteristics of Korean patients with bone metastasis originating from thyroid cancer. Between January 1985 and August 2004, 28 patients with thyroid cancer were diagnosed with bone metastases at the Yonsei Severance Hospital in Seoul, Korea. Their clinical characteristics were analyzed retrospectively. Incidence of bone metastasis from follicular thyroid cancer was 6.8% (9 of 132 patients), and 0.4% (13 of 3,154 patients) from papillary thyroid cancer, with an odds ratio of 17.67 (95% confidence interval; 7.41-42). Twelve patients had no symptoms of bone metastasis. Overall mean number of metastasis sites was 2.6 +/- 1.9, and 12 patients had a solitary bone metastasis. Survival rates between the synchronous and metachronous metastasis groups were not significantly different, and the number of metastasis sites did not affect survival. However, the survival of patients that underwent curative treatment was longer than those with palliation (P = 0.0317). In Korea, the overall incidence of bone metastasis resulting from thyroid cancer was less than our expectation. Many patients were asymptomatic, and had a tendency of undergoing less aggressive or palliative treatment, even though the long-term survival of distant metastasis resulting from thyroid cancer with active treatment is relatively good. Further studies of the prognostic factors and effectiveness of various treatments of these patients are needed to enhance survival.

Adenocarcinoma, Follicular↗

PubMed2005

The influence of adiponectin gene polymorphism on the rosiglitazone response in patients with type 2 diabetes.

OBJECTIVE: The aim of this study was to examine the effects of rosiglitazone on adiponectin and plasma glucose levels in relation with common adiponectin gene (ACDC) polymorphisms. RESEARCH DESIGN AND METHODS: A total of 166 patients with type 2 diabetes were treated with rosiglitazone (4 mg/day) for 12 weeks without changing any of their previous medications. In all, single nucleotide polymorphism (SNP)45 and SNP276 of ACDC were examined. RESULTS: Regarding SNP45, there was a smaller reduction in the fasting plasma glucose (FPG) level and the HbA(1c) value in the carriers of the GG genotype than in the carriers of the other genotypes (P = 0.031 and 0.013, respectively). There was a smaller increase in the serum adiponectin concentration for the GG genotype than for the other genotypes (P = 0.003). Regarding SNP276, there was less reduction in the FPG level for the GG genotype than for the other genotypes (P = 0.001). In the haplotype analysis, the reductions in the FPG and HbA(1c) levels were smaller for the GG homozygote haplotype than for the other haplotypes (P = 0.001 and 0.001, respectively). The increase in the plasma adiponectin concentration for the GG homozygote haplotype was smaller than that of the other haplotypes (P = 0.003). CONCLUSIONS: These data suggest that genetic variations in the adiponectin gene can affect the rosiglitazone treatment response of the circulating adiponectin level and blood glucose control in type 2 diabetic patients.

Adiponectin↗

PubMed2005

Hypercalcemia in hepatic tuberculosis: a case report in Korea.

Although primary hyperparathyroidism and malignant diseases account for approximately 90% of the causes of hypercalcemia, they could occur in association with granulomatous diseases such as tuberculosis or sarcoidosis, especially in developing countries. Hepatic tuberculosis is difficult to diagnosis without suspicion in cases with normal findings on chest radiographs. We report a 70-year-old woman who presented with hypercalcemia due to hepatic tuberculosis. The diagnosis was made by a computed tomography scan and laparoscopic evaluation. After treatment with anti-tuberculosis medication, her hypercalcemia resolved. Increased vitamin D synthesis by activated macrophages in the granuloma tissue is the major mechanism of hypercalcemia in tuberculosis.

Aged↗

PubMed2004

Metabolic significance of nonalcoholic fatty liver disease in nonobese, nondiabetic adults.

BACKGROUND: Obesity and type 2 diabetes are well-known risk factors for the development of nonalcoholic fatty liver disease (NAFLD). However, NAFLD is not rare in nonobese, nondiabetic adults. The aim of this study was to evaluate the metabolic significance of NAFLD in nonobese, nondiabetic adults. METHODS: This study examined 768 nonobese (body mass index [BMI] [calculated as weight in kilograms divided by the square of height in meters], > or =18.5 and <30) (460 normal-weight and 308 overweight subjects), nondiabetic individuals older than 30 years who participated in a medical checkup. All the subjects had negative serologic findings for hepatitis B and C viruses and had an alcohol intake less than 140 g/wk. A standard interview, anthropometrics, a biochemical study, and abdominal ultrasonography were conducted. RESULTS: The prevalence of NAFLD in the enrolled subjects was 23.4%. In the normal-weight (BMI, > or =18.5 and <25) and overweight (BMI, > or =25 and <30) groups, NAFLD was a significant predictor of insulin resistance and other metabolic disorders, including hypertriglyceridemia and hyperuricemia. The odds ratio of the metabolic disorders in subjects with NAFLD compared with those without NAFLD in the normal-weight group was higher than that in the overweight group. Multiple logistic regression analysis showed that sex, waist circumference, triglyceride level, and insulin resistance were independently associated with NAFLD in the normal-weight group. CONCLUSIONS: Nonalcoholic fatty liver disease is closely associated with metabolic disorders, even in nonobese, nondiabetic subjects. Nonalcoholic fatty liver disease can be considered an early predictor of metabolic disorders, particularly in the normal-weight population.

Adult↗

PubMed2004

The correlation between insulin resistance and the visceral fat to skeletal muscle ratio in middle-aged women.

Central obesity with visceral fat accumulation and the amount of skeletal muscle mass may influence insulin sensitivity via its capacity for glucose load uptake. We investigated the relationships among the following metabolic variables: ratio of fat area to skeletal muscle area (VMR), percent ideal body weight, body mass index, waist-to-hip circumference (WHR) and visceral fat to subcutaneous fat ratio (VSR) in 114 nondiabetic middle-aged women. Anthropometric parameters, lipid profiles and sex hormone- binding globulin were measured. Visceral and subcutaneous fat areas at the umbilical level and the skeletal muscle area at the mid-thigh level were measured and computed. 75-gram OGTT tests were performed, along with measuring plasma glucose, insulin and free fatty acid levels, according to which area under the curve of glucose (Glu-AUC), insulin (Ins-AUC), free fatty acid (FFA-AUC) and glucose/insulin ratio (GIR=Glu- AUC/Ins-AUC), were calculated. 1) Triglyceride was more correlated with VSR than VMR. 2) The independent anthropometric parameters for each metabolic variable were In conclusion, VMR for Ins-AUC, WHR for Glu-AUC and total cholesterol, and VSR for triglyceride. 3) For subjects with higher VMR, age, Ins-AUC and triglyceride were significantly higher. 4) Subjects with higher VMR were older and showed higher Ins-AUC and lower GIR than the subjects with lower VMR. In conclusion, VMR is an anthropometric parameter that reflects insulin resistance concerning glucose metabolism, and VSR is thought to be a good parameter that that reflects the serum lipid levels. Further prospective studies are necessary to reevaluate the visceral fat vs. skeletal muscle relationship.

Adipose Tissue↗

PubMed2004

Peroxisomal-proliferator-activated receptor alpha activates transcription of the rat hepatic malonyl-CoA decarboxylase gene: a key regulation of malonyl-CoA level.

MCD (malonyl-CoA decarboxylase), which catalyses decarboxylation of malonyl-CoA, is known to play an important role in the regulation of malonyl-CoA concentration. Recently, it has been observed that the expression of MCD is significantly decreased in the hearts of the PPARalpha (peroxisome-proliferator-activated receptor alpha) (-/-) mice, where the rate of fatty-acid oxidation is decreased by the increased malonyl-CoA level [Campbell, Kozak, Wagner, Altarejos, Dyck, Belke, Severson, Kelly and Lopaschuk (2002) J. Biol. Chem. 277, 4098-4103]. This suggests that MCD may be transcriptionally regulated by PPARalpha. To investigate whether PPARalpha is truly responsible for transcriptional regulation of the rat MCD gene, transient reporter assay was performed in CV-1 cells. The promoter activity was increased by 17-fold in CV-1 cells co-transfected with PPARalpha/retinoid X receptor alpha expression plasmid. In sequence analysis of the promoter region, three putative PPREs (PPAR response elements) were identified, and promoter deletion analysis showed that PPRE2 and PPRE3 were functional. Electrophoretic mobility-shift assays revealed that PPARalpha/retinoid X receptor alpha heterodimer indeed bound to the two PPREs, and the binding specificity of PPARalpha on PPRE was also confirmed by experiments with mutated oligonucleotides. These results indicate that the elements behaved as a responsive site to PPARalpha activation. MCD mRNA levels in WY14643-treated rat hepatoma cells as well as in the liver of fenofibrate-fed Otsuka Long-Evans Tokushima fatty rats were also found to be increased, suggesting that PPARalpha can activate the rat hepatic MCD transcription by binding to the PPREs in the promoter. We propose that MCD performs an important role in understanding the regulatory mechanism between activated PPARalpha and fatty-acid oxidation by altering the malonyl-CoA concentration.

Animals↗

PubMed2004

Targeting of therapeutic gene expression to the liver by using liver-type pyruvate kinase proximal promoter and the SV40 viral enhancer active in multiple cell types.

To achieve the liver-directed expression in sufficient amounts of therapeutic genes for successful and safe gene therapy, natural liver-specific promoters can be used to direct the expression of therapeutic genes in the liver, whereas strong viral enhancers were used to obtain sufficient amounts of expressed therapeutic gene products. However, very often use of either the former or the latter does not guarantee both potent and liver-specific therapeutic gene expression. Here we conglomerate them and thus create a potent tissue-specific promoter by characterizing and using the liver-type pyruvate kinase proximal promoter (LPKPP) harboring its TATA box and a HNF-1alpha binding site. Alone it hardly activated its reporter gene expression in non-hepatocytes or hepatocytes. However, in the presence of the SV40 viral enhancer (SV40VE), which is active in multiple cell types, it was able to potently activate its reporter gene expression specifically in hepatocytes. The tissue-specific activation of the LPKPP by the viral enhancer was attributed to HNF-1alpha binding to the LPKPP. Taken together, these results support the idea that the constitutively active SV40VE could be used to activate the LPKPP in a tissue-specific manner in the presence of HNF-1alpha. To our knowledge, this is the first study to utilize HNF-1alpha and its binding site, in the context of the LPKPP, to generate a basal promoter that is transcriptionally activated potently in a tissue-specific manner by a viral enhancer that is active in multiple cell types.

Cell Line, Tumor↗

PubMed2004

Serum high sensitivity C-reactive protein is associated with carotid intima-media thickness in type 2 diabetes.

BACKGROUND: High sensitivity C-reactive protein (hsCRP) is more sensitive than standard C-reactive protein (CRP) assay in evaluating the risk of coronary heart disease and other atherosclerotic events. By this time, there are several reports that type 2 diabetic subjects have higher serum levels of hsCRP than those of non-diabetic subjects. However, there are few reports about factors which have influence upon the level of serum hsCRP in type 2 diabetic subjects. We had evaluated the association of serum hsCRP level with risk factors of cardiovascular diseases and carotid intima-media thickness (IMT) in type 2 diabetic subjects. METHODS: One hundred and five patients (59 men and 46 women) with type 2 diabetes were recruited. Subjects with severe cardiovascular diseases were excluded. All subjects were undergone carotid ultrasonography for evaluation of carotid IMT. Serum hsCRP concentrations were measured. RESULTS: Serum hsCRP level was correlated with mean left IMT (r = 0.366, P = 0.003), maximal left IMT (r = 0.370, P = 0.002), mean right IMT (r = 0.281, P = 0.023) and maximal right IMT (r = 0.370, P = 0.002), body mass index (r = 0.377, P < 0.001), waist circumference (r = 0.342, P < 0.001), waist-hip ratio (r = 0.229, P = 0.020), serum total cholesterol (r = 0.202, P = 0.024), serum triglyceride (r = 0.292, P = 0.022) and serum low-density lipoprotein (r = 0.133, P = 0.044). CONCLUSION: Our result shows that serum hsCRP level is correlated with carotid IMT and the risk factors of cardiovascular diseases and may be useful to predict accelerated atherosclerotic process in type 2 diabetic subjects.

Adult↗