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Y S Cho

Publications and source records attributed to Y S Cho.

At least 37 records · Page 2Linked to original sources
PubMed2001

Antisense DNAs as multisite genomic modulators identified by DNA microarray.

Antisense oligodeoxynucleotides can selectively block disease-causing genes, and cancer genes have been chosen as potential targets for antisense drugs to treat cancer. However, nonspecific side effects have clouded the true antisense mechanism of action and hampered clinical development of antisense therapeutics. Using DNA microarrays, we have conducted a systematic characterization of gene expression in cells exposed to antisense, either exogenously or endogenously. Here, we show that in a sequence-specific manner, antisense targeted to protein kinase A RIalpha alters expression of the clusters of coordinately expressed genes at a specific stage of cell growth, differentiation, and activation. The genes that define the proliferation-transformation signature are down-regulated, whereas those that define the differentiation-reverse transformation signature are up-regulated in antisense-treated cancer cells and tumors, but not in host livers. In this differentiation signature, the genes showing the highest induction include genes for the G proteins Rap1 and Cdc42. The expression signature induced by the exogenously supplied antisense oligodeoxynucleotide overlaps strikingly with that induced by endogenous antisense gene overexpression. Defining antisense DNAs on the basis of their effects on global gene expression can lead to identification of clinically relevant antisense therapeutics and can identify which molecular and cellular events might be important in complex biological processes, such as cell growth and differentiation.

Adenocarcinoma↗
PubMed2001

Down modulation of IL-18 expression by human papillomavirus type 16 E6 oncogene via binding to IL-18.

To understand modulation of a novel immune-related cytokine, interleukin-18, by human papillomavirus type (HPV) 16 oncogenes, HaCaT, normal keratinocyte cell line, and C-33A, HPV-negative cervical cancer cell line, were prepared to establish stable cell lines expressing E6, E6 mutant (E6m), E6E7, or E7 constitutively. Expressions of various HPV oncogene transcripts were identified by RT-PCR. Expression of HPV oncogene E6 was reversely correlated to the expression of interleukin-18, a novel pro-inflammatory cytokine. The expression of E6 in C-33A, independent of E6 splicing, resulted in decreased IL-18 expression and that of IL-18 was also significantly reduced in HaCaT cells expressing E6. The level of p53 was reduced in C-33A cells expressing E6 whereas not altered in HaCaT cells expressing E6, suggesting that E6 downregulated IL-18 expression via an independent pathway of p53 degradation in HaCaT cells which have a mutated p53 form. However, E7 did not affect IL-18 expression significantly in both C-33A and HaCaT cells. Cotransfection experiments showed that E6 oncogene did not inhibit the activities of IL-18 promoter P1 and P2, suggesting that E6 oncogene indirectly inhibited IL-18 expression. Taken together, E6, E6m and E6/E7 inhibited IL-18 expression with some variation, assuming that cells expressing E6 oncogene can evade immune surveillance by downregulating the expression of immune stimulating cytokine gene, IL-18, and inhibiting the cascade of downstream effects that follow activation of the IL-18 receptor.

Binding, Competitive↗
PubMed2001

Both E6 and E7 oncoproteins of human papillomavirus 16 inhibit IL-18-induced IFN-gamma production in human peripheral blood mononuclear and NK cells.

Cervical carcinoma is the predominant cancer among malignancies in women throughout the world, and human papillomavirus (HPV) 16 is the most common agent linked to human cervical carcinoma. The present study was performed to investigate the mechanisms of immune escape in HPV-induced cervical cancer cells. The presence of HPV oncoproteins E6 and E7 in the extracellular fluids of HPV-containing cervical cancer cell lines SiHa and CaSki was demonstrated by ELISA. The effect of HPV 16 oncoproteins E6 and E7 on the production of IFN-gamma by IL-18 was assessed. E6 and E7 proteins reduced IL-18-induced IFN-gamma production in both primary PBMCs and the NK0 cell line. FACS analysis revealed that the viral oncoproteins reduced the binding of IL-18 to its cellular surface receptors on NK0 cells, whereas there was no effect of oncoproteins on IL-1 binding to its surface IL-1 receptors on D10S, a subclone of the murine Th cell D10.G4.1. In vitro pull-down assays also revealed that the viral oncoproteins and IL-18 bound to IL-18R alpha-chain competitively. These results suggest that the extracellular HPV 16 E6 and E7 proteins may inhibit IL-18-induced IFN-gamma production locally in HPV lesions through inhibition of IL-18 binding to its alpha-chain receptor. Down-modulation of IL-18-induced immune responses by HPV oncoproteins may contribute to viral pathogenesis or carcinogenesis.

Adjuvants, Immunologic↗
PubMed2001

Changes in external ear resonance after ventilation tube (Grommet) insertion in children with otitis media with effusion.

OBJECTIVE: As otitis media with effusion is common in children, the effects of a ventilation tube should be taken into account in the prescription of hearing aids for children. In ears with a ventilation tube, the external auditory canal communicates directly with the middle ear space, and so the impedance of the middle ear may change. Consequently, this will affect external-ear resonance. The aim of this study is to observe the effects of the tympanic membrane perforations caused by the ventilation tube on external-ear resonance. We selected 30 ears with otitis media with effusion to measure external-ear resonance before and after ventilation tube insertion. We compared the external-ear resonance of a control group with that of the otitis media with the effusion group and two types of ventilation-tube groups, respectively. In the subjects who have otitis media with effusion, the average gain of the peak resonance was larger than that in the control group. After ventilation-tube insertion, the amplitude of the gain decreased to the same level as the control group, but a characteristic negative gain appeared around 1000 Hz in about half of all cases. This negative gain was observed more frequently in the ventilation tube with a larger diameter. The raised peak resonance gain in the otitis media with effusion group decreased to a level roughly the same as that of the control group after ventilation-tube insertion. Provision of an additional gain in the low frequencies around 1000 Hz should be considered for patients with a ventilation tube when prescribing hearing aids.

Acoustic Stimulation↗
PubMed2001

Modification of inhibitor binding sites in the cytochrome bf complex by directed mutagenesis of cytochrome b(6) in Synechococcus sp. PCC 7002.

The cytochrome bf complex, which links electron transfer from photosystem II to photosystem I in oxygenic photosynthesis, has not been amenable to site-directed mutagenesis in cyanobacteria. Using the cyanobacterium Synechococcus sp. PCC 7002, we have successfully modified the cytochrome b(6) subunit of the cytochrome bf complex. Single amino acid substitutions in cytochrome b(6) at the positions D148, A154, and S159 revealed altered binding of the quinol-oxidation inhibitors 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone (DBMIB), myxothiazol, and stigmatellin. Cytochrome bf and mitochondrial-type cytochrome bc(1) complexes are closely related in structure and function but exhibit quite different inhibitor specificities. Cytochrome bf complexes are insensitive to myxothiazol and sensitive to DBMIB, whereas cytochrome bc(1) complexes are sensitive to myxothiazol and relatively insensitive to DBMIB. Measurements of flash-induced and steady-state electron transfer rates through the cytochrome bf complex revealed increased resistance to DBMIB in the mutants A154G and S159A, increased resistance to stigmatellin in A154G, and created sensitivity to myxothiazol in the mutant D148G. Therefore these mutations made the cytochrome bf complex more like the cytochrome bc(1) complex. This work demonstrates that cyanobacteria can be used as effective models to investigate structure-function relationships in the cytochrome bf complex.

Alleles↗
PubMed2001

An anti-apoptotic protein human survivin is a direct inhibitor of caspase-3 and -7.

Survivin, an apoptosis inhibitor/cell-cycle regulator, is critically required for suppression of apoptosis and ensuring normal cell division in the G2/M phase of the cell cycle. It is highly expressed in a cell cycle-regulated manner and localizes together with caspase-3 on microtubules within centrosomes. Whether survivin is a physiologically relevant caspase inhibitor has been unclear due to the difficulties with obtaining correctly folded survivin and finding the right conditions for inhibition assay. In this study, recombinant, active human survivin was expressed in Escherichia coli and purified to homogeneity. The protein, existing as a homodimer in solution, binds caspase-3 and -7 tightly with dissociation constants of 20.9 and 11.5 nM, respectively, when evaluated by surface plasmon resonance spectroscopy. Consistently, survivin potently inhibits the cleavage of a physiological substrate poly(ADP-ribose) polymerase and an artificial tetrapeptide by caspase-3 and -7 in vitro with apparent inhibition constants of 36.0 and 16.5 nM, respectively. The data suggest that sequestering caspase-3 and -7 in inhibited states on microtubules is at least one mechanism of survivin in the suppression of default apoptosis in the G2/M phase. The localization of survivin on microtubules, which is essential for its function, should increase the protective activity at the action site.

Apoptosis↗
PubMed2001

Improvement of gene transfer to cervical cancer cell lines using non-viral agents.

Virus-like particles (VLPs) composed of recombinant capsid protein L1 and L2 of human papillomavirus type 16 were conjugated with polylysine (PL) and gene transfer was performed using VLP-PL conjugates to allow the expression of targeted gene. When HeLa cells were incubated with VLP-PL conjugate coupled with plasmid cytomegalovirus beta-galactosidase (pCMVbeta-gal), about 10% of cells were transfected and demonstrated beta-galactosidase activity. Hence chloramphenicol acetyltransferase activity was also expressed significantly in VLP-PL-plasmid simian virus 2 chloramphenicol acetyl transferase (pSV2CAT)-transfected cells, VLP-PL conjugate was tested whether it could transfer a tumor suppressor gene, pCMVp53, to HeLa cells and the exogenously provided p53 gene complexed to VLP-PL conjugate was detected from HeLa cells by polymerase chain reaction (PCR) analysis. Interestingly, additional increase of transfection efficiency was demonstrated in the presence of poloxamer 407 when C-33A cells were transfected with VLP-PL-pCMVbeta-gal complex. The result support the notion that VLP-PL conjugate may be a promising vector to transfer genetic materials into cancer cells and poloxamer 407 can be used for enhancing the transfection efficiency of VLP-PL conjugate.

Capsid↗
PubMed2001

Aberrant expression of Smad4 results in resistance against the growth-inhibitory effect of transforming growth factor-beta in the SiHa human cervical carcinoma cell line.

Smad proteins activated by TGF-beta form complexes with Smad4. Upon activation, these complexes translocate to the nucleus of the cell, where they induce transcription of genes related to inhibition of cell growth, cell differentiation and apoptosis. We investigated the role of Smads in the TGF-beta-mediated signal-transduction cascade in 4 human cervical cancer cell lines: HeLa, Caski, HT-3 and SiHa. Based on our results, SiHa cells show low mRNA expression of mutated Smad4 (Gly(230)Ala, Ala(488)Val) and of Smads 2, 3, 5 and 6. SiHa cells were likewise defective in TGF-beta signaling, as evidenced by a lack of significant growth inhibition following TGF-beta treatment. In addition, TGF-beta did not induce transcription of the PAI-1 gene or change Smad protein levels. Introduction of Smad3 and/or Smad4 into SiHa cells restored TGF-beta signaling, as determined by activation of the 3TP-lux reporter gene and by prominent apoptotic cell death with PAI-1 induction. Analysis of the downstream targets activated by TGF-beta yielded rapid activation of p38 with subsequent phosphorylation of the transcription factor ATF-2 but unchanged SAPK/JNK activation in the 4 cervical cancer cell lines. Our findings demonstrate that (i) decrease of Smad4 mRNA expression is closely associated with defective TGF-beta response and lack of growth inhibition, (ii) activation of PAI-1 by TGF-beta may be Smad4-dependent and (iii) the Smad and the p38 cascades are triggered by TGF-beta independently of each other in human cervical cancer.

Adenoviridae↗
PubMed2001

Serum ferritin as a serologic marker of activity in systemic lupus erythematosus.

To investigate the relationship between serum ferritin and disease activity in systemic lupus erythematosus (SLE), we enrolled 128 patients with SLE (18 males and 110 females). Twenty-eight patients (2 males and 26 females) with rheumatoid arthritis (RA) served as controls. The SLE patients were subdivided into three groups according to Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores: groups A (0-5), B (6-9), and C (> or =10). We prospectively evaluated 48 SLE patients before and after treatment. Serum ferritin and anti-dsDNA antibody were measured by radioimmunometric assay. C-reactive protein (CRP) was measured quantitatively by immunonephelometry. Complements 3 and 4 (C3 and C4) were measured by nephelometry. Serum levels of ferritin during the more active stage of SLE (group C) exceeded those of RA patients and patients at less active stages of SLE (groups A and B). There were no significant differences between RA patients and groups A and B. Serum ferritin was elevated especially in serositis and hematologic manifestation. In this prospective study, changes in SLEDAI scores before and after treatment correlated significantly with serum ferritin levels and inversely to C3 and C4 levels. We confirm that serum ferritin levels can be a useful marker of disease activity in SLE patients.

Adult↗
PubMed2001

Expression of multidrug resistance-related genes in oral squamous cell carcinomas.

To characterize the multidrug resistance (MDR) phenotype in human oral squamous cell carcinomas (OSCCs), the expression levels of four MDR-related genes (multidrug resistance, mdr1; multidrug resistance-associated protein, MRP; glutathione S-transferase-pi, GST-pi; and DNA topoisomerase II, topoII) were analyzed in OSCCs. Fifty-two OSCC tissues and 22 normal oral mucosal tissues were involved in this study. The expression of each gene was analyzed with a reverse-transcription polymerase chain reaction (RT-PCR) method using beta(2)m microglobulin (beta(2)m) mRNA as an endogenous control. The mean values of mdr1, MRP, GST-pi, and topoII gene expression relative to the beta(2)m gene in OSCC tissues were 0.37, 0.75, 0.66, and 1.11; those of normal oral mucosa were 0.40, 0.27, 0.62, and 0.91, respectively. The averaged expression levels of the MRP and topoII gene in OSCC tissues were higher than those of normal oral mucosas (P=0.001 and P=0.02, respectively). The expression levels of four MDR-related genes in OSCCs were not related with the degree of histologic cell differentiation, tumor stage, primary or recurred tumor, or the presence or absence of chemotherapy. Linear regression analysis showed a correlation between the expression levels of MRP and GST-pi in normal oral mucosas (r=0.596, P=0.003) and in OSCCs (r=0.287, P=0.039). The results suggest that MRP expression is activated during the tumorigenesis of OSCCs and that this may play a role in de novo drug resistance in OSCCs. These results should provide further insight into the complex role postulated for MDR-related genes in chemotherapy, carcinogenesis and tumor progression.

Adult↗
PubMed2001

Effect of hesperetin, a citrus flavonoid, on the liver triacylglycerol content and phosphatidate phosphohydrolase activity in orotic acid-fed rats.

The effect of dietary hesperetin on the hepatic lipid content and the enzyme activities involved in triacylglycerol (TG) synthesis in rats fed diets with or without 1% orotic acid (OA) was studied. Hepatic TG content was raised by approximately 5-fold after administration of OA for 10 days. The OA-feeding significantly increased the activity of hepatic microsomal phosphatidate phosphohydrolase (PAP), which is the rate-limiting enzyme for TG synthesis. Hepatic glucose-6-phosphate dehydrogenase (G6PDH) and malic enzyme activities were also increased. An addition of 1% hesperetin to the OA-supplemented diet resulted in the decrease of the hepatic TG content by 44% and of microsomal PAP activity. Dietary hesperetin alone neither affected liver TG content nor PAP activity significantly. OA-feeding caused an increased liver cholesterol level, whereas simultaneous addition of hesperetin and OA reduced its content to the control level. A slight reduction of hepatic cholesterol by hesperetin was also observed in the OA-free dietary group. The present study demonstrated that dietary hesperetin can reduce the hepatic TG accumulation induced by OA, and this was associated with the reduced activity of TG synthetic enzyme, PAP.

Animals↗
PubMed2001

Dramatically accelerated growth and extraordinary gigantism of transgenic mud loach Misgurnus mizolepis.

Transgenic mud loaches (Misgurnus mizolepis), in which the entire transgene originated from the same species, have been generated by microinjecting the mud loach growth hormone (mlGH) gene fused to the mud loach beta-actin promoter. Out of 4,100 eggs injected, 7.5% fish derived from the injected eggs showed dramatically accelerated growth, with a maximum of 35-fold faster growth than their non-transgenic siblings. Many fast-growing transgenic individuals showed extraordinary gigantism: their body weight and total length (largest fish attained to 413 g and 41.5 cm) were larger and longer than even those of 12-year-old normal broodstock (maximum size reached to 89 g and 28 cm). Of 46 transgenic founders tested, 30 individuals transmitted the transgene to next generation with a wide range of germ-line transmission frequencies ranging from 2% to 33%. The growth performance of the subsequent generation (F1) was also dramatically accelerated up to 35-fold, although the levels of enhanced growth were variable among transgenic lines. Three transgenic germ-lines up to F4 were established, showing the expected Mendelian inheritance of the transgene. Expression of GH mRNA in many tissues was detected by RT-PCR analyses. The time required to attain marketable size (10 g) in these transgenic lines was only 30-50 days after fertilization, while at least 6 months in non-transgenic fish. Besides growth enhancement, significantly improved feed-conversion efficiency up to 1.9-fold was also observed.

Actins↗
PubMed2001

Surgical tactics and outcome of treatment in jugular foramen schwannomas.

Seven patients with schwannomas of the jugular foramen were included our study in Samsung Medical Center between 1995 and 1999. Patients with neurofibromatosis were excluded. The records of the seven patients (six surgical case and one nonsurgical case) were retrospectively reviewed. There were six women and one man (mean age, 47 years) with a symptom duration ranging from 3 months to 14 years (mean, 47 months). The predominant symptoms were hearing difficulty, hemifacial spasm and hoarseness. Preoperative audiologic evaluation, computerised tomography (CT), magnetic resonance (MR) imaging, and angiography were performed in most patients. We classified tumours into four types using Kaye and Pellet classification on the basis of radiological and surgical findings. The tumours were: Type A (at cerebellopontine angle) in one; Type B (foraminal) in two; Type C (extracranial and/or foraminal) in two; and Type D (intra- and extracranial) in two cases. We used various surgical approaches such as retrosigmoid suboccipital craniectomy for Type A tumours, infratemporal fossa type A approach (ITFA) for Type C tumours, petro-occipital transsigmoid approach or modified transcochear approach for Type D tumours and ITFA with partial labyrinthectomy for Type B. In the selection of surgical approaches, we took consideration of tumour extension, tumour size, and preoperative hearing function. Facial nerve transposition was not used only in one case of ITFA because of small tumour size (1.5cm). Gross total removal was achieved in five cases, and subtotal removal in one case (Type D tumour) with a single-stage operation. Stereotactic radiosurgery was performed on residual mass in the subtotally removed case. Follow-up period ranged from 13 to 49 months (mean, 27.5 months). There was neither postoperative mortality nor recurrence on follow-up MR imaging. There were two cases of temporary facial nerve palsy and one aggravation of pre-existing low cranial palsy. Two case of sustained vocal cord palsy underwent thyroplasty, but there was no aspiration pneumonia. Persistent cerebrospinal fluid collection was improved with lumboperitoneal shunt. The surgical approaches of each case should be tailored according to their shape and the clinical manifestation. We obtain acceptable outcomes from one-stage operation.

Accessory Nerve↗
PubMed2001

Changes in external ear resonance after 3 types of surgery in the patients with chronic otitis media.

OBJECTIVE: This study was designed to identify the external ear resonance characteristics of patients with tympanic membrane perforation and to investigate subsequent changes in external ear resonance, depending on the length of the postoperative period and which of 3 different types of operation was performed: tympanoplasty with canal wall-up mastoidectomy, epitympanoplasty, and canal wall-down mastoidectomy. STUDY DESIGN AND SETTING: A total of 227 ears of 188 patients and 96 control ears comprised the study. We measured the gain and frequency of the first peak of external ear resonance with a real ear analyzer. RESULTS: Gain and frequency of the first peak recorded in the preoperative group did not differ from those of the control group. However, negative peaks appeared around 1 to 1.5 kHz in half of these ears. The gain increased markedly in all 3 postoperative groups. The canal wall-down mastoidectomy and epitympanoplasty groups showed significantly lower frequencies compared with the tympanoplasty with canal wall-up mastoidectomy and control groups, but there was no difference between them. The increased gain diminished over time, but the peak gain did not equalize with that of the controls, even after 15 months. CONCLUSIONS: Additional gain should be considered of around 1 to 1.5 kHz for hearing aid users with tympanic membrane perforation. Postoperative changes in external ear resonance should be expected in patients with chronic otitis media, suggesting that fine readjustments of the hearing aid may be necessary.

Adolescent↗
PubMed2001

Expression and localization of the aquaporin-8 water channel in rat testis.

Spermatogenesis and sperm maturation and storage are accompanied by significant movements of water, and multiple aquaporin transmembrane water channels (AQPs) have been recognized in the male reproductive tract. Nevertheless, the involvement of aquaporins in male reproductive physiology is mostly unknown. Here the expression and localization of AQP8 in rat spermatogenesis is defined and compared to that of AQP7, another aquaporin expressed in male germ cells. AQP8 mRNA was found in testis but not in epididymis, whereas the AQP7 transcript was present in both locations. By immunoblotting, the AQP8 protein was detected as a 25-kDa band and a 32- to 40-kDa diffuse component corresponding to the core and glycosylated protein, respectively. Membrane fractionation revealed AQP8 both in microsomal and plasma membrane-enriched fractions of rat testis while no apparent bands were detected in epididymis. AQP7 appeared as a 23- to 24-kDa band and was found both in testis and epididymis. By immunofluorescence, AQP8 labeling was found intracellularly as well as over the plasma membrane of germ cells throughout spermatogenesis. AQP7 was present in spermatids and spermatozoa and was predominant over the plasma membrane. AQP8 may be involved in the cytoplasmic condensation occurring during differentiation of spermatids into spermatozoa and in the generation of seminiferous tubule fluid.

Animals↗
PubMed2001

Colonoscopic findings in intestinal Behçet's disease.

The aims of this study were to investigate the clinical and colonoscopic characteristics of patients with intestinal Behçet's disease and to compare the findings of typical and atypical intestinal Behçet's disease. Ninety-four patients diagnosed as having intestinal Behçet's disease were included. Of these, we considered 42 patients as having complete or incomplete type; these fulfilled the international criteria as "typical," and the other 52 patients were classified as having "atypical" intestinal Behçet's disease. Abdominal pain was the most common symptom (92%), followed by diarrhea and gastrointestinal bleeding. All of the 22 patients with a history of surgery had ulcers at the anastomotic site. Most of the patients, who had never been operated on, had lesions in the ileocecal area (96%). Sixty-three patients (67%) had a single ulcer. Many (76%) of the ulcers were larger than 1 cm, and the mean size of the ulcers was 2.9 cm. Most (99%) of the ulcers were round/oval or geographic in shape. Usually ulcers were deep (62%), and their margins discrete (80%). There was no difference in the endoscopic findings of typical and atypical intestinal Behçet's disease. Typical colonoscopic findings in intestinal Behçet's disease were single or a few deep ulcers with discrete margins in the ileocecal area or anastomotic site. Endoscopic characteristics of patients with intestinal involvement in the case of "suspect" or "possible" type of Behçet's disease that lack the systemic manifestations of Behçet's disease were in accord with those in "complete" or "incomplete" types of Behçet's disease, who fulfill the International Study Group for Behçet's Disease criteria.

Adolescent↗