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Biomedical subjects

S Cho

Publications and source records attributed to S Cho.

At least 55 records · Page 3Linked to original sources
PubMed2001

Modelling and prediction for chaotic fir laser attractor using rational function neural network.

Many real-world systems such as irregular ECG signal, volatility of currency exchange rate and heated fluid reaction exhibit highly complex nonlinear characteristic known as chaos. These chaotic systems cannot be retreated satisfactorily using linear system theory due to its high dimensionality and irregularity. This research focuses on prediction and modelling of chaotic FIR (Far InfraRed) laser system for which the underlying equations are not given. This paper proposed a method for prediction and modelling a chaotic FIR laser time series using rational function neural network. Three network architectures, TDNN (Time Delayed Neural Network), RBF (radial basis function) network and the RF (rational function) network, are also presented. Comparisons between these networks performance show the improvements introduced by the RF network in terms of a decrement in network complexity and better ability of predictability.

Infrared Rays↗
PubMed2001

Neural network based automatic diagnosis of children with brain dysfunction.

This paper proposes the use of multilayer perceptron for brain dysfunction diagnosis. The performance of MLP was better than that of Discriminant Analysis and Decision Tree classifiers, with an 85% accuracy rate in an experimental test involving 332 subjects. In addition, the neural network employing Bayesian learning was able to identify the most important input variable. These two results demonstrate that the neural network can be effectively used in the diagnosis of children with brain dysfunction.

Attention Deficit Disorder with Hyperactivity↗
PubMed2001

Regulation of gonadotropin subunit gene transcription by gonadotropin-releasing hormone: measurement of primary transcript ribonucleic acids by quantitative reverse transcription-polymerase chain reaction assays.

GnRH regulates the synthesis and secretion of the pituitary gonadotropins LH and FSH. One of the actions of GnRH on the gonadotropin subunit genes (alpha, LHbeta, and FSHbeta) is the regulation of transcription [messenger RNA (mRNA) synthesis]. Gonadotropin subunit transcription rates increase after gonadectomy and following exogenous GnRH pulses. However, prior studies of subunit mRNA synthesis were limited by the available methodology that did not allow simultaneous measurement of gene transcription and mature mRNA concentrations. The purpose of the current studies was to: 1) develop a reliable and sensitive method for assessing transcription rates by measuring gonadotropin subunit primary transcript RNAs (PT, RNA before intron splicing); 2) investigate the PT responses to GnRH following castration or exogenous GnRH pulses; 3) characterize the half-disappearance time for the three PT species after GnRH withdrawal; and 4) correlate changes in PT concentration with steady-state gonadotropin subunit mRNA levels measured in the same pituitary RNA samples. Using oligonucleotide primers that flanked intron-exon boundaries, quantitative RT-PCR assays for each subunit PT species were developed. These assays require only ng amounts of RNA to measure each gonadotropin subunit PT and allow us to measure both PTs and steady-state mRNAs in a single pituitary RNA sample. Primary transcript concentrations in intact male rats showed a relative abundance of alpha > LHbeta congruent with FSHbeta, similar to the relationship found previously for mRNA levels. Additionally, each PT species was only 1-2% as abundant as the corresponding mRNA. One week after castration, gonadotropin subunit PT levels were increased (alpha: 3-fold, LHbeta: 6-fold, and FSHbeta: 3-fold) in a pattern similar to subunit mRNAs. Administration of GnRH antagonist to 7-day castrate male rats resulted in a rapid decline in PT concentrations with a half-disappearance time of 2.7 h for LHbeta and 0.8 h for FSHbeta, significantly faster than earlier measurements of the half-disappearance time for mature mRNA. Finally, in a GnRH-deficient male rat model, LHbeta and FSHbeta PT concentrations increased 4- to 6-fold 5 min after a GnRH pulse and then declined toward levels seen in control animals. These data indicate that the effects of GnRH on subunit gene transcription are an important determinant of gonadotropin regulation. The appearance and disappearance of PT RNA occurs more rapidly than changes in mature mRNA. Additionally, concentrations are elevated in long term castrates, and following an exogenous GnRH pulse the transcriptional burst is rapid and brief.

Animals↗
PubMed2001

Detection of inducible nitric oxide synthase- and nitrotyrosine-positive cells in the lesions of pericarditis induced by porcine enterovirus serotype 3 infection.

The expression of inducible nitric oxide synthase (iNOS), an enzyme that produces nitric oxide, was examined in the hearts of pigs infected with porcine enterovirus serotype 3 (PEV3). Piglets orally infected with PEV3 developed tremors and paralysis 3-7 days post-infection. Affected animals had pericarditis and myocarditis. There were fibrin and inflammatory cell infiltrates (macrophages and neutrophils) in the pericardial sac and myocardium. Immunohistochemically, the majority of inflammatory cells in the pericardial sac were positive for iNOS and nitrotyrosine, an end product of nitric oxide. These results suggest that iNOS is upregulated in the pericardial lesion, and that increased nitric oxide production plays an important role in the development of PEV3-induced pericarditis and myocarditis.

Animals↗
PubMed2001

Immunohistochemical analysis of CD44s and CD44v6 in endometriosis and adenomyosis : comparison with normal, hyperplastic, and malignant endometrium.

The expression patterns of CD44s and CD44v6 were immunohistochemically compared with those of normal, hyperplastic and malignant endometrium. In normal endometria (n=37), endometrioses (n=46) and adenomyoses (n=20), the surface and glandular epithelial cells were negative for CD44s and CD44v6 in a proliferative pattern and positive in a secretory pattern, whereas the stroma was only positive for CD44s in both proliferative and secretory patterns. The endometrial hyperplasia (4 simple and 9 complex) had the identical patterns with normal proliferative phase of endometrium. Only one case showing complex hyperplasia with atypia was focally positive for CD44s and CD44v6 in glandular epithelia. CD44s and CD44v6 were positive in all endometrial adenocarcinomas (13), except one CD44s-negative case. In summary, the expressions of CD44s and CD44v6 in endometriosis and adenomyosis recapitulated those of normal cyclic endometrium. The expression patterns in endometrial hyperplasia were similar to those in normal proliferative endometrium, whereas the endometrial adenocarcinoma showed abnormal expressions for CD44s and CD44v6. Thus it was considered that the ectopic endometrium in endometriosis and adenomyosis was not aberrant as in endometrial carcinoma on the aspects of immunohistochemical expressions of CD44s and CD44v6.

Adenocarcinoma↗
PubMed2001

Effect in a rat model of heparinized peritoneal dialysis catheters on bacterial colonization and the healing of the exit site.

We performed a prospective, double-blind, randomized study to evaluate whether stable surface heparinization of silicone peritoneal dialysis (PD) catheters prevents bacterial colonization or biofilm formation and improves healing of the exit site. Heparinized catheters were implanted in 20 Sprague-Dawley rats (group H) and non heparinized catheters in another 20 (group C). The PD catheters, constructed of silicon tubing with two polyester cuffs, were patterned after the standard Tenckhoff catheter. A covalent multipoint method of attachment onto polymeric surfaces was used for stable, permanent chemical immobilization of heparin on the PD catheter. Dialysis exchanges (25-mL instillation volume) were performed twice daily for 4 weeks through the permanent catheter. Prophylactic antibiotics were not used. The exit sites were evaluated at 2-week intervals. The extent of biofilm coverage on the intraperitoneal portion of the catheter (obtained at the end of the experiment) was assessed, and sonicated fluid from the catheter tip was cultured for evaluating bacterial colonization of the catheter. Exit-site scores in group H were lower than in group C (p = 0.052) at the end of week 4. Bacterial colonization tended to be less common in group H [2 of 12 catheters (17%)] than in group C [8 of 15 catheters (53%); p = 0.058], but the extent of biofilm, the peritonitis rate, and the inflammation score of tissue adjacent to the cuff were not different between the groups. Those data suggest that heparinized PD catheters can be a practical approach to the prevention of bacterial colonization and can improve healing of the exit site.

Animals↗
PubMed2000

Activation of retinoic acid receptor gamma induces proliferation of immortalized hippocampal progenitor cells.

In the present study, we report evidence that activation of RARgamma promotes cell proliferation in immortalized hippocampal progenitor cell line HiB5. We found that treatment of HiB5 cells with all-trans- (all-trans-RA) or 9-cis-retinoic acid (9-cis-RA) significantly increased the number of dead floating cells as well as viable cells in serum-free defined medium (N2). Flow cytometric analysis of DNA contents revealed that the proportion of apoptotic cells over the whole cell population was not affected by both retinoids. Instead, the proportion of S phase cells was significantly increased by retinoids. Under this condition, bcl-2 mRNA levels were significantly increased over time by retinoid treatment, whereas bax mRNA levels were not affected. This suggests that retinoids increase viable cells by enhancing proliferation rather than by suppressing apoptosis. In an attempt to dissect the molecular mechanism underlying retinoid-induced HiB5 cell proliferation, we examined the expression patterns of retinoid receptors following retinoid treatment. Retinoids induced RARgamma mRNA, which paralleled the increase in the transactivation of strong retinoic acid response element (RARE) reporter construct. Accordingly, treatment of HiB5 cells with RARgamma-selective agonist (CD666) increased HiB5 cell number in a dose-dependent manner, which was blocked by co-treatment with RARgamma-selective antagonist (CD2665). Taken together, these data clearly indicate that activation of RARgamma increases proliferation of immortalized hippocampal progenitor cells.

Alitretinoin↗
PubMed2000

Antimicrobial activity of MHC class I-restricted CD8+ T cells in human tuberculosis.

Studies of mouse models of tuberculosis (TB) infection have indicated a central role for MHC class I-restricted CD8+ T cells in protective immunity. To define antigens and epitopes of Mycobacterium tuberculosis (MTB) proteins that are presented by infected cells to CD8+ T cells, we screened 40 MTB proteins for HLA class I A*0201-binding motifs. Peptides that bound with high affinity to purified HLA molecules were subsequently analyzed for recognition by CD8+ cytotoxic T lymphocytes. We identified three epitopes recognized by CD8+ T cells from patients recovering from TB infection. Those three epitopes were derived from three different antigens: thymidylate synthase (ThyA(30-38)), RNA polymerase beta-subunit (RpoB(127-135)), and a putative phosphate transport system permease protein A-1 (PstA1(75-83)). In addition, CD8+ T cell lines specific for three peptides (ThyA(30-38), PstA1(75-83), and 85B(15-23)) were generated from peripheral blood mononuclear cells of normal HLA-A*0201 donors. These CD8+ T cell lines specifically recognized MTB-infected macrophages, as demonstrated by production of IFN-gamma and lysis of the infected target cells. Finally, CD8+ cytotoxic T lymphocytes reduced the viability of the intracellular MTB, providing evidence that CD8+ T cell recognition of MHC class I-restricted epitopes of these MTB antigens can contribute to effective immunity against the pathogen.

Animals↗
PubMed2000

Antisense palmitoyl protein thioesterase 1 (PPT1) treatment inhibits PPT1 activity and increases cell death in LA-N-5 neuroblastoma cells.

Infantile neuronal ceroid lipofuscinosis (INCL) is a childhood neurodegenerative disease caused by the selective death of cortical neurons and retinal degeneration, as the result of a palmitoyl protein thioesterase 1 (PPT1) deficiency. Recently, we showed that overexpression of PPT1 protects LA-N-5 human neuroblastoma cells against apoptotic death (Cho and Dawson [2000a] J. Neurochem. 74:1478-1488) and we now show that inhibition of PPT1 increases the susceptibility of these cells to apoptotic cell death. Transient transfection of LA-N-5 neuroblastoma cells with PPT1-FLAG resulted in a strong expression of PPT-FLAG-tagged protein as evidenced by Western blot analysis and immunofluorescence. Co-transfection of a reverse-oriented (antisense) PPT1 (AS-PPT1) decreased the expression of PPT-FLAG to almost zero, reduced PPT1 enzyme activity (as measured by an in vitro assay) and increased the susceptibility to apoptosis induced by C(2) ceramide. Similarly, inhibition of PPT1 with a synthetic inhibitor (AcG-palmitoyl diaminoproprionate-VKIKK) (DAP1) (100 microM) increased the susceptibility of the cells to apoptosis induced by either C(2)-ceramide or etoposide, a common chemotherapeutic agent used in the treatment of neuroblastoma. Cells stably overexpressing PPT1 were resistant to apoptosis induced by DAP1 suggesting that the inhibitor has a specific action and confirming that low levels of protein palmitoylation block the death pathway. Drugs that raise the level of protein palmitoylation are pro-apoptotic and PPT1 inhibition may enhance the killing efficacy of chemotherapeutic agents used to kill neuroblastoma-derived cells.

Antineoplastic Agents↗
PubMed2000

Direct activation of capsaicin receptors by products of lipoxygenases: endogenous capsaicin-like substances.

Capsaicin, a pungent ingredient of hot peppers, causes excitation of small sensory neurons, and thereby produces severe pain. A nonselective cation channel activated by capsaicin has been identified in sensory neurons and a cDNA encoding the channel has been cloned recently. However, an endogenous activator of the receptor has not yet been found. In this study, we show that several products of lipoxygenases directly activate the capsaicin-activated channel in isolated membrane patches of sensory neurons. Among them, 12- and 15-(S)-hydroperoxyeicosatetraenoic acids, 5- and 15-(S)-hydroxyeicosatetraenoic acids, and leukotriene B(4) possessed the highest potency. The eicosanoids also activated the cloned capsaicin receptor (VR1) expressed in HEK cells. Prostaglandins and unsaturated fatty acids failed to activate the channel. These results suggest a novel signaling mechanism underlying the pain sensory transduction.

Animals↗
PubMed2000

The impact of bcl-2 expression and bax deficiency on prostate homeostasis in vivo.

Prostatic glandular epithelial cells undergo apoptosis in response to androgen-deprivation. The molecular determinants of androgen-responsiveness in these cells are incompletely understood. Recent evidence suggests that bcl-2 gene family members may be important in this context. We used the probasin promoter to target a human bcl-2 transgene specifically to the prostate in order to assess its impact on conferring resistance to androgen withdrawal in, otherwise sensitive, prostatic glandular epithelial cells in vivo. We examined the contribution of bax to mediating androgen-responsiveness in prostatic glandular epithelial cells using bax knockout mice. The histologic appearance of the prostates from probasin-bcl-2 transgenic mice or bax-/- mice did not differ from those of control littermates. There was no evidence of hyperplastic or neoplastic growth. There was no difference between probasin bcl-2 transgenic mice, bax-/- mice, and control littermates in steady-state levels of apoptosis. Following castration our findings suggest that both bax and bcl-2 may each contribute to the androgen-responsiveness of prostatic glandular epithelial cells. It is apparent from these results, however, that bax is not required to mediate cell death in prostatic glandular epithelial cells following castration. A comparison between the apoptotic indices in the ventral prostate from the probasin-bcl-2 and bax-/- mice following castration suggests that the presence of bcl-2 may be a more important indicator of androgen-sensitivity than a deficiency of bax.

Androgen-Binding Protein↗
PubMed2000

Batten's disease: clues to neuronal protein catabolism in lysosomes.

Neuronal ceroid lipofuscinosis (Batten disease) encompasses a group of 8 or more inherited lysosomal storage diseases, with an overall frequency of 1 in 12,500 births. All are characterized by progressive blindness and dementia and were initially classified on the basis of age of onset, clinical phenotype and ultrastructural characterization of the storage material as granular osmiophilic deposits, curvilinear bodies or fingerprint bodies. Recent research has shown that the various forms of Batten disease result from mutations in at least 8 genes which code for proteins involved in different aspects of lysosomal protein catabolism. These include palmitoyl:protein thioesterase 1 (CLN1), tripeptidylpeptidase 1 (CLN2), cathepsin D (CLN8), and two membrane proteins of unknown function (CLN3 and CLN5). Biochemically, Batten disease is characterized by the accumulation in neurons and other cells of an autofluorescent pigment which has resisted many attempts at analysis. In this review we attempt to relate our current understanding of the nature of the storage material in Batten disease with this genetic information. We conclude that the 8 genes probably code for proteins which facilitate the degradation of post-translationally modified proteins in lysosomes, suggesting that the turnover of these proteins is highest in cortical neurons.

Animals↗
PubMed2000

In vitro depalmitoylation of neurospecific peptides: implication for infantile neuronal ceroid lipofuscinosis.

Palmitoyl protein thioesterase 1 (PPT1) removes palmitate from specific cysteine residues in peptides and proteins. We have previously shown that a palmitoylated myelin glycoprotein. Po octapeptide (IRYCWLRR) can be specifically depalmitoylated by PPT1 in vitro (Cho and Dawson [1998] J. Neurochem. 171 ;323-329). To characterize further the substrate specificity of PPT1, we prepared various palmitoylated oligopeptides, based on palmitoylated sequences from different proteins. A truncated tetrapeptide from Po (RY[palmitoyl]-CW) was as good a substrate as the octapeptide Po, with optimal activity at pH 4.0. In contrast, other peptide substrates showed marked differences. Thus, the deacylation of GAP-43 (MLCCMRR), rhodopsin (VTTLCCGKN), and Galpha subunit (MGCLGNSK) peptides was more efficient at neutral pH (7.4) than at acidic pH (4.0), with the greatest efficiency toward the Galpha peptide (five- to sixfold higher than other substrates). Infantile neuronal ceroid lipofuscinosis (INCL) is caused by PPT1 deficiency, and the absence of enzymatic activity was confirmed with GAP-43 peptide as well as the Po peptide. LA-N-5 human neuroblastoma cells overexpressing PPT1 showed increased depalmitoylation of all the peptide substrates, indicating that these peptides are deacylated by PPT1. An amide derivative of a palmitoylated K-Ras peptide (AcG-palmitoyl diamino propionate-VKIKK) acted as an enzyme pseudosubstrate and inhibited PPT1 enzyme activity in a dose-dependent manner. The peptide itself (AcGCVKIKK) did not affect PPT activity. In summary, PPT1 is able to hydrolyze a range of cysteinyl peptide sequences found in both neuron-specific and ubiquitous (e.g., Galpha) proteins. The inhibitor of PPT1 activity should facilitate the development of a model for INCL and help explain the neuronal death in this disease.

Brain Neoplasms↗
PubMed2000

Carrier detection and prenatal diagnosis of hemophilia A in a Korean population by PCR-based analysis of the BclI/intron 18 and St14 VNTR polymorphisms.

We have undertaken this study to identify the usefulness of polymerase chain reaction (PCR)-based analysis of DNA polymorphisms in the BclI/intron 18 and St14 variable number of tandem repeats (VNTR) loci for carrier detection and prenatal diagnosis of hemophilia A in the Korean population. We have analyzed these polymorphisms in members of 105 unrelated Korean families with severe hemophilia A. The observed heterozygosity rates for the BclI/intron 18 and St14 VNTR polymorphisms were 21.0% and 71.3%, respectively. The BclI/intron 18 polymorphism was less informative in Koreans when compared with Caucasians and Japanese. The allele frequencies for St14 VNTR in Koreans were different from those in Caucasians. Compared with Caucasians, there was a markedly higher occurrence of low molecular weight alleles in Koreans. The observed heterozygosity for the St14 VNTR polymorphism in combination with the BclI/intron 18 polymorphism was 81.9%. These two polymorphisms were applied to determine the carrier status of 107 women from 65 unrelated families, and to assess fetal status in 37 pregnancies. So far, we have experienced one case of misdiagnosis of carriership. Our study demonstrated that the PCR-based analysis of the BclI/intron 18 and St14 VNTR polymorphisms was useful in the carrier detection and prenatal diagnosis of hemophilia A in the Korean population.

DNA↗
PubMed2000

Expression of the alpha2beta1 and alpha3beta1 integrins at the surface of mesothelial cells: a potential attachment site of endometrial cells.

OBJECTIVE: To localize alpha2beta1 and alpha3beta1 integrins in the cell membrane of peritoneal mesothelium in vivo and in vitro. DESIGN: Descriptive study using confocal and two-photon laser-scanning microscopy. SETTING: University-based laboratory. PATIENT(S): Women without endometriosis undergoing surgery for benign conditions. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Peritoneal biopsies (n = 9) and mesothelial monolayer cultures (n = 4) were incubated with antibodies to the alpha2 and alpha3 subunits and to the intact alpha2beta1 and alpha3beta1 integrins. Specimens were examined with laser-scanning microscopy. RESULT(S): The alpha2 and alpha3 subunits and the intact alpha2beta1 and alpha3beta1 integrins were identified at the base of the mesothelial cells (i.e., toward the basement membrane). There was also expression of the alpha2 and alpha3 subunits and the intact alpha2beta1 and alpha3beta1 integrins at the cell surface (i.e., toward the peritoneal cavity). CONCLUSION(S): The resolution of the confocal and two-photon laser-scanning microscope enabled localization of integrins in mesothelial cells. The presence of alpha2beta1 (collagen-laminin receptor) and alpha3beta1 integrins (collagen-laminin-fibronectin receptor) at the base of mesothelial cells suggests a role for these molecules in adhesion to the basement membrane. The presence of these molecules at the cell surface suggests a potential locus for cell adhesion in such processes as endometriosis and cancer metastasis.

Adult↗