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Biomedical subjects

Soo-Jin Lee

Publications and source records attributed to Soo-Jin Lee.

7 recordsLinked to original sources

Involvement of Ca2+, CaMK II and PKA in EGb 761-induced insulin secretion in INS-1 cells.

EGb 761, a standardized form of Ginkgo biloba L. (Ginkgoaceae) leaf extract, was recently reported to increase pancreatic beta-cell function. To determine whether EGb 761 elicits insulin secretion directly, we treated INS-1 rat beta cells with EGb 761 and then measured insulin release. Treatment of EGb 761 (50 microg/ml) significantly stimulated insulin secretion in INS-1 cells, compared with untreated control (p<0.05) and the stimulatory effect of EGb 761 on insulin secretion was dose-dependent. To elucidate the mechanism of EGb 761-induced insulin secretion, we investigated the involvement of calcium. The treatment with nifedipine, an L-type calcium channel blocker, prevented EGb 761-induced insulin secretion and furthermore, EGb 761 itself elevated [Ca(2+)](i), suggesting the involvement of calcium in this process. To identity the protein kinases involved in EGb 761-induced insulin secretion, INS-1 cells were treated with different kinase inhibitors and their effects on EGb 761-induced secretion were investigated. KN62 and H89, calium/calmodulin kinase (CaMK) II and protein kinase A (PKA) inhibitor, respectively, significantly reduced EGb 761-induced insulin secretion. Immunoblotting studies showed an increase in the phosphorylated-forms of CaMK II and of PKA substrates after EGb 761 treatment. Our data suggest that EGb 761-induced insulin secretion is mediated by [Ca(2+)](i) elevation and subsequent activation of CaMK II and PKA.

Animals↗

Should the lower limit of impaired fasting glucose be reduced from 110 mg/dL in Korea?

The aims of this study were to determine if impaired fasting glucose should be redefined as a fasting plasma glucose (FPG) of 100 to 125 mg/dL (5.6-6.9 mmol/L) in Korea. A prospective cohort study was undertaken involving 13189 male workers aged 30 to 59 years who did not have medication for diabetes, a history of any cancer, or a fasting glucose level of 126 mg/dL or higher at the initial examination between January 1999 to December 2000. Subjects were reexamined at periodic annual health examination over a 5-year period. The receiver operating characteristic curve for predicting the future onset of diabetes was derived by plotting the sensitivity against 1 - specificity for a baseline FPG of less than 126 mg/dL. The age- and body mass index-adjusted incidence density of type 2 diabetes mellitus was examined according to the percentile of the distribution for the baseline FPG. The baseline FPG for predicting the future onset of diabetes at a point on the receiver operating characteristic curve that was closest to the ideal 100% sensitivity and 100% specificity was 92 mg/dL. There was a threshold for the age- and body mass index-adjusted incidence density of diabetes in the group with FPG of 93 to 95 mg/dL, at a mean of 93.9 mg/dL. Lowering the lower limit of impaired fasting glucose to 100 mg/dL (5.6 mmol/L) would optimize its sensitivity and specificity for predicting the future onset of diabetes in Korea.

Adult↗

The methylene chloride fraction of Trichosanthis Fructus induces apoptosis in U937 cells through the mitochondrial pathway.

Trichosanthis kirilowii MAXIM has been used as a folk remedy to treat diabetes, leukemia, and breast cancer. In the present study, the apoptotic mechanism of the methylene chloride fraction of Trichosanthis Fructus (MCTF) was investigated in human leukemic U937 cells. MCTF exhibited antiproliferative effectsagainst U937 cells (IC50=ca. 8 microg/ml). Apoptotic bodies were observed in MCTF-treated U937 cells in the TUNEL assay. We also confirmed that MCTF significantly increases annexin V(+)/propidium iodide-cells using FACS analysis. MCTF treatment activated caspase-8, -9 and -3, and led to cleaved poly (ADP-ribose) polymerase and release of cytochrome c into cytosol in a concentration-dependent manner, while MCTF did not affect Bax or Bcl-2 protein levels as shown by Western blot analysis. Taken together, these results indicate that MCTF can induce apoptosis in U937 cells chiefly via a mitochondrial-mediated pathway and suggest that Trichosanthis Fructus can be used in cancer treatment as a chemopreventive agent.

Antineoplastic Agents, Phytogenic↗

Fas-associated factor 1, FAF1, is a member of Fas death-inducing signaling complex.

FAF1 has been introduced as a Fas-binding protein. However, the function of FAF1 in apoptotic execution is not established. Based on the fact that FAF1 is a Fas-binding protein, we asked if FAF1 interacted with other members of the Fas-death-inducing signaling complex (Fas-DISC) such as Fas-associated death domain protein (FADD) and caspase-8. FAF1 could interact with caspase-8 and FADD in vivo as well as in vitro. The death effector domains (DEDs) of caspase-8 and FADD interacted with the amino acid 181-381 region of FAF1, previously known to have apoptotic potential. Considering that FAF1 directly binds to Fas and caspase-8, FAF1 shows similar protein-interacting characteristics to that of FADD. In the coimmunoprecipitation with an anti-Fas antibody (APO-1) in Jurkat cells, endogenous FAF1 was associated with the precipitates in which caspase-8 was present. By confocal microscopic analysis, both Fas and FAF1 were detected in the cytoplasmic membrane before Fas activation, and in the cytoplasm after Fas activation. FADD and caspase-8 colocalized with Fas in Jurkat cells validating the presence of FAF1 in the authentic Fas-DISC. Overexpression of FAF1 in Jurkat cells caused significant apoptotic death. In addition, the FAF1 deletion mutant lacking the N terminus where Fas, FADD, and caspase-8 interact protected Jurkat cells from Fas-induced apoptosis demonstrating dominant-negative phenotype. Cell death by overexpression of FAF1 was suppressed significantly in both FADD- and caspase-8-deficient Jurkat cells when compared with that in their parental Jurkat cells. Collectively, our data show that FAF1 is a member of Fas-DISC acting upstream of caspase-8.

Adaptor Proteins, Signal Transducing↗

Ordered subsets Bayesian tomographic reconstruction using 2-D smoothing splines as priors.

The ordered subsets expectation maximization (OS-EM) algorithm has enjoyed considerable interest for accelerating the well-known EM algorithm for emission tomography. The OS principle has also been applied to several regularized EM algorithms, such as nonquadratic convex minimization-based maximum a posteriori (MAP) algorithms. However, most of these methods have not been as practical as OS-EM due to their complex optimization methods and difficulties in hyperparameter estimation. We note here that, by relaxing the requirement of imposing sharp edges and using instead useful quadratic spline priors, solutions are much easier to compute, and hyperparameter calculation becomes less of a problem. In this work, we use two-dimensional smoothing splines as priors and apply a method of iterated conditional modes for the optimization. In this case, step sizes or line-search algorithms necessary for gradient-based descent methods are avoided. We also accelerate the resulting algorithm using the OS approach and propose a principled way of scaling smoothing parameters to retain the strength of smoothing for different subset numbers. Our experimental results show that the OS approach applied to our quadratic MAP algorithms provides a considerable acceleration while retaining the advantages of quadratic spline priors.

Algorithms↗

Alpha amylase is a major allergenic component in occupational asthma patients caused by porcine pancreatic extract.

Porcine pancreatic extracts (PPE) are composed of alpha-amylase and lipase, which are common components of digestive enzymes. They have been known to cause occupational asthma in exposed workers in pharmaceutical and baking industries, as well as in a laboratory technician, but there has been no report of PPE-induced occupational asthma in medical personnel and their IgE binding components to each component. Four asthmatic subjects showing positive results on PPE-bronchoprovocation testing were enrolled. All of them were nurses working in a university hospital. Their job included grinding and mixing PPE powder for admitted patients. Serum-specific IgE antibodies to PPE, alpha-amylase, and lipase were measured by enzyme linked immunosorbent assay (ELISA). To confirm specificity of IgE binding and cross-allergenicity among the three extracts, ELISA inhibition tests were performed. In order to characterize allergenic components within these three extracts, SDS-PAGE and IgE immunoblot analysis were done. Specific IgE antibodies to PPE, alpha-amylase, and lipase were detectable by ELISA in all study subjects. An alpha-amylase ELISA inhibition test showed significant inhibitions by amylase and PPE, and minimal inhibition by lipase. However, a lipase ELISA inhibition test showed significant inhibitions by alpha-amylase and PPE with a lesser degree of inhibition by lipase. Furthermore, IgE immunoblot analysis showed one IgE binding component (55 kDa) within PPE, six components (55 kDa, 43 kDa, 41 kDa, 32 kDa, 31 kDa, 29 kDa) within alpha-amylase and two components (31 kDa, 29 kDa) within lipase extracts. Thesefindings suggest that inhalation of PPE powder can induce IgE-mediated bronchoconstriction in exposed nurses. Alpha-amylase is a major allergenic component within PPE.

Adult↗

Low-dose spiral CT: application to surface-rendered three-dimensional imaging of central airways.

PURPOSE: The purpose of this work was to assess the utility of low-dose spiral CT for three-dimensional imaging of the central airways. METHOD: Spiral CT was performed in 15 patients using two tube currents (50 and 240 mA), producing 30 CT data sets. Surface-rendered virtual bronchoscopy (VB) and shaded surface display (SSD) images were assessed by three radiologists for image quality. The radiologists were also asked to compare 15 matched pairs each of 50 and 240 mA VB and SSD images, blindly select the 240 mA image, and record differences in diagnostic quality between the matched images. RESULTS: No significant difference in image quality was noted with 50 or 240 mA. Only 51.1% of 240 mA SSD and 51.1% of 240 mA VB images were correctly identified. Differences in diagnostic quality, noted in 84.4% of SSD and 33% of VB image pairs, were not ascribed to image noise. CONCLUSION: Image quality of surface-rendered three-dimensional images of the central airways is preserved using a lower tube current.

Adult↗