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Biomedical subjects

S H Han

Publications and source records attributed to S H Han.

At least 109 records · Page 6Linked to original sources

Mitogen-activated protein kinase kinase antagonized fas-associated death domain protein-mediated apoptosis by induced FLICE-inhibitory protein expression.

Fas and Fas-associated death domain (FADD) play a critical role in the homeostasis of different cell types. The regulation of Fas and FADD-mediated cell death is pivotal to many physiological functions. The activation of T lymphocytes by concanavalin A (Con A) inhibited Fas-mediated cell death. We identified that among the several activation signals downstream of Con A stimulation, mitogen-activated protein (MAP) kinase kinase (MKK) was the major kinase pathway that antagonized Fas-triggered cell death. MKK1 suppressed FADD- but not caspase-3- induced apoptosis, indicating that antagonism occurred early along the Fas-initiated apoptotic cascade. We further demonstrated that activation of MKK1 led to expression of FLIP, a specific inhibitor of FADD. MKK1 inhibition of FADD-induced cell death was abrogated if induction of FLIP was prevented, indicating that FLIP mediates MKK1 suppression of FADD-mediated apoptosis. Our results illustrate a general mechanism by which activation of MAP kinase attenuates apoptotic signals initiated by death receptors in normal and transformed cells.

Adaptor Proteins, Signal Transducing↗

Apoptotic signal of Fas is not mediated by ceramide.

Ceramide has been suggested as the secondary messenger mediating the apoptotic signal for Fas engagement. By using different inhibitors, we demonstrated here that ceramide is unlikely a mediator of Fas-initiated apoptosis. First, cAMP prevented cell death induced by ceramide but not by Fas. Second, ceramide-triggered, but not Fas-triggered, apoptosis was antagonized by the free radical scavenger C60. Third, the metal chelator pyrrolidinedithiocarbamate suppressed ceramide-initiated DNA fragmentation but had no effect on the Fas-induced cell death. Fourth, the SAPK/ERK kinase dominant negative mutant, which attenuated ceramide-induced cell death, did not prevent Fas-induced apoptosis. Finally, activation of NF-kappaB inhibited ceramide-induced but not Fas-initiated apoptosis. The fact that many antagonists of ceramide-induced apoptosis could not suppress Fas-mediated cell death clearly indicates that ceramide is not the mediator for Fas-initiated apoptotic signal.

Apoptosis↗

Interleukin-13 increases prostaglandin E2 (PGE2) production by normal human polymorphonuclear neutrophils by enhancing cyclooxygenase 2 (COX-2) gene expression.

OBJECTIVE: To investigate whether interleukin-13 (IL-13) can affect arachidonic acid metabolism and phagocytic activity of normal human polymorphonuclear neutrophils (PMN). METHODS: Normal human PMN (1 x 10(6) cells/ml) were incubated with different concentrations of IL-13 (0.1-10 ng/ml) for a variety of times (30-120 min). Phagocytosis and intracellular cyclooxygenase-2 (COX-2) were detected by flow cytometry. The expression of COX-1 and COX-2 mRNA was detected by RT-PCR. The concentration of PGE2 in the PMN cultured supernatants was determined by EIA. RESULTS: We found that IL-13 at an optimal concentration of 1 ng/ml significantly enhanced COX-2 gene expression and PGE2 production (121.57 +/- 22.17 pg/ml in IL-13 stimulation vs. 73.16 +/- 11.72 pg/ml in controls) by PMN. In addition, IL-13 stimulated PMN phagocytosis via increased complement receptor type 1 (CR1) and type 3 (CR3), but not IgG Fcgamma receptor type 3 (FcgammaRIII). The cytoplasmic neutral esterase activity of PMN was also enhanced by IL-13 stimulation for 24 h. CONCLUSIONS: These results suggest that IL-13 can stimulate PMN and modulates the inflammatory reactions via the cyclooxygenase pathway.

Cells, Cultured↗

Tortuous common carotid artery encountered during neck dissection.

Anomalies of the carotid artery are rare in clinical experience. To our knowledge a tortuous common carotid artery with an abnormal course encountered during neck dissection has never been reported in the available world literature. During dissection of the lower neck in a 60-year-old Korean man, a tortuous right common carotid artery was found to cross over the lower cervical trachea anteriorly and then was positioned in its usual site in the carotid sheath in the mid-neck.

Carcinoma, Squamous Cell↗

Psychophysical methods and passenger preferences of interior designs.

A psychophysical experiment was conducted to evaluate the interior design alternatives of a high-speed train. Preference of each design alternative was quantitatively measured by using the magnitude estimation technique. Subsequent analyses showed that (1) passenger seats should be able to be arranged in the moving direction of a train, (2) a variety of interior convenience facilities, especially, an audio facility, should be provided to enhance passenger comfort and (3) the design requirements suggested by young passengers could improve the overall preference level. In addition, guidelines for collecting, standardizing, and analyzing the data are suggested when the magnitude estimation technique is used. The use of psychophysical data is expected to be very useful when it is necessary to make engineering decisions based on quantitative preference data.

Adult↗

Coach design for the Korean high-speed train: a systematic approach to passenger seat design and layout.

Proper ergonomic design of a passenger seat and coach layout for a high-speed train is an essential component that is directly related to passenger comfort. In this research, a systematic approach to the design of passenger seats was described and the coach layout which reflected the tradeoff between transportation capacity and passenger comfort was investigated for the Korean high-speed train. As a result, design recommendations and specifications of the passenger seat and its layout were suggested. The whole design process is composed of four stages. A survey and analysis of design requirement was first conducted, which formed the base for designing the first and second class passenger seats. Prototypes were made and evaluated iteratively, and seat arrangement and coach layout were finally obtained. The systematic approach and recommendations suggested in this study are expected to be applicable to the seat design for public transportations and to help modify and redesign existing vehicular seats.

Adult↗

Non-linear dynamical analysis of the EEG in Alzheimer's disease with optimal embedding dimension.

We used non-linear analysis to investigate the dynamical properties underlying the EEG in patients with Alzheimer's disease. We calculated the correlation dimension D2 and the first positive Lyapunov exponent L1. We employed a new method, which was proposed by Kennel et al., to calculate the non-linear invariant measures. That method determined the proper minimum embedding dimension by looking at the behavior of nearest neighbors under a change in the embedding dimension d from d to d + 1. We demonstrated that for limited noisy data, our algorithm was strikingly faster and more accurate than previous ones. Also, we found that, in almost all channels, patients with Alzheimer's disease had significantly lower D2 and L1 values than those for age-approximated healthy controls. These results suggest that brains afflicted by Alzheimer's disease show behaviors which are less chaotic than those of normal healthy brains. In this paper, we show that non-linear analysis can provide a fruitful tool for detecting relative changes, which cannot be detected by conventional linear analysis, in the complexity of brain dynamics. We propose that non-linear dynamical analyses of the EEGs from patients with Alzheimer's disease will be a diagnostic modality in the appropriate clinical setting.

Aged↗

A pilot randomized, controlled trial of the effect of iron depletion on long-term response to alpha-interferon in patients with chronic hepatitis C.

BACKGROUND/AIMS: Some studies have suggested that hepatic iron may influence the response to interferon therapy in chronic hepatitis C patients. We conducted this randomized, controlled trial to evaluate the effect of iron depletion on: (1) aminotransferase activity and hepatitis C RNA levels; and (2) response to interferon therapy in 38 patients with elevated alanine aminotransferase levels and who were HCV RNA positive. METHODS: Seventeen patients underwent a 500-ml phlebotomy every 2 weeks until iron deficiency was achieved. Patients were then started on a 6-month course of alpha-interferon 2b (3 mu tiw). Controls were 21 patients who were monitored for a 6- to 8-week period without phlebotomy prior to interferon therapy. Response to interferon was defined as loss of serum HCV RNA by reverse transcriptase-polymerase chain reaction. Serum HCV RNA was quantitated by bDNA technique. RESULTS: Alanine aminotransferase levels decreased in 15/17 patients after phlebotomy. Mean alanine aminotransferase fell from 156.8 to 89.7 U/l (p=0.008). Changes in iron indices and alanine aminotransferase after phlebotomy were not accompanied by changes in HCV RNA levels. In control patients, neither alanine aminotransferase nor HCV RNA levels changed during the observation period. At the end of 24 weeks of interferon therapy, 7/17 phlebotomized patients had a response, compared to 6/21 control patients (p=ns). After 6 months of follow-up, 5/17 phlebotomized patients remained HCV RNA negative, in contrast to only 1/21 controls (p=0.07). CONCLUSIONS: Iron depletion led to a reduction in aminotransferase levels; this was not accompanied by changes in levels of hepatitis C RNA. There may be an improvement in the sustained response to interferon therapy, but this requires confirmation.

Adult↗

Chemical denaturation of ovalbumin abrogates the induction of oral tolerance of mouse reaginic antibody responses.

The effect of chemical denaturation of ovalbumin (OVA) on the induction of oral tolerance of reaginic antibody responses was studied. Both urea-denatured OVA (UD-OVA) and carboxymethylated UD-OVA (CM-OVA) were purified by centrifugation. When compared with OVA and UD-OVA, CM-OVA had the least sensitizing capacity and allergenicity in IgE responses to OVA. BALB/c IgE, IgG1 and IgG antibody responses were suppressed by OVA, but not by UD-OVA or CM-OVA, fed prior to sensitization with OVA, UD-OVA, or CM-OVA in alum, respectively. The priming effect of specific IgG and IgG1 antibody responses was induced by CM-OVA fed prior to sensitization with OVA or CM-OVA. The proliferation of BALB/c spleen cells and their secretion of T helper type 2 (Th2) cytokines interleukin-4 (IL-4) and IL-5 were also orally tolerized by OVA, but not by denatured OVA. Although denatured OVA is hypoallergenic, the present result indicates that denaturation of a soluble protein prevents the induction of oral tolerance of Th2 responses.

Administration, Oral↗

The effect of human polyclonal anti-dsDNA autoantibodies on apoptotic gene expression in cultured rat glomerular mesangial cells.

In our previous studies, we found that polyclonal anti-double-stranded DNA antibodies (anti-dsDNA) purified from sera of patients with active systemic lupus erythematosus (SLE) were cytotoxic to cultured rat glomerular mesangial cells (RMC) through an apoptotic mechanism. In order to determine whether these nephritogenic antibodies affect the expression of apoptosis-related genes in the tissues, the expression of Fas, p53, c-myc, and bcl-2 genes in the kidneys and livers of 12-week-old normal BALB/c and autoimmune MRL-lpr/lpr mice was detected by a reverse transcription-assisted polymerase chain reaction (RT-PCR). We found the mRNA of the four genes were expressed in the tissues of the normal mice. In contrast, decreased expression of the four genes in the kidney and absent expression of bcl-2 in the liver of the lpr mice were noted. Interestingly, RMC only expressed p53 and c-myc, but not Fas or bcl-2, in culture. The purified polyclonal anti-dsDNA dose-responsively (50-200 IU/ml) suppressed the 3H-thymidine incorporation of RMC after incubation for 48 h. However, the incubation of 100 IU/ml of anti-dsDNA with RMC for 4 h did not affect the expression of these apoptotic genes. The results suggest that anti-dsDNA induce RMC apoptosis via an unidentified mechanism different from Fas, c-myc or p53 pathway.

Animals↗

Inhibition of NF-kappa B/Rel nuclear translocation by dexamethasone: mechanism for the inhibition of iNOS gene expression.

The decrease in NO production was found to correlate well with a decrease in inducible nitric oxide synthase (iNOS) mRNA expression as demonstrated by Northern blot analysis and quantitative RT-PCR. Since the promoter in iNOS gene contains binding motifs for NF-kappa B/Rel, NF-IL6, and Oct which appear to be important for LPS-mediated iNOS induction, the effects of DEX on the activation of these transcription factors were examined. Treatment of DEX to RAW 264.7 cells induced a dose-related inhibition of NF-kappa B/Rel in chloramphenicol acetyltransferase activity, while NF-IL6 or Oct activation was not affected by DEX. Treatment of RAW 264.7 cells with DEX inhibited DNA binding of NF-kappa B/Rel proteins to their cognate DNA site as measured by electrophoretic mobility shift assay. In addition, DEX treatment caused a significant reduction in nuclear c-rel, p65, and p50 protein contents, and these decreases were paralleled by the accumulation of cytoplasmic c-rel, p65, and p50. These results suggest that DEX may inhibit iNOS gene expression by a mechanism involving the blockade of LPS-induced nuclear translocation of NF-kappa B/Rel.

Animals↗

Nephrogenic ascites. Analysis of 16 cases and review of the literature.

Nephrogenic ascites is an entity that manifests as refractory ascites in patients with end-stage renal disease, where portal hypertensive, infectious, and malignant processes have been excluded. Most of these patients are undergoing hemodialysis. Hypoalbuminemia may predispose these uremic patients to ascites formation. The characteristics of the ascitic fluid suggest that the pathogenesis of the ascites is an alteration in peritoneal membrane permeability or impaired resorption due to peritoneal lymphatic channel obstruction. The ascitic fluid has a high protein content, low serum-ascites albumin gradient (SAAG), and low leukocyte count. Daily hemodialysis should be the initial therapy and is successful in one-third to three-fourths of patients within 3 weeks. Continuous ambulatory peritoneal dialysis or insertion of a peritoneovenous shunt are alternative treatments. Other therapies include instillation of intraperitoneal corticosteroids and binephrectomy, which have less predictable outcomes. Renal transplantation is the definitive treatment for nephrogenic ascites. Control of ascites reverses the progressive cachexia associated with uncontrolled disease, resulting in improved quality of life and survival approaching that of end-stage renal disease patients without ascites.

Adult↗

Resolution of recurrent hepatitis B in two liver transplant recipients treated with famciclovir.

Recurrent hepatitis B infection after orthotopic liver transplantation remains problematic despite prophylaxis with hepatitis B immune globulin (anti-HBs IgG). Recently, famciclovir (an oral nucleoside analog) has been shown to have potent antiviral activity against hepatitis B in vitro as well as in patients with chronic hepatitis B. We present two patients who developed recurrent hepatitis B after orthotopic liver transplantation and were treated with famciclovir, 500 mg t.i.d. Both patients subsequently responded with marked improvement in biochemical liver tests and histology, with subsequent loss of hepatitis B surface antigen. Famciclovir is a useful agent in the treatment of hepatitis B in the liver transplant recipient.

2-Aminopurine↗

Suppression of interleukin-2 by the putative endogenous cannabinoid 2-arachidonyl-glycerol is mediated through down-regulation of the nuclear factor of activated T cells.

2-Arachidonyl-glycerol (2-Ara-Gl) recently was identified as a putative endogenous ligand for cannabinoid receptor types CB1 and CB2 by competitive binding. More recent immune function assays demonstrated that 2-Ara-Gl possessed immunomodulatory activity. Because several plant-derived cannabinoids inhibit interleukin-2 (IL-2) expression, 2-Ara-Gl was investigated for its ability to modulate this cytokine. The direct addition of 2-Ara-Gl to mouse splenocyte cultures suppressed phorbol-12-myristate-13-acetate plus ionomycin-induced IL-2 secretion and steady state mRNA expression in a dose-dependent manner. 2-Ara-Gl also produced a marked inhibition of IL-2 promotor activity as determined by transient transfection of EL4.IL-2 cells with a pIL-2-CAT construct. 2-Ara-Gl at 5, 10, 20, and 50 microM suppressed phorbol-12-myristate-13-acetate plus ionomycin-induced IL-2 promotor activity by 18%, 28%, 39%, and 54%, respectively. To further characterize the mechanism for the transcriptional regulation of IL-2 by 2-Ara-Gl, the DNA-binding activity of transcription factors, nuclear factor of activated T cells (NF-AT), nuclear factor for immunoglobulin kappa chain in B cells (NF-kappa B/Rel), activator protein-1(AP-1), octamer, and cAMP-response element binding protein was evaluated by electrophoretic mobility shift assay in mouse splenocytes. In addition, a reporter gene expression system for p(NF-kappa B)3-CAT, p(NF-AT)3-CAT, and p(AP-1)3-CAT was used in transiently transfected EL4.IL-2 cells to determine the effect of 2-Ara-Gl on promoter activity for each of the specific transcription factors. 2-Ara-Gl reduced both the NF-AT-binding and promoter activity in a dose-dependent manner and, to a lesser degree, NF-kappa B/Rel-binding and promoter activity. No significant effect was observed on octamer- and cAMP-response element-binding activity. AP-1 DNA-binding activity was not inhibited by 2-Ara-Gl, but a modest inhibition of promoter activity was observed.

Adjuvants, Immunologic↗

Alkaline serine proteinase: a major allergen of Aspergillus oryzae and its cross-reactivity with Penicillium citrinum.

BACKGROUND: Aspergillus species are common indoor airborne fungi and have been considered as causative agents of human allergic disorders. However, allergens of different Aspergillus species have not been effectively characterized. The object of this study was to identify and characterize IgE-binding components of Aspergillus oryzae. METHODS: Allergens of A. oryzae were identified by immunoblot analysis using sera from asthmatic patients. The N-terminal amino acid sequences of allergens thus identified were determined by Edman degradation. The antigenic and the allergenic cross-reactivities between allergens of different fungi were analyzed by immunoblotting and immunoblot inhibition analysis, respectively, using a monoclonal antibody (MoAb) 55A against the 33-kD major allergen of Penicillium citrinum and a mixture of IgE-containing asthmatic serum samples. RESULTS: Thirteen components of A. oryzae ranging in apparent molecular weight from 16 to 42 kD react with IgE antibodies. A 34-kD component that showed intense IgE-binding reactivity and was detectable in the highest frequency in our asthmatic serum samples tested was considered a major allergen of A. oryzae. The 34-kD component also reacted with MoAb 55A. Results from immunoblot inhibition studies also demonstrated the IgE cross-reactivity between the 34-kD major allergens of A. oryzae and P. citrinum. In addition, the sequence of the N-terminal 18 amino acid residues of the 34-kD major allergen of A. oryzae was found to be identical to that of the alkaline serine proteinase from the same Aspergillus species. CONCLUSION: The 34-kD major allergen of A. oryzae is an alkaline serine proteinase. There is IgE cross-reactivity between the major serine proteinase allergens of A. oryzae and P. citrinum.

Allergens↗

Anticardiolipin and anti-beta2-glycoprotein I antibodies in Behcet's disease.

To investigate prevalence of anticardiolipin antibodies (aCL) in patients with Behcet's disease (BD) and to determine whether they are related to anti-beta2-glycoprotein I antibodies (aGPI), we measured aCL and aGPI in 47 patients of BD and 14 patients of systemic lupus erythematosus (SLE). The levels of aCL and aGPI were determined by conventional enzyme immunoassay for both IgG and IgM classes. Twelve (25.5%) patients with BD were positive for IgG or IgM aCL and no patient was positive for aGPI. Eleven (78.6%) patients with SLE were also positive for aCL and among them, 8 (72.7%) patients were positive for aGPI. Positive IgG aCL patients with BD showed lower level of IgG aCL than those with SLE (15.7+/-7.3 vs 34.1+/-16.0 GPL, p<0.05). There was no relation between the presence of aCL in BD and either dinical activity or clinical features. In the patients with BD, aCL are found but it would not be associated with aGPI as they are in patients with SLE. In patients with BD, aCL seem to be authentic aCL unlike those in patients with SLE and may not be related with vascular complications in BD.

Adult↗

The effects of diffusion blur on Snellen and grating acuity and foveal function in amblyopia.

In order to verify that the effects of diffusion blur on Snellen and grating acuity in amblyopic eyes resemble those obtained from the peripheral or central retina in normal controls, we conducted the following experiment using a liquid crystal window (Edmund Scientific Co.) to produce diffusion blur on Snellen and grating acuity. Spatial frequencies used for a Snellen chart and Teller acuity card were 3.2, 6.5, 13.0, 26.0 cyc/cm at a working distance of 55 cm. The values of diffusive blur on central and peripheral visual acuity obtained from 20 normal healthy control eyes were compared with those values of central visual acuity in 26 amblyopic eyes. The diffusion blur had a strong negative effect on both Snellen and grating acuity in amblyopic eyes, but it had more potent effects on grating acuity (p < 0.05). The diffusion blur values obtained from the central amblyopic retina were more compatible with those of the central retina than with those of the peripheral retina in the control group (p > 0.05). Snellen acuity obtained from diffusion blur overestimated grating acuity in the normal central acuity group and amblyopic central acuity group. The result of this investigation demonstrated that the liquid crystal diffusion blur had a strong negative effect on both Snellen and grating acuity and suggested that the visual function of an amblyopic retina resembled that of a normal central retina.

Adult↗

Characterization of allergens of Penicillium and Aspergillus species.

Penicillium and Aspergillus species are common indoor airborne fungi and have been identified to be important causative agents of extrinsic bronchial asthma. However, little was known about allergens of these ubiquitous fungal species. Results from a survey conducted by us showed that P. citrinum was the most prevalent Penicillium species in the Taipei area. Characterization of allergens by SDS-PAGE-immunoblotting using sera from asthmatic patients showed that there was an IgE cross-reactivity among the 33 KDa group major allergens of P. citrinum, P. notatum and P. brevicompactum. Results obtained from N-terminal amino acid sequence analysis suggest that the 33 KDa major allergens of P. citrinum and P. brevicompactum may be the alkaline serine proteinase of individual Penicillium species. In addition, our results suggest that the 34 KDa major allergen of A. oryzae is also an alkaline serine proteinase. IgE cross-reactivity between the major serine proteinase allergens of A. oryzae and P. citrinum has also been detected. Furthermore, results from cDNA cloning suggest that the 68 KDa allergen of P. notatum is a beta-N-acetyl-glucosaminidase. Lastly, a heat shock protein in the hsp70 family has also been identified as an allergen of P. citrinum. Results obtained in these studies will provide important basis for clinical diagnosis and treatment of mould allergy.

Allergens↗