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Biomedical subjects

S H Lee

Publications and source records attributed to S H Lee.

At least 19 recordsLinked to original sources
PubMed2007

Phenylpropanolamine contained in cold remedies and risk of hemorrhagic stroke.

In this study, we sought to elucidate whether phenylpropanolamine (PPA) in cold remedies (small and divided doses) increases the risk of hemorrhagic stroke (HS). PPA exposure significantly increased the risk, and the risk was much higher in women. In women, linear trends were also found in recency, duration, and dosage of PPA exposure. PPA contained in cold remedies increases the risk of HS, particularly in women.

Adult↗
PubMed2007

Influence of Pediococcus-based probiotic on coccidiosis in broiler chickens.

Coccidiosis is the major parasitic disease of poultry and is caused by the apicomplexan parasites Eimeria. Drugs and live vaccines are the 2 main control measures of the disease; however, due to increasing concerns with prophylactic drug use and the high cost of vaccines, alternative control methods are needed. Recent evidence that various dietary and live microbial supplements can influence host immunity against enteric diseases prompted us to investigate the role of a Pediococcus-based probiotic on coccidiosis in broiler chickens. In the present study, we examined BW gains, oocyst shedding, and antibody responses of broilers fed the commercial probiotic MitoGrow. Day-old chicks were fed either a regular broiler diet or 1 of 2 probiotic diets supplemented with 0.1% (MG 0.1) or 0.2% MitoGrow. Chicks were orally challenged with 5,000 or 10,000 sporulated oocysts of Eimeria acervulina or with 5,000 Eimeria tenella oocysts on d 10 or 12 of age, respectively. In E. acervulina-infected birds, the MG 0.1 group improved (P < 0.05) weight gain as compared with the other 2 groups and reduced (P < 0.05) oocyst shedding in birds infected with 5,000 E. acervulina oocysts. In E. tenella-infected birds, Eimeria-specific antibody levels were higher (P < 0.05) in the Mito-Grow-fed groups, especially in the MG 0.1 birds, compared with the regular diet group, although their oocyst shedding and weight gains were not clearly improved. These results demonstrate that this Pediococcus acidilactici-based probiotic effectively enhances the resistance of birds and partially protects against the negative growth effects associated with coccidiosis, particularly when supplemented at 0.1% MitoGrow of the diet.

Animal Feed↗
PubMed2006

Transdifferentiation of porcine satellite cells to adipoblasts with ciglitizone.

Ciglitizone, a class of thiazolidinediones, acts as a potent activator of the adipose differentiation program in established preadipose cell lines. Thiazolidinediones have also been investigated in diabetic patients and have been reported to act as peroxisome proliferator-activated receptor-gamma ligands. Intramuscular adipogenesis or marbling through transdifferentiation of satellite cells in cattle was successfully conducted earlier. In this report, the effects of ciglitizone on the differentiation pathway of porcine myogenic satellite cells was investigated. Semitendinosus muscle was aseptically taken from 10-d-old piglets under general anesthesia, and porcine satellite cells were obtained and grown to near confluence. Postconfluent cells (d 0) were further cultured in differentiation medium containing an adipogenic mixture plus ciglitizone (10 microM) for 48 h. From d 2 onward, the cells were cultured only in the presence of ciglitizone until d 10. Controls were cultured in differentiation medium only. Exposure of porcine satellite cells to the adipogenic mixture plus ciglitizone generated lipid droplets on d 2, and subsequently, exposure of cells to ciglitizone alone helped in cytoplasmic lipid filling, providing them with the acquisition of adipocyte morphology. An increase (P < 0.05) in the fusion (structures containing 2 to 3 nuclei) of satellite cells was observed, and myosin heavy chain appeared with greater intensity (immunohistochemistry) in the control group from d 2 onward. Adipocyte-specific transcriptional factors (i.e., CCAAT/enhancer binding protein-alpha and peroxisome proliferator-activated receptor-gamma) were predominant during transdifferentiation and were observed with immunohistochemistry, Western blot (approximately 47.2 and approximately 60.4 kDa, respectively), and real-time PCR. Ciglitizone appeared to convert the differentiation pathway of satellite cells into that of adipoblasts.

Adipocytes↗
PubMed2006

DA-9601 inhibits activation of the human mast cell line HMC-1 through inhibition of NF-kappaB.

Mast cell-mediated allergic inflammation is involved in many diseases such as asthma, sinusitis, and rheumatoid arthritis. Mast cells induce synthesis and production of pro-inflammatory cytokines including tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6 with immune regulatory properties. The formulated ethanol extract of Artemisia asiatica Nakai (DA-9601) has been reported to have antioxidative and anti-inflammatory activities. In this report, we investigated the effect of DA-9601 on the expression of pro-inflammatory cytokines by the activated human mast cell line HMC-1 and studied its possible mechanisms of action. DA-9601 dose-dependently decreased the gene expression and production of TNF-alpha, IL-1beta, and IL-6 on phorbol 12-myristate 13-acetate (PMA)- and calcium ionophore A23187-stimulated HMC-1 cells. In addition, DA-9601 attenuated PMA- and A23187-induced activation of NF-kappaB as indicated by inhibition of degradation of IkappaBalpha, nuclear translocation of NF-kappaB, NF-kappaB/DNA binding, and NF-kappaB-dependent gene reporter assay. Our in vitro studies provide evidence that DA-9601 might contribute to the treatment of mast cell-derived allergic inflammatory diseases.

Artemisia↗
PubMed2006

Diazoxide acts more as a PKC-epsilon activator, and indirectly activates the mitochondrial K(ATP) channel conferring cardioprotection against hypoxic injury.

BACKGROUND AND PURPOSE: Diazoxide, a well-known opener of the mitochondrial ATP-sensitive potassium (mitoK(ATP)) channel, has been demonstrated to exert cardioprotective effect against ischemic injury through the mitoK(ATP) channel and protein kinase C (PKC). We aimed to clarify the role of PKC isoforms and the relationship between the PKC isoforms and the mitoK(ATP) channel in diazoxide-induced cardioprotection. EXPERIMENTAL APPROACH: In H9c2 cells and neonatal rat cardiomyocytes, PKC-epsilon activation was examined by Western blotting and kinase assay. Flavoprotein fluorescence, mitochondrial Ca(2+) and mitochondrial membrane potential were measured by confocal microscopy. Cell death was determined by TUNEL assay. KEY RESULTS: Diazoxide (100 microM) induced translocation of PKC-epsilon from the cytosolic to the mitochondrial fraction. Specific blockade of PKC-epsilon by either epsilonV1-2 or dominant negative mutant PKC-epsilon (PKC-epsilon KR) abolished the anti-apoptotic effect of diazoxide. Diazoxide-induced flavoprotein oxidation was inhibited by either epsilonV1-2 or PKC-epsilon KR transfection. Treatment with 5-hydroxydecanoate (5-HD) did not affect translocation and activation of PKC-epsilon induced by diazoxide. Transfection with wild type PKC-epsilon mimicked the flavoprotein-oxidizing effect of diazoxide, and this effect was completely blocked by epsilonV1-2 or 5-HD. Diazoxide prevented the increase in mitochondrial Ca(2+), mitochondrial depolarization and cytochrome c release induced by hypoxia and all these effects of diazoxide were blocked by epsilonV1-2 or 5-HD. CONCLUSIONS AND IMPLICATIONS: Diazoxide induced isoform-specific translocation of PKC-epsilon as an upstream signaling molecule for the mitoK(ATP) channel, rendering cardiomyocytes resistant to hypoxic injury through inhibition of the mitochondrial death pathway.

Animals↗
PubMed2006

Using dominance relationship coefficients based on linkage disequilibrium and linkage with a general complex pedigree to increase mapping resolution.

Dominance (intralocus allelic interactions) plays often an important role in quantitative trait variation. However, few studies about dominance in QTL mapping have been reported in outbred animal or human populations. This is because common dominance effects can be predicted mainly for many full sibs, which do not often occur in outbred or natural populations with a general pedigree. Moreover, incomplete genotypes for such a pedigree make it infeasible to estimate dominance relationship coefficients between individuals. In this study, identity-by-descent (IBD) coefficients are estimated on the basis of population-wide linkage disequilibrium (LD), which makes it possible to track dominance relationships between unrelated founders. Therefore, it is possible to use dominance effects in QTL mapping without full sibs. Incomplete genotypes with a complex pedigree and many markers can be efficiently dealt with by a Markov chain Monte Carlo method for estimating IBD and dominance relationship matrices (D(RM)). It is shown by simulation that the use of D(RM) increases the likelihood ratio at the true QTL position and the mapping accuracy and power with complete dominance, overdominance, and recessive inheritance modes when using 200 genotyped and phenotyped individuals.

Chromosome Mapping↗
PubMed2006

Mutational analysis of the hCDC4 gene in gastric carcinomas.

hCDC4, a ubiquitin ligase, plays a role in the control of cell cycle and chromosome stability. The hCDC4 gene is considered a tumour suppressor gene and is mutated in several human neoplasias, including colorectal and endometrial tumours. Data on the hCDC4 mutation in gastric cancer is, however, lacking. This study explored the possibility that hCDC4 mutation is involved in the development of gastric cancer. The hCDC4 gene in 162 gastric adenocarcinoma tissues was analysed for somatic mutations using a polymerase chain reaction-single strand conformation polymorphism assay. Overall, six hCDC4 mutations were found (3.7%), comprising four missense, one frameshift deletion and one nonsense mutation(s). It is notable that the hCDC4 mutations were found in early as well as in advanced gastric carcinomas. These data indicate that hCDC4 mutation occasionally occurs in gastric carcinomas and suggest that it might play a role in the development of some gastric carcinomas.

Aged↗
PubMed2006

Expressional analysis of anti-apoptotic phospho-BAD protein and mutational analysis of pro-apoptotic BAD gene in hepatocellular carcinomas.

BACKGROUND: It has become clear that, together with proliferation, deregulation of apoptosis plays a pivotal role in tumourigenesis. BAD is a pro-apoptotic Bcl-2 family protein and regulates the intrinsic apoptosis pathway. Phosphorylation of BAD inhibits the apoptosis function of BAD. AIMS: To investigate whether alteration of the phospho-BAD protein and somatic mutation of BAD gene are characteristics of human hepatocellular carcinoma. PATIENTS AND METHODS: We analysed the expression of phospho-BAD in 20 hepatocellular carcinomas by immunohistochemistry. Also, we analysed the BAD gene for the detection of somatic mutations by a single-strand conformation polymorphism assay in 69 hepatocellular carcinomas. RESULTS: Phospho-BAD expression in the non-tumour hepatocytes was seen in all of the hepatocellular carcinomas, while the expression in the cancer cells was observed in 15% (3 of the 20) of the hepatocellular carcinomas. There was no somatic mutation of BAD Bcl-2 homology 3 (BH3) domain in the 69 hepatocellular carcinomas. CONCLUSIONS: The data showed that loss of phospho-BAD expression, but not BAD gene mutation, is a feature of hepatocellular carcinomas. The decreased expression of phospho-BAD in the hepatocellular carcinoma cells compared to the non-tumour hepatocytes suggests that loss of phospho-BAD expression may play a role in hepatocellular tumourigenesis.

BH3 Interacting Domain Death Agonist Protein↗
PubMed2006

Early engraftment kinetics of two units cord blood transplantation.

Cord blood transplantation (CBT) is a promising alternative means of allogeneic stem cell transplantation. However, limited cell doses may compromise outcome. To enhance engraftment, CBT has been conducted using two units with promising results. However, little is known about the mechanism of engraftment. Here, we analyzed the early engraftment kinetics of eight patients given two unit umbilical CBT. Early engraftment kinetics revealed dominancy of one of two units from the day of engraftment (absolute neutrophil count > 0.5 x 10(9)/l). The median value of percentage of the predominant unit by chimerism analysis at the time of engraftment was 88% (60-100%). Two units CBT was found to be a safe, effective and promising alternative treatment option with good engraftment potential. Dominancy occurred early after CBT and is probably influenced by multiple factors.

Acute Disease↗
PubMed2006

Spin waves in the frustrated kagomé lattice antiferromagnet KFe3(OH)6(SO4)2.

The spin wave excitations of the S=5/2 kagomé lattice antiferromagnet KFe3(OH)6(SO4)2 have been measured using high-resolution inelastic neutron scattering. We directly observe a flat mode which corresponds to a lifted "zero energy mode," verifying a fundamental prediction for the kagomé lattice. A simple Heisenberg spin Hamiltonian provides an excellent fit to our spin wave data. The antisymmetric Dzyaloshinskii-Moriya interaction is the primary source of anisotropy and explains the low-temperature magnetization and spin structure.

Journal Article↗
PubMed2006

Simultaneous fine mapping of multiple closely linked quantitative trait Loci using combined linkage disequilibrium and linkage with a general pedigree.

Within a small region (e.g., <10 cM), there can be multiple quantitative trait loci (QTL) underlying phenotypes of a trait. Simultaneous fine mapping of closely linked QTL needs an efficient tool to remove confounded shade effects among QTL within such a small region. We propose a variance component method using combined linkage disequilibrium (LD) and linkage information and a reversible jump Markov chain Monte Carlo (MCMC) sampling for model selection. QTL identity-by-descent (IBD) coefficients between individuals are estimated by a hybrid MCMC combining the random walk and the meiosis Gibbs sampler. These coefficients are used in a mixed linear model and an empirical Bayesian procedure combines residual maximum likelihood (REML) to estimate QTL effects and a reversible jump MCMC that samples the number of QTL and the posterior QTL intensities across the tested region. Note that two MCMC processes are used, i.e., an (internal) MCMC for IBD estimation and an (external) MCMC for model selection. In a simulation study, the use of the multiple-QTL model clearly removes the shade effects between three closely linked QTL located at 1.125, 3.875, and 7.875 cM across the region of 10 cM, using 40 markers at 0.25-cM intervals. It is shown that the use of combined LD and linkage information gives much more useful information compared to using linkage information alone for both single- and multiple-QTL analyses. When using a lower marker density (11 markers at 1-cM intervals), the signal of the second QTL can disappear. Extreme values of past effective size (resulting in extreme levels of LD) decrease the mapping accuracy.

Chromosome Mapping↗
PubMed2006

Assessment of converting from intravenous to oral administration of cyclosporin A in pediatric allogeneic hematopoietic stem cell transplant recipients.

We studied the administration method during a transition period from continuous intravenous (i.v.) infusion to oral administration of cyclosporin A (CsA). Thirty-two pediatric hematopoietic stem cell transplant (HSCT) recipients, between the ages of 8 months and 15.6 years (median 7.1 years) participated in this study. The pharmacokinetic properties of CsA was evaluated during the transition period from i.v. to oral CsA. The daily oral dose of CsA was three times higher than the i.v. dose. Oral dosing began immediately after the continuous infusion was discontinued. Whole-blood CsA concentrations were measured by a monoclonal fluorescence polarization immunoassay (FPIA). The mean+/-s.d. value of bioavailability (F), maximum concentration (C(max)), half-life (t(1/2)) of CsA were 43.1+/-14.4%, 1135.3+/-340.6 ng/ml and 3.1+/-1.2 h, respectively. Mean clearance (CL)+/-s.d. was 480.9+/-103.7, 414.9+/-137.1 and 320+/-51.8 ml/h/kg in patients <20, 20-40 and >40 kg of body weight, respectively. The CsA CL of younger children was significantly greater than for older children (P=0.044). CsA trough levels were maintained within the therapeutic range throughout the transition period. Therefore, our findings suggest that the immediate administration of an oral formulation, after discontinuation of the continuous infusion, would be practical and effective for routine clinical use.

Administration, Oral↗
PubMed2006

The JAK2 V617F mutation in de novo acute myelogenous leukemias.

A missense somatic mutation in JAK2 gene (JAK2 V617F) has recently been reported in chronic myeloproliferative disorders, including polycythemia vera, essential thrombocythemia and myelofibrosis with myeloid metaplasia, strongly suggesting its role in the pathogenesis of myeloid disorders. As activation of JAK2 signaling is occurred in other malignancies as well, we have analysed 558 tissues from common human cancers, including colon, breast and lung carcinomas, and 143 acute adulthood leukemias by polymerase chain reaction -- single strand conformation polymorphism analysis. We found three JAK2 mutations in the 113 acute myelogenous leukemias (AMLs) (2.7%), but none in other cancers. The mutations consisted of two V617F mutations and one K607N mutation. None of the AML patients with the JAK2 V617F mutation had a history of previous hematologic disorders. This is the first report on the JAK2 gene mutation in AML, and the data indicated that the JAK2 gene mutation may not only contribute to the development of chronic myeloid disorders, but also to some AMLs.

Adult↗
PubMed2006

siRNA--getting the message out.

The recent observation that potent and sequence-specific gene silencing by injection of double-stranded RNA (dsRNA) has sparked the phenomenon known as "RNA interference" (RNAi) and has enabled the gene-specific knockdown of drug transport proteins and metabolizing enzymes. The application of small interfering RNAs (siRNAs) is broad and the potential for use as research tools is now well established in vitro. In vivo use is still a challenge that is primarily focused on the difficulty of delivering siRNAs to target cells. The potential use of siRNAs as therapeutic agents is also exciting and holds great promise for future. For the study of drug transporter function in absorption, distribution, metabolism and excretion (ADME) and in the treatment of diseases, siRNA offers a way to gather interpretable mechanistic data-a distinct advantage over the use of "specific" chemical inhibitors. This mini review provides background information on siRNA as well as examples of the use of siRNA as applied to drug transporters.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

Botulinum toxin treatment of children with cerebral palsy - a short review of different injection techniques.

The intramuscular application of botulinum toxin type A (BoNT/A) has emerged to be an established treatment option to reduce muscular hyperactivity due to spasticity in children with cerebral palsy. Accurate injection is a prerequisite for efficient and safe treatment with BoNT/A. So far, treatment procedures have not been standardized. This paper is a short review of different injection techniques, i.e., manual needle placement as well as guidance by electromyography, electrical stimulation, and ultrasound. Advantages and disadvantages of the different injection techniques are discussed with a focus on needle positioning within the targeted muscle, injection close to the neuromuscular junction and diffusion of BoNT/A within the target muscles and through fascia. The additional information gained by each injection technique is weighed in terms of the clinical impact for children with cerebral palsy.

Anti-Dyskinesia Agents↗
PubMed2006

Dual reporter genes enabling cell tracing with viable and reliable selection of various cell types.

Dual reporter genes driven by either a ubiquitous cytomegalovirus (CMV) or a neuro-specific tubulin alpha1 promoter (Talpha1) were constructed. The new genes, CMV (pCMV-GL) or Talpha1 promoter-driven GFP-LacZ (pTalpha1-GL), robustly expressed the fused GFP-LacZ protein reporting constitutive expressions in various cell types including CHO cells, loach and chicken embryos, and neuro-specific expression in differentiating mouse embryonic stem cells, respectively. The dual reporter genes thus provide a versatile tool for the studies of gene expression, cell lineage within the embryo and possibly the fate of stem cells in transplantation experiment, thus facilitating different analyses depending on the experimental purposes.

Animals↗
PubMed2006

The characteristics of tropospheric ozone seasonality observed from ozone soundings at Pohang, Korea.

This paper presents the first analysis of vertical ozone sounding measurements over Pohang, Korea. The main focus is to analyze the seasonal variation of vertical ozone profiles and determine the mechanisms controlling ozone seasonality. The maxima ozone at the surface and in the free troposphere are observed in May and June, respectively. In comparison with the ozone seasonality at Oki (near sea level) and Happo (altitude of 1840 m) in Japan, which are located at the same latitude as of Pohang, we have found that the time of the ozone maximum at the Japanese sites is always a month earlier than at Pohang. Analysis of the wind flow at the surface shows that the wind shifts from westerly to southerly in May over Japan, but in June over Pohang. However, this wind shift above boundary layer occurs a month later. This wind shift results in significantly smaller amounts of ozone because the southerly wind brings clean wet tropical air. It has been suggested that the spring ozone maximum in the lower troposphere is due to polluted air transported from China. However, an enhanced ozone amount over the free troposphere in June appears to have a different origin. A tongue-like structure in the time-height cross-section of ozone concentrations, which starts from the stratosphere and extends to the middle troposphere, suggests that the ozone enhancement occurs due to a gradual migration of ozone from the stratosphere. The high frequency of dry air with elevated ozone concentrations in the upper troposphere in June suggests that the air is transported from the stratosphere. HYSPLIT trajectory analysis supports the hypothesis that enhanced ozone in the free troposphere is not likely due to transport from sources of anthropogenic activity.

Atmosphere↗