Biomedical subjects

Y S Cho

Publications and source records attributed to Y S Cho.

At least 55 records · Page 3Linked to original sources

PubMed2001

Inflammatory pseudotumour involving the skull base and cervical spine.

Inflammatory pseudotumour (IPT) is an idiopathic condition characterized by sclerosing inflammation, which mimics a neoplastic process. IPT involving the skull base and cervical spine is distinctly rare and usually indistinguishable from aggressive neoplasms or infection. We report a case of IPT involving the skull base and cervical spine. Initially the patient complained of headache and hearing loss without other neurological dysfunction. Two cycles of oral systemic steroid therapy resulted in only partial responses. Low dose radiotherapy was followed by quadriparesis as the lesion infiltrated into the cervical vertebral bodies. Subsequently a second course of radiation was administered to the whole cervical spine. Marked improvement was observed clinically and radiologically; however, the patient gradually deteriorated and died of sepsis. Given the aggressive nature of disease and the complications related to the long-term treatment, we suggest that a more aggressive therapeutic approach is suitable in extensive IPT of the skull base.

Cervical Vertebrae↗

PubMed2001

Lack of relationship between vitamin D receptor polymorphism and bone erosion in rheumatoid arthritis.

We performed this study to investigate the possible association between vitamin D receptor (VDR) gene polymorphism and the focal bone erosion in rheumatoid arthritis (RA) patients in Korea. One hundred and fifty-seven RA patients were enrolled and two control groups were selected. The focal bone erosion score was assessed by modified Sharp's method. Genotyping of VDR polymorphisms was performed by polymerase chain reaction and restriction fragment length polymorphism analysis using two restriction enzyme Taq I and Bsm I. Notably, the distribution of VDR genotype in Korean population was different from Caucasians. The frequencies of "tt" and "BB" genotypes were very rare both in RA patients and in control groups. The frequency distribution of the Taq I and Bsm I genotype was not different between RA patients (TT, 93.6%; Tt, 6.4%; tt, 0%; BB, 0.6%; Bb, 5.1%; bb, 94.3%) and control groups (TT, 90.8%; Tt, 7.5%; tt, 1.7%; BB, 1.4%; Bb, 8.1%; bb, 90.5%). There was no significant difference in the focal bone erosion score (mean +/- SD) according to the VDR genotypes of RA patients (TT, 0.92 +/- 1.79; Tt, 0.4 +/- 0.79; Bb, 0.43 +/- 0.80; bb, 0.92 +/- 1.79; p > 0.05). In conclusion, these results suggest that VDR gene polymorphisms are not associated with the focal bone erosion in RA patients in Korea.

Adolescent↗

PubMed2001

The effect of electrical stimulation on the trunk control in young children with spastic diplegic cerebral palsy.

This study was designed to determine the effectiveness of electrical stimulation over the trunk in improving sitting balance in young children with spastic diplegic cerebral palsy who displayed poor trunk control. The subjects ranged in age from 8 to 16 months and were randomly assigned to two groups. Both group had physical therapy for 6 weeks. Electrical stimulation (ES) group had additional electrical stimulation over the abdomen and posterior back muscles. Radiographic studies were carried out on the whole spine while they were sitting before and after treatment. Kyphotic angle, Cobb's angle and lumbo-sacral angle were measured. Additionally, sitting score-Gross Motor Function Measure (GMFM) was also evaluated. There was no difference of these values at initial evaluation between the two groups. Following 6 weeks of intensive therapy, the changes of kyphotic angle and sitting score-GMFM were significantly higher in ES group statistically when compared with those of the control group. The Cobb's angle following treatment was improved in ES group, but not statistically compared with that of control group. This study suggests that electrical stimulation over the trunk become a beneficial therapeutic technique in improving the sitting posture and trunk control in young children with spastic diplegic cerebral palsy.

Cerebral Palsy↗

PubMed2001

Retroperitoneal fibrosis with duodenal stenosis.

Retroperitoneal fibrosis is a rare disease characterized by the formation of dense plaque of fibrous tissue covering the retroperitoneal structures. This disease is commonly presented as ureteral obstruction, but the involvement of duodenum is rare. We report a case of retroperitoneal fibrosis which was complicated with duodenal stenosis and was successfully treated with corticosteroids. A 58-yr-old man, who had history of aorto-iliac bypass graft due to arteriosclerosis obliterans with infrarenal aortic occlusion was admitted to the hospital with abdominal pain and a mass. Abdominal CT scan revealed the periaortic soft tissue mass encircling grafted aorta and stenosis of duodenal third portion. Retroperitoneal fibrosis with duodenal stenosis was diagnosed and prednisolone therapy was initiated. Follow-up CT scan showed that the patient responded to prednisolone therapy with eased pain, shrinking periaortic mass, and reduced duodenal stenosis.

Anti-Inflammatory Agents↗

PubMed2001

The up-right/down-left advantage occurs for both participant- and computer-paced conditions: an empirical observation on Adam, Boon, Paas, and Umiltà (1998).

When up and down stimuli are mapped to left and right keypresses or "left" and "right" vocalizations in a 2-choice reaction task, performance is often better with the up-right/down-left mapping than with the opposite mapping. J. J. Adam, B. Boon, F. G. W. C. Paas, and C. Umiltà (1998) presented evidence that the up-right/down-left advantage is obtained when trials are participant paced but not when they are computer paced. In all, 3 experiments are reported that show no difference in magnitude of the up-right/down-left advantage between computer-paced and participant-paced conditions. The advantage was eliminated, however, in Experiment 3 when a response deadline was imposed. Response speed, rather than participant or computer pacing of trials, is crucial.

Analysis of Variance↗

PubMed2001

Effect of an initiating action on the up-right/down-left advantage for vertically arrayed stimuli and horizontally arrayed responses.

When up and down stimuli are mapped to left and right keypresses or "left" and "right" vocalizations in a 2-choice reaction task, performance is often better with the up-right/down-left mapping than with the opposite mapping. This study investigated whether performance is influenced by the type of initiating action. In all, 4 experiments showed the up-right/down-left advantage to be reduced when the participant's initiating action was a left response compared with when it was a right response. This reduction occurred when the initiating action and response were both keypresses, both were spoken location names, and one was a spoken location name and the other a keypress. The results are consistent with the view that the up-right/down-left advantage is due to asymmetry in coding the alternatives on each dimension, and a distinction between categorical and coordinate spatial codes seems to provide the best explanation of the advantage.

Analysis of Variance↗

PubMed2000

Biochemical characterization of extracellular cAMP-dependent protein kinase as a tumor marker.

In a recent report (Cho et al., Proc. Natl. Acad. Sci. USA 97, 835-840, 2000), we showed that cancer cells of various cell types secrete cAMP-dependent protein kinase (PKA) into the conditioned medium and that in the serum of cancer patients this extracellular PKA (ECPKA) is upregulated 10-fold as compared with normal serum. Here, we characterized the enzymatic properties of ECPKA that is present in the conditioned medium of PC3M prostate cancer cells and in the serum of cancer patients, and we compared ECPKA with PKA found in the cell extracts of PC3M cells. ECPKA present in the conditioned medium and human serum was not activated by cAMP addition, but intracellular PKA activity was totally dependent on the addition of cAMP. This indicates that the ECPKA is present in active, free C subunit form, whereas intracellular PKA is present in inactive holoenzyme form. ECPKA activity increased in a substrate concentration- and time-dependent manner, as did intracellular PKA. Both ECPKA and intracellular PKA activities were specifically inhibited by the PKA inhibitor protein, PKI. However, ECPKA activity was more temperature-sensitive than intracellular PKA; after two cycles of freezing/thawing, only 20% of initial ECPKA activity was detected compared with over 40% of intracellular PKA activity. Western blot analysis revealed the presence of a 40 kDa C(alpha) subunit of PKA in both conditioned medium and in the serum of cancer patients. These results suggest that ECPKA, out of the context of cAMP regulation, may function as a growth factor promoting cell growth and transformation; thus, it may serve as a tumor biomarker.

Biomarkers, Tumor↗

PubMed2000

Characterization of geranium (Pelargonium graveolens) chloroplast EF-Tu cDNA.

A geranium (Pelargonium graveolens) chloroplast translational elongation factor EF-Tu (tufA) cDNA was isolated. The geranium tufA cDNA is 1,584 bp long with 20 bp of 5' untranslated region (UTR) and 139 bp of 3' UTR. It encodes 474 amino acids including a putative chloroplast transit peptide of 65 amino acids. The deduced polypeptides of the geranium tufA cDNA contains four GTP binding sequences in its N-terminal region and two chloroplast EF-Tu signature regions in the C-terminal region. The predicted molecular weight of the mature geranium chloroplast EF-Tu protein was about 45,000 and its amino acid sequence identity with the chloroplast EF-Tu proteins of tobacco, pea, Arabidopsis, rice, and soybean ranges from 85% to 91%. The geranium tufA appears to exist as a single copy gene like Arabidopsis and rice, whereas other known dicot plants have more than one copy in their nuclear genomes.

Amino Acid Sequence↗

PubMed2000

Effect of bioflavonoids extracted from the bark of Pinus maritima on proinflammatory cytokine interleukin-1 production in lipopolysaccharide-stimulated RAW 264.7.

Currently, bioflavonoids have been known to have strong antioxidant capacities, and a variety of efforts have been made to identify the utilities of bioflavonoids in treating various diseases based on their antioxidant capacities. The effects of bioflavonoids extracted from the bark of Pinus maritima Pycnogenol (PYC) on free radical formation, activation of redox sensitive transcription factors, as well as interleukin-1 beta (IL-1 beta) production were investigated in murine macrophage cell lines. PYC exerted strong scavenging activities against reactive oxygen species generated either by H(2)O(2) or PMA in RAW 264.7 and IC-21 cells, respectively. In situ ELISA, immunoblot analysis, and competitive RT-PCR demonstrated that PYC pretreatment of LPS-stimulated RAW 264.7 cells dose-dependently reduced both the production of IL-1 beta and its mRNA levels. Furthermore, in the same cells, PYC blocked the activation of nuclear factor kappa B (NF-kappa B) and activator protein-1 (AP-1), two major transcription factors centrally involved in IL-1 beta gene expression. When RAW 264.7 cells were stimulated with LPS, the inhibitor protein I kappa B largely disappeared from cytosolic fractions. However, pretreatment of the cells with PYC abolished the LPS-induced I kappa B degradation. These results suggest that PYC can inhibit the expression of the proinflammatory cytokine IL-1 by regulating redox-sensitive transcription factors. This study may support the possibility that bioflavonoids including PYC can be used as antiinflammatory and immunosuppressive drugs based on their radical scavenging activities.

Animals↗

PubMed2000

Interaction of two classes of ADP-ribose transfer reactions in immune signaling.

CD38 is a bifunctional ectoenzyme predominantly expressed on hematopoietic cells where its expression correlates with differentiation and proliferation. The two enzyme activities displayed by CD38 are an ADP-ribosyl cyclase and a cyclic adenosine diphosphate ribose (cADPR) hydrolase that catalyzes the synthesis and hydrolysis of cADPR. T lymphocytes can be induced to express CD38 when activated with antibodies against specific antigen receptors. If the activated T cells are then exposed with NAD, cell death by apoptosis occurs. During the exposure of activated T cells to NAD, the CD38 is modified by ecto-mono-ADP-ribosyltransferases (ecto-mono-ADPRTs) specific for cysteine and arginine residues. Arginine-ADP-ribosylation results in inactivation of both cyclase and hydrolase activities of CD38, whereas cysteine-ADP-ribosylation results only in the inhibition of the hydrolase activity. The arginine-ADP-ribosylation causes a decrease in intracellular cADPR and a subsequent decrease in Ca(2+) influx, resulting in apoptosis of the activated T cells. Our results suggest that the interaction of two classes of ecto-ADP-ribose transfer enzymes plays an important role in immune regulation by the selective induction of apoptosis in activated T cells and that cADPR mediated signaling is essential for the survival of activated T cells.

ADP-ribosyl Cyclase↗

PubMed2000

CRE-transcription factor decoy oligonucleotide inhibition of MCF-7 breast cancer cells: cross-talk with p53 signaling pathway.

The CRE, 5'-TGACGTCA-3', has been described as the consensus sequence for the cis-element that directs cAMP-regulated gene expression. Many transcription factors bind to this element and regulate the expression of a wide variety of cellular and viral genes. We have shown that CRE-transcription factor decoy oligonucleotide restrains the growth of cancer cells in vitro and in vivo [Park, Y. G., Nesterova, M., Agrawal, S., and Cho-Chung, Y. S. (1999) J. Biol. Chem. 274, 1573-1580]. The growth inhibition was accompanied by changes in cell morphology and apoptosis. To elucidate the molecular mechanism(s) of the growth inhibition by the CRE-decoy oligonucleotide, we investigated the p53 signaling pathway. Herein, we report that CRE-decoy oligonucleotide treatment results in an increase in the p53 protein level in MCF-7 human breast cancer cells that express wild-type p53. The p21WAF1/Cip1 protein levels were also increased in the CRE-decoy oligonucleotide treated cells accompanying a reduction in Cdk2- and cyclin E-dependent kinase activity and pRb phosphorylation. Pulse-chase experiments reveal that the p53 upregulation was due to increased stability of the protein. The decoy oligonucleotide treatment also enhanced the p53 promotor-directed transcription in vivo along with the increase in p53-CBP (CREB-binding protein) complex formation. Thus, the stabilization and activation of p53 may have contributed to the growth inhibition induced by CRE-transcription factor decoy oligonucleotide in MCF-7 breast cancer cells. This decoy oligonucleotide approach offers great promise as a tool for defining cellular regulatory processes and treating cancer and other diseases.

Breast Neoplasms↗

PubMed2000

Direct interaction of the CD38 cytoplasmic tail and the Lck SH2 domain. Cd38 transduces T cell activation signals through associated Lck.

CD38 ligation has been shown to induce activation of intracellular signaling cascade in T lymphocytes through a Lck-dependent pathway. However, it is not clear how Lck initiates the CD38-mediated signaling process. In the present study, we showed that CD38 and Lck were physically associated through the cytoplasmic tail and the Src homology 2 domain, respectively. This was evidenced by coimmunoprecipitation of Lck with CD38 and Lck with isolated CD38 cytoplasmic domain from T cell lysate, cell lysate of COS-7 cells cotransfected with cDNAs of Lck and CD38, or a mixture of in vitro translated CD38 and Lck. Because the CD38 cytoplasmic domain does not contain any tyrosine residue, the interaction should be independent of phosphotyrosine. The interaction was further confirmed by in vitro interaction between a purified Lck Src homology 2 domain and a nonphosphosynthetic peptide corresponding to the membrane proximal region of the CD38 cytoplasmic domain. In addition, CD38 ligation resulted in an elevated tyrosine kinase activity of the CD38-associated Lck and ultimate activation of interleukin-2 gene transcription. Furthermore, expression of a kinase-deficient Lck mutant suppressed interleukin-2 gene activation in a dose-dependent manner. These results strongly suggested that CD38 ligation indeed tranduced signals for T cell activation using its associated Lck.

ADP-ribosyl Cyclase↗

PubMed2000

Extracellular protein kinase A as a cancer biomarker: its expression by tumor cells and reversal by a myristate-lacking Calpha and RIIbeta subunit overexpression.

Overexpression of cAMP-dependent protein kinase (PKA) type I isozyme is associated with cell proliferation and neoplastic transformation. The presence of PKA on the external surface of LS-174T human colon carcinoma cells has been shown. Here, we show that cancer cells of various cell types excrete PKA into the conditioned medium. This extracellular PKA (ECPKA) is present in active, free catalytic subunit (C subunit) form, and its activity is specifically inhibited by PKA inhibitory protein, PKI. Overexpression of the Calpha or RIalpha subunit gene of PKA in an expression vector, which up-regulates intracellular PKA type I, markedly up-regulates ECPKA expression. In contrast, overexpression of the RIIbeta subunit, which eliminates PKA type I, up-regulates PKA type II, and reverts the transformed phenotype, down-regulates ECPKA. A mutation in the Calpha gene that prevents myristylation allows the intracellular PKA up-regulation but blocks the ECPKA increase, suggesting that the NH(2)-terminal myristyl group of Calpha is required for the ECPKA expression. In serum of cancer patients, the ECPKA expression is up-regulated 10-fold as compared with normal serum. These results indicate that the ECPKA expression is an ordered cellular response of a living cell to actively exclude excess intracellular PKA molecules from the cell. This phenomenon is up-regulated in tumor cells and has an inverse relationship with the hormone dependency of breast cancer. Thus, the extracellular PKA may serve as a potential diagnostic and prognostic marker for cancer.

3T3 Cells↗

PubMed2000

Induction of stress shock proteins DnaK and GroEL by phenoxyherbicide 2,4-D in Burkholderia sp. YK-2 isolated from rice field.

The purpose of this work was to investigate the induction of stress shock proteins in Burkholderia sp. YK-2 in response to the phenoxyherbicide 2,4-dichlorophenoxyacetic acid (2,4-D). The stress shock proteins, which contribute to the resistance of the cytotoxic effect of 2,4-D, were induced at different 2,4-D concentrations in exponentially growing cultures of Burkholderia sp. YK-2. This response involved the induction of a 43-kDa DnaK and 41-kDa GroEL proteins, characterized by SDS-PAGE and Western blot by use of the anti-DnaK and anti-GroEL monoclonal antibodies. The total stress shock proteins were analyzed by 2-D PAGE. Survival of Burkholderia sp. YK-2 with time in the presence of different concentrations of 2,4-D was monitored, and viable counts paralleled the induction of the stress shock proteins in this strain.

2,4-Dichlorophenoxyacetic Acid↗

PubMed2000

Isogenic transgenic homozygous fish induced by artificial parthenogenesis.

As a model system for vertebrate transgenesis, fish have many attractive advantages, especially with respect to the characteristics of eggs, allowing us to produce isogenic, transgenic, homozygous vertebrates by combining with chromosome-set manipulation. Here, we describe the large-scale production of isogenic transgenic homozygous animals using our experimental organism, the mud loach Misgurnus mizolepis, by the simple process of artificial parthenogenesis in a single generation. These isogenic fish have retained transgenic homozygous status in a stable manner during the subsequent 5 years, and exhibited increased levels of transgene expression. Furthermore, their isogenic nature was confirmed by cloned transgenic homozygous offspring produced via another step of parthenogenic reproduction of the isogenic homozygous transgenic fish. These results demonstrate that a combination of transgenesis and artificial parthenogenesis will make the rapid utilization of genetically pure homozygous transgenic system in vertebrate transgenesis possible.

Animals↗

PubMed2000

Mutations of the gene encoding the protein kinase A type I-alpha regulatory subunit in patients with the Carney complex.

Carney complex (CNC) is a multiple neoplasia syndrome characterized by spotty skin pigmentation, cardiac and other myxomas, endocrine tumours and psammomatous melanotic schwannomas. CNC is inherited as an autosomal dominant trait and the genes responsible have been mapped to 2p16 and 17q22-24 (refs 6, 7). Because of its similarities to the McCune-Albright syndrome and other features, such as paradoxical responses to endocrine signals, genes implicated in cyclic nucleotide-dependent signalling have been considered candidates for causing CNC (ref. 10). In CNC families mapping to 17q, we detected loss of heterozygosity (LOH) in the vicinity of the gene (PRKAR1A) encoding protein kinase A regulatory subunit 1-alpha (RIalpha), including a polymorphic site within its 5' region. We subsequently identified three unrelated kindreds with an identical mutation in the coding region of PRKAR1A. Analysis of additional cases revealed the same mutation in a sporadic case of CNC, and different mutations in three other families, including one with isolated inherited cardiac myxomas. Analysis of PKA activity in CNC tumours demonstrated a decreased basal activity, but an increase in cAMP-stimulated activity compared with non-CNC tumours. We conclude that germline mutations in PRKAR1A, an apparent tumour-suppressor gene, are responsible for the CNC phenotype in a subset of patients with this disease.

Acromegaly↗

PubMed2000

Improvement of receptor-mediated gene delivery to HepG2 cells using an amphiphilic gelling agent.

Gene transfer was performed using asialo-oroso-mucoid-polylysine (ASOR-PL) conjugates to allow targeted expression of the gene in cells of hepatic origin. In a gel-electrophoretic analysis, the ASOR-PL conjugate produced a complete DNA retardation effect at the optimal ratio of 222:1 (ASOR-PL conjugate/pCMV beta-gal plasmid). The gene-transfer efficiency of the ASOR-PL conjugate was evaluated in HepG2 cells that express asialoglycoprotein receptor and NIH 3T3 cells that do not. The expression was assayed by 5-bromo-4-chloroindol-3-yl beta-D-galactopyranoside ('X-Gal') staining and Chlorophenol Red beta-D-galactopyranoside. When an expression vector for the tumour-suppressor gene p53, pCMVp53, complexed to ASOR-PL conjugate, was transfected into HepG2 cells, the exogenously provided p53 gene was detected in the HepG2 cells by PCR. To improve the efficiency of DNA delivery and expression of the therapeutic proteins poloxamer 407, a fusogenic peptide, influenza-virus haemagglutinin HA2 and chloroquine were individually incorporated into the system. The expression level of beta-galactosidase in HepG2 cells was increased by about four times by the presence of poloxamer 407, whereas the fusogenic peptide HA2 and chloroquine had no effects. When HepG2 cells were transfected with pCMVp53 in the presence of poloxamer 407, the mRNA of transfected p53 could be detected by reverse transcriptase PCR. The current findings open the possibility that a receptor-mediated gene-delivery system for hepatic gene therapy using ASOR-PL conjugate in combination with poloxamer 407 may be developed in the future.

3T3 Cells↗

PubMed2000

Cytochrome cM from synechocystis 6803. Detection in cells, expression in Escherichia coli, purification and physical characterization.

Based on DNA sequence data a novel c-type cytochrome, cytochrome cM, has been predicted to exist in the cyanobacterium Synechocystis 6803. The precursor protein consists of 105 amino acids with a characteristic heme-binding motif and a hydrophobic domain located at the N-terminal end that is proposed to act as either a signal peptide or a membrane anchor. For the first time we report the detection of cytochrome cM in Synechocystis 6803 using Western blot analysis. The soluble portion cytochrome cM has been overexpressed in Escherichia coli in two forms, one with a poly histidine tag to facilitate purification and one without such a tag. The overexpressed protein has been purified and shown to bind heme, exhibiting an absorption peak in the Soret band near 416 nm and a peak in the alpha band at 550 nm. The extinction coefficient of cytochrome cM is 23.2 +/- 0.5 mM-1.cm-1 for the reduced minus oxidized alpha band peak (550-535 nm). The isoelectric point of cytochrome cM is 5.6 (without the histidine tag), which is significantly lower than the pI of 7.2 predicted from the amino acid sequence. The redox midpoint potential of cytochrome cM expressed in E. coli is 151 +/- 5 mV (pH 7.1), which is quite low compared to other c-type cytochromes in which a histidine and a methionine residue serve as the axial ligands to the heme. This work opens the way for determining the three-dimensional structure of cytochrome cM and investigating its function in cyanobacteria.

Amino Acid Sequence↗